JP2014024838A - Hypoglycemic agonist containing condensed heterocyclic compound as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hypoglycemic agonist containing GPR-119 agonist as an active ingredient.SOLUTION: The present invention provides a compound represented by following formula (I) or salt thereof. In the formula (I), a substituent A represents phenyl, or heteroaryl having five- or six-membered ring, and a substituent B represents (a) Calkyl, Ccycloalkyl, Ccycloalkyl Calkyl, aryl Calkyl, or saturated heterocyclyl Calkyl, (b) -COOR, or (c) heteroaryl having five- or six-membered ring represented by following formula (β).

Description

  The present invention relates to a hypoglycemic agent containing a GPR119 agonist as an active ingredient.

  GPR119 is a G protein-coupled receptor (GPCR) having an endogenous ligand such as oleylethanolamide, which is a natural long chain fatty acid amide. It is known that this receptor is highly expressed in pancreatic β cells, which are insulin-producing cells of the pancreas, and small intestinal endocrine cells involved in incretin secretion. It has been reported that the pancreas is activated by stimulation with a GPR119 agonist and the like and enhances insulin secretion in a hyperglycemic-dependent manner. In addition, activation of small intestine endocrine cells promotes secretion of incretins such as Glucagon-like peptide 1 (GLP-1), which is an antidiabetic hormone, and indirectly induces insulin secretion from pancreatic β cells. Has been reported to be enhanced. The hypoglycemia risk is assumed to be extremely low because it exerts hyperglycemic-dependent insulin secretion and, in turn, hypoglycemic action from both the direct action on the pancreas and the indirect action through incretin secretion from the small intestine. In addition, in the db / db diabetic model mouse, a diabetes onset delay action mainly composed of pancreatic protection has been reported by continuous activation of GPR119 in pancreatic β cells. On the other hand, in high fat diet-fed rats, studies using a GPR119 agonist have been reported to inhibit body weight gain through suppression of feeding, delayed gastric emptying, and the like, and are also expected to have an anti-obesity effect. From the above findings, it is expected that GPR119 agonist can be a novel anti-diabetic drug having both pancreatic protective action and anti-obesity action (see Non-Patent Documents 1 to 3).

As the GPR119 agonist, oleylethanolamide (OEA), which is the aforementioned endogenous ligand, is known. In addition, some compounds such as certain bipiperidinyl derivatives (see Patent Document 1), pyrimidinyl derivatives (see Patent Document 2 and Non-Patent Document 4), oxadiazolyl derivatives (see Patent Document 3), thiazolyl derivatives (see Patent Document 4), etc. However, there is no disclosure of the compound of the present invention.
Further, a compound having a structurally similar condensed heterocyclic structure has been reported, but the position of the substituent introduced into the condensed ring structure is always different from the compound of the present invention, and there is no disclosure of the compound of the present invention ( (See Patent Documents 5 to 12). A compound of the formula (A) shown below, which is structurally similar, has been reported. However, the use of the compound of the present application in that it is intended for a disease caused by activation of p38 kinase such as rheumatoid arthritis. It is different from the use (Patent Document 13).

WO2008 / 076243 WO2007 / 035355 WO2007 / 116229 WO2008 / 083238 WO2005 / 007658 WO2008 / 008887 WO2010 / 009195 WO2008 / 137436 WO2009 / 141238 WO2010 / 009207 WO2010 / 084944 WO2010 / 088518 WO2004 / 010995

Journal of Medicinal Chemistry, 2003, 46 (25), 5294-5297 Bioorganic & Medicinal Chemistry, 2004, 12 (5), 1151-1175. Bioorganic & Medicinal Chemistry Letters, 2004, 14 (9), 2141-2145 Endocrinology, 2004, 149 (5), 2035-2037

  An object of the present invention is to provide a hypoglycemic agent containing an excellent GPR119 agonist as an active ingredient.

  As a result of intensive studies to achieve the above problems, the present inventors have found that a compound represented by the following general formula (I) has an excellent GPR119 agonistic action.

That is, the present invention
(1) The following general formula (I)

（式（Ｉ）中、
置換基Ａは、フェニル又は５若しくは６員のヘテロアリール（該フェニル並びに５若しくは６員のヘテロアリールは、置換されていないか、下記の置換基群Ｚ１から同一に又は異なって選ばれる１〜３個の基で置換されている。）
を示し、
置換基群Ｚ１は、ハロゲン原子、カルバモイル、スルファモイル、シアノ、シアナミド、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、ヒドロキシ、カルバモイル、スルファモイル、Ｃ_3-8シクロアルキル、アリール、ヘテロアリール、部分的に飽和されたヘテロアリール、飽和のヘテロシクリル、Ｃ_1-6アルコキシ、Ｃ_1-6アルコキシカルボニル、モノＣ_1-6アルキルアミノカルボニル、ジＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル、Ｃ_1-6アルキルカルボニルアミノ、Ｃ_1-6アルキルスルホニルアミノ及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）、Ｃ_3-8シクロアルキル、アリール、ヘテロアリール、部分的に飽和されたヘテロアリール、飽和のヘテロシクリル（該Ｃ_3-8シクロアルキル、アリール、ヘテロアリール、部分的に飽和されたヘテロアリール及び飽和のヘテロシクリルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、モノＣ_1-6アルキルアミノカルボニル（該モノＣ_1-6アルキルアミノカルボニルは、置換されていないか、ヒドロキシ、カルバモイル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ、ジＣ_1-6アルキルアミノ及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）、モノＣ_3-8シクロアルキルアミノカルボニル、モノ飽和のヘテロシクリルアミノカルボニル（該モノ飽和のヘテロシクリルアミノカルボニルは、置換されていないか、１〜２個のオキソで置換されている。）、ジＣ_1-6アルキルアミノカルボニル（該ジＣ_1-6アルキルアミノカルボニルは、置換されていないか、ヒドロキシ、シアノ及びＣ_1-6アルコキシからなる群より同一に又は異なって選ばれる１〜２個の基で置換されている。）、飽和のヘテロシクリルカルボニル［該飽和のヘテロシクリルカルボニルは、置換されていないか、ヒドロキシ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、1個のヒドロキシで置換されている。）、モノＣ_1-6アルキルアミノ、ジＣ_1-6アルキルアミノ及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜２個の基で置換されている。］、Ｃ_1-6アルキルスルホニルアミノ、Ｃ_1-6アルキルスルホニル（該Ｃ_1-6アルキルスルホニルは、置換されていないか、ヒドロキシ、カルバモイル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）及びモノＣ_1-6アルキルアミノスルホニル（該モノＣ_1-6アルキルアミノスルホニルは、置換されていないか、１個のヒドロキシで置換されている。）からなる群を示し、
Ｗは、単結合、-Ｏ-、-ＮＨ-、-ＯＣＨ₂-又は-ＣＨ₂Ｏ-を示し、
Ｘは、窒素原子又はＣＲ²¹を示し、
Ｙ¹は、窒素原子又はＣＲ²²を示し、
Ｙ²は、窒素原子又はＣＲ²³を示し、
Ｙ³は、窒素原子又はＣＲ²⁴を示し、
Ｒ²¹、Ｒ²²、Ｒ²³及びＲ²⁴は、同一に又は異なって、水素原子又はＣ_1-6アルキル
を示し、
置換基Ｂは、
（ａ）Ｃ_2-6アルキル（該Ｃ_2-6アルキルは、置換されていないか、ハロゲン原子及びヒドロキシからなる群より選ばれる１〜６個の基で置換されている。）、Ｃ_3-8シクロアルキル、Ｃ_3-8シクロアルキルＣ_1-6アルキル（該Ｃ_3-8シクロアルキルＣ_1-6アルキルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、アリールＣ_1-6アルキル又は飽和のヘテロシクリルＣ_1-6アルキル（該飽和のヘテロシクリルＣ_1-6アルキルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、
（ｂ）−ＣＯＯＲ³¹（Ｒ³¹は、Ｃ_1-6アルキル｛該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_3-8シクロアルキル（該Ｃ_3-8シクロアルキルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１〜３個の基で置換されている。）、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１個のアリールで置換されている。）、アリール［該アリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）及びＣ_1-6アルコキシからなる群より選ばれる１〜３個の基で置換されている。］、ヘテロアリール（該ヘテロアリールは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）、飽和のヘテロシクリル（該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、モノＣ_1-6アルキルアミノ、ジＣ_1-6アルキルアミノ、Ｃ_1-6アルキルスルファニル及びＣ_1-6アルキルスルホニルからなる群より選ばれる１〜６個の基で置換されている。｝、Ｃ_3-8シクロアルキル（該Ｃ_3-8シクロアルキルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１〜３個の基で置換されている。）、アリール又は飽和のヘテロシクリル［該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１個のアリールで置換されている。）で置換されている。］を示す。）、
（ｃ）下記式（β）

(In the formula (I),
Substituent A is phenyl or 5- or 6-membered heteroaryl (the phenyl and 5- or 6-membered heteroaryl are either unsubstituted or selected from the following substituent group Z1 in the same or different manner: 1 to 3 Substituted with 1 group.)
Indicate
Substituent group Z1 is a halogen atom, carbamoyl, sulfamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or halogen atom, hydroxy, carbamoyl, sulfamoyl, C _3-8 Cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl, saturated heterocyclyl, C _1-6 alkoxy, C _1-6 alkoxycarbonyl, mono C _1-6 alkylaminocarbonyl, diC _1-6 alkylamino carbonyl, heterocyclylcarbonyl saturated, substituted with C _1-6 alkylcarbonylamino, C _1-6 alkylsulfonylamino and C _1-6 1 to 3 groups which are identical to or different selected from the group consisting of alkylsulfonyl have.), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated hetero Reels, saturated heterocyclyl (said C _3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl partially saturated heteroaryl and saturated, unsubstituted or substituted, is substituted with 1 to 3 halogen atoms C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is unsubstituted or from the group consisting of hydroxy, carbamoyl, C _3-8 cycloalkyl, C _1-6 alkoxy, diC _1-6 alkylamino and C _1-6 alkylsulfonyl substituted with 1 to 3 groups which are the same or different and selected.), mono-C _3-8 cycloalkyl-aminocarbonyl, heterocyclylcarbonyl aminocarbonyl mono saturated ( Heterocyclylcarbonyl aminocarbonyl mono saturation, unsubstituted or substituted, is substituted with one to two oxo.), Di-C _1-6 alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, substituted Or substituted with one or two groups selected from the group consisting of hydroxy, cyano and C _1-6 alkoxy, the same or different.), A saturated heterocyclylcarbonyl [the saturated heterocyclylcarbonyl is Unsubstituted, hydroxy, C _1-6 alkyl (wherein the C _1-6 alkyl is unsubstituted or substituted with 1 hydroxy), mono C _1-6 alkylamino, di-C substituted with _1-6 1-2 groups identical to or different selected from alkyl amino and the group consisting of C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl, the mono-C _1-6 alkylaminosulfonyl being unsubstituted or substituted with one hydroxy. Show
W represents a single bond, —O—, —NH—, —OCH ₂ — or —CH ₂ O—,
X represents a nitrogen atom or CR ²¹ ;
Y ¹ represents a nitrogen atom or CR ²² ;
Y ² represents a nitrogen atom or CR ²³ ,
Y ³ represents a nitrogen atom or CR ²⁴ ,
R ²¹ , R ²² , R ²³ and R ²⁴ are the same or different and each represents a hydrogen atom or C _1-6 alkyl;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with 1 C _1-6 alkyl). ), Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) ,
(B) -COOR ³¹ (wherein R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), C _1-6 alkoxy (the C _1-6 alkoxy is Unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (the heteroaryl is and is not substituted, it halogen atom and C _1-6 alkyl Substituted with one group selected from the group.), Heterocyclyl saturated heterocyclyl (saturated are unsubstituted or substituted, is substituted with one C _1-6 alkyl.), Mono C Substituted with 1 to 6 groups selected from the group consisting of _1-6 alkylamino, di-C _1-6 alkylamino, C _1-6 alkylsulfanyl and C _1-6 alkylsulfonyl}, C _{3- 8} cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl), aryl or saturated Of the heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with one C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with one aryl). Is replaced.),
(C) The following formula (β)

で表される５又は６員のヘテロアリール［該式（β）で表される５又は６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、ヒドロキシ及びＣ_1-6アルコキシからなる群より選ばれる１〜３個の基で置換されている。）、Ｃ_2-6アルケニル、Ｃ_2-6アルキニル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_1-6アルコキシカルボニル、モノＣ_1-6アルキルアミノカルボニル、ジＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル、モノＣ_1-6アルキルアミノ及びジＣ_1-6アルキルアミノからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。］
を示す。
ただし、下記式（Ａ）で表される構造を除く。

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1- Same or different from the group consisting of ₆ alkoxycarbonyl, mono C _1-6 alkylaminocarbonyl, di C _1-6 alkylaminocarbonyl, saturated heterocyclylcarbonyl, mono C _1-6 alkylamino and di C _1-6 alkylamino 1 chosen Substituted with three groups. ]
Indicates.
However, the structure represented by the following formula (A) is excluded.

で表される化合物又はその製薬学的に許容される塩を有効成分として含有する血糖低下作用薬を提供することである。

Or a pharmaceutically acceptable salt thereof as an active ingredient.

(2) As another aspect of the present invention,
In the general formula (I),
Substituent A is phenyl or 5- or 6-membered heteroaryl (the phenyl and 5- or 6-membered heteroaryl are unsubstituted or selected from the following substituent group Z2 in the same or different manner: 1 to 3 Substituted with 1 group.)
Indicate
Substituent group Z2 is a halogen atom, carbamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted, halogen atom, hydroxy, carbamoyl, C _1-6 alkoxy, and C Substituted with 1 to 3 groups identically or differently selected from the group consisting of _1-6 alkylsulfonyl.), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl , C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl (the mono C _{1- 6} alkylaminocarbonyl is unsubstituted or consists of hydroxy, carbamoyl, C _3-8 cycloalkyl, C _1-6 alkoxy, diC _1-6 alkylamino and C _1-6 alkylsulfonyl. A mono-C _3-8 cycloalkylaminocarbonyl, a mono-saturated heterocyclylaminocarbonyl (the mono-saturated heterocyclylaminocarbonyl is: Unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylaminocarbonyl (the di-C _1-6 alkylaminocarbonyl is unsubstituted, hydroxy, cyano and Substituted with one or two groups selected from the group consisting of C _1-6 alkoxy identically or differently.), Saturated heterocyclylcarbonyl [wherein the saturated heterocyclylcarbonyl is unsubstituted, hydroxy, C _1-6 alkyl (said C _1-6 alkyl is unsubstituted or substituted with substituted with one hydroxy.), mono-C _1-6 alkylamino Is substituted with one to two groups the same or different and selected from the group consisting of di-C _1-6 alkylamino and C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl, the mono-C _1-6 alkylaminosulfonyl being unsubstituted or substituted with one hydroxy. Show
W represents a single bond, —O—, —OCH ₂ — or —CH ₂ O—,
X represents a nitrogen atom or CR ²¹ ;
Y ¹ represents CR ²²
Y ² represents a nitrogen atom or CR ²³ ,
Y ³ represents CR ²⁴ ,
R ²¹ , R ²² , R ²³ and R ²⁴ are the same or different and each represents a hydrogen atom or C _1-6 alkyl;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with 1 C _1-6 alkyl). ), Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) ,
(B) -COOR ³¹ (wherein R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), C _1-6 alkoxy (the C _1-6 alkoxy is Unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (the heteroaryl is and is not substituted, it halogen atom and C _1-6 alkyl Substituted with one group selected from the group.), Heterocyclyl saturated heterocyclyl (saturated are unsubstituted or substituted, is substituted with one C _1-6 alkyl.), Di-C _1-6 alkylamino, and C _1-6 substituted with 1-6 substituents selected from the group consisting of alkylsulfonyl.}, C _3-8 cycloalkyl (said C _3-8 cycloalkyl, substituted Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted] 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl)].
(C) The following formula (β)

で表される５又は６員のヘテロアリール［該式（β）で表される５又は６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、ヒドロキシ及びＣ_1-6アルコキシからなる群より選ばれる１〜３個の基で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_1-6アルコキシカルボニル、飽和のヘテロシクリルカルボニル、及びジＣ_1-6アルキルアミノからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。］
を示す。
ただし、下記式（Ａ）で表される構造を除く。

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1-6 alkoxycarbonyl, saturated It is substituted with 1 to 3 groups selected from the group consisting of heterocyclylcarbonyl and diC _1-6 alkylamino, the same or different. ]
Indicates.
However, the structure represented by the following formula (A) is excluded.

を示す、（１）に記載の化合物又はその製薬学的に許容される塩を有効成分として含有する血糖低下作用薬を提供することである。

It is to provide a hypoglycemic agent containing the compound according to (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

(3) As another aspect of the present invention,
In the general formula (I),
Substituent A is phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are 1 to 3 groups that are not substituted or are the same or different from the following substituent group Z3: Has been replaced.)
Indicate
Substituent group Z3 is a halogen atom, carbamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkylsulfonyl). ), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl, saturated heterocyclyl, C _1-6 alkoxy, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylamino) The carbonyl is unsubstituted or substituted with 1 to 3 groups selected identically or differently from the group consisting of hydroxy, C _1-6 alkoxy and diC _1-6 alkylamino), di. C _1-6 alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted, is substituted with one hydroxy.), heterocyclylcarbonyl saturated [ Heterocyclylcarbonyl Saturated, unsubstituted or substituted with hydroxy, C _1-6 alkyl (said C _1-6 alkyl is unsubstituted or substituted with substituted with one hydroxy.), Di C _1- Substituted with one group selected from the group consisting of ₆ alkylamino and C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl (wherein the C _1-6 alkylsulfonyl is unsubstituted or substituted with one hydroxy), and
W represents a single bond, —O— or —OCH ₂ —;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl or C _3-8 cycloalkyl C _1-6 alkyl,
(B) -COOR ³¹ [wherein R ³¹ is C _1-6 alkyl or C _3-8 cycloalkyl (the C _1-6 alkyl and C _3-8 cycloalkyl are unsubstituted or substituted by 1 to 3 Substituted with a halogen atom)]
(C) The following formula (β)

で表される５又は６員のヘテロアリール［該式（β）で表される５又は６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１個のヒドロキシで置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ及びＣ_1-6アルコキシカルボニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。］
を示す、（１）に記載の化合物又はその製薬学的に許容される塩を提供することである。

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is a non-substituted or halogen atom, C _1-6 alkyl (the C _1-6 Alkyl is unsubstituted or substituted with one hydroxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy and C _1-6 alkoxycarbonyl It is substituted with 1 to 3 groups selected identically or differently. ]
It is providing the compound as described in (1) which shows this, or its pharmaceutically acceptable salt.

(4) As another aspect of the present invention,
The substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy). ), C _3-8 cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl Substituted), aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) Has been.)
It is to provide a hypoglycemic agent containing the compound according to either (1) or (2) or a pharmaceutically acceptable salt thereof as an active ingredient.

(5) As another aspect of the present invention,
Substituent B is (b) -COOR ³¹ (R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl.), C _1-6 alkoxy (the C _{1 -6} alkoxy is unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl And is substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (said heteroaryl is unsubstituted or substituted with a halogen atom and a C _1-6 a Substituted with one group selected from the group consisting of kill.), Heterocyclyl saturated (heterocyclyl saturation is unsubstituted or substituted, it is substituted with one C _1-6 alkyl.) Substituted with 1 to 6 groups selected from the group consisting of di-C _1-6 alkylamino, and C _1-6 alkylsulfonyl}, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl.), Aryl or saturated heterocyclyl [the saturated heterocyclyl is substituted Or is substituted with one C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with one aryl).]
It is to provide a hypoglycemic agent containing the compound according to either (1) or (2) or a pharmaceutically acceptable salt thereof as an active ingredient.

(6) As another aspect of the present invention,
Substituent B is (c) the following formula (β)

で表される５又は６員のヘテロアリール［該式（β）で表される５又は６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、ヒドロキシ及びＣ_1-6アルコキシからなる群より選ばれる１〜３個の基で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_1-6アルコキシカルボニル、飽和のヘテロシクリルカルボニル、及びジＣ_1-6アルキルアミノからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。］
を示す、（１）又は（２）のいずれかに記載の化合物又はその製薬学的に許容される塩を有効成分として含有する血糖低下作用薬を提供することである。

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1-6 alkoxycarbonyl, saturated It is substituted with 1 to 3 groups selected from the group consisting of heterocyclylcarbonyl and diC _1-6 alkylamino, the same or different. ]
It is to provide a hypoglycemic agent containing the compound according to either (1) or (2) or a pharmaceutically acceptable salt thereof as an active ingredient.

(7) As another aspect of the present invention,
Substituent B is (c) the following formula (β)

で表される５又は６員のヘテロアリール［該式（β）で表される５又は６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１個のヒドロキシで置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ及びＣ_1-6アルコキシカルボニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。］
を示す、（１）、（２）、（３）、（６）のいずれかに記載の化合物又はその製薬学的に許容される塩を有効成分として含有する血糖低下作用薬を提供することである。

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is a non-substituted or halogen atom, C _1-6 alkyl (the C _1-6 Alkyl is unsubstituted or substituted with one hydroxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy and C _1-6 alkoxycarbonyl It is substituted with 1 to 3 groups selected identically or differently. ]
By providing a hypoglycemic agent containing the compound according to any one of (1), (2), (3) and (6) or a pharmaceutically acceptable salt thereof as an active ingredient is there.

(8) As another aspect of the present invention,
Provided is a hypoglycemic agent containing as an active ingredient the compound according to any one of (1) to (7) or a pharmaceutically acceptable salt thereof, wherein Y ¹ represents CH and Y ³ represents CH. It is.

(9) As another aspect of the present invention,
It is to provide a hypoglycemic agent containing as an active ingredient the compound according to any one of (1) to (8) or a pharmaceutically acceptable salt thereof, wherein Y ² represents a nitrogen atom.

(10) As another aspect of the present invention,
An object of the present invention is to provide a hypoglycemic agent containing the compound according to any one of (1) to (9) or a pharmaceutically acceptable salt thereof as an active ingredient, wherein X represents a nitrogen atom.

  According to the present invention, it has become possible to provide a compound having an excellent GPR119 agonistic action.

  The present invention provides a compound of general formula (I) or a pharmaceutically acceptable salt thereof having an excellent GPR119 agonistic action.

  Although the compound of this invention is demonstrated in detail below, it does not specifically limit to what was illustrated.

  In the present invention, “n” is normal, “i” is iso, “s” is secondary, “t” and “tert” are tertiary, “c” is cyclo, and “o” is ortho. , “M” represents meta, and “p” represents para.

The “halogen atom” refers to a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.
“C _1-6 alkyl” refers to a linear or branched alkyl having 1 to 6 carbon atoms. For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, 2-methylbutyl, n-hexyl, isohexyl and the like can be mentioned.
“C _2-6 alkyl” refers to a linear or branched alkyl having 2 to 6 carbon atoms. For example, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, 2-methylbutyl, n-hexyl, isohexyl and the like can be mentioned.
“C _2-6 alkenyl” refers to a straight or branched alkenyl having 2 to 6 carbon atoms. Examples include ethenyl, (1E) -propenyl, 2-propenyl, (1E) -butenyl, (1E) -pentenyl, (1E) -hexenyl, isopropenyl, isobutenyl, s-butenyl, isopentenyl and the like.
“C _2-6 alkynyl” refers to linear or branched alkynyl having 2 to 6 carbon atoms. Examples include ethynyl, n-propynyl, n-butynyl, n-pentynyl, n-hexynyl and the like.
“C _3-8 cycloalkyl” refers to a cyclic alkyl having 3 to 8 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.
“Aryl” refers to a monocyclic hydrocarbon aromatic ring or condensed polycyclic aromatic hydrocarbon ring having 6 to 14 carbon atoms. For example, phenyl, naphthyl, anthryl and the like can be mentioned.
“Heteroaryl” is a 5- to 7-membered monocyclic group consisting of one or more atoms selected from the group consisting of oxygen, sulfur and nitrogen and the same or different and 1 to 6 carbon atoms. An aromatic heterocyclic ring or a condensed polycyclic aromatic heterocyclic ring composed of 9 to 14 atoms is shown. Examples include imidazolyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolyl, benzopyrazolyl, benzotriazolyl, quinolyl and the like.
“5- or 6-membered heteroaryl” refers to one or more atoms selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom, or 1 to 5 carbon atoms. Represents a monocyclic aromatic heterocyclic member. Examples include imidazolyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and the like.
“6-membered heteroaryl” is a single-membered 6-membered ring consisting of one or more atoms selected from the group consisting of oxygen, sulfur and nitrogen and the same or different and 1 to 5 carbon atoms. A cyclic aromatic heterocycle is shown. Examples include pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl and the like.
“Partially saturated heteroaryl” refers to one or more atoms selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom, or 1 to 7 carbon atoms. An 8-membered partially saturated monocyclic aromatic heterocycle is shown. For example, oxazolinyl, thiazolinyl and the like can be mentioned.
“Saturated heterocyclyl” is a 4- to 7-membered monocyclic ring composed of one or more atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom, or one to six carbon atoms. A saturated heterocyclic ring is shown. Examples include azetidinyl, pyrrolidinyl, piperidinyl, hexamethyleneiminyl, piperazinyl, pyrazolidinyl, quinuclidinyl, morpholinyl, oxetanyl, oxolanyl, oxanyl and the like.
The "C _3-8 cycloalkyl C _1-6 alkyl" refers to a C _1-6 alkyl having a substituent "C _3-8 cycloalkyl" of the. Examples thereof include cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl and the like.
“Aryl C _1-6 alkyl” refers to C _1-6 alkyl having the above “aryl” as a substituent. Examples include benzyl, phenethyl, naphthylmethyl and the like.
“Heteroaryl C _1-6 alkyl” refers to C _1-6 alkyl having the above-mentioned “heteroaryl” as a substituent. For example, 2-pyridylmethyl, 2-pyridylethyl, 2-quinolylmethyl and the like can be mentioned.
By "partially saturated heteroaryl C _1-6 alkyl" refers to a C _1-6 alkyl having said a "partially saturated heteroaryl" as a substituent. For example, oxazolinylmethyl, thiazolinylmethyl and the like can be mentioned.
"Heterocyclyl C _1-6 alkyl, saturated" refers to a C _1-6 alkyl having a substituent "heterocyclyl saturation" of the. Examples include 2-oxetanylmethyl, 2-tetrahydrofuranylmethyl, 2-tetrahydrofuranylethyl, 3-tetrahydrofuranylmethyl, 4-tetrahydropyranylmethyl and the like.
“C _1-6 alkoxy” refers to a linear or branched alkoxy having 1 to 6 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, t-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy, n-hexyloxy and the like.
“C _1-6 alkoxycarbonyl” refers to a group in which the above “C _1-6 alkoxy” is bonded to carbonyl. Examples thereof include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl and the like.
“Mono C _1-6 alkylamino” refers to an amino having one “C _1-6 alkyl” as a substituent. For example, methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, s-butylamino, t-butylamino, n-pentylamino, isopentylamino, neopentylamino, n-hexylamino , Isohexylamino and the like.
“DiC _1-6 alkylamino” refers to an amino having two of the above “C _1-6 alkyl” as the same or different substituents. For example, dimethylamino, diethylamino, di (n-propyl) amino, di (isopropyl) amino, ethylmethylamino, methyl (n-propyl) amino and the like can be mentioned.
“C _1-6 alkylcarbonyl” refers to a group in which the above “C _1-6 alkyl” is bonded to carbonyl. Examples thereof include acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, isovaleryl and the like.
“C _1-6 alkylcarbonylamino” refers to a group in which the above “C _1-6 alkylcarbonyl” and amino are bonded. Examples include acetylamino, propionylamino, butyrylamino, isobutyrylamino, pivaloylamino, valerylamino, isovalerylamino and the like.
“Mono C _1-6 alkylaminocarbonyl” refers to a group in which the above “mono C _1-6 alkylamino” is bonded to carbonyl. For example, methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, n-butylaminocarbonyl, isobutylaminocarbonyl, s-butylaminocarbonyl, t-butylaminocarbonyl, n-pentylaminocarbonyl, isopentylamino Examples include carbonyl, neopentylaminocarbonyl, n-hexylaminocarbonyl, isohexylaminocarbonyl and the like.
“Mono C _3-8 cycloalkylaminocarbonyl” refers to a group in which amino having one “C _3-8 cycloalkyl” as a substituent and carbonyl are bonded. Examples include cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl, cycloheptylaminocarbonyl, and cyclooctylaminocarbonyl.
“Mono-saturated heterocyclylaminocarbonyl” refers to a group in which amino and carbonyl having one “saturated heterocyclyl” as a substituent is bonded. Examples include pyrrolidinylaminocarbonyl, piperidinylaminocarbonyl, tetrahydrofuranylaminocarbonyl, tetrahydropyranylaminocarbonyl, tetrahydrothiophenylaminocarbonyl, tetrahydrothiopyranylaminocarbonyl and the like.
“DiC _1-6 alkylaminocarbonyl” refers to a group in which the above “diC _1-6 alkylamino” is bonded to carbonyl. Examples thereof include dimethylaminocarbonyl, diethylaminocarbonyl, di (n-propyl) aminocarbonyl, di (isopropyl) aminocarbonyl, ethylmethylaminocarbonyl, methyl (n-propyl) aminocarbonyl, isopropyl (methyl) aminocarbonyl and the like.
The “saturated heterocyclylcarbonyl” refers to a carbonyl having the above “saturated heterocyclyl” as a substituent. Examples include 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 1-hexamethyleneiminylcarbonyl, 1-piperazinylcarbonyl, morpholinocarbonyl and the like.
“C _1-6 alkylsulfanyl” refers to a group in which linear or branched alkyl having 1 to 6 carbon atoms and sulfanyl are bonded. Examples thereof include methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, isobutylsulfanyl, n-hexylsulfanyl and the like.
“C _1-6 alkylsulfonyl” refers to a group in which linear or branched alkyl having 1 to 6 carbon atoms and sulfonyl are bonded. For example, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, n-hexylsulfonyl and the like can be mentioned.
“C _1-6 alkylsulfonylamino” refers to a group in which the above “C _1-6 alkylsulfonyl” is linked to amino. For example, methylsulfonylamino, n-propylsulfonylamino, isobutylsulfonylamino, n-hexylsulfonylamino and the like can be mentioned.
“Mono C _1-6 alkylaminosulfonyl” refers to a group in which the above “mono C _1-6 alkylamino” is bonded to sulfonyl. For example, methylaminosulfonyl, ethylaminosulfonyl, n-propylaminosulfonyl, isopropylaminosulfonyl, n-butylaminosulfonyl, isobutylaminosulfonyl, s-butylaminosulfonyl, t-butylaminosulfonyl, n-pentylaminosulfonyl, isopentylamino Examples include sulfonyl, neopentylaminosulfonyl, n-hexylaminosulfonyl, isohexylaminosulfonyl and the like.
“Oxo” refers to a substituent (═O) in which an oxygen atom is substituted via a double bond. Therefore, when oxo is substituted with a carbon atom, it forms a carbonyl together with the carbon atom, and when one oxo is substituted with one sulfur atom, it forms a sulfinyl together with the sulfur atom, When two oxos are substituted with one sulfur atom, they are combined with the sulfur atom to form a sulfonyl. Specific examples of saturated heterocyclyl substituted with oxo when oxo is substituted with saturated heterocyclyl in the present invention include 2-oxopyrrolidinyl, 2-oxopiperidinyl, 1,1-dioxidetetrahydrothio Phenyl, 1-oxidetetrahydro-2H-thiopyranyl, 1,1-dioxidetetrahydro-2H-thiopyranyl, 1,1-dioxideisothiazolidinyl, 2-oxo-1,3-oxazolidinyl, 6-oxo-1, 1-dihydropyridazinyl and the like can be mentioned.
“5- or 6-membered heteroaryl represented by the formula (β)” means

酸素原子、硫黄原子及び窒素原子からなる群より同一に又は異なって選ばれる１個以上の原子と１〜５個の炭素原子からなる５又は６員の単環式芳香族複素環基を示す。例えば、オキサジアゾリル、ピリジル、ピリミジニル、ピラジニル、ピリダジニル等が挙げられる。

A 5- or 6-membered monocyclic aromatic heterocyclic group consisting of one or more atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom, or the same or different, and 1 to 5 carbon atoms. Examples include oxadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and the like.

Preferred forms of the compound of the present invention are as follows.
That is,
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Substituted with 1 to 3 groups selected from the group consisting of aminocarbonyl, saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl, the same or different;
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl, Substituted with 1 to 3 groups selected from the same or different from the group consisting of saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl;
Preferred W is a single bond or —O—.
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom;

One preferred substituent B is (b) -COOR ³¹
Preferred R ^{31 at} this time is C _1-6 alkyl;
Another preferable substituent B is (c) a 6-membered heteroaryl represented by the following formula (β) (the 6-membered heteroaryl represented by the formula (β) is not substituted or is a halogen atom) , Substituted with one group selected from the group consisting of C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy.

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferable substituent B is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, C _1-6 alkyl, C _2-6 alkenyl, C ₃ Substituted with one group selected from the group consisting of _-8 cycloalkyl and C _1-6 alkoxy.

Other preferred forms are as follows.
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Aminocarbonyl (wherein the mono C _1-6 alkylaminocarbonyl is unsubstituted or selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl, or the same or different; Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _{1- 6} alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with one or two groups selected from the group consisting of the same or different from each other), a saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with one hydroxy) And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl may be substituted, halogen atom, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl ( The mono C _1-6 alkylaminocarbonyl is an unsubstituted or 1 to 2 group selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylamino carbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with 1 to 2 groups selected more or less identically), saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with 1 hydroxy). And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Particularly preferred substituent A is phenyl (the phenyl is unsubstituted or halogen atom, carbamoyl, C _1-6 alkyl, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is Mono-saturated heterocyclyl which is unsubstituted or substituted with one or two groups selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Aminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1-2 oxo), diC _1-6 alkylaminocarbonyl (the diC _1-6 alkylaminocarbonyl is substituted with unsubstituted or substituted with one to two groups the same or different and selected from the group consisting of hydroxy and C _1-6 alkoxy Is.), Heterocyclylcarbonyl in heterocyclylcarbonyl (saturated in saturation and is not substituted is substituted with one hydroxy.) And the same or different from the group consisting of C _1-6 alkylsulfonyl Substituted with 1 to 3 groups selected from
Preferred W is a single bond or —O—.
Further preferred W is a single bond;
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom,
Further preferred X is a nitrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom,
Further preferred Y ³ is a nitrogen atom;

One preferred substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 halogen atoms), C _3-8. Cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) , Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl). Yes,
In this case, more preferred substituent B is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _3-8 cycloalkyl. C _1-6 alkyl or aryl C _1-6 alkyl;
Particularly preferred substituents B at this time are C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with one halogen atom) or C _3-8 cycloalkyl C _{1. -6} alkyl;
Another preferred substituent B is (b) -COOR ³¹
R ³¹ is preferably C _1-6 alkyl [the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is not substituted)] Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl), C _1-6 alkoxy (the C _1-6 alkoxy is not substituted, Substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or 1 to 3) And 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of halogen atoms and C _1-6 alkyl) and saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with 1 C _1-6 alkyl.) Is substituted with 1 to 6 groups selected from the group consisting of: ] C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by ],
R ³¹ is more preferably C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl [the aryl is not substituted or is a halogen atom, C _1-6 Substituted with one group selected from the group consisting of alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms) and C _1-6 alkoxy. Yes. _1-6 selected from the group consisting of heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl). Substituted with 1 group. }, C _3-8 cycloalkyl (wherein the C _3-8 cycloalkyl is unsubstituted or substituted with 1 C _1-6 alkyl) or aryl;
Particularly preferred R ^{31 at} this time is C _1-6 alkyl [the C _1-6 alkyl is unsubstituted or C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or Substituted with one C _1-6 alkyl.), Aryl, heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one halogen atom), selected from the group consisting of Substituted with one group. ];
Another preferable substituent B is (c) a 5- or 6-membered heteroaryl represented by the following formula (β) [the 5- or 6-membered heteroaryl represented by the formula (β) is not substituted. A halogen atom, carbamoyl, cyano, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (wherein the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl , Di-C _1-6 alkylaminocarbonyl and saturated heterocyclylcarbonyl substituted with 1 to 3 groups selected identically or differently. ];

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル［該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。］であり、
このとき特に好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferred substituent B is 2-pyridyl or 2-pyrimidinyl [the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, cyano, C _1-6 alkyl (the C _1-6 alkyl Is unsubstituted or substituted with 1 to 3 halogen atoms.), One selected from the group consisting of C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy Substituted with a group. ],
Particularly preferred substituent B at this time is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, or one selected from the group consisting of a halogen atom and C _1-6 alkyl) Substituted with a group).

  One preferred embodiment of the present invention is the compound shown below or a pharmaceutically acceptable salt thereof in the following formula (III).

ここで、
好ましい置換基Ａは、フェニル又は６員のヘテロアリール（該フェニル及び６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
さらに好ましい置換基Ａは、フェニル又は３−ピリジル（該フェニル及び３−ピリジルは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
好ましいＷは、単結合又は-Ｏ-であり；
置換基Ｂのひとつの好ましい態様は、（ｂ）−ＣＯＯＲ³¹であり、このとき好ましいＲ³¹はＣ_1-6アルキルであり；
置換基Ｂの他の好ましい態様は、（ｃ）下記式（β）で表される６員のヘテロアリール（該６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）であり、さらに好ましい態様は、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）である。

here,
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Substituted with 1 to 3 groups selected from the group consisting of aminocarbonyl, saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl, the same or different;
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl, Substituted with 1 to 3 groups selected from the same or different from the group consisting of saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl;
Preferred W is a single bond or —O—.
One preferred embodiment of substituent B is (b) -COOR ³¹ , wherein preferred R ³¹ is C _1-6 alkyl;
Another preferred embodiment of the substituent B is (c) a 6-membered heteroaryl represented by the following formula (β) (the 6-membered heteroaryl is an unsubstituted, halogen atom, C _1-6 alkyl) , C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy are substituted with one group selected from the group consisting of 2-pyridyl and 2- Pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are unsubstituted or selected from the group consisting of halogen atoms, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy) Substituted with one group).

Another preferred form is the compound shown below or a pharmaceutically acceptable salt thereof in the above formula (III).
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Aminocarbonyl (wherein the mono C _1-6 alkylaminocarbonyl is unsubstituted or selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl, or the same or different; Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _{1- 6} alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with one or two groups selected from the group consisting of the same or different from each other), a saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with one hydroxy) And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl may be substituted, halogen atom, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl ( The mono C _1-6 alkylaminocarbonyl is an unsubstituted or 1 to 2 group selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylamino carbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with 1 to 2 groups selected more or less identically), saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with 1 hydroxy). And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Particularly preferred substituent A is phenyl (the phenyl is unsubstituted or halogen atom, carbamoyl, C _1-6 alkyl, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is Mono-saturated heterocyclyl which is unsubstituted or substituted with one or two groups selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Aminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1-2 oxo), diC _1-6 alkylaminocarbonyl (the diC _1-6 alkylaminocarbonyl is substituted with unsubstituted or substituted with one to two groups the same or different and selected from the group consisting of hydroxy and C _1-6 alkoxy Is.), Heterocyclylcarbonyl in heterocyclylcarbonyl (saturated in saturation and is not substituted is substituted with one hydroxy.) And the same or different from the group consisting of C _1-6 alkylsulfonyl Substituted with 1 to 3 groups selected from
Preferred W is a single bond or —O—.
Further preferred W is a single bond;
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom,
Further preferred X is a nitrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom,
Further preferred Y ³ is a nitrogen atom;

One preferred substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 halogen atoms), C _3-8. Cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) , Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl). Yes,
In this case, more preferred substituent B is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _3-8 cycloalkyl. C _1-6 alkyl or aryl C _1-6 alkyl;
Particularly preferred substituents B at this time are C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with one halogen atom) or C _3-8 cycloalkyl C _{1. -6} alkyl;
Another preferred substituent B is (b) -COOR ³¹
R ³¹ is preferably C _1-6 alkyl [the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is not substituted)] Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl), C _1-6 alkoxy (the C _1-6 alkoxy is not substituted, Substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or 1 to 3) And 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of halogen atoms and C _1-6 alkyl) and saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with 1 C _1-6 alkyl.) Is substituted with 1 to 6 groups selected from the group consisting of: ] C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by ],
R ³¹ is more preferably C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl [the aryl is not substituted or is a halogen atom, C _1-6 Substituted with one group selected from the group consisting of alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms) and C _1-6 alkoxy. Yes. _1-6 selected from the group consisting of heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl). Substituted with 1 group. }, C _3-8 cycloalkyl (wherein the C _3-8 cycloalkyl is unsubstituted or substituted with 1 C _1-6 alkyl) or aryl;
Particularly preferred R ^{31 at} this time is C _1-6 alkyl [the C _1-6 alkyl is unsubstituted or C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or Substituted with one C _1-6 alkyl.), Aryl, heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one halogen atom), selected from the group consisting of Substituted with one group. ];
Another preferable substituent B is (c) a 5- or 6-membered heteroaryl represented by the following formula (β) [the 5- or 6-membered heteroaryl represented by the formula (β) is not substituted. A halogen atom, carbamoyl, cyano, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (wherein the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl , Di-C _1-6 alkylaminocarbonyl and saturated heterocyclylcarbonyl substituted with 1 to 3 groups selected identically or differently. ];

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル［該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。］であり、
このとき特に好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferred substituent B is 2-pyridyl or 2-pyrimidinyl [the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, cyano, C _1-6 alkyl (the C _1-6 alkyl Is unsubstituted or substituted with 1 to 3 halogen atoms.), One selected from the group consisting of C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy Substituted with a group. ],
Particularly preferred substituent B at this time is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, or one selected from the group consisting of a halogen atom and C _1-6 alkyl) Substituted with a group).

  Another preferred embodiment of the present invention is the compound shown below or a pharmaceutically acceptable salt thereof in the following formula (IV).

ここで、
好ましい置換基Ａは、フェニル又は６員のヘテロアリール（該フェニル及び６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
さらに好ましい置換基Ａは、フェニル又は３−ピリジル（該フェニル及び３−ピリジルは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
好ましいＷは、単結合又は-Ｏ-であり；
置換基Ｂのひとつの好ましい態様は、（ｂ）−ＣＯＯＲ³¹であり、このとき好ましいＲ³¹はＣ_1-6アルキルであり；
置換基Ｂの他の好ましい態様は、（ｃ）下記式（β）で表される６員のヘテロアリール（該６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）であり、さらに好ましい態様は、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）である。

here,
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Substituted with 1 to 3 groups selected from the group consisting of aminocarbonyl, saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl, the same or different;
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl, Substituted with 1 to 3 groups selected from the same or different from the group consisting of saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl;
Preferred W is a single bond or —O—.
One preferred embodiment of substituent B is (b) -COOR ³¹ , wherein preferred R ³¹ is C _1-6 alkyl;
Another preferred embodiment of the substituent B is (c) a 6-membered heteroaryl represented by the following formula (β) (the 6-membered heteroaryl is an unsubstituted, halogen atom, C _1-6 alkyl) , C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy are substituted with one group selected from the group consisting of 2-pyridyl and 2- Pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are unsubstituted or selected from the group consisting of halogen atoms, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy) Substituted with one group).

Another preferred form is the compound shown below or a pharmaceutically acceptable salt thereof in the above formula (IV).
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Aminocarbonyl (wherein the mono C _1-6 alkylaminocarbonyl is unsubstituted or selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl, or the same or different; Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _{1- 6} alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with one or two groups selected from the group consisting of the same or different from each other), a saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with one hydroxy) And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl may be substituted, halogen atom, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl ( The mono C _1-6 alkylaminocarbonyl is an unsubstituted or 1 to 2 group selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylamino carbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with 1 to 2 groups selected more or less identically), saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with 1 hydroxy). And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Particularly preferred substituent A is phenyl (the phenyl is unsubstituted or halogen atom, carbamoyl, C _1-6 alkyl, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is Mono-saturated heterocyclyl which is unsubstituted or substituted with one or two groups selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Aminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1-2 oxo), diC _1-6 alkylaminocarbonyl (the diC _1-6 alkylaminocarbonyl is substituted with unsubstituted or substituted with one to two groups the same or different and selected from the group consisting of hydroxy and C _1-6 alkoxy Is.), Heterocyclylcarbonyl in heterocyclylcarbonyl (saturated in saturation and is not substituted is substituted with one hydroxy.) And the same or different from the group consisting of C _1-6 alkylsulfonyl Substituted with 1 to 3 groups selected from
Preferred W is a single bond or —O—.
Further preferred W is a single bond;
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom,
Further preferred X is a nitrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom,
Further preferred Y ³ is a nitrogen atom;

One preferred substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 halogen atoms), C _3-8. Cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) , Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl). Yes,
In this case, more preferred substituent B is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _3-8 cycloalkyl. C _1-6 alkyl or aryl C _1-6 alkyl;
Particularly preferred substituents B at this time are C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with one halogen atom) or C _3-8 cycloalkyl C _{1. -6} alkyl;
Another preferred substituent B is (b) -COOR ³¹
R ³¹ is preferably C _1-6 alkyl [the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is not substituted)] Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl), C _1-6 alkoxy (the C _1-6 alkoxy is not substituted, Substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or 1 to 3) And 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of halogen atoms and C _1-6 alkyl) and saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with 1 C _1-6 alkyl.) Is substituted with 1 to 6 groups selected from the group consisting of: ] C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by ],
R ³¹ is more preferably C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl [the aryl is not substituted or is a halogen atom, C _1-6 Substituted with one group selected from the group consisting of alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms) and C _1-6 alkoxy. Yes. _1-6 selected from the group consisting of heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl). Substituted with 1 group. }, C _3-8 cycloalkyl (wherein the C _3-8 cycloalkyl is unsubstituted or substituted with 1 C _1-6 alkyl) or aryl;
Particularly preferred R ^{31 at} this time is C _1-6 alkyl [the C _1-6 alkyl is unsubstituted or C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or Substituted with one C _1-6 alkyl.), Aryl, heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one halogen atom), selected from the group consisting of Substituted with one group. ];
Another preferable substituent B is (c) a 5- or 6-membered heteroaryl represented by the following formula (β) [the 5- or 6-membered heteroaryl represented by the formula (β) is not substituted. A halogen atom, carbamoyl, cyano, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (wherein the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl , Di-C _1-6 alkylaminocarbonyl and saturated heterocyclylcarbonyl substituted with 1 to 3 groups selected identically or differently. ];

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル［該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。］であり、
このとき特に好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferred substituent B is 2-pyridyl or 2-pyrimidinyl [the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, cyano, C _1-6 alkyl (the C _1-6 alkyl Is unsubstituted or substituted with 1 to 3 halogen atoms.), One selected from the group consisting of C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy Substituted with a group. ],
Particularly preferred substituent B at this time is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, or one selected from the group consisting of a halogen atom and C _1-6 alkyl) Substituted with a group).

  Another preferred embodiment of the present invention is the compound shown below or a pharmaceutically acceptable salt thereof in the following formula (V).

ここで、
好ましい置換基Ａは、フェニル又は６員のヘテロアリール（該フェニル及び６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
さらに好ましい置換基Ａは、フェニル又は３−ピリジル（該フェニル及び３−ピリジルは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
好ましいＷは、単結合又は-Ｏ-であり；
置換基Ｂのひとつの好ましい態様は、（ｂ）−ＣＯＯＲ³¹であり、このとき好ましいＲ³¹はＣ_1-6アルキルであり；
置換基Ｂの他の好ましい態様は、（ｃ）下記式（β）で表される６員のヘテロアリール（該６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）であり、さらに好ましい態様は、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）である。

here,
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Substituted with 1 to 3 groups selected from the group consisting of aminocarbonyl, saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl, the same or different;
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl, Substituted with 1 to 3 groups selected from the same or different from the group consisting of saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl;
Preferred W is a single bond or —O—.
One preferred embodiment of substituent B is (b) -COOR ³¹ , wherein preferred R ³¹ is C _1-6 alkyl;
Another preferred embodiment of the substituent B is (c) a 6-membered heteroaryl represented by the following formula (β) (the 6-membered heteroaryl is an unsubstituted, halogen atom, C _1-6 alkyl) , C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy are substituted with one group selected from the group consisting of 2-pyridyl and 2- Pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are unsubstituted or selected from the group consisting of halogen atoms, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy) Substituted with one group).

Another preferred form is the compound shown below or a pharmaceutically acceptable salt thereof in the above formula (V).
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Aminocarbonyl (wherein the mono C _1-6 alkylaminocarbonyl is unsubstituted or selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl, or the same or different; Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _{1- 6} alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with one or two groups selected from the group consisting of the same or different from each other), a saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with one hydroxy) And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl may be substituted, halogen atom, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl ( The mono C _1-6 alkylaminocarbonyl is an unsubstituted or 1 to 2 group selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylamino carbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with 1 to 2 groups selected more or less identically), saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with 1 hydroxy). And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Particularly preferred substituent A is phenyl (the phenyl is unsubstituted or halogen atom, carbamoyl, C _1-6 alkyl, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is Mono-saturated heterocyclyl which is unsubstituted or substituted with one or two groups selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Aminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1-2 oxo), diC _1-6 alkylaminocarbonyl (the diC _1-6 alkylaminocarbonyl is substituted with unsubstituted or substituted with one to two groups the same or different and selected from the group consisting of hydroxy and C _1-6 alkoxy Is.), Heterocyclylcarbonyl in heterocyclylcarbonyl (saturated in saturation and is not substituted is substituted with one hydroxy.) And the same or different from the group consisting of C _1-6 alkylsulfonyl Substituted with 1 to 3 groups selected from
Preferred W is a single bond or —O—.
Further preferred W is a single bond;
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom,
Further preferred X is a nitrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom,
Further preferred Y ³ is a nitrogen atom;

One preferred substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 halogen atoms), C _3-8. Cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) , Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl). Yes,
In this case, more preferred substituent B is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _3-8 cycloalkyl. C _1-6 alkyl or aryl C _1-6 alkyl;
Particularly preferred substituents B at this time are C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with one halogen atom) or C _3-8 cycloalkyl C _{1. -6} alkyl;
Another preferred substituent B is (b) -COOR ³¹
R ³¹ is preferably C _1-6 alkyl [the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is not substituted)] Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl), C _1-6 alkoxy (the C _1-6 alkoxy is not substituted, Substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or 1 to 3) And 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of halogen atoms and C _1-6 alkyl) and saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with 1 C _1-6 alkyl.) Is substituted with 1 to 6 groups selected from the group consisting of: ] C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by ],
R ³¹ is more preferably C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl [the aryl is not substituted or is a halogen atom, C _1-6 Substituted with one group selected from the group consisting of alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms) and C _1-6 alkoxy. Yes. _1-6 selected from the group consisting of heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl). Substituted with 1 group. }, C _3-8 cycloalkyl (wherein the C _3-8 cycloalkyl is unsubstituted or substituted with 1 C _1-6 alkyl) or aryl;
Particularly preferred R ^{31 at} this time is C _1-6 alkyl [the C _1-6 alkyl is unsubstituted or C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or Substituted with one C _1-6 alkyl.), Aryl, heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one halogen atom), selected from the group consisting of Substituted with one group. ];
Another preferable substituent B is (c) a 5- or 6-membered heteroaryl represented by the following formula (β) [the 5- or 6-membered heteroaryl represented by the formula (β) is not substituted. A halogen atom, carbamoyl, cyano, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (wherein the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl , Di-C _1-6 alkylaminocarbonyl and saturated heterocyclylcarbonyl substituted with 1 to 3 groups selected identically or differently. ];

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル［該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。］であり、
このとき特に好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferred substituent B is 2-pyridyl or 2-pyrimidinyl [the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, cyano, C _1-6 alkyl (the C _1-6 alkyl Is unsubstituted or substituted with 1 to 3 halogen atoms.), One selected from the group consisting of C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy Substituted with a group. ],
Particularly preferred substituent B at this time is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, or one selected from the group consisting of a halogen atom and C _1-6 alkyl) Substituted with a group).

  Another preferred embodiment of the present invention is the compound shown below or a pharmaceutically acceptable salt thereof in the following formula (VI).

ここで、
好ましい置換基Ａは、フェニル又は６員のヘテロアリール（該フェニル及び６員のヘテロアリールは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
さらに好ましい置換基Ａは、フェニル又は３−ピリジル（該フェニル及び３−ピリジルは、置換されていないか、ハロゲン原子、カルバモイル、Ｃ_1-6アルキル、ヘテロアリール、モノＣ_1-6アルキルアミノカルボニル、飽和のヘテロシクリルカルボニル及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）であり；
好ましいＷは、単結合又は-Ｏ-であり；
置換基Ｂのひとつの好ましい態様は、（ｂ）−ＣＯＯＲ³¹であり、このとき好ましいＲ³¹はＣ_1-6アルキルであり；
置換基Ｂの他の好ましい態様は、（ｃ）下記式（β）で表される６員のヘテロアリール（該６員のヘテロアリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）であり、さらに好ましい態様は、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。）である。

here,
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Substituted with 1 to 3 groups selected from the group consisting of aminocarbonyl, saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl, the same or different;
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl, Substituted with 1 to 3 groups selected from the same or different from the group consisting of saturated heterocyclylcarbonyl and C _1-6 alkylsulfonyl;
Preferred W is a single bond or —O—.
One preferred embodiment of substituent B is (b) -COOR ³¹ , wherein preferred R ³¹ is C _1-6 alkyl;
Another preferred embodiment of the substituent B is (c) a 6-membered heteroaryl represented by the following formula (β) (the 6-membered heteroaryl is an unsubstituted, halogen atom, C _1-6 alkyl) , C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy are substituted with one group selected from the group consisting of 2-pyridyl and 2- Pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are unsubstituted or selected from the group consisting of halogen atoms, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy) Substituted with one group).

Another preferred form is the compound shown below or a pharmaceutically acceptable salt thereof in the above formula (VI).
Preferred substituents A are phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are unsubstituted or halogen atoms, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkyl Aminocarbonyl (wherein the mono C _1-6 alkylaminocarbonyl is unsubstituted or selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl, or the same or different; Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _{1- 6} alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with one or two groups selected from the group consisting of the same or different from each other), a saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with one hydroxy) And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Further preferred substituent A is phenyl or 3-pyridyl (the phenyl and 3-pyridyl may be substituted, halogen atom, carbamoyl, C _1-6 alkyl, heteroaryl, mono C _1-6 alkylaminocarbonyl ( The mono C _1-6 alkylaminocarbonyl is an unsubstituted or 1 to 2 group selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Monosaturated heterocyclylaminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylamino carbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted with hydroxy and C _1-6 alkoxy Substituted with 1 to 2 groups selected more or less identically), saturated heterocyclylcarbonyl (the saturated heterocyclylcarbonyl is unsubstituted or substituted with 1 hydroxy). And 1 to 3 groups selected identically or differently from the group consisting of C _1-6 alkylsulfonyl).
Particularly preferred substituent A is phenyl (the phenyl is unsubstituted or halogen atom, carbamoyl, C _1-6 alkyl, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is Mono-saturated heterocyclyl which is unsubstituted or substituted with one or two groups selected from the group consisting of hydroxy, carbamoyl, C _1-6 alkoxy and C _1-6 alkylsulfonyl. Aminocarbonyl (the monosaturated heterocyclylaminocarbonyl is unsubstituted or substituted with 1-2 oxo), diC _1-6 alkylaminocarbonyl (the diC _1-6 alkylaminocarbonyl is substituted with unsubstituted or substituted with one to two groups the same or different and selected from the group consisting of hydroxy and C _1-6 alkoxy Is.), Heterocyclylcarbonyl in heterocyclylcarbonyl (saturated in saturation and is not substituted is substituted with one hydroxy.) And the same or different from the group consisting of C _1-6 alkylsulfonyl Substituted with 1 to 3 groups selected from
Preferred W is a single bond or —O—.
Further preferred W is a single bond;
Preferred X is a nitrogen atom or CR ²¹ ,
Preferred R ^{21 at} this time is a hydrogen atom,
Further preferred X is a nitrogen atom;
Preferred Y ¹ is CR ²²
Preferred R ^{22 at} this time is a hydrogen atom;
Preferred Y ² is a nitrogen atom or CR ²³ ,
Preferred R ^{23 at} this time is a hydrogen atom;
Further preferred Y ² is a nitrogen atom;
Preferred Y ³ is a nitrogen atom or CR ²⁴ ,
Preferred R ^{24 at} this time is a hydrogen atom,
Further preferred Y ³ is a nitrogen atom;

One preferred substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 halogen atoms), C _3-8. Cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) , Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl). Yes,
In this case, more preferred substituent B is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _3-8 cycloalkyl. C _1-6 alkyl or aryl C _1-6 alkyl;
Particularly preferred substituents B at this time are C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with one halogen atom) or C _3-8 cycloalkyl C _{1. -6} alkyl;
Another preferred substituent B is (b) -COOR ³¹
R ³¹ is preferably C _1-6 alkyl [the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is not substituted)] Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl), C _1-6 alkoxy (the C _1-6 alkoxy is not substituted, Substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or 1 to 3) And 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of halogen atoms and C _1-6 alkyl) and saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with 1 C _1-6 alkyl.) Is substituted with 1 to 6 groups selected from the group consisting of: ] C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by ],
R ³¹ is more preferably C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl [the aryl is not substituted or is a halogen atom, C _1-6 Substituted with one group selected from the group consisting of alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms) and C _1-6 alkoxy. Yes. _1-6 selected from the group consisting of heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl). Substituted with 1 group. }, C _3-8 cycloalkyl (wherein the C _3-8 cycloalkyl is unsubstituted or substituted with 1 C _1-6 alkyl) or aryl;
Particularly preferred R ^{31 at} this time is C _1-6 alkyl [the C _1-6 alkyl is unsubstituted or C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or Substituted with one C _1-6 alkyl.), Aryl, heteroaryl (wherein the heteroaryl is unsubstituted or substituted with one halogen atom), selected from the group consisting of Substituted with one group. ];
Another preferable substituent B is (c) a 5- or 6-membered heteroaryl represented by the following formula (β) [the 5- or 6-membered heteroaryl represented by the formula (β) is not substituted. A halogen atom, carbamoyl, cyano, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 to 3 halogen atoms), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (wherein the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl , Di-C _1-6 alkylaminocarbonyl and saturated heterocyclylcarbonyl substituted with 1 to 3 groups selected identically or differently. ];

このときさらに好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル［該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）、Ｃ_2-6アルケニル、Ｃ_3-8シクロアルキル及びＣ_1-6アルコキシからなる群より選ばれる１個の基で置換されている。］であり、
このとき特に好ましい置換基Ｂは、２−ピリジル又は２−ピリミジニル（該２−ピリジル及び２−ピリミジニルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）である。

In this case, more preferred substituent B is 2-pyridyl or 2-pyrimidinyl [the 2-pyridyl and 2-pyrimidinyl are not substituted, halogen atom, cyano, C _1-6 alkyl (the C _1-6 alkyl Is unsubstituted or substituted with 1 to 3 halogen atoms.), One selected from the group consisting of C _2-6 alkenyl, C _3-8 cycloalkyl and C _1-6 alkoxy Substituted with a group. ],
Particularly preferred substituent B at this time is 2-pyridyl or 2-pyrimidinyl (the 2-pyridyl and 2-pyrimidinyl are not substituted, or one selected from the group consisting of a halogen atom and C _1-6 alkyl) Substituted with a group).

  The compound of the present invention is a compound having a condensed heterocyclic ring, and may be a pharmaceutically acceptable salt thereof (hereinafter referred to as “the compound of the present invention” as appropriate).

  Examples of pharmaceutically acceptable salts include hydrochlorides, hydrobromides, hydroiodides, phosphates, sulfates, nitrates, mineral salts such as methanesulfonate, ethanesulfone, and the like. Acid salt, benzenesulfonate, p-toluenesulfonate, sulfonate such as trifluoromethanesulfonate, oxalate, tartrate, citrate, maleate, succinate, acetate, benzoate Acid addition salts such as acid salts, mandelate, ascorbate, lactate, gluconate, malate, glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, aspartic acid Amino acid salts such as salts, or inorganic or ammonium salts such as lithium salts, sodium salts, potassium salts, calcium salts, magnesium salts, triethylamine salts, Isopropylamine salt, salts with organic bases such as cyclohexylamine salts. The salt includes a hydrated salt.

  The compounds of the present invention may have asymmetric centers, in which case various optical isomers exist. Thus, the compounds of the present invention may exist as separate optically active forms of (R) and (S) and as racemates or (RS) mixtures. In addition, in the case of a compound having two or more asymmetric centers, diastereomers by respective optical isomerism also exist. The compounds of the present invention also include those containing all these types in any proportion. For example, diastereomers can be separated by methods well known to those skilled in the art, such as fractional crystallization, and optically active forms can be obtained by organic chemistry techniques well known for this purpose. it can. The compound of the present invention may have geometric isomers such as cis isomer and trans isomer. The compound of the present invention includes those isomers and those containing these isomers in an arbitrary ratio.

The compound of the present invention has a GPR119 agonistic action. Therefore, the compound of the present invention causes pancreatic β cell GLP-1 receptor activation through direct activation of pancreatic β cell GPR119 or small intestine GLP-1 secretion, and increases insulin secretion from pancreatic β cells in a hyperglycemic-dependent manner. Can correct hyperglycemia. In addition, pancreatic β-cell dysfunction and exhaustion are alleviated or improved by pancreatic β-cell protective action through activation of pancreatic β-cell GPR119. Therefore, it can be used as a new drug therapy having a different mechanism of action from existing anti-diabetic drugs. Diabetes includes type I diabetes, type II diabetes, and other diabetes due to specific causes.
The compound of the present invention can also be used for the treatment or prevention of diabetes-related diseases such as obesity, hyperlipidemia, hypertension, metabolic syndrome, edema, hyperuricemia, and gout.
Since the compound of the present invention has a pancreatic β-cell protective action, it can be used to improve the prognosis at the time of islet transplantation.
In addition, the compounds of the present invention include ketoacidosis, microangiopathy (retinopathy, nephropathy), arteriosclerosis (atherosclerosis, myocardial infarction, cerebral infarction, peripheral artery occlusion, etc.), neuropathy (sensory nerve, motor Nerves, autonomic nerves, etc.), foot gangrene, infections and other diabetic complications.
The compound of the present invention can also be used in combination with a therapeutic agent for diabetes, a therapeutic agent for diabetic complications, a therapeutic agent for hyperlipidemia, a therapeutic agent for hypertension and the like having a different mechanism of action other than the GPR119 agonistic action. By combining the compound of the present invention with other drugs, an additive effect can be expected when used in combination with the above-mentioned diseases rather than the effects obtained with a single agent.

Examples of antidiabetics and diabetic complications that can be used in combination include insulin preparations, insulin fragments or derivatives (INS-1), oral insulin preparations, insulin resistance improving drugs (PPARγ agonists, PPARα / γ agonists, PPARδ). Agonists, PPARα / γ / δ agonists, etc.) (eg, pioglitazone, rosiglitazone, GW-501516, GW-590735, ABT-335, AZD-6610, AVE-8133), α-glucosidase inhibitors (eg, voglibose, acarbose, Miglitol), biguanide drugs (eg, metformin, buformin, phenformin), insulin secretagogues (eg, glibenclamide, glimepiride, repaglinide, nateglinide, mitiglinide), glucagon receptor antagonist , Insulin receptor kinase promoter, dipeptidyl peptidase IV inhibitor (eg, vildagliptin, alogliptin, sitagliptin, linagliptin, saxagliptin), SGLT inhibitor (eg, sagliflozin, canagliflozin, dapagliflozin, TS-071, ASP -1941), PTP1b inhibitors (eg, sodium vanadate), glucose 6 phosphatase inhibitors, glycogen phosphorylase inhibitors (eg, PSN-357, FR-258900), FBPase inhibitors (eg, MB-07803), PEPCK inhibition Drug, pyruvate dehydrogenase kinase inhibitor, D-kaileunositol, GSK3 inhibitor, GLP-1 agonist (eg, liraglutide, exenatide), GIP agonist, amylin agonist (eg, Plumlintide), somatostatin receptor agonist, glucocorticoid receptor antagonist, 11 beta HSD1 inhibitor (eg, AMG-221, INCB-13739), protein kinase C inhibitor (eg, ruboxistaurin), IKKβ inhibitor, beta 3-adrenergic receptor agonist (eg, AJ-9679), phosphatidylinositol kinase inhibitor, phosphatidylinositol phosphatase inhibitor, ACC inhibitor, GPR40 receptor agonist, GPR120 receptor agonist, TGR5 receptor agonist, AMPK activity And glucokinase activators, FGF21, FGF analogs, aldose reductase inhibitors, AGE inhibitors and the like.
Examples of diabetes-related diseases that can be used in combination include HMG-CoA reductase inhibitors, squalene synthase inhibitors, bile acid adsorbents, IBAT inhibitors, CETP inhibitors, CPT inhibitors, fibrate drugs, ACAT Inhibitor, MGAT inhibitor, DGAT inhibitor, cholesterol absorption inhibitor, pancreatic lipase inhibitor, MTP inhibitor, nicotinic acid derivative, LXR agonist, LDL receptor promoter, angiotensin converting enzyme inhibitor, angiotensin II antagonist, diuretic , Calcium antagonists, endothelin converting enzyme inhibitors, endothelin receptor antagonists, appetite suppressants, uric acid production inhibitors, uric acid excretion promoters, and the like.

  The compound of the present invention can be administered alone or in combination with a pharmaceutically or pharmaceutically acceptable carrier or diluent.

  In order to use the compound of the present invention as a medicine, any form of a solid composition, a liquid composition and other compositions may be used, and the optimum one is selected as necessary. The medicament of the present invention can be produced by blending the compound of the present invention with a pharmaceutically acceptable carrier. Specifically, conventional excipients, extenders, binders, disintegrants, coating agents, sugar coatings, pH adjusters, solubilizers or aqueous or non-aqueous solvents are added, and tablets are prepared by conventional pharmaceutical techniques. Pills, capsules, granules, powders, powders, solutions, emulsions, suspensions, injections, and the like. Examples of excipients and extenders include lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, olive oil, sesame oil, cocoa butter, ethylene glycol, and other commonly used ones. it can.

  The compound of the present invention can be formulated by forming an inclusion compound with α, β, γ-cyclodextrin, methylated cyclodextrin or the like.

  When the compound of the present invention is used as a GPR119 agonist or the like, the compound of the present invention may be orally or parenterally administered as it is. Moreover, you may administer orally or parenterally as an agent which contains this invention compound as an active ingredient. Parenteral administration includes intravenous administration, nasal administration, transdermal administration, subcutaneous administration, intramuscular administration, and sublingual administration.

  The dose of the compound of the present invention varies depending on the administration subject, administration route, target disease, symptom and the like. For example, when orally administered to an adult diabetic patient, the dose is usually 0.1 mg to 1000 mg, preferably 1 mg. It is desirable to administer this amount once to three times a day.

  In order to evaluate the agonistic action of GPR119 of the compound of the present invention, for example, it can be carried out according to a known technique such as the method described in the test method.

  Although the manufacturing method of the compound concerning this compound is demonstrated in detail, it does not specifically limit to what was illustrated. Moreover, the solvent used for the reaction is not particularly limited as long as it does not inhibit each reaction.

  Hereafter, the manufacturing method of compound (I) is demonstrated.

  Compound (I) can be produced by a method known per se, for example, the production methods 1 to 12 shown below or a method analogous thereto. In each of the following production methods, the raw material compound may be used as a salt, and examples thereof include the above-mentioned “pharmaceutically acceptable salts”.

Among the compounds (I) of the present invention, compound (I-2) in which X is CR ²¹ and W is a single bond can be produced, for example, by the following production method 1, production method 2, or a method analogous thereto.
Production method 1:

[式中、Ｕａ、Ｕｄはハロゲン原子を、Ｕｂは脱離基又はヒドロキシを、Ｕｃはボロン酸エステル又はボロン酸を、その他の記号は前記と同意義を示す。]
Ｕａ、Ｕｄで示される「ハロゲン原子」としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられる。
Ｕｂで示される「脱離基」としては、例えば、塩素原子、臭素原子、ヨウ素原子、メタンスルホニルオキシ、ｐ−トルエンスルホニルオキシ、トリフルオロメタンスルホニルオキシ、ベンゼンスルホニルオキシ等が挙げられる。

[Wherein Ua and Ud are halogen atoms, Ub is a leaving group or hydroxy, Uc is a boronic acid ester or boronic acid, and other symbols are as defined above. ]
Examples of the “halogen atom” represented by Ua and Ud include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
Examples of the “leaving group” represented by Ub include a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, p-toluenesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy and the like.

[Step 1]
This step is a method for producing compound (1-b) from compound (1-a).
This step is a known method, for example, Bioorganic & Medicinal Chemistry Letters, 2007, 15, 2441-2452, Tetrahedron Letters, 2002, 43, 2695-2697, Synthesis, 2006, 20, 3506-3514, WO 2008/088692 and the like. It can carry out by the method of description or a method according to it.
Examples of the reagent used in this step include alkali metal nitrites such as sodium nitrite, nitrites such as t-butyl nitrite and isoamyl nitrite. The amount of the reagent used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-a).
Examples of the solvent used in the reaction include acidic solvents such as an acetic acid-water mixed solvent, a trifluoroacetic acid-water mixed solvent, hydrochloric acid, and an aqueous sulfuric acid solution, and these solvents may be mixed and used at an appropriate ratio.
These reactions can be usually performed at −30 ° C. to reflux temperature for 1 to 24 hours.

[Step 2]
This step is a method for producing compound (1-d) by reacting compound (1-b) with compound (1-c).
When Ub of compound (1-c) is a leaving group, this reaction can be performed in the presence of a base.
The amount of (1-c) in the compound used in this step is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the base used are usually tertiary aliphatic amines such as triethylamine, N, N-diisopropylethylamine, 1,8-diazabicyclo [4,3,0] undec-7-ene, and hydrogen such as sodium hydride. Alkali metal hydroxides such as alkali metal halides and potassium hydroxide, alkali metal carbonates such as cesium carbonate, potassium carbonate and sodium carbonate, alkali metal alkoxides such as potassium t-butoxide and the like. The amount of the base used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the solvent used in the reaction include solvents that do not participate in the reaction, such as tetrahydrofuran, dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, and N-methylpyrrolidone. May be used as a mixture.
These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.
When Ub of the compound (1-c) is hydroxy, this reaction can be carried out using a known method, so-called Mitsunobu reaction (Synthesis, 1981, 1-28) or a method analogous thereto.
The amount of (1-c) in the compound used in this step is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the azo compound to be used usually include diethyl azodicarboxylate, diisopropyl azodicarboxylate, 1,1′-azobis (N, N-dimethylformamide) and the like. The amount of the azo compound used is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the phosphine compound used usually include triphenylphosphine and tributylphosphine. The amount of the phosphine compound used is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the solvent used in the reaction include solvents that do not participate in the reaction such as tetrahydrofuran, 1,4-dioxane, diethyl ether, chloroform, dichloromethane, toluene, N, N-dimethylformamide, dimethyl sulfoxide, and the like. You may mix and use by the ratio.
These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.
Alternatively, this step can be performed using a method described in the literature (Tetrahedron Letters, 1995, 36, 2531-2534, Tetrahedron Letters, 1996, 37, 2463-2466).
Examples of the reagent used in this step include (cyanomethylene) trimethylphosphorane, (cyanomethylene) tributylphosphorane, and the like. The amount of the reagent used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-b).
Examples of the solvent used for the reaction include the same solvents as described above.
These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.

[Step 3]
This step is a method for producing compound (I-2) by reacting compound (1-d) with compound (1-e).
This reaction is a so-called Suzuki-Miyaura coupling reaction in the presence of a palladium catalyst and a base (Tetrahedron Letters, 1979, 20, 3437-3440, Chemical reviews, 1995, 95, 2457-2483) or It can carry out by the method according to it.
The amount of (1-e) in the compound used in this step is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the palladium catalyst used include tetrakis (triphenylphosphine) palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex, bis (triphenylphosphine) palladium (II ) Dichloride and the like. The amount of the palladium catalyst to be used is generally 0.01 to 0.5 equivalent, preferably 0.05 to 0.3 equivalent, relative to 1 equivalent of compound (1-d).
Examples of the base to be used include alkali metal carbonates such as potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate and aqueous solutions thereof, potassium fluoride, cesium fluoride, triethylamine and the like. The amount of the base used is usually 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the solvent used in the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, ethanol and the like, which are not involved in the reaction. May be mixed and used at an appropriate ratio.
These reactions can usually be performed at room temperature to 180 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.
The compound (I-2) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

[Step 4]
This step is a method for producing compound (1-f) from compound (1-d).
When Uc of compound (1-f) is a boronic ester, this reaction can be carried out by a known method (Journal of Organic Chemistry, 1995, 60, 7508-7510) or a method analogous thereto.
The amount of bis (pinacolato) diboron used in this step is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the palladium catalyst used usually include tetrakis (triphenylphosphine) palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride, dichloromethane complex, and the like. The amount of the palladium catalyst to be used is generally 0.01 to 1 equivalent, preferably 0.05 to 0.5 equivalent, relative to 1 equivalent of compound (1-d).
Examples of the base used usually include potassium acetate and triethylamine. The amount of the base used is usually 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the solvent used in the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, N, N-dimethylacetamide and other solvents that do not participate in the reaction. These solvents may be mixed and used at an appropriate ratio.
These reactions can usually be performed at room temperature to 120 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.
Alternatively, this reaction can be performed by a known method (Journal of the American Chemical Society, 2002, 124, 13179-13184) or a method analogous thereto.
The amount of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane used in this step is 1 to 5 equivalents relative to 1 equivalent of compound (1-d), Preferably 1.1 to 2.5 equivalents.
Examples of the base to be used usually include n-butyl lithium and t-butyl lithium. The amount of the base to be used is generally 1 to 5 equivalents, preferably 1.1 to 2.5 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the solvent used in this reaction include solvents that do not participate in the reaction, such as tetrahydrofuran and 1,2-dimethoxyethane, and these solvents may be used by mixing at an appropriate ratio.
These reactions can usually be performed at −78 ° C. to room temperature for 0.5 to 5 hours.
When Uc of compound (1-f) is boronic acid, this reaction can be carried out by a known method (Journal of Organic Chemistry, 1999, 64, 9430-9443) or a method analogous thereto.
The amount of trimethoxyborate used in this step is 1 to 5 equivalents, preferably 1.1 to 2.2 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the base used usually include n-butyl lithium and s-butyl lithium. The amount of the base to be used is generally 1 to 5 equivalents, preferably 1 to 2.2 equivalents, relative to 1 equivalent of compound (1-d).
Examples of the solvent used in this reaction include solvents that do not participate in the reaction, such as tetrahydrofuran, 1,2-dimethoxyethane, and diethyl ether, and these solvents may be used in a mixture at an appropriate ratio.
These reactions can be carried out usually at -78 ° C to room temperature for 0.5 to 5 hours.

[Step 5]
This step is a method for producing compound (I-2) by reacting compound (1-f) with compound (1-g).
This reaction is performed according to the Suzuki-Miyaura coupling reaction described in Step 3 of Production Method 1.
The compound (I-2) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

The compound (1-a), the compound (1-c), the compound (1-e) and the compound (1-g) used as the starting compound in the production method 1 can be produced by a method known per se.
Production method 2:

[式中、Ｕｅはトリフルオロメタンスルホニルオキシを示し、その他の記号は前記と同意義を示す。]

[Wherein Ue represents trifluoromethanesulfonyloxy, and other symbols are as defined above. ]

[Step 1]
This step is a method for producing compound (2-b) by reacting compound (2-a) with di-tert-butyl dicarbonate in the presence of a base.
The amount of di-tert-butyl dicarbonate used in this reaction is 1 to 3 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of compound (2-a).
Examples of the base used usually include triethylamine, pyridine, N, N-dimethyl-4-aminopyridine, N, N-diisopropylethylamine, aqueous sodium hydroxide, aqueous sodium bicarbonate, and the like. The amount of the base used is usually 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (2-a).
Examples of the solvent used in the reaction include solvents that do not participate in the reaction, such as chloroform, dichloromethane, diethyl ether, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, ethyl acetate, acetonitrile, and the like. You may mix and use.
These reactions are usually carried out at 0 to 100 ° C. for 1 to 24 hours.

[Step 2]
This step is a method for producing compound (2-c) by reacting compound (2-b) with trifluoromethanesulfonic anhydride in the presence of a base.
The amount of trifluoromethanesulfonic anhydride used in this reaction is 1 to 3 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of compound (2-b).
Examples of the base used include tertiary aliphatic amines such as N, N-diisopropylethylamine and triethylamine, and pyridine. The amount of the base used is usually 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (2-b).
Examples of the solvent used include solvents that do not participate in the reaction, such as chloroform, diethyl ether, tetrahydrofuran, and 1,4-dioxane, and these solvents may be mixed and used at an appropriate ratio.
These reactions can be usually performed at 0 ° C. to room temperature for 1 to 24 hours.

[Step 3]
This step is a method for producing compound (2-d) by reacting compound (2-c) under acidic conditions.
In this reaction, for example, an acid such as 4M hydrogen chloride / ethyl acetate solution, 4M hydrogen chloride / 1,4-dioxane solution, or trifluoroacetic acid is usually used. The amount of the acid used is 5 to 50 equivalents, preferably 10 to 30 equivalents, relative to 1 equivalent of compound (2-c).
Examples of the solvent used in the reaction include ethyl acetate, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, chloroform, dichloromethane, and other solvents that do not participate in the reaction. These solvents are mixed in an appropriate ratio. It may be used.
These reactions can be usually performed at 0 ° C. to room temperature for 1 to 24 hours.

[Process 4]
This step is a method for producing compound (2-e) from compound (2-d).
This reaction can be carried out according to the method described in Process 1 of Production Method 1.

[Process 5]
This step is a method for producing compound (2-f) by reacting compound (2-e) with compound (1-e).
This reaction can be carried out according to the Suzuki-Miyaura coupling reaction described in Step 3 of Production Method 1.

[Step 6]
This step is a method for producing compound (I-2) by reacting compound (2-f) with compound (1-c).
This reaction can be performed according to the method described in Step 2 of Production Method 1.
The compound (I-2) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  The compound (2-a) used as a raw material compound in the production method 2 can be obtained by a method known per se.

Among the compounds (I) of the present invention, the compound (I-3) wherein X is a nitrogen atom and W is a single bond can be produced, for example, by the following production method 3 or a method analogous thereto.
Production method 3:

[式中、Ｕｆはハロゲン原子を、その他の記号は前記と同意義を示す。]
Ｕｆで示される「ハロゲン原子」としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられる。

[Wherein Uf represents a halogen atom, and other symbols are as defined above. ]
Examples of the “halogen atom” represented by Uf include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

[Step 1]
This step is a method for producing compound (3-c) by reacting compound (3-a) with compound (3-b) in the presence of a base.
The amount of (3-b) in the compound used in this step is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (3-a).
As the base to be used, for example, tertiary aliphatic amines such as triethylamine, N, N-diisopropylethylamine, 1,8-diazabicyclo [4,3,0] undec-7-ene, cesium carbonate, potassium carbonate, Examples include alkali metal carbonates such as sodium carbonate and alkali metal alkoxides such as potassium t-butoxide. The amount of the base used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (3-a).
Examples of the solvent used for the reaction include dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran and the like, which are not involved in the reaction. You may mix and use.
These reactions can be usually performed at room temperature to 100 ° C. for 1 to 24 hours.

[Step 2]
This step is a method for producing compound (3-d) by reducing compound (3-c).
This reaction is carried out using a method that is carried out in the presence of a metal and an acid in a solvent that does not participate in the reaction.
Examples of the metal used usually include iron, zinc, indium, tin chloride and the like. The amount of the metal used is 1 to 50 equivalents, preferably 3 to 30 equivalents, relative to 1 equivalent of compound (3-c).
Examples of the acid used include ammonium chloride, acetic acid, hydrochloric acid and the like. The amount of the acid used is 0.01 to 500 equivalents, preferably 0.1 to 300 equivalents, relative to 1 equivalent of compound (3-c).
Examples of the solvent used in the reaction include water, ethanol, methanol, tetrahydrofuran, ethyl acetate, and the like. These solvents may be used by mixing at an appropriate ratio, or may be solventless.
These reactions can usually be performed at 0 ° C. to reflux temperature for 1 to 24 hours.
Or this reaction is performed using the method performed in the solvent which does not participate in reaction in presence of a metal and a hydrogen source.
Examples of the metal used include palladium, nickel, platinum and the like. The amount of the metal used is 0.1 to 1 equivalent, preferably 0.1 to 0.5 equivalent, relative to 1 equivalent of compound (3-c).
Examples of the hydrogen source used in the reaction include hydrogen gas, and the hydrogen pressure at that time is from normal pressure to 10 atm, and preferably from normal pressure to 4 atm.
Further, formic acid, ammonium formate, cyclohexene, or the like may be used as a hydrogen source.
Examples of the solvent used in the reaction include methanol, ethanol, water, tetrahydrofuran, chloroform, dichloromethane, ethyl acetate and the like, and these solvents may be used by mixing at an appropriate ratio. These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.

[Step 3]
This step is a method for producing compound (3-e) from compound (3-d).
This reaction can be carried out by a known method such as described in Tetrahedron Letters, 2006, 47, 8661-8665, European Journal of Organic Chemistry, 2005, 15, 3271-3278, Bioorganic & Medicinal Chemistry, 68, 46, 1446, etc. It can carry out by the method of or the method according to it.
Examples of the reagent used in this step include alkali metal nitrites such as sodium nitrite, nitrites such as t-butyl nitrite and isoamyl nitrite. The amount of the reagent used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (3-d).
Examples of the solvent used in the reaction include an acetic acid-water mixed solvent, a trifluoroacetic acid-water mixed solvent, an acidic solvent such as hydrochloric acid and an aqueous sulfuric acid solution, and the like, and these solvents may be mixed and used at an appropriate ratio. .
These reactions can be usually performed at −30 ° C. to reflux temperature for 1 to 24 hours.

[Step 4]
This step is a method for producing compound (I-3) by reacting compound (3-e) with compound (1-e) in the presence of a palladium catalyst and a base.
This reaction can be carried out according to the Suzuki-Miyaura coupling reaction described in Step 3 of Production Method 1.

[Step 5]
This step is a method for producing compound (3-f) from compound (3-e).
This reaction can be performed according to the method described in Process 4 of Production Method 1.

[Step 6]
This step is a method for producing compound (I-3) by reacting compound (3-f) with compound (1-g) in the presence of a palladium catalyst and a base.
This reaction can be carried out according to the Suzuki-Miyaura coupling reaction described in Step 3 of Production Method 1.
The compound (I-3) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  The compound (3-a) and the compound (3-b) used as raw material compounds in the production method 3 can be produced by a method known per se.

The compound (I-3) can also be produced, for example, by the following production method 4 or a method analogous thereto.
Production method 4:

［式中の記号は前記と同意義を示す。］

[The symbols in the formula are as defined above. ]

[Step 1]
This step is a method for producing compound (4-c) by reacting compound (4-a) with compound (4-b) in the presence of a reducing reagent.
This reaction can be performed in the presence or absence of an acid in a solvent that does not participate in the reaction.
The amount of compound (4-b) used in this reaction is 0.5 to 10 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (4-a). Examples of the reducing reagent used in this reaction include sodium triacetoxyborohydride, sodium borohydride, lithium borohydride, sodium cyanoborohydride, lithium aluminum hydride and the like. The amount of the reagent used is 1 equivalent to 10 equivalents, preferably 1 equivalent to 3 equivalents, relative to 1 equivalent of compound (4-a).
These reactions can be usually performed at 0 to 0 ° C. for 1 to 48 hours.
Alternatively, this reaction can be carried out using a catalytic reduction reaction using a hydrogen source such as hydrogen gas in the presence of a metal catalyst such as palladium, instead of using the above-described reducing reagent. This catalytic reduction reaction can be carried out according to the method described in Step 2 of Production Method 3.

[Step 2]
This step is a method for producing a compound (4-d) by cyclizing the compound (4-c). This reaction can be carried out according to the method described in Step 3 of Production Method 3.

[Step 3]
This step is a method for producing compound (I-3) by reacting compound (4-d) with compound (1-e) in the presence of a palladium catalyst and a base.
This reaction can be carried out according to the Suzuki-Miyaura coupling reaction described in Step 3 of Production Method 1.
The compound (I-3) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  The compound (4-a) used as a raw material compound in the production method 4 can be obtained by a method known per se.

Among the compounds (I) of the present invention, the compound (I-4) in which W is —OCH ₂ — can be produced, for example, by the following production method 5 or a method analogous thereto.
Production method 5:

［式中の記号は前記と同意義を示す。］

[The symbols in the formula are as defined above. ]

[Step 1]
This step is a method for producing compound (5-b) by reacting compound (5-a) with compound (1-c).
This reaction can be performed according to the method described in Step 2 of Production Method 1.

[Step 2]
This step is a method for producing compound (5-c) by reducing compound (5-b).
Examples of the reducing agent used in this reaction include lithium aluminum hydride, lithium borohydride, sodium borohydride, borane-tetrahydrofuran complex, borane-dimethyl sulfide complex, diisobutylaluminum hydride and the like. The amount of the reducing agent used is 0.5 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (5-b).
Examples of the solvent used in this reaction include solvents that do not participate in the reaction, such as tetrahydrofuran, diethyl ether, 1,4-dioxane, ethanol, methanol, and the like, and these solvents may be used in an appropriate ratio.
These reactions can be usually performed at 0 ° C. to reflux temperature for 0.5 to 24 hours.

[Step 3]
This step is a method for producing compound (I-4) by reacting compound (5-c) with compound (5-d).
This reaction can be performed according to the Mitsunobu reaction described in Step 2 of Production Method 1.
Thus obtained compound (I-4) can be isolated and purified by a known separation and purification means, for example, concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  The compound (5-a) used as a raw material compound in the production method 5 can be obtained by a method known per se.

Among the compounds (I) of the present invention, the compound (I-5) in which W is —O— or the compound (I-6) in which —NH— is produced, for example, by the following production method 6 or a method analogous thereto. be able to.
Production method 6:

[式中、Ｕｇはハロゲン原子又はボロン酸を示し、その他の記号は前記と同意義を示す。]
Ｕｇで示されるハロゲン原子としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられる。
本製造法は、化合物（６−ａ）と、化合物（５−ｄ）又は化合物（６−ｂ）を反応させることにより、化合物(Ｉ−５)又は化合物(Ｉ−６)を製造する方法である。
Ｕｇがハロゲン原子である場合、本反応は、公知の方法、例えば、Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ，２０１０，７５，１７９１−１７９４に記載の方法又はそれに準じた方法により行うことができる。
本反応に用いられる化合物（５−ｄ）及び化合物（６−ｂ）の量は、化合物（６−ａ）１当量に対して０．５から３当量であり、好ましくは１から２当量である。本反応に用いられる銅試薬としては、銅、ヨウ化銅（Ｉ）、臭化銅（Ｉ）、塩化銅（Ｉ）、酢酸銅（II）、酸化銅（Ｉ）、酸化銅（II）等が挙げられる。銅試薬の量は、通常０．０１から１０当量であり、好ましくは０．０５から５当量である。
用いられる配位子としては、例えば、トランス−シクロヘキサンジアミン、トランス−１，２−ビス（メチルアミノ）シクロヘキサン、Ｎ，Ｎ’−ジメチルエチレンジアミン、１，１０−フェナントロリン、８−ヒドロキシキノリン、ピコリン酸、プロリン、２−イソブチリルシクロヘキサノン、Ｎ，Ｎ−ジメチルグリシン、ピロール−２−カルボン酸等が挙げられる。配位子の量は、通常０．０１から１０当量であり、好ましくは０．０５から５当量である。又は配位子を用いなくても良い。
塩基としては、例えば炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素ナトリウム等のアルカリ金属炭酸塩、リン酸三カリウム等のアルカリ金属リン酸塩、酢酸セシウム等が挙げられる。用いられる塩基の量は、１から５当量であり、好ましくは１から３当量である。又は塩基を用いなくても良い。
反応に用いられる溶媒としては、Ｎ，Ｎ−ジメチルホルムアミド、ジメチルスルホキシド、トルエン、ジオキサン、Ｎ−メチルピロリドン等の反応に関与しない溶媒が挙げられ、これらの溶媒は適宜の割合で混合して用いてもよい。
これらの反応は、通常室温から２００℃で、１から２４時間で行うことができ、またマイクロ波照射下でも行うことができる。
又は、本反応は、パラジウム触媒及び塩基の存在下、並びに配位子の存在下、又は非存在下で行う方法により行うことができる。
本反応に用いられる化合物（５−ｄ）及び化合物（６−ｂ）の量は、化合物（６−ａ）１当量に対して０．５から３当量であり、好ましくは１から２当量である。
本反応に用いられるパラジウム触媒としては、例えば、酢酸パラジウム（II）、トリス（ジベンジリデンアセトン）ジパラジウム、ジクロロビス（トリフェニルホスフィン）パラジウム（II）、テトラキス（トリフェニルホスフィン）パラジウム（０）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体等が挙げられる。パラジウム触媒の量は、化合物（６−ａ）１当量に対して、通常０．０１から１当量であり、好ましくは０．１から０．５当量である。
用いられる配位子としては、例えば、２−（ジｔ−ブチルホスフィノ）ビフェニル、トリフェニルホスフィン、２−（ジｔ−ブチルホスフィノ）−１，１’−ビナフチル、２−ジシクロヘキシルホスフィノ−２’−（Ｎ，Ｎ−ジメチルアミノ）ビフェニル等が挙げられる。用いられる配位子の量は、化合物（６−ａ）１当量に対して、通常０．０２から２当量であり、好ましくは０．２から１当量である。
塩基としては、例えばカリウム ｔ−ブトキシド、ナトリウム ｔ−ブトキシド、ナトリウムフェノキシド等のアルカリ金属アルコキシド、炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素ナトリウム等のアルカリ金属炭酸塩、リン酸カリウム等のアルカリ金属リン酸塩、塩化リチウム等が挙げられる。用いられる塩基の量は、化合物（６−ａ）１当量に対して、１から５当量であり、好ましくは１から３当量である。
反応に用いられる溶媒としては、Ｎ，Ｎ−ジメチルホルムアミド、ジメチルスルホキシド、トルエン、１，４−ジオキサン、１，２−ジメトキシエタン、テトラヒドロフラン等の反応に関与しない溶媒が挙げられ、これらの溶媒は適宜の割合で混合して用いてもよい。
これらの反応は、通常室温から２００℃で、１から２４時間で行うことができ、またマイクロ波照射下でも行うことができる。
Ｕｇがボロン酸である場合、公知の方法、例えば、Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，１９９８，３９，２９３３−２９３６、 ｉｂｉｄ．，１９９８，３９，２９３７−２９４０に記載の方法又はそれに準じた方法により行うことができる。
本反応に用いられる化合物（５−ｄ）及び化合物（６−ｂ）の量は、化合物（６−ａ）１当量に対して０．５から３当量であり、好ましくは１から２当量である。
本反応に用いられる金属塩としては、酢酸銅（II）等が挙げられる。反応に用いられる酢酸銅（II）の量は、０．５から３当量であり、好ましくは１から２当量である。本反応に用いられる塩基としては、例えばトリエチルアミン、ピリジン等が挙げられる。用いられる塩基の量は、化合物（６−ａ）１当量に対して、３から１５当量であり、好ましくは５から１０当量である。
反応に用いられる溶媒としては、クロロホルム、ジクロロメタン等の反応に関与しない溶媒が挙げられ、これらの溶媒は適宜の割合で混合して用いてもよい。
これらの反応は、通常室温から還流温度で、１から２４時間で行うことができる。
このようにして得られる化合物(Ｉ−５)及び化合物(Ｉ−６)は、公知の分離精製手段、例えば濃縮、減圧濃縮、再沈殿、溶媒抽出、結晶化、クロマトグラフィー等により単離精製することができる。

[Wherein Ug represents a halogen atom or a boronic acid, and other symbols are as defined above. ]
Examples of the halogen atom represented by Ug include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
This production method is a method for producing compound (I-5) or compound (I-6) by reacting compound (6-a) with compound (5-d) or compound (6-b). is there.
When Ug is a halogen atom, this reaction can be carried out by a known method, for example, the method described in Journal of Organic Chemistry, 2010, 75, 1791-1794, or a method analogous thereto.
The amount of compound (5-d) and compound (6-b) used in this reaction is 0.5 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (6-a). . Examples of the copper reagent used in this reaction include copper, copper (I) iodide, copper (I) bromide, copper (I) chloride, copper (II) acetate, copper (I) oxide, copper (II) oxide and the like. Is mentioned. The amount of the copper reagent is usually 0.01 to 10 equivalents, preferably 0.05 to 5 equivalents.
Examples of the ligand used include trans-cyclohexanediamine, trans-1,2-bis (methylamino) cyclohexane, N, N′-dimethylethylenediamine, 1,10-phenanthroline, 8-hydroxyquinoline, picolinic acid, Examples include proline, 2-isobutyrylcyclohexanone, N, N-dimethylglycine, and pyrrole-2-carboxylic acid. The amount of the ligand is usually 0.01 to 10 equivalents, preferably 0.05 to 5 equivalents. Or it is not necessary to use a ligand.
Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogen carbonate, alkali metal phosphates such as tripotassium phosphate, cesium acetate, and the like. The amount of base used is 1 to 5 equivalents, preferably 1 to 3 equivalents. Alternatively, a base may not be used.
Examples of the solvent used for the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, dioxane, N-methylpyrrolidone, and the like, which are not involved in the reaction. Also good.
These reactions can usually be performed at room temperature to 200 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.
Alternatively, this reaction can be carried out by a method performed in the presence of a palladium catalyst and a base, and in the presence or absence of a ligand.
The amount of compound (5-d) and compound (6-b) used in this reaction is 0.5 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (6-a). .
Examples of the palladium catalyst used in this reaction include palladium acetate (II), tris (dibenzylideneacetone) dipalladium, dichlorobis (triphenylphosphine) palladium (II), tetrakis (triphenylphosphine) palladium (0), [ 1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex and the like. The amount of the palladium catalyst is usually 0.01 to 1 equivalent, preferably 0.1 to 0.5 equivalent, relative to 1 equivalent of the compound (6-a).
Examples of the ligand used include 2- (di-t-butylphosphino) biphenyl, triphenylphosphine, 2- (di-t-butylphosphino) -1,1′-binaphthyl, and 2-dicyclohexylphosphino- 2 ′-(N, N-dimethylamino) biphenyl and the like can be mentioned. The amount of the ligand used is usually 0.02 to 2 equivalents, preferably 0.2 to 1 equivalent, relative to 1 equivalent of compound (6-a).
Examples of the base include alkali metal alkoxides such as potassium t-butoxide, sodium t-butoxide and sodium phenoxide, alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate and sodium bicarbonate, and alkali metal phosphorus such as potassium phosphate. Examples thereof include acid salts and lithium chloride. The amount of the base used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (6-a).
Examples of the solvent used for the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran and the like, which are not involved in the reaction. You may mix and use by the ratio.
These reactions can usually be performed at room temperature to 200 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.
When Ug is boronic acid, known methods such as Tetrahedron Letters, 1998, 39, 2933-2936, ibid. 1998, 39, 2937-2940, or a method analogous thereto.
The amount of compound (5-d) and compound (6-b) used in this reaction is 0.5 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (6-a). .
Examples of the metal salt used in this reaction include copper (II) acetate. The amount of copper (II) acetate used in the reaction is 0.5 to 3 equivalents, preferably 1 to 2 equivalents. Examples of the base used in this reaction include triethylamine, pyridine and the like. The amount of the base used is 3 to 15 equivalents, preferably 5 to 10 equivalents, relative to 1 equivalent of compound (6-a).
Examples of the solvent used in the reaction include solvents that do not participate in the reaction, such as chloroform and dichloromethane, and these solvents may be used by mixing at an appropriate ratio.
These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.
The thus obtained compound (I-5) and compound (I-6) are isolated and purified by a known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like. be able to.

  In addition, the compound (6-a) used as a raw material compound by the said manufacturing method 6 can be manufactured by the above-mentioned manufacturing method 1, manufacturing method 3, manufacturing method 4, or the method according to these.

Among the compounds (I) of the present invention, compound (I-7) in which W is —CH ₂ O— can be produced, for example, by the following production method 7 or a method analogous thereto.
Production method 7:

[式中、Ｕｈはハロゲン原子又はヒドロキシを、その他の記号は前記と同意義を示す。]
Ｕｈで示される「ハロゲン原子」としては、塩素原子、臭素原子及びヨウ素原子が挙げられる。

[Wherein Uh represents a halogen atom or hydroxy, and other symbols are as defined above. ]
Examples of the “halogen atom” represented by Uh include a chlorine atom, a bromine atom, and an iodine atom.

[Process 1]
This step is a method for producing compound (7-b) from compound (7-a).
This reaction is carried out by a known method, for example, the method described in Journal of Organic Chemistry, 2005, 70, 7353-7363, Synlett, 2009, 4, 615-619 or a method analogous thereto.
Hydrogen peroxide etc. are mentioned as an oxidizing agent used for this process. The amount of the reagent used is 1 to 500 equivalents, preferably 5 to 300 equivalents, relative to 1 equivalent of compound (7-a).
Examples of the solvent used in the reaction include water, methanol, tetrahydrofuran, diethyl ether, dimethyl sulfoxide, dichloromethane, chloroform, and other solvents that do not participate in the reaction, and these solvents may be mixed and used at an appropriate ratio.
These reactions can be usually performed at room temperature to reflux temperature for 1 to 24 hours.

[Process 2]
This step is a method for producing compound (I-7) by reacting compound (7-b) with compound (7-c).
When Uh is a halogen atom, this reaction can be carried out by a known method, for example, in the presence of a base, in a solvent that does not participate in the reaction.
The amount of compound (7-c) used in this reaction is 0.5 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (7-b).
Examples of the base used in this reaction include alkali metal carbonates such as potassium carbonate, cesium carbonate and sodium carbonate, alkali metal alkoxides such as potassium t-butoxide, and sodium hydride. The amount of the base used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (7-b).
Examples of the solvent used for the reaction include N, N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, tetrahydrofuran, acetonitrile, and the like, which are not involved in the reaction. These solvents are used by mixing at an appropriate ratio. May be.
These reactions can be usually performed at room temperature to 200 ° C. for 1 to 24 hours.
When Uh is hydroxy, this reaction can be carried out according to the method described in Step 2 of Production Method 1.
Thus obtained compound (I-7) can be isolated and purified by a known separation and purification means, for example, concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  In addition, the compound (7-a) used as a raw material compound in the said manufacturing method 7 can be obtained by the above-mentioned manufacturing method 1, manufacturing method 3, or the method according to these.

Among the compounds (I) of the present invention, the compound (I-10) in which the substituent B is represented by R ¹ can be produced, for example, by the following production method 8 or a method analogous thereto.
Production method 8:

[式中、Ｕｉはハロゲン原子を示す。Ｒ¹はＣ_2-6アルキル（該Ｃ_2-6アルキルは、置換されていないか、ハロゲン原子及びヒドロキシからなる群より選ばれる１〜６個の基で置換されている。）、Ｃ_3-8シクロアルキル、Ｃ_3-8シクロアルキルＣ_1-6アルキル（該Ｃ_3-8シクロアルキルＣ_1-6アルキルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、アリールＣ_1-6アルキル又は飽和のヘテロシクリルＣ_1-6アルキル（該飽和のヘテロシクリルＣ_1-6アルキルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）を示す。Ｒ¹¹はＣ_１-５アルキル（該Ｃ_１-５アルキルは、置換されていないか、ハロゲン原子及びヒドロキシからなる群より選ばれる１〜６個の基で置換されている。）、Ｃ_3-8シクロアルキル（該Ｃ_3-8シクロアルキルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、アリール又は飽和のヘテロシクリル（該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）を示し、
Ｒ¹²は、水素原子又はＣ_１-４アルキルを示し、
Ｒ¹¹とＲ¹²は隣接する炭素原子と一緒になってＣ_3-8シクロアルキル又は飽和のヘテロシクリル（該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）を形成してもよく、その他の記号は前記と同意義を示す。]
Ｕｉで示される「ハロゲン原子」としては、塩素原子、臭素原子及びヨウ素原子が挙げられる。Ｒ¹¹で示される「Ｃ_１-５アルキル」は、炭素原子を１から５個有する直鎖状又は分岐状のアルキルを示し、Ｒ¹²で示される「Ｃ_１-４アルキル」は、炭素原子を１から４個有する直鎖状又は分岐状のアルキルを示す。

[Wherein Ui represents a halogen atom. R ¹ is C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with 1 C _1-6 alkyl). ), Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) Indicates. R ¹¹ is C _1-5 alkyl (the C _1-5 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with one C _1-6 alkyl), aryl or saturated heterocyclyl (the saturated heterocyclyl is substituted Or is substituted with one C _1-6 alkyl).
R ¹² represents a hydrogen atom or C _1-4 alkyl;
R ¹¹ and R ¹² together with adjacent carbon atoms are C _3-8 cycloalkyl or saturated heterocyclyl (the saturated heterocyclyl is unsubstituted or substituted with one C _1-6 alkyl) The other symbols have the same meanings as described above. ]
Examples of the “halogen atom” represented by Ui include a chlorine atom, a bromine atom, and an iodine atom. “C _1-5 alkyl” represented by R ¹¹ represents linear or branched alkyl having 1 to 5 carbon atoms, and “C _1-4 alkyl” represented by R ¹² represents carbon atoms. A linear or branched alkyl having 1 to 4 is shown.

[Process 1]
This step is a method for producing compound (8-a) by reacting compound (I-9) under acidic conditions.
This reaction can be performed according to the method described in Step 3 of Production Method 2.

[Process 2]
This step is a process for producing compound (I-10) by reacting compound (8-a) with compound (8-b) in the presence of a base and in the presence or absence of potassium iodide. It is.
The amount of compound (8-b) used in this reaction is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (8-a).
Examples of the compound (8-b) used in this reaction include 1-iodopropane, 1-iodo-2-methylpropane, 1-iodo-2-methylbutane, cyclopropylmethyl bromide, cyclopentylmethyl iodide, and cyclohexylmethyl. Bromide, 1-bromo-3-methylbutane, (s)-(+)-3-bromo-2-methylpropan-1-ol, 1-chloro-2-methylpropan-2-ol, cyclohexyl bromide, 2- ( Bromomethyl) -1,1,1,3,3,3-hexafluoropropane, neopentyl bromide, benzyl bromide and the like.
Examples of the base used for the reaction include alkali metal carbonates such as potassium carbonate and cesium carbonate. The amount of the base used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (8-a).
Examples of the solvent used in the reaction include acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, tetrahydrofuran, and the like, which are not involved in the reaction. These solvents are used in an appropriate ratio. May be.
These reactions can be usually performed at room temperature to 100 ° C. for 1 to 24 hours.
Moreover, this process can also be implemented by the reductive amination reaction of a compound (8-a) and a compound (8-c). In this case, it can be performed according to the method described in Step 1 of Production Method 4.
Thus obtained compound (I-10) can be isolated and purified by a known separation and purification means, for example, concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  In addition, the compound (I-9) used as a raw material compound in the said manufacturing method 8 can be manufactured by the above-mentioned manufacturing method 1-manufacturing method 7, or a method according to these.

Among the compounds (I) of the present invention, the compound (I-11) in which the substituent B is —COOR ³¹ can be produced, for example, by the following production method 9 or a method analogous thereto.
Production method 9:

[式中、Ｒ³¹は、Ｃ_1-6アルキル｛該Ｃ_1-6アルキルは、置換されていないか、ハロゲン原子、シアノ、Ｃ_3-8シクロアルキル（該Ｃ_3-8シクロアルキルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１〜３個の基で置換されている。）、Ｃ_1-6アルコキシ（該Ｃ_1-6アルコキシは、置換されていないか、１個のアリールで置換されている。）、アリール［該アリールは、置換されていないか、ハロゲン原子、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１〜３個のハロゲン原子で置換されている。）及びＣ_1-6アルコキシからなる群より選ばれる１〜３個の基で置換されている。］、ヘテロアリール（該ヘテロアリールは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１個の基で置換されている。）、飽和のヘテロシクリル（該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキルで置換されている。）、モノＣ_1-6アルキルアミノ、ジＣ_1-6アルキルアミノ、Ｃ_1-6アルキルスルファニル及びＣ_1-6アルキルスルホニルからなる群より選ばれる１〜６個の基で置換されている。｝、Ｃ_3-8シクロアルキル（該Ｃ_3-8シクロアルキルは、置換されていないか、ハロゲン原子及びＣ_1-6アルキルからなる群より選ばれる１〜３個の基で置換されている。）、アリール又は飽和のヘテロシクリル［該飽和のヘテロシクリルは、置換されていないか、１個のＣ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、１個のアリールで置換されている。）で置換されている。］を示し、その他の記号は前記と同意義を示す。]
本製造法は、化合物（８−ａ）を置換基Ｂに対応するカーバメート化試薬と反応させることにより化合物(Ｉ−１１)を製造する方法である。 本反応に用いられるカーバメート化試薬の量は、化合物（８−ａ）１当量に対して１から５当量であり、好ましくは１から３当量である。
カーバメート化試薬は市販で入手することができるほか、対応するアルコール（Ｒ^３１ＯＨ）と縮合剤から塩基の存在下で調製することもできる。この際の縮合剤としては、トリホスゲン、ホスゲン、ｐ−ニトロフェニルクロロホルメート、１，１´−カルボニルジイミダゾール等が挙げられる。この際の縮合剤の量は、対応するアルコールに対して０．５〜３当量、好ましくは１等量である。
反応に用いられる塩基としては、例えばＮ，Ｎ−ジイソプロピルエチルアミン、トリエチルアミン等の第３級脂肪族アミン、炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素ナトリウム等のアルカリ金属炭酸塩、水酸化ナトリウム、ピリジン、Ｎ，Ｎ−ジメチル−４−アミノピリジン等が挙げられる。用いられる塩基の量は、１から５当量であり、好ましくは１から３当量である。
反応に用いられる溶媒としてはＮ，Ｎ−ジメチルホルミアミド、クロロホルム、ジクロロメタン、１，４−ジオキサン、１，２−ジメトキシエタン、テトラヒドロフラン、メタノール、エタノール、水、酢酸エチル、アセトニトリル、アセトン、トルエン等の反応に関与しない溶媒が挙げられ、これらの溶媒は適宜の割合で混合して用いてもよい。
これらの反応は、通常０℃から１００℃で、１から１２時間で行うことができる。
このようにして得られる化合物(Ｉ−１１)は、公知の分離精製手段、例えば濃縮、減圧濃縮、再沈殿、溶媒抽出、結晶化、クロマトグラフィー等により単離精製することができる。

[Wherein R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), C _1-6 alkoxy (the C _1-6 alkoxy is substituted). Or substituted with one aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted, Substituted with 1 to 3 halogen atoms) and 1 to 3 groups selected from the group consisting of C _1-6 alkoxy. ], Heteroaryl (the heteroaryl is unsubstituted or substituted with one group selected from the group consisting of a halogen atom and C _1-6 alkyl), saturated heterocyclyl (the saturated heterocyclyl Is unsubstituted or substituted with one C _1-6 alkyl.), Mono C _1-6 alkylamino, diC _1-6 alkylamino, C _1-6 alkylsulfanyl and C _1- Substituted with 1 to 6 groups selected from the group consisting of ₆ alkylsulfonyl. }, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl). ), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl) Is replaced by And other symbols are as defined above. ]
This production method is a method for producing compound (I-11) by reacting compound (8-a) with a carbamate reagent corresponding to substituent B. The amount of the carbamate reagent used in this reaction is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (8-a).
The carbamate reagent can be obtained commercially or prepared from the corresponding alcohol (R ³¹ OH) and a condensing agent in the presence of a base. Examples of the condensing agent at this time include triphosgene, phosgene, p-nitrophenyl chloroformate, 1,1′-carbonyldiimidazole, and the like. In this case, the amount of the condensing agent is 0.5 to 3 equivalents, preferably 1 equivalent, with respect to the corresponding alcohol.
Examples of the base used in the reaction include tertiary aliphatic amines such as N, N-diisopropylethylamine and triethylamine, alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate and sodium bicarbonate, sodium hydroxide and pyridine. , N, N-dimethyl-4-aminopyridine and the like. The amount of base used is 1 to 5 equivalents, preferably 1 to 3 equivalents.
Solvents used for the reaction include N, N-dimethylformamide, chloroform, dichloromethane, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran, methanol, ethanol, water, ethyl acetate, acetonitrile, acetone, toluene, etc. Solvents that do not participate in the reaction are mentioned, and these solvents may be mixed and used at an appropriate ratio.
These reactions are usually performed at 0 to 100 ° C. for 1 to 12 hours.
The compound (I-11) thus obtained can be isolated and purified by known separation and purification means such as concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  In addition, the compound (8-a) used as a raw material compound by the said manufacturing method 9 can be manufactured by the method according to the process 1 of the above-mentioned manufacturing method 8, or these.

  Among the compounds (I) of the present invention, the substituent B is represented by the following formula (β):

で表される５又は６員のヘテロアリールである化合物(Ｉ−１２)は、例えば下記製造法１０又はこれらに準ずる方法により製造することができる。
製造法１０：

Compound (I-12) which is a 5- or 6-membered heteroaryl represented by the formula can be produced, for example, by the following production method 10 or a method analogous thereto.
Production method 10:

[式中、Ｕｊは脱離基を示す。その他の記号は前記と同意義を示す。]
Ｕｊで示される「脱離基」としては、例えば、フッ素原子、塩素原子、臭素原子、ヨウ素原子、メタンスルホニルオキシ、ｐ−トルエンスルホニルオキシ、トリフルオロメタンスルホニルオキシ、ベンゼンスルホニルオキシ等が挙げられる。
本製造法は、化合物（８−ａ）と化合物（１０−ａ）より化合物(Ｉ−１２)を製造する方法である。

[Wherein Uj represents a leaving group. Other symbols are as defined above. ]
Examples of the “leaving group” represented by Uj include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, p-toluenesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy and the like.
This production method is a method for producing compound (I-12) from compound (8-a) and compound (10-a).

(Method A)
This reaction can be performed in the presence or absence of a base in a solvent that does not participate in the reaction.
The amount of compound (10-a) used in this reaction is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (8-a).
The compound (10-a) used in this reaction is a halogenated 5- or 6-membered heteroaryl corresponding to the substituent B, and examples thereof include 2-chloro-5-ethylpyrimidine, 2-chloro-5- Methylpyrimidine, 2,5-dichloropyrimidine, 2-chloro-5-fluoropyrimidine, 2-chloro-5-methoxypyrimidine, methyl 2-chloropyrimidin-5-ylcarboxylate, 2,5-dibromopyridine, 3,6- Examples include dichloropyrazine.
Examples of the base used in the reaction include tertiary aliphatic amines such as N, N-diisopropylethylamine and triethylamine, and alkali metal carbonates such as pyridine, cesium carbonate and potassium carbonate. The amount of base used is 1 to 5 equivalents, preferably 1 to 3 equivalents.
Examples of the solvent used in the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, 1,4-dioxane, tetrahydrofuran, 2-propanol and the like, which are not involved in the reaction. You may mix and use.
These reactions can usually be performed at room temperature to 180 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.

(Method B)
This reaction can be carried out in a solvent that does not participate in the reaction in the presence of a palladium catalyst and a base in an atmosphere of an inert gas such as argon or nitrogen.
The compound (10-a) used in this reaction is a halide described in (Method A).
The amount of compound (10-a) used in the reaction is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (8-a).
Examples of the palladium catalyst used in the reaction include (1,3-diisopropylimidazol-2-ylidene) (3-chloropyridyl) palladium (II) dichloride, [1,1′-bis (diphenylphosphino) ferrocene] palladium. (II) Dichloride Dichloromethane complex, palladium (II) acetate, tris (dibenzylideneacetone) dipalladium, dichlorobis (triphenylphosphine) palladium (II), tetrakis (triphenylphosphine) palladium (0) and the like. The amount of the palladium catalyst used is usually 0.01 to 1 equivalent, preferably 0.1 to 0.5 equivalent.
In this reaction, a ligand may coexist. Examples of the ligand include 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2- (di-t-butylphosphino) biphenyl, and 2- (dicyclohexylphosphino) -2 ′. , 4 ′, 6′-triisopropylbiphenyl, 2-dicyclohexylphosphino-2 ′-(N, N-dimethylamino) biphenyl, and the like. The amount of the ligand used is usually from 0.01 to 1 equivalent, preferably from 0.1 to 0.5 equivalent.
Examples of the base used in the reaction include alkali metal alkoxides such as potassium t-butoxide, sodium t-butoxide and sodium phenoxide, alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate and sodium bicarbonate, potassium phosphate and the like And alkali metal phosphates, lithium chloride and the like. The amount of base used is 1 to 5 equivalents, preferably 1 to 3 equivalents.
Examples of the solvent used in the reaction include N, N-dimethylformamide, dimethyl sulfoxide, toluene, 1,4-dioxane, 1,2-dimethoxyethane, tetrahydrofuran and the like, which are not involved in the reaction. You may mix and use by a ratio.
These reactions can usually be performed at room temperature to 180 ° C. for 1 to 24 hours, and can also be performed under microwave irradiation.
Thus obtained compound (I-12) can be isolated and purified by a known separation and purification means, for example, concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  In addition, the compound (8-a) used as a raw material compound by the said manufacturing method 10 can be obtained by the method according to the process 1 of the above-mentioned manufacturing method 8, or these.

Among the compounds (I) of the present invention, the compound (I-13) having R ^a R ^b NCO— on the substituent A can be produced, for example, by the following production method 11 or a method analogous thereto.
Production method 11:

｛式中、Ｒ^aＲ^bＮＨで表される化合物（１１−ｂ）は、モノＣ_1-6アルキルアミン（該モノＣ_1-6アルキルアミンは、置換されていないか、ヒドロキシ、カルバモイル、Ｃ_3-8シクロアルキル、Ｃ_1-6アルコキシ、ジＣ_1-6アルキルアミノ及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜３個の基で置換されている。）、モノＣ_3-8シクロアルキルアミン、モノ飽和のヘテロシクリルアミン（該モノ飽和のヘテロシクリルアミンは、置換されていないか、１〜２個のオキソで置換されている。）、ジＣ_1-6アルキルアミン（該ジＣ_1-6アルキルアミンは、置換されていないか、ヒドロキシ、シアノ及びＣ_1-6アルコキシからなる群より同一に又は異なって選ばれる１〜２個の基で置換されている。）、環内に少なくとも１つの窒素原子を含有する飽和のヘテロシクリル［該環内に少なくとも１つの窒素原子を含有する飽和のヘテロシクリルは、置換されていないか、ヒドロキシ、Ｃ_1-6アルキル（該Ｃ_1-6アルキルは、置換されていないか、1個のヒドロキシで置換されている。）、モノＣ_1-6アルキルアミノ、ジＣ_1-6アルキルアミノ及びＣ_1-6アルキルスルホニルからなる群より同一に又は異なって選ばれる１〜２個の基で置換されている。］を示し、その他の記号は前記と同意義を示す。｝
本製造法は、化合物（１１−ａ）と化合物（１１−ｂ）より化合物(Ｉ−１３)を製造する方法である。
本反応は、公知の方法、例えば縮合剤を用いて、塩基及び活性化剤の存在下又は非存在下、反応に関与しない溶媒中で行うことができる。
本反応に用いられる化合物（１１−ｂ）の量は、化合物（１１−ａ）１当量に対して１から５当量であり、好ましくは１から３当量である。
反応に用いられる縮合剤としては、例えば１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩、Ｎ，Ｎ’−ジシクロヘキシルカルボジイミド、シアノホスホン酸ジエチル、プロピルホスホニックアンハイドライド等が挙げられる。用いられる縮合剤の量は、化合物（１１−ａ）１当量に対して、１から５当量であり、好ましくは１から３当量である。
反応に用いられる活性化剤としては、例えば、Ｎ−ヒドロキシベンゾトリアゾール一水和物、Ｎ−ヒドロキシスクシンイミド等が挙げられる。用いられる活性化剤の量は、化合物（１１−ａ）１当量に対して、１から５当量であり、好ましくは１から２当量である。
反応に用いられる塩基としては、例えば、Ｎ，Ｎ−ジイソプロピルエチルアミン、トリエチルアミン等の第３級脂肪族アミン、ピリジン等が挙げられる。用いられる塩基の量は、化合物（１１−ａ）１当量に対して、１から５当量であり、好ましくは１から２当量である。
反応に用いられる溶媒としては、Ｎ，Ｎ−ジメチルホルムアミド、ジクロロメタン、クロロホルム、１，２−ジクロロエタン、トルエン、テトラヒドロフラン、水等の反応に関与しない溶媒が挙げられ、これらの溶媒は適宜の割合で混合して用いてもよい。
これらの反応は、通常０℃から還流温度で、１から２４時間で行うことができる。
このようにして得られる化合物(Ｉ−１３)は、公知の分離精製手段、例えば濃縮、減圧濃縮、再沈殿、溶媒抽出、結晶化、クロマトグラフィー等により単離精製することができる。

{In the formula, the compound (11-b) represented by R ^a R ^b NH is a mono C _1-6 alkylamine (the mono C _1-6 alkylamine is not substituted, hydroxy, carbamoyl, C Substituted with 1 to 3 groups selected from the group consisting of _3-8 cycloalkyl, C _1-6 alkoxy, diC _1-6 alkylamino and C _1-6 alkylsulfonyl. , Mono C _3-8 cycloalkylamine, monosaturated heterocyclylamine (the monosaturated heterocyclylamine is unsubstituted or substituted with 1 to 2 oxo), diC _1-6 alkyl Amine (the di-C _1-6 alkylamine is unsubstituted or substituted with 1-2 groups selected identically or differently from the group consisting of hydroxy, cyano and C _1-6 alkoxy. ), At least one in the ring A saturated heterocyclyl containing at least one nitrogen atom in the ring is unsubstituted or substituted with hydroxy, C _1-6 alkyl (wherein the C _1-6 alkyl is substituted Or substituted with one hydroxy), selected from the group consisting of mono-C _1-6 alkylamino, di-C _1-6 alkylamino and C _1-6 alkylsulfonyl, identically or differently Substituted with 1 to 2 groups. And other symbols are as defined above. }
This production method is a method for producing compound (I-13) from compound (11-a) and compound (11-b).
This reaction can be performed by a known method, for example, using a condensing agent in the presence or absence of a base and an activator in a solvent that does not participate in the reaction.
The amount of compound (11-b) used in this reaction is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (11-a).
Examples of the condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, N, N′-dicyclohexylcarbodiimide, diethyl cyanophosphonate, propylphosphonic anhydride and the like. The amount of the condensing agent to be used is 1 to 5 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of compound (11-a).
Examples of the activator used in the reaction include N-hydroxybenzotriazole monohydrate, N-hydroxysuccinimide and the like. The amount of the activator used is 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (11-a).
Examples of the base used in the reaction include tertiary aliphatic amines such as N, N-diisopropylethylamine and triethylamine, and pyridine. The amount of the base used is 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of compound (11-a).
Examples of the solvent used for the reaction include N, N-dimethylformamide, dichloromethane, chloroform, 1,2-dichloroethane, toluene, tetrahydrofuran, water, and the like, which are not involved in the reaction. These solvents are mixed at an appropriate ratio. May be used.
These reactions can usually be performed at 0 ° C. to reflux temperature for 1 to 24 hours.
The compound (I-13) thus obtained can be isolated and purified by known separation and purification means, for example, concentration, concentration under reduced pressure, reprecipitation, solvent extraction, crystallization, chromatography and the like.

  In addition, the compound (11-a) used as a raw material compound by the said manufacturing method 11 can be manufactured by the above-mentioned manufacturing method 1-manufacturing method 10 or the method according to these.

Among the compounds (I) of the present invention, the compound (I-14) in which W is a single bond, —O— or —NH— can be produced, for example, by the following production method 12 or a method analogous thereto.
Production method 12:

[式中、Ｕはハロゲン原子を示す。W’は単結合、-O-又は-NH-を示し、その他の記号は前記と同意義を示す。]

[Wherein U represents a halogen atom. W ′ represents a single bond, —O— or —NH—, and the other symbols are as defined above. ]

[Step 1]
This step is a method for producing a compound (12-b) by bonding the substituent B to the compound (12-a). This reaction can be carried out according to the method described in Production Method 8, Production Method 9, or Production Method 10.

[Step 2]
This step is a method for producing compound (I-14) by bonding substituent A to compound (12-b). This reaction can be carried out according to the method described in Process 3 of Production Method 1 or Production Method 6.
In addition, the compound (12-a) used as a raw material compound in the said manufacturing method 12 is the compound (1-d) of the above-mentioned manufacturing method 1, the compound (3-e) of the manufacturing method 3, and the compound of the manufacturing method 4 ( 4-d), or in the compound (6-a) of production method 6, when the substituent B is, for example, a t-butyloxycarbonyl group, this substituent is converted according to the method described in step 3 of production method 2. It can be obtained by deprotection.

  The present invention will be described in more detail with reference to the following Reference Examples, Examples, Test Examples and Formulation Examples, which are not intended to limit the present invention, and may be changed without departing from the scope of the present invention. Also good.

  In the following Reference Examples and Examples, NH silica gel column chromatography refers to column chromatography separation and purification using NH 2 type silica gel (Chromatolex (registered trademark) NH 2 type, Fuji Silysia Chemical Ltd.). The ratio of elution solvent indicates a volume ratio unless otherwise specified.

Abbreviations used in this specification have the following meanings.
s: singlet
d: doublet
t: triplet
q: quartet
sxt: sextet
dd: double doublet (double doublet)
dt: double triplet
m: multiplet
br: broad
J: Coupling constant
Hz: Hertz
CDCl ₃ : deuterated chloroform DMSO-d ₆ : deuterated dimethyl sulfoxide METHANOL-d ₄ : deuterated methanol

¹ H-NMR (proton nuclear magnetic resonance spectrum) was measured by the following Fourier transform NMR.
200 MHz: Gemini 2000 (Agilent Technologies)
300 MHz: Inova300 (Agilent Technologies)
500 MHz: JNM-ECA500 (JEOL)
600 MHz: JNM-ECA600 (JEOL)
For analysis, ACD / SpecManager ver. 12.01 (trade name) or the like was used. Peaks with very gentle protons such as hydroxyl groups and amino groups are not described.

MS (mass spectrum) was measured with the following apparatus.
LCMS-2010EV (Shimadzu)
LCMS-IT-TOF (Shimadzu)
Agilent 6150 (Agilent)
LCQ Deca XP (ThermoFisher Scientific)
As an ionization method, an ESI (Electrospray Ionization) method or a dual ionization method of ESI and APCI (Atmospheric Pressure Chemical Ionization) method was used. The data described the actual value (found). Usually, a molecular ion peak is observed, but in the case of a compound having a tert-butoxycarbonyl group (-Boc), a peak from which a tert-butoxycarbonyl group or a tert-butyl group is eliminated is observed as a fragment ion. There is also. In the case of a compound having a hydroxyl group (—OH), a peak from which H ₂ O is eliminated may be observed as a fragment peak. In the case of a salt, a free molecular ion peak or a fragment ion peak is usually observed.

Waters SunFire ^™ Prep C18OBD ^™ 5 μm (ID 30 mm, Length 50 mm) was used for the preparative HPLC column. The preparative conditions were as follows: rate: 40 mL / min, element: A = acetonitrile, B = 0.1% trifluoroacetic acid aqueous solution, gradient: 10-95%.

  The phase separator used in the text was ISOLUTE (registered trademark) Phase Separator manufactured by Biotage.

  The compound name is ACD / Name ver. It was named using 12.01 (trade name) or the like.

Reference example A
tert-Butyl 4-[(methylsulfonyl) oxy] piperidine-1-carboxylate

１−（ｔｅｒｔ−ブトキシカルボニル）−４−ヒドロキシピペリジン（１０．０ｇ）のクロロホルム（２５０ｍｌ）溶液へ、氷冷下、トリエチルアミン（２１ｍｌ）、メシルクロライド（６．９ｍｌ）を加え室温にて１時間攪拌した。反応液に水を加えクロロホルムにて抽出し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１）にて精製後、ヘキサンで粉末化し、表題化合物（１２．０ｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.70 - 2.07 (m, 4 H) 3.04 (s, 3 H) 3.21 - 3.38 (m, 2 H) 3.62 - 3.79 (m, 2 H) 4.80 - 4.96 (m, 1 H).
参考例Ｂ−１
４−（１Ｈ−テトラゾル−１−イル）フェノール

Triethylamine (21 ml) and mesyl chloride (6.9 ml) were added to a solution of 1- (tert-butoxycarbonyl) -4-hydroxypiperidine (10.0 g) in chloroform (250 ml) under ice cooling, and the mixture was stirred at room temperature for 1 hour. did. Water was added to the reaction mixture, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1) and pulverized with hexane to give the title compound (12.0 g) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.70-2.07 (m, 4 H) 3.04 (s, 3 H) 3.21-3.38 (m, 2 H) 3.62-3.79 (m , 2 H) 4.80-4.96 (m, 1 H).
Reference Example B-1
4- (1H-tetrazol-1-yl) phenol

市販の４−アミノフェノール（１８．０ｇ）の酢酸（１５０ｍｌ）溶液へ、窒素雰囲気下、７５℃にてオルトギ酸トリエチル（２４．５ｇ）を加え４時間攪拌し、アジ化ナトリウム（３４．３ｇ）を加え同温にて４時間攪拌後、室温にて一晩攪拌した。さらに７５℃にて１２時間攪拌後、室温にて一晩攪拌した。反応液へ水を加え、析出した結晶を濾取した。得られた結晶をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１）にて精製後、酢酸エチル−ジエチルエーテルで再結晶し、表題化合物（８．６７ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 6.94 - 7.00 (m, 2 H) 7.64 - 7.70 (m, 2 H) 9.92 (s, 1 H) 10.14 (br. s, 1 H).
MS ESI/APCI Dual posi: 163[M+H]⁺, 185[M+Na]⁺.
MS ESI/APCI Dual nega: 161[M-H]^-.
参考例Ｂ−２
４−（１Ｈ−テトラゾル−１−イル）フェニル トリフルオロメタンスルホナート

To a solution of commercially available 4-aminophenol (18.0 g) in acetic acid (150 ml), triethyl orthoformate (24.5 g) was added at 75 ° C. under a nitrogen atmosphere, and the mixture was stirred for 4 hours. Sodium azide (34.3 g) After stirring at the same temperature for 4 hours, the mixture was stirred overnight at room temperature. The mixture was further stirred at 75 ° C. for 12 hours and then stirred overnight at room temperature. Water was added to the reaction solution, and the precipitated crystals were collected by filtration. The obtained crystals were purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1) and recrystallized from ethyl acetate-diethyl ether to give the title compound (8.67 g) as a brown powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 6.94-7.00 (m, 2 H) 7.64-7.70 (m, 2 H) 9.92 (s, 1 H) 10.14 (br. S, 1 H).
MS ESI / APCI Dual posi: 163 [M + H] ⁺ , 185 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 161 [MH] ^- .
Reference Example B-2
4- (1H-tetrazol-1-yl) phenyl trifluoromethanesulfonate

参考例Ｂ−１で得られた化合物（７００ｍｇ）のクロロホルム懸濁液（１３ｍｌ）にピリジン（５２３μｌ）を加え、氷冷下、無水トリフルオロメタンスルホン酸（８５０μｌ）を滴下し、同温にて１５分間、室温にて１５時間攪拌した。反応液に水を加えてからクロロホルムを減圧留去し、得られた水溶液を酢酸エチルで抽出した。有機層を２Ｍ塩酸、飽和食塩水で洗浄、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４９：１〜１：１）にて精製し、表題化合物（１．１３ｇ）を薄茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δppm 7.51 - 7.59 (m, 2 H) 7.83 - 7.91 (m, 2 H) 9.04 (s, 1 H).
MS ESI/APCI Dual nega: 329[M+Cl]^-.
参考例Ｃ
１−（４−ブロモフェニル）−１Ｈ−１，２，３−トリアゾール

Pyridine (523 μl) was added to a chloroform suspension (13 ml) of the compound (700 mg) obtained in Reference Example B-1, and trifluoromethanesulfonic anhydride (850 μl) was added dropwise under ice cooling. Stir for 15 minutes at room temperature. Water was added to the reaction solution, chloroform was distilled off under reduced pressure, and the resulting aqueous solution was extracted with ethyl acetate. The organic layer was washed with 2M hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 49: 1 to 1: 1) to obtain the title compound (1.13 g) as a light brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δppm 7.51-7.59 (m, 2 H) 7.83-7.91 (m, 2 H) 9.04 (s, 1 H).
MS ESI / APCI Dual nega: 329 [M + Cl] ^- .
Reference example C
1- (4-Bromophenyl) -1H-1,2,3-triazole

封管中、１−ブロモ−４−ヨードベンゼン（６．２０ｇ）、１Ｈ−１，２，３−トリアゾール（１．０３ｇ）、ヨウ化銅（２．７６ｇ）、Ｎ，Ｎ’−ジメチルエチレンジアミン（４．７ｍｌ）、ナトリウム ｔｅｒｔ−ブトキシド（４．２０ｇ）、１−メチル−２−ピロリドン（２９ｍｌ）の懸濁液を、１３０℃にて３．５時間撹拌した。室温へ冷却し、飽和塩化アンモニウム水溶液（２０ｍｌ）、２８％アンモニア水（５ｍｌ）を加えて激しく撹拌した後、セライト（登録商標）ろ過を行った。ろ液を酢酸エチルで抽出し、得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝７：３〜１：１）にて精製後、表題化合物（５６５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 7.70 - 8.98 (m, 6 H).
MS ESI/APCI Dual posi: 224[M+H]⁺.
参考例Ｄ−１
１−ブロモ−４−［（２−メトキシエチル）スルホニル］ベンゼン

In a sealed tube, 1-bromo-4-iodobenzene (6.20 g), 1H-1,2,3-triazole (1.03 g), copper iodide (2.76 g), N, N′-dimethylethylenediamine ( 4.7 ml), a suspension of sodium tert-butoxide (4.20 g), 1-methyl-2-pyrrolidone (29 ml) was stirred at 130 ° C. for 3.5 hours. The mixture was cooled to room temperature, saturated aqueous ammonium chloride solution (20 ml) and 28% aqueous ammonia (5 ml) were added and vigorously stirred, and then filtered through Celite (registered trademark). The filtrate was extracted with ethyl acetate, the obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (developing solvent hexane: ethyl acetate = 7: 3-1: 1) to give the title compound (565 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 7.70-8.98 (m, 6 H).
MS ESI / APCI Dual posi: 224 [M + H] ⁺ .
Reference Example D-1
1-Bromo-4-[(2-methoxyethyl) sulfonyl] benzene

ＷＯ２００７／０４０４４０に記載の方法に従って実験を行い、表題化合物（８００ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.23 (s, 3 H) 3.38 (t, J=6.1 Hz, 2 H) 3.75 (t, J=6.1 Hz, 2 H) 7.67 - 7.74 (m, 2 H) 7.75 - 7.81 (m, 2 H).
MS ESI/APCI Dual posi: 279[M+H]⁺.
参考例Ｄ−２
２−［（４−ブロモフェニル）スルホニル］エタノール

An experiment was performed according to the method described in WO2007 / 040440 to obtain the title compound (800 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.23 (s, 3 H) 3.38 (t, J = 6.1 Hz, 2 H) 3.75 (t, J = 6.1 Hz, 2 H) 7.67-7.74 (m, 2 H) 7.75-7.81 (m, 2 H).
MS ESI / APCI Dual posi: 279 [M + H] ⁺ .
Reference Example D-2
2-[(4-Bromophenyl) sulfonyl] ethanol

２−クロロエタノール（１．４ｍｌ）を用いて、ＷＯ２００７／０４０４４０に記載の方法に従って実験を行い、表題化合物（６０１ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.59 (t, J=6.4 Hz, 1 H) 3.32 - 3.39 (m, 2 H) 3.98 - 4.07 (m, 2 H) 7.71 - 7.77 (m, 2 H) 7.78 - 7.84 (m, 2 H).
MS ESI/APCI Dual posi: 287[M+Na]⁺.
MS ESI/APCI Dual nega: 299[M+Cl]^-.
参考例Ｄ−３
２−［（４−ブロモフェニル）スルホニル］アセトアミド

An experiment was performed using 2-chloroethanol (1.4 ml) according to the method described in WO2007 / 040440 to obtain the title compound (601 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.59 (t, J = 6.4 Hz, 1 H) 3.32-3.39 (m, 2 H) 3.98-4.07 (m, 2 H) 7.71-7.77 (m, 2 H) 7.78-7.84 (m, 2 H).
MS ESI / APCI Dual posi: 287 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 299 [M + Cl] ^- .
Reference Example D-3
2-[(4-Bromophenyl) sulfonyl] acetamide

２−ブロモアセトアミド（１．６ｇ）を用いて、ＷＯ２００７／０４０４４０に記載の方法に従って実験を行い、表題化合物（９１８ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 4.02 (s, 2 H) 5.66 (br. s, 1 H) 6.63 (br. s, 1 H) 7.70 - 7.84 (m, 4 H).
MS ESI/APCI Dual posi: 300[M+Na]⁺.
MS ESI/APCI Dual nega: 276[M-H]^-.
参考例Ｄ−４
１−［（４−ブロモフェニル）スルホニル］−２−メチルプロパン−２−オール

An experiment was conducted using 2-bromoacetamide (1.6 g) according to the method described in WO2007 / 040440 to obtain the title compound (918 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 4.02 (s, 2 H) 5.66 (br. S, 1 H) 6.63 (br. S, 1 H) 7.70-7.84 (m, 4 H).
MS ESI / APCI Dual posi: 300 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 276 [MH] ^- .
Reference Example D-4
1-[(4-Bromophenyl) sulfonyl] -2-methylpropan-2-ol

アルゴン雰囲気下、4-ブロモフェニルメチルスルホン（１．０ｇ）のテトラヒドロフラン（４３ｍｌ）溶液へ、−６０℃以下にて、ヘキサメチルジシラザンリチウム（１．０Ｍテトラヒドロフラン溶液，６．４ｍｌ）を滴下し、同温にて３０分撹拌後、アセトン（６．２ｍｌ）を滴下した。同温にて３０分撹拌後、メタノールを加えて室温へ昇温した。反応液を減圧留去した後、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝７５：２５〜６５：３５）にて精製し、表題化合物（８６０ｍｇ）を無色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 6 H) 3.30 (s, 2 H) 3.53 (s, 1 H) 7.69 - 7.83 (m, 4 H).
MS ESI/APCI Dual posi: 315[M+Na]⁺.
参考例Ｄ−５
２−［（４−ブロモ−２−フルオロフェニル）スルホニル］エタノール

Under an argon atmosphere, hexamethyldisilazane lithium (1.0 M tetrahydrofuran solution, 6.4 ml) was added dropwise to a solution of 4-bromophenylmethylsulfone (1.0 g) in tetrahydrofuran (43 ml) at −60 ° C. or lower. After stirring at the same temperature for 30 minutes, acetone (6.2 ml) was added dropwise. After stirring at the same temperature for 30 minutes, methanol was added and the temperature was raised to room temperature. After the reaction solution was distilled off under reduced pressure, the obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 75: 25-65: 35) to obtain the title compound (860 mg) as a colorless oily substance. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 6 H) 3.30 (s, 2 H) 3.53 (s, 1 H) 7.69-7.83 (m, 4 H).
MS ESI / APCI Dual posi: 315 [M + Na] ⁺ .
Reference Example D-5
2-[(4-Bromo-2-fluorophenyl) sulfonyl] ethanol

亜硫酸ナトリウム（４６１ｍｇ）、炭酸水素ナトリウム（９２１ｍｇ）の水（１８ｍｌ）懸濁液へ、９０℃にて４−ブロモ−２−フルオロベンゼンスルホニルクロライド（１．０ｇ）を加え、１時間撹拌した。ここへ２−クロロエタノール（１．３ｍｌ）を加えて、加熱還流下２０時間撹拌した。冷却後、反応液を酢酸エチルで抽出し、得られた有機層を無水硫酸ナトリウムで乾燥して濾過した。濾液を減圧下濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝６０：４０〜４０：６０）にて精製し、表題化合物（４１６ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.51 - 3.58 (m, 2 H) 4.03 - 4.09 (m, 2 H) 7.44 - 7.56 (m, 2 H) 7.80 - 7.87 (m, 1 H).
MS ESI/APCI Dual posi: 305[M+Na]⁺.
参考例Ｄ−６
２−［（４−ブロモ−３−フルオロフェニル）スルホニル］エタノール

4-Bromo-2-fluorobenzenesulfonyl chloride (1.0 g) was added to a suspension of sodium sulfite (461 mg) and sodium hydrogen carbonate (921 mg) in water (18 ml) at 90 ° C., and the mixture was stirred for 1 hour. To this was added 2-chloroethanol (1.3 ml), and the mixture was stirred with heating under reflux for 20 hours. After cooling, the reaction solution was extracted with ethyl acetate, and the resulting organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 60: 40-40: 60) to give the title compound (416 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.51-3.58 (m, 2 H) 4.03-4.09 (m, 2 H) 7.44-7.56 (m, 2 H) 7.80-7.87 (m, 1 H).
MS ESI / APCI Dual posi: 305 [M + Na] ⁺ .
Reference Example D-6
2-[(4-Bromo-3-fluorophenyl) sulfonyl] ethanol

４−ブロモ−３−フルオロベンゼンスルホニルクロライド（１．０ｇ）を用い、参考例Ｄ−５と同様の操作にて反応及び精製を行い、表題化合物（４５０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.34 - 3.41 (m, 2 H) 4.00 - 4.08 (m, 2 H) 7.59 - 7.65 (m, 1 H) 7.66 - 7.73 (m, 1 H) 7.78 - 7.86 (m, 1 H).
MS ESI/APCI Dual posi: 305[M+Na]⁺.
参考例Ｄ−７
３−［（４−ブロモフェニル）スルホニル］プロパン−１−オール

Using 4-bromo-3-fluorobenzenesulfonyl chloride (1.0 g), the reaction and purification were carried out in the same manner as in Reference Example D-5, to obtain the title compound (450 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.34-3.41 (m, 2 H) 4.00-4.08 (m, 2 H) 7.59-7.65 (m, 1 H) 7.66-7.73 (m, 1 H) 7.78 -7.86 (m, 1 H).
MS ESI / APCI Dual posi: 305 [M + Na] ⁺ .
Reference Example D-7
3-[(4-Bromophenyl) sulfonyl] propan-1-ol

４−ブロモベンゼンスルホニルクロライド（２．０ｇ）と３−ブロモ−１−プロパノール（２．０ｍｌ）を用い、参考例Ｄ−５と同様の操作にて反応及び精製を行い、表題化合物（１．７ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53 - 1.67 (m, 1 H) 1.92 - 2.06 (m, 2 H) 3.19 - 3.29 (m, 2 H) 3.70 - 3.81 (m, 2 H) 7.69 - 7.83 (m, 4 H).
MS ESI/APCI Dual posi: 279[M+H]⁺.
参考例Ｄ−８
１−ブロモ−２，５−ジフルオロ−４−（メチルスルホニル）ベンゼン

4-Bromobenzenesulfonyl chloride (2.0 g) and 3-bromo-1-propanol (2.0 ml) were used for the reaction and purification in the same manner as in Reference Example D-5, and the title compound (1.7 g )
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53-1.67 (m, 1 H) 1.92-2.06 (m, 2 H) 3.19-3.29 (m, 2 H) 3.70-3.81 (m, 2 H) 7.69 -7.83 (m, 4 H).
MS ESI / APCI Dual posi: 279 [M + H] ⁺ .
Reference Example D-8
1-Bromo-2,5-difluoro-4- (methylsulfonyl) benzene

亜硫酸ナトリウム（２６０ｍｇ）と炭酸水素ナトリウム（５１９ｍｇ）の水（１０ｍｌ）溶液へ、４−ブロモ−２，５−ジフルオロベンゼンスルホニルクロライド（６００ｍｇ）を加え加熱還流下１時間攪拌した。反応液を室温へ冷却後、ヨウ化メチル（３８５μｌ）、テトラブチルアンモニウムブロマイド（３３２ｍｇ）を加え１時間攪拌した。反応液に水を加え酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜４：１）にて精製し、表題化合物（４２７ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.23 (d, J=0.9 Hz, 3 H) 7.53 (dd, J=8.4, 4.8 Hz, 1 H) 7.74 (dd, J=7.0, 5.7 Hz, 1 H).
MS ESI/APCI Dual posi: 270[M+H]⁺.
参考例Ｅ−１
（４−シアノ−２−フルオロフェニル）ボロン酸

4-Bromo-2,5-difluorobenzenesulfonyl chloride (600 mg) was added to a solution of sodium sulfite (260 mg) and sodium bicarbonate (519 mg) in water (10 ml), and the mixture was stirred for 1 hour with heating under reflux. After cooling the reaction solution to room temperature, methyl iodide (385 μl) and tetrabutylammonium bromide (332 mg) were added and stirred for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 4: 1) to obtain the title compound (427 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.23 (d, J = 0.9 Hz, 3 H) 7.53 (dd, J = 8.4, 4.8 Hz, 1 H) 7.74 (dd, J = 7.0, 5.7 Hz, 1 H).
MS ESI / APCI Dual posi: 270 [M + H] ⁺ .
Reference Example E-1
(4-Cyano-2-fluorophenyl) boronic acid

ＥＰ２００９００７８０６に記載の方法に従って実験を行った
市販の３−フルオロ−４−ヨードベンゾニトリル（５．００ｇ）のテトラヒドロフラン（４０．５ｍｌ）溶液へ、−７８℃にてイソプロピルマグネシウムクロリド（１．０Ｍテトラヒドロフラン溶液，２４．３ｍｌ）を加え、同温にて１時間攪拌した。トリイソプロピルボラート（５．７１ｇ）を加え、室温にて３時間攪拌後、１Ｍ塩酸を加え、室温にて３０分間攪拌した。飽和食塩水を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。残渣の粉末をヘキサン−酢酸エチル混合溶液で洗浄し、表題化合物（２．８７ｇ）を灰色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 7.59 - 7.76 (m, 3 H).
MS ESI/APCI Dual posi: 166[M+H]⁺.
MS ESI/APCI Dual nega: 164[M-H]^-.
参考例Ｅ−２
３−フルオロ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Experiments were performed according to the method described in EP2009007806. Commercially available 3-fluoro-4-iodobenzonitrile (5.00 g) in tetrahydrofuran (40.5 ml) solution at −78 ° C. with isopropylmagnesium chloride (1.0 M tetrahydrofuran solution) 24.3 ml) and stirred at the same temperature for 1 hour. Triisopropyl borate (5.71 g) was added, and the mixture was stirred at room temperature for 3 hr. 1 M hydrochloric acid was added, and the mixture was stirred at room temperature for 30 min. Saturated saline was added, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The residual powder was washed with a mixed solution of hexane-ethyl acetate to give the title compound (2.87 g) as a gray powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 7.59-7.76 (m, 3 H).
MS ESI / APCI Dual posi: 166 [M + H] ⁺ .
MS ESI / APCI Dual nega: 164 [MH] ^- .
Reference Example E-2
3-Fluoro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ，２００８，３１７１−３１７８．に記載の方法に従って実験を行った。
アルゴン雰囲気下、脱水ジエチルエーテル（５０ｍｌ）へ、−８０℃にて２．７６Ｍ ｎ−ブチルリチウムヘキサン溶液（１８．１ｍｌ）を加え、市販の１，４−ジブロモ−２−フルオロベンゼン（１２．７ｇ）の脱水ジエチルエーテル（３０ｍｌ）溶液を滴下し、同温にて３０分間撹拌した。次いで、市販の２−メトキシ−４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン（７．９０ｇ）を滴下し、脱水テトラヒドロフラン（７０ｍｌ）を加え、−７０℃にて３０分間撹拌した。さらに、２．７６Ｍ ｎ−ブチルリチウムヘキサン溶液（１９．６ｍｌ）を滴下し、−６５℃にて２０分間撹拌した。最後に、反応系中へ二酸化炭素ガスをバブリングしながら−４０℃まで昇温した。同温にて１．５Ｍ硫酸水溶液（５０ｍｌ）を少しずつ加え、室温まで昇温した後、酢酸エチルで抽出を行い、有機層を飽和食塩水で洗浄、溶媒を減圧留去して無色固体を得た。得られた固体を水で懸濁、ろ取、ヘキサンで洗浄、乾燥し、表題化合物（１０．９ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 12 H) 7.71 - 7.77 (m, 1 H) 7.80 - 7.90 (m, 2 H).
MS ESI/APCI Dual nega: 265[M-H]^-.
参考例Ｅ−３
４−（ジヒドロキシボラニル）−３，５−ジフルオロ安息香酸

European Journal of Organic Chemistry, 2008, 3171-3178. The experiment was performed according to the method described in.
Under argon atmosphere, 2.76 M n-butyllithium hexane solution (18.1 ml) was added to dehydrated diethyl ether (50 ml) at −80 ° C., and commercially available 1,4-dibromo-2-fluorobenzene (12.7 g) was added. ) In anhydrous diethyl ether (30 ml) was added dropwise and stirred at the same temperature for 30 minutes. Subsequently, commercially available 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.90 g) was added dropwise, dehydrated tetrahydrofuran (70 ml) was added, and the mixture was kept at −70 ° C. for 30 minutes. Stir. Further, 2.76M n-butyllithium hexane solution (19.6 ml) was added dropwise, and the mixture was stirred at −65 ° C. for 20 minutes. Finally, the temperature was raised to −40 ° C. while bubbling carbon dioxide gas into the reaction system. A 1.5M aqueous sulfuric acid solution (50 ml) was added little by little at the same temperature, and the mixture was warmed to room temperature, extracted with ethyl acetate, the organic layer was washed with saturated brine, and the solvent was distilled off under reduced pressure to give a colorless solid. Obtained. The obtained solid was suspended in water, collected by filtration, washed with hexane and dried to give the title compound (10.9 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 12 H) 7.71-7.77 (m, 1 H) 7.80-7.90 (m, 2 H).
MS ESI / APCI Dual nega: 265 [MH] ^- .
Reference Example E-3
4- (Dihydroxyboranyl) -3,5-difluorobenzoic acid

Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，２００８，４９（１９），３１５２に記載の方法に従って実験を行った。
市販の３，５−ジフルオロ安息香酸（３．００ｇ）のテトラヒドロフラン（９４．９ｍｌ）溶液へ、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（４．８５ｇ）を加え、−７８℃にて１．０２Ｍ ｓ−ブチルリチウムシクロヘキサン−ヘキサン混合溶液（４４．７ｍｌ）を加え、同温にて８０分間攪拌した。トリメチルボラート（４．１５ｇ）を加え、室温にて２時間攪拌した。反応液に３Ｍ塩酸を加え、溶媒を減圧留去した。残渣の水層を酢酸エチルにて抽出し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。残渣の粉末をヘキサンで洗浄し、表題化合物（１．３４ｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 7.42 - 7.49 (m, 2 H).
参考例Ｅ−４
３−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Experiments were performed according to the method described in Tetrahedron Letters, 2008, 49 (19), 3152.
N, N, N ′, N′-tetramethylethylenediamine (4.85 g) was added to a solution of commercially available 3,5-difluorobenzoic acid (3.00 g) in tetrahydrofuran (94.9 ml) at −78 ° C. A 1.02 M s-butyllithium cyclohexane-hexane mixed solution (44.7 ml) was added, and the mixture was stirred at the same temperature for 80 minutes. Trimethyl borate (4.15 g) was added and stirred at room temperature for 2 hours. 3M hydrochloric acid was added to the reaction solution, and the solvent was distilled off under reduced pressure. The aqueous layer of the residue was extracted with ethyl acetate, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The residual powder was washed with hexane to give the title compound (1.34 g) as a pale yellow powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 7.42-7.49 (m, 2 H).
Reference Example E-4
3-Methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

市販の４−ブロモ−３−メチル安息香酸（２．００ｇ）、ビス（ピナコラト）ジボロン（２．８２ｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（３８０ｍｇ）、酢酸カリウム（３．６６ｇ）のＮ，Ｎ−ジメチルホルムアミド（４０ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１２０℃にて３０分間撹拌した。冷却後反応液へ水と酢酸エチルを加えてセライト（登録商標）ろ過した後、酢酸エチルで水層を洗浄した。反応液に３Ｍ塩酸を加え、酢酸エチルにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１００：０〜７０：３０）にて精製し、表題化合物（２．５２ｇ）を淡黄色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 2.59 (s, 3 H) 7.81 - 7.95 (m, 3 H).
MS ESI/APCI Dual nega: 261[M-H]^-.
参考例Ｅ−５
２−フルオロ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Commercially available 4-bromo-3-methylbenzoic acid (2.00 g), bis (pinacolato) diboron (2.82 g), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex ( 380 mg), potassium acetate (N in 3.66 g), N-dimethylformamide (40 ml) suspension, micro web - Bed reactor (Biotage, Inc. Initiator Sixty ^TM (trade name) with a), microwave irradiation The mixture was stirred at 120 ° C. for 30 minutes. After cooling, water and ethyl acetate were added to the reaction solution and filtered through Celite (registered trademark), and then the aqueous layer was washed with ethyl acetate. To the reaction solution was added 3M hydrochloric acid, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 100: 0 to 70:30) to obtain the title compound (2.52 g) as a pale yellow solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 2.59 (s, 3 H) 7.81-7.95 (m, 3 H).
MS ESI / APCI Dual nega: 261 [MH] ^- .
Reference Example E-5
2-Fluoro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

市販の４−ブロモ−２−フルオロ安息香酸（１．０２ｇ）を用いて、参考例Ｅ−４と同様の操作にて反応及び精製を行い、表題化合物（１．１３ｇ）を淡黄色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 7.49 - 7.66 (m, 2 H) 7.99 (t, J=7.4 Hz, 1 H).
MS ESI/APCI Dual posi: 267[M+H]⁺, 289[M+Na]⁺.
MS ESI/APCI Dual nega: 265[M-H]^-.
参考例Ｅ−６
２−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Using commercially available 4-bromo-2-fluorobenzoic acid (1.02 g), the reaction and purification were carried out in the same manner as in Reference Example E-4 to give the title compound (1.13 g) as a pale yellow oily substance. Obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 7.49-7.66 (m, 2 H) 7.99 (t, J = 7.4 Hz, 1 H).
MS ESI / APCI Dual posi: 267 [M + H] ⁺ , 289 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 265 [MH] ^- .
Reference Example E-6
2-Methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

市販の４−ブロモ−２−メチル安息香酸（１．００ｇ）を用いて、参考例Ｅ−４と同様の操作にて反応及び精製を行い、表題化合物（１．３０ｇ）を淡黄色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 2.65 (s, 3 H) 7.66 - 7.74 (m, 2 H) 8.03 (d, J=8.2 Hz, 1 H).
MS ESI/APCI Dual nega: 261[M-H]^-.
参考例Ｅ−７
４，４，５，５−テトラメチル−２−｛４−［（メチルスルホニル）メチル］フェニル｝−１，３，２−ジオキサボロラン
（１）１−ブロモ−４−［（メチルスルホニル）メチル］ベンゼン

The reaction and purification were carried out in the same manner as in Reference Example E-4 using commercially available 4-bromo-2-methylbenzoic acid (1.00 g) to obtain the title compound (1.30 g) as a pale yellow solid. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 2.65 (s, 3 H) 7.66-7.74 (m, 2 H) 8.03 (d, J = 8.2 Hz, 1 H).
MS ESI / APCI Dual nega: 261 [MH] ^- .
Reference Example E-7
4,4,5,5-tetramethyl-2- {4-[(methylsulfonyl) methyl] phenyl} -1,3,2-dioxaborolane (1) 1-bromo-4-[(methylsulfonyl) methyl] benzene

市販の１−ブロモ−４−（ブロモメチル）ベンゼン（１．００ｇ）のＮ，Ｎ−ジメチルホルムアミド（８．００ｍｌ）溶液へ、メタンスルフィン酸ナトリウム（８１７ｍｇ）を加え、６０℃にて２時間攪拌した。反応液へ水を加え、析出した粉末をろ取し、水、ヘキサンにて洗浄した。得られた粉末を減圧乾燥し、表題化合物（８６０ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.78 (s, 3 H) 4.20 (s, 2 H) 7.24 - 7.34 (m, 2 H) 7.51 - 7.61 (m, 2 H).
MS ESI/APCI Dual posi: 271[M+Na]⁺.
MS ESI/APCI Dual nega: 283[M+Cl]^-.
（２）４，４，５，５−テトラメチル−２−｛４−［（メチルスルホニル）メチル］フェニル｝−１，３，２−ジオキサボロラン

Sodium methanesulfinate (817 mg) was added to a commercially available solution of 1-bromo-4- (bromomethyl) benzene (1.00 g) in N, N-dimethylformamide (8.00 ml), and the mixture was stirred at 60 ° C. for 2 hours. . Water was added to the reaction solution, and the precipitated powder was collected by filtration and washed with water and hexane. The obtained powder was dried under reduced pressure to obtain the title compound (860 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.78 (s, 3 H) 4.20 (s, 2 H) 7.24-7.34 (m, 2 H) 7.51-7.61 (m, 2 H).
MS ESI / APCI Dual posi: 271 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 283 [M + Cl] ^- .
(2) 4,4,5,5-tetramethyl-2- {4-[(methylsulfonyl) methyl] phenyl} -1,3,2-dioxaborolane

参考例Ｅ−７（１）で得られた化合物（２００ｍｇ）のジメチルスルホキシド（２．６８ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（３０６ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（６５．５ｍｇ）、酢酸カリウム（３９４ｍｇ）を加え、１００℃にて２時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１）にて精製し、表題化合物（２１５ｍｇ）を薄茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.73 (s, 3 H) 4.26 (s, 2 H) 7.37 - 7.46 (m, 2 H) 7.81 - 7.89 (m, 2 H).
MS ESI/APCI Dual nega: 331[M+Cl]^-.
参考例Ｅ−８
２−［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］プロパン−２−オール
（１）２−（４−ブロモフェニル）プロパン−２−オール

To a solution of the compound (200 mg) obtained in Reference Example E-7 (1) in dimethyl sulfoxide (2.68 ml), bis (pinacolato) diboron (306 mg), [1,1′-bis (diphenylphosphino) ferrocene] Palladium (II) dichloride dichloromethane complex (65.5 mg) and potassium acetate (394 mg) were added, and the mixture was stirred at 100 ° C. for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1) to obtain the title compound (215 mg) as a light brown powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.73 (s, 3 H) 4.26 (s, 2 H) 7.37-7.46 (m, 2 H) 7.81-7.89 (m, 2 H).
MS ESI / APCI Dual nega: 331 [M + Cl] ^- .
Reference Example E-8
2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] propan-2-ol (1) 2- (4-bromophenyl) propane-2 -All

市販の１−（４−ブロモフェニル）エタノン（２．００ｇ）のテトラヒドロフラン（５０．０ｍｌ）溶液へ、−７８℃にて１Ｍ メチルマグネシウムブロミドテトラヒドロフラン溶液（３０．１ｍｌ）を加え、室温にて１５時間攪拌した。飽和塩化アンモニウム水溶液を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜４：１）にて精製し、表題化合物（３６８ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.57 (s, 6 H) 7.30 - 7.53 (m, 4 H).
MS ESI/APCI Dual nega: 213[M-H]^-.
（２）２−［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］プロパン−２−オール

To a commercially available solution of 1- (4-bromophenyl) ethanone (2.00 g) in tetrahydrofuran (50.0 ml) was added 1M methylmagnesium bromide tetrahydrofuran solution (30.1 ml) at −78 ° C., and the mixture was stirred at room temperature for 15 hours. Stir. A saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 4: 1) to give the title compound (368 mg) as a colorless oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.57 (s, 6 H) 7.30-7.53 (m, 4 H).
MS ESI / APCI Dual nega: 213 [MH] ^- .
(2) 2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] propan-2-ol

参考例Ｅ−８（１）で得られた化合物（３６８ｍｇ）のジメチルスルホキシド（５．７０ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（５２１ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１４０ｍｇ）、酢酸カリウム（５０３ｍｇ）を加え、８０℃にて２時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１）にて精製し、表題化合物（５３５ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.34 (s, 12 H) 1.58 (s, 6 H) 7.45 - 7.56 (m, 2 H) 7.74 - 7.86 (m, 2 H).
MS ESI/APCI Dual posi: 263[M+H]⁺.
参考例Ｅ−９
２−［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］アセトアミド
（１）２−（４−ブロモフェニル）アセトアミド

To a dimethyl sulfoxide (5.70 ml) solution of the compound (368 mg) obtained in Reference Example E-8 (1), bis (pinacolato) diboron (521 mg), [1,1′-bis (diphenylphosphino) ferrocene] Palladium (II) dichloride dichloromethane complex (140 mg) and potassium acetate (503 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1) to give the title compound (535 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.34 (s, 12 H) 1.58 (s, 6 H) 7.45-7.56 (m, 2 H) 7.74-7.86 (m, 2 H).
MS ESI / APCI Dual posi: 263 [M + H] ⁺ .
Reference Example E-9
2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] acetamide (1) 2- (4-Bromophenyl) acetamide

市販の２−（４−ブロモフェニル）酢酸（２．００ｇ）、２８％アンモニア水（６７９ｍｇ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（２．１５ｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（１．７２ｇ）、トリエチルアミン（１．１３ｇ）のＮ，Ｎ−ジメチルホルムアミド（４６．５ｍｌ）溶液を室温で１５時間撹拌した。反応液へ酢酸エチルを加え、水で洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥した。乾燥剤を濾別後、溶媒を減圧下留去し、得られた残渣をヘキサン−酢酸エチル混合溶液で懸濁撹拌した後、固体をろ取し、表題化合物（１．３１ｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.54 (s, 2 H) 7.11 - 7.22 (m, 2 H) 7.44 - 7.54 (m, 2 H).
MS ESI/APCI Dual posi: 214[M+H]⁺.
MS ESI/APCI Dual nega: 212[M-H]^-.
（２）２−［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］アセトアミド

Commercially available 2- (4-bromophenyl) acetic acid (2.00 g), 28% aqueous ammonia (679 mg), N-ethyl-N′-3-dimethylaminopropylcarbodiimide hydrochloride (2.15 g), 1-hydroxybenzo A solution of triazol monohydrate (1.72 g) and triethylamine (1.13 g) in N, N-dimethylformamide (46.5 ml) was stirred at room temperature for 15 hours. Ethyl acetate was added to the reaction solution and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate. After the desiccant was filtered off, the solvent was distilled off under reduced pressure. The resulting residue was suspended and stirred in a hexane-ethyl acetate mixed solution, and the solid was collected by filtration to give the title compound (1.31 g) as a colorless powder. Obtained.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.54 (s, 2 H) 7.11-7.22 (m, 2 H) 7.44-7.54 (m, 2 H).
MS ESI / APCI Dual posi: 214 [M + H] ⁺ .
MS ESI / APCI Dual nega: 212 [MH] ^- .
(2) 2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] acetamide

参考例Ｅ−９（１）で得られた化合物（５００ｍｇ）を用い、参考例Ｅ−８（２）と同様の方法で合成を行い、表題化合物（３５４ｍｇ）を茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 3.61 (s, 2 H) 7.25 - 7.34 (m, 2 H) 7.76 - 7.85 (m, 2 H).
MS ESI/APCI Dual posi: 262[M+H]⁺, 284[M+Na]⁺.
MS ESI/APCI Dual nega: 260[M-H]^-.
参考例Ｅ−１０
２，５−ジフルオロ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Using the compound (500 mg) obtained in Reference Example E-9 (1), synthesis was performed in the same manner as in Reference Example E-8 (2) to obtain the title compound (354 mg) as a brown powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 3.61 (s, 2 H) 7.25-7.34 (m, 2 H) 7.76-7.85 (m, 2 H).
MS ESI / APCI Dual posi: 262 [M + H] ⁺ , 284 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 260 [MH] ^- .
Reference Example E-10
2,5-difluoro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

アルゴン雰囲気下、ｎ−ブチルリチウム（２．６４Ｍヘキサン溶液、１．３９ｍｌ）のジエチルエーテル（４ｍｌ）溶液に−７８℃で１，４−ジブロモ−２，５−ジフルオロベンゼン（１．００ｇ）のジエチルエーテル（３ｍｌ）溶液を滴下し、３０分間撹拌後、２−メトキシ-４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン（５８１ｍｇ）のジエチルエーテル（６ｍｌ）溶液を滴下した。同温で３０分間撹拌後、さらにｎ−ブチルリチウム（２．６４Ｍヘキサン溶液、１．５０ｍｌ）を滴下し、３０分間撹拌して、ドライアイスを加えた。−４０℃まで昇温しながら１時間攪拌後、１Ｍ硫酸水溶液を加えた。室温に昇温後、酢酸エチルを加えて分液操作を行った。得られた水層を酢酸エチルにて抽出し、有機層を飽和食塩水で洗浄した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１０：０〜８：２）にて精製し、表題化合物（５３１ｍｇ）を淡黄色固体として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.31 (s, 12 H) 7.33 - 7.46 (m, 1 H) 7.48 - 7.61 (m, 1 H).
参考例Ｅ−１１
２−［２，５−ジフルオロ−４−（メチルスルファニル）フェニル］−４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン
（１）４−ブロモ−２，５−ジフルオロベンゼンチオール

A solution of 1,4-dibromo-2,5-difluorobenzene (1.00 g) in diethyl ether (4 ml) in n-butyllithium (2.64 M hexane solution, 1.39 ml) at −78 ° C. under an argon atmosphere. An ether (3 ml) solution was added dropwise, and after stirring for 30 minutes, a solution of 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (581 mg) in diethyl ether (6 ml) was added dropwise. After stirring at the same temperature for 30 minutes, n-butyllithium (2.64 M hexane solution, 1.50 ml) was further added dropwise, stirred for 30 minutes, and dry ice was added. After stirring for 1 hour while raising the temperature to −40 ° C., 1M aqueous sulfuric acid solution was added. After raising the temperature to room temperature, ethyl acetate was added to carry out a liquid separation operation. The obtained aqueous layer was extracted with ethyl acetate, and the organic layer was washed with saturated brine. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent chloroform: methanol = 10: 0 to 8: 2) to obtain the title compound (531 mg) as a pale yellow solid.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.31 (s, 12 H) 7.33-7.46 (m, 1 H) 7.48-7.61 (m, 1 H).
Reference Example E-11
2- [2,5-difluoro-4- (methylsulfanyl) phenyl] -4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1) 4-bromo-2,5-difluorobenzenethiol

４−ブロモ−２，５−ジフルオロベンゼンスルホニルクロライド（２．０３ｇ）のＮ，Ｎ−ジメチルホルムアミド（０．４ｍｌ）−クロロホルム（１５ｍｌ）混合溶液へトリフェニルホスフィン（５．４８ｇ）を加え、室温で３時間攪拌した。反応液へ１Ｍ塩酸を加えクロロホルムにて抽出した。有機層を濃縮後、得られた残渣へ１Ｍ水酸化ナトリウム水溶液を加え、縣濁液をセライト（登録商標）濾過し、濾液をジエチルエーテルにて抽出洗浄した。得られた水層へ１Ｍ塩酸を加え中和した後、ジエチルエーテルで２回抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１）にて精製し、表題化合物（５６１ｍｇ）を薄茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.69 (d, J=1.8 Hz, 1 H) 7.08 (dd, J=8.1, 6.4 Hz, 1 H) 7.22 - 7.36 (m, 1 H)．
MS ESI/APCI Dual nega: 222[M-H]^-.
（２）１−ブロモ−２，５−ジフルオロ−４−（メチルスルファニル）ベンゼン

Triphenylphosphine (5.48 g) was added to a mixed solution of 4-bromo-2,5-difluorobenzenesulfonyl chloride (2.03 g) in N, N-dimethylformamide (0.4 ml) -chloroform (15 ml) at room temperature. Stir for 3 hours. 1M Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. After concentrating the organic layer, 1 M aqueous sodium hydroxide solution was added to the resulting residue, the suspension was filtered through Celite (registered trademark), and the filtrate was extracted and washed with diethyl ether. The resulting aqueous layer was neutralized with 1M hydrochloric acid, and then extracted twice with diethyl ether. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1) to obtain the title compound (561 mg) as a light brown powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.69 (d, J = 1.8 Hz, 1 H) 7.08 (dd, J = 8.1, 6.4 Hz, 1 H) 7.22-7.36 (m, 1 H).
MS ESI / APCI Dual nega: 222 [MH] ^- .
(2) 1-bromo-2,5-difluoro-4- (methylsulfanyl) benzene

参考例Ｅ−１１（１）で得られた化合物（５６０ｍｇ）のテトラヒドロフラン（３ｍｌ）溶液へ、氷冷下、水素化ナトリウム（６０％オイル懸濁、１２０ｍｇ）を加え５分攪拌後、ヨウ化メチル（１７１μｌ）を加え室温で１０分攪拌した。反応液へ１Ｍ塩酸を加え、クロロホルムにて抽出した。得られた有機層を水で洗浄し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別した。溶媒を減圧留去して得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜９：１）にて精製し、表題化合物（４２５ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.46 (s, 3 H) 6.93 - 7.03 (m, 1 H) 7.23 (dd, J=8.6, 5.9 Hz, 1 H).
（３）２−［２，５−ジフルオロ−４−（メチルスルファニル）フェニル］−４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン

To a solution of the compound (560 mg) obtained in Reference Example E-11 (1) in tetrahydrofuran (3 ml) was added sodium hydride (60% oil suspension, 120 mg) under ice-cooling, and the mixture was stirred for 5 minutes, and then methyl iodide. (171 μl) was added and stirred at room temperature for 10 minutes. 1M Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was washed with water and dried over anhydrous sodium sulfate, and then the desiccant was filtered off. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 9: 1) to obtain the title compound (425 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.46 (s, 3 H) 6.93-7.03 (m, 1 H) 7.23 (dd, J = 8.6, 5.9 Hz, 1 H).
(3) 2- [2,5-difluoro-4- (methylsulfanyl) phenyl] -4,4,5,5-tetramethyl-1,3,2-dioxaborolane

参考例Ｅ−１１（２）で得られた化合物（３０５ｍｇ）を用いて、参考例Ｅ−７（２）と同様の操作にて反応及び精製を行い、表題化合物（１３８ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.47 (s, 3 H) 6.84 (dd, J=9.2, 5.7 Hz, 1 H) 7.33 (dd, J=9.7, 4.8 Hz, 1 H).
参考例Ｅ−１２
ｔｅｒｔ−ブチル（ジメチル）（２−｛［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］スルファニル｝エトキシ）シラン
（１）４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ベンゼンチオール

Using the compound (305 mg) obtained in Reference Example E-11 (2), the reaction and purification were conducted in the same manner as in Reference Example E-7 (2) to obtain the title compound (138 mg) as a colorless powder. It was.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.47 (s, 3 H) 6.84 (dd, J = 9.2, 5.7 Hz, 1 H) 7.33 (dd, J = 9.7, 4.8 Hz, 1 H).
Reference Example E-12
tert-butyl (dimethyl) (2-{[4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] sulfanyl} ethoxy) silane (1) 4- ( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzenethiol

４−メルカプトフェニルボロン酸（２．０ｇ）、ピナコール（１．６ｇ）、無水硫酸マグネシウム（３．３ｇ）のクロロホルム（５９ｍｌ）懸濁液を室温で１時間撹拌した。反応液を濾過後、濾液を減圧下濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（ノルマルヘキサン：酢酸エチル＝８５：１５〜７５：２５）にて精製し、表題化合物（３．４ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 12 H) 3.48 (s, 1 H) 7.21 - 7.28 (m, 2 H) 7.62 - 7.69 (m, 2 H).
MS ESI/APCI Dual nega: 235[M-H]^-.
（２）ｔｅｒｔ−ブチル（ジメチル）（２−｛［４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）フェニル］スルファニル｝エトキシ）シラン

A suspension of 4-mercaptophenylboronic acid (2.0 g), pinacol (1.6 g) and anhydrous magnesium sulfate (3.3 g) in chloroform (59 ml) was stirred at room temperature for 1 hour. After the reaction solution was filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (normal hexane: ethyl acetate = 85: 15 to 75:25) to give the title compound (3.4 g). Obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 12 H) 3.48 (s, 1 H) 7.21-7.28 (m, 2 H) 7.62-7.69 (m, 2 H).
MS ESI / APCI Dual nega: 235 [MH] ^- .
(2) tert-butyl (dimethyl) (2-{[4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] sulfanyl} ethoxy) silane

参考例Ｅ−１２（１）で得られた化合物（３００ｍｇ）のテトラヒドロフラン（７ｍｌ）及びＮ，Ｎ−ジメチルホルムアミド（７ｍｌ）溶液へ、氷冷下にて水素化ナトリウム（６０％オイル懸濁、６１ｍｇ）を加え、５分撹拌後（２−ブロモエトキシ）−ｔｅｒｔ−ブチルジメチルシラン（３３０μｌ）を加えた。氷浴をはずした後３時間撹拌を行い、反応液へ水を加え、酢酸エチル／ノルマルヘキサン（１：１）で抽出した。得られた有機層を水で洗浄し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別した。濾液を減圧下濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（ノルマルヘキサン：酢酸エチル＝９９：１〜９４：６）にて精製し、表題化合物（４４２ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.05 (s, 6 H) 0.89 (s, 9 H) 1.34 (s, 12 H) 3.10 (t, J=7.1 Hz, 2 H) 3.80 (t, J=7.1 Hz, 2 H) 7.28 - 7.32 (m, 2 H) 7.66 - 7.72 (m, 2 H).
参考例Ｅ−１３
３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン−２−カルボニトリル

To a solution of the compound (300 mg) obtained in Reference Example E-12 (1) in tetrahydrofuran (7 ml) and N, N-dimethylformamide (7 ml), sodium hydride (60% oil suspension, 61 mg) under ice-cooling. ) Was added and after stirring for 5 minutes, (2-bromoethoxy) -tert-butyldimethylsilane (330 μl) was added. After removing the ice bath, the mixture was stirred for 3 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate / normal hexane (1: 1). The obtained organic layer was washed with water and dried over anhydrous sodium sulfate, and then the desiccant was filtered off. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (normal hexane: ethyl acetate = 99: 1 to 94: 6) to obtain the title compound (442 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.05 (s, 6 H) 0.89 (s, 9 H) 1.34 (s, 12 H) 3.10 (t, J = 7.1 Hz, 2 H) 3.80 (t, J = 7.1 Hz, 2 H) 7.28-7.32 (m, 2 H) 7.66-7.72 (m, 2 H).
Reference Example E-13
3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-2-carbonitrile

窒素雰囲気下、２，２，６，６−テトラメチルピペリジン（１０．０ｇ）のテトラヒドロフラン（１００ｍｌ）溶液へ、−３０℃にてｎ−ブチルリチウム（２．６４Ｍ ヘキサン溶液，２７ｍｌ）を滴下した後、−７８℃にてトリイソプロピルボラート（１５．６ｇ）を加え５分攪拌した。反応液へ２−シアノピリジン（６．１５ｇ）のテトラヒドロフラン（１００ｍｌ）溶液を滴下し室温で一晩攪拌後、酢酸（４．７ｍｌ）、ピナコール（１０．５ｇ）を加え室温で２時間攪拌した。反応液へ１０％リン酸二水素カリウム水溶液を加え、クロロホルムにて抽出した。さらに水層へ３Ｍ塩酸を加えクロロホルムにて抽出した。先に得られた有機層と合わせて無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１〜クロロホルム：メタノール＝９：１）にて精製後、得られた残渣を酢酸エチルに溶解し、水で洗浄した。有機層を濃縮し、得られた残渣を再度シリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１〜クロロホルム：メタノール＝９：１）にて精製し表題化合物（４．１２ｇ）を無色固体として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 7.48 (dd, J=7.9, 4.8 Hz, 1 H) 8.18 (dd, J=7.9, 2.0 Hz, 1 H) 8.75 (dd, J=4.8, 2.0 Hz, 1 H).
参考例Ｅ−１４
［２−（ジフルオロメチル）ピリジン−３−イル］ボロン酸
（１）３−ブロモ−２−（ジフルオロメチル）ピリジン

After dropwise addition of n-butyllithium (2.64 M hexane solution, 27 ml) at −30 ° C. to a tetrahydrofuran (100 ml) solution of 2,2,6,6-tetramethylpiperidine (10.0 g) in a nitrogen atmosphere. Triisopropyl borate (15.6 g) was added at −78 ° C., and the mixture was stirred for 5 minutes. To the reaction solution was added dropwise a solution of 2-cyanopyridine (6.15 g) in tetrahydrofuran (100 ml), and the mixture was stirred overnight at room temperature. Acetic acid (4.7 ml) and pinacol (10.5 g) were added, and the mixture was stirred at room temperature for 2 hr. To the reaction solution was added 10% aqueous potassium dihydrogen phosphate solution, and the mixture was extracted with chloroform. Further, 3M hydrochloric acid was added to the aqueous layer and the mixture was extracted with chloroform. The organic layer obtained previously was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1 to chloroform: methanol = 9: 1), and the obtained residue was dissolved in ethyl acetate, Washed with. The organic layer was concentrated, and the resulting residue was purified again by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1 to chloroform: methanol = 9: 1) to give the title compound (4.12 g). ) Was obtained as a colorless solid.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 7.48 (dd, J = 7.9, 4.8 Hz, 1 H) 8.18 (dd, J = 7.9, 2.0 Hz, 1 H) 8.75 ( dd, J = 4.8, 2.0 Hz, 1 H).
Reference Example E-14
[2- (Difluoromethyl) pyridin-3-yl] boronic acid (1) 3-bromo-2- (difluoromethyl) pyridine

３−ブロモ−２−ホルミルピリジン（４２０ｍｇ）のクロロホルム（１０．０ｍｌ）溶液へビス（２−メトキシエチル）アミノサルファートリフルオリド（１．５０ｇ）を加え、室温にて１時間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１）にて精製し、表題化合物（３９０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 6.59 - 7.20 (m, 1 H) 7.27 - 7.37 (m, 1 H) 7.92 - 8.03 (m, 1 H) 8.65 (dd, J=4.6, 1.5 Hz, 1 H).
（２）［２−（ジフルオロメチル）ピリジン−３−イル］ボロン酸

Bis (2-methoxyethyl) aminosulfur trifluoride (1.50 g) was added to a chloroform (10.0 ml) solution of 3-bromo-2-formylpyridine (420 mg), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1) to obtain the title compound (390 mg) as a colorless oily substance.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 6.59-7.20 (m, 1 H) 7.27-7.37 (m, 1 H) 7.92-8.03 (m, 1 H) 8.65 (dd, J = 4.6, 1.5 Hz , 1 H).
(2) [2- (Difluoromethyl) pyridin-3-yl] boronic acid

ｎ−ブチルリチウム（２．６０Ｍ ヘキサン溶液，０．４４ｍｌ）のジエチルエーテル（９．００ｍｌ）溶液へ、−７８℃にて参考例Ｅ−１４（１）で得られた化合物（２００ｍｇ）のジエチルエーテル（５．００ｍｌ）溶液を加え、同温で１時間攪拌した。反応液へ−７８℃にてトリイソプロピルボラート（２１６ｍｇ）のジエチルエーテル（５．００ｍｌ）溶液を滴下した後、室温へ昇温し１時間攪拌した。反応液へ５％水酸化ナトリウム水溶液を加えた後、氷冷下、水層へ３Ｍ塩酸を加えｐＨ６〜７へ調製した。酢酸エチルにて３回抽出し、合わせた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をジエチルエーテルにて洗浄し表題化合物（３３ｍｇ）を茶色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 6.83 - 7.45 (m, 1 H) 7.46 - 7.56 (m, 1 H) 8.02 (d, J=7.9 Hz, 1 H) 8.65 (dd, J=4.8, 1.8 Hz, 1 H).
参考例Ｅ−１５
５−フルオロ−２−メチル−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン
（１）３−ブロモ−５−フルオロ−２−メチルピリジン

n-Butyllithium (2.60M hexane solution, 0.44 ml) in diethyl ether (9.00 ml) at −78 ° C. with diethyl ether of the compound (200 mg) obtained in Reference Example E-14 (1) (5.00 ml) solution was added and stirred at the same temperature for 1 hour. A solution of triisopropyl borate (216 mg) in diethyl ether (5.00 ml) was added dropwise to the reaction solution at −78 ° C., and then the mixture was warmed to room temperature and stirred for 1 hour. After adding 5% aqueous sodium hydroxide solution to the reaction solution, 3M hydrochloric acid was added to the aqueous layer under ice cooling to adjust the pH to 6-7. The mixture was extracted three times with ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was washed with diethyl ether to give the title compound (33 mg) as a brown powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 6.83-7.45 (m, 1 H) 7.46-7.56 (m, 1 H) 8.02 (d, J = 7.9 Hz, 1 H) 8.65 (dd, J = (4.8, 1.8 Hz, 1 H).
Reference Example E-15
5-Fluoro-2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1) 3-bromo-5-fluoro-2-methylpyridine

２，３−ジブロモ−５−フルオロピリジン（９３０ｍｇ）の１，４−ジオキサン（８.００ｍｌ）溶液へ、メチルボロン酸（６５５ｍｇ）、テトラキス（トリフェニルホスフィン）パラジウム（２１０ｍｇ）、炭酸カリウム（１．５１ｇ）、水（１．７０ｍｌ）を加え、１１０℃にて一晩攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９９：１〜９７：３）にて精製後、分取用ＴＬＣ（展開溶媒 ヘキサン：酢酸エチル＝９５：５で２回展開）で精製し、表題化合物（１３３ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.64 (d, J=1.3 Hz, 3 H) 7.61 (dd, J=7.5, 2.6 Hz, 1 H) 8.32 (d, J=2.6 Hz, 1 H).
（２）５−フルオロ−２−メチル−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン

To a solution of 2,3-dibromo-5-fluoropyridine (930 mg) in 1,4-dioxane (8.00 ml), methylboronic acid (655 mg), tetrakis (triphenylphosphine) palladium (210 mg), potassium carbonate (1.51 g) ) And water (1.70 ml) were added, and the mixture was stirred at 110 ° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 99: 1 to 97: 3) and then preparative TLC (developing solvent hexane: ethyl acetate = 95: 5, developed twice). To give the title compound (133 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.64 (d, J = 1.3 Hz, 3 H) 7.61 (dd, J = 7.5, 2.6 Hz, 1 H) 8.32 (d, J = 2.6 Hz, 1 H ).
(2) 5-Fluoro-2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine

参考例Ｅ−１５（１）で得られた化合物（１３３ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（７．００ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（２３１ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（２９．０ｍｇ）、酢酸カリウム（２０６ｍｇ）を加え、８０℃にて４時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：４）にて精製した。得られた残渣へ水を加え析出した結晶を濾別し、水層を酢酸エチルにて抽出後、溶媒を減圧留去し表題化合物（２９ｍｇ）を黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.71 (d, J=1.3 Hz, 3 H) 7.73 (dd, J=8.8, 3.1 Hz, 1 H) 8.35 (d, J=3.1 Hz, 1 H).
参考例Ｅ−１６
４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン−３−カルボニトリル
（１）（３−シアノピリジン−４−イル）ボロン酸

To a solution of the compound (133 mg) obtained in Reference Example E-15 (1) in N, N-dimethylformamide (7.00 ml), bis (pinacolato) diboron (231 mg), [1,1′-bis (diphenylphosphine) Fino) ferrocene] palladium (II) dichloride dichloromethane complex (29.0 mg) and potassium acetate (206 mg) were added, and the mixture was stirred at 80 ° C. for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 4). Water was added to the resulting residue, and the precipitated crystals were filtered off. The aqueous layer was extracted with ethyl acetate, and the solvent was evaporated under reduced pressure to give the title compound (29 mg) as a yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.71 (d, J = 1.3 Hz, 3 H) 7.73 (dd, J = 8.8, 3.1 Hz, 1 H) 8.35 (d, J = 3.1 Hz, 1 H).
Reference Example E-16
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-3-carbonitrile (1) (3-cyanopyridin-4-yl) boronic acid

２，２，６，６−テトラメチルピペリジン（５．７０ｇ）のテトラヒドロフラン（３８．４ｍｌ）溶液へ、−３０℃にてｎ−ブチルリチウム（２．６４Ｍ ヘキサン溶液，１４．６ｍｌ）を滴下し、０℃にて１５分間攪拌した。−７８℃にて３−シアノピリジン（２．００ｇ）のテトラヒドロフラン（１９．２ｍｌ）溶液を加え、３０分間攪拌した。同温にてトリイソプロピルボラート（７．２２ｇ）を加え、１５分間攪拌した。室温まで昇温し、反応液へ水を加えた。水層をジエチルエーテルで洗浄後、１Ｍ塩酸を加えてｐＨ６とし、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別、溶媒を減圧留去し、表題化合物（４５０ｍｇ）を茶色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 7.67 (d, J=5.0 Hz, 1 H) 8.68 (d, J=5.0 Hz, 1 H) 8.82 (s, 1 H).
（２）４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン−３−カルボニトリル

To a solution of 2,2,6,6-tetramethylpiperidine (5.70 g) in tetrahydrofuran (38.4 ml), n-butyllithium (2.64 M hexane solution, 14.6 ml) was added dropwise at −30 ° C., Stir at 0 ° C. for 15 minutes. A solution of 3-cyanopyridine (2.00 g) in tetrahydrofuran (19.2 ml) was added at −78 ° C., and the mixture was stirred for 30 minutes. Triisopropyl borate (7.22 g) was added at the same temperature and stirred for 15 minutes. The temperature was raised to room temperature, and water was added to the reaction solution. The aqueous layer was washed with diethyl ether, adjusted to pH 6 with 1M hydrochloric acid, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to obtain the title compound (450 mg) as a brown powder.
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 7.67 (d, J = 5.0 Hz, 1 H) 8.68 (d, J = 5.0 Hz, 1 H) 8.82 (s, 1 H).
(2) 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-3-carbonitrile

参考例Ｅ−１６（１）で得られた化合物（３８０ｍｇ）のトルエン（１２．８ｍｌ）懸濁液にピナコール（３０４ｍｇ）、硫酸マグネシウム（１．５５ｇ）を加え、室温にて１５時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別、溶媒を減圧留去し、表題化合物（１１０ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 1.18 (s, 12 H) 7.64 - 7.68 (m, 1 H) 8.64 - 8.67 (m, 1 H) 8.79 - 8.82 (m, 1 H).
参考例Ｅ−１７
２−フルオロ−５−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸
（１）４−ブロモ−２−フルオロ−５−メチル安息香酸

Pinacol (304 mg) and magnesium sulfate (1.55 g) were added to a toluene (12.8 ml) suspension of the compound (380 mg) obtained in Reference Example E-16 (1), and the mixture was stirred at room temperature for 15 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound (110 mg) as a light brown powder.
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 1.18 (s, 12 H) 7.64-7.68 (m, 1 H) 8.64-8.67 (m, 1 H) 8.79-8.82 (m, 1 H).
Reference Example E-17
2-Fluoro-5-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid (1) 4-bromo-2-fluoro-5-methyl benzoic acid

アルゴン雰囲気下、２，５−ジブロモ−４−フルオロトルエン（２．５ｇ）のテトラヒドロフラン（４７ｍｌ）溶液に−７８℃でｎ−ブチルリチウム（２．６４Ｍヘキサン溶液、３．７ｍｌ）を滴下し、３０分間撹拌後、ドライアイスを加えた。室温に昇温後、１Ｍ水酸化ナトリウム水溶液、酢酸エチルを加えて分液操作を行った。有機層から、さらに１Ｍ水酸化ナトリウム水溶液で抽出後、水層を飽和塩化アンモニウム水溶液で中和した。この水層からクロロホルムで２回抽出し、無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去して、表題化合物（１．９ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.42 (s, 3 H) 7.41 (d, J=9.9 Hz, 1 H) 7.88 (d, J=7.5 Hz, 1 H).
（２）２−フルオロ−５−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Under an argon atmosphere, n-butyllithium (2.64 M hexane solution, 3.7 ml) was added dropwise to a solution of 2,5-dibromo-4-fluorotoluene (2.5 g) in tetrahydrofuran (47 ml) at −78 ° C. After stirring for minutes, dry ice was added. After raising the temperature to room temperature, a 1M aqueous sodium hydroxide solution and ethyl acetate were added to carry out a liquid separation operation. The organic layer was further extracted with 1M aqueous sodium hydroxide solution, and the aqueous layer was neutralized with saturated aqueous ammonium chloride solution. The aqueous layer was extracted twice with chloroform, dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure to obtain the title compound (1.9 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.42 (s, 3 H) 7.41 (d, J = 9.9 Hz, 1 H) 7.88 (d, J = 7.5 Hz, 1 H).
(2) 2-Fluoro-5-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

参考例Ｅ−１７（１）で得られた化合物（１．０ｇ）、ビス（ピナコラト）ジボロン（１．３ｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（０．１８ｇ）、酢酸カリウム（１．７ｇ）のＮ，Ｎ−ジメチルホルムアミド（７．５ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^ＴＭ（商品名））を用いて、マイクロウェーブ照射下１２０℃にて３０分間撹拌した。室温に昇温後、１Ｍ水酸化ナトリウム水溶液、酢酸エチルを加えて分液操作を行った。有機層から、さらに１Ｍ水酸化ナトリウム水溶液で抽出後、水層を飽和塩化アンモニウム水溶液で中和した。この水層からクロロホルムで２回抽出し、無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去して、表題化合物（１．１ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21 - 1.31 (m, 12 H) 2.10 (s, 3 H) 7.42 - 7.56 (m, 1 H) 7.68 - 7.84 (m, 1 H).
参考例Ｅ−１８
２−メトキシ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Compound (1.0 g) obtained in Reference Example E-17 (1), bis (pinacolato) diboron (1.3 g), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane A suspension of a complex (0.18 g) and potassium acetate (1.7 g) in N, N-dimethylformamide (7.5 ml) was added to a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). And stirred for 30 minutes at 120 ° C. under microwave irradiation. After raising the temperature to room temperature, a 1M aqueous sodium hydroxide solution and ethyl acetate were added to carry out a liquid separation operation. The organic layer was further extracted with 1M aqueous sodium hydroxide solution, and the aqueous layer was neutralized with saturated aqueous ammonium chloride solution. The aqueous layer was extracted twice with chloroform, dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure to obtain the title compound (1.1 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21-1.31 (m, 12 H) 2.10 (s, 3 H) 7.42-7.56 (m, 1 H) 7.68-7.84 (m, 1 H).
Reference Example E-18
2-Methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

４−ブロモ−２−メトキシ安息香酸（１．００ｇ）を用い、参考例Ｅ−４と同様の操作にて反応を行い、表題化合物（６１０ｍｇ）を茶色油状物質として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.96 (s, 12 H) 4.12 (s, 3 H) 7.45 (s, 1 H) 7.55 - 7.58 (m, 1 H) 8.15 - 8.18 (m, 1 H).
参考例Ｅ−１９
３−メトキシ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

4-Bromo-2-methoxybenzoic acid (1.00 g) was used in the same manner as in Reference Example E-4 to give the title compound (610 mg) as a brown oil.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.96 (s, 12 H) 4.12 (s, 3 H) 7.45 (s, 1 H) 7.55-7.58 (m, 1 H) 8.15-8.18 (m, 1 H).
Reference Example E-19
3-Methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

４−ブロモ−３−メトキシ安息香酸（５００ｍｇ）を用い、参考例Ｅ−４と同様の操作にて反応を行い、表題化合物（４８０ｍｇ）を茶色油状物質として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 12 H) 3.90 (s, 3 H) 7.55 (s, 1 H) 7.67 - 7.70 (m, 1 H) 7.72 - 7.76 (m, 1 H).
参考例Ｅ−２０
メチル ３−シアノ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ベンゾエート
（１）メチル ３−シアノ−４−ヒドロキシベンゾエート

4-Bromo-3-methoxybenzoic acid (500 mg) was used in the same manner as in Reference Example E-4 to give the title compound (480 mg) as a brown oil.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 12 H) 3.90 (s, 3 H) 7.55 (s, 1 H) 7.67-7.70 (m, 1 H) 7.72-7.76 (m, 1 H).
Reference Example E-20
Methyl 3-cyano-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate (1) Methyl 3-cyano-4-hydroxybenzoate

市販のメチル ４−ヒドロキシ−３−ヨードベンゾエート（５．００ｇ）のＮ，Ｎ−ジメチルホルムアミド（１８．０ｍｌ）溶液へ、シアン化銅（１．７７ｇ）、シアン化ナトリウム（８８ｍｇ）を加え、１１０℃にて１０時間攪拌した。反応液に水を加え、ろ過した。ろ液に飽和食塩水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 酢酸エチル）にて精製し、表題化合物（２．４３ｇ）を黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 3.91 (s, 3 H) 7.04 - 7.08 (m, 1 H) 8.10 - 8.14 (m, 1 H) 8.20 - 8.25 (m, 1 H).
MS ESI nega: 176[M-H]^-.
（２）メチル ３−シアノ−４−｛［（トリフルオロメチル）スルホニル］オキシ｝ベンゾエート

To a commercially available solution of methyl 4-hydroxy-3-iodobenzoate (5.00 g) in N, N-dimethylformamide (18.0 ml) was added copper cyanide (1.77 g) and sodium cyanide (88 mg). Stir at 10 ° C. for 10 hours. Water was added to the reaction solution and filtered. Saturated brine was added to the filtrate, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate) to obtain the title compound (2.43 g) as a yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 3.91 (s, 3 H) 7.04-7.08 (m, 1 H) 8.10-8.14 (m, 1 H) 8.20-8.25 (m, 1 H).
MS ESI nega: 176 [MH] ^- .
(2) Methyl 3-cyano-4-{[(trifluoromethyl) sulfonyl] oxy} benzoate

参考例Ｅ−２０（１）で得られた化合物（８００ｍｇ）のクロロホルム（１５．１ｍｌ）溶液へ、０℃にてトリエチルアミン（６８５ｍｇ）、Ｎ，Ｎ−ジメチル−４−アミノピリジン（５５．２ｍｇ）、トリフルオロメタンスルホン酸無水物（１．９１ｇ）を加え、室温にて１時間攪拌した。反応系を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１００：０〜９０：１０）にて精製し、表題化合物（１．０１ｇ）を薄黄色油状物質として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 3.99 (s, 3 H) 7.57 - 7.62 (m, 1 H) 8.35 - 8.40 (m, 1 H) 8.42 - 8.46 (m, 1 H).
（３）メチル ３−シアノ−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ベンゾエート

To a solution of the compound (800 mg) obtained in Reference Example E-20 (1) in chloroform (15.1 ml) at 0 ° C., triethylamine (685 mg), N, N-dimethyl-4-aminopyridine (55.2 mg). , Trifluoromethanesulfonic anhydride (1.91 g) was added, and the mixture was stirred at room temperature for 1 hour. The reaction system was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 100: 0 to 90:10) to give the title compound (1.01 g) as a pale yellow oily substance. Obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 3.99 (s, 3 H) 7.57-7.62 (m, 1 H) 8.35-8.40 (m, 1 H) 8.42-8.46 (m, 1 H).
(3) Methyl 3-cyano-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate

参考例Ｅ−２０（２）で得られた化合物（１．１３ｇ）の１，４−ジオキサン（１８．３ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（１．１１ｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（２９８ｍｇ）、酢酸カリウム（１．７９ｇ）を加え、１００℃にて１５時間攪拌した。反応液をセライト（登録商標）ろ過し、ろ液を減圧濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝２：１）にて精製し、表題化合物（９８５ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 3.96 (s, 3 H) 7.95 - 7.99 (m, 1 H) 8.18 - 8.22 (m, 1 H) 8.32 - 8.35 (m, 1 H).
参考例Ｅ−２１
４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）−３−（トリフルオロメチル）安息香酸

To a solution of the compound (1.13 g) obtained in Reference Example E-20 (2) in 1,4-dioxane (18.3 ml), bis (pinacolato) diboron (1.11 g), [1,1′-bis (Diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (298 mg) and potassium acetate (1.79 g) were added, and the mixture was stirred at 100 ° C. for 15 hours. The reaction solution was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 2: 1) to obtain the title compound (985 mg) as a light brown powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 3.96 (s, 3 H) 7.95-7.99 (m, 1 H) 8.18-8.22 (m, 1 H) 8.32-8.35 (m , 1 H).
Reference Example E-21
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -3- (trifluoromethyl) benzoic acid

４−ブロモ−３−（トリフルオロメチル）安息香酸（１．００ｇ）を用いて、参考例Ｅ−４と同様の操作にて反応及び精製を行い、表題化合物（８８７ｍｇ）を黒色油状物質として得た。
MS ESI/APCI Dual nega: 315[M-H]^-.
参考例Ｅ−２２
２，５−ジメチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

4-Bromo-3- (trifluoromethyl) benzoic acid (1.00 g) was used for the reaction and purification in the same manner as in Reference Example E-4 to obtain the title compound (887 mg) as a black oily substance. It was.
MS ESI / APCI Dual nega: 315 [MH] ^- .
Reference Example E-22
2,5-Dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

２，５−ジブロモ−ｐ−キシレン（３．００ｇ）を用いて、参考例Ｅ−１７（１）および参考例Ｅ−１７（２）と同様の操作にて反応及び精製を行い、表題化合物（２．５３ｇ）を黒色固体として得た。
MS ESI/APCI Dual nega: 275[M-H]^-.
参考例Ｅ−２３
メチル ３，５−ジメチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ベンゾエート
（１）メチル ３，５−ジメチル−４−｛［（トリフルオロメチル）スルホニル］オキシ｝ベンゾエート

Using 2,5-dibromo-p-xylene (3.00 g), the reaction and purification were conducted in the same manner as in Reference Example E-17 (1) and Reference Example E-17 (2), and the title compound ( 2.53 g) was obtained as a black solid.
MS ESI / APCI Dual nega: 275 [MH] ^- .
Reference Example E-23
Methyl 3,5-dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate (1) methyl 3,5-dimethyl-4-{[(tri Fluoromethyl) sulfonyl] oxy} benzoate

４−ヒドロキシ−３，５−ジメチル安息香酸（１．００ｇ）のメタノール（２０ｍｌ）溶液へ濃硫酸（１ｍｌ）を加え、加熱還流下にて５時間攪拌した。反応液を減圧濃縮して得られた残渣を酢酸エチルに溶解させ、水、飽和炭酸水素ナトリウム水溶液、飽和食塩水で洗浄した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去し、４−ヒドロキシ−３，５−ジメチル安息香酸 メチルエステルを得た。得られた４−ヒドロキシ−３，５−ジメチル安息香酸 メチルエステルのクロロホルム（６ｍｌ）溶液へピリジン（５１６μｌ）を加え、氷冷下、無水トリフルオロメタンスルホン酸（１．０８ｍｌ）を滴下し、同温にて１時間、室温にて２時間攪拌した。氷冷下再度ピリジン（１．０３ｍｌ）と無水トリフルオロメタンスルホン酸（２．１６ｍｌ）を滴下し、室温にて一晩攪拌した。反応液に１Ｍ塩酸を加え、クロロホルムで抽出した。有機層を飽和食塩水で洗浄、フェーズセパレーターに通して、溶媒を減圧留去し、表題化合物（１．８８ｇ）を橙色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.43 (s, 6 H) 3.92 (s, 3 H) 7.79 - 7.83 (m, 2 H).
MS ESI/APCI Dual posi: 335[M+Na]⁺.
（２）メチル ３，５−ジメチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ベンゾエート

Concentrated sulfuric acid (1 ml) was added to a solution of 4-hydroxy-3,5-dimethylbenzoic acid (1.00 g) in methanol (20 ml), and the mixture was stirred for 5 hours under heating to reflux. The residue obtained by concentrating the reaction solution under reduced pressure was dissolved in ethyl acetate, and washed with water, saturated aqueous sodium hydrogen carbonate solution, and saturated brine. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure to obtain 4-hydroxy-3,5-dimethylbenzoic acid methyl ester. Pyridine (516 μl) was added to a chloroform (6 ml) solution of the obtained 4-hydroxy-3,5-dimethylbenzoic acid methyl ester, and trifluoromethanesulfonic anhydride (1.08 ml) was added dropwise under ice cooling. For 1 hour and at room temperature for 2 hours. Under ice cooling, pyridine (1.03 ml) and trifluoromethanesulfonic anhydride (2.16 ml) were added dropwise, and the mixture was stirred overnight at room temperature. To the reaction solution was added 1M hydrochloric acid, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, passed through a phase separator, and the solvent was evaporated under reduced pressure to give the title compound (1.88 g) as an orange oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.43 (s, 6 H) 3.92 (s, 3 H) 7.79-7.83 (m, 2 H).
MS ESI / APCI Dual posi: 335 [M + Na] ⁺ .
(2) Methyl 3,5-dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate

参考例Ｅ−２３（１）で得られた化合物（８５０ｍｇ）を用いて、参考例Ｅ−４と同様の操作にて反応及び精製を行い、表題化合物（７９０ｍｇ）を淡黄色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 2.43 (s, 6 H) 3.89 (s, 3 H) 7.61 (s, 2 H).
参考例Ｅ−２４
２，６−ジメチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Using the compound (850 mg) obtained in Reference Example E-23 (1), the reaction and purification were performed in the same manner as in Reference Example E-4 to obtain the title compound (790 mg) as a pale yellow oily substance. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 12 H) 2.43 (s, 6 H) 3.89 (s, 3 H) 7.61 (s, 2 H).
Reference Example E-24
2,6-Dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

５−ブロモ−２−ヨード−ｍ−キシレン（３．００ｇ）を用いて、参考例Ｅ−１７（１）および参考例Ｅ−１７（２）と同様の操作にて反応及び精製を行い、表題化合物（１．３６ｇ）を茶色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.35 - 2.42 (m, 6 H) 7.45 - 7.52 (m, 2 H).
MS ESI/APCI Dual nega: 275[M-H]^-.
参考例Ｅ−２５
５−フルオロ−２−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Using 5-bromo-2-iodo-m-xylene (3.00 g), the reaction and purification were conducted in the same manner as in Reference Example E-17 (1) and Reference Example E-17 (2). Compound (1.36 g) was obtained as a brown oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 12 H) 2.35-2.42 (m, 6 H) 7.45-7.52 (m, 2 H).
MS ESI / APCI Dual nega: 275 [MH] ^- .
Reference Example E-25
5-Fluoro-2-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

アルゴン雰囲気下、２，５−ジブロモ−４−フルオロトルエン（２．５ｇ）のテトラヒドロフラン（１５ｍｌ）溶液に−７８℃でｎ−ブチルリチウム（２．６４Ｍヘキサン溶液、３．７ｍｌ）を滴下し、３０分間撹拌後、２−イソプロピルオキシ-４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン（１．９ｇ）のテトラヒドロフラン（１０ｍｌ）溶液を滴下した。同温で３０分間撹拌後、さらにｎ−ブチルリチウム（２．６４Ｍヘキサン溶液、３．９ｍｌ）を滴下し、３０分間撹拌して、ドライアイスを加えた。室温に昇温後、１Ｍ水酸化ナトリウム水溶液、酢酸エチルを加えて分液操作を行った。有機層から、さらに１Ｍ水酸化ナトリウム水溶液で抽出後、水層を飽和塩化アンモニウム水溶液で中和した。この水層からクロロホルムで２回抽出した。合わせた有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去して、表題化合物（１．９ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 - 1.45 (m, 12 H) 2.59 (s, 3 H) 7.56 - 7.77 (m, 2 H).
参考例Ｅ−２６
２−フルオロ−３−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

Under an argon atmosphere, n-butyllithium (2.64 M hexane solution, 3.7 ml) was added dropwise to a solution of 2,5-dibromo-4-fluorotoluene (2.5 g) in tetrahydrofuran (15 ml) at −78 ° C., 30 After stirring for minutes, a solution of 2-isopropyloxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.9 g) in tetrahydrofuran (10 ml) was added dropwise. After stirring at the same temperature for 30 minutes, n-butyllithium (2.64 M hexane solution, 3.9 ml) was further added dropwise, stirred for 30 minutes, and dry ice was added. After raising the temperature to room temperature, a 1M aqueous sodium hydroxide solution and ethyl acetate were added to carry out a liquid separation operation. The organic layer was further extracted with 1M aqueous sodium hydroxide solution, and the aqueous layer was neutralized with saturated aqueous ammonium chloride solution. The aqueous layer was extracted twice with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure to obtain the title compound (1.9 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28-1.45 (m, 12 H) 2.59 (s, 3 H) 7.56-7.77 (m, 2 H).
Reference Example E-26
2-Fluoro-3-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

２，５−ジブロモ−６−フルオロトルエン（１．００ｇ）を用いて、参考例Ｅ−１７（１）および参考例Ｅ−１７（２）と同様の操作にて反応及び精製を行い、表題化合物（６５８ｍｇ）を黒色油状物質として得た。
MS ESI/APCI Dual posi: 303[M+Na]⁺.
MS ESI/APCI Dual nega: 279[M-H]^-.
参考例Ｅ−２７
３−フルオロ−２−メチル−４−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）安息香酸

The title compound was subjected to reaction and purification using 2,5-dibromo-6-fluorotoluene (1.00 g) in the same manner as in Reference Example E-17 (1) and Reference Example E-17 (2). (658 mg) was obtained as a black oil.
MS ESI / APCI Dual posi: 303 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 279 [MH] ^- .
Reference Example E-27
3-Fluoro-2-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid

２，５−ジブロモ−６−フルオロトルエン（１．００ｇ）を用いて、参考例Ｅ−２５と同様の操作にて反応及び精製を行い、表題化合物（１．３２ｇ）を無色粉末として得た。
MS ESI/APCI Dual nega: 279[M-H]^-.
参考例Ｆ−１
５−ブロモピリジン−２−カルボキサミド

The reaction and purification were carried out in the same manner as in Reference Example E-25 using 2,5-dibromo-6-fluorotoluene (1.00 g) to obtain the title compound (1.32 g) as a colorless powder.
MS ESI / APCI Dual nega: 279 [MH] ^- .
Reference Example F-1
5-Bromopyridine-2-carboxamide

５−ブロモピリジン−２−カルボン酸（５００ｍｇ）、２８％アンモニア水（２００μｌ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（６１８ｍｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（４９３ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１０ｍｌ）溶液を室温で一晩撹拌した。反応液へ酢酸エチルを加え、水で洗浄し、無水硫酸ナトリウムで乾燥した。乾燥剤を濾別後、溶媒を減圧下留去し、得られた残渣をイソプロピルエーテルで懸濁撹拌した後、固体をろ取し、表題化合物（３４０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.68 (br. s., 1 H) 7.72 (br. s., 1 H) 7.96 - 8.03 (m, 1 H) 8.07 - 8.13 (m, 1 H) 8.61 - 8.66 (m, 1 H).
MS ESI/APCI Dual posi: 201[M+H]⁺.
MS ESI/APCI Dual posi: 199[M-H]^-.
参考例Ｆ−２
５−ブロモ−Ｎ−メチルピリジン−２−カルボキサミド

5-bromopyridine-2-carboxylic acid (500 mg), 28% aqueous ammonia (200 μl), N-ethyl-N′-3-dimethylaminopropylcarbodiimide hydrochloride (618 mg), 1-hydroxybenzotriazole monohydrate A solution of the Japanese product (493 mg) in N, N-dimethylformamide (10 ml) was stirred at room temperature overnight. Ethyl acetate was added to the reaction solution, washed with water, and dried over anhydrous sodium sulfate. The desiccant was filtered off, the solvent was evaporated under reduced pressure, and the resulting residue was suspended and stirred in isopropyl ether, and the solid was collected by filtration to give the title compound (340 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.68 (br. S., 1 H) 7.72 (br. S., 1 H) 7.96-8.03 (m, 1 H) 8.07-8.13 (m, 1 H ) 8.61-8.66 (m, 1 H).
MS ESI / APCI Dual posi: 201 [M + H] ⁺ .
MS ESI / APCI Dual posi: 199 [MH] ^- .
Reference Example F-2
5-Bromo-N-methylpyridine-2-carboxamide

５−ブロモピリジン−２−カルボン酸（５００ｍｇ）、４０％メチルアミン水溶液（２５０μＬ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（６１８ｍｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（４９３ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１０ｍｌ）溶液を室温で一晩撹拌した。反応液へ酢酸エチルを加え、水で洗浄し、無水硫酸ナトリウムで乾燥した。乾燥剤を濾別後、溶媒を減圧下留去し、得られた残渣ををシリカゲルカラムクロマトグラフィ−（展開溶媒 ヘキサン：酢酸エチル＝６５：３５〜１：１）で精製し、表題化合物（４３８ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.03 (d, J=5.1 Hz, 3 H) 7.89 (br. s, 1 H) 7.95 - 8.01 (m, 1 H) 8.07 - 8.14 (m, 1 H) 8.58 - 8.62 (m, 1 H).
MS ESI/APCI Dual posi: 215[M+H]⁺.
MS ESI/APCI Dual posi: 213[M-H]^-.
参考例Ｆ−３
５−ブロモ−Ｎ−（プロパン−２−イル）ピリジン−２−カルボキサミド

5-bromopyridine-2-carboxylic acid (500 mg), 40% aqueous methylamine solution (250 μL), N-ethyl-N′-3-dimethylaminopropylcarbodiimide hydrochloride (618 mg), 1-hydroxybenzotriazole mono A solution of hydrate (493 mg) in N, N-dimethylformamide (10 ml) was stirred at room temperature overnight. Ethyl acetate was added to the reaction solution, washed with water, and dried over anhydrous sodium sulfate. After filtering off the desiccant, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 65: 35-1: 1) to give the title compound (438 mg). Got.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.03 (d, J = 5.1 Hz, 3 H) 7.89 (br. S, 1 H) 7.95-8.01 (m, 1 H) 8.07-8.14 (m, 1 H) 8.58-8.62 (m, 1 H).
MS ESI / APCI Dual posi: 215 [M + H] ⁺ .
MS ESI / APCI Dual posi: 213 [MH] ^- .
Reference Example F-3
5-Bromo-N- (propan-2-yl) pyridine-2-carboxamide

イソプロピルアミン（２８０μｌ）を用い、参考例Ｆ−２と同様の方法で合成を行い、表題化合物（５５０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J=6.5 Hz, 6 H) 4.17 - 4.35 (m, 1 H) 7.73 (br. s., 1 H) 7.97 (dd, J=8.2, 2.2 Hz, 1 H) 8.09 (d, J=8.2 Hz, 1 H) 8.59 (d, J=2.2 Hz, 1 H).
MS ESI/APCI Dual posi: 243[M+H]⁺.
MS ESI/APCI Dual posi: 241[M-H]^-.
参考例Ｆ−４
５−ブロモ−Ｎ−（２−ヒドロキシエチル）ピリジン−２−カルボキサミド

Synthesis was performed using isopropylamine (280 μl) in the same manner as in Reference Example F-2 to obtain the title compound (550 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J = 6.5 Hz, 6 H) 4.17-4.35 (m, 1 H) 7.73 (br. S., 1 H) 7.97 (dd, J = 8.2, 2.2 Hz, 1 H) 8.09 (d, J = 8.2 Hz, 1 H) 8.59 (d, J = 2.2 Hz, 1 H).
MS ESI / APCI Dual posi: 243 [M + H] ⁺ .
MS ESI / APCI Dual posi: 241 [MH] ^- .
Reference Example F-4
5-Bromo-N- (2-hydroxyethyl) pyridine-2-carboxamide

エタノールアミン（２００μｌ）を用い、参考例Ｆ−２と同様の方法で合成を行い、表題化合物（４０４ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.65 - 2.74 (m, 1 H) 3.60 - 3.69 (m, 2 H) 3.80 - 3.90 (m, 2 H) 7.95 - 8.02 (m, 1 H) 8.05 - 8.11 (m, 1 H) 8.29 (br. s., 1 H) 8.58 - 8.63 (m, 1 H).
MS ESI/APCI Dual posi: 245[M+H]⁺.
参考例Ｆ−５
５−ブロモ−Ｎ，Ｎ−ジメチルピリジン−２−カルボキサミド

Synthesis was performed using ethanolamine (200 μl) in the same manner as in Reference Example F-2 to obtain the title compound (404 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.65-2.74 (m, 1 H) 3.60-3.69 (m, 2 H) 3.80-3.90 (m, 2 H) 7.95-8.02 (m, 1 H) 8.05 -8.11 (m, 1 H) 8.29 (br.s., 1 H) 8.58-8.63 (m, 1 H).
MS ESI / APCI Dual posi: 245 [M + H] ⁺ .
Reference Example F-5
5-Bromo-N, N-dimethylpyridine-2-carboxamide

ジメチルアミン塩酸塩（２６３ｍｇ）を用い、参考例Ｆ−２と同様の方法で合成を行い、表題化合物（２７７ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.10 (s, 3 H) 3.14 (s, 3 H) 7.58 (dd, J=8.4, 0.8 Hz, 1 H) 7.93 (dd, J=8.4, 2.3 Hz, 1 H) 8.65 (dd, J=2.3, 0.8 Hz, 1 H).
MS ESI/APCI Dual posi: 229[M+H]⁺.
参考例Ｆ−６
５−ブロモ−Ｎ−（プロパン−２−イル）ピリミジン−２−カルボキサミド

Synthesis was performed in the same manner as in Reference Example F-2 using dimethylamine hydrochloride (263 mg) to obtain the title compound (277 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.10 (s, 3 H) 3.14 (s, 3 H) 7.58 (dd, J = 8.4, 0.8 Hz, 1 H) 7.93 (dd, J = 8.4, 2.3 (Hz, 1 H) 8.65 (dd, J = 2.3, 0.8 Hz, 1 H).
MS ESI / APCI Dual posi: 229 [M + H] ⁺ .
Reference Example F-6
5-Bromo-N- (propan-2-yl) pyrimidine-2-carboxamide

５−ブロモピリミジン−２−カルボン酸（５００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（５．０ｍｌ）溶液にイソプロピルアミン（３１８μｌ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（５６５ｍｇ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（７０７ｍｇ）を加え、室温にて一晩攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜０：１）にて精製し、表題化合物（３９６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.7 Hz, 6 H) 4.22 - 4.44 (m, 1 H) 7.72 (br. s, 1 H) 7.60 - 7.84 (m, 1 H) 8.91 (s, 2 H).
参考例Ｇ−１
３−クロロ−６−エテニルピリダジン

To a solution of 5-bromopyrimidine-2-carboxylic acid (500 mg) in N, N-dimethylformamide (5.0 ml) was added isopropylamine (318 μl), 1-hydroxybenzotriazole monohydrate (565 mg), N- Ethyl-N′-3-dimethylaminopropylcarbodiimide hydrochloride (707 mg) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 0: 1) to obtain the title compound (396 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.7 Hz, 6 H) 4.22-4.44 (m, 1 H) 7.72 (br. S, 1 H) 7.60-7.84 (m, 1 H) 8.91 (s, 2 H).
Reference example G-1
3-Chloro-6-ethenylpyridazine

３，６−ジクロロピリダジン（１．３ｇ）、トリビニルボロキサンピリジン錯体（６９３ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（７１ｍｇ）、炭酸カリウム（２．０５ｇ）の１，４−ジオキサン（１．３ｍｌ）−水（５．２ｍｌ）混合溶液をマイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１２０℃にて３０分間攪拌した。反応液の有機層を分離後、水層をトルエンで抽出した。合わせた有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９０：１０〜６５：３５）にて精製し、表題化合物（４６１ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.74 (dd, J=11.0, 0.5 Hz, 1 H) 6.24 (dd, J=17.7, 0.5 Hz, 1 H) 7.04 (dd, J=17.7, 11.0 Hz, 1 H) 7.45 - 7.50 (m, 1 H) 7.58 (d, J=8.9 Hz, 1 H).
参考例Ｇ−２
２−クロロ−５−シクロプロピルピリミジン

3,6-dichloropyridazine (1.3 g), trivinylboroxanepyridine complex (693 mg), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (71 mg), potassium carbonate ( 2.05 g) in 1,4-dioxane (1.3 ml) - water (5.2 ml) mixed solution micro web - Bed reactor (Biotage, Inc. Initiator Sixty ^TM (trade name)) using a micro web - The mixture was stirred at 120 ° C. for 30 minutes under irradiation. The organic layer of the reaction solution was separated, and the aqueous layer was extracted with toluene. The combined organic layers were dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 90: 10-65: 35) to give the title compound (461 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.74 (dd, J = 11.0, 0.5 Hz, 1 H) 6.24 (dd, J = 17.7, 0.5 Hz, 1 H) 7.04 (dd, J = 17.7, 11.0 (Hz, 1 H) 7.45-7.50 (m, 1 H) 7.58 (d, J = 8.9 Hz, 1 H).
Reference Example G-2
2-Chloro-5-cyclopropylpyrimidine

５−ブロモ−２−クロロピリミジン（２．０ｇ）、シクロプロピルボロン酸（１．１５ｇ）、リン酸三カリウム（７．６８ｇ）酢酸パラジウム（II）（１１６ｍｇ）のトルエン（２０ｍｌ）−水（１．０ｍｌ）混合溶液へ、トリシクロヘキシルホスフィン（１８％トルエン溶液）（１．７２ｍｌ）を加え、アルゴン雰囲気下、１００℃で４時間撹拌した。反応液の有機層を分離後、水層を酢酸エチルで抽出した。合わせた有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１００：０〜９１：９）にて精製し、表題化合物（８７９ｍｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.75 - 0.83 (m, 2 H) 1.10 - 1.18 (m, 2 H) 1.80 - 1.93 (m, 1 H) 8.36 (s, 2 H).
MS ESI/APCI Dual posi: 155[M+H]⁺.
参考例Ｇ−３
２−クロロ−５−（２−メチルプロプ−１−エン−１−イル）ピリミジン

5-Bromo-2-chloropyrimidine (2.0 g), cyclopropylboronic acid (1.15 g), tripotassium phosphate (7.68 g) palladium (II) acetate (116 mg) in toluene (20 ml) -water (1 To the mixed solution, tricyclohexylphosphine (18% toluene solution) (1.72 ml) was added, and the mixture was stirred at 100 ° C. for 4 hours under an argon atmosphere. The organic layer of the reaction solution was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 100: 0 to 91: 9) to give the title compound (879 mg) as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.75-0.83 (m, 2 H) 1.10-1.18 (m, 2 H) 1.80-1.93 (m, 1 H) 8.36 (s, 2 H).
MS ESI / APCI Dual posi: 155 [M + H] ⁺ .
Reference Example G-3
2-Chloro-5- (2-methylprop-1-en-1-yl) pyrimidine

２−メチル−１−プロペニルボロン酸 ピナコールエステル（２．４５ｇ）を用いて参考例Ｇ−２と同様の方法で合成を行い、表題化合物（１．３６ｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.87 (d, J=0.8 Hz, 3 H) 1.97 (d, J=1.4 Hz, 3 H) 6.11 (dt, J=1.4, 0.8 Hz, 1 H) 8.48 (s, 2 H).
MS ESI/APCI Dual posi: 169[M+H]⁺.
参考例Ｇ−４
２−クロロ−５−（プロプ−１−エン−２−イル）ピリミジン

Synthesis was performed in the same manner as in Reference Example G-2 using 2-methyl-1-propenylboronic acid pinacol ester (2.45 g) to obtain the title compound (1.36 g) as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.87 (d, J = 0.8 Hz, 3 H) 1.97 (d, J = 1.4 Hz, 3 H) 6.11 (dt, J = 1.4, 0.8 Hz, 1 H ) 8.48 (s, 2 H).
MS ESI / APCI Dual posi: 169 [M + H] ⁺ .
Reference example G-4
2-Chloro-5- (prop-1-en-2-yl) pyrimidine

イソプロペニルボロン酸 ピナコールエステル（２．２６ｇ）を用いて参考例Ｇ−２と同様の方法で合成を行い、表題化合物（９７０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17 (dd, J=1.6, 0.8 Hz, 3 H) 5.28 - 5.33 (m, 1 H) 5.47 - 5.52 (m, 1 H) 8.68 (s, 2 H).
MS ESI/APCI Dual posi: 155[M+H]⁺.
参考例Ｇ−５
２−クロロ−５−（プロパン−２−イル）ピリミジン

Synthesis was performed in the same manner as in Reference Example G-2 using isopropenylboronic acid pinacol ester (2.26 g) to obtain the title compound (970 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17 (dd, J = 1.6, 0.8 Hz, 3 H) 5.28-5.33 (m, 1 H) 5.47-5.52 (m, 1 H) 8.68 (s, 2 H).
MS ESI / APCI Dual posi: 155 [M + H] ⁺ .
Reference example G-5
2-Chloro-5- (propan-2-yl) pyrimidine

水素雰囲気下、参考例Ｇ−４で得られた化合物（１０ｇ）、酸化白金（１．０ｇ）の酢酸エチル／エタノール（１：１）（１２０ｍｌ）懸濁液を室温にて６時間攪拌した。反応液を減圧下濃縮後、残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝８０：２０）にて精製し、表題化合物（１０ｇ）を無色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J=7.0 Hz, 6 H) 2.88 - 3.04 (m, 1 H) 8.49 - 8.51 (m, 2 H).
MS ESI/APCI Dual posi: 157[M+H]⁺.
参考例Ｇ−６
２−クロロ−５−（プロパン−２−イル）ピリジン
（１）２−クロロ−５−（プロプ−１−エン−２−イル）ピリジン

Under a hydrogen atmosphere, a suspension of the compound (10 g) obtained in Reference Example G-4 and platinum oxide (1.0 g) in ethyl acetate / ethanol (1: 1) (120 ml) was stirred at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 80: 20) to give the title compound (10 g) as a colorless oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J = 7.0 Hz, 6 H) 2.88-3.04 (m, 1 H) 8.49-8.51 (m, 2 H).
MS ESI / APCI Dual posi: 157 [M + H] ⁺ .
Reference example G-6
2-Chloro-5- (propan-2-yl) pyridine (1) 2-Chloro-5- (prop-1-en-2-yl) pyridine

アルゴン雰囲気下２−クロロ−５−ヨードピリジン（１．０ｇ）、イソプロペニルボロン酸ピナコールエステル（７７０ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（２４０ｍｇ）、炭酸セシウム（２．７ｇ）のアセトニトリル（２５ｍｌ）溶液を８０℃で５時間攪拌した。冷却後反応液へ水を加え、酢酸エチルにて抽出した。有機層を飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥し、乾燥剤を濾別した。溶媒を減圧下濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１００：０〜９１：９）にて精製後、生じた固体を除去し、表題化合物（３９０ｍｇ）を無色油状物質して得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13 - 2.17 (m, 3 H) 5.18 - 5.22 (m, 1 H) 5.39 - 5.43 (m, 1 H) 7.28 (dd, J=8.3, 0.6 Hz, 1 H) 7.71 (dd, J=8.3, 2.6 Hz, 1 H) 8.47 (d, J=2.6 Hz, 1 H).
MS ESI/APCI Dual posi: 154[M+H]⁺.
（２）２−クロロ−５−（プロパン−２−イル）ピリジン

2-chloro-5-iodopyridine (1.0 g), isopropenylboronic acid pinacol ester (770 mg), tetrakis (triphenisphosphine) palladium (240 mg), cesium carbonate (2.7 g) in acetonitrile (25 ml) under argon atmosphere The solution was stirred at 80 ° C. for 5 hours. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the desiccant was filtered off. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 100: 0 to 91: 9), and then the resulting solid was removed to give the title compound (390 mg). Obtained as a colorless oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13-2.17 (m, 3 H) 5.18-5.22 (m, 1 H) 5.39-5.43 (m, 1 H) 7.28 (dd, J = 8.3, 0.6 Hz , 1 H) 7.71 (dd, J = 8.3, 2.6 Hz, 1 H) 8.47 (d, J = 2.6 Hz, 1 H).
MS ESI / APCI Dual posi: 154 [M + H] ⁺ .
(2) 2-Chloro-5- (propan-2-yl) pyridine

水素雰囲気下、参考例Ｇ−６で得られた化合物（３８０ｍｇ）、酸化白金（３８ｍｇ）のエタノール（３．８ｍｌ）懸濁液を室温にて５時間攪拌後、さらに酸化白金（１５ｍｇ）を加え、室温にて１３時間攪拌した。反応液を減圧下濃縮後、残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム）にて精製し、表題化合物（２３０ｍｇ）を無色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 - 1.30 (m, 6 H) 2.86 - 3.02 (m, 1 H) 7.23 - 7.27 (m, 1 H) 7.48 - 7.53 (m, 1 H) 8.25 (d, J=2.5 Hz, 1 H).
MS ESI/APCI Dual posi: 156[M+H]⁺.
参考例Ｇ−７
２−クロロ−５−エチルピリジン
（１）２−クロロ−５−エテニルピリジン

Under a hydrogen atmosphere, a suspension of the compound obtained in Reference Example G-6 (380 mg) and platinum oxide (38 mg) in ethanol (3.8 ml) was stirred at room temperature for 5 hours, and further platinum oxide (15 mg) was added. And stirred at room temperature for 13 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: chloroform) to give the title compound (230 mg) as a colorless oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24-1.30 (m, 6 H) 2.86-3.02 (m, 1 H) 7.23-7.27 (m, 1 H) 7.48-7.53 (m, 1 H) 8.25 (d, J = 2.5 Hz, 1 H).
MS ESI / APCI Dual posi: 156 [M + H] ⁺ .
Reference example G-7
2-Chloro-5-ethylpyridine (1) 2-Chloro-5-ethenylpyridine

アルゴン雰囲気下２−クロロ−５−ヨードピリジン（１．０ｇ）、トリブチルビニルすず（１．５ｇ）、ビス(トリフェニルホスフィン)パラジウム(II)ジクロリド（１５０ｍｇ）の１，４−ジオキサン（２５ｍｌ）溶液を８０℃で５時間攪拌した。反応液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１００：０〜９１：９）にて精製し、表題化合物（４１０ｍｇ）を無色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.39 - 5.45 (m, 1 H) 5.78 - 5.85 (m, 1 H) 6.62 - 6.74 (m, 1 H) 7.27 - 7.33 (m, 1 H) 7.66 - 7.75 (m, 1 H) 8.34 - 8.41 (m, 1 H).
MS ESI/APCI Dual posi: 139[M+H]⁺.
（２）２−クロロ−５−エチルピリジン

1,4-dioxane (25 ml) solution of 2-chloro-5-iodopyridine (1.0 g), tributylvinyltin (1.5 g), bis (triphenylphosphine) palladium (II) dichloride (150 mg) under an argon atmosphere Was stirred at 80 ° C. for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 100: 0 to 91: 9) to give the title compound (410 mg) as a colorless oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 5.39-5.45 (m, 1 H) 5.78-5.85 (m, 1 H) 6.62-6.74 (m, 1 H) 7.27-7.33 (m, 1 H) 7.66 -7.75 (m, 1 H) 8.34-8.41 (m, 1 H).
MS ESI / APCI Dual posi: 139 [M + H] ⁺ .
(2) 2-Chloro-5-ethylpyridine

参考例Ｇ−７（１）で得られた化合物（３５０ｍｇ）を用いて参考例Ｇ−６（２）と同様の方法で表題化合物（２３０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21 - 1.29 (m, 3 H) 2.64 (q, J=7.6 Hz, 2 H) 7.21 - 7.29 (m, 1 H) 7.45 - 7.52 (m, 1 H) 8.20 - 8.26 (m, 1 H).
MS ESI/APCI Dual posi: 141[M+H]⁺.
参考例Ｇ−８
２−クロロ−５−（１，１−ジフルオロエチル）ピリミジン

The title compound (230 mg) was obtained in the same manner as in Reference Example G-6 (2) using the compound (350 mg) obtained in Reference Example G-7 (1).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21-1.29 (m, 3 H) 2.64 (q, J = 7.6 Hz, 2 H) 7.21-7.29 (m, 1 H) 7.45-7.52 (m, 1 H) 8.20-8.26 (m, 1 H).
MS ESI / APCI Dual posi: 141 [M + H] ⁺ .
Reference example G-8
2-Chloro-5- (1,1-difluoroethyl) pyrimidine

１−（２−クロロピリミジン−５−イル）エタノン（１００ｍｇ）を用いて、参考例Ｅ−１４（１）と同様の操作にて反応及び精製を行い、表題化合物（５４ｍｇ）を薄茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.00 (t, J=18.2 Hz, 3 H) 8.77 (s, 2 H).
MS ESI/APCI Dual posi: 179[M+H]⁺.
MS ESI/APCI Dual nega: 177[M-H]^-.
参考例Ｇ−９
２−クロロ−５−（２，２−ジフルオロエチル）ピリミジン
（１）２−クロロ−５−［（Ｚ）−２−エトキシエテニル］ピリミジン

Using 1- (2-chloropyrimidin-5-yl) ethanone (100 mg), the reaction and purification were conducted in the same manner as in Reference Example E-14 (1) to give the title compound (54 mg) as a light brown powder. Obtained.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.00 (t, J = 18.2 Hz, 3 H) 8.77 (s, 2 H).
MS ESI / APCI Dual posi: 179 [M + H] ⁺ .
MS ESI / APCI Dual nega: 177 [MH] ^- .
Reference example G-9
2-chloro-5- (2,2-difluoroethyl) pyrimidine (1) 2-chloro-5-[(Z) -2-ethoxyethenyl] pyrimidine

５−ブロモ−２−クロロピリミジン（１．００ｇ）のＮ，Ｎ−ジメチルホルムアミド（１０．３ｍｌ）溶液へ、（Ｚ）−１−エトキシ−２−（トリブチルスタニル）エテン（２．０５ｇ）、ジクロロビス（トリフェニルホスフィン）パラジウム（３６３ｍｇ）を加え、８０℃にて３時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出し、水洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣にアセトニトリルを加え、ヘキサンで洗浄した。アセトニトリル層を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１）にて精製し、表題化合物（５３６ｍｇ）を薄黄色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.38 (t, J=7.0 Hz, 3 H) 4.07 (q, J=7.0 Hz, 2 H) 5.12 (d, J=6.6 Hz, 1 H) 6.46 (d, J=6.6 Hz, 1 H) 8.80 (s, 2 H).
MS ESI/APCI Dual posi: 185[M+H]⁺.
（２）（２−クロロピリミジン−５−イル）アセトアルデヒド

To a solution of 5-bromo-2-chloropyrimidine (1.00 g) in N, N-dimethylformamide (10.3 ml), (Z) -1-ethoxy-2- (tributylstannyl) ethene (2.05 g), Dichlorobis (triphenylphosphine) palladium (363 mg) was added, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. Acetonitrile was added to the resulting residue and washed with hexane. The acetonitrile layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1) to obtain the title compound (536 mg) as a pale yellow oily substance.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.38 (t, J = 7.0 Hz, 3 H) 4.07 (q, J = 7.0 Hz, 2 H) 5.12 (d, J = 6.6 Hz, 1 H) 6.46 (d, J = 6.6 Hz, 1 H) 8.80 (s, 2 H).
MS ESI / APCI Dual posi: 185 [M + H] ⁺ .
(2) (2-Chloropyrimidin-5-yl) acetaldehyde

参考例Ｇ−９（１）で得られた化合物（５３６ｍｇ）のテトラヒドロフラン（９．６８ｍｌ）溶液へ、２Ｍ塩酸を加え、６０℃にて７時間攪拌した。反応液へ飽和食塩水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜１：２）にて精製し、表題化合物（２２０ｍｇ）を薄黄色油状物質として得た
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.83 (s, 2 H) 8.50 (s, 2 H) 9.87 (s, 1 H).
MS ESI/APCI Dual posi: 157[M+H]⁺.
MS ESI/APCI Dual nega: 155[M-H]^-.
（３）２−クロロ−５−（２，２−ジフルオロエチル）ピリミジン

To a solution of the compound (536 mg) obtained in Reference Example G-9 (1) in tetrahydrofuran (9.68 ml) was added 2M hydrochloric acid, and the mixture was stirred at 60 ° C. for 7 hours. Saturated saline was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 1: 2) to obtain the title compound (220 mg) as a pale yellow oily substance.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.83 (s, 2 H) 8.50 (s, 2 H) 9.87 (s, 1 H).
MS ESI / APCI Dual posi: 157 [M + H] ⁺ .
MS ESI / APCI Dual nega: 155 [MH] ^- .
(3) 2-Chloro-5- (2,2-difluoroethyl) pyrimidine

参考例Ｇ−９（２）で得られた化合物（１００ｍｇ）を用いて、参考例Ｅ−１４（１）と同様の操作にて反応及び精製を行い、表題化合物（５９ｍｇ）を薄黄色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.04 - 3.30 (m, 2 H) 5.70 - 6.34 (m, 1 H) 8.56 (s, 2 H).
MS ESI/APCI Dual posi: 179[M+H]⁺.
参考例Ｇ−１０
２−クロロ−５−（２−フルオロエチル）ピリミジン
（１）２−（２−クロロピリミジン−５−イル）エタノール

Using the compound (100 mg) obtained in Reference Example G-9 (2), the reaction and purification were conducted in the same manner as in Reference Example E-14 (1) to give the title compound (59 mg) as a pale yellow oily substance. Got as.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 3.04-3.30 (m, 2 H) 5.70-6.34 (m, 1 H) 8.56 (s, 2 H).
MS ESI / APCI Dual posi: 179 [M + H] ⁺ .
Reference example G-10
2-chloro-5- (2-fluoroethyl) pyrimidine (1) 2- (2-chloropyrimidin-5-yl) ethanol

参考例Ｇ−９（２）で得られた化合物（１２０ｍｇ）のメタノール（７．６６ｍｌ）溶液へ、水素化ホウ素ナトリウム（３１．９ｍｇ）を加え、室温にて１時間攪拌した。反応液へ水、飽和食塩水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（４０ｍｇ）を薄黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.85 (t, J=6.1 Hz, 2 H) 3.91 (t, J=6.1 Hz, 2 H) 8.55 (s, 2 H).
MS ESI/APCI Dual posi: 159[M+H]⁺.
（２）２−クロロ−５−（２−フルオロエチル）ピリミジン

Sodium borohydride (31.9 mg) was added to a methanol (7.66 ml) solution of the compound (120 mg) obtained in Reference Example G-9 (2), and the mixture was stirred at room temperature for 1 hour. Water and saturated brine were added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound (40 mg) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.85 (t, J = 6.1 Hz, 2 H) 3.91 (t, J = 6.1 Hz, 2 H) 8.55 (s, 2 H).
MS ESI / APCI Dual posi: 159 [M + H] ⁺ .
(2) 2-Chloro-5- (2-fluoroethyl) pyrimidine

参考例Ｇ−１０（１）で得られた化合物（４０ｍｇ）を用いて、参考例Ｅ−１４（１）と同様の操作にて反応及び精製を行い、表題化合物（１５ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.90 - 3.12 (m, 2 H) 4.51 - 4.83 (m, 2 H) 8.55 (s, 2 H).
MS ESI/APCI Dual posi: 161[M+H]⁺.
参考例Ｇ−１１
３−（プロパン−２−イル）−５−（トリクロロメチル）−１，２，４−オキサジアゾール

Using the compound (40 mg) obtained in Reference Example G-10 (1), the reaction and purification were conducted in the same manner as in Reference Example E-14 (1) to give the title compound (15 mg) as a colorless oily substance. Obtained.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.90-3.12 (m, 2 H) 4.51-4.83 (m, 2 H) 8.55 (s, 2 H).
MS ESI / APCI Dual posi: 161 [M + H] ⁺ .
Reference Example G-11
3- (propan-2-yl) -5- (trichloromethyl) -1,2,4-oxadiazole

Ｎ´−ヒドロキシ−２−メチルプロパンイミダミド（１．００ｇ）のクロロホルム（３２．６ｍｌ）溶液に０℃にて、ピリジン（１．０１ｇ）、２，２，２−トリクロロアセチルクロリド（１．９６ｇ）を加え、室温にて１５時間攪拌した。反応液へ水を加え、クロロホルムにて抽出し、水洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（１．６９ｇ）を薄黄色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.40 (d, J=7.0 Hz, 6 H) 3.09 - 3.25 (m, 1 H).
MS ESI/APCI Dual posi: 229[M+H]⁺.
参考例Ｇ−１２
２−クロロピリミジン−５−カルボニトリル

N′-hydroxy-2-methylpropaneimidamide (1.00 g) in chloroform (32.6 ml) at 0 ° C. with pyridine (1.01 g), 2,2,2-trichloroacetyl chloride (1.96 g). ) And stirred at room temperature for 15 hours. Water was added to the reaction solution, extracted with chloroform, and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound (1.69 g) as a pale yellow oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.40 (d, J = 7.0 Hz, 6 H) 3.09-3.25 (m, 1 H).
MS ESI / APCI Dual posi: 229 [M + H] ⁺ .
Reference example G-12
2-chloropyrimidine-5-carbonitrile

後掲した参考例Ｇ−１３で得られた化合物（１００ｍｇ）のクロロホルム（６．３５ｍｌ）懸濁液へ、０℃にてトリエチルアミン（１２９ｍｇ）、無水トリフルオロ酢酸（１３３ｍｇ）を加え、室温にて１時間攪拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１）にて精製し、表題化合物（５４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 8.91 (s, 2 H).
参考例Ｇ−１３
２−クロロピリミジン−５−カルボキサミド

Triethylamine (129 mg) and trifluoroacetic anhydride (133 mg) were added to a suspension of the compound (100 mg) obtained in Reference Example G-13 below in chloroform (6.35 ml) at 0 ° C., and at room temperature. Stir for 1 hour. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1) to give the title compound (54 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 8.91 (s, 2 H).
Reference Example G-13
2-chloropyrimidine-5-carboxamide

２−クロロピリミジン−５−カルボン酸（２００ｍｇ）のテトラヒドロフラン（４．２０ｍｌ）懸濁液へ、塩化オキサリル（４８０ｍｇ）、Ｎ，Ｎ−ジメチルホルムアミド（９．２１ｍｇ）を加え、室温にて２時間攪拌した。反応系を減圧濃縮した。得られた残渣にテトラヒドロフラン（４．２０ｍｌ）を加え、０℃にて３０％アンモニア水を加え、室温にて１時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（１３５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 9.03 (s, 2 H).
MS ESI posi: 158[M+H]⁺.
MS ESI nega: 156[M-H]^-.
参考例Ｇ−１４
アゼチジン−１−イル（２−クロロピリミジン−５−イル）メタノン

Oxalyl chloride (480 mg) and N, N-dimethylformamide (9.21 mg) were added to a suspension of 2-chloropyrimidine-5-carboxylic acid (200 mg) in tetrahydrofuran (4.20 ml), and the mixture was stirred at room temperature for 2 hours. did. The reaction system was concentrated under reduced pressure. Tetrahydrofuran (4.20 ml) was added to the obtained residue, 30% aqueous ammonia was added at 0 ° C., and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure to obtain the title compound (135 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 9.03 (s, 2 H).
MS ESI posi: 158 [M + H] ⁺ .
MS ESI nega: 156 [MH] ^- .
Reference example G-14
Azetidin-1-yl (2-chloropyrimidin-5-yl) methanone

２−クロロピリミジン−５−カルボン酸（１００ｍｇ）とアゼチジン（２８．８ｍｇ）を用いて、参考例Ｇ−１３と同様の操作にて反応及び精製を行い、表題化合物（９０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.40 - 2.49 (m, 2 H) 4.23 - 4.33 (m, 2 H) 4.34 - 4.44 (m, 2 H) 8.88 (s, 2 H).
MS ESI posi: 198[M+H]⁺.
参考例Ｇ−１５
５−クロロピラジン−２−カルボニトリル
（１）５−クロロピラジン−２−カルボキサミド

The reaction and purification were conducted in the same manner as in Reference Example G-13 using 2-chloropyrimidine-5-carboxylic acid (100 mg) and azetidine (28.8 mg) to give the title compound (90 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.40-2.49 (m, 2 H) 4.23-4.33 (m, 2 H) 4.34-4.44 (m, 2 H) 8.88 (s, 2 H).
MS ESI posi: 198 [M + H] ⁺ .
Reference Example G-15
5-chloropyrazine-2-carbonitrile (1) 5-chloropyrazine-2-carboxamide

５−クロロピラジン−２−カルボン酸（５００ｍｇ）を用いて、参考例Ｇ−１３と同様の操作にて反応及び精製を行い、表題化合物（３８４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 5.58 - 5.81 (m, 1 H) 7.37 - 7.63 (m, 1 H) 8.55 (d, J=0.8 Hz, 1 H) 9.19 (d, J=0.8 Hz, 1 H).
MS ESI posi: 158[M+H]⁺.
（２）５−クロロピラジン−２−カルボニトリル

The reaction and purification were carried out in the same manner as in Reference Example G-13 using 5-chloropyrazine-2-carboxylic acid (500 mg) to give the title compound (384 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 5.58-5.81 (m, 1 H) 7.37-7.63 (m, 1 H) 8.55 (d, J = 0.8 Hz, 1 H) 9.19 (d, J = 0.8 Hz, 1 H).
MS ESI posi: 158 [M + H] ⁺ .
(2) 5-chloropyrazine-2-carbonitrile

参考例Ｇ−１５（１）で得られた化合物（２７８ｍｇ）を用いて、参考例Ｇ−１２と同様の操作にて反応及び精製を行い、表題化合物（２４０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 8.72 (s, 2 H).
参考例Ｇ−１６
２−ブロモ−５−（メトキシメチル）ピリジン

Using the compound (278 mg) obtained in Reference Example G-15 (1), the reaction and purification were performed in the same manner as in Reference Example G-12 to obtain the title compound (240 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 8.72 (s, 2 H).
Reference Example G-16
2-Bromo-5- (methoxymethyl) pyridine

水素化ナトリウム（６０％オイル懸濁、２５５ｍｇ）のテトラヒドロフラン（１０ｍｌ）懸濁液に（６−ブロモピリジン−３−イル）メタノール（１．００ｇ）を加え室温で1時間攪拌した。ヨウ化メチル（６２２μｌ）を加えさらに2時間、室温で攪拌した。反応溶液に水を加え、水層を酢酸エチルで抽出、有機層を乾燥、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜４：１）にて精製し、表題化合物（５３１ｍｇ）を薄黄色液体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.41 (s, 3 H) 4.43 (s, 2 H) 7.44 - 7.59 (m, 2 H) 8.29 - 8.36 (m, 1 H).
参考例Ｇ−１７
２−（６−ブロモピリジン−３−イル）プロパン−２−オール

To a suspension of sodium hydride (60% oil suspension, 255 mg) in tetrahydrofuran (10 ml) was added (6-bromopyridin-3-yl) methanol (1.00 g), and the mixture was stirred at room temperature for 1 hour. Methyl iodide (622 μl) was added, and the mixture was further stirred at room temperature for 2 hours. Water was added to the reaction solution, the aqueous layer was extracted with ethyl acetate, and the organic layer was dried and concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 4: 1) to obtain the title compound (531 mg) as a pale yellow liquid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.41 (s, 3 H) 4.43 (s, 2 H) 7.44-7.59 (m, 2 H) 8.29-8.36 (m, 1 H).
Reference Example G-17
2- (6-Bromopyridin-3-yl) propan-2-ol

２，５−ジブロモピリジン（１０．０ｇ）を用いてＷＯ２００９１１７４２１に記載の方法に従って実験を行い、表題化合物（１．７０ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (s, 6 H) 7.41 - 7.47 (m, 1 H) 7.67 - 7.73 (m, 1 H) 8.46 - 8.49 (m, 1 H).
参考例Ｇ−１８
２−ブロモ−５−（２−メトキシプロパン−２−イル）ピリジン

An experiment was performed using 2,5-dibromopyridine (10.0 g) according to the method described in WO200917421 to obtain the title compound (1.70 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (s, 6 H) 7.41-7.47 (m, 1 H) 7.67-7.73 (m, 1 H) 8.46-8.49 (m, 1 H).
Reference Example G-18
2-Bromo-5- (2-methoxypropan-2-yl) pyridine

ＷＯ２００６０２８０２９に記載の方法に従って実験を行い、表題化合物（３３ｍｇ）を得た。
参考例Ｈ−１
２−メチル−６−（メチルスルホニル）ピリジン−３−オール
（１）６−ヨード−２−メチルピリジン−３−オール

The experiment was performed according to the method described in WO2006028029 to obtain the title compound (33 mg).
Reference Example H-1
2-Methyl-6- (methylsulfonyl) pyridin-3-ol (1) 6-iodo-2-methylpyridin-3-ol

２−メチルピリジン−３−オール（２．００ｇ）へ水（６１．０ｍｌ）、炭酸ナトリウム（３．８９ｇ）、ヨウ素（５．１３ｇ）を加え、室温にて５時間攪拌した。反応液を酢酸エチルで抽出し、得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣を酢酸エチル−ヘキサン混合溶液にて再結晶し、表題化合物（１．３０ｇ）を薄黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.48 (s, 3 H) 6.77 (d, J=7.8 Hz, 1 H) 7.41 (d, J=7.8 Hz, 1 H).
MS ESI/APCI Dual posi: 236[M+H]⁺.
MS ESI/APCI Dual nega: 234[M-H]^-.
（２）２−メチル−６−（メチルスルホニル）ピリジン−３−オール

Water (61.0 ml), sodium carbonate (3.89 g) and iodine (5.13 g) were added to 2-methylpyridin-3-ol (2.00 g), and the mixture was stirred at room temperature for 5 hours. The reaction solution was extracted with ethyl acetate, the obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from an ethyl acetate-hexane mixed solution to give the title compound (1.30 g) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.48 (s, 3 H) 6.77 (d, J = 7.8 Hz, 1 H) 7.41 (d, J = 7.8 Hz, 1 H).
MS ESI / APCI Dual posi: 236 [M + H] ⁺ .
MS ESI / APCI Dual nega: 234 [MH] ^- .
(2) 2-Methyl-6- (methylsulfonyl) pyridin-3-ol

参考例Ｈ−１（１）で得られた化合物（５００ｍｇ）のジメチルスルホキシド（７．０９ｍｌ）溶液へ、メタンスルフィン酸ナトリウム（２６１ｍｇ）、ヨウ化銅（４０．６ｍｇ）、Ｌ−プロリン（４９．０ｍｇ）、水酸化ナトリウム（１７．０ｍｇ）を加え、アルゴン雰囲気下、１１０℃にて８時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２）にて精製し、表題化合物（２０６ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 2.41 (s, 3 H) 3.15 (s, 3 H) 7.32 (d, J=8.4 Hz, 1 H) 7.74 (d, J=8.4 Hz, 1 H).
MS ESI/APCI Dual posi: 188[M+H]⁺.
MS ESI/APCI Dual nega: 186[M-H]^-.
参考例Ｈ−２
５−ヒドロキシ−６−メチルピリジン−２−カルボニトリル

To a solution of the compound (500 mg) obtained in Reference Example H-1 (1) in dimethyl sulfoxide (7.09 ml), sodium methanesulfinate (261 mg), copper iodide (40.6 mg), L-proline (49. 0 mg) and sodium hydroxide (17.0 mg) were added, and the mixture was stirred at 110 ° C. for 8 hours under an argon atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2) to give the title compound (206 mg) as a colorless powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 2.41 (s, 3 H) 3.15 (s, 3 H) 7.32 (d, J = 8.4 Hz, 1 H) 7.74 (d, J = 8.4 Hz, 1 H).
MS ESI / APCI Dual posi: 188 [M + H] ⁺ .
MS ESI / APCI Dual nega: 186 [MH] ^- .
Reference Example H-2
5-hydroxy-6-methylpyridine-2-carbonitrile

参考例Ｈ−１（１）で得られた化合物（４００ｍｇ）のピリジン（３．４０ｍｌ）溶液へ、シアン化銅（１９８ｍｇ）を加え、１１０℃にて３時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜１：２）にて精製し、表題化合物（１９０ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.54 (s, 3 H) 7.11 (d, J=8.2 Hz, 1 H) 7.46 (d, J=8.2 Hz, 1 H).
MS ESI/APCI Dual posi: 135[M+H]⁺.
MS ESI/APCI Dual nega: 133[M-H]^-.
参考例Ｈ−３
５−（メチルスルホニル）ピリジン−３−オール

Copper cyanide (198 mg) was added to a solution of the compound (400 mg) obtained in Reference Example H-1 (1) in pyridine (3.40 ml), and the mixture was stirred at 110 ° C. for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 1: 2) to give the title compound (190 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.54 (s, 3 H) 7.11 (d, J = 8.2 Hz, 1 H) 7.46 (d, J = 8.2 Hz, 1 H).
MS ESI / APCI Dual posi: 135 [M + H] ⁺ .
MS ESI / APCI Dual nega: 133 [MH] ^- .
Reference Example H-3
5- (Methylsulfonyl) pyridin-3-ol

５−ブロモピリジン−３−オール（１．００ｇ）を用いて、参考例Ｈ−１（２）と同様の操作にて反応及び精製を行い、表題化合物（２３８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 3.29 (s, 3 H) 7.57 - 7.61 (m, 1 H) 8.41 - 8.45 (m, 1 H) 8.51 - 8.55 (m, 1 H).
MS ESI/APCI Dual posi: 174[M+H]⁺.
MS ESI/APCI Dual nega: 172[M-H]^-.
参考例Ｈ−４
３−フルオロ−４−（メチルスルファニル）フェノール
（１）２−（４−ブロモ−３−フルオロフェノキシ）テトラヒドロ−２Ｈ−ピラン

5-Bromopyridin-3-ol (1.00 g) was used for reaction and purification in the same manner as in Reference Example H-1 (2) to give the title compound (238 mg) as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 3.29 (s, 3 H) 7.57-7.61 (m, 1 H) 8.41-8.45 (m, 1 H) 8.51-8.55 (m, 1 H).
MS ESI / APCI Dual posi: 174 [M + H] ⁺ .
MS ESI / APCI Dual nega: 172 [MH] ^- .
Reference Example H-4
3-Fluoro-4- (methylsulfanyl) phenol (1) 2- (4-bromo-3-fluorophenoxy) tetrahydro-2H-pyran

４−ブロモ−３−フルオロフェノール（１．００ｇ）のクロロホルム（５．２４ｍｌ）溶液へ、３，４−ジヒドロ−２Ｈピラン（６６１ｍｇ）、ｐ−トルエンスルホン酸ピリジニウム（１３２ｍｇ）を加え、室温にて１５時間攪拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１）にて精製し、表題化合物（１．２４ｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.56 - 2.08 (m, 6 H) 3.54 - 3.68 (m, 1 H) 3.76 - 3.92 (m, 1 H) 5.33 - 5.40 (m, 1 H) 6.70 - 6.80 (m, 1 H) 6.84 - 6.93 (m, 1 H) 7.34 - 7.46 (m, 1 H).
MS ESI/APCI Dual nega: 273[M-H]^-.
（２）２−［３−フルオロ−４−（メチルスルファニル）フェノキシ］テトラヒドロ−２Ｈ−ピラン

To a solution of 4-bromo-3-fluorophenol (1.00 g) in chloroform (5.24 ml) was added 3,4-dihydro-2Hpyran (661 mg) and pyridinium p-toluenesulfonate (132 mg) at room temperature. Stir for 15 hours. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1) to give the title compound (1.24 g) as a colorless oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.56-2.08 (m, 6 H) 3.54-3.68 (m, 1 H) 3.76-3.92 (m, 1 H) 5.33-5.40 (m, 1 H) 6.70 -6.80 (m, 1 H) 6.84-6.93 (m, 1 H) 7.34-7.46 (m, 1 H).
MS ESI / APCI Dual nega: 273 [MH] ^- .
(2) 2- [3-Fluoro-4- (methylsulfanyl) phenoxy] tetrahydro-2H-pyran

参考例Ｈ−４（１）で得られた化合物（１．２４ｇ）のテトラヒドロフラン（１５．０ｍｌ）溶液へ、−７８℃にて２．６４Ｍ ｎ−ブチルリチウムヘキサン溶液（１．８８ｍｌ）を加え、同温にて１時間攪拌した。ジメチルジスルフィド（４６７ｍｇ）を加え、同温にて１時間攪拌した。反応液に飽和塩化アンモニウム水溶液を加え、酢酸エチルにて抽出し、水、飽和食塩水にて洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１）にて精製し、表題化合物（８７０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 - 2.10 (m, 6 H) 2.41 (s, 3 H) 3.54 - 3.69 (m, 1 H) 3.79 - 3.95 (m, 1 H) 5.34 - 5.42 (m, 1 H) 6.76 - 6.88 (m, 2 H) 7.21 - 7.33 (m, 1 H).
MS ESI/APCI Dual posi: 243[M+H]⁺.
（３）３−フルオロ−４−（メチルスルファニル）フェノール

To a solution of the compound (1.24 g) obtained in Reference Example H-4 (1) in tetrahydrofuran (15.0 ml) was added a 2.64M n-butyllithium hexane solution (1.88 ml) at −78 ° C., Stir for 1 hour at the same temperature. Dimethyl disulfide (467 mg) was added and stirred at the same temperature for 1 hour. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with water and saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1) to give the title compound (870 mg) as a colorless oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49-2.10 (m, 6 H) 2.41 (s, 3 H) 3.54-3.69 (m, 1 H) 3.79-3.95 (m, 1 H) 5.34-5.42 (m, 1 H) 6.76-6.88 (m, 2 H) 7.21-7.33 (m, 1 H).
MS ESI / APCI Dual posi: 243 [M + H] ⁺ .
(3) 3-Fluoro-4- (methylsulfanyl) phenol

参考例Ｈ−４（２）で得られた化合物（８７０ｍｇ）のメタノール（３５．９ｍｌ）溶液へ、ｐ−トルエンスルホン酸ピリジニウム（９０．２ｍｇ）を加え、室温にて１５時間攪拌した。反応液に飽和炭酸水素ナトリウム水溶液を加え、メタノールを減圧留去した。得られた残渣に水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１９：１〜４：１）にて精製し、表題化合物（３７０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.41 (s, 3 H) 4.99 (br. s, 1 H) 6.54 - 6.66 (m, 2 H) 7.18 - 7.32 (m, 1 H).
MS ESI/APCI Dual nega: 157[M-H]^-.
参考例Ｈ−５
２−フルオロ−４−（メチルスルファニル）フェノール
（１）２−（４−ブロモ−２−フルオロフェノキシ）テトラヒドロ−２Ｈ−ピラン

Pyridinium p-toluenesulfonate (90.2 mg) was added to a solution of the compound (870 mg) obtained in Reference Example H-4 (2) in methanol (35.9 ml), and the mixture was stirred at room temperature for 15 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and methanol was distilled off under reduced pressure. Water was added to the resulting residue and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane: ethyl acetate = 19: 1-4: 1) to give the title compound (370 mg) as a colorless oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.41 (s, 3 H) 4.99 (br. S, 1 H) 6.54-6.66 (m, 2 H) 7.18-7.32 (m, 1 H).
MS ESI / APCI Dual nega: 157 [MH] ^- .
Reference Example H-5
2-Fluoro-4- (methylsulfanyl) phenol (1) 2- (4-bromo-2-fluorophenoxy) tetrahydro-2H-pyran

４−ブロモ−２−フルオロフェノール（１．００ｇ）を用いて、参考例Ｈ−４（１）と同様の操作にて反応及び精製を行い、表題化合物（１．３５ｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 - 2.11 (m, 6 H) 3.55 - 3.69 (m, 1 H) 3.82 - 3.98 (m, 1 H) 5.41 (t, J=2.6 Hz, 1 H) 7.01 - 7.32 (m, 3 H).
MS ESI/APCI Dual nega: 273[M-H]^-.
（２）２−［２−フルオロ−４−（メチルスルファニル）フェノキシ］テトラヒドロ−２Ｈ−ピラン

4-Bromo-2-fluorophenol (1.00 g) was used for the reaction and purification in the same manner as in Reference Example H-4 (1) to give the title compound (1.35 g) as a colorless oil. It was.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49-2.11 (m, 6 H) 3.55-3.69 (m, 1 H) 3.82-3.98 (m, 1 H) 5.41 (t, J = 2.6 Hz, 1 H) 7.01-7.32 (m, 3 H).
MS ESI / APCI Dual nega: 273 [MH] ^- .
(2) 2- [2-Fluoro-4- (methylsulfanyl) phenoxy] tetrahydro-2H-pyran

参考例Ｈ−５（１）で得られた化合物（１．３５ｇ）を用いて、参考例Ｈ−４（２）と同様の操作にて反応及び精製を行い、表題化合物（９３０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.50 - 2.13 (m, 6 H) 2.45 (s, 3 H) 3.53 - 3.69 (m, 1 H) 3.85 - 4.03 (m, 1 H) 5.39 (t, J=3.1 Hz, 1 H) 6.86 - 7.20 (m, 3 H).
MS ESI/APCI Dual posi: 243[M+H]⁺.
（３）２−フルオロ−４−（メチルスルファニル）フェノール

Using the compound (1.35 g) obtained in Reference Example H-5 (1), the reaction and purification were conducted in the same manner as in Reference Example H-4 (2), and the title compound (930 mg) was obtained as a colorless oil Obtained as material.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.50-2.13 (m, 6 H) 2.45 (s, 3 H) 3.53-3.69 (m, 1 H) 3.85-4.03 (m, 1 H) 5.39 (t , J = 3.1 Hz, 1 H) 6.86-7.20 (m, 3 H).
MS ESI / APCI Dual posi: 243 [M + H] ⁺ .
(3) 2-Fluoro-4- (methylsulfanyl) phenol

参考例Ｈ−５（２）で得られた化合物（９３０ｍｇ）を用いて、参考例Ｈ−４（３）と同様の操作にて反応及び精製を行い、表題化合物（５３０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.45 (s, 3 H) 5.06 (d, J=4.0 Hz, 1 H) 6.79 - 7.12 (m, 3 H).
MS ESI/APCI Dual nega: 157[M-H]^-.
参考例Ｉ−１
１−｛［（１，１−ジフルオロ−２−メチルプロパン−２−イル）オキシ］カルボニル｝−３−メチル−１Ｈ−イミダゾル−３−イウム

Using the compound (930 mg) obtained in Reference Example H-5 (2), the reaction and purification were conducted in the same manner as in Reference Example H-4 (3) to give the title compound (530 mg) as a colorless oil. Obtained.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.45 (s, 3 H) 5.06 (d, J = 4.0 Hz, 1 H) 6.79-7.12 (m, 3 H).
MS ESI / APCI Dual nega: 157 [MH] ^- .
Reference Example I-1
1-{[(1,1-Difluoro-2-methylpropan-2-yl) oxy] carbonyl} -3-methyl-1H-imidazol-3-ium

ジフルオロ酢酸エチルを用いて文献記載の方法（Ｂｉｏｏｒｇａｎｉｃ ＆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ，２０１１，１９，１５８０−１５９３）と同様の方法で反応を行い、表題化合物を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.64 - 1.70 (m, 6 H) 3.94 (s, 3 H) 6.09 - 6.52 (m, 1 H) 7.86 (t, J=1.9 Hz, 1 H) 8.09 (t, J=1.9 Hz, 1 H) 9.80 - 9.85 (m, 1 H).
MS ESI/APCI Dual nega: 381[M+Cl]^-.
参考例Ｉ−２
１−｛［（１−フルオロ−２−メチルプロパン−２−イル）オキシ］カルボニル｝−３−メチル−１Ｈ−イミダゾル−３−イウム

The title compound was obtained using ethyl difluoroacetate in the same manner as described in the literature (Bioorganic & Medicinal Chemistry, 2011, 19, 1580-1593).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.64-1.70 (m, 6 H) 3.94 (s, 3 H) 6.09-6.52 (m, 1 H) 7.86 (t, J = 1.9 Hz, 1 H ) 8.09 (t, J = 1.9 Hz, 1 H) 9.80-9.85 (m, 1 H).
MS ESI / APCI Dual nega: 381 [M + Cl] ^- .
Reference Example I-2
1-{[(1-Fluoro-2-methylpropan-2-yl) oxy] carbonyl} -3-methyl-1H-imidazol-3-ium

フルオロ酢酸エチルを用いて、文献記載の方法（Ｂｉｏｏｒｇａｎｉｃ ＆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ，２０１１，１９，１５８０−１５９３）と同様の方法で反応を行い、表題化合物を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.62 (s, 1 H) 1.63 (s, 3 H) 3.94 (s, 3 H) 4.57 - 4.77 (m, 2 H) 7.84 - 7.89 (m, 1 H) 8.07 - 8.13 (m, 1 H) 9.81 - 9.88 (m, 1 H).
MS ESI/APCI Dual nega: 381[M+Cl]^-.
参考例１
ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−インダゾル−１−イル）ピペリジン−１−カルボキシラート
（１）５−ブロモ−１Ｈ−インダゾール

The title compound was obtained using ethyl fluoroacetate in the same manner as described in the literature (Bioorganic & Medicinal Chemistry, 2011, 19, 1580-1593).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.62 (s, 1 H) 1.63 (s, 3 H) 3.94 (s, 3 H) 4.57-4.77 (m, 2 H) 7.84-7.89 (m, 1 H) 8.07-8.13 (m, 1 H) 9.81-9.88 (m, 1 H).
MS ESI / APCI Dual nega: 381 [M + Cl] ^- .
Reference example 1
tert-Butyl 4- (5-Bromo-1H-indazol-1-yl) piperidine-1-carboxylate (1) 5-Bromo-1H-indazole

市販の４−ブロモ−２−メチルアニリン（１０．４８ｇ）の酢酸溶液（３００ｍｌ）へ亜硝酸ナトリウム（３．８９ｇ ）、水（１０ｍｌ）を加え、室温で５時間攪拌した。反応液を濃縮後、飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製後、ヘキサンで結晶化し、表題化合物（６．８１ｇ）を茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 7.35 - 7.43 (m, 1 H) 7.45 - 7.52 (m, 1 H) 7.92 (d, J=2.2 Hz, 1 H) 8.03 (d, J=0.9 Hz, 1 H)．
MS ESI/APCI Dual nega: 195[M-H]^-.
（２）ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−インダゾル−１−イル）ピペリジン−１−カルボキシラート

Sodium nitrite (3.89 g) and water (10 ml) were added to a commercially available acetic acid solution (300 ml) of 4-bromo-2-methylaniline (10.48 g), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated, saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1) and crystallized from hexane to give the title compound (6.81 g) as a brown powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 7.35-7.43 (m, 1 H) 7.45-7.52 (m, 1 H) 7.92 (d, J = 2.2 Hz, 1 H) 8.03 (d, J = 0.9 Hz, 1 H).
MS ESI / APCI Dual nega: 195 [MH] ^- .
(2) tert-butyl 4- (5-bromo-1H-indazol-1-yl) piperidine-1-carboxylate

参考例１（１）で得られた化合物（６．８１ｇ）のＮ，Ｎ−ジメチルホルムアミド（２００ｍｌ）溶液へ、水素化ナトリウム（６０％オイル懸濁、２．１２ｇ）を加え室温で１０分攪拌後、参考例Ａで得られた化合物（１４．８ｇ）を加え９０℃にて２時間攪拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１〜１：１）にて精製し、表題化合物（６．９７ｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 1.95 - 2.03 (m, 2 H) 2.15 - 2.25 (m, 2 H) 2.88 - 3.02 (m, 2 H) 4.21 - 4.38 (m, 2 H) 4.48 - 4.55 (m, 1 H) 7.33 (d, J=8.8 Hz, 1 H) 7.44 (dd, J=8.8, 1.7 Hz, 1 H) 7.87 (d, J=1.7 Hz, 1 H) 7.93 (s, 1 H).
参考例２
ｔｅｒｔ−ブチル ４−［５−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

Sodium hydride (60% oil suspension, 2.12 g) was added to a solution of the compound (6.81 g) obtained in Reference Example 1 (1) in N, N-dimethylformamide (200 ml) and stirred at room temperature for 10 minutes. Thereafter, the compound (14.8 g) obtained in Reference Example A was added and stirred at 90 ° C. for 2 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1 to 1: 1) to obtain the title compound (6.97 g) as a pale yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 1.95-2.03 (m, 2 H) 2.15-2.25 (m, 2 H) 2.88-3.02 (m, 2 H) 4.21-4.38 (m, 2 H) 4.48-4.55 (m, 1 H) 7.33 (d, J = 8.8 Hz, 1 H) 7.44 (dd, J = 8.8, 1.7 Hz, 1 H) 7.87 (d, J = 1.7 Hz, 1 H) 7.93 (s, 1 H).
Reference example 2
tert-Butyl 4- [5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indazol-1-yl] piperidine-1-carboxylate

参考例１（２）で得られた化合物（３．００ｇ）の１，４−ジオキサン（５０ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（２．４０ｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（３２２ｍｇ）、酢酸カリウム（３．１０ｇ）を加え、１００℃にて３．５時間攪拌した。冷却後反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をヘキサン−酢酸エチル混合溶液に溶解させ、不溶の不純物を濾別した。濾液を濃縮後、シリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１０：０〜８：２）にて精製し、表題化合物（３．２３ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (s, 4 H) 1.37 (s, 9 H) 1.49 (s, 8 H) 2.01 (br. d, J=12.9 Hz, 2 H) 2.23 (qd, J=12.2, 4.0 Hz, 2 H) 2.96 (br. t, J=12.2 Hz, 2 H) 4.32 (br. d, J=9.0 Hz, 2 H) 4.50 - 4.63 (m, 1 H) 7.43 (d, J=8.5 Hz, 1 H) 7.78 (dd, J=8.5, 1.1 Hz, 1 H) 8.01 (s, 1 H) 8.27 (s, 1 H).
MS ESI/APCI Dual posi: 428[M+H]⁺, 450[M+Na]⁺.
参考例３
５−ブロモ−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−インダゾール

To a solution of the compound (3.00 g) obtained in Reference Example 1 (2) in 1,4-dioxane (50 ml), bis (pinacolato) diboron (2.40 g), [1,1′-bis (diphenylphosphino) ) Ferrocene] palladium (II) dichloride dichloromethane complex (322 mg) and potassium acetate (3.10 g) were added and stirred at 100 ° C. for 3.5 hours. After cooling, water was added to the reaction solution, followed by extraction with ethyl acetate, and the resulting organic layer was washed with saturated brine. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in a hexane-ethyl acetate mixed solution, and insoluble impurities were separated by filtration. The filtrate was concentrated and purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 10: 0 to 8: 2) to give the title compound (3.23 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (s, 4 H) 1.37 (s, 9 H) 1.49 (s, 8 H) 2.01 (br.d, J = 12.9 Hz, 2 H) 2.23 ( qd, J = 12.2, 4.0 Hz, 2 H) 2.96 (br. t, J = 12.2 Hz, 2 H) 4.32 (br. d, J = 9.0 Hz, 2 H) 4.50-4.63 (m, 1 H) 7.43 (d, J = 8.5 Hz, 1 H) 7.78 (dd, J = 8.5, 1.1 Hz, 1 H) 8.01 (s, 1 H) 8.27 (s, 1 H).
MS ESI / APCI Dual posi: 428 [M + H] ⁺ , 450 [M + Na] ⁺ .
Reference example 3
5-Bromo-1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazole

参考例１（２）で得られた化合物（５０５ｍｇ）のメタノール（１０ｍｌ）溶液へ４Ｍ塩化水素・１，４−ジオキサン溶液（１０ｍｌ）を加え、室温で１時間攪拌した。反応液を濃縮し、５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−インダゾール 塩酸塩を得た。得られた５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−インダゾール 塩酸塩のジメチルスルホキシド（１０ｍｌ）溶液へ炭酸セシウム（２．１３ｇ）、２−クロロ−５−エチルピリミジン（３８７ｍｇ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１８０℃にて２０分攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：ヘキサン＝１：４〜９：１）にて精製後、ヘキサンで粉末化し、表題化合物（３５４ｍｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.8 Hz, 3 H) 2.06 - 2.12 (m, 2 H) 2.23 - 2.32 (m, 2 H) 2.49 (q, J=7.8 Hz, 2 H) 3.07 - 3.15 (m, 2 H) 4.62 - 4.69 (m, 1 H) 4.91 - 4.97 (m, 2 H) 7.37 (d, J=8.7 Hz, 1 H) 7.45 (dd, J=8.7, 1.6 Hz, 1 H) 7.87 (d, J=1.6 Hz, 1 H) 7.92 (s, 1 H) 8.20 (s, 2 H).
MS ESI/APCI Dual posi: 386[M+H]⁺.
参考例４
４−｛１−［１−（ｔｅｒｔ−ブトキシカルボニル）ピペリジン−４−イル］−１Ｈ−インダゾル−５−イル｝安息香酸

To a solution of the compound (505 mg) obtained in Reference Example 1 (2) in methanol (10 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (10 ml), and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated to give 5-bromo-1- (piperidin-4-yl) -1H-indazole hydrochloride. To a solution of the obtained 5-bromo-1- (piperidin-4-yl) -1H-indazole hydrochloride in dimethyl sulfoxide (10 ml), cesium carbonate (2.13 g) and 2-chloro-5-ethylpyrimidine (387 mg) were added. In addition, the mixture was stirred at 180 ° C. for 20 minutes under microwave irradiation using a microwave reaction device (Initiator Sixty ^™ (trade name) manufactured by Biotage). Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent: chloroform: hexane = 1: 4 to 9: 1) and then powdered with hexane to give the title compound (354 mg) as a pale yellow powder. Got as.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.8 Hz, 3 H) 2.06-2.12 (m, 2 H) 2.23-2.32 (m, 2 H) 2.49 (q, J = 7.8 Hz, 2 H) 3.07-3.15 (m, 2 H) 4.62-4.69 (m, 1 H) 4.91-4.97 (m, 2 H) 7.37 (d, J = 8.7 Hz, 1 H) 7.45 (dd, J = (8.7, 1.6 Hz, 1 H) 7.87 (d, J = 1.6 Hz, 1 H) 7.92 (s, 1 H) 8.20 (s, 2 H).
MS ESI / APCI Dual posi: 386 [M + H] ⁺ .
Reference example 4
4- {1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -1H-indazol-5-yl} benzoic acid

参考例１（２）で得られた化合物（１．００ｇ）のＮ，Ｎ−ジメチルホルムアミド（２０ｍｌ）溶液へ、４−カルボキシフェニルボロン酸（５２４ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（２１２ｍｇ）、２Ｍ炭酸ナトリウム水溶液（３．９ｍｌ）を加え、１００℃にて１時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた水層へ１５％クエン酸水溶液を加え、酢酸エチルにて抽出した。先に得られた有機層と合わせて無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（６７２ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.44 (s, 9 H) 1.92 - 1.98 (m, 4 H) 2.93 - 3.10 (m, 2 H) 4.06 - 4.16 (m, 2 H) 4.87 - 4.95 (m, 1 H) 7.78 (dd, J=8.7, 1.8 Hz, 1 H) 7.81 - 7.87 (m, 3 H) 8.02 (d, J=8.7 Hz, 2 H) 8.12 (s, 1 H) 8.16 (s, 1 H).
MS ESI/APCI Dual posi: 444[M+Na]⁺.
MS ESI/APCI Dual nega: 420[M-H]^-.
参考例５
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−インダゾル−５−イル｝安息香酸

To a solution of the compound (1.00 g) obtained in Reference Example 1 (2) in N, N-dimethylformamide (20 ml), 4-carboxyphenylboronic acid (524 mg), [1,1′-bis (diphenylphosphino) ) Ferrocene] palladium (II) dichloride dichloromethane complex (212 mg), 2M aqueous sodium carbonate solution (3.9 ml) were added, and the mixture was stirred at 100 ° C. for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. A 15% aqueous citric acid solution was added to the obtained aqueous layer, and the mixture was extracted with ethyl acetate. The organic layer obtained previously was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 0 to 1: 1) to obtain the title compound (672 mg) as a light brown powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.44 (s, 9 H) 1.92-1.98 (m, 4 H) 2.93-3.10 (m, 2 H) 4.06-4.16 (m, 2 H) 4.87- 4.95 (m, 1 H) 7.78 (dd, J = 8.7, 1.8 Hz, 1 H) 7.81-7.87 (m, 3 H) 8.02 (d, J = 8.7 Hz, 2 H) 8.12 (s, 1 H) 8.16 (s, 1 H).
MS ESI / APCI Dual posi: 444 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 420 [MH] ^- .
Reference Example 5
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazol-5-yl} benzoic acid

参考例３で得られた化合物（１１３ｍｇ）のＮ，Ｎ-ジメチルホルムアミド（２ｍｌ）溶液へ、４−カルボキシフェニルボロン酸（７３ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１２ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．４４ｍｌ）を加え、１００℃にて２時間攪拌した。４−カルボキシフェニルボロン酸（２４ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（２４ｍｇ）を追加し、同温で４時間攪拌した。反応液を室温へ冷却後、１Ｍ水酸化ナトリウム水溶液を加え、ジエチルエーテルにて水層を洗浄した。得られた水層をクロロホルムで抽出し、有機層を１０％クエン酸水溶液、水で順次洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９：１〜１：１〜クロロホルム：メタノール＝９：１）にて精製し、表題化合物（６１ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 1.99 - 2.05 (m, 4 H) 2.49- 2.56 (m, 2 H) 3.12 - 3.20 (m, 2 H) 4.76 - 4.82 (m, 2 H) 5.00 - 5.07 (m, 1 H) 7.75 - 7.84 (m, 3 H) 7.89 (d, J=8.7 Hz, 1 H) 8.01 (d, J=8.3 Hz, 2 H) 8.11 - 8.14(m, 2 H) 8.29 (s, 2 H).
MS ESI/APCI Dual nega: 426[M-H]^-.
参考例６−Ａ
６−メチル−１Ｈ−インダゾル−５−イル トリフルオロメタンスルホナート
（１）ｔｅｒｔ−ブチル （４−ヒドロキシ−２，５−ジメチルフェニル）カルバマート

To a solution of the compound (113 mg) obtained in Reference Example 3 in N, N-dimethylformamide (2 ml), 4-carboxyphenylboronic acid (73 mg), [1,1′-bis (diphenylphosphino) ferrocene] palladium ( II) Dichloride Dichloromethane complex (12 mg), 2M sodium carbonate aqueous solution (0.44 ml) were added, and the mixture was stirred at 100 ° C. for 2 hours. 4-Carboxyphenylboronic acid (24 mg), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (24 mg) was added, and the mixture was stirred at the same temperature for 4 hours. The reaction mixture was cooled to room temperature, 1M aqueous sodium hydroxide solution was added, and the aqueous layer was washed with diethyl ether. The obtained aqueous layer was extracted with chloroform, and the organic layer was washed successively with a 10% aqueous citric acid solution and water. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 9: 1 to 1: 1 to chloroform: methanol = 9: 1) to obtain the title compound (61 mg) as a light brown powder. .
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 1.99-2.05 (m, 4 H) 2.49- 2.56 (m, 2 H) 3.12-3.20 (m, 2 H) 4.76-4.82 (m, 2 H) 5.00-5.07 (m, 1 H) 7.75-7.84 (m, 3 H) 7.89 (d, J = 8.7 Hz, 1 H) 8.01 (d, J = 8.3 Hz , 2 H) 8.11-8.14 (m, 2 H) 8.29 (s, 2 H).
MS ESI / APCI Dual nega: 426 [MH] ^- .
Reference Example 6-A
6-Methyl-1H-indazol-5-yl trifluoromethanesulfonate (1) tert-butyl (4-hydroxy-2,5-dimethylphenyl) carbamate

市販の４−アミノ−２，５−ジメチルフェノール（５．００ｇ）のメタノール溶液（７３ｍｌ）へ、トリエチルアミン（１０．２ｍｌ）、二炭酸ジ−ｔｅｒｔ−ブチル（８．７５ｇ）を加え、室温で１３時間攪拌した。反応液を濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９５：５〜７０：３０）にて精製し、表題化合物（６．９６ｇ）を紫色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.14 (s, 3 H) 2.15 (s, 3 H) 5.25 (br. s., 1 H) 6.02 (br. s., 1 H) 6.48 (s, 1 H) 7.23 (s, 1 H).
MS ESI/APCI Dual nega: 236[M-H]^-.
（２）４−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，５−ジメチルフェニル トリフルオロメタンスルホナート

Triethylamine (10.2 ml) and di-tert-butyl dicarbonate (8.75 g) were added to a commercially available methanol solution (73 ml) of 4-amino-2,5-dimethylphenol (5.00 g). Stir for hours. The reaction mixture was concentrated, and the obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 95: 5-70: 30) to give the title compound (6.96 g) as a purple powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.14 (s, 3 H) 2.15 (s, 3 H) 5.25 (br. S., 1 H) 6.02 (br. S. , 1 H) 6.48 (s, 1 H) 7.23 (s, 1 H).
MS ESI / APCI Dual nega: 236 [MH] ^- .
(2) 4-[(tert-Butoxycarbonyl) amino] -2,5-dimethylphenyl trifluoromethanesulfonate

参考例６−Ａ（１）で得られた化合物（６．９５ｇ）のクロロホルム溶液（１００ｍｌ）へ、ピリジン（３．５５ｍｌ）を加え、内温１８℃以下にて無水トリフルオロメタンスルホン酸（５．７７ｍｌ）滴下した。室温で５分間攪拌した後、反応液に氷水を加え、有機層を２Ｍ塩酸、飽和食塩水で洗浄、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（１０．９ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.23 (s, 3 H) 2.33 (s, 3 H) 6.27 (br. s., 1 H) 7.01 (s, 1 H) 7.87 (s, 1 H).
MS ESI/APCI Dual nega: 368[M-H]^-.
（３）４−アミノ−２，５−ジメチルフェニル トリフルオロメタンスルホナート

Pyridine (3.55 ml) was added to a chloroform solution (100 ml) of the compound (6.95 g) obtained in Reference Example 6-A (1), and trifluoromethanesulfonic anhydride (5. 77 ml) was added dropwise. After stirring at room temperature for 5 minutes, ice water was added to the reaction mixture, the organic layer was washed with 2M hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound. (10.9 g) was obtained as a brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.23 (s, 3 H) 2.33 (s, 3 H) 6.27 (br. S., 1 H) 7.01 (s, 1 H ) 7.87 (s, 1 H).
MS ESI / APCI Dual nega: 368 [MH] ^- .
(3) 4-amino-2,5-dimethylphenyl trifluoromethanesulfonate

参考例６−Ａ（２）で得られた化合物（１０．８ｇ）の酢酸エチル懸濁液（２０ｍｌ）へ４Ｍ塩化水素・酢酸エチル溶液（４５ｍｌ）を加え、室温にて１５時間攪拌した。反応液に飽和炭酸水素ナトリウム水溶液を加えて２層を分離し、有機層を飽和食塩水で洗浄、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（８．０５ｇ）を茶色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13 (s, 3 H) 2.26 (s, 3 H) 3.65 (br. s., 2 H) 6.53 (s, 1 H) 6.90 (s, 1 H).
MS ESI/APCI Dual posi: 270[M+H]⁺.
（４）６−メチル−１Ｈ−インダゾル−５−イル トリフルオロメタンスルホナート

To a suspension (20 ml) of the compound (10.8 g) obtained in Reference Example 6-A (2) was added 4M hydrogen chloride / ethyl acetate solution (45 ml), and the mixture was stirred at room temperature for 15 hours. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the two layers were separated. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound ( 8.05 g) was obtained as a brown oil.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13 (s, 3 H) 2.26 (s, 3 H) 3.65 (br. S., 2 H) 6.53 (s, 1 H) 6.90 (s, 1 H ).
MS ESI / APCI Dual posi: 270 [M + H] ⁺ .
(4) 6-Methyl-1H-indazol-5-yl trifluoromethanesulfonate

参考例６−Ａ（３）で得られた化合物（８．０５ｇ）の酢酸溶液（４０ｍｌ）へ、内温４〜９℃で亜硝酸ナトリウム水溶液（８．５ｍｌ）を加え、室温にて２０時間攪拌した。反応液に水を加え、酢酸エチルで抽出を行い、有機層を、飽和食塩水で洗浄、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去して残渣を得た。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９５：５〜６５：３５）にて精製し、表題化合物（４．０２ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.51 (s, 3 H) 7.42 (s, 1 H) 7.67 (s, 1 H) 8.09 (s, 1 H).
MS ESI/APCI Dual posi: 281[M+H]⁺.
MS ESI/APCI Dual nega: 279[M-H]^-, 315[M+Cl]^-.
参考例６−Ｂ
４−メチル−１Ｈ−インダゾル−５−イル トリフルオロメタンスルホナート
（１）ｔｅｒｔ−ブチル （４−ヒドロキシ−２，３−ジメチルフェニル）カルバマート

To an acetic acid solution (40 ml) of the compound (8.05 g) obtained in Reference Example 6-A (3), an aqueous sodium nitrite solution (8.5 ml) was added at an internal temperature of 4-9 ° C., and the mixture was stirred at room temperature for 20 hours. Stir. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give a residue. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 95: 5-65: 35) to obtain the title compound (4.02 g) as a brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.51 (s, 3 H) 7.42 (s, 1 H) 7.67 (s, 1 H) 8.09 (s, 1 H).
MS ESI / APCI Dual posi: 281 [M + H] ⁺ .
MS ESI / APCI Dual nega: 279 [MH] ^- , 315 [M + Cl] ^- .
Reference Example 6-B
4-Methyl-1H-indazol-5-yl trifluoromethanesulfonate (1) tert-butyl (4-hydroxy-2,3-dimethylphenyl) carbamate

市販の４−アミノ−２，３−キシレノール（５．００ｇ）を用いて参考例６−Ａ（１）と同様の方法で合成を行い、表題化合物（７．２４ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.13 (s, 3 H) 2.15 (s, 3 H) 5.23 (br. s., 1 H) 6.05 (br. s., 1 H) 6.52 (d, J=8.5 Hz, 1 H) 7.07 (d, J=8.5 Hz, 1 H).
MS ESI/APCI Dual nega: 236[M-H]^-.
（２）４−［（ｔｅｒｔ−ブトキシカルボニル）アミノ］−２，３−ジメチルフェニル トリフルオロメタンスルホナート

Synthesis was performed in the same manner as in Reference Example 6-A (1) using commercially available 4-amino-2,3-xylenol (5.00 g) to obtain the title compound (7.24 g) as a brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.13 (s, 3 H) 2.15 (s, 3 H) 5.23 (br. S., 1 H) 6.05 (br. S. , 1 H) 6.52 (d, J = 8.5 Hz, 1 H) 7.07 (d, J = 8.5 Hz, 1 H).
MS ESI / APCI Dual nega: 236 [MH] ^- .
(2) 4-[(tert-Butoxycarbonyl) amino] -2,3-dimethylphenyl trifluoromethanesulfonate

参考例６−Ｂ（１）で得られた化合物（７．２３ｇ）を用いて参考例６−Ａ（２）と同様の方法で合成を行い、表題化合物（１１．１ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.20 (s, 3 H) 2.30 (s, 3 H) 6.28 (br. s., 1 H) 7.09 (d, J=9.0 Hz, 1 H) 7.68 (d, J=9.0 Hz, 1 H).
MS ESI/APCI Dual nega: 368[M-H]^-.
（３）４−アミノ−２，３−ジメチルフェニル トリフルオロメタンスルホナート

Using the compound (7.23 g) obtained in Reference Example 6-B (1), synthesis was performed in the same manner as in Reference Example 6-A (2) to obtain the title compound (11.1 g) as a brown powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.20 (s, 3 H) 2.30 (s, 3 H) 6.28 (br. S., 1 H) 7.09 (d, J = (9.0 Hz, 1 H) 7.68 (d, J = 9.0 Hz, 1 H).
MS ESI / APCI Dual nega: 368 [MH] ^- .
(3) 4-amino-2,3-dimethylphenyl trifluoromethanesulfonate

参考例６−Ｂ（２）で得られた化合物（１１．１ｇ）を用いて参考例６−Ａ（３）と同様の方法で合成を行い、表題化合物（８．２０ｇ）を茶色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.10 (s, 3 H) 2.26 (s, 3 H) 3.68 (br. s., 2 H) 6.54 (d, J=8.7 Hz, 1 H) 6.92 (d, J=8.7 Hz, 1 H).
MS ESI/APCI Dual posi: 270[M+H]⁺.
（４）４−メチル−１Ｈ−インダゾル−５−イル トリフルオロメタンスルホナート

The compound (11.1 g) obtained in Reference Example 6-B (2) was synthesized in the same manner as in Reference Example 6-A (3) to give the title compound (8.20 g) as a brown oily substance. Obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.10 (s, 3 H) 2.26 (s, 3 H) 3.68 (br. S., 2 H) 6.54 (d, J = 8.7 Hz, 1 H) 6.92 (d, J = 8.7 Hz, 1 H).
MS ESI / APCI Dual posi: 270 [M + H] ⁺ .
(4) 4-Methyl-1H-indazol-5-yl trifluoromethanesulfonate

参考例６−Ｂ（３）で得られた化合物（８．２０ｇ）を用いて参考例６−Ａ（４）と同様の方法で合成を行い、表題化合物（５．４６ｇ）を茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.65 (s, 3 H) 7.24 - 7.31 (m, 1 H) 7.35 - 7.42 (m, 1 H) 8.17 (s, 1 H).
MS ESI/APCI Dual posi: 281[M+H]⁺.
MS ESI/APCI Dual nega: 279[M-H]^-, 315[M+Cl]^-.
参考例７
ｔｅｒｔ−ブチル ４−［５−（ヒドロキシメチル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート
（１）メチル １−［１−（ｔｅｒｔ−ブトキシカルボニル）ピペリジン−４−イル］−１Ｈ−インダゾール−５−カルボキシラート

Synthesis was performed in the same manner as in Reference Example 6-A (4) using the compound (8.20 g) obtained in Reference Example 6-B (3), and the title compound (5.46 g) was obtained as a brown powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.65 (s, 3 H) 7.24-7.31 (m, 1 H) 7.35-7.42 (m, 1 H) 8.17 (s, 1 H).
MS ESI / APCI Dual posi: 281 [M + H] ⁺ .
MS ESI / APCI Dual nega: 279 [MH] ^- , 315 [M + Cl] ^- .
Reference Example 7
tert-butyl 4- [5- (hydroxymethyl) -1H-indazol-1-yl] piperidine-1-carboxylate (1) methyl 1- [1- (tert-butoxycarbonyl) piperidin-4-yl] -1H -Indazole-5-carboxylate

市販のメチル １Ｈ−インダゾール−５−カルボキラート（２００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１０ｍｌ）溶液へ、炭酸セシウム（７４３ｍｇ）、参考例Ａで得られた化合物（４７８ｍｇ）を加え、８０℃にて３時間攪拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。得られた有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４９：１〜１：１）にて精製し、表題化合物（２１７ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.99 - 2.06 (m, 2 H) 2.20 - 2.29 (m, 2 H) 2.92 - 3.03 (m, 2 H) 3.95 (s, 3 H) 4.25 - 4.40 (m, 2 H) 4.55 - 4.62 (m, 1 H) 7.46 (d, J=8.5 Hz, 1 H) 8.06 (d, J=8.5 Hz, 1 H) 8.10 (s, 1 H) 8.52 (s, 1 H).
MS ESI/APCI Dual posi: 382[M+Na]⁺.
（２）ｔｅｒｔ−ブチル ４−［５−（ヒドロキシメチル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

To a commercially available solution of methyl 1H-indazole-5-carboxylate (200 mg) in N, N-dimethylformamide (10 ml) was added cesium carbonate (743 mg) and the compound obtained in Reference Example A (478 mg), and the mixture was heated to 80 ° C. And stirred for 3 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 49: 1 to 1: 1) to obtain the title compound (217 mg) as a light brown powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.99-2.06 (m, 2 H) 2.20-2.29 (m, 2 H) 2.92-3.03 (m, 2 H) 3.95 (s , 3 H) 4.25-4.40 (m, 2 H) 4.55-4.62 (m, 1 H) 7.46 (d, J = 8.5 Hz, 1 H) 8.06 (d, J = 8.5 Hz, 1 H) 8.10 (s, 1 H) 8.52 (s, 1 H).
MS ESI / APCI Dual posi: 382 [M + Na] ⁺ .
(2) tert-butyl 4- [5- (hydroxymethyl) -1H-indazol-1-yl] piperidine-1-carboxylate

参考例７（１）で得られた化合物（１００ｍｇ）のテトラヒドロフラン（２ｍｌ）溶液へ、氷冷下、水素化リチウムアルミニウム（１４ｍｇ）を加え、同温で1時間攪拌した。氷冷化、反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１〜０：１）にて精製し、表題化合物（７０ｍｇ）を無色固体として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.93 - 2.09 (m, 2 H) 2.11 - 2.35 (m, 2 H) 2.86 - 3.06 (m, 2 H) 4.21 - 4.41 (m, 2 H) 4.46 - 4.64 (m, 1 H) 4.79 (d, J=5.7 Hz, 2 H) 7.38 - 7.47 (m, 2 H) 7.72 (s, 1 H) 7.99 (s, 1 H).
MS ESI/APCI Dual posi: 354[M+Na]⁺.
参考例８
ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−ベンゾトリアゾル−１−イル）ピペリジン−１−カルボキシラート
（１）ｔｅｒｔ−ブチル ４−［（４−ブロモ−２−ニトロフェニル）アミノ］ピペリジン−１−カルボキシラート

To a solution of the compound (100 mg) obtained in Reference Example 7 (1) in tetrahydrofuran (2 ml) was added lithium aluminum hydride (14 mg) under ice cooling, and the mixture was stirred at the same temperature for 1 hour. The mixture was ice-cooled, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 4: 1 to 0: 1) to obtain the title compound (70 mg) as a colorless solid.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9 H) 1.93-2.09 (m, 2 H) 2.11-2.35 (m, 2 H) 2.86-3.06 (m, 2 H) 4.21-4.41 (m, 2 H) 4.46-4.64 (m, 1 H) 4.79 (d, J = 5.7 Hz, 2 H) 7.38-7.47 (m, 2 H) 7.72 (s, 1 H) 7.99 (s, 1 H) .
MS ESI / APCI Dual posi: 354 [M + Na] ⁺ .
Reference Example 8
tert-butyl 4- (5-bromo-1H-benzotriazol-1-yl) piperidine-1-carboxylate (1) tert-butyl 4-[(4-bromo-2-nitrophenyl) amino] piperidine-1 -Carboxylate

市販の４−ブロモ−１−フルオロ−２−ニトロベンゼン（２５．０ｇ）のジメチルスルホキシド（１１４ｍｌ）溶液へ、ｔｅｒｔ−ブチル ４−アミノピペリジン−１−カルボキシラート（２０．７ｇ）、炭酸セシウム（３７．１ｇ）を加え１００℃にて１時間攪拌した。冷却後反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をヘキサン−酢酸エチル混合溶液で再結晶し、粉末をろ取、ヘキサン洗浄した。ろ液を減圧濃縮し、得られた残渣をヘキサン−酢酸エチル混合溶液で再結晶し、粉末をろ取、ヘキサン洗浄した。得られた粉末を合わせて減圧乾燥し、表題化合物（４０．５ｇ）を橙色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 1.43 - 1.69 (m, 2 H) 1.96 - 2.13 (m, 2 H) 2.94 - 3.15 (m, 2 H) 3.54 - 3.76 (m, 1 H) 3.93 - 4.12 (m, 2 H) 6.79 (d, J=9.2 Hz, 1 H) 7.49 (dd, J=9.2, 2.4 Hz, 1 H) 8.00 - 8.13 (m, 1 H) 8.32 (d, J=2.4 Hz, 1 H).
MS ESI/APCI Dual posi: 422[M+Na]⁺.
MS ESI/APCI Dual nega: 398[M-H]^-.
（２）ｔｅｒｔ−ブチル ４−［（２−アミノ−４−ブロモフェニル）アミノ］ピペリジン−１−カルボキシラート

To a solution of commercially available 4-bromo-1-fluoro-2-nitrobenzene (25.0 g) in dimethyl sulfoxide (114 ml), tert-butyl 4-aminopiperidine-1-carboxylate (20.7 g), cesium carbonate (37. 1 g) was added and stirred at 100 ° C. for 1 hour. After cooling, water was added to the reaction solution, followed by extraction with ethyl acetate, and the resulting organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized with a hexane-ethyl acetate mixed solution, and the powder was collected by filtration and washed with hexane. The filtrate was concentrated under reduced pressure, and the resulting residue was recrystallized with a hexane-ethyl acetate mixed solution, and the powder was collected by filtration and washed with hexane. The obtained powders were combined and dried under reduced pressure to give the title compound (40.5 g) as an orange powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 1.43-1.69 (m, 2 H) 1.96-2.13 (m, 2 H) 2.94-3.15 (m, 2 H) 3.54-3.76 (m, 1 H) 3.93-4.12 (m, 2 H) 6.79 (d, J = 9.2 Hz, 1 H) 7.49 (dd, J = 9.2, 2.4 Hz, 1 H) 8.00-8.13 (m, 1 H) 8.32 (d, J = 2.4 Hz, 1 H).
MS ESI / APCI Dual posi: 422 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 398 [MH] ^- .
(2) tert-butyl 4-[(2-amino-4-bromophenyl) amino] piperidine-1-carboxylate

参考例８（１）で得られた化合物（４０．５ｇ）のエタノール（３３７ｍｌ）懸濁液へ、氷冷下、鉄粉（２８．２ｇ）、塩化アンモニウム（５４０ｍｇ）／水（１０１ｍｌ）溶液を加え、７８℃にて５時間攪拌した。反応液をろ過し、ろ液を減圧濃縮した。残渣に飽和食塩水を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（３７．４ｇ）を茶色ガム状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.24 - 1.51 (m, 2 H) 1.47 (s, 9 H) 1.91 - 2.09 (m, 2 H) 2.84 - 3.03 (m, 2 H) 3.24 - 3.45 (m, 1 H) 3.94 - 4.12 (m, 2 H) 6.52 (d, J=8.4 Hz, 1 H) 6.81 - 6.92 (m, 2 H).
MS ESI/APCI Dual posi: 392[M+Na]⁺.
MS ESI/APCI Dual nega: 404[M+Cl]^-.
（３）ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−ベンゾトリアゾル−１−イル）ピペリジン−１−カルボキシラート

To an ethanol (337 ml) suspension of the compound (40.5 g) obtained in Reference Example 8 (1), under ice cooling, a solution of iron powder (28.2 g), ammonium chloride (540 mg) / water (101 ml) was added. In addition, the mixture was stirred at 78 ° C. for 5 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. To the residue was added saturated brine, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was removed under reduced pressure to give the title compound (37.4 g) as a brown gum.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.24-1.51 (m, 2 H) 1.47 (s, 9 H) 1.91-2.09 (m, 2 H) 2.84-3.03 (m, 2 H) 3.24-3.45 (m, 1 H) 3.94-4.12 (m, 2 H) 6.52 (d, J = 8.4 Hz, 1 H) 6.81-6.92 (m, 2 H).
MS ESI / APCI Dual posi: 392 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 404 [M + Cl] ^- .
(3) tert-butyl 4- (5-bromo-1H-benzotriazol-1-yl) piperidine-1-carboxylate

参考例８（２）で得られた化合物（３７．４ｇ）の酢酸溶液（３３７ｍｌ）へ、氷冷下、亜硝酸ナトリウム（１０．５ｇ）／水（３３．７ｍｌ）溶液を加え、室温にて１時間攪拌した。反応液へ水を加え、室温にて１時間攪拌し、析出した粉末をろ取し、水、ヘキサンにて洗浄した。得られた粉末にクロロホルム、飽和食塩水を加え、クロロホルムにて抽出し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム）にて精製後、ヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（２９．３ｇ）を薄茶色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δppm 1.50 (s, 9 H) 2.08 - 2.46 (m, 4 H) 2.92 - 3.14 (m, 2 H) 4.24 - 4.44 (m, 2 H) 4.71 - 4.90 (m, 1 H) 7.45 (d, J=8.8 Hz, 1 H) 7.58 (dd, J=8.8, 1.8 Hz, 1 H) 8.24 (d, J=1.8 Hz, 1 H).
MS ESI/APCI Dual posi: 381[M+H]⁺, 403[M+Na]⁺.
MS ESI/APCI Dual nega: 415[M+Cl]^-.
参考例９
ｔｅｒｔ−ブチル ４−［５−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

To an acetic acid solution (337 ml) of the compound (37.4 g) obtained in Reference Example 8 (2), a sodium nitrite (10.5 g) / water (33.7 ml) solution was added under ice cooling, and at room temperature. Stir for 1 hour. Water was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. The precipitated powder was collected by filtration and washed with water and hexane. Chloroform and saturated brine were added to the obtained powder, followed by extraction with chloroform, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent: chloroform) and recrystallized from a mixed solution of hexane-ethyl acetate to obtain the title compound (29.3 g) as a light brown powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δppm 1.50 (s, 9 H) 2.08-2.46 (m, 4 H) 2.92-3.14 (m, 2 H) 4.24-4.44 (m, 2 H) 4.71-4.90 ( m, 1 H) 7.45 (d, J = 8.8 Hz, 1 H) 7.58 (dd, J = 8.8, 1.8 Hz, 1 H) 8.24 (d, J = 1.8 Hz, 1 H).
MS ESI / APCI Dual posi: 381 [M + H] ⁺ , 403 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 415 [M + Cl] ^- .
Reference Example 9
tert-Butyl 4- [5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例８（３）で得られた化合物（３．００ｇ）を用いて、参考例２と同様の方法で合成を行い、表題化合物（２．７０ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 9 H) 1.51 (s, 8 H) 1.56 (s, 4 H) 2.09 - 2.23 (m, 2 H) 2.26 - 2.43 (m, 2 H) 2.94 - 3.11 (m, 2 H) 4.25 - 4.41 (m, 2 H) 4.76 - 4.90 (m, 1 H) 7.53 (dd, J=8.3, 0.9 Hz, 1 H) 7.88 (dd, J=8.3, 0.9 Hz, 1 H) 8.56 (s, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺, 451[M+Na]⁺.
参考例１０
５−ブロモ−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール
（１）５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール 塩酸塩

Using the compound (3.00 g) obtained in Reference Example 8 (3), synthesis was performed in the same manner as in Reference Example 2 to obtain the title compound (2.70 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 9 H) 1.51 (s, 8 H) 1.56 (s, 4 H) 2.09-2.23 (m, 2 H) 2.26-2.43 (m, 2 H) 2.94-3.11 (m, 2 H) 4.25-4.41 (m, 2 H) 4.76-4.90 (m, 1 H) 7.53 (dd, J = 8.3, 0.9 Hz, 1 H) 7.88 (dd, J = 8.3 , 0.9 Hz, 1 H) 8.56 (s, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ , 451 [M + Na] ⁺ .
Reference Example 10
5-Bromo-1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole (1) 5-Bromo-1- (piperidin-4-yl) -1H-benzo Triazole hydrochloride

参考例８（３）で得られた化合物（１５．０ｇ）のメタノール（７９ｍｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（１９７ｍｌ）を加え、室温で２．５時間撹拌した。反応液を濃縮し、表題化合物（１４．３ｇ）を紫色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.23 - 2.34 (m, 2 H) 2.42 - 2.58 (m, 2 H) 3.06 - 3.25 (m, 2 H) 3.41 - 3.54 (m, 2 H) 5.23 - 5.37 (m, 1 H) 7.76 (dd, J=8.8, 1.8 Hz, 1 H) 8.04 (d, J=8.8 Hz, 1 H) 8.34 - 8.41 (m, 1 H).
MS ESI/APCI Dual posi: 281[M+H]⁺.
MS ESI/APCI Dual nega: 315[M+Cl]^-.
（２）５−ブロモ−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール

To a suspension of the compound (15.0 g) obtained in Reference Example 8 (3) in methanol (79 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (197 ml), and the mixture was stirred at room temperature for 2.5 hours. . The reaction mixture was concentrated to give the title compound (14.3 g) as a purple powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.23-2.34 (m, 2 H) 2.42-2.58 (m, 2 H) 3.06-3.25 (m, 2 H) 3.41-3.54 (m, 2 H) 5.23-5.37 (m, 1 H) 7.76 (dd, J = 8.8, 1.8 Hz, 1 H) 8.04 (d, J = 8.8 Hz, 1 H) 8.34-8.41 (m, 1 H).
MS ESI / APCI Dual posi: 281 [M + H] ⁺ .
MS ESI / APCI Dual nega: 315 [M + Cl] ^- .
(2) 5-Bromo-1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole

参考例１０（１）で得られた化合物（１４．３ｇ）のＮ，Ｎ−ジメチルホルムアミド（１８６ｍｌ）懸濁液へ、２−クロロ−5−エチルピリミジン（８．４１ｇ）、炭酸セシウム（６４．１ｇ）を加え、８０℃にて１２時間、９５℃にて４時間撹拌した。反応液に氷水（５００ｍｌ）を加えて１．５時間氷冷撹拌した後、生じた沈殿物をろ取、水で洗浄、乾燥し、薄茶色粉末（１２．２ｇ）を得た。得られた化合物をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝２：１）にて精製し、表題化合物（１１．５ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.18 - 2.30 (m, 2 H) 2.31 - 2.56 (m, 4 H) 3.17 (ddd, J=13.9, 11.6, 2.8 Hz, 2 H) 4.85 - 5.03 (m, 3 H) 7.44 - 7.50 (m, 1 H) 7.54 - 7.60 (m, 1 H) 8.19 - 8.27 (m, 3 H).
MS ESI/APCI Dual posi: 387[M+H]⁺, 409[M+Na]⁺.
参考例１１
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）−１Ｈ−ベンゾトリアゾール

To a suspension of the compound (14.3 g) obtained in Reference Example 10 (1) in N, N-dimethylformamide (186 ml), 2-chloro-5-ethylpyrimidine (8.41 g) and cesium carbonate (64. 1 g) was added, and the mixture was stirred at 80 ° C. for 12 hours and at 95 ° C. for 4 hours. Ice water (500 ml) was added to the reaction mixture, and the mixture was stirred with ice cooling for 1.5 hours. The resulting precipitate was collected by filtration, washed with water, and dried to give a light brown powder (12.2 g). The obtained compound was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 2: 1) to obtain the title compound (11.5 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.18-2.30 (m, 2 H) 2.31-2.56 (m, 4 H) 3.17 (ddd, J = 13.9 , 11.6, 2.8 Hz, 2 H) 4.85-5.03 (m, 3 H) 7.44-7.50 (m, 1 H) 7.54-7.60 (m, 1 H) 8.19-8.27 (m, 3 H).
MS ESI / APCI Dual posi: 387 [M + H] ⁺ , 409 [M + Na] ⁺ .
Reference Example 11
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H -Benzotriazole

参考例１０（２）で得られた化合物（１５０ｍｇ）を用いて、参考例２と同様の方法で合成を行い、表題化合物（１５０ｍｇ）を淡桃色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19 - 1.28 (m, 11 H) 1.38 (s, 4 H) 2.19 - 2.31 (m, 2 H) 2.31 - 2.56 (m, 4 H) 3.11 - 3.25 (m, 2 H) 4.89 - 5.03 (m, 3 H) 7.52 - 7.58 (m, 1 H) 7.87 (d, J=8.4 Hz, 1 H) 8.22 (s, 2 H) 8.56 (s, 1 H).
MS ESI/APCI Dual posi: 435[M+H]⁺.
参考例１２
５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール 塩酸塩

Using the compound (150 mg) obtained in Reference Example 10 (2), synthesis was performed in the same manner as in Reference Example 2 to obtain the title compound (150 mg) as a pale pink powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19-1.28 (m, 11 H) 1.38 (s, 4 H) 2.19-2.31 (m, 2 H) 2.31-2.56 (m, 4 H) 3.11-3.25 (m, 2 H) 4.89-5.03 (m, 3 H) 7.52-7.58 (m, 1 H) 7.87 (d, J = 8.4 Hz, 1 H) 8.22 (s, 2 H) 8.56 (s, 1 H) .
MS ESI / APCI Dual posi: 435 [M + H] ⁺ .
Reference Example 12
5- [4- (Methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-benzotriazole hydrochloride

後掲した実施例１１−１で得られた化合物（６９４ｍｇ）のメタノール（５．０７ｍｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（１５．２ｍｌ）を加え、室温にて３時間攪拌した。反応液を減圧濃縮し、得られた粉末を酢酸エチルにて洗浄し、表題化合物（６１０ｍｇ）を薄桃色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 2.22 - 2.62 (m, 4 H) 3.07 - 3.35 (m, 2 H) 3.28 (s, 3 H) 3.35 - 3.60 (m, 2 H) 5.21 - 5.41 (m, 1 H) 7.96 - 8.16 (m, 6 H) 8.49 (s, 1 H).
MS ESI/APCI Dual posi: 357[M+H]⁺, 379[M+Na]⁺.
MS ESI/APCI Dual nega: 391[M+Cl]^-.
参考例１３
４−｛１−［１−（ｔｅｒｔ−ブトキシカルボニル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝安息香酸

A 4M hydrogen chloride / 1,4-dioxane solution (15.2 ml) was added to a suspension of the compound obtained in Example 11-1 (694 mg) in methanol (5.07 ml), and the mixture was added at room temperature. Stir for hours. The reaction mixture was concentrated under reduced pressure, and the obtained powder was washed with ethyl acetate to give the title compound (610 mg) as a pale pink powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 2.22-2.62 (m, 4 H) 3.07-3.35 (m, 2 H) 3.28 (s, 3 H) 3.35-3.60 (m, 2 H) 5.21- 5.41 (m, 1 H) 7.96-8.16 (m, 6 H) 8.49 (s, 1 H).
MS ESI / APCI Dual posi: 357 [M + H] ⁺ , 379 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 391 [M + Cl] ^- .
Reference Example 13
4- {1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -1H-benzotriazol-5-yl} benzoic acid

参考例８（３）で得られた化合物（３００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（３．９３ｍｌ）溶液へ、４−（ジヒドロキシボラニル）安息香酸（１５７ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（３２．１ｍｇ）、２Ｍ炭酸ナトリウム水溶液（１．１８ｍｌ）を加え、１００℃にて１時間攪拌した。反応液へ水を加え、酢酸エチルで水層を洗浄した。水層に１５％クエン酸水溶液を加え、析出した粉末をろ取し、水、ヘキサンにて洗浄した。得られた粉末をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（３００ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.12 - 2.52 (m, 4 H) 2.96 - 3.18 (m, 2 H) 4.28 - 4.46 (m, 2 H) 4.79 - 4.99 (m, 1 H) 7.62 - 7.71 (m, 1 H) 7.72 - 7.83 (m, 3 H) 8.19 - 8.28 (m, 2 H) 8.33 (s, 1 H).
MS ESI/APCI Dual posi: 423[M+H]⁺, 445[M+Na]⁺.
MS ESI/APCI Dual nega: 421[M-H]^-.
参考例１３−Ｂ
４−｛１−［１−（ｔｅｒｔ−ブトキシカルボニル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−３−フルオロ安息香酸

To a solution of the compound (300 mg) obtained in Reference Example 8 (3) in N, N-dimethylformamide (3.93 ml), 4- (dihydroxyboranyl) benzoic acid (157 mg), [1,1′-bis ( Diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (32.1 mg), 2M aqueous sodium carbonate solution (1.18 ml) were added, and the mixture was stirred at 100 ° C. for 1 hour. Water was added to the reaction solution, and the aqueous layer was washed with ethyl acetate. A 15% aqueous citric acid solution was added to the aqueous layer, and the precipitated powder was collected by filtration and washed with water and hexane. The obtained powder was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 0 to 1: 1) to obtain the title compound (300 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.12-2.52 (m, 4 H) 2.96-3.18 (m, 2 H) 4.28-4.46 (m, 2 H) 4.79-4.99 (m, 1 H) 7.62-7.71 (m, 1 H) 7.72-7.83 (m, 3 H) 8.19-8.28 (m, 2 H) 8.33 (s, 1 H).
MS ESI / APCI Dual posi: 423 [M + H] ⁺ , 445 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 421 [MH] ^- .
Reference Example 13-B
4- {1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -1H-benzotriazol-5-yl} -3-fluorobenzoic acid

参考例９で得られた化合物（１００ｍｇ）、４−ブロモ−３−フルオロ安息香酸（７７ｍｇ）、テトラキス（トリフェニルホスフィン）パラジウム（１０ｍｇ）、２Ｍ炭酸ナトリウム水溶液（３５０μｌ）の１，２−ジメトキシエタン（２．４ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１３０℃にて３０分間撹拌した。冷却後反応液へ水を加え、酢酸エチルにて抽出した。有機層を飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥し、乾燥剤を濾別した。溶媒を減圧下濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９８：２〜８５：１５）にて精製し、表題化合物（７０ｍｇ）を淡褐色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.45 (s, 9 H) 1.99 - 2.24 (m, 4 H) 4.07 - 4.23 (m, 2 H) 5.11 - 5.24 (m, 1 H) 7.73 - 7.85 (m, 3 H) 7.85 - 7.92 (m, 1 H) 8.09 (d, J=8.7 Hz, 1 H) 8.28 (s, 1 H).
MS ESI/APCI Dual posi: 463[M+Na]⁺
参考例１４−Ａ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝安息香酸

1,2-dimethoxyethane of the compound obtained in Reference Example 9 (100 mg), 4-bromo-3-fluorobenzoic acid (77 mg), tetrakis (triphenylphosphine) palladium (10 mg), 2M aqueous sodium carbonate solution (350 μl). The suspension (2.4 ml) was stirred for 30 minutes at 130 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the desiccant was filtered off. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 98: 2-85: 15) to obtain the title compound (70 mg) as a light brown powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.45 (s, 9 H) 1.99-2.24 (m, 4 H) 4.07-4.23 (m, 2 H) 5.11-5.24 (m, 1 H) 7.73- 7.85 (m, 3 H) 7.85-7.92 (m, 1 H) 8.09 (d, J = 8.7 Hz, 1 H) 8.28 (s, 1 H).
MS ESI / APCI Dual posi: 463 [M + Na] ⁺
Reference Example 14-A
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} benzoic acid

参考例１０（２）で得られた化合物（１００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２．５８ｍｌ）溶液へ、４−（ジヒドロキシボラニル）安息香酸（６４．３ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１０．５ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．３８７ｍｌ）を加え、１００℃にて２時間攪拌した。反応液へ水、酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液にて逆抽出した。水層に１５％クエン酸水溶液を加え、析出した粉末をろ取し、ヘキサンにて洗浄した。得られた粉末をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：０〜１：２）にて精製し、表題化合物（８５ｍｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.09 - 2.18 (m, 2 H) 2.20 - 2.26 (m, 2 H) 2.47 (q, J=7.6 Hz, 2 H) 3.18 - 3.25 (m, 2 H) 4.80 - 4.86 (m, 2 H) 5.26 - 5.33 (m, 1 H) 7.93 (d, J=8.4 Hz, 2 H) 7.96 (dd, J=8.6, 1.4 Hz, 1 H) 8.05 (d, J=8.4 Hz, 2 H) 8.09 (d, J=8.6 Hz, 1 H) 8.31 (s, 2 H) 8.40 - 8.42 (m, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺, 451[M+Na]⁺.
MS ESI/APCI Dual nega: 427[M-H]^-.
参考例１４−Ｂ
３−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝安息香酸

To a solution of the compound (100 mg) obtained in Reference Example 10 (2) in N, N-dimethylformamide (2.58 ml), 4- (dihydroxyboranyl) benzoic acid (64.3 mg), [1,1′- Bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (10.5 mg), 2M aqueous sodium carbonate solution (0.387 ml) were added, and the mixture was stirred at 100 ° C. for 2 hours. Water and ethyl acetate were added to the reaction solution, and the mixture was back extracted with a saturated aqueous sodium hydrogen carbonate solution. A 15% aqueous citric acid solution was added to the aqueous layer, and the precipitated powder was collected by filtration and washed with hexane. The obtained powder was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 0 to 1: 2) to obtain the title compound (85 mg) as a pale yellow powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.09-2.18 (m, 2 H) 2.20-2.26 (m, 2 H) 2.47 (q, J = 7.6 Hz, 2 H) 3.18-3.25 (m, 2 H) 4.80-4.86 (m, 2 H) 5.26-5.33 (m, 1 H) 7.93 (d, J = 8.4 Hz, 2 H) 7.96 (dd, J = 8.6, 1.4 Hz, 1 H) 8.05 (d, J = 8.4 Hz, 2 H) 8.09 (d, J = 8.6 Hz, 1 H) 8.31 (s, 2 H) 8.40-8.42 (m, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ , 451 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 427 [MH] ^- .
Reference Example 14-B
3- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} benzoic acid

参考例１０（２）で得られた化合物（１．００ｇ）と３−カルボキシフェニルボロン酸（６４２ｍｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（０．９８ｇ）を灰色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.05 - 2.30 (m, 4 H) 2.43 - 2.49 (m, 2 H) 3.16 - 3.28 (m, 2 H) 4.83 (br. d, J=13.8 Hz, 2 H) 5.23 - 5.36 (m, 1 H) 7.62 (t, J=7.8 Hz, 1 H) 7.90 - 8.05 (m, 3 H) 8.08 (d, J=8.5 Hz, 1 H) 8.25 - 8.36 (m, 4 H).
MS ESI/APCI Dual posi: 429[M+H]⁺.
MS ESI/APCI Dual nega: 427[M-H]^-.
参考例１４−Ｃ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−３−フルオロ安息香酸

Using the compound (1.00 g) obtained in Reference Example 10 (2) and 3-carboxyphenylboronic acid (642 mg), the reaction and purification were carried out in the same manner as in Reference Example 14-A to give the title compound ( 0.98 g) was obtained as a gray powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.05-2.30 (m, 4 H) 2.43-2.49 (m, 2 H) 3.16-3.28 (m, 2 H) 4.83 (br.d, J = 13.8 Hz, 2 H) 5.23-5.36 (m, 1 H) 7.62 (t, J = 7.8 Hz, 1 H) 7.90-8.05 (m, 3 H) 8.08 (d , J = 8.5 Hz, 1 H) 8.25-8.36 (m, 4 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ .
MS ESI / APCI Dual nega: 427 [MH] ^- .
Reference Example 14-C
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -3-fluorobenzoic acid

参考例１０（２）で得られた化合物（１５０ｍｇ）と、参考例Ｅ−２で得られた化合物（１５５ｍｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（１４２ｍｇ）を灰色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.17 (t, J=7.5 Hz, 3 H) 2.09 - 2.30 (m, 4 H) 2.46 - 2.53 (m, 2 H) 3.20 - 3.35 (m, 2 H) 4.82 (br. d, J=13.4 Hz, 2 H) 5.27 - 5.39 (m, 1 H) 7.75 - 7.85 (m, 3 H) 7.87 - 7.92 (m, 1 H) 8.12 (d, J=8.7 Hz, 1 H) 8.28 (s, 1 H) 8.37 (s, 2 H).
MS ESI/APCI Dual posi: 447[M+H]⁺.
MS ESI/APCI Dual nega: 445[M-H]^-.
参考例１４−Ｄ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−３，５−ジフルオロ安息香酸

Using the compound (150 mg) obtained in Reference Example 10 (2) and the compound (155 mg) obtained in Reference Example E-2, the reaction and purification were performed in the same manner as in Reference Example 14-A. The title compound (142 mg) was obtained as a gray powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.17 (t, J = 7.5 Hz, 3 H) 2.09-2.30 (m, 4 H) 2.46-2.53 (m, 2 H) 3.20-3.35 (m, 2 H) 4.82 (br.d, J = 13.4 Hz, 2 H) 5.27-5.39 (m, 1 H) 7.75-7.85 (m, 3 H) 7.87-7.92 (m, 1 H) 8.12 (d, J = 8.7 Hz, 1 H) 8.28 (s, 1 H) 8.37 (s, 2 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ .
MS ESI / APCI Dual nega: 445 [MH] ^- .
Reference Example 14-D
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -3,5-difluorobenzoic acid

参考例１０（２）で得られた化合物（１００ｍｇ）と参考例Ｅ−３で得られた化合物（１０４ｍｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（５３ｍｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.21 - 2.62 (m, 6 H) 3.14 - 3.31 (m, 2 H) 4.90 - 5.12 (m, 3 H) 7.55 - 7.64 (m, 1 H) 7.66 - 7.81 (m, 3 H) 8.24 (s, 3 H).
MS ESI/APCI Dual posi: 465[M+H]⁺.
MS ESI/APCI Dual nega: 463[M-H]^-.
参考例１４−Ｅ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−３−メチル安息香酸

Using the compound (100 mg) obtained in Reference Example 10 (2) and the compound (104 mg) obtained in Reference Example E-3, the reaction and purification were performed in the same manner as in Reference Example 14-A. Compound (53 mg) was obtained as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.21-2.62 (m, 6 H) 3.14-3.31 (m, 2 H) 4.90-5.12 (m, 3 H) 7.55-7.64 (m, 1 H) 7.66-7.81 (m, 3 H) 8.24 (s, 3 H).
MS ESI / APCI Dual posi: 465 [M + H] ⁺ .
MS ESI / APCI Dual nega: 463 [MH] ^- .
Reference Example 14-E
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -3-methylbenzoic acid

参考例１０（２）で得られた化合物（２．００ｇ）と参考例Ｅ−４で得られた化合物（２．０３ｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（１．２７ｇ）を黒色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.06 - 2.29 (m, 4 H) 2.32 (s, 3 H) 2.40 - 2.48 (m, 2 H) 3.15 - 3.28 (m, 2 H) 4.83 (br. d, J=13.4 Hz, 2 H) 5.22 - 5.38 (m, 1 H) 7.41 (d, J=7.9 Hz, 1 H) 7.55 - 7.61 (m, 1 H) 7.85 (dd, J=7.8, 1.6 Hz, 1 H) 7.92 (s, 1 H) 8.05 (d, J=7.8 Hz, 2 H) 8.31 (s, 2 H) 12.96 (br. s., 1 H).
MS ESI/APCI Dual posi: 443[M+H]⁺.
MS ESI/APCI Dual nega: 441[M-H]^-.
参考例１４−Ｆ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−２−フルオロ安息香酸

Using the compound (2.00 g) obtained in Reference Example 10 (2) and the compound (2.03 g) obtained in Reference Example E-4, the reaction and purification were carried out in the same manner as in Reference Example 14-A. To give the title compound (1.27 g) as a black powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.06-2.29 (m, 4 H) 2.32 (s, 3 H) 2.40-2.48 (m, 2 H ) 3.15-3.28 (m, 2 H) 4.83 (br.d, J = 13.4 Hz, 2 H) 5.22-5.38 (m, 1 H) 7.41 (d, J = 7.9 Hz, 1 H) 7.55-7.61 (m , 1 H) 7.85 (dd, J = 7.8, 1.6 Hz, 1 H) 7.92 (s, 1 H) 8.05 (d, J = 7.8 Hz, 2 H) 8.31 (s, 2 H) 12.96 (br. S. , 1 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ .
MS ESI / APCI Dual nega: 441 [MH] ^- .
Reference Example 14-F
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -2-fluorobenzoic acid

参考例１０（２）で得られた化合物（１．１０ｇ）と参考例Ｅ−５で得られた化合物（１．１３ｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（５６８ｍｇ）を灰色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.5 Hz, 3 H) 1.99 - 2.31 (m, 4 H) 2.40 - 2.47 (m, 2 H) 3.14 - 3.26 (m, 2 H) 4.82 (br. d, J=12.9 Hz, 2 H) 5.21 - 5.37 (m, 1 H) 7.68 - 7.83 (m, 2 H) 7.89 - 8.03 (m, 2 H) 8.06 - 8.12 (m, 1 H) 8.31 (s, 2 H) 8.48 (s, 1 H).
MS ESI/APCI Dual posi: 447[M+H]⁺.
MS ESI/APCI Dual nega: 445[M-H]^-.
参考例１４−Ｇ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−２−メチル安息香酸

Using the compound (1.10 g) obtained in Reference Example 10 (2) and the compound (1.13 g) obtained in Reference Example E-5, the reaction and purification were carried out in the same manner as in Reference Example 14-A. To give the title compound (568 mg) as a gray powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.5 Hz, 3 H) 1.99-2.31 (m, 4 H) 2.40-2.47 (m, 2 H) 3.14-3.26 (m, 2 H) 4.82 (br.d, J = 12.9 Hz, 2 H) 5.21-5.37 (m, 1 H) 7.68-7.83 (m, 2 H) 7.89-8.03 (m, 2 H) 8.06-8.12 (m, (1 H) 8.31 (s, 2 H) 8.48 (s, 1 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ .
MS ESI / APCI Dual nega: 445 [MH] ^- .
Reference Example 14-G
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -2-methylbenzoic acid

参考例１０（２）で得られた化合物（１．１６ｇ）と参考例Ｅ−６で得られた化合物（１．１８ｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（８３０ｍｇ）を灰色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.04 - 2.31 (m, 4 H) 2.41 - 2.46 (m, 2 H) 2.63 (s, 3 H) 3.15 - 3.28 (m, 2 H) 4.83 (br. d, J=13.2 Hz, 2 H) 5.22 - 5.36 (m, 1 H) 7.68 - 7.78 (m, 2 H) 7.92 - 7.98 (m, 2 H) 8.04 - 8.12 (m, 1 H) 8.31 (s, 2 H) 8.39 (s, 1 H) 12.84 (br. s., 1 H).
MS ESI/APCI Dual posi: 443[M+H]⁺.
MS ESI/APCI Dual nega: 441[M-H]^-.
参考例１４−Ｈ
２−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝ピリミジン−５−カルボン酸

Using the compound (1.16 g) obtained in Reference Example 10 (2) and the compound (1.18 g) obtained in Reference Example E-6, the reaction and purification were carried out in the same manner as in Reference Example 14-A. To give the title compound (830 mg) as a gray powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.04-2.31 (m, 4 H) 2.41-2.46 (m, 2 H) 2.63 (s, 3 H ) 3.15-3.28 (m, 2 H) 4.83 (br.d, J = 13.2 Hz, 2 H) 5.22-5.36 (m, 1 H) 7.68-7.78 (m, 2 H) 7.92-7.98 (m, 2 H ) 8.04-8.12 (m, 1 H) 8.31 (s, 2 H) 8.39 (s, 1 H) 12.84 (br. S., 1 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ .
MS ESI / APCI Dual nega: 441 [MH] ^- .
Reference Example 14-H
2- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} pyrimidine-5-carboxylic acid

参考例１１で得られた化合物（６４５ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１５ｍｌ）溶液へ、2-クロロピリミジン-5-カルボン酸メチル（３３３ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（６８ｍｇ）、２Ｍ炭酸ナトリウム水溶液（２．２ｍｌ）を加え、１００℃にて１時間攪拌した。室温へ冷却後、反応液へ水を加え、クロロホルムにて抽出し、得られた有機層を水、飽和食塩水にて順次洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝４９：１〜１９：１）にて精製を行い、メチル ２−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝ピリミジン−５−カルボキシラート（３７１ｍｇ）を得た。得られたメチル ２−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝ピリミジン−５−カルボキシラート（３７１ｍｇ）へ２．５Ｍ水酸化ナトリウム水溶液（２ｍｌ）、テトラヒドロフラン（５ｍｌ）、メタノール（５ｍｌ）を加え、室温で一晩撹拌した後、減圧留去を行った。得られた残渣へクエン酸水溶液を加え、クロロホルム抽出を行い、得られた有機層を無水硫酸ナトリウムで乾燥後、ろ過、減圧留去し、表題化合物（３６７ｍｇ）を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.11 - 1.21 (m, 3 H) 2.04 - 2.32 (m, 4 H) 2.40 - 2.54 (m, 2 H) 3.12 - 3.33 (m, 2 H) 4.77 - 4.90 (m, 2 H) 5.24 - 5.38 (m, 1 H) 8.12 - 8.18 (m, 1 H) 8.31 (s, 2 H) 8.64 - 8.70 (m, 1 H) 9.07 - 9.10 (m, 1 H) 9.33 (s, 2 H).
MS ESI/APCI Dual posi: 431[M+H]⁺.
MS ESI/APCI Dual nega: 429[M-H]^-.
参考例１５
ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−１イル）ピペリジン−１−カルボキシラート
（１）５−アミノ−２−ブロモ−４−メチルピリジン

To a solution of the compound (645 mg) obtained in Reference Example 11 in N, N-dimethylformamide (15 ml), methyl 2-chloropyrimidine-5-carboxylate (333 mg), [1,1′-bis (diphenylphosphino) Ferrocene] palladium (II) dichloride dichloromethane complex (68 mg), 2M aqueous sodium carbonate solution (2.2 ml) were added, and the mixture was stirred at 100 ° C. for 1 hr. After cooling to room temperature, water was added to the reaction solution, extracted with chloroform, and the resulting organic layer was washed successively with water and saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 49: 1 to 19: 1) to obtain methyl 2- {1- [1- (5-ethylpyrimidin-2-yl) piperidine. -4-yl] -1H-benzotriazol-5-yl} pyrimidine-5-carboxylate (371 mg) was obtained. To the resulting methyl 2- {1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} pyrimidin-5-carboxylate (371 mg) A 5 M aqueous sodium hydroxide solution (2 ml), tetrahydrofuran (5 ml) and methanol (5 ml) were added, and the mixture was stirred overnight at room temperature, and then distilled off under reduced pressure. A citric acid aqueous solution was added to the resulting residue, followed by extraction with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to obtain the title compound (367 mg).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.11-1.21 (m, 3 H) 2.04-2.32 (m, 4 H) 2.40-2.54 (m, 2 H) 3.12-3.33 (m, 2 H) 4.77-4.90 (m, 2 H) 5.24-5.38 (m, 1 H) 8.12-8.18 (m, 1 H) 8.31 (s, 2 H) 8.64-8.70 (m, 1 H) 9.07-9.10 (m, 1 H) 9.33 (s, 2 H).
MS ESI / APCI Dual posi: 431 [M + H] ⁺ .
MS ESI / APCI Dual nega: 429 [MH] ^- .
Reference Example 15
tert-Butyl 4- (5-Bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate (1) 5-Amino-2-bromo-4-methylpyridine

市販の２−ブロモ−４−メチル−ニトロピリジン（５．００ｇ）のテトラヒドロフラン（３０ｍｌ）溶液にラネーニッケル（水懸濁液）を加え、水素雰囲気下、室温で終夜攪拌した。反応液をセライト（登録商標）濾過後、濾液を濃縮し得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（４．０２ｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15 (d, J=0.9 Hz, 3 H) 3.62 (br. s., 2H) 7.14 (s, 1 H) 7.78 (s, 1 H)．
（２）５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Raney nickel (aqueous suspension) was added to a solution of commercially available 2-bromo-4-methyl-nitropyridine (5.00 g) in tetrahydrofuran (30 ml), and the mixture was stirred overnight at room temperature in a hydrogen atmosphere. The reaction mixture was filtered through Celite (registered trademark), the filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1) to give the title compound (4. 02g) was obtained as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15 (d, J = 0.9 Hz, 3 H) 3.62 (br. S., 2H) 7.14 (s, 1 H) 7.78 (s, 1 H).
(2) 5-Bromo-1H-pyrazolo [3,4-c] pyridine

参考例１５（１）で得られた５−アミノ−２−ブロモ−４−メチルピリジン（４．００ｇ）の酢酸（３００ｍｌ）溶液に亜硝酸ナトリウム（１．４８ｇ）を加え、室温で終夜攪拌した。反応液を濃縮後、得られた残渣を酢酸エチルに溶解し、飽和炭酸水素ナトリウム水溶液、飽和食塩水で洗浄、無水硫酸マグネシウムで乾燥した後、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（２．４８ｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.86 - 7.90 (m, 1 H) 8.09 - 8.14 (m, 1 H) 8.83 - 8.88 (m, 1 H)．
MS ESI/APCI Dual posi:198[M+H]⁺.
（３）ｔｅｒｔ−ブチル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−１イル）ピペリジン−１−カルボキシラート

Sodium nitrite (1.48 g) was added to a solution of 5-amino-2-bromo-4-methylpyridine (4.00 g) obtained in Reference Example 15 (1) in acetic acid (300 ml) and stirred overnight at room temperature. . After concentrating the reaction solution, the resulting residue was dissolved in ethyl acetate, washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1) to obtain the title compound (2.48 g) as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.86-7.90 (m, 1 H) 8.09-8.14 (m, 1 H) 8.83-8.88 (m, 1 H).
MS ESI / APCI Dual posi: 198 [M + H] ⁺ .
(3) tert-butyl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

参考例１５（２）で得られた５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン（７．８０ｇ）、参考例Ａで得られたｔｅｒｔ−ブチル ４−［（メチルスルホニル）オキシ］ピペリジン−１−カルボキシレート（１６．５ｇ）、炭酸セシウム（２５．７ｇ）のＮ，Ｎ−ジメチルホルムアミド（１２０ｍｌ）の混合液を８０℃にて３時間半攪拌した。反応溶液を濃縮した後、獲られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：４）にて精製し、表題化合物（５．３８ｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δppm 1.50 (s, 9 H) 1.96 - 2.13 (m, 2 H) 2.14 - 2.34 (m, 2 H) 2.87 - 3.09 (m, 2 H) 4.19 - 4.47 (m, 2 H) 4.56 - 4.73 (m, 1 H) 7.78 - 7.85 (m, 1 H) 8.00 (s, 1 H) 8.77 (s, 1 H)．
参考例１６
５−ブロモ−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

5-Bromo-1H-pyrazolo [3,4-c] pyridine (7.80 g) obtained in Reference Example 15 (2), tert-butyl 4-[(methylsulfonyl) oxy] obtained in Reference Example A A mixture of piperidine-1-carboxylate (16.5 g) and cesium carbonate (25.7 g) in N, N-dimethylformamide (120 ml) was stirred at 80 ° C. for 3.5 hours. After the reaction solution was concentrated, the obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 4) to obtain the title compound (5.38 g) as a yellow powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δppm 1.50 (s, 9 H) 1.96-2.13 (m, 2 H) 2.14-2.34 (m, 2 H) 2.87-3.09 (m, 2 H) 4.19-4.47 ( m, 2 H) 4.56-4.73 (m, 1 H) 7.78-7.85 (m, 1 H) 8.00 (s, 1 H) 8.77 (s, 1 H).
Reference Example 16
5-Bromo-1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

参考例１５（３）で得られた化合物（４．７０ｇ）のメタノール（１００ｍｌ）溶液へ４Ｍ塩化水素・１，４−ジオキサン溶液（１００ｍｌ）を加え、室温で1時間攪拌した。溶媒を減圧留去し、５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン塩酸塩を得た。得られた５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン塩酸塩のジメチルスルホキシド（９０ｍｌ）溶液へ２−クロロ−５−エチルピリミジン（３．４９ｇ）、炭酸セシウム（１９．５ｇ）を加え、１８０℃にて３０分攪拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。得られた有機層を一部濃縮後、水を加え、析出した結晶を濾取した。得られた結晶をヘキサンで洗浄後、クロロホルムで溶解し、シリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：０〜１：１）にて精製後、ヘキサンで粉末化し、表題化合物（３．２６ｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.11 - 2.18 (m, 2 H) 2.24 - 2.33 (m, 2 H) 2.49 (q, J=7.6 Hz, 2 H) 3.11 - 3.19 (m, 2 H) 4.74 - 4.82 (m, 1 H) 4.92 - 4.98 (m, 2 H) 7.82 (s, 1 H) 7.98 (s, 1 H) 8.21 (s, 2 H) 8.80 (s, 1 H).
MS ESI/APCI Dual posi: 387[M+H]⁺.
参考例１７
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝安息香酸の合成

To a methanol (100 ml) solution of the compound (4.70 g) obtained in Reference Example 15 (3) was added 4M hydrogen chloride / 1,4-dioxane solution (100 ml), and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure to obtain 5-bromo-1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine hydrochloride. To a solution of the obtained 5-bromo-1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine hydrochloride in dimethyl sulfoxide (90 ml) was added 2-chloro-5-ethylpyrimidine (3.49 g). ), Cesium carbonate (19.5 g) was added, and the mixture was stirred at 180 ° C. for 30 minutes. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was partially concentrated, water was added, and the precipitated crystals were collected by filtration. The obtained crystals are washed with hexane, dissolved in chloroform, purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 0 to 1: 1), and then powdered with hexane to give the title compound (3. 26 g) was obtained as a pale yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.11-2.18 (m, 2 H) 2.24-2.33 (m, 2 H) 2.49 (q, J = 7.6 Hz, 2 H) 3.11-3.19 (m, 2 H) 4.74-4.82 (m, 1 H) 4.92-4.98 (m, 2 H) 7.82 (s, 1 H) 7.98 (s, 1 H) 8.21 (s, 2 H) 8.80 (s, 1 H).
MS ESI / APCI Dual posi: 387 [M + H] ⁺ .
Reference Example 17
Synthesis of 4- {1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} benzoic acid

参考例１６で得られた化合物（２．００ｇ）、４−（ジヒドロキシボラニル）安息香酸（１．２８ｇ）、テトラキス（トリフェニスホスフィン）パラジウム（３００ｍｇ）、２Ｍ炭酸ナトリウム水溶液（４ｍｌ）のエタノール（４０ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１６０℃にて３０分間撹拌した。冷却後反応液へ水と酢酸エチルを加えてセライト（登録商標）ろ過した後、酢酸エチルで水層を洗浄した。水層に濃塩酸を加えて析出した粉末をろ取し、水、ヘキサンにて洗浄し、表題化合物（１．３５ｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.5 Hz, 3 H) 1.95 - 2.15 (m, 4 H) 2.42 - 2.48 (m, 2 H) 3.11 - 3.23 (m, 2 H) 4.81 (br. d, J=13.7 Hz, 2 H) 5.16 - 5.29 (m, 1 H) 8.03 (d, J=8.5 Hz, 2 H) 8.20 (d, J=8.5 Hz, 2 H) 8.26 (s, 1 H) 8.30 (s, 2 H) 8.39 (d, J=1.2 Hz, 1 H) 9.40 (br. s, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺.
MS ESI/APCI Dual nega: 427[M-H]^-.
参考例１８
６−ブロモ−３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン
（１）ｔｅｒｔ−ブチル ［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］カルバマート

Compound (2.00 g) obtained in Reference Example 16, 4- (dihydroxyboranyl) benzoic acid (1.28 g), tetrakis (triphenisphosphine) palladium (300 mg), 2M aqueous sodium carbonate solution (4 ml) in ethanol (4 ml) (40 ml) The suspension was stirred for 30 minutes at 160 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, water and ethyl acetate were added to the reaction solution and filtered through Celite (registered trademark), and then the aqueous layer was washed with ethyl acetate. Concentrated hydrochloric acid was added to the aqueous layer, and the precipitated powder was collected by filtration and washed with water and hexane to obtain the title compound (1.35 g) as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.5 Hz, 3 H) 1.95-2.15 (m, 4 H) 2.42-2.48 (m, 2 H) 3.11-3.23 (m, 2 H) 4.81 (br.d, J = 13.7 Hz, 2 H) 5.16-5.29 (m, 1 H) 8.03 (d, J = 8.5 Hz, 2 H) 8.20 (d, J = 8.5 Hz, 2 H) 8.26 (s, 1 H) 8.30 (s, 2 H) 8.39 (d, J = 1.2 Hz, 1 H) 9.40 (br.s, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ .
MS ESI / APCI Dual nega: 427 [MH] ^- .
Reference Example 18
6-Bromo-3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine (1) tert-butyl [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] carbamate

市販のｔｅｒｔ−ブチル ピペリジン−４−イルカルバマート（３．００ｇ）のＮ，Ｎ−ジメチルホルムアミド（４９．９ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（３．２０ｇ）、炭酸セシウム（２４．４ｇ）を加え、７０℃にて１５時間攪拌した。反応液に水を加え、析出した粉末をろ取し、水で洗浄した。得られた粉末を減圧乾燥し、表題化合物（３．４０ｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.18 (t, J=7.6 Hz, 3 H) 1.28 - 1.41 (m, 2 H) 1.45 (s, 9 H) 1.92 - 2.10 (m, 2 H) 2.46 (q, J=7.6 Hz, 2 H) 2.94 - 3.13 (m, 2 H) 3.57 - 3.82 (m, 1 H) 4.38 - 4.52 (m, 1 H) 4.52 - 4.67 (m, 2 H) 8.16 (s, 2 H).
MS ESI/APCI Dual posi: 307[M+H]⁺, 329[M+Na]⁺.
MS ESI/APCI Dual nega: 305[M-H]^-, 341[M+Cl]^-.
（２）１−（５−エチルピリミジン−２−イル）ピペリジン−４−アミン

To a solution of commercially available tert-butyl piperidin-4-ylcarbamate (3.00 g) in N, N-dimethylformamide (49.9 ml), 2-chloro-5-ethylpyrimidine (3.20 g), cesium carbonate (24 4 g) was added and stirred at 70 ° C. for 15 hours. Water was added to the reaction solution, and the precipitated powder was collected by filtration and washed with water. The obtained powder was dried under reduced pressure to obtain the title compound (3.40 g) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.18 (t, J = 7.6 Hz, 3 H) 1.28-1.41 (m, 2 H) 1.45 (s, 9 H) 1.92-2.10 (m, 2 H) 2.46 (q, J = 7.6 Hz, 2 H) 2.94-3.13 (m, 2 H) 3.57-3.82 (m, 1 H) 4.38-4.52 (m, 1 H) 4.52-4.67 (m, 2 H) 8.16 ( s, 2 H).
MS ESI / APCI Dual posi: 307 [M + H] ⁺ , 329 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 305 [MH] ^- , 341 [M + Cl] ^- .
(2) 1- (5-Ethylpyrimidin-2-yl) piperidin-4-amine

参考例１８（１）で得られた化合物（３．４０ｇ）のメタノール（１８．５ｍｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（５５．５ｍｌ）を加え、室温にて３時間攪拌した。反応液を減圧濃縮し、残渣の粉末をヘキサン−酢酸エチル混合溶液にて洗浄した。得られた粉末に飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（２．２８ｇ）を淡黄色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.18 (t, J=7.6 Hz, 3 H) 1.24 - 1.42 (m, 2 H) 1.81 - 1.96 (m, 2 H) 2.45 (q, J=7.6 Hz, 2 H) 2.84 - 3.04 (m, 3 H) 4.56 - 4.70 (m, 2 H) 8.16 (s, 2 H).
MS ESI/APCI Dual posi: 207[M+H]⁺
（３）２−ブロモ−５−フルオロピリジン １−オキシド

To a suspension of the compound (3.40 g) obtained in Reference Example 18 (1) in methanol (18.5 ml), 4M hydrogen chloride / 1,4-dioxane solution (55.5 ml) was added, and the mixture was stirred at room temperature. Stir for hours. The reaction solution was concentrated under reduced pressure, and the residual powder was washed with a mixed solution of hexane-ethyl acetate. A saturated aqueous sodium hydrogen carbonate solution was added to the obtained powder, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure to obtain the title compound (2.28 g) as a pale yellow oily substance.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.18 (t, J = 7.6 Hz, 3 H) 1.24-1.42 (m, 2 H) 1.81-1.96 (m, 2 H) 2.45 (q, J = 7.6 (Hz, 2 H) 2.84-3.04 (m, 3 H) 4.56-4.70 (m, 2 H) 8.16 (s, 2 H).
MS ESI / APCI Dual posi: 207 [M + H] ⁺
(3) 2-Bromo-5-fluoropyridine 1-oxide

市販の２−ブロモ−５−フルオロピリジン（２．００ｇ）のクロロホルム（２２．７ｍｌ）溶液へ、氷冷下、尿素・過酸化水素（２．１４ｇ）、無水トリフルオロ酢酸（４．７７ｇ）を加え、室温にて１５時間攪拌した。氷冷下、反応液へ飽和亜硫酸ナトリウム水溶液を加え、室温にて１５分間攪拌した。飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（２．１８ｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 6.98 (ddd, J=9.2, 6.6, 2.6 Hz, 1 H) 7.63 (dd, J=9.2, 6.6 Hz, 1 H) 8.34 (dd, J=4.0, 2.6 Hz, 1 H).
MS ESI/APCI Dual posi: 192[M+H]⁺.
MS ESI/APCI Dual nega: 190[M-H]^-.
（４）２−ブロモ−５−フルオロ−４−ニトロピリジン １−オキシド

To a commercially available solution of 2-bromo-5-fluoropyridine (2.00 g) in chloroform (22.7 ml), urea / hydrogen peroxide (2.14 g) and trifluoroacetic anhydride (4.77 g) were added under ice cooling. The mixture was further stirred at room temperature for 15 hours. A saturated aqueous sodium sulfite solution was added to the reaction mixture under ice cooling, and the mixture was stirred at room temperature for 15 minutes. A saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure to obtain the title compound (2.18 g) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 6.98 (ddd, J = 9.2, 6.6, 2.6 Hz, 1 H) 7.63 (dd, J = 9.2, 6.6 Hz, 1 H) 8.34 (dd, J = 4.0 , 2.6 Hz, 1 H).
MS ESI / APCI Dual posi: 192 [M + H] ⁺ .
MS ESI / APCI Dual nega: 190 [MH] ^- .
(4) 2-Bromo-5-fluoro-4-nitropyridine 1-oxide

参考例１８（３）で得られた化合物（３．７９ｇ）の濃硫酸（６５．８ｍｌ）溶液へ、氷冷下、発煙硝酸（３２．９ｍｌ）を加え、１００℃にて４時間攪拌した。反応液を氷水に加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（３．７２ｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 8.43 (d, J=5.8 Hz, 1 H) 8.45 (d, J=8.6 Hz, 1 H).
MS ESI/APCI Dual posi: 237[M+H]⁺.
MS ESI/APCI Dual nega: 235[M-H]^-.
（５）６−ブロモ−Ｎ−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−４−ニトロピリジン−３−アミン １−オキシド

Fuming nitric acid (32.9 ml) was added to a concentrated sulfuric acid (65.8 ml) solution of the compound (3.79 g) obtained in Reference Example 18 (3) under ice cooling, and the mixture was stirred at 100 ° C. for 4 hours. The reaction solution was added to ice water and extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure to obtain the title compound (3.72 g) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 8.43 (d, J = 5.8 Hz, 1 H) 8.45 (d, J = 8.6 Hz, 1 H).
MS ESI / APCI Dual posi: 237 [M + H] ⁺ .
MS ESI / APCI Dual nega: 235 [MH] ^- .
(5) 6-bromo-N- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -4-nitropyridin-3-amine 1-oxide

参考例１８（４）で得られた化合物（７００ｍｇ）のジメチルスルホキシド（９．８３ｍｌ）溶液へ、参考例１８（２）で得られた化合物（６０９ｍｇ）、炭酸セシウム（１．１５ｇ）を加え、室温にて１時間攪拌した。反応液に水を加え、酢酸エチルにて抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去し、表題化合物（１．０８ｇ）を黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.20 (t, J=7.6 Hz, 3 H) 1.50 - 1.73 (m, 2 H) 2.07 - 2.24 (m, 2 H) 2.49 (q, J=7.6 Hz, 2 H) 3.11 - 3.32 (m, 2 H) 3.51 - 3.73 (m, 1 H) 4.54 - 4.71 (m, 2 H) 7.71 - 7.82 (m, 1 H) 8.20 (s, 3 H) 8.42 (s, 1 H).
MS ESI/APCI Dual posi: 423[M+H]⁺, 445[M+Na]⁺.
MS ESI/APCI Dual nega: 421[M-H]^-.
（６）６−ブロモ−Ｎ³−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］ピリジン−３，４−ジアミン

To a solution of the compound (700 mg) obtained in Reference Example 18 (4) in dimethyl sulfoxide (9.83 ml), the compound (609 mg) obtained in Reference Example 18 (2) and cesium carbonate (1.15 g) were added. Stir at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure to obtain the title compound (1.08 g) as a yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.20 (t, J = 7.6 Hz, 3 H) 1.50-1.73 (m, 2 H) 2.07-2.24 (m, 2 H) 2.49 (q, J = 7.6 (Hz, 2 H) 3.11-3.32 (m, 2 H) 3.51-3.73 (m, 1 H) 4.54-4.71 (m, 2 H) 7.71-7.82 (m, 1 H) 8.20 (s, 3 H) 8.42 ( s, 1 H).
MS ESI / APCI Dual posi: 423 [M + H] ⁺ , 445 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 421 [MH] ^- .
(6) 6-Bromo -N ³ - [1- (5- ethyl-pyrimidin-2-yl) piperidin-4-yl] pyridine-3,4-diamine

参考例１８（５）で得られた化合物（１．０８ｇ）の酢酸（８．５１ｍｌ）溶液へ、鉄粉（７１２ｍｇ）を加え、１００℃にて２時間攪拌した。反応液に水を加え、酢酸エチルにて抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：１）にて精製し、表題化合物（６９６ｍｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.19 (t, J=7.6 Hz, 3 H) 1.32 - 1.54 (m, 2 H) 1.99 - 2.16 (m, 2 H) 2.47 (q, J=7.6 Hz, 2 H) 3.00 - 3.17 (m, 2 H) 3.29 - 3.48 (m, 1 H) 4.05 - 4.18 (m, 2 H) 4.55 - 4.69 (m, 2 H) 6.74 (s, 1 H) 7.69 (s, 1 H) 8.18 (s, 2 H).
MS ESI/APCI Dual posi: 377[M+H]⁺.
（７）６−ブロモ−３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Iron powder (712 mg) was added to a solution of the compound (1.08 g) obtained in Reference Example 18 (5) in acetic acid (8.51 ml), and the mixture was stirred at 100 ° C. for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 1) to obtain the title compound (696 mg) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.19 (t, J = 7.6 Hz, 3 H) 1.32-1.54 (m, 2 H) 1.99-2.16 (m, 2 H) 2.47 (q, J = 7.6 Hz, 2 H) 3.00-3.17 (m, 2 H) 3.29-3.48 (m, 1 H) 4.05-4.18 (m, 2 H) 4.55-4.69 (m, 2 H) 6.74 (s, 1 H) 7.69 ( s, 1 H) 8.18 (s, 2 H).
MS ESI / APCI Dual posi: 377 [M + H] ⁺ .
(7) 6-Bromo-3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例１８（６）で得られた化合物（５０ｍｇ）のトリフルオロ酢酸（１．３３ｍｌ）溶液へ、亜硝酸ナトリウム（１３．７ｍｇ）／水（０．１３３ｍｌ）溶液を加え、室温にて１時間攪拌した。反応液を減圧濃縮し、残渣に飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム）にて精製後、ヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（３４ｍｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.23 - 2.45 (m, 4 H) 2.51 (q, J=7.6 Hz, 2 H) 3.11 - 3.30 (m, 2 H) 4.92 - 5.19 (m, 3 H) 8.17 (d, J=1.3 Hz, 1 H) 8.23 (s, 2 H) 8.93 (d, J=1.3 Hz, 1 H).
MS ESI/APCI Dual posi: 388[M+H]⁺, 410[M+Na]⁺.
参考例１９
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）−１Ｈ−インダゾール

To a solution of the compound (50 mg) obtained in Reference Example 18 (6) in trifluoroacetic acid (1.33 ml), a sodium nitrite (13.7 mg) / water (0.133 ml) solution was added, and the mixture was stirred at room temperature for 1 hour. Stir. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent: chloroform) and recrystallized from a mixed solution of hexane-ethyl acetate to obtain the title compound (34 mg) as a pale yellow powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.23-2.45 (m, 4 H) 2.51 (q, J = 7.6 Hz, 2 H) 3.11-3.30 ( m, 2 H) 4.92-5.19 (m, 3 H) 8.17 (d, J = 1.3 Hz, 1 H) 8.23 (s, 2 H) 8.93 (d, J = 1.3 Hz, 1 H).
MS ESI / APCI Dual posi: 388 [M + H] ⁺ , 410 [M + Na] ⁺ .
Reference Example 19
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H -Indazole

参考例３で得られた化合物（９６０ｍｇ）の１，４−ジオキサン（２５ｍｌ）溶液へ、ビス（ピナコラト）ジボロン（８１９ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１０１ｍｇ）、酢酸カリウム（９７４ｍｇ）を加え、加熱還流下にて５時間攪拌した。室温へ冷却後、反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝８５：１５〜７０：３０）にて精製し、得られた固体をイソプロピルエーテルに懸濁した後、撹拌を行った。固体を濾取し、表題化合物（６６２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.6 Hz, 3 H) 1.37 (s, 12 H) 2.04 - 2.16 (m, 2 H) 2.21 - 2.38 (m, 2 H) 2.49 (q, J=7.6 Hz, 2 H) 3.04 - 3.19 (m, 2 H) 4.63 - 4.78 (m, 1 H) 4.87 - 5.00 (m, 2 H) 7.44 - 7.49 (m, 1 H) 7.75 - 7.82 (m, 1 H) 7.99 (s, 1 H) 8.20 (s, 2 H) 8.25 - 8.29 (m, 1 H).
MS ESI/APCI Dual posi: 434[M+H]⁺.
参考例２０
５−（２−メチルピリジン−３−イル）−１−（ピペリジン−４−イル）−１Ｈ−インダゾール
（１）ｔｅｒｔ−ブチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

To a solution of the compound obtained in Reference Example 3 (960 mg) in 1,4-dioxane (25 ml), bis (pinacolato) diboron (819 mg), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) Dichloride dichloromethane complex (101 mg) and potassium acetate (974 mg) were added, and the mixture was stirred with heating under reflux for 5 hours. After cooling to room temperature, water was added to the reaction solution, followed by extraction with ethyl acetate, and the resulting organic layer was washed with saturated brine. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 85: 15 to 70:30), and the resulting solid was suspended in isopropyl ether and then stirred. The solid was collected by filtration to give the title compound (662 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.6 Hz, 3 H) 1.37 (s, 12 H) 2.04-2.16 (m, 2 H) 2.21-2.38 (m, 2 H) 2.49 (q, J = 7.6 Hz, 2 H) 3.04-3.19 (m, 2 H) 4.63-4.78 (m, 1 H) 4.87-5.00 (m, 2 H) 7.44-7.49 (m, 1 H) 7.75- 7.82 (m, 1 H) 7.99 (s, 1 H) 8.20 (s, 2 H) 8.25-8.29 (m, 1 H).
MS ESI / APCI Dual posi: 434 [M + H] ⁺ .
Reference Example 20
5- (2-methylpyridin-3-yl) -1- (piperidin-4-yl) -1H-indazole (1) tert-butyl 4- [5- (2-methylpyridin-3-yl) -1H- Indazol-1-yl] piperidine-1-carboxylate

参考例１（２）で得られた化合物（２．０ｇ）と２−メチル−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン（１．７ｇ）を用いて参考例４と同様の操作にて反応及び精製を行い、表題化合物（２．０ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 2.01 - 2.14 (m, 2 H) 2.18 - 2.37 (m, 2 H) 2.53 (s, 3 H) 2.88 - 3.08 (m, 2 H) 4.22 - 4.47 (m, 2 H) 4.54 - 4.67 (m, 1 H) 7.17 - 7.24 (m, 1 H) 7.34 (dd, J=8.7, 1.6 Hz, 1 H) 7.49 - 7.54 (m, 1 H) 7.56 (dd, J=7.6, 1.9 Hz, 1 H) 7.65 - 7.68 (m, 1 H) 8.05 (s, 1 H) 8.52 (dd, J=4.9, 1.9 Hz, 1 H).
（２）５−（２−メチルピリジン−３−イル）−１−（ピペリジン−４−イル）−１Ｈ−インダゾール

The compound (2.0 g) obtained in Reference Example 1 (2) and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1 And 7 g) were used for the reaction and purification in the same manner as in Reference Example 4 to obtain the title compound (2.0 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 2.01-2.14 (m, 2 H) 2.18-2.37 (m, 2 H) 2.53 (s, 3 H) 2.88-3.08 (m , 2 H) 4.22-4.47 (m, 2 H) 4.54-4.67 (m, 1 H) 7.17-7.24 (m, 1 H) 7.34 (dd, J = 8.7, 1.6 Hz, 1 H) 7.49-7.54 (m , 1 H) 7.56 (dd, J = 7.6, 1.9 Hz, 1 H) 7.65-7.68 (m, 1 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.9, 1.9 Hz, 1 H).
(2) 5- (2-Methylpyridin-3-yl) -1- (piperidin-4-yl) -1H-indazole

参考例２０（１）で得られた化合物（１．９ｇ）のメタノール（１６ｍｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（３２ｍｌ）を加え、室温にて２時間撹拌した。反応液へ酢酸エチル（２００ｍｌ）を加えて氷浴下で冷却した。生じた結晶をろ取、乾燥後、これを１M水酸化ナトリウム水溶液、クロロホルムを用いて加熱溶解させ、２層を分離後、水層からクロロホルムでさらに抽出した。有機層を合わせ、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去して表題化合物（２．２ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.02 - 2.14 (m, 2 H) 2.16 - 2.33 (m, 2 H) 2.53 (s, 3 H) 2.86 (td, J=12.6, 2.7 Hz, 2 H) 3.26 - 3.38 (m, 2 H) 4.49 - 4.64 (m, 1 H) 7.20 (dd, J=7.6, 5.0 Hz, 1 H) 7.33 (dd, J=8.7, 1.7 Hz, 1 H) 7.52 - 7.59 (m, 2 H) 7.63 - 7.68 (m, 1 H) 8.05 (s, 1 H) 8.52 (dd, J=4.8, 1.7 Hz, 1 H).
参考例２１
５−（２−メチルピリジン−３−イル）−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール
（１）ｔｅｒｔ−ブチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

To a methanol (16 ml) suspension of the compound (1.9 g) obtained in Reference Example 20 (1) was added 4M hydrogen chloride / 1,4-dioxane solution (32 ml), and the mixture was stirred at room temperature for 2 hours. Ethyl acetate (200 ml) was added to the reaction solution and cooled in an ice bath. The resulting crystals were collected by filtration and dried, and this was heated and dissolved using a 1M aqueous sodium hydroxide solution and chloroform, the two layers were separated, and further extracted from the aqueous layer with chloroform. The organic layers were combined, dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure to obtain the title compound (2.2 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.02-2.14 (m, 2 H) 2.16-2.33 (m, 2 H) 2.53 (s, 3 H) 2.86 (td, J = 12.6, 2.7 Hz, 2 H) 3.26-3.38 (m, 2 H) 4.49-4.64 (m, 1 H) 7.20 (dd, J = 7.6, 5.0 Hz, 1 H) 7.33 (dd, J = 8.7, 1.7 Hz, 1 H) 7.52- 7.59 (m, 2 H) 7.63-7.68 (m, 1 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.8, 1.7 Hz, 1 H).
Reference Example 21
5- (2-Methylpyridin-3-yl) -1- (piperidin-4-yl) -1H-benzotriazole (1) tert-butyl 4- [5- (2-methylpyridin-3-yl) -1H -Benzotriazol-1-yl] piperidine-1-carboxylate

参考例８で得られた化合物（２．０ｇ）と２−メチル−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン（１．７ｇ）を用いて参考例４と同様の操作にて反応及び精製を行い、表題化合物（１．７ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16 - 2.28 (m, 2 H) 2.30 - 2.48 (m, 2 H) 2.52 (s, 3 H) 2.95 - 3.16 (m, 2 H) 4.26 - 4.45 (m, 2 H) 4.82 - 4.95 (m, 1 H) 7.21 - 7.26 (m, 1 H) 7.46 (dd, J=8.5, 1.8 Hz, 1 H) 7.57 (dd, J=7.7, 1.8 Hz, 1 H) 7.63 (dd, J=8.5, 0.8 Hz, 1 H) 7.99 - 8.04 (m, 1 H) 8.56 (dd, J=4.9, 1.8 Hz, 1 H).
（２）５−（２−メチルピリジン−３−イル）−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール

The compound (2.0 g) obtained in Reference Example 8 and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (1.7 g) Was used for the reaction and purification in the same manner as in Reference Example 4 to obtain the title compound (1.7 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16-2.28 (m, 2 H) 2.30-2.48 (m, 2 H) 2.52 (s, 3 H) 2.95-3.16 (m , 2 H) 4.26-4.45 (m, 2 H) 4.82-4.95 (m, 1 H) 7.21-7.26 (m, 1 H) 7.46 (dd, J = 8.5, 1.8 Hz, 1 H) 7.57 (dd, J = 7.7, 1.8 Hz, 1 H) 7.63 (dd, J = 8.5, 0.8 Hz, 1 H) 7.99-8.04 (m, 1 H) 8.56 (dd, J = 4.9, 1.8 Hz, 1 H).
(2) 5- (2-Methylpyridin-3-yl) -1- (piperidin-4-yl) -1H-benzotriazole

参考例２１（１）で得られた化合物（１．６ｇ）を用いて参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（１．２ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17 - 2.28 (m, 2 H) 2.30 - 2.46 (m, 2 H) 2.53 (s, 3 H) 2.90 (td, J=12.3, 2.7 Hz, 2 H) 3.32 - 3.42 (m, 2 H) 4.79 - 4.92 (m, 1 H) 7.20 - 7.26 (m, 1 H) 7.44 (dd, J=8.5, 1.7 Hz, 1 H) 7.58 (dd, J=7.6, 1.7 Hz, 1 H) 7.69 (dd, J=8.6, 0.9 Hz, 1 H) 8.01 (dd, J=1.5, 0.9 Hz, 1 H) 8.56 (dd, J=4.9, 1.8 Hz, 1 H).
参考例２２
２，５−ジフルオロ−４−（１−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ベンゾトリアゾル−５−イル）安息香酸
（１）５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール

Using the compound (1.6 g) obtained in Reference Example 21 (1), the reaction and purification were carried out in the same manner as in Reference Example 20 (2) to obtain the title compound (1.2 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17-2.28 (m, 2 H) 2.30-2.46 (m, 2 H) 2.53 (s, 3 H) 2.90 (td, J = 12.3, 2.7 Hz, 2 H) 3.32-3.42 (m, 2 H) 4.79-4.92 (m, 1 H) 7.20-7.26 (m, 1 H) 7.44 (dd, J = 8.5, 1.7 Hz, 1 H) 7.58 (dd, J = 7.6 , 1.7 Hz, 1 H) 7.69 (dd, J = 8.6, 0.9 Hz, 1 H) 8.01 (dd, J = 1.5, 0.9 Hz, 1 H) 8.56 (dd, J = 4.9, 1.8 Hz, 1 H).
Reference Example 22
2,5-difluoro-4- (1- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -1H-benzotriazol-5-yl) benzoic acid (1) 5-bromo- 1- (Piperidin-4-yl) -1H-benzotriazole

参考例８で得られた化合物（５．００ｇ）のメタノール（４３．７ｍｌ）縣濁液へ、４M塩化水素・１，４−ジオキサン溶液（８５．０ｍｌ）を加え、室温で２時間攪拌した。酢酸エチル（１３０ｍｌ）を加えて一晩攪拌し、生じた沈殿物をろ取して目的物の塩酸塩（４．８０ｇ）を得た。得られた粉末に１M水酸化ナトリウム水溶液を加え、クロロホルムにて抽出した。有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をクロロホルム−ヘキサンから再結晶し、表題化合物（３．２９ｇ）を淡赤色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.10 - 2.22 (m, 2 H) 2.23 - 2.40 (m, 2 H) 2.80 - 2.94 (m, 2 H) 3.28 - 3.40 (m, 2 H) 4.71 - 4.84 (m, 1 H) 7.45 - 7.61 (m, 2 H) 8.21 - 8.25 (m, 1 H).
MS ESI/APCI Dual posi: 281[M+H]⁺.
（２）プロパン−２−イル ４−（５−ブロモ−１Ｈ−ベンゾトリアゾル−１−イル）ピペリジン−１−カルボキシラート

To a suspension of the compound (5.00 g) obtained in Reference Example 8 in methanol (43.7 ml), 4M hydrogen chloride / 1,4-dioxane solution (85.0 ml) was added and stirred at room temperature for 2 hours. Ethyl acetate (130 ml) was added and stirred overnight, and the resulting precipitate was collected by filtration to give the desired hydrochloride (4.80 g). A 1M aqueous sodium hydroxide solution was added to the obtained powder, and the mixture was extracted with chloroform. The organic layer was passed through a phase separator and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from chloroform-hexane to give the title compound (3.29 g) as a pale-red powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.10-2.22 (m, 2 H) 2.23-2.40 (m, 2 H) 2.80-2.94 (m, 2 H) 3.28-3.40 (m, 2 H) 4.71 -4.84 (m, 1 H) 7.45-7.61 (m, 2 H) 8.21-8.25 (m, 1 H).
MS ESI / APCI Dual posi: 281 [M + H] ⁺ .
(2) Propan-2-yl 4- (5-bromo-1H-benzotriazol-1-yl) piperidine-1-carboxylate

参考例２２（１）で得られた化合物（２．００ｇ）のクロロホルム（７０ｍｌ）溶液へ、トリエチルアミン（１．９８ｍｌ）、クロロぎ酸イソプロピル（１．２２ｍｌ）を加え室温にて１時間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１０：０〜７：３）にて精製し、表題化合物（２．８０ｍｇ）を淡赤色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.10 - 2.23 (m, 2 H) 2.24 - 2.42 (m, 2 H) 2.98 - 3.15 (m, 2 H) 4.28 - 4.47 (m, 2 H) 4.74 - 4.89 (m, 1 H) 4.90 - 5.05 (m, 1 H) 7.42 - 7.49 (m, 1 H) 7.55 - 7.62 (m, 1 H) 8.21 - 8.27 (m, 1 H).
MS ESI/APCI Dual posi: 367[M+H]⁺.
（３）２，５−ジフルオロ−４−（１−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ベンゾトリアゾル−５−イル）安息香酸

Triethylamine (1.98 ml) and isopropyl chloroformate (1.22 ml) were added to a chloroform (70 ml) solution of the compound (2.00 g) obtained in Reference Example 22 (1), and the mixture was stirred at room temperature for 1 hour. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 10: 0-7: 3) to give the title compound (2.80 mg) as a pale red solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.10-2.23 (m, 2 H) 2.24-2.42 (m, 2 H) 2.98-3.15 (m, 2 H) 4.28-4.47 (m, 2 H) 4.74-4.89 (m, 1 H) 4.90-5.05 (m, 1 H) 7.42-7.49 (m, 1 H) 7.55-7.62 (m, 1 H) 8.21-8.27 (m, 1 H).
MS ESI / APCI Dual posi: 367 [M + H] ⁺ .
(3) 2,5-Difluoro-4- (1- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -1H-benzotriazol-5-yl) benzoic acid

参考例２２（２）で得られた化合物（１．４０ｇ）と参考例Ｅ−１０で得られた化合物（１．１６ｇ）を用いて、参考例１７−１と同様の操作にて反応及び精製を行い、表題化合物（５３７ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.23 (d, J=6.4 Hz, 6 H) 2.00 - 2.25 (m, 4 H) 2.98 - 3.23 (m, 2 H) 4.08 - 4.26 (m, 2 H) 4.75 - 4.90 (m, 1 H) 5.13 - 5.28 (m, 1 H) 7.62 - 7.87 (m, 3 H) 8.11 (d, J=8.7 Hz, 1 H) 8.34 (s, 1 H).
MS ESI/APCI Dual nega: 443[M-H]^-.
参考例２３−Ａ
５−ブロモ−１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (1.40 g) obtained in Reference Example 22 (2) and the compound (1.16 g) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17-1. To give the title compound (537 mg) as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.23 (d, J = 6.4 Hz, 6 H) 2.00-2.25 (m, 4 H) 2.98-3.23 (m, 2 H) 4.08-4.26 (m, 2 H) 4.75-4.90 (m, 1 H) 5.13-5.28 (m, 1 H) 7.62-7.87 (m, 3 H) 8.11 (d, J = 8.7 Hz, 1 H) 8.34 (s, 1 H).
MS ESI / APCI Dual nega: 443 [MH] ^- .
Reference Example 23-A
5-Bromo-1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

後掲した参考例２５で得られた化合物（２．５ｇ）と参考例Ｇ−２で合成した化合物（２．２ｇ）を用いて、後掲した実施例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（１．９ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57 - 0.64 (m, 2 H) 0.88 - 0.96 (m, 2 H) 1.68 - 1.80 (m, 1 H) 2.07 - 2.19 (m, 2 H) 2.20 - 2.37 (m, 2 H) 3.07 - 3.21 (m, 2 H) 4.69 - 4.84 (m, 1 H) 4.88 - 4.99 (m, 2 H) 7.80 - 7.83 (m, 1 H) 7.98 (s, 1 H) 8.15 (s, 2 H) 8.79 (t, J=0.9 Hz, 1 H).
参考例２３−Ｂ
５−ブロモ−１−｛１−［５−（プロパン−２−イル）ピリミジン−２−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (2.5 g) obtained in Reference Example 25 described later and the compound (2.2 g) synthesized in Reference Example G-2, the same operation as in Example 8-1 (4) described later The title compound (1.9 g) was obtained by reaction and purification at
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.64 (m, 2 H) 0.88-0.96 (m, 2 H) 1.68-1.80 (m, 1 H) 2.07-2.19 (m, 2 H) 2.20 -2.37 (m, 2 H) 3.07-3.21 (m, 2 H) 4.69-4.84 (m, 1 H) 4.88-4.99 (m, 2 H) 7.80-7.83 (m, 1 H) 7.98 (s, 1 H ) 8.15 (s, 2 H) 8.79 (t, J = 0.9 Hz, 1 H).
Reference Example 23-B
5-Bromo-1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridine

後掲した参考例２５で得られた化合物（２．０ｇ）と参考例Ｇ−５で合成した化合物（２．２ｇ）を用いて後掲した実施例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（２．０ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.25 (d, J=7.0 Hz, 6 H) 2.06 - 2.20 (m, 2 H) 2.21 - 2.38 (m, 2 H) 2.73 - 2.87 (m, 1 H) 3.08 - 3.22 (m, 2 H) 4.71 - 4.86 (m, 1 H) 4.90 - 5.02 (m, 2 H) 7.82 (d, J=1.2 Hz, 1 H) 7.98 - 8.00 (m, 1 H) 8.22 - 8.26 (m, 2 H) 8.80 (t, J=1.0 Hz, 1 H).
参考例２３−Ｃ
５−ブロモ−１−［１−（５−クロロピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (2.0 g) obtained in Reference Example 25 described later and the compound (2.2 g) synthesized in Reference Example G-5, the same operation as in Example 8-1 (4) described later was performed. The reaction and purification were carried out to obtain the title compound (2.0 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.25 (d, J = 7.0 Hz, 6 H) 2.06-2.20 (m, 2 H) 2.21-2.38 (m, 2 H) 2.73-2.87 (m, 1 H) 3.08-3.22 (m, 2 H) 4.71-4.86 (m, 1 H) 4.90-5.02 (m, 2 H) 7.82 (d, J = 1.2 Hz, 1 H) 7.98-8.00 (m, 1 H) 8.22-8.26 (m, 2 H) 8.80 (t, J = 1.0 Hz, 1 H).
Reference Example 23-C
5-Bromo-1- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

後掲した参考例２５で得られた化合物（２．０ｇ）と２，５−ジクロロピリミジン（２．１ｇ）を用いて、後掲した実施例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（１．８ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.08 - 2.37 (m, 4 H) 3.12 - 3.25 (m, 2 H) 4.72 - 4.85 (m, 1 H) 4.87 - 4.98 (m, 2 H) 7.83 (d, J=1.1 Hz, 1 H) 7.98 - 8.00 (m, 1 H) 8.26 (s, 2 H) 8.78 - 8.81 (m, 1 H).
参考例２３−Ｄ
プロパン−２−イル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

Using the compound (2.0 g) obtained in Reference Example 25 described later and 2,5-dichloropyrimidine (2.1 g), the reaction was carried out in the same manner as in Example 8-1 (4) described later. And purification was performed to obtain the title compound (1.8 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.08-2.37 (m, 4 H) 3.12-3.25 (m, 2 H) 4.72-4.85 (m, 1 H) 4.87-4.98 (m, 2 H) 7.83 (d, J = 1.1 Hz, 1 H) 7.98-8.00 (m, 1 H) 8.26 (s, 2 H) 8.78-8.81 (m, 1 H).
Reference Example 23-D
Propan-2-yl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

後掲する参考例２５で得られた化合物（７．９１ｇ）を用いて、参考例２２（２）と同様の操作にて反応及び精製を行い、表題化合物（５．９６ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J=6.2 Hz, 6 H) 2.01 - 2.13 (m, 2 H) 2.15 - 2.32 (m, 2 H) 2.95 - 3.12 (m, 2 H) 4.27 - 4.46 (m, 2 H) 4.60 - 4.73 (m, 1 H) 4.89 - 5.03 (m, 1 H) 7.83 (d, J=1.1 Hz, 1 H) 8.01 (s, 1 H) 8.77 (s, 1 H).
MS ESI/APCI Dual posi: 367[M+H]⁺.
参考例２３−Ｅ
１−フルオロ−２−メチルプロパン−２−イル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

Using the compound (7.91 g) obtained in Reference Example 25 described later, the reaction and purification were conducted in the same manner as in Reference Example 22 (2) to obtain the title compound (5.96 g) as a colorless powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J = 6.2 Hz, 6 H) 2.01-2.13 (m, 2 H) 2.15-2.32 (m, 2 H) 2.95-3.12 (m, 2 H) 4.27-4.46 (m, 2 H) 4.60-4.73 (m, 1 H) 4.89-5.03 (m, 1 H) 7.83 (d, J = 1.1 Hz, 1 H) 8.01 (s, 1 H) 8.77 ( s, 1 H).
MS ESI / APCI Dual posi: 367 [M + H] ⁺ .
Reference Example 23-E
1-fluoro-2-methylpropan-2-yl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

後掲した参考例２５で得られた化合物（２．５ｇ）のクロロホルム（５０ｍｌ）溶液へ、参考例Ｉ−２で得られた化合物（３．８ｇ）、トリエチルアミン（１９ｍＬ）を順次加え、１時間撹拌した。ＴＬＣで反応の終了を確認後、反応液をクロロホルムで希釈し、水洗浄した。有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム−酢酸エチル）で２回精製後、クロロホルム−ヘキサンで再結晶を行い、表題化合物（１．３ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 - 1.53 (m, 6 H) 1.99 - 2.33 (m, 4 H) 2.90 - 3.16 (m, 2 H) 4.20 - 4.72 (m, 5 H) 7.83 (d, J=1.2 Hz, 1 H) 7.98 - 8.03 (m, 1 H) 8.75 - 8.78 (m, 1 H).
参考例２３−Ｆ
１，１−ジフルオロ−２−メチルプロパン−２−イル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

The compound (3.8 g) obtained in Reference Example I-2 and triethylamine (19 mL) were sequentially added to a chloroform (50 ml) solution of the compound (2.5 g) obtained in Reference Example 25 described later for 1 hour. Stir. After confirming the completion of the reaction by TLC, the reaction solution was diluted with chloroform and washed with water. The organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified twice by silica gel column chromatography (developing solvent: chloroform-ethyl acetate) and recrystallized from chloroform-hexane to obtain the title compound (1.3 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51-1.53 (m, 6 H) 1.99-2.33 (m, 4 H) 2.90-3.16 (m, 2 H) 4.20-4.72 (m, 5 H) 7.83 (d, J = 1.2 Hz, 1 H) 7.98-8.03 (m, 1 H) 8.75-8.78 (m, 1 H).
Reference Example 23-F
1,1-difluoro-2-methylpropan-2-yl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

後掲した参考例２５で得られた化合物（２．５ｇ）と参考例Ｉ−１で得られた化合物（２．７ｇ）を用いて参考例２３−Ｅと同様の操作にて反応及び精製を行い、表題化合物（３．１ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 - 1.56 (m, 6 H) 2.00 - 2.15 (m, 2 H) 2.15 - 2.33 (m, 2 H) 2.91 - 3.19 (m, 2 H) 4.15 - 4.41 (m, 2 H) 4.60 - 4.72 (m, 1 H) 5.97 - 6.37 (m, 1 H) 7.83 (d, J=1.0 Hz, 1 H) 8.00 - 8.02 (m, 1 H) 8.77 (t, J=1.0 Hz, 1 H).
参考例２３−Ｇ
２，２−ジメチルプロピル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

The reaction and purification were carried out in the same manner as in Reference Example 23-E using the compound (2.5 g) obtained in Reference Example 25 and the compound (2.7 g) obtained in Reference Example I-1. The title compound (3.1 g) was obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52-1.56 (m, 6 H) 2.00-2.15 (m, 2 H) 2.15-2.33 (m, 2 H) 2.91-3.19 (m, 2 H) 4.15 -4.41 (m, 2 H) 4.60-4.72 (m, 1 H) 5.97-6.37 (m, 1 H) 7.83 (d, J = 1.0 Hz, 1 H) 8.00-8.02 (m, 1 H) 8.77 (t , J = 1.0 Hz, 1 H).
Reference Example 23-G
2,2-dimethylpropyl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

２，２−ジメチル−１−プロパノール（２．２６ｇ）のテトラヒドロフラン（８０ｍｌ）溶液へ、トリホスゲン（２．６７ｇ）を加え、室温で１時間攪拌した。反応液を氷冷し、トリエチルアミン（７．１４ｍｌ）を加えた。氷冷下２０分攪拌した後に後掲した参考例２５で得られた化合物（３．６１ｇ）を反応溶液の中へ加え、更に室温で３０分間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を飽和食塩水にて洗浄した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣を２−プロパノール−ヘキサンから再結晶し、表題化合物（３．１９ｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 0.97 (s, 9 H) 1.97 - 2.40 (m, 4 H) 2.95 - 3.21 (m, 2 H) 3.83 (s, 2 H) 4.26 - 4.49 (m, 2 H) 4.57 - 4.79 (m, 1 H) 7.80 - 7.85 (m, 1 H) 8.01 (s, 1 H) 8.78 (s, 1 H).
MS ESI/APCI Dual posi: 395[M+H]⁺.
参考例２４−Ａ
５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Triphosgene (2.67 g) was added to a solution of 2,2-dimethyl-1-propanol (2.26 g) in tetrahydrofuran (80 ml), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was ice-cooled and triethylamine (7.14 ml) was added. After stirring for 20 minutes under ice cooling, the compound (3.61 g) obtained in Reference Example 25 described below was added into the reaction solution, and the mixture was further stirred at room temperature for 30 minutes. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from 2-propanol-hexane to give the title compound (3.19 g) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 0.97 (s, 9 H) 1.97-2.40 (m, 4 H) 2.95-3.21 (m, 2 H) 3.83 (s, 2 H) 4.26-4.49 (m , 2 H) 4.57-4.79 (m, 1 H) 7.80-7.85 (m, 1 H) 8.01 (s, 1 H) 8.78 (s, 1 H).
MS ESI / APCI Dual posi: 395 [M + H] ⁺ .
Reference Example 24-A
5- [4- (Methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine

後掲した実施例２２−１で得られた化合物（５．０ｇ）を用いて参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（２．５ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06 - 2.18 (m, 2 H) 2.19 - 2.35 (m, 2 H) 2.83 - 2.95 (m, 2 H) 3.10 (s, 3 H) 3.32 (s., 2 H) 4.63 - 4.76 (m, 1 H) 8.02 - 8.07 (m, 2 H) 8.11 - 8.15 (m, 2 H) 8.21 - 8.27 (m, 6 H) 9.12 - 9.15 (m, 1 H).
参考例２４−Ｂ
５−［２−フルオロ−４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The title compound (2.5 g) was obtained by performing the reaction and purification in the same manner as in Reference Example 20 (2) using the compound (5.0 g) obtained in Example 22-1 described later.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06-2.18 (m, 2 H) 2.19-2.35 (m, 2 H) 2.83-2.95 (m, 2 H) 3.10 (s, 3 H) 3.32 (s ., 2 H) 4.63-4.76 (m, 1 H) 8.02-8.07 (m, 2 H) 8.11-8.15 (m, 2 H) 8.21-8.27 (m, 6 H) 9.12-9.15 (m, 1 H) .
Reference Example 24-B
5- [2-Fluoro-4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine

後掲した実施例４９−３で得られた化合物（４．１ｇ）を用いて参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（２．２ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06 - 2.19 (m, 2 H) 2.19 - 2.36 (m, 2 H) 2.83 - 2.95 (m, 2 H) 3.11 (s, 3 H) 3.28 - 3.40 (m, 2 H) 4.63 - 4.77 (m, 1 H) 7.75 - 7.88 (m, 2 H) 8.14 (s, 1 H) 8.23 (t, J=1.5 Hz, 1 H) 8.30 - 8.38 (m, 1 H) 9.15 (t, J=1.0 Hz, 1 H).
参考例２４−Ｃ
５−（２−メチルピリジン−３−イル）−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (4.1 g) obtained in Example 49-3 described later, the reaction and purification were carried out in the same manner as in Reference Example 20 (2) to obtain the title compound (2.2 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06-2.19 (m, 2 H) 2.19-2.36 (m, 2 H) 2.83-2.95 (m, 2 H) 3.11 (s, 3 H) 3.28-3.40 (m, 2 H) 4.63-4.77 (m, 1 H) 7.75-7.88 (m, 2 H) 8.14 (s, 1 H) 8.23 (t, J = 1.5 Hz, 1 H) 8.30-8.38 (m, 1 H) 9.15 (t, J = 1.0 Hz, 1 H).
Reference Example 24-C
5- (2-Methylpyridin-3-yl) -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine

後掲した実施例５０−１で得られた化合物（１．０３ｇ）を用いて、参考例２２（１）と同様の操作にて反応及び精製を行い、表題化合物（０．７１ｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.08 - 2.37 (m, 4 H) 2.62 (s, 3 H) 2.83 - 2.97 (m, 2 H) 3.28 - 3.42 (m, 2 H) 4.63 - 4.77 (m, 1 H) 7.21 - 7.27 (m, 1 H) 7.69 - 7.78 (m, 2 H) 8.11 (s, 1 H) 8.52 - 8.58 (m, 1 H) 9.08 - 9.16 (m, 1 H).
MS ESI/APCI Dual posi: 294[M+H]⁺.
参考例２５
５−ブロモ−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (1.03 g) obtained in Example 50-1 described later, the reaction and purification were performed in the same manner as in Reference Example 22 (1), and the title compound (0.71 g) was pale yellow Obtained as a powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.08-2.37 (m, 4 H) 2.62 (s, 3 H) 2.83-2.97 (m, 2 H) 3.28-3.42 (m, 2 H) 4.63-4.77 (m, 1 H) 7.21-7.27 (m, 1 H) 7.69-7.78 (m, 2 H) 8.11 (s, 1 H) 8.52-8.58 (m, 1 H) 9.08-9.16 (m, 1 H).
MS ESI / APCI Dual posi: 294 [M + H] ⁺ .
Reference Example 25
5-Bromo-1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine

参考例１５で得られた化合物（１５ｇ）を用いて参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（１１ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.02 - 2.12 (m, 2 H) 2.13 - 2.21 (m, 1 H) 2.21 - 2.29 (m, 1 H) 2.86 (td, J=12.5, 2.7 Hz, 2 H) 3.27 - 3.36 (m, 2 H) 4.53 - 4.67 (m, 1 H) 7.82 (d, J=1.1 Hz, 1 H) 8.00 (s, 1 H) 8.80 (t, J=1.0 Hz, 1 H).
参考例２６−Ａ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−２−フルオロ安息香酸

Using the compound (15 g) obtained in Reference Example 15, the reaction and purification were carried out in the same manner as in Reference Example 20 (2) to obtain the title compound (11 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.02-2.12 (m, 2 H) 2.13-2.21 (m, 1 H) 2.21-2.29 (m, 1 H) 2.86 (td, J = 12.5, 2.7 Hz , 2 H) 3.27-3.36 (m, 2 H) 4.53-4.67 (m, 1 H) 7.82 (d, J = 1.1 Hz, 1 H) 8.00 (s, 1 H) 8.80 (t, J = 1.0 Hz, 1 H).
Reference Example 26-A
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -2-fluorobenzoic acid

参考例１６で得られた化合物（２００ｍｇ）と参考例Ｅ−５で得られた化合物（２０６ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（１４６ｍｇ）を黒色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.16 - 1.27 (m, 3 H) 2.12 - 2.57 (m, 6 H) 3.10 - 3.26 (m, 2 H) 4.77 - 5.04 (m, 3 H) 7.00 - 8.27 (m, 7 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 447[M+H]⁺.
参考例２６−Ｂ
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−２，５−ジフルオロ安息香酸

Using the compound (200 mg) obtained in Reference Example 16 and the compound (206 mg) obtained in Reference Example E-5, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound (146 mg). Obtained as a black powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.16-1.27 (m, 3 H) 2.12-2.57 (m, 6 H) 3.10-3.26 (m, 2 H) 4.77-5.04 (m, 3 H) 7.00 -8.27 (m, 7 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ .
Reference Example 26-B
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -2,5-difluorobenzoic acid

参考例１６で得られた化合物（１００ｍｇ）と参考例Ｅ−１０で得られた化合物（７８．０ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（７８．８ｍｇ）を茶色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.5 Hz, 3 H) 1.94 - 2.17 (m, 4 H) 2.41 - 2.55 (m, 2 H) 3.09 - 3.24 (m, 2 H) 4.74 - 4.88 (m, 2 H) 5.18 - 5.33 (m, 1 H) 7.67 - 7.78 (m, 1 H) 7.86 - 7.97 (m, 1 H) 8.24 - 8.35 (m, 4 H) 9.45 (s, 1 H).
MS ESI/APCI Dual nega: 463[M-H]^-.
参考例２６−Ｃ
２−フルオロ−４−（１−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）安息香酸

Using the compound (100 mg) obtained in Reference Example 16 and the compound (78.0 mg) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17, and the title compound (78 .8 mg) was obtained as a brown powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.5 Hz, 3 H) 1.94-2.17 (m, 4 H) 2.41-2.55 (m, 2 H) 3.09-3.24 (m, 2 H) 4.74-4.88 (m, 2 H) 5.18-5.33 (m, 1 H) 7.67-7.78 (m, 1 H) 7.86-7.97 (m, 1 H) 8.24-8.35 (m, 4 H) 9.45 ( s, 1 H).
MS ESI / APCI Dual nega: 463 [MH] ^- .
Reference Example 26-C
2-Fluoro-4- (1- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) benzoic acid

参考例２３−Dで得られた化合物（９００ｍｇ）と参考例Ｅ−５で得られた化合物（９７８ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（５４０ｍｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 1.23 (d, J=6.2 Hz, 6 H) 1.84 - 2.15 (m, 4 H) 2.92 - 3.20 (m, 2 H) 4.04 - 4.28 (m, 2 H) 4.72 - 4.91 (m, 1 H) 5.00 - 5.24 (m, 1 H) 7.90 - 8.13 (m, 3 H) 8.31 (s, 1 H) 8.49 (s, 1 H) 9.38 (s, 1 H).
MS ESI/APCI Dual posi: 427[M+H]⁺.
参考例２６−Ｄ
３−フルオロ−４−（１−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）安息香酸

Using the compound (900 mg) obtained in Reference Example 23-D and the compound (978 mg) obtained in Reference Example E-5, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound (540 mg ) Was obtained as a pale yellow powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 1.23 (d, J = 6.2 Hz, 6 H) 1.84-2.15 (m, 4 H) 2.92-3.20 (m, 2 H) 4.04-4.28 (m, 2 H) 4.72-4.91 (m, 1 H) 5.00-5.24 (m, 1 H) 7.90-8.13 (m, 3 H) 8.31 (s, 1 H) 8.49 (s, 1 H) 9.38 (s, 1 H ).
MS ESI / APCI Dual posi: 427 [M + H] ⁺ .
Reference Example 26-D
3-Fluoro-4- (1- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) benzoic acid

参考例２３−Dで得られた化合物（１．００ｇ）と参考例Ｅ−２で得られた化合物（１．０９ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（１．１５ｇ）を淡黄色粉末として得た。
¹H NMR (200 MHz, DMSO-d₆) δ ppm 1.23 (d, J=6.2 Hz, 6 H) 1.85 - 2.18 (m, 4 H) 2.94 - 3.20 (m, 2 H) 4.06 - 4.28 (m, 2 H) 4.73 - 4.93 (m, 1 H) 4.99 - 5.27 (m, 1 H) 7.74 - 7.94 (m, 2 H) 8.10 - 8.21 (m, 1 H) 8.23 - 8.28 (m, 1 H) 8.32 (s, 1 H) 9.42 (s, 1 H).
MS ESI/APCI Dual posi: 427[M+H]⁺.
参考例２６−Ｅ
２，５−ジフルオロ−４−（１−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）安息香酸

Using the compound (1.00 g) obtained in Reference Example 23-D and the compound (1.09 g) obtained in Reference Example E-2, the reaction and purification were carried out in the same manner as in Reference Example 17, The title compound (1.15 g) was obtained as a pale yellow powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ ppm 1.23 (d, J = 6.2 Hz, 6 H) 1.85-2.18 (m, 4 H) 2.94-3.20 (m, 2 H) 4.06-4.28 (m, 2 H) 4.73-4.93 (m, 1 H) 4.99-5.27 (m, 1 H) 7.74-7.94 (m, 2 H) 8.10-8.21 (m, 1 H) 8.23-8.28 (m, 1 H) 8.32 ( s, 1 H) 9.42 (s, 1 H).
MS ESI / APCI Dual posi: 427 [M + H] ⁺ .
Reference Example 26-E
2,5-difluoro-4- (1- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) benzoic acid

参考例２３−Ｄで得られた化合物（１．２ｇ）と参考例Ｅ−１０で得られた化合物（０．９５ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（０．９５ｇ）を得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.05 - 2.16 (m, 2 H) 2.24 - 2.36 (m, 2 H) 2.98 - 3.18 (m, 2 H) 4.29 - 4.55 (m, 2 H) 4.73 - 4.83 (m, 1 H) 4.94 - 5.03 (m, 1 H) 7.80 - 7.87 (m, 1 H) 7.92 - 8.01 (m, 1 H) 8.16 (s, 1 H) 8.27 (s, 1 H) 9.19 (s, 1 H).
参考例２６−Ｆ
４−（１−｛１−［（２，２−ジメチルプロポキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）−２，５−ジフルオロ安息香酸

Using the compound (1.2 g) obtained in Reference Example 23-D and the compound (0.95 g) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17, The title compound (0.95 g) was obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.05-2.16 (m, 2 H) 2.24-2.36 (m, 2 H) 2.98-3.18 (m, 2 H) 4.29-4.55 (m, 2 H) 4.73-4.83 (m, 1 H) 4.94-5.03 (m, 1 H) 7.80-7.87 (m, 1 H) 7.92-8.01 (m, 1 H) 8.16 (s , 1 H) 8.27 (s, 1 H) 9.19 (s, 1 H).
Reference Example 26-F
4- (1- {1-[(2,2-dimethylpropoxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) -2,5-difluorobenzoic acid

参考例２３−Gで得られた化合物（１．６ｇ）と参考例Ｅ−１０で得られた化合物（１．２ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（０．９７ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (s, 9 H) 2.07 - 2.42 (m, 4 H) 3.02 - 3.24 (m, 2 H) 3.85 (s, 2 H) 4.30 - 4.51 (m, 2 H) 4.72 - 4.87 (m, 1 H) 7.81 - 7.89 (m, 1 H) 7.95 - 8.04 (m, 1 H) 8.17 (s, 1 H) 8.28 - 8.31 (m, 1 H) 9.17 (s, 1 H).

参考例２６−Ｇ
４−（１−｛１−［（シクロブチルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）−２，５−ジフルオロ安息香酸
（１）シクロブチル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

Using the compound (1.6 g) obtained in Reference Example 23-G and the compound (1.2 g) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17, The title compound (0.97 g) was obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (s, 9 H) 2.07-2.42 (m, 4 H) 3.02-3.24 (m, 2 H) 3.85 (s, 2 H) 4.30-4.51 (m , 2 H) 4.72-4.87 (m, 1 H) 7.81-7.89 (m, 1 H) 7.95-8.04 (m, 1 H) 8.17 (s, 1 H) 8.28-8.31 (m, 1 H) 9.17 (s , 1 H).

Reference Example 26-G
4- (1- {1-[(cyclobutyloxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) -2,5-difluorobenzoic acid (1) Cyclobutyl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

参考例２５で得られた化合物（２．００ｇ）とシクロブタノール（１．０３ｇ）を用いて、参考例２３−Gと同様の操作にて反応及び精製を行い、表題化合物（２．５８ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53 - 1.86 (m, 2 H) 1.99 - 2.44 (m, 8 H) 2.95 - 3.15 (m, 2 H) 4.27 - 4.44 (m, 2 H) 4.60 - 4.73 (m, 1 H) 4.91 - 5.04 (m, 1 H) 7.81 - 7.85 (m, 1 H) 7.98 - 8.03 (m, 1 H) 8.75 - 8.79 (m, 1 H).
MS ESI/APCI Dual posi: 379[M+H]⁺.
（２）４−（１−｛１−［（シクロブチルオキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）−２，５−ジフルオロ安息香酸

Using the compound (2.00 g) obtained in Reference Example 25 and cyclobutanol (1.03 g), the reaction and purification were carried out in the same manner as in Reference Example 23-G, and the title compound (2.58 g) was obtained. Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53-1.86 (m, 2 H) 1.99-2.44 (m, 8 H) 2.95-3.15 (m, 2 H) 4.27-4.44 (m, 2 H) 4.60 -4.73 (m, 1 H) 4.91-5.04 (m, 1 H) 7.81-7.85 (m, 1 H) 7.98-8.03 (m, 1 H) 8.75-8.79 (m, 1 H).
MS ESI / APCI Dual posi: 379 [M + H] ⁺ .
(2) 4- (1- {1-[(cyclobutyloxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) -2,5-difluorobenzoic acid

参考例２６−G（１）で得られた化合物（１．５０ｇ）と参考例Ｅ−１０で得られた化合物（１．２０ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（１．１１ｇ）を橙色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.46 - 1.82 (m, 2 H) 1.87 - 2.17 (m, 6 H) 2.19 - 2.37 (m, 2 H) 2.94 - 3.23 (m, 2 H) 4.07 - 4.24 (m, 2 H) 4.81 - 4.96 (m, 1 H) 5.05 - 5.22 (m, 1 H) 7.68 - 7.82 (m, 1 H) 7.87 - 8.01 (m, 1 H) 8.27 - 8.40 (m, 2 H) 9.42 (s, 1 H).
MS ESI/APCI Dual nega: 455[M-H]^-.
参考例２６−Ｈ
４−（１−｛１−［（シクロブチルメトキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）−２，５−ジフルオロ安息香酸
（１）シクロブチルメチル ４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボキシラート

Using the compound (1.50 g) obtained in Reference Example 26-G (1) and the compound (1.20 g) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17. To give the title compound (1.11 g) as an orange powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.46-1.82 (m, 2 H) 1.87-2.17 (m, 6 H) 2.19-2.37 (m, 2 H) 2.94-3.23 (m, 2 H) 4.07-4.24 (m, 2 H) 4.81-4.96 (m, 1 H) 5.05-5.22 (m, 1 H) 7.68-7.82 (m, 1 H) 7.87-8.01 (m, 1 H) 8.27-8.40 (m , 2 H) 9.42 (s, 1 H).
MS ESI / APCI Dual nega: 455 [MH] ^- .
Reference Example 26-H
4- (1- {1-[(cyclobutylmethoxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) -2,5-difluorobenzoic acid (1) Cyclobutylmethyl 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carboxylate

参考例２５で得られた化合物（２．００ｇ）とシクロブタンメタノール（１．２２ｇ）を用いて、参考例２３−Gと同様の操作にて反応及び精製を行い、表題化合物（２．５４ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.71 - 2.34 (m, 10 H) 2.56 - 2.74 (m, 1 H) 2.97 - 3.15 (m, 2 H) 4.10 (d, J=6.7 Hz, 2 H) 4.26 - 4.48 (m, 2 H) 4.60 - 4.74 (m, 1 H) 7.79 - 7.85 (m, 1 H) 8.00 (s, 1 H) 8.77 (s, 1 H).
MS ESI/APCI Dual posi: 393[M+H]⁺.
（２）４−（１−｛１−［（シクロブチルメトキシ）カルボニル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル）−２，５−ジフルオロ安息香酸

Using the compound (2.00 g) obtained in Reference Example 25 and cyclobutanemethanol (1.22 g), the reaction and purification were performed in the same manner as in Reference Example 23-G, and the title compound (2.54 g) was obtained. Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.71-2.34 (m, 10 H) 2.56-2.74 (m, 1 H) 2.97-3.15 (m, 2 H) 4.10 (d, J = 6.7 Hz, 2 H) 4.26-4.48 (m, 2 H) 4.60-4.74 (m, 1 H) 7.79-7.85 (m, 1 H) 8.00 (s, 1 H) 8.77 (s, 1 H).
MS ESI / APCI Dual posi: 393 [M + H] ⁺ .
(2) 4- (1- {1-[(cyclobutylmethoxy) carbonyl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridin-5-yl) -2,5-difluorobenzoic acid

参考例２６−H（１）で得られた化合物（１．８０ｇ）と参考例Ｅ−１０で得られた化合物（１．３９ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（５９３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.67 - 2.15 (m, 10 H) 2.52 - 2.69 (m, 2 H) 2.98 - 3.20 (m, 2 H) 4.03 (d, J=6.7 Hz, 2 H) 4.10 - 4.24 (m, 2 H) 5.07 - 5.23 (m, 1 H) 7.76 (dd, J=11.0, 6.0 Hz, 1 H) 7.94 (dd, J=11.0, 6.0 Hz, 1 H) 8.32 (s, 1 H) 8.36 (s, 1 H) 9.43 (s, 1 H).
MS ESI/APCI Dual nega: 469[M-H]^-.
参考例２６−Ｉ
４−［１−（１−｛［（１，１−ジフルオロ−２−メチルプロパン−２−イル）オキシ］カルボニル｝ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル］−２，５−ジフルオロ安息香酸

Using the compound (1.80 g) obtained in Reference Example 26-H (1) and the compound (1.39 g) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17. To give the title compound (593 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.67-2.15 (m, 10 H) 2.52-2.69 (m, 2 H) 2.98-3.20 (m, 2 H) 4.03 (d, J = 6.7 Hz, 2 H) 4.10-4.24 (m, 2 H) 5.07-5.23 (m, 1 H) 7.76 (dd, J = 11.0, 6.0 Hz, 1 H) 7.94 (dd, J = 11.0, 6.0 Hz, 1 H) 8.32 (s, 1 H) 8.36 (s, 1 H) 9.43 (s, 1 H).
MS ESI / APCI Dual nega: 469 [MH] ^- .
Reference Example 26-I
4- [1- (1-{[(1,1-difluoro-2-methylpropan-2-yl) oxy] carbonyl} piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine-5 -Yl] -2,5-difluorobenzoic acid

参考例２３−Ｆで得られた化合物（５２０ｍｇ）と参考例Ｅ−１０で得られた化合物（３７７ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（２５９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.49 (s, 6 H) 1.89 - 2.15 (m, 4 H) 2.95 - 3.23 (m, 2 H) 4.02 - 4.22 (m, 2 H) 5.07 - 5.23 (m, 1 H) 6.07 - 6.52 (m, 1 H) 7.77 (dd, J=11.0, 6.1 Hz, 1 H) 7.94 (dd, J=11.0, 6.1 Hz, 1 H) 8.32 (s, 1 H) 8.36 (s, 1 H) 9.42 (s, 1 H).
MS ESI/APCI Dual nega: 493[M-H]^-.
参考例２６−Ｊ
２，５−ジフルオロ−４−［１−（１−｛［（１−フルオロ−２−メチルプロパン−２−イル）オキシ］カルボニル｝ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル］安息香酸

Using the compound (520 mg) obtained in Reference Example 23-F and the compound (377 mg) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound (259 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.49 (s, 6 H) 1.89-2.15 (m, 4 H) 2.95-3.23 (m, 2 H) 4.02-4.22 (m, 2 H) 5.07- 5.23 (m, 1 H) 6.07-6.52 (m, 1 H) 7.77 (dd, J = 11.0, 6.1 Hz, 1 H) 7.94 (dd, J = 11.0, 6.1 Hz, 1 H) 8.32 (s, 1 H ) 8.36 (s, 1 H) 9.42 (s, 1 H).
MS ESI / APCI Dual nega: 493 [MH] ^- .
Reference Example 26-J
2,5-difluoro-4- [1- (1-{[(1-fluoro-2-methylpropan-2-yl) oxy] carbonyl} piperidin-4-yl) -1H-pyrazolo [3,4-c ] Pyridin-5-yl] benzoic acid

参考例２３−Ｅで得られた化合物（５００ｍｇ）と参考例Ｅ−１０で得られた化合物（３７９ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（５７．４ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.44 (s, 3 H) 1.44 (s, 3 H) 1.86 - 2.13 (m, 4 H) 3.06 (d, J=1.0 Hz, 2 H) 4.13 (d, J=12.3 Hz, 2 H) 4.54 (d, J=1.0 Hz, 2 H) 5.04 - 5.20 (m, 1 H) 7.58 (dd, J=11.0, 6.3 Hz, 1 H) 7.78 (dd, J=11.0, 6.3 Hz, 1 H) 8.25 (s, 1 H) 8.33 (s, 1 H) 9.39 (s, 1 H).
MS ESI/APCI Dual nega: 475[M-H]^-.
参考例２７
５−［４−（メチルスルホニル）フェノキシ］−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (500 mg) obtained in Reference Example 23-E and the compound (379 mg) obtained in Reference Example E-10, the reaction and purification were carried out in the same manner as in Reference Example 17, and the title compound (57 .4 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.44 (s, 3 H) 1.44 (s, 3 H) 1.86-2.13 (m, 4 H) 3.06 (d, J = 1.0 Hz, 2 H) 4.13 (d, J = 12.3 Hz, 2 H) 4.54 (d, J = 1.0 Hz, 2 H) 5.04-5.20 (m, 1 H) 7.58 (dd, J = 11.0, 6.3 Hz, 1 H) 7.78 (dd, J = 11.0, 6.3 Hz, 1 H) 8.25 (s, 1 H) 8.33 (s, 1 H) 9.39 (s, 1 H).
MS ESI / APCI Dual nega: 475 [MH] ^- .
Reference Example 27
5- [4- (Methylsulfonyl) phenoxy] -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine

後掲した実施例６１−１で得られた化合物（１．５ｇ）を用いて、参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（１．２ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.05 - 2.32 (m, 4 H) 2.80 - 2.93 (m, 2 H) 3.05 (s, 3 H) 3.27 - 3.39 (m, 2 H) 4.55 - 4.70 (m, 1 H) 7.13 - 7.18 (m, 2 H) 7.33 (d, J=1.0 Hz, 1 H) 7.89 - 7.94 (m, 2 H) 8.05 - 8.07 (m, 1 H) 8.74 (t, J=1.0 Hz, 1 H).
参考例２８
プロパン−２−イル ４−（６−ブロモ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート
（１）プロパン−２−イル ４−［（６−ブロモ−４−ニトロ−１−オキシドピリジン−３−イル）アミノ］ピペリジン−１−カルボキシラート

Using the compound (1.5 g) obtained in Example 61-1 described later, the reaction and purification were carried out in the same manner as in Reference Example 20 (2) to obtain the title compound (1.2 g). .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.05-2.32 (m, 4 H) 2.80-2.93 (m, 2 H) 3.05 (s, 3 H) 3.27-3.39 (m, 2 H) 4.55-4.70 (m, 1 H) 7.13-7.18 (m, 2 H) 7.33 (d, J = 1.0 Hz, 1 H) 7.89-7.94 (m, 2 H) 8.05-8.07 (m, 1 H) 8.74 (t, J = 1.0 Hz, 1 H).
Reference Example 28
Propan-2-yl 4- (6-bromo-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) piperidin-1-carboxylate (1) Propan-2-yl 4 -[(6-Bromo-4-nitro-1-oxidepyridin-3-yl) amino] piperidine-1-carboxylate

参考例１８（４）で得られた化合物（５．５０ｇ）とイソプロピル ４−アミノピペリジン−１−カルボキシレート（４．３２ｇ）を用いて、参考例１８（５）と同様の操作にて反応及び精製を行い、表題化合物（９．４９ｇ）を橙色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.06 - 1.34 (m, 6 H) 1.43 - 1.65 (m, 2 H) 1.98 - 2.24 (m, 2 H) 2.96 - 3.16 (m, 2 H) 3.42 - 3.66 (m, 1 H) 3.94 - 4.28 (m, 2 H) 4.70 - 5.15 (m, 1 H) 7.74 (d, J=7.6 Hz, 1 H) 8.17 (s, 1 H) 8.42 (s, 1 H).
MS ESI/APCI Dual posi: 421[M+Na]⁺.
MS ESI/APCI Dual nega: 433[M+Cl]^-.
（２）プロパン−２−イル ４−［（４−アミノ−６−ブロモピリジン−３−イル）アミノ］ピペリジン−１−カルボキシラート

Using the compound (5.50 g) obtained in Reference Example 18 (4) and isopropyl 4-aminopiperidine-1-carboxylate (4.32 g), the reaction and reaction were carried out in the same manner as in Reference Example 18 (5). Purification was performed to give the title compound (9.49 g) as an orange powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.06-1.34 (m, 6 H) 1.43-1.65 (m, 2 H) 1.98-2.24 (m, 2 H) 2.96-3.16 (m, 2 H) 3.42 -3.66 (m, 1 H) 3.94-4.28 (m, 2 H) 4.70-5.15 (m, 1 H) 7.74 (d, J = 7.6 Hz, 1 H) 8.17 (s, 1 H) 8.42 (s, 1 H).
MS ESI / APCI Dual posi: 421 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 433 [M + Cl] ^- .
(2) Propan-2-yl 4-[(4-amino-6-bromopyridin-3-yl) amino] piperidine-1-carboxylate

参考例２８（１）で得られた化合物（９．４９ｇ）を用いて、参考例１８（６）と同様の操作にて反応及び精製を行い、表題化合物（１０ｇ）を赤色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.06 - 1.53 (m, 8 H) 1.89 - 2.01 (m, 2 H) 2.93 (br-t, J=11.4 Hz, 2 H) 3.31 (br. s., 1 H) 3.98 - 4.23 (m, 3 H) 4.91 (dt, J=12.2, 5.9 Hz, 2 H) 6.74 (s, 1 H) 7.65 (s, 1 H).
MS ESI/APCI Dual posi: 357[M+H]⁺.
MS ESI/APCI Dual nega: 391[M+Cl]^-.
（３）プロパン−２−イル ４−（６−ブロモ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (9.49 g) obtained in Reference Example 28 (1), the reaction and purification were carried out in the same manner as in Reference Example 18 (6) to obtain the title compound (10 g) as a red oily substance. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.06-1.53 (m, 8 H) 1.89-2.01 (m, 2 H) 2.93 (br-t, J = 11.4 Hz, 2 H) 3.31 (br. S ., 1 H) 3.98-4.23 (m, 3 H) 4.91 (dt, J = 12.2, 5.9 Hz, 2 H) 6.74 (s, 1 H) 7.65 (s, 1 H).
MS ESI / APCI Dual posi: 357 [M + H] ⁺ .
MS ESI / APCI Dual nega: 391 [M + Cl] ^- .
(3) Propan-2-yl 4- (6-bromo-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) piperidine-1-carboxylate

参考例２８（２）で得られた化合物（１０ｇ）を用いて、参考例１８（７）と同様の操作にて反応及び精製を行い、表題化合物（３．６５ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.17 - 2.46 (m, 4 H) 3.10 (br. s., 2 H) 4.29 - 4.55 (m, 2 H) 4.89 - 5.07 (m, 2 H) 8.18 (d, J=1.1 Hz, 1 H) 8.93 (d, J=1.1 Hz, 1 H).
MS ESI/APCI Dual posi: 390[M+Na]⁺.
MS ESI/APCI Dual nega: 402[M+Cl]^-.
参考例２９
ｔｅｒｔ−ブチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート
（１）Ｎ^３−（１−ベンジルピペリジン−４−イル）−６−クロロピリジン−３，４−ジアミン

Using the compound (10 g) obtained in Reference Example 28 (2), the reaction and purification were performed in the same manner as in Reference Example 18 (7) to obtain the title compound (3.65 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.17-2.46 (m, 4 H) 3.10 (br. S., 2 H) 4.29-4.55 (m, 2 H) 4.89-5.07 (m, 2 H) 8.18 (d, J = 1.1 Hz, 1 H) 8.93 (d, J = 1.1 Hz, 1 H).
MS ESI / APCI Dual posi: 390 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 402 [M + Cl] ^- .
Reference Example 29
tert-Butyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) piperidine-1-carboxylate (1) N ^3- (1-Benzylpiperidine -4-yl) -6-chloropyridine-3,4-diamine

６−クロロ−３，４−ピリジンジアミン（４４ｇ）の１，２−ジクロロエタン（３０６ｍｌ）溶液へ、酢酸（３０６ｍｌ）、１−ベンジルピペリジン−４−オン（６９．５ｇ）を加え、０℃にて水素化トリアセトキシホウ素ナトリウム（７７．８ｇ）を加え、室温にて１時間攪拌した。反応液にクロロホルムを加え、１０％水酸化ナトリウム水溶液を加えて中和した。クロロホルムにて抽出し、有機層を減圧濃縮した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 酢酸エチル）にて精製し、得られた残渣をヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（４１ｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.46 - 1.55 (m, 2 H) 1.95 - 2.02 (m, 2 H) 2.09 - 2.16 (m, 2 H) 2.83 - 2.90 (m, 2 H) 3.09 - 3.18 (m, 1 H) 3.52 (s, 2 H) 4.05 - 4.13 (m, 2 H) 6.57 (s, 1 H) 7.25 - 7.34 (m, 5 H) 7.64 (s, 1 H).
MS ESI/APCI Dual posi: 317[M+H]⁺.
MS ESI/APCI Dual nega: 315[M-H]^-.
（２）３−（１−ベンジルピペリジン−４−イル）−６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Acetic acid (306 ml) and 1-benzylpiperidin-4-one (69.5 g) were added to a solution of 6-chloro-3,4-pyridinediamine (44 g) in 1,2-dichloroethane (306 ml) at 0 ° C. Sodium triacetoxyborohydride (77.8 g) was added, and the mixture was stirred at room temperature for 1 hour. Chloroform was added to the reaction solution, and neutralized by adding a 10% aqueous sodium hydroxide solution. Extraction was performed with chloroform, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent: ethyl acetate), and the obtained residue was recrystallized from a hexane-ethyl acetate mixed solution to obtain the title compound (41 g) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.46-1.55 (m, 2 H) 1.95-2.02 (m, 2 H) 2.09-2.16 (m, 2 H) 2.83-2.90 (m, 2 H) 3.09 -3.18 (m, 1 H) 3.52 (s, 2 H) 4.05-4.13 (m, 2 H) 6.57 (s, 1 H) 7.25-7.34 (m, 5 H) 7.64 (s, 1 H).
MS ESI / APCI Dual posi: 317 [M + H] ⁺ .
MS ESI / APCI Dual nega: 315 [MH] ^- .
(2) 3- (1-Benzylpiperidin-4-yl) -6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridine

参考例２９（１）で得られた化合物（４０ｇ）を用いて、参考例１８（７）と同様の操作にて反応及び精製を行い、表題化合物（３２．５ｇ）を黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.18 - 2.25 (m, 2 H) 2.27 - 2.35 (m, 2 H) 2.43 - 2.53 (m, 2 H) 3.10 - 3.17 (m, 2 H) 3.63 (s, 2 H) 4.79 - 4.86 (m, 1 H) 7.27 - 7.39 (m, 5 H) 7.99 (d, J=1.2 Hz, 1 H) 8.97 (d, J=1.2 Hz, 1 H).
MS ESI posi: 328[M+H]⁺.
（３）ｔｅｒｔ−ブチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (40 g) obtained in Reference Example 29 (1), the reaction and purification were performed in the same manner as in Reference Example 18 (7) to obtain the title compound (32.5 g) as a yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.18-2.25 (m, 2 H) 2.27-2.35 (m, 2 H) 2.43-2.53 (m, 2 H) 3.10-3.17 (m, 2 H) 3.63 (s, 2 H) 4.79-4.86 (m, 1 H) 7.27-7.39 (m, 5 H) 7.99 (d, J = 1.2 Hz, 1 H) 8.97 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 328 [M + H] ⁺ .
(3) tert-butyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) piperidine-1-carboxylate

参考例２９（２）で得られた化合物（１５ｇ）のクロロホルム（１５３ｍｌ）溶液へ、１−クロロエチルクロロホルメート（８．５０ｇ）を加え、６０℃にて１時間攪拌した。反応系を減圧濃縮し、得られた残渣にメタノール（１５３ｍｌ）を加え、６０℃にて１時間攪拌した。反応系を減圧濃縮し、得られた残渣に飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別、溶媒を減圧留去した。得られた残渣にクロロホルム（１６８ｍｌ）、トリエチルアミン（６．１３ｇ）、ジ−ｔ−ブチル−ジカーボネート（１３．２ｇ）を加え、室温にて１時間攪拌した。反応系を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝３：１）にて精製し、表題化合物（１０．７ｇ）を黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.20 - 2.27 (m, 2 H) 2.28 - 2.38 (m, 2 H) 2.98 - 3.14 (m, 2 H) 4.28 - 4.47 (m, 2 H) 4.91 - 4.99 (m, 1 H) 8.00 (d, J=0.8 Hz, 1 H) 8.94 (d, J=0.8 Hz, 1 H).
MS ESI posi: 338[M+H]⁺, 360[M+Na]⁺.
参考例３０
６−クロロ−３−（ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

1-Chloroethyl chloroformate (8.50 g) was added to a chloroform (153 ml) solution of the compound (15 g) obtained in Reference Example 29 (2), and the mixture was stirred at 60 ° C. for 1 hour. The reaction system was concentrated under reduced pressure, methanol (153 ml) was added to the obtained residue, and the mixture was stirred at 60 ° C. for 1 hr. The reaction system was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the resulting residue, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. Chloroform (168 ml), triethylamine (6.13 g) and di-t-butyl-dicarbonate (13.2 g) were added to the resulting residue, and the mixture was stirred at room temperature for 1 hour. The reaction system was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 3: 1) to obtain the title compound (10.7 g) as a yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.20-2.27 (m, 2 H) 2.28-2.38 (m, 2 H) 2.98-3.14 (m, 2 H) 4.28-4.47 (m, 2 H) 4.91-4.99 (m, 1 H) 8.00 (d, J = 0.8 Hz, 1 H) 8.94 (d, J = 0.8 Hz, 1 H).
MS ESI posi: 338 [M + H] ⁺ , 360 [M + Na] ⁺ .
Reference Example 30
6-Chloro-3- (piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例２９（２）で得られた化合物（２．７ｇ）のクロロホルム（２５ｍｌ）溶液へ、１−クロロエチルクロロホルメート（１．５ｇ）を加え、６０℃にて１時間攪拌した。反応系に飽和炭酸水素ナトリウム溶液を加え、水層をクロロホルムで抽出した。有機層をフェーズセパレーターに通して乾燥後、濃縮して得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 酢酸エチル：ヘキサン ＝ ０：１〜２：３、メタノール：クロロホルム＝０：１〜１：１）にて精製した。得られた生成物にメタノール（２０ｍｌ）を加え、６０℃にて１時間攪拌した。反応系を濃縮した後、残渣にクロロホルム加え、飽和炭酸水素ナトリウム水溶液で洗浄した。有機層をフェーズセパレーターに通して乾燥後、濃縮して表題化合物（１．２ｇ）を黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d6) δ ppm 2.03 - 2.16 (m, 4 H) 2.65 - 2.78 (m, 2 H) 3.07 - 3.19 (m, 2 H) 5.06 - 5.24 (m, 1 H) 8.27 (d, J=1.1 Hz, 2 H) 9.38 (d, J=1.1 Hz, 2 H).
参考例３１
４−｛３−［１−（ｔｅｒｔ−ブトキシカルボニル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸

1-Chloroethyl chloroformate (1.5 g) was added to a chloroform (25 ml) solution of the compound (2.7 g) obtained in Reference Example 29 (2), and the mixture was stirred at 60 ° C. for 1 hour. Saturated sodium hydrogen carbonate solution was added to the reaction system, and the aqueous layer was extracted with chloroform. The organic layer was passed through a phase separator, dried, and then concentrated. The resulting residue was subjected to NH silica gel column chromatography (developing solvent: ethyl acetate: hexane = 0: 1 to 2: 3, methanol: chloroform = 0: 1 to 1: Purified in 1). Methanol (20 ml) was added to the obtained product, and the mixture was stirred at 60 ° C. for 1 hour. The reaction system was concentrated, chloroform was added to the residue, and the mixture was washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was passed through a phase separator, dried and concentrated to give the title compound (1.2 g) as a yellow powder.
¹ H NMR (300 MHz, DMSO-d6) δ ppm 2.03-2.16 (m, 4 H) 2.65-2.78 (m, 2 H) 3.07-3.19 (m, 2 H) 5.06-5.24 (m, 1 H) 8.27 (d, J = 1.1 Hz, 2 H) 9.38 (d, J = 1.1 Hz, 2 H).
Reference Example 31
4- {3- [1- (tert-butoxycarbonyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3-difluoro benzoic acid

参考例２９で得られた化合物（３．００ｇ）、４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（２．６９ｇ）、テトラキス（トリフェニスホスフィン）パラジウム（５１３ｍｇ）、１Ｍ炭酸水素ナトリウム水溶液（１８ｍｌ）のエタノール（９０ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１２０℃にて３０分間撹拌した。冷却後反応液へ酢酸エチルを加え、２Ｍ水酸化カリウム水溶液にて逆抽出した。水層に飽和塩化アンモニウム水溶液を加えて析出した粉末をろ取し、表題化合物（９００ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.45 (s, 9 H) 1.97 - 2.32 (m, 4 H) 2.95 - 3.17 (m, 3 H) 4.08 - 4.20 (m, 2 H) 5.25 - 5.41 (m, 1 H) 7.38 - 7.51 (m, 1 H) 7.59 - 7.70 (m, 1 H) 8.41 (d, J=1.2 Hz, 1 H) 9.60 (d, J=1.2 Hz, 1 H).
MS ESI posi: 460[M+H]⁺.
参考例３２−Ａ
｛２，３−ジフルオロ−４−［３−（ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］フェニル｝［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］メタノン
（１）ｔｅｒｔ−ブチル ４−［６−（２，３−ジフルオロ−４−｛［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］カルボニル｝フェニル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル］ピペリジン−１−カルボキシラート

Compound (3.00 g) obtained in Reference Example 29, 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (2.69 g), tetrakis (triphenisphosphine) palladium (513 mg), 1M sodium bicarbonate A suspension of an aqueous solution (18 ml) in ethanol (90 ml) was stirred for 30 minutes at 120 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, ethyl acetate was added to the reaction mixture, and the mixture was back extracted with 2M aqueous potassium hydroxide solution. Saturated aqueous ammonium chloride solution was added to the aqueous layer, and the precipitated powder was collected by filtration to give the title compound (900 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.45 (s, 9 H) 1.97-2.32 (m, 4 H) 2.95-3.17 (m, 3 H) 4.08-4.20 (m, 2 H) 5.25-5.41 (m, 1 H) 7.38-7.51 (m, 1 H) 7.59-7.70 (m, 1 H) 8.41 (d, J = 1.2 Hz, 1 H) 9.60 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 460 [M + H] ⁺ .
Reference Example 32-A
{2,3-difluoro-4- [3- (piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl] phenyl} [(3R)- 3-hydroxypyrrolidin-1-yl] methanone (1) tert-butyl 4- [6- (2,3-difluoro-4-{[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} phenyl)- 3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl] piperidine-1-carboxylate

参考例３１で得られた化合物（２．８０ｇ）のＮ，Ｎ−ジメチルホルムアミド（７０ｍｌ）溶液へ、３−ヒドロキシピロリジン（７９８ｍｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（１．４０ｇ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（１．７５ｇ）を加え、室温にて一晩攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をヘキサン−クロロホルムで再結晶し、表題化合物（２．３９ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 1.80 - 1.89 (m, 1 H) 1.99 - 2.21 (m, 2 H) 2.22 - 2.47 (m, 4 H) 3.01 - 3.15 (m, 2 H) 3.33 - 3.91 (m, 4 H) 4.29 - 4.69 (m, 3 H) 4.95 - 5.11 (m, 1 H) 7.29 - 7.38 (m, 1 H) 7.84 - 7.94 (m, 1 H) 8.48 (q, J=1.2 Hz, 1 H) 9.25 (d, J=1.2 Hz, 1 H).
MS ESI posi: 529[M+H]⁺.
（２）｛２，３−ジフルオロ−４−［３−（ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］フェニル｝［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］メタノン

To a solution of the compound (2.80 g) obtained in Reference Example 31 in N, N-dimethylformamide (70 ml), 3-hydroxypyrrolidine (798 mg), 1-hydroxybenzotriazole monohydrate (1.40 g). ), N-ethyl-N′-3-dimethylaminopropylcarbodiimide hydrochloride (1.75 g) was added, and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from hexane-chloroform to obtain the title compound (2.39 g) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 1.80-1.89 (m, 1 H) 1.99-2.21 (m, 2 H) 2.22-2.47 (m, 4 H) 3.01-3.15 (m, 2 H) 3.33-3.91 (m, 4 H) 4.29-4.69 (m, 3 H) 4.95-5.11 (m, 1 H) 7.29-7.38 (m, 1 H) 7.84-7.94 (m, 1 H ) 8.48 (q, J = 1.2 Hz, 1 H) 9.25 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 529 [M + H] ⁺ .
(2) {2,3-difluoro-4- [3- (piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl] phenyl} [( 3R) -3-Hydroxypyrrolidin-1-yl] methanone

参考例３２−Ａ（１）で得られた化合物（２．３９ｇ）を用いて、参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（１．６３ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.95 - 2.51 (m, 7 H) 2.86 - 3.00 (m, 2 H) 3.32 - 3.42 (m, 2 H) 3.43 - 3.91 (m, 4 H) 4.44 - 4.68 (m, 1 H) 4.91 - 5.08 (m, 1 H) 7.33 (ddd, J=8.2, 6.1, 4.4 Hz, 1 H) 7.89 (ddd, J=8.2, 6.1, 1.7 Hz, 1 H) 8.47 (q, J=1.2 Hz, 1 H) 9.30 (d, J=1.2 Hz, 1 H).
参考例３２−Ｂ
Ｎ−エチル−２，３−ジフルオロ−４−［３−（ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］ベンズアミド
（１）ｔｅｒｔ−ブチル ４−｛６−［４−（エチルカルバモイル）−２，３−ジフルオロフェニル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル｝ピペリジン−１−カルボキシラート

The compound (2.39 g) obtained in Reference Example 32-A (1) was subjected to reaction and purification in the same manner as in Reference Example 20 (2), and the title compound (1.63 g) was obtained as a colorless powder. Got as.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.95-2.51 (m, 7 H) 2.86-3.00 (m, 2 H) 3.32-3.42 (m, 2 H) 3.43-3.91 (m, 4 H) 4.44 -4.68 (m, 1 H) 4.91-5.08 (m, 1 H) 7.33 (ddd, J = 8.2, 6.1, 4.4 Hz, 1 H) 7.89 (ddd, J = 8.2, 6.1, 1.7 Hz, 1 H) 8.47 (q, J = 1.2 Hz, 1 H) 9.30 (d, J = 1.2 Hz, 1 H).
Reference Example 32-B
N-ethyl-2,3-difluoro-4- [3- (piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl] benzamide (1) tert-Butyl 4- {6- [4- (ethylcarbamoyl) -2,3-difluorophenyl] -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl} piperidine-1 -Carboxylate

参考例３１で得られた化合物（１．００ｇ）と７０％エチルアミン水溶液（２１０ｍｇ）を用いて、参考例３２−Ａ（１）と同様の操作にて反応及び精製を行い、表題化合物（６００ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J=7.3 Hz, 3 H) 1.52 (s, 9 H) 2.22 - 2.47 (m, 4 H) 3.01 - 3.05 (m, 2 H) 3.49 - 3.64 (m, 2 H) 4.40 (br. s., 2 H) 4.95 - 5.09 (m, 1 H) 6.64 (br. s., 1 H) 7.93 - 8.00 (m, 2 H) 8.52 (t, J=1.2 Hz, 1 H) 9.26 (d, J=1.2 Hz, 1 H).
（２）Ｎ−エチル−２，３−ジフルオロ−４−［３−（ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］ベンズアミド

Using the compound (1.00 g) obtained in Reference Example 31 and 70% aqueous ethylamine solution (210 mg), the reaction and purification were carried out in the same manner as in Reference Example 32-A (1) to give the title compound (600 mg). Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J = 7.3 Hz, 3 H) 1.52 (s, 9 H) 2.22-2.47 (m, 4 H) 3.01-3.05 (m, 2 H) 3.49-3.64 (m, 2 H) 4.40 (br. S., 2 H) 4.95-5.09 (m, 1 H) 6.64 (br. S., 1 H) 7.93-8.00 (m, 2 H) 8.52 (t , J = 1.2 Hz, 1 H) 9.26 (d, J = 1.2 Hz, 1 H).
(2) N-ethyl-2,3-difluoro-4- [3- (piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl] benzamide

参考例３２−Ｂ（１）で得られた化合物（６００ｍｇ）を用いて、参考例２０（２）と同様の操作にて反応及び精製を行い、表題化合物（４８４ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J=7.2 Hz, 3 H) 2.20 - 2.50 (m, 4 H) 2.85 - 3.00 (m, 2 H) 3.35 - 3.42 (m, 2 H) 3.50 - 3.63 (m, 2 H) 4.90 - 5.08 (m, 1 H) 6.69 (br. s., 1 H) 7.87 - 8.04 (m, 2 H) 8.51 (t, J=1.2 Hz, 1 H) 9.30 (d, J=1.2 Hz, 1 H).
参考例３３−Ａ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−フルオロ安息香酸

Using the compound (600 mg) obtained in Reference Example 32-B (1), the reaction and purification were performed in the same manner as in Reference Example 20 (2) to obtain the title compound (484 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J = 7.2 Hz, 3 H) 2.20-2.50 (m, 4 H) 2.85-3.00 (m, 2 H) 3.35-3.42 (m, 2 H) 3.50-3.63 (m, 2 H) 4.90-5.08 (m, 1 H) 6.69 (br. S., 1 H) 7.87-8.04 (m, 2 H) 8.51 (t, J = 1.2 Hz, 1 H ) 9.30 (d, J = 1.2 Hz, 1 H).
Reference Example 33-A
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluorobenzoic acid

参考例１８で得られた化合物（１００ｍｇ）と参考例Ｅ−４で得られた化合物（１０３ｍｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（７４．１ｍｇ）を灰色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.09 - 2.38 (m, 4 H) 2.41 - 2.49 (m, 2 H) 3.14 - 3.28 (m, 1 H) 4.77 - 4.89 (m, 1 H) 5.44 (br. s., 1 H) 7.67 (d, J=8.2 Hz, 1 H) 7.89 (d, J=9.9 Hz, 2 H) 8.32 (s, 2 H) 8.65 (s, 1 H) 9.54 - 9.60 (m, 1 H).
MS ESI/APCI Dual nega: 446[M-H]^-.
参考例３３−Ｂ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３−フルオロ安息香酸

Using the compound (100 mg) obtained in Reference Example 18 and the compound (103 mg) obtained in Reference Example E-4, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound (74.1 mg). ) Was obtained as a gray powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.09-2.38 (m, 4 H) 2.41-2.49 (m, 2 H) 3.14-3.28 (m, 1 H) 4.77-4.89 (m, 1 H) 5.44 (br. S., 1 H) 7.67 (d, J = 8.2 Hz, 1 H) 7.89 (d, J = 9.9 Hz, 2 H) 8.32 (s, 2 H) 8.65 (s, 1 H) 9.54-9.60 (m, 1 H).
MS ESI / APCI Dual nega: 446 [MH] ^- .
Reference Example 33-B
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 -Fluorobenzoic acid

参考例１８で得られた化合物（５００ｍｇ）と参考例Ｅ−２で得られた化合物（５１４ｍｇ）を用いて、参考例１４−Ａと同様の操作にて反応及び精製を行い、表題化合物（３７６ｍｇ）を薄紫色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.13 - 2.23 (m, 2 H) 2.30 - 2.37 (m, 2 H) 2.47 (q, J=7.6 Hz, 2 H) 3.19 - 3.26 (m, 2 H) 4.80 - 4.87 (m, 2 H) 5.42 - 5.51 (m, 1 H) 7.80 - 7.84 (m, 1 H) 7.90 - 7.94 (m, 1 H) 8.13 - 8.18 (m, 1 H) 8.31 (s, 2 H) 8.48 (s, 1 H) 9.66 (d, J=1.2 Hz, 1 H).
MS ESI posi: 448[M+H]⁺.
参考例３３−Ｃ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，５−ジフルオロ安息香酸

Using the compound obtained in Reference Example 18 (500 mg) and the compound obtained in Reference Example E-2 (514 mg), the reaction and purification were carried out in the same manner as in Reference Example 14-A to give the title compound (376 mg ) Was obtained as a light purple powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.13-2.23 (m, 2 H) 2.30-2.37 (m, 2 H) 2.47 (q, J = 7.6 Hz, 2 H) 3.19-3.26 (m, 2 H) 4.80-4.87 (m, 2 H) 5.42-5.51 (m, 1 H) 7.80-7.84 (m, 1 H) 7.90-7.94 (m, 1 H ) 8.13-8.18 (m, 1 H) 8.31 (s, 2 H) 8.48 (s, 1 H) 9.66 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 448 [M + H] ⁺ .
Reference Example 33-C
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 , 5-Difluorobenzoic acid

参考例１８で得られた化合物（５００ｍｇ）、参考例Ｅ−１０で得られた化合物（５４９ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（７４．５ｍｇ）、２Ｍ炭酸セシウム水溶液（１．２９ｍｌ）のエタノール（１２．９ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^ＴＭ（商品名））を用いて、マイクロウェーブ照射下１５０℃にて３０分間撹拌した。冷却後、反応液へ２Ｍ炭酸セシウム水溶液を加え、酢酸エチルで水層を洗浄した。水層に１Ｍ塩酸を加えて酸性にし、クロロホルム−メタノール（１０：１）混合溶液にて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣の粉末をヘキサン−酢酸エチル混合溶液で洗浄し、表題化合物（２９０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.13 - 2.22 (m, 2 H) 2.30 - 2.36 (m, 2 H) 2.47 (q, J=7.6 Hz, 4 H) 3.19 - 3.26 (m, 2 H) 4.80 - 4.86 (m, 2 H) 5.44 - 5.52 (m, 1 H) 7.78 - 7.83 (m, 1 H) 7.92 - 7.97 (m, 1 H) 8.32 (s, 2 H) 8.54 (s, 1 H) 9.66 - 9.68 (m, 1 H).
参考例３３−Ｄ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−フルオロ−５−メチル安息香酸

Ethanol of compound obtained in Reference Example 18 (500 mg), compound obtained in Reference Example E-10 (549 mg), tetrakis (triphenisphosphine) palladium (74.5 mg), 2M aqueous cesium carbonate solution (1.29 ml) (12.9 ml) The suspension was stirred at 150 ° C. for 30 minutes under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, 2M aqueous cesium carbonate solution was added to the reaction solution, and the aqueous layer was washed with ethyl acetate. The aqueous layer was acidified with 1M hydrochloric acid, and extracted with a mixed solution of chloroform-methanol (10: 1). The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue powder was washed with a mixed solution of hexane-ethyl acetate to give the title compound (290 mg) as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.13-2.22 (m, 2 H) 2.30-2.36 (m, 2 H) 2.47 (q, J = 7.6 Hz, 4 H) 3.19-3.26 (m, 2 H) 4.80-4.86 (m, 2 H) 5.44-5.52 (m, 1 H) 7.78-7.83 (m, 1 H) 7.92-7.97 (m, 1 H ) 8.32 (s, 2 H) 8.54 (s, 1 H) 9.66-9.68 (m, 1 H).
Reference Example 33-D
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluoro-5-methylbenzoic acid

参考例１８で得られた化合物（０．５ｇ）と参考例Ｅ−１７で得られた化合物（１．０ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（０．４２ｇ）を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.11 - 1.22 (m, 3 H) 2.10 - 2.52 (m, 9 H) 3.13 - 3.28 (m, 2 H) 4.70 - 4.93 (m, 2 H) 5.36 - 5.55 (m, 1 H) 7.23 - 7.35 (m, 1 H) 7.68 - 7.77 (m, 1 H) 8.20 - 8.27 (m, 1 H) 8.32 (s, 2 H) 9.52 - 9.64 (m, 1 H).
参考例３３−Ｅ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−メチル安息香酸

Using the compound (0.5 g) obtained in Reference Example 18 and the compound (1.0 g) obtained in Reference Example E-17, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound. (0.42 g) was obtained.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.11-1.22 (m, 3 H) 2.10-2.52 (m, 9 H) 3.13-3.28 (m, 2 H) 4.70-4.93 (m, 2 H) 5.36-5.55 (m, 1 H) 7.23-7.35 (m, 1 H) 7.68-7.77 (m, 1 H) 8.20-8.27 (m, 1 H) 8.32 (s, 2 H) 9.52-9.64 (m, 1 H).
Reference Example 33-E
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Methylbenzoic acid

参考例１８で得られた化合物（５００ｍｇ）と参考例Ｅ−６で得られた化合物（５０６ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（３３４ｍｇ）を薄茶色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.09 - 1.25 (m, 3 H) 2.08 - 2.38 (m, 4 H) 2.41 - 2.47 (m, 2 H) 2.63 (s, 3 H) 3.13 - 3.30 (m, 2 H) 4.78 - 4.89 (m, 2 H) 5.44 (br. s., 1 H) 7.93 (d, J=8.2 Hz, 1 H) 8.04 - 8.19 (m, 2 H) 8.32 (s, 2 H) 8.71 (s, 1 H) 9.59 (s, 1 H).
MS ESI/APCI Dual posi: 444[M+H]⁺.
MS ESI/APCI Dual nega: 442[M-H]^-.
参考例３３−Ｆ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−メトキシ安息香酸

Using the compound (500 mg) obtained in Reference Example 18 and the compound (506 mg) obtained in Reference Example E-6, the reaction and purification were carried out in the same manner as in Reference Example 33-C, to give the title compound (334 mg). ) As a light brown powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.09-1.25 (m, 3 H) 2.08-2.38 (m, 4 H) 2.41-2.47 (m, 2 H) 2.63 (s, 3 H) 3.13- 3.30 (m, 2 H) 4.78-4.89 (m, 2 H) 5.44 (br. S., 1 H) 7.93 (d, J = 8.2 Hz, 1 H) 8.04-8.19 (m, 2 H) 8.32 (s , 2 H) 8.71 (s, 1 H) 9.59 (s, 1 H).
MS ESI / APCI Dual posi: 444 [M + H] ⁺ .
MS ESI / APCI Dual nega: 442 [MH] ^- .
Reference Example 33-F
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Methoxybenzoic acid

参考例１８で得られた化合物（５６８ｍｇ）、参考例Ｅ−１８で得られた化合物（６１０ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（３５０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J=7.8 Hz, 3 H) 2.33 - 2.40 (m, 2 H) 2.40 - 2.49 (m, 2 H) 2.52 (q, J=7.8 Hz, 2 H) 3.20 - 3.28 (m, 2 H) 4.22 (s, 3 H) 4.98 - 5.06 (m, 2 H) 5.13 - 5.21 (m, 1 H) 7.76 - 7.80 (m, 1 H) 7.92 (s, 1 H) 8.24 (s, 2 H) 8.31 (d, J=8.3 Hz, 1 H) 8.44 (s, 1 H) 9.24 (s, 1 H).
MS ESI posi: 460[M+H]⁺.
参考例３３−Ｇ
２−クロロ−４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

Using the compound (568 mg) obtained in Reference Example 18 and the compound (610 mg) obtained in Reference Example E-18, the reaction and purification were carried out in the same manner as in Reference Example 33-C, to give the title compound (350 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J = 7.8 Hz, 3 H) 2.33-2.40 (m, 2 H) 2.40-2.49 (m, 2 H) 2.52 (q, J = 7.8 Hz, 2 H) 3.20-3.28 (m, 2 H) 4.22 (s, 3 H) 4.98-5.06 (m, 2 H) 5.13-5.21 (m, 1 H) 7.76-7.80 (m, 1 H) 7.92 ( s, 1 H) 8.24 (s, 2 H) 8.31 (d, J = 8.3 Hz, 1 H) 8.44 (s, 1 H) 9.24 (s, 1 H).
MS ESI posi: 460 [M + H] ⁺ .
Reference Example 33-G
2-Chloro-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Ile} benzoic acid

参考例１８で得られた化合物（５００ｍｇ）のエタノール（１．３ｍｌ）溶液へ、４−カルボキシ−３−クロロフェニルボロン酸（３８７ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（７４．０ｍｇ）、２Ｍ炭酸セシウム水溶液（０．１３ｍｌ）を加え、８０℃にて４．５時間攪拌した。冷却後反応液へ２Ｍ水酸化カリウム水溶液と酢酸エチルを加え、２Ｍ水酸化カリウム水溶液にて逆抽出した。水層に飽和塩化アンモニウム水溶液を加えて析出した粉末をろ取し、表題化合物（４３３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.07 - 2.23 (m, 2 H) 2.25 - 2.38 (m, 2 H) 2.39 - 2.47 (m, 2 H) 3.16 - 3.28 (m, 2 H) 4.78 - 4.89 (m, 2 H) 5.34 - 5.50 (m, 1 H) 7.49 (d, J=7.9 Hz, 1 H) 8.04 (d, J=7.9 Hz, 1 H) 8.13 (s, 1 H) 8.32 (s, 2 H) 8.65 (s, 1 H) 9.56 (s, 1 H).
MS ESI/APCI Dual posi: 464[M+H]⁺.
MS ESI/APCI Dual nega: 462[M-H]^-.
参考例３３−Ｈ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−（トリフルオロメチル）安息香酸

To a solution of the compound (500 mg) obtained in Reference Example 18 in ethanol (1.3 ml), 4-carboxy-3-chlorophenylboronic acid (387 mg), tetrakis (triphenisphosphine) palladium (74.0 mg), 2M cesium carbonate An aqueous solution (0.13 ml) was added, and the mixture was stirred at 80 ° C. for 4.5 hours. After cooling, 2M aqueous potassium hydroxide solution and ethyl acetate were added to the reaction solution, and back extraction was performed with 2M aqueous potassium hydroxide solution. Saturated aqueous ammonium chloride solution was added to the aqueous layer, and the precipitated powder was collected by filtration to give the title compound (433 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.07-2.23 (m, 2 H) 2.25-2.38 (m, 2 H) 2.39-2.47 (m, 2 H) 3.16-3.28 (m, 2 H) 4.78-4.89 (m, 2 H) 5.34-5.50 (m, 1 H) 7.49 (d, J = 7.9 Hz, 1 H) 8.04 (d, J = 7.9 Hz , 1 H) 8.13 (s, 1 H) 8.32 (s, 2 H) 8.65 (s, 1 H) 9.56 (s, 1 H).
MS ESI / APCI Dual posi: 464 [M + H] ⁺ .
MS ESI / APCI Dual nega: 462 [MH] ^- .
Reference Example 33-H
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -(Trifluoromethyl) benzoic acid

参考例１８で得られた化合物（４００ｍｇ）と４−カルボキシ−３−（トリフルオロメチル）フェニルボロン酸（３６１ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（４１６ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.11 - 1.21 (m, 3 H) 2.07 - 2.38 (m, 4 H) 2.41 - 2.46 (m, 2 H) 3.17 - 3.23 (m, 4 H) 4.77 - 4.89 (m, 2 H) 5.39 - 5.54 (m, 1 H) 7.96 (d, J=8.1 Hz, 1 H) 8.32 (s, 2 H) 8.58 (d, J=8.1 Hz, 1 H) 8.65 (s, 1 H) 8.91 (s, 1 H) 9.64 (s, 1 H).
MS ESI/APCI Dual nega: 496[M-H}^-.
参考例３３−Ｉ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３−メチル安息香酸

Using the compound (400 mg) obtained in Reference Example 18 and 4-carboxy-3- (trifluoromethyl) phenylboronic acid (361 mg), the reaction and purification were performed in the same manner as in Reference Example 33-C. The title compound (416 mg) was obtained as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.11-1.21 (m, 3 H) 2.07-2.38 (m, 4 H) 2.41-2.46 (m, 2 H) 3.17-3.23 (m, 4 H) 4.77-4.89 (m, 2 H) 5.39-5.54 (m, 1 H) 7.96 (d, J = 8.1 Hz, 1 H) 8.32 (s, 2 H) 8.58 (d, J = 8.1 Hz, 1 H) 8.65 (s, 1 H) 8.91 (s, 1 H) 9.64 (s, 1 H).
MS ESI / APCI Dual nega: 496 [MH} ^- .
Reference Example 33-I
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 -Methylbenzoic acid

参考例１８で得られた化合物（４００ｍｇ）と参考例Ｅ−４で得られた化合物（４０５ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（３７２ｍｇ）を灰色粉末として得た。
¹¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.08 - 2.34 (m, 4 H) 2.37 (s, 3 H) 2.41 - 2.47 (m, 2 H) 3.17 - 3.28 (m, 2 H) 4.78 - 4.90 (m, 2 H) 5.37 - 5.52 (m, 1 H) 7.47 (d, J=8.2 Hz, 1 H) 7.77 - 7.90 (m, 2 H) 8.17 (s, 1 H) 8.32 (s, 2 H) 9.58 (s, 1 H).
MS ESI/APCI Dual nega: 442[M-H]^-.
参考例３３−Ｊ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３−メトキシ安息香酸

Using the compound (400 mg) obtained in Reference Example 18 and the compound (405 mg) obtained in Reference Example E-4, the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (372 mg ) Was obtained as a gray powder.
¹¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.08-2.34 (m, 4 H) 2.37 (s, 3 H) 2.41-2.47 (m, 2 H ) 3.17-3.28 (m, 2 H) 4.78-4.90 (m, 2 H) 5.37-5.52 (m, 1 H) 7.47 (d, J = 8.2 Hz, 1 H) 7.77-7.90 (m, 2 H) 8.17 (s, 1 H) 8.32 (s, 2 H) 9.58 (s, 1 H).
MS ESI / APCI Dual nega: 442 [MH] ^- .
Reference Example 33-J
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 -Methoxybenzoic acid

参考例１８で得られた化合物（４４７ｍｇ）、参考例Ｅ−１９で得られた化合物（４８０ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（４６０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.12 - 2.21 (m, 2 H) 2.29 - 2.35 (m, 2 H) 2.47 (q, J=7.6 Hz, 2 H) 3.18 - 3.26 (m, 2 H) 3.94 (s, 3 H) 4.80 - 4.86 (m, 2 H) 5.41 - 5.48 (m, 1 H) 7.67 - 7.70 (m, 2 H) 7.97 - 8.00 (m, 1 H) 8.31 (s, 2 H) 8.53 (d, J=1.2 Hz, 1 H) 9.58 (d, J=1.2 Hz, 1 H).
MS ESI posi: 460[M+H]⁺.
参考例３３−Ｋ
３−シアノ−４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

Using the compound obtained in Reference Example 18 (447 mg) and the compound obtained in Reference Example E-19 (480 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (460 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.12-2.21 (m, 2 H) 2.29-2.35 (m, 2 H) 2.47 (q, J = 7.6 Hz, 2 H) 3.18-3.26 (m, 2 H) 3.94 (s, 3 H) 4.80-4.86 (m, 2 H) 5.41-5.48 (m, 1 H) 7.67-7.70 (m, 2 H) 7.97 -8.00 (m, 1 H) 8.31 (s, 2 H) 8.53 (d, J = 1.2 Hz, 1 H) 9.58 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 460 [M + H] ⁺ .
Reference Example 33-K
3-cyano-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6 Ile} benzoic acid

参考例１８で得られた化合物（５４１ｍｇ）の１，４−ジオキサン（１３．９ｍｌ）溶液に、参考例Ｅ−２０で得られた化合物（６００ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（８０．３ｍｇ）、フッ化セシウム（４２２ｍｇ）、ヨウ化銅（２６．５ｍｇ）を加え、１００℃にて５時間攪拌した。反応液に水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣にメタノール（９．６０ｍｌ）、２Ｍ水酸化ナトリウム水溶液を加え、室温にて３時間攪拌した。反応液に水、エタノールを加え、１Ｍ水酸化ナトリウム水溶液で抽出した。水層を集め、１Ｍ塩酸で中和し、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別、溶媒を減圧留去し、表題化合物（４８４ｍｇ）を黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J=7.7 Hz, 3 H) 2.33 - 2.42 (m, 2 H) 2.42 - 2.50 (m, 2 H) 2.52 (q, J=7.7 Hz, 2 H) 3.19 - 3.30 (m, 2 H) 4.97 - 5.07 (m, 2 H) 5.14 - 5.23 (m, 1 H) 8.09 - 8.30 (m, 5 H) 8.39 - 8.48 (m, 1 H) 9.30 - 9.37 (m, 1 H).
MS ESI posi: 455[M+H]⁺.
参考例３３−Ｌ
３−クロロ−４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

To a 1,4-dioxane (13.9 ml) solution of the compound (541 mg) obtained in Reference Example 18, the compound (600 mg) obtained in Reference Example E-20, tetrakis (triphenisphosphine) palladium (80.3 mg). ), Cesium fluoride (422 mg) and copper iodide (26.5 mg) were added, and the mixture was stirred at 100 ° C. for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. Methanol (9.60 ml) and 2M aqueous sodium hydroxide solution were added to the resulting residue, and the mixture was stirred at room temperature for 3 hours. Water and ethanol were added to the reaction solution, and the mixture was extracted with 1M aqueous sodium hydroxide solution. The aqueous layer was collected, neutralized with 1M hydrochloric acid, and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to give the title compound (484 mg) as a yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J = 7.7 Hz, 3 H) 2.33-2.42 (m, 2 H) 2.42-2.50 (m, 2 H) 2.52 (q, J = 7.7 Hz, 2 H) 3.19-3.30 (m, 2 H) 4.97-5.07 (m, 2 H) 5.14-5.23 (m, 1 H) 8.09-8.30 (m, 5 H) 8.39-8.48 (m, 1 H) 9.30-9.37 (m, 1 H).
MS ESI posi: 455 [M + H] ⁺ .
Reference Example 33-L
3-chloro-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6 Ile} benzoic acid

参考例１８で得られた化合物（５００ｍｇ）と４−カルボキシ−２−クロロフェニルボロン酸（３８７ｍｇ）を用いて、参考例３３−Ｇと同様の操作にて反応及び精製を行い、表題化合物（４６６ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.07 - 2.27 (m, 2 H) 2.28 - 2.39 (m, 2 H) 2.41 - 2.48 (m, 2 H) 3.13 - 3.29 (m, 2 H) 4.77 - 4.93 (m, 2 H) 5.37 - 5.54 (m, 1 H) 7.59 (d, J=7.6 Hz, 1 H) 7.89 (d, J=7.6 Hz, 1 H) 7.98 (s, 1 H) 8.25 - 8.36 (m, 3 H) 9.60 (s, 1 H).
MS ESI/APCI Dual posi: 464[M+H]⁺.
MS ESI/APCI Dual nega: 462[M-H]^-.
参考例３３−Ｍ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３−（トリフルオロメチル）安息香酸

Using the compound (500 mg) obtained in Reference Example 18 and 4-carboxy-2-chlorophenylboronic acid (387 mg), the reaction and purification were performed in the same manner as in Reference Example 33-G, and the title compound (466 mg) Was obtained as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.07-2.27 (m, 2 H) 2.28-2.39 (m, 2 H) 2.41-2.48 (m, 2 H) 3.13-3.29 (m, 2 H) 4.77-4.93 (m, 2 H) 5.37-5.54 (m, 1 H) 7.59 (d, J = 7.6 Hz, 1 H) 7.89 (d, J = 7.6 Hz , 1 H) 7.98 (s, 1 H) 8.25-8.36 (m, 3 H) 9.60 (s, 1 H).
MS ESI / APCI Dual posi: 464 [M + H] ⁺ .
MS ESI / APCI Dual nega: 462 [MH] ^- .
Reference Example 33-M
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 -(Trifluoromethyl) benzoic acid

参考例１８で得られた化合物（５００ｍｇ）と４−カルボキシ−２−（トリフルオロメチル）フェニルボロン酸（６１１ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（２１０ｍｇ）を黒色ガム状物質として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.22 - 1.34 (m, 3 H) 2.31 - 2.59 (m, 6 H) 3.19 - 3.33 (m, 2 H) 4.96 - 5.09 (m, 2 H) 5.12 - 5.27 (m, 1 H) 7.59 - 7.70 (m, 1 H) 7.83 - 7.91 (m, 1 H) 8.25 - 8.32 (m, 1 H) 8.35 - 8.40 (m, 2 H) 8.56 (s, 1 H) 9.28 (d, J=1.2 Hz, 1 H).
MS ESI posi: 498[M+H]⁺.
参考例３３−Ｎ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸

Using the compound (500 mg) obtained in Reference Example 18 and 4-carboxy-2- (trifluoromethyl) phenylboronic acid (611 mg), the reaction and purification were performed in the same manner as in Reference Example 33-C, The title compound (210 mg) was obtained as a black gum.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.22-1.34 (m, 3 H) 2.31-2.59 (m, 6 H) 3.19-3.33 (m, 2 H) 4.96-5.09 (m, 2 H) 5.12-5.27 (m, 1 H) 7.59-7.70 (m, 1 H) 7.83-7.91 (m, 1 H) 8.25-8.32 (m, 1 H) 8.35-8.40 (m, 2 H) 8.56 (s, 1 H) 9.28 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 498 [M + H] ⁺ .
Reference Example 33-N
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 , 3-Difluorobenzoic acid

参考例１８で得られた化合物（１．００ｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（６２４ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（５４７ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6, 3 H) 2.03 - 2.38 (m, 4 H) 2.39 - 2.47 (m, 2 H) 3.13 - 3.28 (m, 2 H) 4.75 - 4.92 (m, 2 H) 5.37 - 5.55 (m, 1 H) 7.39 - 7.44 (m, 1 H) 7.58 - 7.67 (m, 1 H) 8.31 (s, 2 H) 8.39 (s, 1 H) 9.62 (d, J=1.4 Hz, 1 H).
MS ESI posi: 465[M+H]⁺.
参考例３３−Ｏ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，５−ジメチル安息香酸

Using the compound (1.00 g) obtained in Reference Example 18 and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (624 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C. To give the title compound (547 mg) as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6, 3 H) 2.03-2.38 (m, 4 H) 2.39-2.47 (m, 2 H) 3.13-3.28 (m, 2 H) 4.75-4.92 (m, 2 H) 5.37-5.55 (m, 1 H) 7.39-7.44 (m, 1 H) 7.58-7.67 (m, 1 H) 8.31 (s, 2 H) 8.39 (s, 1 H) 9.62 (d, J = 1.4 Hz, 1 H).
MS ESI posi: 465 [M + H] ⁺ .
Reference Example 33-O
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 , 5-Dimethylbenzoic acid

参考例１８で得られた化合物（５００ｍｇ）と参考例Ｅ−２２で得られた化合物（５３４ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（２７４ｍｇ）を薄茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.28 - 2.59 (m, 9 H) 2.67 (s, 3 H) 3.16 - 3.34 (m, 2 H) 4.94 - 5.27 (m, 3 H) 7.38 (s, 1 H) 7.95 - 8.12 (m, 2 H) 8.17 - 8.32 (m, 2 H) 9.26 (s, 1 H).
MS ESI nega: 456[M-H]^-.
参考例３３−Ｐ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３，５−ジメチル安息香酸

Using the compound (500 mg) obtained in Reference Example 18 and the compound (534 mg) obtained in Reference Example E-22, the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (274 mg ) As a light brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.28-2.59 (m, 9 H) 2.67 (s, 3 H) 3.16-3.34 (m, 2 H) 4.94-5.27 (m, 3 H) 7.38 (s, 1 H) 7.95-8.12 (m, 2 H) 8.17-8.32 (m, 2 H) 9.26 (s, 1 H).
MS ESI nega: 456 [MH] ^- .
Reference Example 33-P
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 , 5-Dimethylbenzoic acid

参考例１８で得られた化合物（８００ｍｇ）と参考例Ｅ−２３で得られた化合物（７６１ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（２８５ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.17 - 1.27 (m, 3 H) 2.09 (s, 6 H) 2.22 - 2.59 (m, 6 H) 3.14 - 3.33 (m, 2 H) 4.93 - 5.29 (m, 3 H) 7.82 - 7.95 (m, 3 H) 8.17 - 8.32 (m, 2 H) 9.25 - 9.33 (m, 1 H).
MS ESI posi: 458[M+H]⁺.
MS ESI nega: 456[M-H]^-.
参考例３３−Ｑ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，６−ジメチル安息香酸

Using the compound obtained in Reference Example 18 (800 mg) and the compound obtained in Reference Example E-23 (761 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (285 mg ) Was obtained as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.17-1.27 (m, 3 H) 2.09 (s, 6 H) 2.22-2.59 (m, 6 H) 3.14-3.33 (m, 2 H) 4.93-5.29 (m, 3 H) 7.82-7.95 (m, 3 H) 8.17-8.32 (m, 2 H) 9.25-9.33 (m, 1 H).
MS ESI posi: 458 [M + H] ⁺ .
MS ESI nega: 456 [MH] ^- .
Reference Example 33-Q
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 , 6-Dimethylbenzoic acid

参考例１８で得られた化合物（８００ｍｇ）と参考例Ｅ−２４で得られた化合物（１．０５ｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（５８５ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.07 - 2.54 (m, 12 H) 3.11 - 3.30 (m, 2 H) 4.75 - 4.90 (m, 2 H) 5.36 - 5.52 (m, 1 H) 7.90 (s, 2 H) 8.32 (s, 2 H) 8.61 (s, 1 H) 9.55 (s, 1 H).
MS ESI nega: 456[M-H]^-.
参考例３３−Ｒ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−５−フルオロ−２−メチル安息香酸

Using the compound (800 mg) obtained in Reference Example 18 and the compound (1.05 g) obtained in Reference Example E-24, the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (585 mg) was obtained as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.07-2.54 (m, 12 H) 3.11-3.30 (m, 2 H) 4.75-4.90 (m, 2 H) 5.36-5.52 (m, 1 H) 7.90 (s, 2 H) 8.32 (s, 2 H) 8.61 (s, 1 H) 9.55 (s, 1 H).
MS ESI nega: 456 [MH] ^- .
Reference Example 33-R
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -5 -Fluoro-2-methylbenzoic acid

参考例１８で得られた化合物（０．５ｇ）と参考例Ｅ−２５で得られた化合物（０．５４ｇ）を用いて、参考例１７と同様の操作にて反応及び精製を行い、表題化合物（０．５４ｇ）を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.5 Hz, 3 H) 2.09 - 2.49 (m, 6 H) 2.59 (s, 3 H) 3.14 - 3.29 (m, 2 H) 4.76 - 4.91 (m, 2 H) 5.37 - 5.54 (m, 1 H) 7.74 (d, J=11.8 Hz, 1 H) 7.89 - 7.99 (m, 1 H) 8.32 (s, 2 H) 8.45 (s, 1 H) 9.61 - 9.66 (m, 1 H).
参考例３３−Ｓ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−フルオロ−３−メチル安息香酸

Using the compound (0.5 g) obtained in Reference Example 18 and the compound (0.54 g) obtained in Reference Example E-25, the reaction and purification were carried out in the same manner as in Reference Example 17, to obtain the title compound. (0.54 g) was obtained.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.5 Hz, 3 H) 2.09-2.49 (m, 6 H) 2.59 (s, 3 H) 3.14-3.29 (m, 2 H ) 4.76-4.91 (m, 2 H) 5.37-5.54 (m, 1 H) 7.74 (d, J = 11.8 Hz, 1 H) 7.89-7.99 (m, 1 H) 8.32 (s, 2 H) 8.45 (s , 1 H) 9.61-9.66 (m, 1 H).
Reference Example 33-S
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluoro-3-methylbenzoic acid

参考例１８で得られた化合物（５００ｍｇ）と参考例Ｅ−２６で得られた化合物（５４１ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（１００ｍｇ）を茶色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.7 Hz, 3 H) 2.12 - 2.49 (m, 9 H) 3.14 - 3.28 (m, 2 H) 4.78 - 4.90 (m, 2 H) 5.40 - 5.54 (m, 1 H) 7.37 - 7.44 (m, 1 H) 7.74 - 7.82 (m, 1 H) 8.27 (s, 1 H) 8.32 (s, 2 H) 9.62 (s, 1 H).
MS ESI nega: 460[M-H]^-.
参考例３３−Ｔ
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−３−フルオロ−２−メチル安息香酸

Using the compound obtained in Reference Example 18 (500 mg) and the compound obtained in Reference Example E-26 (541 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (100 mg ) As a brown powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.7 Hz, 3 H) 2.12-2.49 (m, 9 H) 3.14-3.28 (m, 2 H) 4.78-4.90 (m, 2 H) 5.40-5.54 (m, 1 H) 7.37-7.44 (m, 1 H) 7.74-7.82 (m, 1 H) 8.27 (s, 1 H) 8.32 (s, 2 H) 9.62 (s, 1 H ).
MS ESI nega: 460 [MH] ^- .
Reference Example 33-T
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -3 -Fluoro-2-methylbenzoic acid

参考例１８で得られた化合物（８００ｍｇ）と参考例Ｅ−２７で得られた化合物（９８１ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（７９７ｍｇ）を橙色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.4 Hz, 2 H) 2.12 - 2.21 (m, 2 H) 2.29 - 2.36 (m, 2 H) 2.44 - 2.51 (m, 5 H) 3.17 - 3.26 (m, 2 H) 4.79 - 4.86 (m, 2 H) 5.41 - 5.49 (m, 1 H) 7.53 - 7.59 (m, 1 H) 7.73 - 7.79 (m, 1 H) 8.32 (s, 2 H) 8.38 (s, 1 H) 9.58 - 9.62 (m, 1 H).
MS ESI posi: 462[M+H]⁺.
MS ESI nega: 460[M-H]^-.
参考例３４−Ａ
２，３−ジフルオロ−４−（３−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）安息香酸

Using the compound obtained in Reference Example 18 (800 mg) and the compound obtained in Reference Example E-27 (981 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (797 mg ) As an orange powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.4 Hz, 2 H) 2.12-2.21 (m, 2 H) 2.29-2.36 (m, 2 H) 2.44-2.51 (m, 5 H) 3.17-3.26 (m, 2 H) 4.79-4.86 (m, 2 H) 5.41-5.49 (m, 1 H) 7.53-7.59 (m, 1 H) 7.73-7.79 (m, 1 H) 8.32 ( s, 2 H) 8.38 (s, 1 H) 9.58-9.62 (m, 1 H).
MS ESI posi: 462 [M + H] ⁺ .
MS ESI nega: 460 [MH] ^- .
Reference Example 34-A
2,3-difluoro-4- (3- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5-c] pyridine- 6-yl) benzoic acid

参考例２８で得られた化合物（５００ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（６４４ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（５５９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.24 (d, J=6.2 Hz, 6 H) 2.04 - 2.34 (m, 4 H) 3.02 - 3.21 (m, 2 H) 4.10 - 4.27 (m, 2 H) 4.77 - 4.91 (m, 1 H) 5.27 - 5.43 (m, 1 H) 7.48 (t, J=7.5 Hz, 1 H) 7.61 - 7.71 (m, 1 H) 8.41 (s, 1 H) 9.61 (s, 1 H).
MS ESI nega: 444[M-H]^-.
参考例３４−Ｂ
２−フルオロ−４−（３−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）安息香酸

Using the compound (500 mg) obtained in Reference Example 28 and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (644 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C. The title compound (559 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.24 (d, J = 6.2 Hz, 6 H) 2.04-2.34 (m, 4 H) 3.02-3.21 (m, 2 H) 4.10-4.27 (m, 2 H) 4.77-4.91 (m, 1 H) 5.27-5.43 (m, 1 H) 7.48 (t, J = 7.5 Hz, 1 H) 7.61-7.71 (m, 1 H) 8.41 (s, 1 H) 9.61 (s, 1 H).
MS ESI nega: 444 [MH] ^- .
Reference Example 34-B
2-Fluoro-4- (3- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il) Benzoic acid

参考例２８で得られた化合物（３００ｍｇ）と参考例Ｅ−５で得られた化合物（２２５ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（２６３ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.23 (d, J=6.2 Hz, 6 H) 2.04 - 2.32 (m, 4 H) 3.01 - 3.22 (m, 2 H) 4.10 - 4.28 (m, 2 H) 4.77 - 4.89 (m, 1 H) 5.27 - 5.42 (m, 1 H) 7.95 - 8.21 (m, 3 H) 8.82 - 8.85 (m, 1 H) 9.58 - 9.62 (m, 1 H).
参考例３４−Ｃ
３−フルオロ−４−（３−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）安息香酸

Using the compound (300 mg) obtained in Reference Example 28 and the compound (225 mg) obtained in Reference Example E-5, the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (263 mg ) Was obtained as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.23 (d, J = 6.2 Hz, 6 H) 2.04-2.32 (m, 4 H) 3.01-3.22 (m, 2 H) 4.10-4.28 (m, 2 H) 4.77-4.89 (m, 1 H) 5.27-5.42 (m, 1 H) 7.95-8.21 (m, 3 H) 8.82-8.85 (m, 1 H) 9.58-9.62 (m, 1 H).
Reference Example 34-C
3-Fluoro-4- (3- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il) Benzoic acid

参考例２８で得られた化合物（５００ｍｇ）と参考例Ｅ−２で得られた化合物（５４２ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（６１６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.24 (d, J=6.4 Hz, 6 H) 2.04 - 2.34 (m, 4 H) 3.02 - 3.20 (m, 2 H) 4.20 (m, 2 H) 4.77 - 4.90 (m, 1 H) 5.28 - 5.44 (m, 1 H) 7.77 - 7.86 (m, 1 H) 7.92 (dd, J=8.0, 1.3 Hz, 1 H) 8.14 (t, J=8.0 Hz, 1 H) 8.49 (s, 1 H) 9.65 (s, 1 H).
MS ESI nega: 426[M-H]^-.
参考例３４−Ｄ
２，５−ジフルオロ−４−（３−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）安息香酸

Using the compound (500 mg) obtained in Reference Example 28 and the compound (542 mg) obtained in Reference Example E-2, the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (616 mg). ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.24 (d, J = 6.4 Hz, 6 H) 2.04-2.34 (m, 4 H) 3.02-3.20 (m, 2 H) 4.20 (m, 2 H ) 4.77-4.90 (m, 1 H) 5.28-5.44 (m, 1 H) 7.77-7.86 (m, 1 H) 7.92 (dd, J = 8.0, 1.3 Hz, 1 H) 8.14 (t, J = 8.0 Hz , 1 H) 8.49 (s, 1 H) 9.65 (s, 1 H).
MS ESI nega: 426 [MH] ^- .
Reference Example 34-D
2,5-difluoro-4- (3- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5-c] pyridine- 6-yl) benzoic acid

参考例２８で得られた化合物（１．１０ｇ）と参考例Ｅ−１０で得られた化合物（１．２８ｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（３５２ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.23 (d, J=6.2 Hz, 6 H) 1.88 - 2.12 (m, 4 H) 2.97 - 3.19 (m, 2 H) 4.08 - 4.25 (m, 2 H) 4.76 - 4.89 (m, 1 H) 5.06 - 5.22 (m, 1 H) 7.77 (dd, J=11.7, 6.4 Hz, 1 H) 7.95 (dd, J=11.7, 6.4 Hz, 1 H) 8.32 (s, 1 H) 8.36 (s, 1 H) 9.43 (s, 1 H).
MS ESI nega: 443[M-H]^-.
参考例３４−Ｅ
３−メチル−４−（３−｛１−［（プロパン−２−イルオキシ）カルボニル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）安息香酸

Using the compound obtained in Reference Example 28 (1.10 g) and the compound obtained in Reference Example E-10 (1.28 g), the reaction and purification were performed in the same manner as in Reference Example 33-C. The title compound (352 mg) was obtained as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.23 (d, J = 6.2 Hz, 6 H) 1.88-2.12 (m, 4 H) 2.97-3.19 (m, 2 H) 4.08-4.25 (m, 2 H) 4.76-4.89 (m, 1 H) 5.06-5.22 (m, 1 H) 7.77 (dd, J = 11.7, 6.4 Hz, 1 H) 7.95 (dd, J = 11.7, 6.4 Hz, 1 H) 8.32 (s, 1 H) 8.36 (s, 1 H) 9.43 (s, 1 H).
MS ESI nega: 443 [MH] ^- .
Reference Example 34-E
3-methyl-4- (3- {1-[(propan-2-yloxy) carbonyl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il) Benzoic acid

参考例２８で得られた化合物（５００ｍｇ）と参考例Ｅ−４で得られた化合物（５３４ｍｇ）を用いて、参考例３３−Ｃと同様の操作にて反応及び精製を行い、表題化合物（４８５ｍｇ）を無色ガム状物質として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.24 (d, J=6.2 Hz, 6 H) 2.06 - 2.33 (m, 4 H) 2.40 (s, 3 H) 3.02 - 3.20 (m, 2 H) 4.10 - 4.30 (m, 2 H) 4.78 - 4.89 (m, 1 H) 5.28 - 5.43 (m, 1 H) 7.58 (d, J=8.1 Hz, 1 H) 7.83 - 7.96 (m, 2 H) 8.24 (s, 1 H) 9.59 (s, 1 H).
MS ESI nega: 422[M-H]^-.
参考例３５−Ａ
４−｛３−［１−（５−クロロピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸
（１）６−クロロ−３−［１−（５−クロロピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Using the compound obtained in Reference Example 28 (500 mg) and the compound obtained in Reference Example E-4 (534 mg), the reaction and purification were carried out in the same manner as in Reference Example 33-C to give the title compound (485 mg ) Was obtained as a colorless gum.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.24 (d, J = 6.2 Hz, 6 H) 2.06-2.33 (m, 4 H) 2.40 (s, 3 H) 3.02-3.20 (m, 2 H ) 4.10-4.30 (m, 2 H) 4.78-4.89 (m, 1 H) 5.28-5.43 (m, 1 H) 7.58 (d, J = 8.1 Hz, 1 H) 7.83-7.96 (m, 2 H) 8.24 (s, 1 H) 9.59 (s, 1 H).
MS ESI nega: 422 [MH] ^- .
Reference Example 35-A
4- {3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 , 3-Difluorobenzoic acid (1) 6-chloro-3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5- c] pyridine

参考例３０で得られた化合物（８００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１６．８ｍｌ）溶液へ、２，５−ジクロロピリミジン（６０２ｍｇ）、炭酸セシウム（２．２０ｇ）を加え、７０℃にて１５時間攪拌した。反応液へ水を加え、析出物をろ取、水、続いてヘキサンにて洗浄し、表題化合物（１．００ｇ）を薄黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.29 - 2.43 (m, 4 H) 3.21 - 3.30 (m, 2 H) 4.93 - 5.00 (m, 2 H) 5.08 (s, 1 H) 8.00 (d, J=1.2 Hz, 1 H) 8.29 (s, 2 H) 8.94 (d, J=1.2 Hz, 1 H).
MS ESI posi: 350[M+H]⁺.
（２）４−｛３−［１−（５−クロロピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸

To a solution of the compound obtained in Reference Example 30 (800 mg) in N, N-dimethylformamide (16.8 ml), 2,5-dichloropyrimidine (602 mg) and cesium carbonate (2.20 g) were added, and at 70 ° C. Stir for 15 hours. Water was added to the reaction mixture, and the precipitate was collected by filtration and washed with water and then with hexane to obtain the title compound (1.00 g) as a pale yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.29-2.43 (m, 4 H) 3.21-3.30 (m, 2 H) 4.93-5.00 (m, 2 H) 5.08 (s, 1 H) 8.00 (d , J = 1.2 Hz, 1 H) 8.29 (s, 2 H) 8.94 (d, J = 1.2 Hz, 1 H).
MS ESI posi: 350 [M + H] ⁺ .
(2) 4- {3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl } -2,3-Difluorobenzoic acid

参考例３５−Ａ（１）で得られた化合物（８００ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（９２３ｍｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（２００ｍｇ）を薄黄色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 2.15 - 2.25 (m, 2 H) 2.32 - 2.38 (m, 2 H) 3.23 - 3.35 (m, 2 H) 4.76 - 4.84 (m, 2 H) 5.45 - 5.53 (m, 1 H) 7.56 - 7.63 (m, 1 H) 7.71 - 7.78 (m, 1 H) 8.46 (s, 1 H) 8.48 (s, 2 H) 9.65 (s, 1 H).
MS ESI posi: 472[M+H]⁺.
MS ESI nega: 470[M-H]^-.
参考例３５−Ｂ
２，３−ジフルオロ−４−｛３−［１−（５−メチルピリジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸
（１）６−クロロ−３−［１−（５−メチルピリジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Using the compound (800 mg) obtained in Reference Example 35-A (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (923 mg), the reaction and reaction were performed in the same manner as in Reference Example 31. Purification was performed to give the title compound (200 mg) as a pale yellow powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 2.15-2.25 (m, 2 H) 2.32-2.38 (m, 2 H) 3.23-3.35 (m, 2 H) 4.76-4.84 (m, 2 H) 5.45-5.53 (m, 1 H) 7.56-7.63 (m, 1 H) 7.71-7.78 (m, 1 H) 8.46 (s, 1 H) 8.48 (s, 2 H) 9.65 (s, 1 H).
MS ESI posi: 472 [M + H] ⁺ .
MS ESI nega: 470 [MH] ^- .
Reference Example 35-B
2,3-difluoro-4- {3- [1- (5-methylpyridin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine- 6-yl} benzoic acid (1) 6-chloro-3- [1- (5-methylpyridin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5- c] pyridine

参考例３０で得られた化合物（５００ｍｇ）、２−ブロモ−５−メチルピリジン（５４３ｍｇ）、トリス（ジベンジリデンアセトン）ジパラジウム（１９２ｍｇ）、ｒａｃ−２，２’−ビス（ジフェニルホスフィノ）−１，１’−ビナフチル（３９２ｍｇ）、ナトリウム ｔｅｒｔ−ブトキシド（３０３ｍｇ）のジメトキシエタン溶液（２０ｍｌ）をアルゴン雰囲気下、９０℃で３時間攪拌した。温度を室温まで下げた後、反応溶液をセライト（登録商標）濾過し、濾液を濃縮した。得られた残差をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜０：１）で精製、さらに酢酸エチル−エタノール−ヘキサンから再結晶して、表題化合物（３８０ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.24 (s, 7 H) 3.02 - 3.24 (m, 2 H) 4.39 - 4.60 (m, 2 H) 4.94 - 5.19 (m, 1 H) 6.66 - 6.76 (m, 1 H) 7.32 - 7.43 (m, 1 H) 7.97 - 8.02 (m, 1 H) 8.04 - 8.10 (m, 1 H) 8.90 - 8.96 (m, 1 H).
MS ESI/APCI Dual posi: 329[M+H]⁺, 351[M+Na]⁺.
（２）２，３−ジフルオロ−４−｛３−［１−（５−メチルピリジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

Compound (500 mg) obtained in Reference Example 30, 2-bromo-5-methylpyridine (543 mg), tris (dibenzylideneacetone) dipalladium (192 mg), rac-2,2′-bis (diphenylphosphino)- A solution of 1,1′-binaphthyl (392 mg) and sodium tert-butoxide (303 mg) in dimethoxyethane (20 ml) was stirred at 90 ° C. for 3 hours under an argon atmosphere. After the temperature was lowered to room temperature, the reaction solution was filtered through Celite (registered trademark), and the filtrate was concentrated. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 0: 1) and recrystallized from ethyl acetate-ethanol-hexane to give the title compound (380 mg) as a colorless product. Obtained as a powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.24 (s, 7 H) 3.02-3.24 (m, 2 H) 4.39-4.60 (m, 2 H) 4.94-5.19 (m, 1 H) 6.66-6.76 (m, 1 H) 7.32-7.43 (m, 1 H) 7.97-8.02 (m, 1 H) 8.04-8.10 (m, 1 H) 8.90-8.96 (m, 1 H).
MS ESI / APCI Dual posi: 329 [M + H] ⁺ , 351 [M + Na] ⁺ .
(2) 2,3-difluoro-4- {3- [1- (5-methylpyridin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c ] Pyridin-6-yl} benzoic acid

参考例３５−Ｂ（１）で得られた化合物（３３０ｍｇ）を用いて、参考例３１と同様の反応、精製を行い、表題化合物（２２２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.16 - 2.45 (m, 7 H) 3.27 - 3.75 (m, 2 H) 4.45 - 4.60 (m, 2 H) 5.43 - 5.63 (m, 1 H) 7.95 (s, 5 H) 8.54 (s, 1 H) 9.70 (s, 1 H).
MS ESI/APCI Dual posi: 451[M+H]⁺.
参考例３５−Ｃ
２，３−ジフルオロ−４−［３−（１−｛［（１−メチルシクロプロピル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸
（１）（１−メチルシクロプロピル）メチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (330 mg) obtained in Reference Example 35-B (1), the same reaction and purification as in Reference Example 31 were carried out to obtain the title compound (222 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.16-2.45 (m, 7 H) 3.27-3.75 (m, 2 H) 4.45-4.60 (m, 2 H) 5.43-5.63 (m, 1 H) 7.95 (s, 5 H) 8.54 (s, 1 H) 9.70 (s, 1 H).
MS ESI / APCI Dual posi: 451 [M + H] ⁺ .
Reference Example 35-C
2,3-difluoro-4- [3- (1-{[(1-methylcyclopropyl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c ] Pyridin-6-yl] benzoic acid (1) (1-methylcyclopropyl) methyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) Piperidine-1-carboxylate

参考例３０で得られた化合物（１．００ｇ）と１−メチルシクロプロパンメタノール（７２５ｍｇ）を用いて、参考例２３−Ｇと同様の操作にて反応及び精製を行い、表題化合物（８９０ｍｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.37 - 0.41 (m, 2 H) 0.50 - 0.54 (m, 2 H) 1.16 (s, 3 H) 2.23 - 2.31 (m, 2 H) 2.32 - 2.41 (m, 2 H) 3.05 - 3.26 (m, 2 H) 3.95 (s, 2 H) 4.36 - 4.49 (m, 2 H) 4.93 - 5.02 (m, 1 H) 8.01 (d, J=0.8 Hz, 1 H) 8.94 (d, J=0.8 Hz, 1 H).
MS ESI posi: 350[M+H]⁺.
（２）２，３−ジフルオロ−４−［３−（１−｛［（１−メチルシクロプロピル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸

Using the compound (1.00 g) obtained in Reference Example 30 and 1-methylcyclopropanemethanol (725 mg), the reaction and purification were conducted in the same manner as in Reference Example 23-G, and the title compound (890 mg) was obtained. Obtained as a pale yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.37-0.41 (m, 2 H) 0.50-0.54 (m, 2 H) 1.16 (s, 3 H) 2.23-2.31 (m, 2 H) 2.32-2.41 (m, 2 H) 3.05-3.26 (m, 2 H) 3.95 (s, 2 H) 4.36-4.49 (m, 2 H) 4.93-5.02 (m, 1 H) 8.01 (d, J = 0.8 Hz, 1 H) 8.94 (d, J = 0.8 Hz, 1 H).
MS ESI posi: 350 [M + H] ⁺ .
(2) 2,3-Difluoro-4- [3- (1-{[(1-methylcyclopropyl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4 5-c] pyridin-6-yl] benzoic acid

参考例３５−Ｃ（１）で得られた化合物（４５０ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（３９１ｍｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（４１４ｍｇ）を薄黄色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 0.32 - 0.38 (m, 2 H) 0.47 - 0.53 (m, 2 H) 1.12 (s, 3 H) 2.09 - 2.21 (m, 2 H) 2.25 - 2.33 (m, 2 H) 3.04 - 3.26 (m, 2 H) 3.88 (s, 2 H) 4.18 - 4.25 (m, 2 H) 5.33 - 5.42 (m, 1 H) 7.38 - 7.46 (m, 1 H) 7.60 - 7.66 (m, 1 H) 8.38 - 8.43 (m, 1 H) 9.59 - 9.62 (m, 1 H).
MS ESI posi: 472[M+H]⁺.
MS ESI nega: 470[M-H]^-.
参考例３５−Ｄ
４−［３−（１−｛［（２Ｒ）−ブタン−２−イルオキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］−２，３−ジフルオロ安息香酸
（１）（２Ｒ）−ブタン−２−イル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (450 mg) obtained in Reference Example 35-C (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (391 mg), the reaction and reaction were carried out in the same manner as in Reference Example 31. Purification was performed to give the title compound (414 mg) as a pale yellow powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 0.32-0.38 (m, 2 H) 0.47-0.53 (m, 2 H) 1.12 (s, 3 H) 2.09-2.21 (m, 2 H) 2.25- 2.33 (m, 2 H) 3.04-3.26 (m, 2 H) 3.88 (s, 2 H) 4.18-4.25 (m, 2 H) 5.33-5.42 (m, 1 H) 7.38-7.46 (m, 1 H) 7.60-7.66 (m, 1 H) 8.38-8.43 (m, 1 H) 9.59-9.62 (m, 1 H).
MS ESI posi: 472 [M + H] ⁺ .
MS ESI nega: 470 [MH] ^- .
Reference Example 35-D
4- [3- (1-{[(2R) -butan-2-yloxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Yl] -2,3-difluorobenzoic acid (1) (2R) -butan-2-yl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridine-3- Yl) piperidine-1-carboxylate

参考例３０で得られた化合物（５００ｍｇ）と（Ｒ）−（−）−２−ブタノール（３１２ｍｇ）を用いて、参考例２３−Ｇと同様の操作にて反応及び精製を行い、表題化合物（７１１ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.94 (t, J=7.5 Hz, 3 H) 1.27 (d, J=6.4 Hz, 3 H) 1.55 - 1.72 (m, 2 H) 2.19 - 2.45 (m, 4 H) 3.02 - 3.21 (m, 2 H) 4.31 - 4.51 (m, 2 H) 4.75 - 5.03 (m, 2 H) 8.01 (d, J=1.1 Hz, 1 H) 8.94 (d, J=1.1 Hz, 1 H).
MS ESI/APCI Dual posi: 360[M+Na]⁺.
（２）４−［３−（１−｛［（２Ｒ）−ブタン−２−イルオキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］−２，３−ジフルオロ安息香酸

Using the compound (500 mg) obtained in Reference Example 30 and (R)-(−)-2-butanol (312 mg), the reaction and purification were performed in the same manner as in Reference Example 23-G, and the title compound ( 711 mg) as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.94 (t, J = 7.5 Hz, 3 H) 1.27 (d, J = 6.4 Hz, 3 H) 1.55-1.72 (m, 2 H) 2.19-2.45 ( m, 4 H) 3.02-3.21 (m, 2 H) 4.31-4.51 (m, 2 H) 4.75-5.03 (m, 2 H) 8.01 (d, J = 1.1 Hz, 1 H) 8.94 (d, J = 1.1 Hz, 1 H).
MS ESI / APCI Dual posi: 360 [M + Na] ⁺ .
(2) 4- [3- (1-{[(2R) -butan-2-yloxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridine -6-yl] -2,3-difluorobenzoic acid

参考例３５−Ｄ（１）で得られた化合物（７１１ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（６３７ｍｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（２６３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.90 (t, J=7.4 Hz, 3 H) 1.20 (d, J=6.2 Hz, 3 H) 1.45 - 1.68 (m, 2 H) 2.00 - 2.36 (m, 4 H) 3.00 - 3.22 (m, 2 H) 4.10 - 4.26 (m, 2 H) 4.60 - 4.74 (m, 1 H) 5.26 - 5.45 (m, 1 H) 7.40 - 7.49 (m, 1 H) 7.60 - 7.68 (m, 1 H) 8.39 - 8.43 (m, 1 H) 9.60 (d, J=1.2 Hz, 1 H).
参考例３５−Ｅ
２，３−ジフルオロ−４−［３−（１−｛［（１Ｓ）−１−フェニルエトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸
（１）（１Ｓ）−１−フェニルエチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (711 mg) obtained in Reference Example 35-D (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (637 mg), the reaction and Purification was performed to give the title compound (263 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 0.90 (t, J = 7.4 Hz, 3 H) 1.20 (d, J = 6.2 Hz, 3 H) 1.45-1.68 (m, 2 H) 2.00-2.36 (m, 4 H) 3.00-3.22 (m, 2 H) 4.10-4.26 (m, 2 H) 4.60-4.74 (m, 1 H) 5.26-5.45 (m, 1 H) 7.40-7.49 (m, 1 H ) 7.60-7.68 (m, 1 H) 8.39-8.43 (m, 1 H) 9.60 (d, J = 1.2 Hz, 1 H).
Reference Example 35-E
2,3-difluoro-4- [3- (1-{[(1S) -1-phenylethoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c ] Pyridin-6-yl] benzoic acid (1) (1S) -1-phenylethyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) Piperidine-1-carboxylate

参考例３０で得られた化合物（１．０ｇ）、（１Ｓ）−１−フェニルエタノール（１．５ｇ）を用いて参考例２３−Ｇと同様の反応、精製を行い、表題化合物（０．８ｇ）を薄黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (d, J=6.5 Hz, 3 H) 2.18 - 2.45 (m, 4 H) 3.02 - 3.25 (m, 2 H) 4.37 - 4.50 (m, 2 H) 4.89 - 5.05 (m, 1 H) 5.87 (q, J=6.5 Hz, 1 H) 7.28 - 7.41 (m, 5 H) 8.00 (s, 1 H) 8.91 (s, 1 H).
MS ESI/APCI Dual posi: 408[M+H]⁺.
（２）２，３−ジフルオロ−４−［３−（１−｛［（１Ｓ）−１−フェニルエトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸

Using the compound (1.0 g) obtained in Reference Example 30 and (1S) -1-phenylethanol (1.5 g), the same reaction and purification as in Reference Example 23-G were carried out, and the title compound (0.8 g ) Was obtained as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (d, J = 6.5 Hz, 3 H) 2.18-2.45 (m, 4 H) 3.02-3.25 (m, 2 H) 4.37-4.50 (m, 2 H) 4.89-5.05 (m, 1 H) 5.87 (q, J = 6.5 Hz, 1 H) 7.28-7.41 (m, 5 H) 8.00 (s, 1 H) 8.91 (s, 1 H).
MS ESI / APCI Dual posi: 408 [M + H] ⁺ .
(2) 2,3-difluoro-4- [3- (1-{[(1S) -1-phenylethoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4 5-c] pyridin-6-yl] benzoic acid

参考例３５−Ｅ（１）で得られた化合物（４００ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（３３８ｍｇ）を用いて、を用いて、参考例３１と同様の反応、精製を行い、表題化合物（３００ｍｇ）を薄黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (d, J=6.2 Hz, 3 H) 2.18 - 2.48 (m, 4 H) 3.03 - 3.28 (m, 2 H) 4.35 - 4.54 (m, 2 H) 4.93 - 5.14 (m, 1 H) 5.81 - 5.95 (m, 1 H) 7.29 - 7.42 (m, 5 H) 7.66 - 7.98 (m, 2 H) 8.34 - 8.54 (m, 1 H) 9.18 - 9.35 (m, 1 H).
MS ESI/APCI Dual posi: 508[M+H]⁺, 530[M+Na]⁺.
参考例３５−Ｆ
２，３−ジフルオロ−４−［３−（１−｛［（５−フルオロピリジン−２−イル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸
（１）（５−フルオロピリジン−２−イル）メチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (400 mg) obtained in Reference Example 35-E (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (338 mg), the same reaction as in Reference Example 31 The title compound (300 mg) was obtained as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.59 (d, J = 6.2 Hz, 3 H) 2.18-2.48 (m, 4 H) 3.03-3.28 (m, 2 H) 4.35-4.54 (m, 2 H) 4.93-5.14 (m, 1 H) 5.81-5.95 (m, 1 H) 7.29-7.42 (m, 5 H) 7.66-7.98 (m, 2 H) 8.34-8.54 (m, 1 H) 9.18-9.35 (m, 1 H).
MS ESI / APCI Dual posi: 508 [M + H] ⁺ , 530 [M + Na] ⁺ .
Reference Example 35-F
2,3-difluoro-4- [3- (1-{[(5-fluoropyridin-2-yl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4 5-c] pyridin-6-yl] benzoic acid (1) (5-fluoropyridin-2-yl) methyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] Pyridin-3-yl) piperidine-1-carboxylate

５−フルオロ−２−ヒドロキシメチルピリジン（３７４ｍｇ）のクロロホルム（１５ｍｌ）溶液にクロロぎ酸４−ニトロフェニル（５９４ｍｇ）とトリエチルアミン（８１９μｌ）を加え、室温で３時間攪拌した。その中へ参考例３０で得られた化合物（３５０ｍｇ）とトリエチルアミン（８１９μｌ）を加え、室温でさらに一晩攪拌した。反応液に１Ｍ水酸化カリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層を１Ｍ水酸化カリウム水溶液にて洗浄後、フェーズセパレーターを通して、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１００：０〜９５：５）にて精製後、ヘキサンで粉末化し、表題化合物（５３０ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.18 - 2.47 (m, 4 H) 3.08 - 3.30 (m, 2 H) 4.34 - 4.52 (m, 2 H) 4.89 - 5.07 (m, 1 H) 5.24 - 5.30 (m, 2 H) 7.37 - 7.45 (m, 2 H) 8.01 (d, J=1.1 Hz, 1 H) 8.48 (d, J=2.2 Hz, 1 H) 8.94 (d, J=1.1 Hz, 1 H).
MS ESI/APCI Dual posi: 413[M+Na]⁺.
MS ESI/APCI Dual nega: 425[M+Cl]^-.
（２）２，３−ジフルオロ−４−［３−（１−｛［（５−フルオロピリジン−２−イル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸

To a solution of 5-fluoro-2-hydroxymethylpyridine (374 mg) in chloroform (15 ml) were added 4-nitrophenyl chloroformate (594 mg) and triethylamine (819 μl), and the mixture was stirred at room temperature for 3 hours. The compound (350 mg) obtained in Reference Example 30 and triethylamine (819 μl) were added thereto, and the mixture was further stirred overnight at room temperature. To the reaction solution was added 1M aqueous potassium hydroxide solution, and the mixture was extracted with chloroform. The obtained organic layer was washed with 1M aqueous potassium hydroxide solution, and then the solvent was distilled off under reduced pressure through a phase separator. The obtained residue was purified by NH silica gel column chromatography (developing solvent: chloroform: methanol = 100: 0 to 95: 5) and then pulverized with hexane to obtain the title compound (530 mg) as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.18-2.47 (m, 4 H) 3.08-3.30 (m, 2 H) 4.34-4.52 (m, 2 H) 4.89-5.07 (m, 1 H) 5.24 -5.30 (m, 2 H) 7.37-7.45 (m, 2 H) 8.01 (d, J = 1.1 Hz, 1 H) 8.48 (d, J = 2.2 Hz, 1 H) 8.94 (d, J = 1.1 Hz, 1 H).
MS ESI / APCI Dual posi: 413 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 425 [M + Cl] ^- .
(2) 2,3-difluoro-4- [3- (1-{[(5-fluoropyridin-2-yl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl] benzoic acid

参考例３５−Ｆ（１）で得られた化合物（５３０ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（４１１ｍｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（９６．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.09 - 2.36 (m, 4 H) 3.22 - 3.41 (m, 2 H) 4.16 - 4.33 (m, 2 H) 5.20 (s, 2 H) 5.29 - 5.47 (m, 1 H) 7.39 - 7.49 (m, 1 H) 7.51 - 7.58 (m, 1 H) 7.60 - 7.69 (m, 1 H) 7.74 - 7.83 (m, 1 H) 8.38 - 8.45 (m, 1 H) 8.54 - 8.60 (m, 1 H) 9.62 (d, J=1.2 Hz, 1 H).
MS ESI/APCI Dual nega: 511[M-H]^-.
参考例３５−Ｇ
４−｛３−［１−（２，２−ジメチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸
（１）６−クロロ−３−［１−（２，２−ジメチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Using the compound obtained in Reference Example 35-F (1) (530 mg) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (411 mg), the reaction and Purification was performed to give the title compound (96.8 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.09-2.36 (m, 4 H) 3.22-3.41 (m, 2 H) 4.16-4.33 (m, 2 H) 5.20 (s, 2 H) 5.29- 5.47 (m, 1 H) 7.39-7.49 (m, 1 H) 7.51-7.58 (m, 1 H) 7.60-7.69 (m, 1 H) 7.74-7.83 (m, 1 H) 8.38-8.45 (m, 1 H) 8.54-8.60 (m, 1 H) 9.62 (d, J = 1.2 Hz, 1 H).
MS ESI / APCI Dual nega: 511 [MH] ^- .
Reference Example 35-G
4- {3- [1- (2,2-dimethylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3 -Difluorobenzoic acid (1) 6-chloro-3- [1- (2,2-dimethylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例３０で得られた化合物（０．５ｇ）、ピバルアルデヒド（０．９４ｍｌ）、酢酸（０．５ｍｌ）のテトラヒドロフラン（２．５ｍｌ）−Ｎ，Ｎ−ジメチルホルムアミド（２．５ｍｌ）懸濁液にナトリウムトリアセトキシボロヒドリド（２．２ｇ）を室温で加えて、一晩撹拌後、６０℃で１時間撹拌した。反応液に飽和炭酸水素ナトリウム水溶液を加えた後、クロロホルムで２回抽出した。その後、有機層を５％食塩水で洗浄し、無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（１回目：展開溶媒 クロロホルム：メタノール＝９９：１〜９０：１０、２回目：展開溶媒 ヘキサン：酢酸エチル＝９９：５〜７５：２５）にて精製し、表題化合物（０．５ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.92 (s, 9 H) 2.07 - 2.23 (m, 4 H) 2.35 - 2.63 (m, 4 H) 2.96 - 3.12 (m, 2 H) 4.68 - 4.83 (m, 1 H) 7.99 (d, J=1.1 Hz, 1 H) 8.97 (d, J=1.1 Hz, 1 H).
（２）４−｛３−［１−（２，２−ジメチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸

A suspension of the compound (0.5 g), pivalaldehyde (0.94 ml), and acetic acid (0.5 ml) obtained in Reference Example 30 in tetrahydrofuran (2.5 ml) -N, N-dimethylformamide (2.5 ml). Sodium triacetoxyborohydride (2.2 g) was added to the solution at room temperature, stirred overnight, and then stirred at 60 ° C. for 1 hour. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the mixture was extracted twice with chloroform. Thereafter, the organic layer was washed with 5% brine, dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (first time: developing solvent chloroform: methanol = 99: 1 to 90:10, second time: developing solvent hexane: ethyl acetate = 99: 5-75: 25). To give the title compound (0.5 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.92 (s, 9 H) 2.07-2.23 (m, 4 H) 2.35-2.63 (m, 4 H) 2.96-3.12 (m, 2 H) 4.68-4.83 (m, 1 H) 7.99 (d, J = 1.1 Hz, 1 H) 8.97 (d, J = 1.1 Hz, 1 H).
(2) 4- {3- [1- (2,2-dimethylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl}- 2,3-difluorobenzoic acid

参考例３５−Ｇ（１）で得られた化合物（０．２８ｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（０．２８ｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、粗表題化合物（０．４２ｇ）を得た。
MS ESI/APCI Dual posi: 430[M+H]⁺.
MS ESI/APCI Dual nega: 428[M-H]^-.
参考例３５−Ｈ
２，３−ジフルオロ−４−｛３−［１−（２−フルオロ−２−メチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸
（１）１−［４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−イル］−２−メチルプロパン−２−オール

Reference Example 35-Operation similar to Reference Example 31 using the compound (0.28 g) obtained in G (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (0.28 g) And purification was performed to obtain a crude title compound (0.42 g).
MS ESI / APCI Dual posi: 430 [M + H] ⁺ .
MS ESI / APCI Dual nega: 428 [MH] ^- .
Reference Example 35-H
2,3-difluoro-4- {3- [1- (2-fluoro-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine- 6-yl} benzoic acid (1) 1- [4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl) piperidin-1-yl] -2 -Methylpropan-2-ol

参考例３０で得られた化合物（０．５ｇ）、イソブチレンオキシド（０．２９ｍｌ）のメタノール（５ｍｌ）懸濁液を一晩還流した。反応液を濃縮後、残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝８０：２０〜２５：７５）にて精製し、表題化合物（０．６ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 6 H) 2.14 - 2.29 (m, 2 H) 2.38 - 2.73 (m, 6 H) 3.11 - 3.26 (m, 2 H) 4.72 - 4.88 (m, 1 H) 7.98 - 8.02 (m, 1 H) 8.92 - 8.99 (m, 1 H).
（２）６−クロロ−３−［１−（２−フルオロ−２−メチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

A suspension of the compound (0.5 g) obtained in Reference Example 30 and isobutylene oxide (0.29 ml) in methanol (5 ml) was refluxed overnight. After the reaction solution was concentrated, the residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 80: 20 to 25:75) to obtain the title compound (0.6 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 6 H) 2.14-2.29 (m, 2 H) 2.38-2.73 (m, 6 H) 3.11-3.26 (m, 2 H) 4.72-4.88 (m, 1 H) 7.98-8.02 (m, 1 H) 8.92-8.99 (m, 1 H).
(2) 6-chloro-3- [1- (2-fluoro-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例３５−Ｈ（１）で得られた化合物（０．６ｇ）のクロロホルム（６ｍｌ）溶液に、ビス（２−メトキシエチル）アミノ硫酸トリフルオリド（０．３ｍｌ）を加えて一晩撹拌した。反応液に飽和炭酸水素ナトリウム水溶液を加えた後、クロロホルムで２回抽出した。有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９９：５〜７５：２５）にて精製し、表題化合物（０．４ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36 - 1.47 (m, 6 H) 2.15 - 2.26 (m, 2 H) 2.43 - 2.53 (m, 4 H) 2.82 - 2.88 (m, 1 H) 3.16 - 3.24 (m, 2 H) 3.50 - 3.56 (m, 1 H) 4.69 - 4.86 (m, 1 H) 7.99 (d, J=1.2 Hz, 1 H) 8.97 (d, J=1.2 Hz, 1 H).
（３）２，３−ジフルオロ−４−｛３−［１−（２−フルオロ−２−メチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

Bis (2-methoxyethyl) aminosulfuric trifluoride (0.3 ml) was added to a chloroform (6 ml) solution of the compound (0.6 g) obtained in Reference Example 35-H (1) and stirred overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the mixture was extracted twice with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 99: 5-75: 25) to obtain the title compound (0.4 g).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.36-1.47 (m, 6 H) 2.15-2.26 (m, 2 H) 2.43-2.53 (m, 4 H) 2.82-2.88 (m, 1 H) 3.16 -3.24 (m, 2 H) 3.50-3.56 (m, 1 H) 4.69-4.86 (m, 1 H) 7.99 (d, J = 1.2 Hz, 1 H) 8.97 (d, J = 1.2 Hz, 1 H) .
(3) 2,3-difluoro-4- {3- [1- (2-fluoro-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c ] Pyridin-6-yl} benzoic acid

参考例３５−Ｈ（２）で得られた化合物（０．３４ｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（０．３３ｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、粗表題化合物（０．７７ｇ）を得た。
MS ESI/APCI Dual posi: 434[M+H]⁺.
MS ESI/APCI Dual nega: 432[M-H]^-.
参考例３５−Ｉ
４−｛３−［１−（シクロプロピルメチル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸
（１）６−クロロ−３−［１−（シクロプロピルメチル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Reference Example 35-Operation similar to Reference Example 31 using the compound (0.34 g) obtained in H (2) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (0.33 g) The reaction and purification were conducted to obtain the crude title compound (0.77 g).
MS ESI / APCI Dual posi: 434 [M + H] ⁺ .
MS ESI / APCI Dual nega: 432 [MH] ^- .
Reference Example 35-I
4- {3- [1- (cyclopropylmethyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3-difluorobenzoic acid Acid (1) 6-chloro-3- [1- (cyclopropylmethyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例３０で得られた化合物（０．４０ｇ）とシクロプロパンカルボアルデヒド（０．５ｍｌ）を用いて、参考例３５−Ｇ（１）と同様の操作にて反応及び精製を行い、表題化合物（０．３５ｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.11 - 0.21 (m, 2 H) 0.52 - 0.64 (m, 2 H) 0.82 - 1.02 (m, 1 H) 2.14 - 2.63 (m, 8 H) 3.23 - 3.40 (m, 2 H) 4.78 - 4.92 (m, 1 H) 7.99 (d, J=1.2 Hz, 1 H) 9.00 (d, J=1.2 Hz, 1 H).
（２）４−｛３−［１−（シクロプロピルメチル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２，３−ジフルオロ安息香酸

Using the compound (0.40 g) obtained in Reference Example 30 and cyclopropanecarbaldehyde (0.5 ml), the reaction and purification were performed in the same manner as in Reference Example 35-G (1), and the title compound ( 0.35 g) was obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.11-0.21 (m, 2 H) 0.52-0.64 (m, 2 H) 0.82-1.02 (m, 1 H) 2.14-2.63 (m, 8 H) 3.23 -3.40 (m, 2 H) 4.78-4.92 (m, 1 H) 7.99 (d, J = 1.2 Hz, 1 H) 9.00 (d, J = 1.2 Hz, 1 H).
(2) 4- {3- [1- (cyclopropylmethyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3 -Difluorobenzoic acid

参考例３５−Ｉ（１）で得られた化合物（０．３４ｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（０．３５ｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、粗表題化合物（０．３１ｇ）を得た。
MS ESI/APCI Dual posi: 414[M+H]⁺.
MS ESI/APCI Dual nega: 412[M-H]^-.
参考例３５−Ｊ
４−｛３−［１−（５−クロロピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−フルオロ−５−メチル安息香酸

The same operations as in Reference Example 31 were carried out using the compound (0.34 g) obtained in Reference Example 35-I (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (0.35 g). The reaction and purification were conducted to obtain the crude title compound (0.31 g).
MS ESI / APCI Dual posi: 414 [M + H] ⁺ .
MS ESI / APCI Dual nega: 412 [MH] ^- .
Reference Example 35-J
4- {3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluoro-5-methylbenzoic acid

参考例３５−Ａ（１）で得られた化合物（４００ｍｇ）と参考例Ｅ−１７で得られた化合物（１．３７ｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（１００ｍｇ）を茶色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.35 - 2.51 (m, 7 H) 3.24 - 3.33 (m, 2 H) 4.95 - 5.03 (m, 2 H) 5.13 - 5.22 (m, 1 H) 7.51 - 7.58 (m, 1 H) 7.93 - 8.00 (m, 1 H) 8.06 - 8.11 (m, 1 H) 8.30 (s, 2 H) 9.24 - 9.28 (m, 1 H).
MS ESI posi: 468[M+H]⁺.
参考例３５−Ｋ
２−フルオロ−５−メチル−４−［３−（１−｛［（１−メチルシクロプロピル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸
（１）（１−メチルシクロプロピル）メチル ４−（６−クロロ−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル）ピペリジン−１−カルボキシラート

Using the compound (400 mg) obtained in Reference Example 35-A (1) and the compound (1.37 g) obtained in Reference Example E-17, the reaction and purification were performed in the same manner as in Reference Example 31. The title compound (100 mg) was obtained as a brown powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.35-2.51 (m, 7 H) 3.24-3.33 (m, 2 H) 4.95-5.03 (m, 2 H) 5.13-5.22 (m, 1 H) 7.51 -7.58 (m, 1 H) 7.93-8.00 (m, 1 H) 8.06-8.11 (m, 1 H) 8.30 (s, 2 H) 9.24-9.28 (m, 1 H).
MS ESI posi: 468 [M + H] ⁺ .
Reference Example 35-K
2-Fluoro-5-methyl-4- [3- (1-{[(1-methylcyclopropyl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [4,5 -C] pyridin-6-yl] benzoic acid (1) (1-methylcyclopropyl) methyl 4- (6-chloro-3H- [1,2,3] triazolo [4,5-c] pyridine-3- Yl) piperidine-1-carboxylate

１−メチルシクロプロパンメタノール（３２７μｌ）を脱水テトラヒドロフラン（１７ｍｌ）に溶解し、トリホスゲン（３５０ｍｇ）を加えた。反応液を氷冷し、トリエチルアミン（９３６μｌ）を加えた後、参考例３０で得られた化合物（４００ｍｇ）を加え、そのまま１時間撹拌した。反応液に水を加えてクロロホルムにて抽出し、有機層をフェーズセパレーターに通した後、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ノルマルヘキサン：酢酸エチル＝５０：５０〜３０：７０）にて精製し、表題化合物（４７６ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.36 - 0.42 (m, 2 H) 0.48 - 0.55 (m, 2 H) 1.16 (s, 3 H) 2.19 - 2.45 (m, 4 H) 3.05 - 3.23 (m, 2 H) 3.95 (s, 2 H) 4.37 - 4.50 (m, 2 H) 4.91 - 5.04 (m, 1 H) 8.01 (d, J=1.2 Hz, 1 H) 8.94 (d, J=1.2 Hz, 2 H).
MS ESI/APCI Dual posi: 372[M+Na]⁺.
（２）２−フルオロ−５−メチル−４−［３−（１−｛［（１−メチルシクロプロピル）メトキシ］カルボニル｝ピペリジン−４−イル）−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル］安息香酸

1-methylcyclopropanemethanol (327 μl) was dissolved in dehydrated tetrahydrofuran (17 ml), and triphosgene (350 mg) was added. The reaction mixture was ice-cooled, triethylamine (936 μl) was added, the compound (400 mg) obtained in Reference Example 30 was added, and the mixture was stirred as it was for 1 hr. Water was added to the reaction solution and the mixture was extracted with chloroform. The organic layer was passed through a phase separator and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (normal hexane: ethyl acetate = 50: 50-30: 70) to obtain the title compound (476 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.36-0.42 (m, 2 H) 0.48-0.55 (m, 2 H) 1.16 (s, 3 H) 2.19-2.45 (m, 4 H) 3.05-3.23 (m, 2 H) 3.95 (s, 2 H) 4.37-4.50 (m, 2 H) 4.91-5.04 (m, 1 H) 8.01 (d, J = 1.2 Hz, 1 H) 8.94 (d, J = 1.2 Hz, 2 H).
MS ESI / APCI Dual posi: 372 [M + Na] ⁺ .
(2) 2-Fluoro-5-methyl-4- [3- (1-{[(1-methylcyclopropyl) methoxy] carbonyl} piperidin-4-yl) -3H- [1,2,3] triazolo [ 4,5-c] pyridin-6-yl] benzoic acid

参考例３５−Ｋ（１）で得られた化合物（５００ｍｇ）、参考例Ｅ−１７で得られた化合物（１．７２ｇ）、テトラキス（トリフェニルホスフィン）パラジウム（１６５ｍｇ）、２Ｍ炭酸ナトリウム水溶液（２．９ｍｌ）のエタノール（２０ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１６０℃にて３０分間撹拌した。冷却後反応液へ水を加え、クロロホルムにて抽出し、有機層をフェーズセパレーターに通した後、減圧下濃縮した。得られた残渣を分取ＨＰＬＣで精製し、表題化合物（１００ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.35 - 0.44 (m, 2 H) 0.49 - 0.57 (m, 2 H) 1.18 (s, 3 H) 2.25 - 2.54 (m, 4 H) 2.39 (s, 3 H) 3.08 - 3.30 (m, 2 H) 3.97 (s, 2 H) 4.38 - 4.55 (m, 2 H) 5.01 - 5.17 (m, 1 H) 7.28 - 7.35 (m, 1 H) 7.96 - 8.04 (m, 1 H) 8.13 (s, 1 H) 9.38 (s, 1 H).
MS ESI/APCI Dual nega: 466[M-H]^-.
実施例１−１
ｔｅｒｔ−ブチル ４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−インダゾル−１−イル｝ピペリジン−１−カルボキシラート

Compound (500 mg) obtained in Reference Example 35-K (1), compound (1.72 g) obtained in Reference Example E-17, tetrakis (triphenylphosphine) palladium (165 mg), 2M aqueous sodium carbonate solution (2 (9 ml) in ethanol (20 ml) was stirred for 30 minutes at 160 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, water was added to the reaction solution, followed by extraction with chloroform. The organic layer was passed through a phase separator and then concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give the title compound (100 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.35-0.44 (m, 2 H) 0.49-0.57 (m, 2 H) 1.18 (s, 3 H) 2.25-2.54 (m, 4 H) 2.39 (s , 3 H) 3.08-3.30 (m, 2 H) 3.97 (s, 2 H) 4.38-4.55 (m, 2 H) 5.01-5.17 (m, 1 H) 7.28-7.35 (m, 1 H) 7.96-8.04 (m, 1 H) 8.13 (s, 1 H) 9.38 (s, 1 H).
MS ESI / APCI Dual nega: 466 [MH] ^- .
Example 1-1
tert-Butyl 4- {5- [4- (methylsulfonyl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

参考例１（２）で得られた化合物（２００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（３ｍｌ）溶液へ、４−（メチルスルホニル）フェニルボロン酸（１２８ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（４３ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．８ｍｌ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１１０℃にて３０分攪拌した。反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：４）にて精製後、ジエチルエーテル−ヘキサン混合溶液で粉末化し、表題化合物（１３６ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM‐d) δ ppm 1.50 (s, 9 H) 1.97 ‐ 2.13 (m, 2 H) 2.15 ‐ 2.38 (m, 2 H) 2.89 ‐ 3.08 (m, 2 H) 3.11 (s, 3 H) 4.23 ‐ 4.43 (m, 2 H) 4.51 ‐ 4.70 (m, 1 H) 7.50 ‐ 7.60 (m, 1 H) 7.61 ‐ 7.68 (m, 1 H) 7.76 ‐ 7.86 (m, 2 H) 7.95 ‐ 8.02 (m, 2 H) 8.03 ‐ 8.07 (m, 1 H) 8.09 (s, 1 H).
MS ESI/APCI Dual posi: 478[M+Na]⁺.

To a solution of the compound (200 mg) obtained in Reference Example 1 (2) in N, N-dimethylformamide (3 ml), 4- (methylsulfonyl) phenylboronic acid (128 mg), [1,1′-bis (diphenylphosphine) ) ferrocene] palladium (II) dichloride dichloromethane complex (43 mg), added 2M aqueous sodium carbonate solution (0.8 ml), a micro web - Bed reactor (Biotage, Inc. Initiator Sixty ^TM (trade name)) was used to micro The mixture was stirred at 110 ° C. for 30 minutes under wave irradiation. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 4) and then powdered with a mixed solution of diethyl ether-hexane to give the title compound (136 mg) as a colorless powder. It was.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.97-2.13 (m, 2 H) 2.15-2.38 (m, 2 H) 2.89-3.08 (m, 2 H) 3.11 (s , 3 H) 4.23-4.43 (m, 2 H) 4.51-4.70 (m, 1 H) 7.50-7.60 (m, 1 H) 7.61-7.68 (m, 1 H) 7.76-7.86 (m, 2 H) 7.95 -8.02 (m, 2 H) 8.03-8.07 (m, 1 H) 8.09 (s, 1 H).
MS ESI / APCI Dual posi: 478 [M + Na] ⁺ .

  The following Examples 1-2 to 1-3 were also synthesized according to the method described in Example 1-1 using the boronic acid corresponding to the compound obtained in Reference Example 1 (2). . The structure, NMR data, and MS data of these compounds are shown in Table 1-1.

Example 2-1
tert-Butyl 4- {5- [4- (1H-tetrazol-1-yl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

参考例２で得られた化合物（１５０ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１．５ｍｌ）溶液へ、参考例Ｂ−２で得られた化合物（１５５ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１４．３ｍｇ）、２Ｍ炭酸ナトリウム水溶液（５２５μｌ）を加え、１００℃にて１．５時間攪拌した。反応液を減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９０：１０〜０：１００）で精製し、表題化合物（１００ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.97 - 2.12 (m, 2 H) 2.17 - 2.37 (m, 2 H) 2.91 - 3.09 (m, 2 H) 4.35 (br. d, J=7.8 Hz, 2 H) 4.53 - 4.69 (m, 1 H) 7.53 - 7.60 (m, 1 H) 7.62 - 7.69 (m, 1 H) 7.75 - 7.88 (m, 4 H) 7.98 (s, 1 H) 8.09 (s, 1 H) 9.03 (s, 1 H).
MS ESI/APCI Dual posi: 468[M+Na]⁺.

To a solution of the compound obtained in Reference Example 2 (150 mg) in N, N-dimethylformamide (1.5 ml), the compound obtained in Reference Example B-2 (155 mg), [1,1′-bis (diphenylphosphine). Fino) ferrocene] palladium (II) dichloride dichloromethane complex (14.3 mg), 2M aqueous sodium carbonate solution (525 μl) were added, and the mixture was stirred at 100 ° C. for 1.5 hours. The residue obtained by concentrating the reaction solution under reduced pressure was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 90: 10 to 0: 100) to obtain the title compound (100 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.97-2.12 (m, 2 H) 2.17-2.37 (m, 2 H) 2.91-3.09 (m, 2 H) 4.35 (br d, J = 7.8 Hz, 2 H) 4.53-4.69 (m, 1 H) 7.53-7.60 (m, 1 H) 7.62-7.69 (m, 1 H) 7.75-7.88 (m, 4 H) 7.98 (s , 1 H) 8.09 (s, 1 H) 9.03 (s, 1 H).
MS ESI / APCI Dual posi: 468 [M + Na] ⁺ .

  The following Examples 2-2 to 2-3 are also described in Example 2-1 using the compound obtained in Reference Example 2 and the compound obtained in Reference Example C, or the corresponding halogen compound. Synthesized according to the method. The structure, NMR data, and MS data of these compounds are shown in Table 2-1.

Example 3-1
Propan-2-yl 4- {5- [4- (methylsulfonyl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

実施例１−１で得られた化合物（２３９ｍｇ）のメタノール（３０ｍｌ）溶液へ４Ｍ塩化水素・１，４−ジオキサン溶液（１０ｍｌ）を加え、室温にて１時間攪拌した。反応液へ８Ｍ水酸化ナトリウム水溶液を加え、クロロホルムで抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜０：１〜クロロホルム：メタノール＝９：１）にて精製し、５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−インダゾール（１７４ｍｇ）を無色ガム状物質として得た。得られた５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−インダゾール（８８ｍｇ）のクロロホルム（２ｍｌ）溶液へ、トリエチルアミン（１０５μｌ）、クロロぎ酸イソプロピル（４７ｍｇ）を加え室温にて４時間攪拌した。反応液へ水を加え、クロロホルムで抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：４）にて精製後、ヘキサン−ジエチルエーテル混合液で粉末化し、表題化合物（８６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.27 (d, J=6.4 Hz, 6 H) 2.02 - 2.09 (m, 2 H) 2.22 - 2.31 (m, 2 H) 2.97 - 3.06 (m, 2 H) 3.11 (s, 3 H) 4.31 - 4.43 (m, 2 H) 4.58 - 4.64 (m, 1 H) 4.93 - 4.99 (m, 1 H) 7.55 (d, J=8.7 Hz, 1 H) 7.63 (d, J=8.7 Hz, 1 H) 7.78 - 7.82 (m, 2 H) 7.97 (s, 1 H) 8.00 - 8.03 (m, 2 H) 8.08 (s, 1 H).
MS ESI/APCI Dual posi: 442[M+H]⁺.
実施例３−２
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−インダゾール

To a solution of the compound obtained in Example 1-1 (239 mg) in methanol (30 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (10 ml), and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 8M aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 0: 1 to chloroform: methanol = 9: 1) to give 5- [4- (methylsulfonyl) phenyl]. -1- (Piperidin-4-yl) -1H-indazole (174 mg) was obtained as a colorless gum. To a solution of the obtained 5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-indazole (88 mg) in chloroform (2 ml), triethylamine (105 μl) and isopropyl chloroformate (47 mg) ) And stirred at room temperature for 4 hours. Water was added to the reaction solution and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 4) and then pulverized with a hexane-diethyl ether mixture to give the title compound (86 mg) as a colorless powder. Obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.27 (d, J = 6.4 Hz, 6 H) 2.02-2.09 (m, 2 H) 2.22-2.31 (m, 2 H) 2.97-3.06 (m, 2 H) 3.11 (s, 3 H) 4.31-4.43 (m, 2 H) 4.58-4.64 (m, 1 H) 4.93-4.99 (m, 1 H) 7.55 (d, J = 8.7 Hz, 1 H) 7.63 ( d, J = 8.7 Hz, 1 H) 7.78-7.82 (m, 2 H) 7.97 (s, 1 H) 8.00-8.03 (m, 2 H) 8.08 (s, 1 H).
MS ESI / APCI Dual posi: 442 [M + H] ⁺ .
Example 3-2
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-indazole

実施例３−１で得られた５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−インダゾール（７０ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（４３ｍｇ）、Ｎ，Ｎ−ジイソプロピルエチルアミン（１０５μｌ）を加え、１００℃にて一晩攪拌した。２−クロロ−５−エチルピリミジン（４３ｍｇ）、Ｎ，Ｎ−ジイソプロピルエチルアミン（１０５μｌ）を追加し、１００℃にて６時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９：１〜１：１）にて精製した。さらにＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：ヘキサン＝１：１〜１：０）にて精製後、ジエチルエーテル−ヘキサン混合溶液で粉末化し、表題化合物（６３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ 1.21 (t, J=7.6 Hz, 3 H) 2.10 - 2.16 (m, 2 H) 2.28 - 2.36 (m, 2 H) 2.49 (q, J=7.6 Hz, 2 H) 3.10 (s, 3 H) 3.11 - 3.17 (m, 2 H) 4.71 - 4.78 (m, 1 H) 4.95 - 4.99 (m, 2 H) 7.58 - 7.61 (m, 1 H) 7.63 - 7.65 (m, 1 H) 7.80 - 7.83 (m, 2 H) 7.97 (s, 1 H) 8.00 - 8.03 (m, 2 H) 8.07 (s, 1 H) 8.20 (s, 2 H).
MS ESI/APCI Dual posi: 462[M+H]⁺.

To a solution of 5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-indazole (70 mg) obtained in Example 3-1 in N, N-dimethylformamide (2 ml), 2-Chloro-5-ethylpyrimidine (43 mg) and N, N-diisopropylethylamine (105 μl) were added, and the mixture was stirred at 100 ° C. overnight. 2-Chloro-5-ethylpyrimidine (43 mg) and N, N-diisopropylethylamine (105 μl) were added, and the mixture was stirred at 100 ° C. for 6 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 9: 1 to 1: 1). Further, the residue was purified by NH silica gel column chromatography (developing solvent: chloroform: hexane = 1: 1 to 1: 0) and then powdered with a diethyl ether-hexane mixed solution to obtain the title compound (63 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ 1.21 (t, J = 7.6 Hz, 3 H) 2.10-2.16 (m, 2 H) 2.28-2.36 (m, 2 H) 2.49 (q, J = 7.6 Hz , 2 H) 3.10 (s, 3 H) 3.11-3.17 (m, 2 H) 4.71-4.78 (m, 1 H) 4.95-4.99 (m, 2 H) 7.58-7.61 (m, 1 H) 7.63-7.65 (m, 1 H) 7.80-7.83 (m, 2 H) 7.97 (s, 1 H) 8.00-8.03 (m, 2 H) 8.07 (s, 1 H) 8.20 (s, 2 H).
MS ESI / APCI Dual posi: 462 [M + H] ⁺ .

  The following Examples 3-3 to 3-14 were also prepared using the halogen compounds corresponding to the compounds obtained in Examples 1-1 to 1-3 and Examples 2-1 and 2-2. 1 and 3-2 were synthesized in accordance with the method described. The structures, NMR data, and MS data of these compounds are shown in Tables 3-1 to 3-2.

Example 4-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazol-5-yl} -N-methylbenzamide

参考例３で得られた化合物（５４ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２ｍｌ）溶液へ、４−（Ｎ−メチルアミノカルボニル）フェニルボロン酸（３０ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１１ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．２ｍｌ）を加え、１００℃にて１時間攪拌した。４−（Ｎ−メチルアミノカルボニル）フェニルボロン酸（３０ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１１ｍｇ）を追加し１００℃にて１時間攪拌した。反応液を室温へ冷却後、水を加え、析出物をセライト（登録商標）濾過にて濾取した。得られた析出物をクロロホルムにて溶解した後、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：０〜１：１）にて精製後、ジエチルエーテルで粉末化し、表題化合物（２４ｍｇ）を薄茶色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.3 Hz, 3 H) 2.11 - 2.15 (m, 2 H) 2.28 - 2.37 (m, 2 H) 2.48 (q, J=7.3 Hz, 2 H) 3.05 (d, J=4.6 Hz, 3 H) 3.12 - 3.17 (m, 2 H) 4.70 - 4.77 (m, 1 H) 4.94 - 4.98 (m, 2 H) 6.13 - 6.17 (m, 1 H) 7.56 (d, J=8.7 Hz, 1 H) 7.64 (d, J=8.7 Hz, 1 H) 7.66 - 7.71 (m, 2 H) 7.83 - 7.86 (m, 2 H) 7.95 (s, 1 H) 8.05 (s, 1 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 441[M+H]⁺.

To a solution of the compound obtained in Reference Example 3 (54 mg) in N, N-dimethylformamide (2 ml), 4- (N-methylaminocarbonyl) phenylboronic acid (30 mg), [1,1′-bis (diphenylphosphine) Fino) ferrocene] palladium (II) dichloride dichloromethane complex (11 mg), 2M aqueous sodium carbonate solution (0.2 ml) were added, and the mixture was stirred at 100 ° C. for 1 hour. 4- (N-methylaminocarbonyl) phenylboronic acid (30 mg), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (11 mg) was added, and the mixture was stirred at 100 ° C. for 1 hour. did. The reaction mixture was cooled to room temperature, water was added, and the precipitate was collected by filtration through Celite (registered trademark). The obtained precipitate was dissolved in chloroform, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 0 to 1: 1) and then triturated with diethyl ether to give the title compound (24 mg) as a pale brown powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.3 Hz, 3 H) 2.11-2.15 (m, 2 H) 2.28-2.37 (m, 2 H) 2.48 (q, J = 7.3 Hz, 2 H) 3.05 (d, J = 4.6 Hz, 3 H) 3.12-3.17 (m, 2 H) 4.70-4.77 (m, 1 H) 4.94-4.98 (m, 2 H) 6.13-6.17 (m, 1 H) 7.56 (d, J = 8.7 Hz, 1 H) 7.64 (d, J = 8.7 Hz, 1 H) 7.66-7.71 (m, 2 H) 7.83-7.86 (m, 2 H) 7.95 (s, 1 H) 8.05 (s, 1 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 441 [M + H] ⁺ .

  The following Examples 4-2 to 4-5 were also synthesized according to the method described in Example 4-1 using the boronic acid corresponding to the compound obtained in Reference Example 3. The structure, NMR data, and MS data of these compounds are shown in Table 4-1.

Example 5-1
tert-Butyl 4- {5- [4- (propan-2-ylcarbamoyl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

参考例４で得られた化合物（１０５ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２ｍｌ）溶液へ、イソプロピルアミン（１５ｍｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（３８ｍｇ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（４８ｍｇ）を加え、室温にて２日間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４９：１〜１：４）にて精製後、ジエチルエーテル−ヘキサン混合溶液で粉末化し、表題化合物（９１ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.4 Hz, 6 H) 1.50 (s, 9 H) 2.00 - 2.08 (m, 2 H) 2.20 - 2.32 (m, 2 H) 2.91 - 3.06 (m, 2 H) 4.25 - 4.44 (m, 3 H) 4.56 - 4.64 (m, 1 H) 5.94 (d, J=7.8 Hz, 1 H) 7.53 (d, J=8.8 Hz, 1 H) 7.65 (dd, J=8.8, 1.6 Hz, 1 H) 7.67 - 7.70 (m, 2 H) 7.82 - 7.86 (m, 2 H) 7.95 (s, 1 H) 8.07 (s, 1 H).
MS ESI/APCI Dual posi: 463[M+H]⁺, 485[M+Na]⁺.
MS ESI/APCI Dual nega: 461[M-H]^-.

To a solution of the compound (105 mg) obtained in Reference Example 4 in N, N-dimethylformamide (2 ml), isopropylamine (15 mg), 1-hydroxybenzotriazole monohydrate (38 mg), N-ethyl- N′-3-dimethylaminopropylcarbodiimide hydrochloride (48 mg) was added, and the mixture was stirred at room temperature for 2 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 49: 1 to 1: 4) and then pulverized with a mixed solution of diethyl ether-hexane to give the title compound (91 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.4 Hz, 6 H) 1.50 (s, 9 H) 2.00-2.08 (m, 2 H) 2.20-2.32 (m, 2 H) 2.91-3.06 (m, 2 H) 4.25-4.44 (m, 3 H) 4.56-4.64 (m, 1 H) 5.94 (d, J = 7.8 Hz, 1 H) 7.53 (d, J = 8.8 Hz, 1 H ) 7.65 (dd, J = 8.8, 1.6 Hz, 1 H) 7.67-7.70 (m, 2 H) 7.82-7.86 (m, 2 H) 7.95 (s, 1 H) 8.07 (s, 1 H).
MS ESI / APCI Dual posi: 463 [M + H] ⁺ , 485 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 461 [MH] ^- .

  The following Examples 5-2 and 5-3 were also synthesized according to the method described in Example 5-1 by using the compound obtained in Reference Example 4 and the corresponding amine. The structure, NMR data, and MS data of these compounds are shown in Table 5-1.

Example 6-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazol-5-yl} -N- (propan-2-yl) benzamide

実施例５−１で得られた化合物（８８ｍｇ）のメタノール（２ｍｌ）溶液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（２ｍｌ）を加え、室温で３時間攪拌した。反応液を濃縮後、得られた残渣のＮ，Ｎ−ジメチルホルムアミド（２ｍｌ）溶液へ、炭酸セシウム（３１０ｍｇ）、２−クロロ−５−エチルピリミジン（５５ｍｇ）を加え、８０℃にて２日間攪拌した。反応液へ水を加え、析出した結晶を濾取した。得られた結晶をクロロホルムにて溶解後、シリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９：１〜１：１）にて精製後、ジエチルエーテルで粉末化し、表題化合物（７２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 1.29 (d, J=6.4 Hz, 6 H) 2.11 - 2.17 (m, 2 H) 2.27 - 2.37 (m, 2 H) 2.49 (q, J=7.6 Hz, 2 H) 3.10 - 3.19 (m, 2 H) 4.29 - 4.37 (m, 1 H) 4.70 - 4.77 (m, 1 H) 4.92 - 4.99 (m, 2 H) 5.94 (d, J=7.8 Hz, 1 H) 7.57 (d, J=8.9 Hz, 1 H) 7.65 (dd, J=8.9, 1.8 Hz, 1 H) 7.67 - 7.70 (m, 2 H) 7.83 - 7.86 (m, 2 H) 7.95 (s, 1 H) 8.05 (s, 1 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 469[M+H]⁺.
実施例７−１
４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−インダゾル−５−イル｝−Ｎ−（２−ヒドロキシエチル）ベンズアミド

To a solution of the compound obtained in Example 5-1 (88 mg) in methanol (2 ml), 4M hydrogen chloride / 1,4-dioxane solution (2 ml) was added and stirred at room temperature for 3 hours. After concentrating the reaction solution, cesium carbonate (310 mg) and 2-chloro-5-ethylpyrimidine (55 mg) were added to a solution of the obtained residue in N, N-dimethylformamide (2 ml), and the mixture was stirred at 80 ° C. for 2 days. did. Water was added to the reaction solution, and the precipitated crystals were collected by filtration. The obtained crystals are dissolved in chloroform, purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 9: 1 to 1: 1), and triturated with diethyl ether to give the title compound (72 mg) as a colorless powder. Got as.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 1.29 (d, J = 6.4 Hz, 6 H) 2.11-2.17 (m, 2 H) 2.27-2.37 ( m, 2 H) 2.49 (q, J = 7.6 Hz, 2 H) 3.10-3.19 (m, 2 H) 4.29-4.37 (m, 1 H) 4.70-4.77 (m, 1 H) 4.92-4.99 (m, 2 H) 5.94 (d, J = 7.8 Hz, 1 H) 7.57 (d, J = 8.9 Hz, 1 H) 7.65 (dd, J = 8.9, 1.8 Hz, 1 H) 7.67-7.70 (m, 2 H) 7.83-7.86 (m, 2 H) 7.95 (s, 1 H) 8.05 (s, 1 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 469 [M + H] ⁺ .
Example 7-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazol-5-yl} -N- (2-hydroxyethyl) benzamide

参考例５で得られた化合物（６０ｍｇ）とエタノールアミン（１３ｍｇ）を用いて実施例５−１と同様の方法で表題化合物（４０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.12 - 2.17 (m, 2 H) 2.28 - 2.37 (m, 2 H) 2.45 - 2.52 (m, 3 H) 3.11 - 3.18 (m, 2 H) 3.66 - 3.71 (m, 2 H) 3.85 - 3.90 (m, 2 H) 4.70 - 4.77 (m, 1 H) 4.93 - 4.99 (m, 2 H) 6.60 - 6.65 (m, 1 H) 7.57 (d, J=8.7 Hz, 1 H) 7.65 (dd, J=8.7, 1.4 Hz, 1 H) 7.69 - 7.72 (m, 2 H) 7.86 - 7.90 (m, 2 H) 7.96 (s, 1 H) 8.06 (s, 1 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 471[M+H]⁺.
MS ESI/APCI Dual nega: 469[M-H]^-.

The title compound (40 mg) was obtained as a colorless powder in the same manner as in Example 5-1 using the compound (60 mg) obtained in Reference Example 5 and ethanolamine (13 mg).
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.12-2.17 (m, 2 H) 2.28-2.37 (m, 2 H) 2.45-2.52 (m, 3 H) 3.11-3.18 (m, 2 H) 3.66-3.71 (m, 2 H) 3.85-3.90 (m, 2 H) 4.70-4.77 (m, 1 H) 4.93-4.99 (m, 2 H) 6.60-6.65 (m, 1 H) 7.57 (d, J = 8.7 Hz, 1 H) 7.65 (dd, J = 8.7, 1.4 Hz, 1 H) 7.69-7.72 (m, 2 H) 7.86-7.90 (m, 2 H) 7.96 (s, 1 H) 8.06 (s, 1 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 471 [M + H] ⁺ .
MS ESI / APCI Dual nega: 469 [MH] ^- .

  Example 7-2 below was also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 5 and N-isopropylmethylamine. The structure, NMR data, and MS data of the compound are shown in Table 6-1.

Example 8-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazole (1) 6-methyl-5- [4- (Methylsulfonyl) phenyl] -1H-indazole

参考例６−Ａ（４）で得られた化合物（１．５０ｇ）のＮ，Ｎ−ジメチルホルムアミド（３０ｍｌ）懸濁液へ、４−（メチルスルホニル）フェニルボロン酸（３．２１ｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（４３７ｍｇ）、２Ｍ炭酸ナトリウム水溶液（１０．７ｍｌ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１３０℃にて３０分攪拌した。反応液へ水を加え、酢酸エチルで抽出し、得られた有機層を飽和食塩水で洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１９：１〜１：１）で精製し、表題化合物（１．１６ｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.36 (s, 3 H) 3.14 (s, 3 H) 7.43 (d, J=0.8 Hz, 1 H) 7.53 - 7.61 (m, 3 H) 7.98 - 8.04 (m, 2 H) 8.05 - 8.11 (m, 1 H).
MS ESI/APCI Dual posi: 287[M+H]⁺, 309[M+Na]⁺.
MS ESI/APCI Dual nega: 285[M-H]^-.

To a suspension of the compound (1.50 g) obtained in Reference Example 6-A (4) in N, N-dimethylformamide (30 ml), 4- (methylsulfonyl) phenylboronic acid (3.21 g), [1 , 1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (437 mg), 2M aqueous sodium carbonate (10.7 ml) were added, and a microwave reactor (Initiator Sixty ^™ (product of Biotage) (product) No.) was stirred for 30 minutes at 130 ° C. under microwave irradiation. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 19: 1 to 1: 1) to obtain the title compound (1.16 g) as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.36 (s, 3 H) 3.14 (s, 3 H) 7.43 (d, J = 0.8 Hz, 1 H) 7.53-7.61 (m, 3 H) 7.98- 8.04 (m, 2 H) 8.05-8.11 (m, 1 H).
MS ESI / APCI Dual posi: 287 [M + H] ⁺ , 309 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 285 [MH] ^- .

(2) tert-butyl 4- {6-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

実施例８−１（１）で得られた化合物（３００ｍｇ）のジメチルスルホキシド（４．０ｍｌ）溶液へ、参考例Ａで得られた化合物（５７９ｍｇ）、炭酸セシウム（１．０２ｇ）を加え、９０℃にて１．５時間撹拌した。反応液へ水を加え、酢酸エチルで抽出し、得られた有機層を水で２回洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：１）で精製し、表題化合物（２０４ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.99 - 2.11 (m, 2 H) 2.16 - 2.34 (m, 2 H) 2.38 (s, 3 H) 2.91 - 3.07 (m, 2 H) 3.14 (s, 3 H) 4.25 - 4.43 (m, 2 H) 4.51 - 4.64 (m, 1 H) 7.36 (s, 1 H) 7.52 - 7.59 (m, 3 H) 7.97 - 8.04 (m, 3 H).
MS ESI/APCI Dual posi: 470[M+H]⁺, 492[M+Na]⁺.
MS ESI/APCI Dual nega: 504[M+Cl]^-.

To a solution of the compound (300 mg) obtained in Example 8-1 (1) in dimethyl sulfoxide (4.0 ml), the compound (579 mg) obtained in Reference Example A and cesium carbonate (1.02 g) were added. Stir at 1.5 ° C. for 1.5 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the resulting organic layer was washed twice with water. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 1) to obtain the title compound (204 mg) as a pale yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.99-2.11 (m, 2 H) 2.16-2.34 (m, 2 H) 2.38 (s, 3 H) 2.91-3.07 (m , 2 H) 3.14 (s, 3 H) 4.25-4.43 (m, 2 H) 4.51-4.64 (m, 1 H) 7.36 (s, 1 H) 7.52-7.59 (m, 3 H) 7.97-8.04 (m , 3 H).
MS ESI / APCI Dual posi: 470 [M + H] ⁺ , 492 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 504 [M + Cl] ^- .

(3) 6-methyl-5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-indazole hydrochloride

実施例８−１（２）で得られた化合物（２００ｍｇ）のメタノール（０．８５ｍｌ）懸濁液に４Ｍ塩化水素・１，４−ジオキサン溶液（２．１ｍｌ）を加え、室温にて１３時間攪拌した。反応液を減圧濃縮し、表題化合物（１７６ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.08 - 2.18 (m, 2 H) 2.28 - 2.43 (m, 5 H) 3.07 - 3.22 (m, 2 H) 3.29 (s, 3 H) 3.41 - 3.53 (m, 2 H) 4.94 - 5.06 (m, 1 H) 7.62 - 7.68 (m, 3 H) 7.71 (s, 1 H) 7.96 - 8.03 (m, 2 H) 8.10 (s, 1 H).
MS ESI/APCI Dual posi: 370[M+H]⁺.
MS ESI/APCI Dual nega: 404[M+Cl]^-.

To a suspension of the compound (200 mg) obtained in Example 8-1 (2) in methanol (0.85 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (2.1 ml), and 13 hours at room temperature. Stir. The reaction mixture was concentrated under reduced pressure to give the title compound (176 mg) as a pale yellow powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.08-2.18 (m, 2 H) 2.28-2.43 (m, 5 H) 3.07-3.22 (m, 2 H) 3.29 (s, 3 H) 3.41- 3.53 (m, 2 H) 4.94-5.06 (m, 1 H) 7.62-7.68 (m, 3 H) 7.71 (s, 1 H) 7.96-8.03 (m, 2 H) 8.10 (s, 1 H).
MS ESI / APCI Dual posi: 370 [M + H] ⁺ .
MS ESI / APCI Dual nega: 404 [M + Cl] ^- .

(4) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazole

実施例８−１（３）で得られた化合物（８２ｍｇ）のジメチルスルホキシド（２．０ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（４３ｍｇ）、炭酸セシウム（３２９ｍｇ）を加え、１２０℃にて４時間撹拌した。反応液へ水を加え、酢酸エチルで抽出し、得られた有機層を水で２回洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９５：５〜５０：５０）で精製後、メタノール（１．５ｍｌ）で再結晶を行い、表題化合物（２９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.07 - 2.19 (m, 2 H) 2.24 - 2.36 (m, 2 H) 2.38 (s, 3 H) 2.49 (q, J=7.6 Hz, 2 H) 3.08 - 3.22 (m, 5 H) 4.63 - 4.78 (m, 1 H) 4.90 - 5.02 (m, 2 H) 7.40 (s, 1 H) 7.51 - 7.59 (m, 3 H) 7.94 - 8.04 (m, 3 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 476[M+H]⁺.
MS ESI/APCI Dual nega: 510[M+Cl]^-.

To a solution of the compound obtained in Example 8-1 (3) (82 mg) in dimethyl sulfoxide (2.0 ml), 2-chloro-5-ethylpyrimidine (43 mg) and cesium carbonate (329 mg) were added, and the mixture was heated to 120 ° C. And stirred for 4 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the resulting organic layer was washed twice with water. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 95: 5-50: 50) and recrystallized from methanol (1.5 ml) to give the titled compound (29 mg) as a colorless powder. Obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.07-2.19 (m, 2 H) 2.24-2.36 (m, 2 H) 2.38 (s, 3 H) 2.49 (q, J = 7.6 Hz, 2 H) 3.08-3.22 (m, 5 H) 4.63-4.78 (m, 1 H) 4.90-5.02 (m, 2 H) 7.40 (s, 1 H) 7.51-7.59 ( m, 3 H) 7.94-8.04 (m, 3 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 476 [M + H] ⁺ .
MS ESI / APCI Dual nega: 510 [M + Cl] ^- .

Example 8-2
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -4-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazole (1) 4-methyl-5 [4- (Methylsulfonyl) phenyl] -1H-indazole

参考例６−Ｂ（４）で得られた化合物（１．５０ｇ）を用いて参考例８−１（１）と同様の操作にて反応及び精製を行い、表題化合物（１．１１ｇ）を薄茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.56 (s, 3 H) 3.14 (s, 3 H) 7.24 - 7.33 (m, 1 H) 7.39 - 7.46 (m, 1 H) 7.54 - 7.62 (m, 2 H) 7.98 - 8.05 (m, 2 H) 8.19 (s, 1 H).
MS ESI/APCI Dual posi: 287[M+H]⁺, 309[M+Na]⁺.
MS ESI/APCI Dual nega: 285[M-H]^-.
（２）ｔｅｒｔ−ブチル ４−｛４−メチル−５−［４−（メチルスルホニル）フェニル］−１Ｈ−インダゾル−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (1.50 g) obtained in Reference Example 6-B (4), the reaction and purification were performed in the same manner as in Reference Example 8-1 (1), and the title compound (1.11 g) was diluted with light brown. Obtained as a colored powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.56 (s, 3 H) 3.14 (s, 3 H) 7.24-7.33 (m, 1 H) 7.39-7.46 (m, 1 H) 7.54-7.62 (m , 2 H) 7.98-8.05 (m, 2 H) 8.19 (s, 1 H).
MS ESI / APCI Dual posi: 287 [M + H] ⁺ , 309 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 285 [MH] ^- .
(2) tert-butyl 4- {4-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazol-1-yl} piperidine-1-carboxylate

実施例８−２（１）で得られた化合物（３００ｍｇ）を用いて参考例８−１（２）と同様の操作にて反応及び精製を行い、表題化合物（３３５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.99 - 2.10 (m, 2 H) 2.18 - 2.35 (m, 2 H) 2.53 (s, 3 H) 2.90 - 3.07 (m, 2 H) 3.13 (s, 3 H) 4.25 - 4.42 (m, 2 H) 4.52 - 4.65 (m, 1 H) 7.24 - 7.30 (m, 1 H) 7.34 - 7.40 (m, 1 H) 7.53 - 7.60 (m, 2 H) 7.98 - 8.04 (m, 2 H) 8.09 (s, 1 H).
MS ESI/APCI Dual posi: 470[M+H]⁺, 492[M+Na]⁺.
MS ESI/APCI Dual nega: 504[M+Cl]^-.
（３）４−メチル−５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−インダゾール

Using the compound (300 mg) obtained in Example 8-2 (1), the reaction and purification were carried out in the same manner as in Reference Example 8-1 (2) to obtain the title compound (335 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.99-2.10 (m, 2 H) 2.18-2.35 (m, 2 H) 2.53 (s, 3 H) 2.90-3.07 (m , 2 H) 3.13 (s, 3 H) 4.25-4.42 (m, 2 H) 4.52-4.65 (m, 1 H) 7.24-7.30 (m, 1 H) 7.34-7.40 (m, 1 H) 7.53-7.60 (m, 2 H) 7.98-8.04 (m, 2 H) 8.09 (s, 1 H).
MS ESI / APCI Dual posi: 470 [M + H] ⁺ , 492 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 504 [M + Cl] ^- .
(3) 4-Methyl-5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-indazole

実施例８−２（２）で得られた化合物（３３０ｍｇ）を用いて参考例８−１（３）と同様の方法で合成を行い、表題化合物（３０５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.06 - 2.19 (m, 2 H) 2.26 - 2.45 (m, 2 H) 2.50 (s, 3 H) 3.06 - 3.24 (m, 2 H) 3.29 (s, 3 H) 3.39 - 3.53 (m, 2 H) 4.95 - 5.09 (m, 1 H) 7.35 (d, J=8.7 Hz, 1 H) 7.62 - 7.72 (m, 3 H) 7.97 - 8.05 (m, 2 H) 8.28 (s, 1 H).
MS ESI/APCI Dual posi: 370[M+H]⁺.
MS ESI/APCI Dual nega: 404[M+Cl]^-.
（４）１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−６−メチル−５−［４−（メチルスルホニル）フェニル］−１Ｈ−インダゾール

The title compound (305 mg) was obtained as a colorless powder by synthesis using the compound (330 mg) obtained in Example 8-2 (2) in the same manner as in Reference Example 8-1 (3).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.06-2.19 (m, 2 H) 2.26-2.45 (m, 2 H) 2.50 (s, 3 H) 3.06-3.24 (m, 2 H) 3.29 ( s, 3 H) 3.39-3.53 (m, 2 H) 4.95-5.09 (m, 1 H) 7.35 (d, J = 8.7 Hz, 1 H) 7.62-7.72 (m, 3 H) 7.97-8.05 (m, (2 H) 8.28 (s, 1 H).
MS ESI / APCI Dual posi: 370 [M + H] ⁺ .
MS ESI / APCI Dual nega: 404 [M + Cl] ^- .
(4) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6-methyl-5- [4- (methylsulfonyl) phenyl] -1H-indazole

実施例８−２（３）で得られた化合物（１００ｍｇ）を用いて参考例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（４２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.07 - 2.18 (m, 2 H) 2.24 - 2.41 (m, 2 H) 2.44 - 2.56 (m, 5 H) 3.07 - 3.21 (m, 5 H) 4.65 - 4.79 (m, 1 H) 4.91 - 5.02 (m, 2 H) 7.23 - 7.30 (m, 1 H) 7.37 - 7.44 (m, 1 H) 7.53 - 7.60 (m, 2 H) 7.98 - 8.04 (m, 2 H) 8.08 (s, 1 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 476[M+H]⁺.
MS ESI/APCI Dual nega: 510[M+Cl]^-.
実施例９−１
ｔｅｒｔ−ブチル ４−（５−｛［４−（メチルスルホニル）フェノキシ］メチル｝−１Ｈ−インダゾル−１−イル）ピペリジン−１−カルボキシラート

Using the compound (100 mg) obtained in Example 8-2 (3), the reaction and purification were carried out in the same manner as in Reference Example 8-1 (4) to obtain the title compound (42 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.07-2.18 (m, 2 H) 2.24-2.41 (m, 2 H) 2.44-2.56 (m, 5 H) 3.07-3.21 (m, 5 H) 4.65-4.79 (m, 1 H) 4.91-5.02 (m, 2 H) 7.23-7.30 (m, 1 H) 7.37-7.44 (m, 1 H) 7.53-7.60 (m, 2 H) 7.98-8.04 (m, 2 H) 8.08 (s, 1 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 476 [M + H] ⁺ .
MS ESI / APCI Dual nega: 510 [M + Cl] ^- .
Example 9-1
tert-Butyl 4- (5-{[4- (methylsulfonyl) phenoxy] methyl} -1H-indazol-1-yl) piperidine-1-carboxylate

参考例７（２）で得られた化合物（７０ｍｇ）のテトラヒドロフラン（２ｍｌ）溶液へ、４−（メチルスルホニル）フェノール（７２ｍｇ）、１，１’−アゾビス（Ｎ，Ｎ−ジメチルホルムアミド）（７２ｍｇ）、トリ−ｎ−ブチルホスフィン（１０５μｌ）を加え、室温にて一晩攪拌した。反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和炭酸水素ナトリウム水溶液、飽和食塩水にて順次洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製後、ジエチルエーテルで粉末化し、表題化合物（９９ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.43 (s, 9 H) 1.89 - 1.96 (m, 4 H) 2.92 - 3.07 (m, 2 H) 3.15 (s, 3 H) 4.04 - 4.14 (m, 2 H) 4.81 - 4.90 (m, 1 H) 5.31 (s, 2 H) 7.26 (d, J=8.7 Hz, 2 H) 7.47 - 7.52 (m, 1 H) 7.77 (d, J=9.2 Hz, 1 H) 7.84 (d, J=8.7 Hz, 2 H) 7.87 (s, 1 H) 8.10 (s, 1 H).
MS ESI/APCI Dual posi: 508[M+Na]⁺.
MS ESI/APCI Dual nega: 484[M-H]^-.

To a solution of the compound (70 mg) obtained in Reference Example 7 (2) in tetrahydrofuran (2 ml), 4- (methylsulfonyl) phenol (72 mg), 1,1′-azobis (N, N-dimethylformamide) (72 mg) , Tri-n-butylphosphine (105 μl) was added and stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1) and triturated with diethyl ether to give the title compound (99 mg) as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.43 (s, 9 H) 1.89-1.96 (m, 4 H) 2.92-3.07 (m, 2 H) 3.15 (s, 3 H) 4.04-4.14 ( m, 2 H) 4.81-4.90 (m, 1 H) 5.31 (s, 2 H) 7.26 (d, J = 8.7 Hz, 2 H) 7.47-7.52 (m, 1 H) 7.77 (d, J = 9.2 Hz , 1 H) 7.84 (d, J = 8.7 Hz, 2 H) 7.87 (s, 1 H) 8.10 (s, 1 H).
MS ESI / APCI Dual posi: 508 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 484 [MH] ^- .

  Example 9-2 below is also based on the method described in Example 7-1 using the compound obtained in Reference Example 7 (2) and the compound obtained in Reference Example B-1. Synthesized. Table 7-1 shows the structures, NMR data, and MS data of these compounds.

Example 10-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5-{[4- (methylsulfonyl) phenoxy] methyl} -1H-indazole

実施例９−１で得られた化合物（６７ｍｇ）のメタノール（６ｍｌ）溶液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（３ｍｌ）を加え室温にて３時間攪拌した。反応液へ２Ｍ水酸化ナトリウム水溶液を加えた後、クロロホルムで抽出した。得られた有機層を無水硫酸ナトリウムで乾燥し、乾燥剤を濾別後、溶媒を減圧留去し５−｛［４−（メチルスルホニル）フェノキシ］メチル｝−１−（ピペリジン−４−イル）−１Ｈ−インダゾール（５６ｍｇ）を得た。得られた５−｛［４−（メチルスルホニル）フェノキシ］メチル｝−１−（ピペリジン−４−イル）−１Ｈ−インダゾール（５６ｍｇ）を用いて実施例３−２と同様の操作にて反応及び精製を行い、表題化合物（２２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.5 Hz, 3 H) 2.08 - 2.13 (m, 2 H) 2.28 - 2.35 (m, 2 H) 2.49 (q, J=7.5 Hz, 2 H) 3.02 (s, 3 H) 3.10 - 3.17 (m, 2 H) 4.67 - 4.73 (m, 1 H) 4.91 - 4.97 (m, 2 H) 5.23 (s, 2 H) 7.11 (d, J=8.8 Hz, 2 H) 7.44 (d, J=8.9 Hz, 1 H) 7.53 (d, J=8.9 Hz, 1 H) 7.79 (s, 1 H) 7.87 (d, J=8.8 Hz, 2 H) 8.00 (s, 1 H) 8.20 (s, 2 H).
MS ESI/APCI Dual posi: 492[M+H]⁺, 514[M+Na]⁺.
MS ESI/APCI Dual nega: 490[M-H]^-.

To a solution of the compound obtained in Example 9-1 (67 mg) in methanol (6 ml), 4M hydrogen chloride / 1,4-dioxane solution (3 ml) was added and stirred at room temperature for 3 hours. To the reaction solution was added 2M aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated under reduced pressure to remove 5-{[4- (methylsulfonyl) phenoxy] methyl} -1- (piperidin-4-yl). -1H-indazole (56 mg) was obtained. The obtained 5-{[4- (methylsulfonyl) phenoxy] methyl} -1- (piperidin-4-yl) -1H-indazole (56 mg) was used for the reaction in the same manner as in Example 3-2. Purification was performed to give the title compound (22 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.5 Hz, 3 H) 2.08-2.13 (m, 2 H) 2.28-2.35 (m, 2 H) 2.49 (q, J = 7.5 Hz, 2 H) 3.02 (s, 3 H) 3.10-3.17 (m, 2 H) 4.67-4.73 (m, 1 H) 4.91-4.97 (m, 2 H) 5.23 (s, 2 H) 7.11 (d, J = 8.8 Hz, 2 H) 7.44 (d, J = 8.9 Hz, 1 H) 7.53 (d, J = 8.9 Hz, 1 H) 7.79 (s, 1 H) 7.87 (d, J = 8.8 Hz, 2 H ) 8.00 (s, 1 H) 8.20 (s, 2 H).
MS ESI / APCI Dual posi: 492 [M + H] ⁺ , 514 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 490 [MH] ^- .

  Example 10-2 below was also synthesized according to the method described in Example 10-1, using the compound obtained in Example 9-2 and 2-chloro-5-ethylpyrimidine. The structure, NMR data, and MS data of these compounds are shown in Table 8-1.

Example 11-1
tert-Butyl 4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例８（３）で得られた化合物（３００ｍｇ）を用いて、実施例１−１と同様の操作にて反応及び精製を行い、表題化合物（９０ｍｇ）を薄茶色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.15 - 2.27 (m, 2 H) 2.29 - 2.47 (m, 2 H) 2.98 - 3.15 (m, 2 H) 3.12 (s, 3 H) 4.29 - 4.43 (m, 2 H) 4.82 - 4.96 (m, 1 H) 7.68 (dd, J=8.6, 0.8 Hz, 1 H) 7.75 (dd, J=8.6, 1.6 Hz, 1 H) 7.81 - 7.87 (m, 2 H) 8.04 - 8.09 (m, 2 H) 8.29 - 8.31 (m, 1 H).
MS ESI/APCI Dual posi: 457[M+H]⁺, 479[M+Na]⁺.
MS ESI/APCI Dual nega: 491[M+Cl]^-.

Using the compound (300 mg) obtained in Reference Example 8 (3), the reaction and purification were performed in the same manner as in Example 1-1 to obtain the title compound (90 mg) as a light brown powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.15-2.27 (m, 2 H) 2.29-2.47 (m, 2 H) 2.98-3.15 (m, 2 H) 3.12 (s , 3 H) 4.29-4.43 (m, 2 H) 4.82-4.96 (m, 1 H) 7.68 (dd, J = 8.6, 0.8 Hz, 1 H) 7.75 (dd, J = 8.6, 1.6 Hz, 1 H) 7.81-7.87 (m, 2 H) 8.04-8.09 (m, 2 H) 8.29-8.31 (m, 1 H).
MS ESI / APCI Dual posi: 457 [M + H] ⁺ , 479 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 491 [M + Cl] ^- .

The following Examples 11-2 to 11-8 were also synthesized according to the method described in Example 1-1 using the boronic acid corresponding to the compound obtained in Reference Example 8 (3). . The structures, NMR data, and MS data of these compounds are shown in Tables 9-1 to 9-2.

Example 12-1
tert-Butyl 4- {5- [4- (1H-1,2,3-triazol-1-yl) phenyl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例９で得られた化合物（２００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（５ｍｌ）溶液へ、参考例Ｃで得られた化合物（１５７ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（３８ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．７ｍｌ）を加え、１００℃にて１時間攪拌した。室温へ冷却後、反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を水、飽和食塩水にて順次洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜１：２）にて精製後、分取用ＴＬＣ（展開溶媒 ヘキサン：酢酸エチル＝１：２で２回続けて展開した）にて精製を行い、表題化合物（１３０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16 - 2.27 (m, 2 H) 2.30 - 2.47 (m, 2 H) 2.97 - 3.16 (m, 2 H) 4.29 - 4.45 (m, 2 H) 4.82 - 4.95 (m, 1 H) 7.64 - 7.92 (m, 7 H) 8.05 - 8.08 (m, 1 H) 8.28 - 8.32 (m, 1 H).
MS ESI/APCI Dual posi: 468[M+Na]⁺.
MS ESI/APCI Dual nega: 480[M+Cl]^-.

To a N, N-dimethylformamide (5 ml) solution of the compound (200 mg) obtained in Reference Example 9, the compound (157 mg) obtained in Reference Example C, [1,1′-bis (diphenylphosphino) ferrocene] Palladium (II) dichloride dichloromethane complex (38 mg), 2M aqueous sodium carbonate solution (0.7 ml) were added, and the mixture was stirred at 100 ° C. for 1 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed successively with water and saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 1: 2), and then subjected to preparative TLC (developing solvent hexane: ethyl acetate = 1: 2) twice. The title compound (130 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16-2.27 (m, 2 H) 2.30-2.47 (m, 2 H) 2.97-3.16 (m, 2 H) 4.29-4.45 (m, 2 H) 4.82-4.95 (m, 1 H) 7.64-7.92 (m, 7 H) 8.05-8.08 (m, 1 H) 8.28-8.32 (m, 1 H).
MS ESI / APCI Dual posi: 468 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 480 [M + Cl] ^- .

The following Example 12-2 was also synthesized according to the method described in Example 12-1, using the compound obtained in Reference Example 9 and the compound obtained in Reference Example B-2. The structures, NMR data, and MS data of these compounds are shown in Table 10-1.

Example 13-1
Propan-2-yl 4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例１２で得られた化合物（１００ｍｇ）のクロロホルム（２．５５ｍｌ）溶液へ、トリエチルアミン（２５８ｍｇ）、クロロぎ酸イソプロピル（４６．８ｍｇ）を加え、室温にて３時間攪拌した。反応液に水を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜０：１）にて精製後、ヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（８０ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.2 Hz, 6 H) 2.12 - 2.53 (m, 4 H) 3.01 - 3.20 (m, 2 H) 3.12 (s, 3 H) 4.30 - 4.49 (m, 2 H) 4.79 - 5.08 (m, 2 H) 7.67 (d, J=8.8 Hz, 1 H) 7.75 (dd, J=8.8, 1.6 Hz, 1 H) 7.79 - 7.89 (m, 2 H) 8.01 - 8.11 (m, 2 H) 8.28 - 8.32 (m, 1 H).
MS ESI/APCI Dual posi: 443[M+H]⁺, 465[M+Na]⁺.
MS ESI/APCI Dual nega: 477[M+Cl]^-.
実施例１３−２
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

Triethylamine (258 mg) and isopropyl chloroformate (46.8 mg) were added to a solution of the compound (100 mg) obtained in Reference Example 12 in chloroform (2.55 ml), and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution and extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 0: 1) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (80 mg) as a colorless powder. Obtained.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.2 Hz, 6 H) 2.12-2.53 (m, 4 H) 3.01-3.20 (m, 2 H) 3.12 (s, 3 H) 4.30-4.49 (m, 2 H) 4.79-5.08 (m, 2 H) 7.67 (d, J = 8.8 Hz, 1 H) 7.75 (dd, J = 8.8, 1.6 Hz, 1 H) 7.79-7.89 (m, 2 H) 8.01-8.11 (m, 2 H) 8.28-8.32 (m, 1 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ , 465 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 477 [M + Cl] ^- .
Example 13-2
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（２００ｍｇ）の２−プロパノール（５．０９ｍｌ）懸濁液へ、Ｎ，Ｎ−ジイソプロピルエチルアミン（５２６ｍｇ）、２−クロロ−５−エチルピリミジン（１４５ｍｇ）を加え、８０℃にて９０時間攪拌した。反応液に水を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２）にて精製後、ヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（７４ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.7 Hz, 3 H) 2.20 - 2.60 (m, 6 H) 3.12 (s, 3 H) 3.12 - 3.30 (m, 2 H) 4.90 - 5.12 (m, 3 H) 7.65 - 7.79 (m, 2 H) 7.80 - 7.89 (m, 2 H) 8.01 - 8.11 (m, 2 H) 8.24 (s, 2 H) 8.29 (s, 1 H).
MS ESI/APCI Dual posi: 463[M+H]⁺, 485[M+Na]⁺.
MS ESI/APCI Dual nega: 497[M+Cl]^-.

To a suspension of the compound (200 mg) obtained in Reference Example 12 in 2-propanol (5.09 ml), N, N-diisopropylethylamine (526 mg) and 2-chloro-5-ethylpyrimidine (145 mg) were added. Stir at 90 ° C. for 90 hours. Water was added to the reaction solution and extracted with chloroform. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (74 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.7 Hz, 3 H) 2.20-2.60 (m, 6 H) 3.12 (s, 3 H) 3.12-3.30 (m, 2 H) 4.90-5.12 (m, 3 H) 7.65-7.79 (m, 2 H) 7.80-7.89 (m, 2 H) 8.01-8.11 (m, 2 H) 8.24 (s, 2 H) 8.29 (s, 1 H) .
MS ESI / APCI Dual posi: 463 [M + H] ⁺ , 485 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 497 [M + Cl] ^- .

In Examples 13-3 to 13-6 and 13-16 to 13-20 below, the compound obtained in Reference Example 12, the compound obtained in Reference Example G-2 and Reference Example G-3, or the corresponding halogen The compounds were synthesized according to the method described in Example 13-2, and 13-7 to 13-15 were compounds obtained in Examples 11-2 to 11-6 and Example 12-1. Was synthesized in accordance with the methods described in Reference Example 12 and Example 13-2. The structures, NMR data, and MS data of these compounds are shown in Tables 11-1 to 11-3.

Example 13-21
(4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} phenyl) cyanamide (1) 1- (piperidin-4-yl ) -5- [4- (1H-tetrazol-1-yl) phenyl] -1H-benzotriazole hydrochloride

実施例１２−２で得られた化合物（３９ｍｇ）のメタノール（２９０μｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（８７４μｌ）を加え、室温にて１４時間撹拌した。反応液を濃縮し、表題化合物（４０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 2.24 - 2.62 (m, 4 H) 3.12 - 3.28 (m, 2 H) 3.48 - 3.60 (m, 2 H) 5.25 - 5.38 (m, 1 H) 8.02 - 8.14 (m, 6 H) 8.48 - 8.50 (m, 1 H) 10.19 (s, 1 H).
MS ESI/APCI Dual posi: 347[M+H]⁺.
MS ESI/APCI Dual nega: 381[M+Cl]^-.
（２）（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝フェニル）シアナミド

A 4M hydrogen chloride / 1,4-dioxane solution (874 μl) was added to a suspension of the compound (39 mg) obtained in Example 12-2 in methanol (290 μl), and the mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated to give the title compound (40 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 2.24-2.62 (m, 4 H) 3.12-3.28 (m, 2 H) 3.48-3.60 (m, 2 H) 5.25-5.38 (m, 1 H) 8.02-8.14 (m, 6 H) 8.48-8.50 (m, 1 H) 10.19 (s, 1 H).
MS ESI / APCI Dual posi: 347 [M + H] ⁺ .
MS ESI / APCI Dual nega: 381 [M + Cl] ^- .
(2) (4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} phenyl) cyanamide

実施例１３−２１（１）で得られた化合物（３８ｍｇ）のジメチルスルホキシド（１．０ｍｌ）懸濁液へ、２−クロロ−5−エチルピリミジン（２８ｍｇ）、炭酸セシウム（１６２ｍｇ）を加え、１００℃にて６時間撹拌した。反応液に水を加えて、酢酸エチルで２回抽出を行った。有機層合わせて水で２回洗浄、無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９９：１〜９２：８）で精製し、表題化合物（２５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.5 Hz, 3 H) 2.04 - 2.28 (m, 4 H) 2.40 - 2.55 (m, 2 H) 3.14 - 3.55 (m, 4 H) 4.75 - 4.88 (m, 2 H) 5.19 - 5.33 (m, 1 H) 7.08 (d, J=8.5 Hz, 2 H) 7.78 (d, J=8.5 Hz, 2 H) 7.85 (dd, J=8.7, 1.5 Hz, 1 H) 8.02 (d, J=8.7 Hz, 1 H) 8.25 (s, 1 H) 8.28 - 8.34 (m, 2 H).
MS ESI/APCI Dual posi: 425[M+H]⁺, 447[M+Na]⁺.
MS ESI/APCI Dual nega: 423[M-H]^-.

To a suspension of the compound (38 mg) obtained in Example 13-21 (1) in dimethylsulfoxide (1.0 ml), 2-chloro-5-ethylpyrimidine (28 mg) and cesium carbonate (162 mg) were added. Stir at 6 ° C. for 6 hours. Water was added to the reaction solution, and extraction was performed twice with ethyl acetate. The organic layers were combined, washed twice with water and dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform: methanol = 99: 1 to 92: 8) to give the title compound (25 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.5 Hz, 3 H) 2.04-2.28 (m, 4 H) 2.40-2.55 (m, 2 H) 3.14-3.55 (m, 4 H) 4.75-4.88 (m, 2 H) 5.19-5.33 (m, 1 H) 7.08 (d, J = 8.5 Hz, 2 H) 7.78 (d, J = 8.5 Hz, 2 H) 7.85 (dd, J = 8.7, 1.5 Hz, 1 H) 8.02 (d, J = 8.7 Hz, 1 H) 8.25 (s, 1 H) 8.28-8.34 (m, 2 H).
MS ESI / APCI Dual posi: 425 [M + H] ⁺ , 447 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 423 [MH] ^- .

Example 14-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- (2-methylpyridin-3-yl) -1H-benzotriazole

参考例１０（２）で得られた化合物（１００ｍｇ）と２−メチル−３−（４，４，５，５−テトラメチル−１，３，２−ジオキサボロラン−２−イル）ピリジン（８４．９ｍｇ）を用いて、実施例４−１と同様の操作にて反応及び精製を行い、表題化合物（８６ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.7 Hz, 3 H) 2.23 - 2.58 (m, 6 H) 2.53 (s, 3 H) 3.12 - 3.30 (m, 2 H) 4.92 - 5.10 (m, 3 H) 7.23 (dd, J=7.5, 4.8 Hz, 1 H) 7.44 (dd, J=8.6, 1.4 Hz, 1 H) 7.57 (dd, J=7.5, 1.8 Hz, 1 H) 7.65 (d, J=8.6 Hz, 1 H) 7.99 - 8.03 (m, 1 H) 8.23 (s, 2 H) 8.55 (dd, J=4.8, 1.8 Hz, 1 H).
MS ESI/APCI Dual posi: 400[M+H]⁺, 422[M+Na]⁺.
MS ESI/APCI Dual nega: 434[M+Cl]^-.

The compound (100 mg) obtained in Reference Example 10 (2) and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (84.9 mg) The title compound (86 mg) was obtained as a colorless powder by performing the reaction and purification in the same manner as in Example 4-1.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.7 Hz, 3 H) 2.23-2.58 (m, 6 H) 2.53 (s, 3 H) 3.12-3.30 (m, 2 H) 4.92-5.10 (m, 3 H) 7.23 (dd, J = 7.5, 4.8 Hz, 1 H) 7.44 (dd, J = 8.6, 1.4 Hz, 1 H) 7.57 (dd, J = 7.5, 1.8 Hz, 1 H ) 7.65 (d, J = 8.6 Hz, 1 H) 7.99-8.03 (m, 1 H) 8.23 (s, 2 H) 8.55 (dd, J = 4.8, 1.8 Hz, 1 H).
MS ESI / APCI Dual posi: 400 [M + H] ⁺ , 422 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 434 [M + Cl] ^- .

  The following Examples 14-2 to 14-9 were also prepared in Example 14-1 using the compound obtained in Reference Example 10 (2) and the compound obtained in Reference Example E-7 or the corresponding boronic acid. Synthesized according to the method described. The structures, NMR data, and MS data of these compounds are shown in Table 12-1.

Example 14-10
1- [1- (5-Methylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylaminocarbonyl) phenyl] -1H-benzotriazole

参考例１０（１）で得られた化合物（２９４ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（８．０ｍｌ）溶液に、２−クロロ−５−メチルピリミジン（２０２ｍｇ）、炭酸セシウム（１．１５ｇ）を加え、１２０℃にて４．５時間撹拌した。反応液を室温まで冷却後、酢酸エチルで希釈した。有機層を水で３回、次いで飽和食塩水で洗浄し、無水硫酸マグネシウム乾燥後、減圧下に濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９８：２）にて精製し、５−ブロモ−１−［１−（５−メチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール（２００ｍｇ）を無色粉末として得た。得られた５−ブロモ−１−［１−（５−メチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール（１００ｍｇ）と４−（メチルアミノカルボニル）フェニルボロン酸（７２ｍｇ）を用いて、実施例４−１と同様の操作にて反応及び精製を行い、表題化合物（８８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.17 (s, 3 H) 2.26 - 2.32 (m, 2 H) 2.40 - 2.48 (m, 2 H) 3.06 (d, J=5.0 Hz, 3 H) 3.16 - 3.23 (m, 2 H) 4.95 - 5.03 (m, 3 H) 7.66 (d, J=8.7 Hz, 1 H) 7.71 (d, J=8.7 Hz, 2 H) 7.74 (dd, J=8.7, 1.7 Hz, 1 H) 7.88 (d, J=8.7 Hz, 2 H) 8.21 (s, 2 H) 8.27 (s, 1 H).
MS ESI posi: 428[M+H]⁺.

To a N, N-dimethylformamide (8.0 ml) solution of the compound (294 mg) obtained in Reference Example 10 (1), 2-chloro-5-methylpyrimidine (202 mg) and cesium carbonate (1.15 g) were added. , And stirred at 120 ° C. for 4.5 hours. The reaction solution was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed 3 times with water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 98: 2), and 5-bromo-1- [1- (5-methylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole (200 mg) was obtained as a colorless powder. 5-Bromo-1- [1- (5-methylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole (100 mg) and 4- (methylaminocarbonyl) phenylboronic acid (72 mg) Was used for the reaction and purification in the same manner as in Example 4-1, to give the title compound (88 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.17 (s, 3 H) 2.26-2.32 (m, 2 H) 2.40-2.48 (m, 2 H) 3.06 (d, J = 5.0 Hz, 3 H) 3.16-3.23 (m, 2 H) 4.95-5.03 (m, 3 H) 7.66 (d, J = 8.7 Hz, 1 H) 7.71 (d, J = 8.7 Hz, 2 H) 7.74 (dd, J = 8.7, 1.7 Hz, 1 H) 7.88 (d, J = 8.7 Hz, 2 H) 8.21 (s, 2 H) 8.27 (s, 1 H).
MS ESI posi: 428 [M + H] ⁺ .

Example 14-11
5- [4- (Methylaminocarbonyl) phenyl] -1- [1- (5-fluoropyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole

参考例１０（１）で得られた化合物（２９４ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（８．０ｍｌ）溶液に、２−クロロ−５−フルオロピリミジン（２０９ｍｇ）、炭酸セシウム（１．１５ｇ）を加え、１２０℃で４．５時間撹拌した。反応液を室温まで冷却後、酢酸エチルで希釈した。有機層を水で３回、次いで飽和食塩水で洗浄し、無水硫酸マグネシウム乾燥後、減圧下に濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９０：１０）にて精製し、５−ブロモ−１−［１−（５−フルオロピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール（２４８ｍｇ）を無色粉末として得た。得られた５−ブロモ−１−［１−（５−フルオロピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール化合物（１２４ｍｇ）と４−（メチルアミノカルボニル）フェニルボロン酸（８８ｍｇ）を用いて、実施例４−１と同様の操作にて反応及び精製を行い、表題化合物（８８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.27 - 2.32 (m, 2 H) 2.40 - 2.48 (m, 2 H) 3.06 (d, J=4.6 Hz, 3 H) 3.20 - 3.27 (m, 2 H) 4.91 - 4.96 (m, 2 H) 4.96 - 5.03 (m, 1 H) 6.18 - 6.23 (m, 1 H) 7.65 (d, J=8.7 Hz, 1 H) 7.71 (d, J=8.2 Hz, 2 H) 7.75 (dd, J=8.7, 1.7 Hz, 1 H) 7.88 (d, J=8.2 Hz, 2 H) 8.25 (s, 2 H) 8.27 (s, 1 H).
MS ESI posi: 432[M+H]⁺.

To a N, N-dimethylformamide (8.0 ml) solution of the compound (294 mg) obtained in Reference Example 10 (1), 2-chloro-5-fluoropyrimidine (209 mg) and cesium carbonate (1.15 g) were added. , And stirred at 120 ° C. for 4.5 hours. The reaction solution was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed 3 times with water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 90: 10), and 5-bromo-1- [1- (5-fluoropyrimidin-2-yl) piperidin-4-yl ] -1H-benzotriazole (248 mg) was obtained as a colorless powder. The obtained 5-bromo-1- [1- (5-fluoropyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole compound (124 mg) and 4- (methylaminocarbonyl) phenylboronic acid (88 mg) The title compound (88 mg) was obtained as a colorless powder by performing the reaction and purification in the same manner as in Example 4-1.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.27-2.32 (m, 2 H) 2.40-2.48 (m, 2 H) 3.06 (d, J = 4.6 Hz, 3 H) 3.20-3.27 (m, 2 H) 4.91-4.96 (m, 2 H) 4.96-5.03 (m, 1 H) 6.18-6.23 (m, 1 H) 7.65 (d, J = 8.7 Hz, 1 H) 7.71 (d, J = 8.2 Hz, 2 H) 7.75 (dd, J = 8.7, 1.7 Hz, 1 H) 7.88 (d, J = 8.2 Hz, 2 H) 8.25 (s, 2 H) 8.27 (s, 1 H).
MS ESI posi: 432 [M + H] ⁺ .

  The following Examples 14-12 were also synthesized according to the method described in Example 14-11 using the boronic acid corresponding to the compound obtained in Reference Example 10 (1). The structure, NMR data, and MS data of these compounds are shown in Table 12-2.

Example 15-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (1H-tetrazol-1-yl) phenyl] -1H-benzotriazole

参考例１１で得られた化合物（５０ｍｇ）の１，２−ジメトキシエタン（１．２ｍｌ）懸濁液へ、参考例Ｂ−２で得られた化合物（４１ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（４．７ｍｇ）、２Ｍ炭酸ナトリウム水溶液（１７３μｌ）を加え、８０℃にて５時間攪拌した。反応液を濃縮して得られた残渣を、シリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１００：０〜８５：１５）で精製後、分取用ＴＬＣ（展開溶媒 クロロホルム：メタノール＝２０：１）で精製後、さらにＮＨ−ＴＬＣ（展開溶媒 ヘキサン：クロロホルム＝２：１で１２回続けて展開後、ヘキサン：クロロホルム＝１：１で５回続けて展開した）で精製を行い、表題化合物（１１ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.24 - 2.35 (m, 2 H) 2.37 - 2.57 (m, 4 H) 3.13 - 3.29 (m, 2 H) 4.94 - 5.09 (m, 3 H) 7.66 - 7.79 (m, 2 H) 7.80 - 7.91 (m, 4 H) 8.24 (s, 2 H) 8.27 - 8.34 (m, 1 H) 9.06 (s, 1 H).
MS ESI/APCI Dual posi: 453[M+H]⁺.
MS ESI/APCI Dual nega: 487[M+Cl]^-.

To a suspension of the compound (50 mg) obtained in Reference Example 11 in 1,2-dimethoxyethane (1.2 ml), the compound (41 mg) obtained in Reference Example B-2, [1,1′-bis ( Diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (4.7 mg), 2M aqueous sodium carbonate solution (173 μl) were added, and the mixture was stirred at 80 ° C. for 5 hours. The residue obtained by concentrating the reaction solution was purified by silica gel column chromatography (developing solvent chloroform: methanol = 100: 0 to 85:15) and then preparative TLC (developing solvent chloroform: methanol = 20: 1). The product was further purified with NH-TLC (developing solvent hexane: chloroform = 2: 1, continuously developed 12 times and then developed hexane: chloroform = 1: 1, 5 times successively) to give the title compound (11 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.24-2.35 (m, 2 H) 2.37-2.57 (m, 4 H) 3.13-3.29 (m, 2 H) 4.94-5.09 (m, 3 H) 7.66-7.79 (m, 2 H) 7.80-7.91 (m, 4 H) 8.24 (s, 2 H) 8.27-8.34 (m, 1 H) 9.06 (s, 1 H).
MS ESI / APCI Dual posi: 453 [M + H] ⁺ .
MS ESI / APCI Dual nega: 487 [M + Cl] ^- .

  The following Examples 15-2 to 15-10 were also carried out using the compound obtained in Reference Example 11 and the compounds obtained in Reference Examples D-1 to D-4 and Reference Examples F-1 to F-5. Synthesized according to the method described in Example 15-1. The structures, NMR data, and MS data of these compounds are shown in Tables 13-1 to 13-2.

Example 16-1
5- [4- (Methylsulfonyl) phenyl] -1- (1-propylpiperidin-4-yl) -1H-benzotriazole

参考例１２で得られた化合物（５０ｍｇ）、１−ヨードプロパン（４３ｍｇ）、炭酸カリウム（５３ｍｇ）のアセトニトリル（１ｍｌ）溶液を、１００℃にて封管中一晩攪拌した。反応溶液を濾過した後、濾液を濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１：０〜９：１）にて精製し、表題化合物（５０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.96 (t, J=7.3 Hz, 3 H) 1.50 - 1.69 (m, 2 H) 2.14 - 2.33 (m, 4 H) 2.37 - 2.63 (m, 4 H) 3.12 (s, 3 H) 3.13 - 3.23 (m, 2 H) 4.72 - 4.86 (m, 1 H) 7.68 - 7.78 (m, 2 H) 7.81 - 7.87 (m, 2 H) 8.02 - 8.10 (m, 2 H) 8.25 - 8.31 (m, 1 H).
MS ESI/APCI Dual posi: 399[M+H]⁺.

A solution of the compound obtained in Reference Example 12 (50 mg), 1-iodopropane (43 mg), and potassium carbonate (53 mg) in acetonitrile (1 ml) was stirred overnight at 100 ° C. in a sealed tube. After the reaction solution was filtered, the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 1: 0 to 9: 1) to obtain the title compound (50 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.96 (t, J = 7.3 Hz, 3 H) 1.50-1.69 (m, 2 H) 2.14-2.33 (m, 4 H) 2.37-2.63 (m, 4 H) 3.12 (s, 3 H) 3.13-3.23 (m, 2 H) 4.72-4.86 (m, 1 H) 7.68-7.78 (m, 2 H) 7.81-7.87 (m, 2 H) 8.02-8.10 (m , 2 H) 8.25-8.31 (m, 1 H).
MS ESI / APCI Dual posi: 399 [M + H] ⁺ .

  The following Examples 16-2 to 16-11 were also synthesized according to the method described in Example 16-1 using the compound obtained in Reference Example 12 and the corresponding alkyl halide. The structures, NMR data, and MS data of these compounds are shown in Tables 14-1 to 14-2.

Example 17-1
tert-Butyl 4- {5- [4- (propan-2-ylcarbamoyl) phenyl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例１３で得られた化合物（１００ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（１０７ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.6 Hz, 6 H) 1.51 (s, 9 H) 2.11 - 2.49 (m, 4 H) 2.96 - 3.17 (m, 2 H) 4.27 - 4.44 (m, 3 H) 4.76 - 4.98 (m, 1 H) 5.89 - 6.02 (m, 1 H) 7.60 - 7.79 (m, 4 H) 7.82 - 7.92 (m, 2 H) 8.25 - 8.30 (m, 1 H).
MS ESI/APCI Dual posi: 464[M+H]⁺, 486[M+Na]⁺.
MS ESI/APCI Dual nega: 498[M+Cl]^-.

The compound (100 mg) obtained in Reference Example 13 was used for reaction and purification in the same manner as in Example 5-1, to give the title compound (107 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.6 Hz, 6 H) 1.51 (s, 9 H) 2.11-2.49 (m, 4 H) 2.96-3.17 (m, 2 H) 4.27-4.44 (m, 3 H) 4.76-4.98 (m, 1 H) 5.89-6.02 (m, 1 H) 7.60-7.79 (m, 4 H) 7.82-7.92 (m, 2 H) 8.25-8.30 (m , 1 H).
MS ESI / APCI Dual posi: 464 [M + H] ⁺ , 486 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 498 [M + Cl] ^- .

  The following Examples 17-2 to 17-5 were also synthesized according to the method described in Example 17-1 using the compound obtained in Reference Example 13 or 13-B and the corresponding amine. The structures, NMR data, and MS data of these compounds are shown in Table 15-1.

Example 18-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -N- (propan-2-yl) benzamide

実施例１７−１で得られた化合物（８０ｍｇ）のメタノール（０．５７５ｍｌ）懸濁液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（１．７３ｍｌ）を加え、室温にて３時間攪拌した。反応液を減圧濃縮し、４−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］−Ｎ−（プロパン−２−イル）ベンズアミド 塩酸塩（６９ｍｇ）を無色粉末として得た。得られた４−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］−Ｎ−（プロパン−２−イル）ベンズアミド 塩酸塩（６９ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１．７３ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（５９．２ｍｇ）、炭酸セシウム（２８２ｍｇ）を加え、７０℃にて６０時間攪拌した。反応液に水を加え、析出した粉末をろ取し、水、ヘキサンにて洗浄した。得られた粉末をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：１〜１：２）にて精製し、表題化合物（４０ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δppm 1.23 (t, J=7.6 Hz, 3 H) 1.30 (d, J=6.6 Hz, 6 H) 2.19 - 2.61 (m, 4 H) 2.51 (q, J=7.6 Hz, 2 H) 3.11 - 3.31 (m, 2 H) 4.21 - 4.44 (m, 1 H) 4.90 - 5.10 (m, 3 H) 5.92 - 6.03 (m, 1 H) 7.61 - 7.79 (m, 4 H) 7.80 - 7.93 (m, 2 H) 8.23 (s, 2 H) 8.26 (s, 1 H).
MS ESI/APCI Dual posi: 470[M+H]⁺, 492[M+Na]⁺.
MS ESI/APCI Dual nega: 468[M-H]^-, 504[M+Cl]^-.

To a suspension of the compound (80 mg) obtained in Example 17-1 in methanol (0.575 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (1.73 ml), and the mixture was stirred at room temperature for 3 hours. . The reaction solution was concentrated under reduced pressure to give 4- [1- (piperidin-4-yl) -1H-benzotriazol-5-yl] -N- (propan-2-yl) benzamide hydrochloride (69 mg) as a colorless powder. Obtained. The obtained 4- [1- (piperidin-4-yl) -1H-benzotriazol-5-yl] -N- (propan-2-yl) benzamide hydrochloride (69 mg) in N, N-dimethylformamide ( To the solution was added 2-chloro-5-ethylpyrimidine (59.2 mg) and cesium carbonate (282 mg), and the mixture was stirred at 70 ° C. for 60 hours. Water was added to the reaction solution, and the precipitated powder was collected by filtration and washed with water and hexane. The obtained powder was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 1: 1 to 1: 2) to give the title compound (40 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δppm 1.23 (t, J = 7.6 Hz, 3 H) 1.30 (d, J = 6.6 Hz, 6 H) 2.19-2.61 (m, 4 H) 2.51 (q, J = 7.6 Hz, 2 H) 3.11-3.31 (m, 2 H) 4.21-4.44 (m, 1 H) 4.90-5.10 (m, 3 H) 5.92-6.03 (m, 1 H) 7.61-7.79 (m, 4 H) 7.80-7.93 (m, 2 H) 8.23 (s, 2 H) 8.26 (s, 1 H).
MS ESI / APCI Dual posi: 470 [M + H] ⁺ , 492 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 468 [MH] ^- , 504 [M + Cl] ^- .

  The following Examples 18-2 to 18-8 are also described in Example 18-1 using the halogen compounds corresponding to the compounds obtained in Examples 17-1, 17-4, and 17-5. Synthesized according to The structures, NMR data, and MS data of these compounds are shown in Tables 16-1 to 16-2.

Example 18-9
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -N- (2-hydroxyethyl) benzamide

実施例１７−４で得られた化合物（５２０ｍｇ）のメタノール（３．７ｍｌ）懸濁液へ４Ｍ塩化水素・１，４−ジオキサン溶液(１１．２ｍｌ)を滴下し、室温下２時間撹拌した。減圧下溶媒を留去し、残留物を酢酸エチル−ヘキサン（１：１）混合液で洗浄、減圧下乾燥することでＮ−（２−ヒドロキシエチル）−４−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］ベンズアミド 塩酸塩（４８０ｍｇ）を白色粉末として得た。得られたＮ−（２−ヒドロキシエチル）−４−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］ベンズアミド 塩酸塩（８７ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２．２ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（５２μｌ）、炭酸セシウム（３５３ｍｇ）を加え、窒素雰囲気下７０℃にて１６時間撹拌した。室温へ冷却した後、反応液へ水を加え、酢酸エチルにて３回抽出し、得られた有機層を合わせ飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９７：３〜２０：３）にて精製し、表題化合物（２３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.6 Hz, 3 H) 2.08 - 2.30 (m, 4 H) 2.42 - 2.52 (m, 2 H) 3.15 - 3.28 (m, 2 H) 3.33 - 3.42 (m, 2 H) 3.49 - 3.59 (m, 2 H) 4.71 - 4.88 (m, 3 H) 5.22 - 5.36 (m, 1 H) 7.85 - 8.02 (m, 5 H) 8.04 - 8.11 (m, 1 H) 8.31 (s, 2 H) 8.38 - 8.41 (m, 1 H) 8.52 (t, J=5.7 Hz, 1 H)．
MS ESI/APCI Dual posi: 472[M+H]⁺, 494[M+Na]⁺.
MS ESI/APCI Dual nega: 470[M-H]^-, 506[M+Cl]^-.
実施例１８−１０
５−［４−（４，５−ジヒドロ−１，３−オキサゾール−２−イル）フェニル］−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾール

To a suspension of the compound (520 mg) obtained in Example 17-4 in methanol (3.7 ml), 4M hydrogen chloride / 1,4-dioxane solution (11.2 ml) was added dropwise and stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and the residue was washed with a mixed solution of ethyl acetate-hexane (1: 1) and dried under reduced pressure to give N- (2-hydroxyethyl) -4- [1- (piperidine-4- Yl) -1H-benzotriazol-5-yl] benzamide hydrochloride (480 mg) was obtained as a white powder. The resulting N- (2-hydroxyethyl) -4- [1- (piperidin-4-yl) -1H-benzotriazol-5-yl] benzamide hydrochloride (87 mg) in N, N-dimethylformamide (2 .2 ml) solution was added 2-chloro-5-ethylpyrimidine (52 μl) and cesium carbonate (353 mg) and stirred at 70 ° C. for 16 hours under nitrogen atmosphere. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The obtained organic layers were combined and washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 97: 3 to 20: 3) to obtain the title compound (23 mg) as a colorless powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.16 (t, J = 7.6 Hz, 3 H) 2.08-2.30 (m, 4 H) 2.42-2.52 (m, 2 H) 3.15-3.28 (m, 2 H) 3.33-3.42 (m, 2 H) 3.49-3.59 (m, 2 H) 4.71-4.88 (m, 3 H) 5.22-5.36 (m, 1 H) 7.85-8.02 (m, 5 H) 8.04- 8.11 (m, 1 H) 8.31 (s, 2 H) 8.38-8.41 (m, 1 H) 8.52 (t, J = 5.7 Hz, 1 H).
MS ESI / APCI Dual posi: 472 [M + H] ⁺ , 494 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 470 [MH] ^- , 506 [M + Cl] ^- .
Example 18-10
5- [4- (4,5-Dihydro-1,3-oxazol-2-yl) phenyl] -1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzo Triazole

実施例１８−９で得られたＮ−（２−ヒドロキシエチル）−４−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］ベンズアミド 塩酸塩（７５ｍｇ）のジメチルスルホキシド（２ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（４５μｌ）、炭酸セシウム（３０４ｍｇ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１８０℃にて１５分撹拌した。室温へ冷却した後、反応液へ水を加え、酢酸エチルにて３回抽出し、得られた有機層を合わせ飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１：０〜１０：１）にて精製した後、得られた固体をクロロホルム−ヘキサンより再結晶させ表題化合物（２４ｍｇ）を白色固体として得た。
¹H NMR (300 MHz, CHLOROFORM−d) δ ppm 1.23 (t, J=7.5 Hz, 3 H) 2.24 - 2.34 (m, 2 H) 2.35 - 2.57 (m, 4 H) 3.13 - 3.27 (m, 2 H) 4.06 - 4.15 (m, 2 H) 4.42 - 4.52 (m, 2 H) 4.93 - 5.06 (m, 3 H) 7.60 - 7.79 (m, 4 H) 8.03 - 8.09 (m, 2 H) 8.23 (s, 2 H) 8.27 - 8.30 (m, 1 H)．
MS ESI/APCI Dual posi: 454[M+H]⁺, 476[M+Na]⁺.
MS ESI/APCI Dual nega: 488[M+Cl]^-.

N- (2-hydroxyethyl) -4- [1- (piperidin-4-yl) -1H-benzotriazol-5-yl] benzamide obtained in Example 18-9 Hydrochloride (75 mg) in dimethyl sulfoxide (2 ml) To the solution, 2-chloro-5-ethylpyrimidine (45 μl) and cesium carbonate (304 mg) were added, and a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage) was used. The mixture was stirred at 180 ° C. for 15 minutes under irradiation. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The obtained organic layers were combined and washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 1: 0 to 10: 1), and then the obtained solid was recrystallized from chloroform-hexane to give the title compound (24 mg) as a white solid. Got as.
¹ H NMR (300 MHz, CHLOROFORM−d) δ ppm 1.23 (t, J = 7.5 Hz, 3 H) 2.24-2.34 (m, 2 H) 2.35-2.57 (m, 4 H) 3.13-3.27 (m, 2 H) 4.06-4.15 (m, 2 H) 4.42-4.52 (m, 2 H) 4.93-5.06 (m, 3 H) 7.60-7.79 (m, 4 H) 8.03-8.09 (m, 2 H) 8.23 (s , 2 H) 8.27-8.30 (m, 1 H).
MS ESI / APCI Dual posi: 454 [M + H] ⁺ , 476 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 488 [M + Cl] ^- .

  The following Examples 18-11 to 18-14 were also obtained from N- (2-hydroxyethyl) -4- [1- (piperidin-4-yl) -1H-benzotriazole-obtained in Example 18-9. 5-yl] benzamide Synthesized according to the method described in Examples 18-9 and 18-10, using hydrochloride and the corresponding halogen compound. The structures, NMR data, and MS data of these compounds are shown in Tables 16-3 to 16-4.

Example 19-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -N, N-dimethylbenzamide

参考例１４−Ａで得られた化合物（１０２ｍｇ）、ジメチルアミン塩酸塩（２９ｍｇ）、トリエチルアミン（５０μｌ）を用いて実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（９４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.8 Hz, 3 H) 2.25 - 2.32 (m, 2 H) 2.40 - 2.48 (m, 2 H) 2.51 (q, J=7.8 Hz, 2 H) 3.04 - 3.17 (m, 6 H) 3.17 - 3.24 (m, 2 H) 4.96 - 5.03 (m, 3 H) 7.54 (d, J=7.8 Hz, 2 H) 7.63 - 7.70 (m, 3 H) 7.73 (dd, J=8.7, 1.4 Hz, 1 H) 8.23 (s, 2 H) 8.26 (s, 1 H).
MS ESI/APCI Dual posi: 456[M+H]⁺.

The compound (102 mg) obtained in Reference Example 14-A, dimethylamine hydrochloride (29 mg), and triethylamine (50 μl) were used for reaction and purification in the same manner as in Example 5-1, and the title compound (94 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.8 Hz, 3 H) 2.25-2.32 (m, 2 H) 2.40-2.48 (m, 2 H) 2.51 (q, J = 7.8 Hz, 2 H) 3.04-3.17 (m, 6 H) 3.17-3.24 (m, 2 H) 4.96-5.03 (m, 3 H) 7.54 (d, J = 7.8 Hz, 2 H) 7.63-7.70 (m, 3 H) 7.73 (dd, J = 8.7, 1.4 Hz, 1 H) 8.23 (s, 2 H) 8.26 (s, 1 H).
MS ESI / APCI Dual posi: 456 [M + H] ⁺ .

  The following Examples 19-2 to 19-68 are also based on the method described in Example 5-1 using the compounds obtained in Reference Examples 14-A to 14-H and the corresponding amines. Synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 17-1 to 17-11.

Example 20-1
1- [1- (5-Ethylpyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole (1) 1- [1- (5-bromo Pyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（４００ｍｇ）および炭酸セシウム（１．６６ｇ）のジメチルスルホキシド（８ｍｌ）懸濁液をマイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１８０℃にて２０分間攪拌後、反応液に水を加えクロロホルムにて抽出した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９５：５〜６５：３５）にて２回精製後、クロロホルム−ヘキサンで粉末化し、表題化合物（１７０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.23 - 2.38 (m, 2 H) 2.41 - 2.58 (m, 2 H) 3.12 (s, 3 H) 3.14 - 3.26 (m, 2 H) 4.45 - 4.56 (m, 2 H) 4.92 - 5.05 (m, 1 H) 6.65 - 6.71 (m, 1 H) 7.60 (dd, J=8.9, 2.6 Hz, 1 H) 7.66 - 7.77 (m, 2 H) 7.84 (d, J=8.7 Hz, 2 H) 8.06 (d, J=8.7 Hz, 2 H) 8.23 - 8.26 (m, 1 H) 8.29 - 8.31 (m, 1 H).
（２）１−［１−（５−エテニルピリジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

Using parts reactor (Biotage, Inc. Initiator Sixty ^TM (trade name)) - the compound obtained in Reference Example 12 (400 mg) and cesium carbonate dimethylsulfoxide (8 ml) suspension micro web of (1.66 g) After stirring for 20 minutes at 180 ° C. under microwave irradiation, water was added to the reaction solution and the mixture was extracted with chloroform. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified twice by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 95: 5-65: 35) and then powdered with chloroform-hexane to give the title compound (170 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.23-2.38 (m, 2 H) 2.41-2.58 (m, 2 H) 3.12 (s, 3 H) 3.14-3.26 (m, 2 H) 4.45-4.56 (m, 2 H) 4.92-5.05 (m, 1 H) 6.65-6.71 (m, 1 H) 7.60 (dd, J = 8.9, 2.6 Hz, 1 H) 7.66-7.77 (m, 2 H) 7.84 (d , J = 8.7 Hz, 2 H) 8.06 (d, J = 8.7 Hz, 2 H) 8.23-8.26 (m, 1 H) 8.29-8.31 (m, 1 H).
(2) 1- [1- (5-Ethenylpyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

実施例２０−１（１）で得られた化合物（１４２ｍｇ）、トリブチル（ビニル）チン（９６μｌ）、ビス（トリフェニルホスフィン）パラジウム（II）ジクロリド（９．７ｍｇ）の１，４−ジオキサン（１．５ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、１５０℃にて３０分攪拌した。反応液をセライト（登録商標）ろ過後、ろ液を減圧濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９５：５〜６５：３５）にて精製後、クロロホルム−ヘキサン混合溶液で結晶化し、表題化合物（３３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.25 - 2.38 (m, 2 H) 2.43 - 2.60 (m, 2 H) 3.12 (s, 3 H) 3.15 - 3.27 (m, 2 H) 4.52 - 4.64 (m, 2 H) 4.94 - 5.07 (m, 1 H) 5.13 - 5.19 (m, 1 H) 5.57 - 5.66 (m, 1 H) 6.58 - 6.70 (m, 1 H) 6.73 - 6.79 (m, 1 H) 7.64 - 7.77 (m, 3 H) 7.84 (d, J=8.7 Hz, 2 H) 8.06 (d, J=8.7 Hz, 2 H) 8.20 - 8.23 (m, 1 H) 8.29 - 8.31 (m, 1 H).
（３）１−［１−（５−エチルピリジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

Compound (142 mg) obtained in Example 20-1 (1), tributyl (vinyl) tin (96 μl), bis (triphenylphosphine) palladium (II) dichloride (9.7 mg) of 1,4-dioxane (1 0.5 ml) The suspension was stirred at 150 ° C. for 30 minutes using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 95: 5-65: 35) and crystallized from a chloroform-hexane mixed solution to give the title compound (33 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.25-2.38 (m, 2 H) 2.43-2.60 (m, 2 H) 3.12 (s, 3 H) 3.15-3.27 (m, 2 H) 4.52-4.64 (m, 2 H) 4.94-5.07 (m, 1 H) 5.13-5.19 (m, 1 H) 5.57-5.66 (m, 1 H) 6.58-6.70 (m, 1 H) 6.73-6.79 (m, 1 H ) 7.64-7.77 (m, 3 H) 7.84 (d, J = 8.7 Hz, 2 H) 8.06 (d, J = 8.7 Hz, 2 H) 8.20-8.23 (m, 1 H) 8.29-8.31 (m, 1 H).
(3) 1- [1- (5-Ethylpyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

実施例２０−１（２）で得られた化合物（３３ｍｇ）および水酸化パラジウム（II）（６．６ｍｇ）の１，４−ジオキサン（２ｍ１）懸濁液を水素雰囲気下、室温で一晩攪拌した。反応液をセライト（登録商標）ろ過後、ろ液を減圧濃縮した。得られた残渣をクロロホルム−ヘキサンで再結晶し、表題化合物（２３ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.5 Hz, 3 H) 2.26 - 2.36 (m, 2 H) 2.45 - 2.62 (m, 4 H) 3.07 - 3.20 (m, 5 H) 4.46 - 4.56 (m, 2 H) 4.92 - 5.03 (m, 1 H) 6.71 - 6.78 (m, 1 H) 7.37 - 7.44 (m, 1 H) 7.67 - 7.77 (m, 2 H) 7.84 (d, J=8.5 Hz, 2 H) 8.02 - 8.11 (m, 3 H) 8.28 - 8.32 (m, 1 H).
MS ESI/APCI Dual posi: 462[M+H]⁺, 484[M+Na]⁺.

A suspension of the compound (33 mg) obtained in Example 20-1 (2) and palladium hydroxide (II) (6.6 mg) in 1,4-dioxane (2m1) was stirred overnight at room temperature under a hydrogen atmosphere. did. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from chloroform-hexane to obtain the title compound (23 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.5 Hz, 3 H) 2.26-2.36 (m, 2 H) 2.45-2.62 (m, 4 H) 3.07-3.20 (m, 5 H) 4.46-4.56 (m, 2 H) 4.92-5.03 (m, 1 H) 6.71-6.78 (m, 1 H) 7.37-7.44 (m, 1 H) 7.67-7.77 (m, 2 H) 7.84 (d , J = 8.5 Hz, 2 H) 8.02-8.11 (m, 3 H) 8.28-8.32 (m, 1 H).
MS ESI / APCI Dual posi: 462 [M + H] ⁺ , 484 [M + Na] ⁺ .

Example 20-2
1- [1- (6-Ethylpyridazin-3-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole (1) 1- [1- (6-E Tenylpyridazin-3-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（３００ｍｇ）、参考例Ｇ−１で得られた化合物（２１５ｍｇ）および炭酸セシウム（１．２ｇ）のジメチルスルホキシド（２ｍｌ）懸濁液をマイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、１８０℃にて３０分間攪拌した。反応液に水とクロロホルムを加えた後、セライト（登録商標）ろ過し、不溶物を除去した。ろ液の有機層を水で２回洗浄後、無水硫酸マグネシウムで乾燥し、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９０：１０〜４０：６０）にて２回精製し、表題化合物（１０７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.30 - 2.44 (m, 2 H) 2.46 - 2.64 (m, 2 H) 3.12 (s, 3 H) 3.28 - 3.42 (m, 2 H) 4.61 - 4.73 (m, 2 H) 4.95 - 5.11 (m, 1 H) 5.44 - 5.53 (m, 1 H) 5.94 - 6.04 (m, 1 H) 6.89 - 7.07 (m, 2 H) 7.47 (d, J=9.5 Hz, 1 H) 7.64 - 7.78 (m, 2 H) 7.84 (d, J=8.5 Hz, 2 H) 8.06 (d, J=8.5 Hz, 2 H) 8.29 - 8.33 (m, 1 H).
（２）１−［１−（６−エチルピリダジン−３−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

A suspension of the compound (300 mg) obtained in Reference Example 12, the compound (215 mg) obtained in Reference Example G-1 and cesium carbonate (1.2 g) in dimethyl sulfoxide (2 ml) was subjected to a microwave reactor ( The mixture was stirred at 180 ° C. for 30 minutes using Initiator Sixty ^™ (trade name) manufactured by Biotage. Water and chloroform were added to the reaction solution, followed by Celite (registered trademark) filtration to remove insoluble matters. The organic layer of the filtrate was washed twice with water and then dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified twice by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 90: 10-40: 60) to obtain the title compound (107 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.30-2.44 (m, 2 H) 2.46-2.64 (m, 2 H) 3.12 (s, 3 H) 3.28-3.42 (m, 2 H) 4.61-4.73 (m, 2 H) 4.95-5.11 (m, 1 H) 5.44-5.53 (m, 1 H) 5.94-6.04 (m, 1 H) 6.89-7.07 (m, 2 H) 7.47 (d, J = 9.5 Hz , 1 H) 7.64-7.78 (m, 2 H) 7.84 (d, J = 8.5 Hz, 2 H) 8.06 (d, J = 8.5 Hz, 2 H) 8.29-8.33 (m, 1 H).
(2) 1- [1- (6-Ethylpyridazin-3-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

実施例２０−２（１）で得られた化合物（１０７ｍｇ）を用いて、実施例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（４５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.35 (t, J=7.9 Hz, 3 H) 2.28 - 2.42 (m, 2 H) 2.45 - 2.63 (m, 2 H) 2.89 (q, J=7.9 Hz, 2 H) 3.12 (s, 3 H) 3.22 - 3.37 (m, 2 H) 4.54 - 4.67 (m, 2 H) 4.95 - 5.10 (m, 1 H) 7.02 (d, J=9.3 Hz, 1 H) 7.18 (d, J=9.3 Hz, 1 H) 7.66 - 7.78 (m, 2 H) 7.84 (d, J=8.5 Hz, 2 H) 8.06 (d, J=8.5 Hz, 2 H) 8.28 - 8.32 (m, 1 H).
MS ESI/APCI Dual posi: 463[M+H]⁺.
MS ESI/APCI Dual nega: 497[M+Cl]^-.
実施例２０−３
メチル ２−（４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−イル）ピリミジン−５−カルボキシラート

Using the compound (107 mg) obtained in Example 20-2 (1), the reaction and purification were carried out in the same manner as in Example 20-1 (3) to obtain the title compound (45 mg) as a colorless powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.35 (t, J = 7.9 Hz, 3 H) 2.28-2.42 (m, 2 H) 2.45-2.63 (m, 2 H) 2.89 (q, J = 7.9 Hz, 2 H) 3.12 (s, 3 H) 3.22-3.37 (m, 2 H) 4.54-4.67 (m, 2 H) 4.95-5.10 (m, 1 H) 7.02 (d, J = 9.3 Hz, 1 H ) 7.18 (d, J = 9.3 Hz, 1 H) 7.66-7.78 (m, 2 H) 7.84 (d, J = 8.5 Hz, 2 H) 8.06 (d, J = 8.5 Hz, 2 H) 8.28-8.32 ( m, 1 H).
MS ESI / APCI Dual posi: 463 [M + H] ⁺ .
MS ESI / APCI Dual nega: 497 [M + Cl] ^- .
Example 20-3
Methyl 2- (4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidine-5-carboxylate

参考例１２で得られた化合物（４００ｍｇ）とメチル ２−クロロピリミジン−５−カルボキシラート（３５１ｍｇ）を用いて、参考例２０−１（１）と同様の操作にて反応及び精製を行い、表題化合物（２３０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.28 - 2.55 (m, 4 H) 3.12 (s, 3 H) 3.29 - 3.43 (m, 2 H) 3.91 (s, 3 H) 4.98 - 5.19 (m, 3 H) 7.64 - 7.78 (m, 2 H) 7.84 (d, J=8.7 Hz, 2 H) 8.06 (d, J=8.7 Hz, 2 H) 8.29 - 8.32 (m, 1 H) 8.90 (s, 2 H).
実施例２０−４
［２−（４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−イル）ピリミジン−５−イル］メタノール

Using the compound (400 mg) obtained in Reference Example 12 and methyl 2-chloropyrimidine-5-carboxylate (351 mg), the reaction and purification were carried out in the same manner as in Reference Example 20-1 (1). Compound (230 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.28-2.55 (m, 4 H) 3.12 (s, 3 H) 3.29-3.43 (m, 2 H) 3.91 (s, 3 H) 4.98-5.19 (m , 3 H) 7.64-7.78 (m, 2 H) 7.84 (d, J = 8.7 Hz, 2 H) 8.06 (d, J = 8.7 Hz, 2 H) 8.29-8.32 (m, 1 H) 8.90 (s, 2 H).
Example 20-4
[2- (4- {5- [4- (Methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidin-5-yl] methanol

実施例２０−３で得られた化合物（１４０ｍｇ）のテトラヒドロフラン（２８ｍｌ）懸濁液を氷浴で冷却後、リチウムアルミニウムヒドリド（２２ｍｇ）を加えて室温で３時間攪拌し、さらにリチウムアルミニウムヒドリド（２２ｍｇ）を加えて１時間攪拌した。反応液に水、６Ｍ水酸化ナトリウム水溶液を加えた後、クロロホルムで抽出した。有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９９：１〜９５：５）にて精製後、クロロホルム−ヘキサンで粉末化し、表題化合物（６０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.57 - 1.63 (m, 1 H) 2.23 - 2.52 (m, 4 H) 3.12 (s, 3 H) 3.18 - 3.33 (m, 2 H) 4.58 (d, J=5.4 Hz, 2 H) 4.95 - 5.12 (m, 3 H) 7.66 - 7.78 (m, 2 H) 7.84 (d, J=8.4 Hz, 2 H) 8.06 (d, J=8.4 Hz, 2 H) 8.27 - 8.32 (m, 1 H) 8.39 (s, 2 H).
MS ESI/APCI Dual posi: 465[M+H]⁺.
MS ESI/APCI Dual nega: 499[M+Cl]^-.
実施例２０−５
２−［２−（４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−イル）ピリミジン−５−イル］プロパン−２−オール

A tetrahydrofuran (28 ml) suspension of the compound (140 mg) obtained in Example 20-3 was cooled in an ice bath, lithium aluminum hydride (22 mg) was added, and the mixture was stirred at room temperature for 3 hours, and further lithium aluminum hydride (22 mg). ) Was added and stirred for 1 hour. Water and 6M aqueous sodium hydroxide solution were added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 99: 1 to 95: 5) and then powdered with chloroform-hexane to give the title compound (60 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.57-1.63 (m, 1 H) 2.23-2.52 (m, 4 H) 3.12 (s, 3 H) 3.18-3.33 (m, 2 H) 4.58 (d , J = 5.4 Hz, 2 H) 4.95-5.12 (m, 3 H) 7.66-7.78 (m, 2 H) 7.84 (d, J = 8.4 Hz, 2 H) 8.06 (d, J = 8.4 Hz, 2 H ) 8.27-8.32 (m, 1 H) 8.39 (s, 2 H).
MS ESI / APCI Dual posi: 465 [M + H] ⁺ .
MS ESI / APCI Dual nega: 499 [M + Cl] ^- .
Example 20-5
2- [2- (4- {5- [4- (Methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidin-5-yl] propan-2-ol

実施例２０−３で得られた化合物（８０ｍｇ）のクロロホルム（４ｍｌ）懸濁液を氷浴で冷却後、メチルマグネシウムクロリド（３Ｍジエチルエーテル溶液、１．１ｍｌ）を加えて室温で２時間攪拌し、さらにメチルマグネシウムクロリド（３Ｍジエチルエーテル溶液，１．０ｍｌ）を加えて１時間攪拌した。反応液に６Ｍ水酸化ナトリウム水溶液、クロロホルムを加え、セライト（登録商標）を通してろ過した。ろ液の有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム〜クロロホルム：メタノール＝９５：５）にて精製し、表題化合物（１３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61 (s, 6 H) 2.23 - 2.54 (m, 4 H) 3.12 (s, 3 H) 3.17 - 3.31 (m, 2 H) 4.94 - 5.09 (m, 3 H) 7.67 - 7.77 (m, 2 H) 7.80 - 7.87 (m, 2 H) 8.02 - 8.09 (m, 2 H) 8.26 - 8.32 (m, 1 H) 8.51 (s, 2 H).
実施例２０−６
５−［４−（メチルスルホニル）フェニル］−１−｛１−［５−（プロプ−１−エン−２−イル）ピリミジン−２−イル］ピペリジン−４−イル｝−１Ｈ−ベンゾトリアゾール

A chloroform (4 ml) suspension of the compound (80 mg) obtained in Example 20-3 was cooled in an ice bath, methylmagnesium chloride (3M diethyl ether solution, 1.1 ml) was added, and the mixture was stirred at room temperature for 2 hours. Further, methylmagnesium chloride (3M diethyl ether solution, 1.0 ml) was added and stirred for 1 hour. A 6M aqueous sodium hydroxide solution and chloroform were added to the reaction solution, followed by filtration through Celite (registered trademark). The organic layer of the filtrate was dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform to chloroform: methanol = 95: 5) to obtain the title compound (13 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61 (s, 6 H) 2.23-2.54 (m, 4 H) 3.12 (s, 3 H) 3.17-3.31 (m, 2 H) 4.94-5.09 (m , 3 H) 7.67-7.77 (m, 2 H) 7.80-7.87 (m, 2 H) 8.02-8.09 (m, 2 H) 8.26-8.32 (m, 1 H) 8.51 (s, 2 H).
Example 20-6
5- [4- (Methylsulfonyl) phenyl] -1- {1- [5- (prop-1-en-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-benzotriazole

実施例２０−３で得られた化合物（１００ｍｇ）のテトラヒドロフラン（２ｍｌ）懸濁液に室温でメチルマグネシウムクロリド（３Ｍジエチルエーテル溶液，１．３６ｍｌ）を加えて室温で１時間、６０℃にて３時間攪拌した。反応液に２Ｍ塩酸を加えてクロロホルムで２回抽出した。有機層を無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９５：５〜７０：３０〜クロロホルム：メタノール＝９０：１０）にて精製し、表題化合物（９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.09 - 2.14 (m, 3 H) 2.26 - 2.54 (m, 4 H) 3.12 (s, 3 H) 3.19 - 3.33 (m, 2 H) 4.96 - 5.11 (m, 4 H) 5.27 - 5.32 (m, 1 H) 7.66 - 7.77 (m, 2 H) 7.80 - 7.87 (m, 2 H) 8.01 - 8.10 (m, 2 H) 8.27 - 8.32 (m, 1 H) 8.49 (s, 2 H).
MS ESI/APCI Dual posi: 475[M+H]⁺.
MS ESI/APCI Dual nega: 509[M+Cl]^-.
実施例２０−７
５−［４−（メチルスルホニル）フェニル］−１−｛１−［５−（プロパン−２−イル）ピリミジン−２−イル］ピペリジン−４−イル｝−１Ｈ−ベンゾトリアゾール

Methyl magnesium chloride (3M diethyl ether solution, 1.36 ml) was added to a suspension of the compound (100 mg) obtained in Example 20-3 in tetrahydrofuran (2 ml) at room temperature, and the mixture was added at room temperature for 1 hour at 60 ° C. for 3 hours. Stir for hours. 2M hydrochloric acid was added to the reaction solution, and the mixture was extracted twice with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 95: 5-70: 30-chloroform: methanol = 90: 10) to obtain the title compound (9 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.09-2.14 (m, 3 H) 2.26-2.54 (m, 4 H) 3.12 (s, 3 H) 3.19-3.33 (m, 2 H) 4.96-5.11 (m, 4 H) 5.27-5.32 (m, 1 H) 7.66-7.77 (m, 2 H) 7.80-7.87 (m, 2 H) 8.01-8.10 (m, 2 H) 8.27-8.32 (m, 1 H ) 8.49 (s, 2 H).
MS ESI / APCI Dual posi: 475 [M + H] ⁺ .
MS ESI / APCI Dual nega: 509 [M + Cl] ^- .
Example 20-7
5- [4- (Methylsulfonyl) phenyl] -1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-benzotriazole

実施例２０−６で得られた化合物（９０ｍｇ）を用いて、参考例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（６２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 - 1.30 (m, 6 H) 2.25 - 2.35 (m, 2 H) 2.37 - 2.52 (m, 2 H) 2.75 - 2.89 (m, 1 H) 3.12 (s, 3 H) 3.15 - 3.27 (m, 2 H) 4.95 - 5.06 (m, 3 H) 7.67 - 7.76 (m, 2 H) 7.81 - 7.86 (m, 2 H) 8.03 - 8.08 (m, 2 H) 8.26 (s, 2 H) 8.29 (dd, J=1.6, 0.9 Hz, 1 H).
MS ESI/APCI Dual posi: 477[M+H]⁺, 499[M+Na]⁺.
MS ESI/APCI Dual nega: 511[M+Cl]^-.
実施例２０−８
１−｛１−［５−（２−メチルプロピル）ピリミジン−２−イル］ピペリジン−４−イル｝−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

Using the compound (90 mg) obtained in Example 20-6, the reaction and purification were carried out in the same manner as in Reference Example 20-1 (3) to obtain the title compound (62 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22-1.30 (m, 6 H) 2.25-2.35 (m, 2 H) 2.37-2.52 (m, 2 H) 2.75-2.89 (m, 1 H) 3.12 (s, 3 H) 3.15-3.27 (m, 2 H) 4.95-5.06 (m, 3 H) 7.67-7.76 (m, 2 H) 7.81-7.86 (m, 2 H) 8.03-8.08 (m, 2 H ) 8.26 (s, 2 H) 8.29 (dd, J = 1.6, 0.9 Hz, 1 H).
MS ESI / APCI Dual posi: 477 [M + H] ⁺ , 499 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 511 [M + Cl] ^- .
Example 20-8
1- {1- [5- (2-Methylpropyl) pyrimidin-2-yl] piperidin-4-yl} -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

実施例１３−２０で得られた化合物（９０ｍｇ）を用いて、参考例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（１６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.89 - 0.97 (m, 6 H) 1.72 - 1.87 (m, 1 H) 2.25 - 2.36 (m, 4 H) 2.38 - 2.54 (m, 2 H) 3.12 (s, 3 H) 3.15 - 3.27 (m, 2 H) 4.95 - 5.08 (m, 3 H) 7.68 - 7.77 (m, 2 H) 7.81 - 7.87 (m, 2 H) 8.03 - 8.09 (m, 2 H) 8.18 (s, 2 H) 8.28 - 8.31 (m, 1 H).
MS ESI/APCI Dual posi: 491[M+H]⁺, 513[M+Na]⁺.
MS ESI/APCI Dual nega: 525[M+Cl]^-.
実施例２０−９
１−［１−（５−メチルピラジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

Using the compound (90 mg) obtained in Example 13-20, the reaction and purification were conducted in the same manner as in Reference Example 20-1 (3) to obtain the title compound (16 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.89-0.97 (m, 6 H) 1.72-1.87 (m, 1 H) 2.25-2.36 (m, 4 H) 2.38-2.54 (m, 2 H) 3.12 (s, 3 H) 3.15-3.27 (m, 2 H) 4.95-5.08 (m, 3 H) 7.68-7.77 (m, 2 H) 7.81-7.87 (m, 2 H) 8.03-8.09 (m, 2 H ) 8.18 (s, 2 H) 8.28-8.31 (m, 1 H).
MS ESI / APCI Dual posi: 491 [M + H] ⁺ , 513 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 525 [M + Cl] ^- .
Example 20-9
1- [1- (5-Methylpyrazin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（１９２ｍｇ）をテトラヒドロフラン（４ｍｌ）およびクロロホルム（１ｍｌ）に溶解し、ここに飽和炭酸水素ナトリウム水溶液（５ｍｌ）を加え、室温にて終夜撹拌した。減圧下有機溶媒を除去した後、ダイヤイオンＨＰ２０を充填したカラム管に通し、充填剤を蒸留水で洗浄した後、吸着物質をアセトンにより溶出した。溶出液を減圧下濃縮することで５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール（１３９ｍｇ）を淡灰色粉末として得た。
マイクロウェーブ反応容器に上記反応で得られた５−［４−（メチルスルホニル）フェニル］−１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾール（１００ｍｇ）、（１，３−ジイソプロピルイミダゾール−２−イリデン）（３−クロロピリジル）パラジウム（II）ジクロリド（７．６ｍｇ）、炭酸セシウム（２７４ｍｇ）を入れセプタムで容器を密閉し、容器内をアルゴン置換した。乾燥１，２−ジメトキシエタン（２．５ｍｌ）を加えた後、８０℃にて１時間撹拌した。この反応系へ１Ｍ ２−ブロモ−５−メチルピラジンの１，２−ジメトキシエタン溶液(３３７μｌ)を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１２０℃にて１時間撹拌した。室温へ冷却した後、反応液へ水を加え、酢酸エチルにて３回抽出し、得られた有機層を合わせ飽和食塩水にて洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１：０〜９：１）にて精製し、さらにクロロホルム−ヘキサンから再結晶することで表題化合物（７１ｍｇ）を淡黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM−d) δ ppm 2.28 - 2.40 (m, 2 H) 2.42 - 2.46 (m, 3 H) 2.47 - 2.62 (m, 2 H) 3.12 (s, 3 H) 3.16 - 3.29 (m, 2 H) 4.45 - 4.58 (m, 2 H) 4.93 - 5.07 (m, 1 H) 7.66 - 7.72 (m, 1 H) 7.72 - 7.78 (m, 1 H) 7.80 - 7.87 (m, 2 H) 8.00 - 8.03 (m, 1 H) 8.04 - 8.09 (m, 2 H) 8.17 - 8.20 (m, 1 H) 8.29 - 8.32 (m, 1 H)．
MS ESI/APCI Dual posi: 449[M+H]⁺, 471[M+Na]⁺.
実施例２１−１
ｔｅｒｔ−ブチル ４−［５−（６−クロロ−２−メチルピリミジン−４−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

The compound (192 mg) obtained in Reference Example 12 was dissolved in tetrahydrofuran (4 ml) and chloroform (1 ml), saturated aqueous sodium hydrogen carbonate solution (5 ml) was added thereto, and the mixture was stirred at room temperature overnight. After removing the organic solvent under reduced pressure, it was passed through a column tube filled with Diaion HP20, the filler was washed with distilled water, and the adsorbed material was eluted with acetone. The eluate was concentrated under reduced pressure to obtain 5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-benzotriazole (139 mg) as a light gray powder.
In a microwave reaction vessel, 5- [4- (methylsulfonyl) phenyl] -1- (piperidin-4-yl) -1H-benzotriazole (100 mg), (1,3-diisopropylimidazole-2) obtained by the above reaction -Iridene) (3-chloropyridyl) palladium (II) dichloride (7.6 mg) and cesium carbonate (274 mg) were added, and the container was sealed with a septum, and the inside of the container was replaced with argon. After adding dry 1,2-dimethoxyethane (2.5 ml), the mixture was stirred at 80 ° C. for 1 hour. A 1M 2-bromo-5-methylpyrazine solution in 1,2-dimethoxyethane (337 μl) was added to the reaction system, and a micro-wave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage) was used. The mixture was stirred at 120 ° C. for 1 hour under wave irradiation. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The obtained organic layers were combined and washed with saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 1: 0 to 9: 1), and further recrystallized from chloroform-hexane to give the title compound (71 mg) as a pale yellow powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.28-2.40 (m, 2 H) 2.42-2.46 (m, 3 H) 2.47-2.62 (m, 2 H) 3.12 (s, 3 H) 3.16-3.29 (m, 2 H) 4.45-4.58 (m, 2 H) 4.93-5.07 (m, 1 H) 7.66-7.72 (m, 1 H) 7.72-7.78 (m, 1 H) 7.80-7.87 (m, 2 H ) 8.00-8.03 (m, 1 H) 8.04-8.09 (m, 2 H) 8.17-8.20 (m, 1 H) 8.29-8.32 (m, 1 H).
MS ESI / APCI Dual posi: 449 [M + H] ⁺ , 471 [M + Na] ⁺ .
Example 21-1
tert-Butyl 4- [5- (6-chloro-2-methylpyrimidin-4-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例９で得られた化合物（１００ｍｇ）と４，６−ジクロロ−２−メチルピリミジン（５７ｍｇ）を用いて、実施例２−１と同様の操作にて反応及び精製を行い、表題化合物（８１．２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.15 - 2.26 (m, 2 H) 2.30 - 2.46 (m, 2 H) 2.81 (s, 3 H) 2.99 - 3.14 (m, 2 H) 4.36 (br. d, J=12.1 Hz, 2 H) 4.80 - 4.96 (m, 1 H) 7.62 - 7.71 (m, 2 H) 8.25 - 8.33 (m, 1 H) 8.78 (dd, J=1.5, 0.7 Hz, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺, 451[M+Na]⁺.
MS ESI/APCI Dual nega: 463[M+Cl]^-.
実施例２１−２
ｔｅｒｔ−ブチル ４−［５−（６−シアノ−２−メチルピリミジン−４−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

Using the compound (100 mg) obtained in Reference Example 9 and 4,6-dichloro-2-methylpyrimidine (57 mg), the reaction and purification were carried out in the same manner as in Example 2-1, and the title compound (81 0.2 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.15-2.26 (m, 2 H) 2.30-2.46 (m, 2 H) 2.81 (s, 3 H) 2.99-3.14 (m , 2 H) 4.36 (br.d, J = 12.1 Hz, 2 H) 4.80-4.96 (m, 1 H) 7.62-7.71 (m, 2 H) 8.25-8.33 (m, 1 H) 8.78 (dd, J = 1.5, 0.7 Hz, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ , 451 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 463 [M + Cl] ^- .
Example 21-2
tert-Butyl 4- [5- (6-cyano-2-methylpyrimidin-4-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

実施例２１−１で得られた化合物（６２．４ｍｇ）のＮ−メチルピロリドン（２ｍｌ）溶液へ、シアン化ナトリウム（４２．８ｍｇ）、１，４−ジアザビシクロ［２．２．２］オクタン （１６．３ｍｇ）を加え８０℃にて４時間攪拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜６：４）にて精製し、表題化合物（３６．３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16 - 2.27 (m, 2 H) 2.38 (dq, J=3.9, 12.1 Hz, 2 H) 2.88 (s, 3 H) 2.98 - 3.13 (m, 2 H) 4.36 (br. d, J=11.8 Hz, 2 H) 4.80 - 4.96 (m, 1 H) 7.70 (d, J=8.9 Hz, 1 H) 7.93 (s, 1 H) 8.31 (dd, J=8.9, 1.6 Hz, 1 H) 8.84 (d, J=0.8 Hz, 1 H).
MS ESI/APCI Dual posi: 442[M+Na]⁺.
MS ESI/APCI Dual nega: 454[M+Cl]^-.
実施例２１−３
６−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−２−メチルピリミジン−４−カルボニトリル

To a solution of the compound (62.4 mg) obtained in Example 21-1 in N-methylpyrrolidone (2 ml), sodium cyanide (42.8 mg), 1,4-diazabicyclo [2.2.2] octane (16 3 mg) and stirred at 80 ° C. for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1-6: 4) to give the title compound (36.3 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.52 (s, 9 H) 2.16-2.27 (m, 2 H) 2.38 (dq, J = 3.9, 12.1 Hz, 2 H) 2.88 (s, 3 H) 2.98-3.13 (m, 2 H) 4.36 (br.d, J = 11.8 Hz, 2 H) 4.80-4.96 (m, 1 H) 7.70 (d, J = 8.9 Hz, 1 H) 7.93 (s, 1 H ) 8.31 (dd, J = 8.9, 1.6 Hz, 1 H) 8.84 (d, J = 0.8 Hz, 1 H).
MS ESI / APCI Dual posi: 442 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 454 [M + Cl] ^- .
Example 21-3
6- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -2-methylpyrimidine-4-carbonitrile

実施例２１−２で得られた化合物（９０ｍｇ）のメタノール（１ｍｌ）懸濁液に４Ｍ塩化水素・１，４−ジオキサン溶液（３ｍｌ）を加え、室温にて３０分間攪拌した。その後反応液を減圧濃縮した。
得られた残渣をＮ，Ｎ−ジメチルホルムアミド（２．５ｍｌ）溶液に溶解し、２−クロロ−５−エチルピリミジン（６１．０ｍｇ）、炭酸セシウム（３５０ｍｇ）を加え７０℃にて終夜攪拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝８：２〜４：６）にて精製し、表題化合物（７．３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.7 Hz, 3 H) 2.25 - 2.34 (m, 2 H) 2.35 - 2.57 (m, 4 H) 2.88 (s, 3 H) 3.14 - 3.28 (m, 2 H) 4.93 - 5.08 (m, 3 H) 7.72 (d, J=8.9 Hz, 1 H) 7.93 (s, 1 H) 8.24 (s, 2 H) 8.29 (d, J=8.2 Hz, 1 H) 8.83 (s, 1 H).
MS ESI/APCI Dual posi: 426[M+H]⁺, 448[M+Na]⁺.
MS ESI/APCI Dual nega: 460[M+Cl]^-.
実施例２１−４
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−（６−メトキシ−２−メチルピリミジン−４−イル）−１Ｈ−ベンゾトリアゾール

To a suspension of the compound (90 mg) obtained in Example 21-2 in methanol (1 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (3 ml), and the mixture was stirred at room temperature for 30 minutes. Thereafter, the reaction solution was concentrated under reduced pressure.
The obtained residue was dissolved in an N, N-dimethylformamide (2.5 ml) solution, 2-chloro-5-ethylpyrimidine (61.0 mg) and cesium carbonate (350 mg) were added, and the mixture was stirred at 70 ° C. overnight. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 8: 2-4: 6) to give the title compound (7.3 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.7 Hz, 3 H) 2.25-2.34 (m, 2 H) 2.35-2.57 (m, 4 H) 2.88 (s, 3 H) 3.14-3.28 (m, 2 H) 4.93-5.08 (m, 3 H) 7.72 (d, J = 8.9 Hz, 1 H) 7.93 (s, 1 H) 8.24 (s, 2 H) 8.29 (d, J = 8.2 Hz, 1 H) 8.83 (s, 1 H).
MS ESI / APCI Dual posi: 426 [M + H] ⁺ , 448 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 460 [M + Cl] ^- .
Example 21-4
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- (6-methoxy-2-methylpyrimidin-4-yl) -1H-benzotriazole

実施例２１−１で得られた化合物（１５０ｍｇ）のメタノール（１ｍｌ）懸濁液に４Ｍ塩化水素・１，４−ジオキサン溶液（３ｍｌ）を加え、室温にて終夜攪拌した。その後反応液を減圧濃縮した。
得られた残渣、２−クロロ−５−エチルピリミジン（１００ｍｇ）、炭酸セシウム（５７０ｍｇ）のジメチルスルホキシド（３．５ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１８０℃にて２０分間撹拌した。反応液を室温へ冷却後、水を加え、酢酸エチルにて抽出した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：クロロホルム＝８：２〜５：５）にて精製後、ヘキサン−酢酸エチルで結晶化し、表題化合物（６０．２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.23 - 2.34 (m, 2 H) 2.35 - 2.46 (m, 2 H) 2.51 (q, J=7.6 Hz, 2 H) 2.71 (s, 3 H) 3.14 - 3.26 (m, 2 H) 4.03 (s, 3 H) 4.92 - 5.05 (m, 3 H) 6.99 (s, 1 H) 7.65 (d, J=8.9 Hz, 1 H) 8.19 - 8.26 (m, 3 H) 8.69 (s, 1 H).
MS ESI/APCI Dual posi: 431[M+H]⁺, 453[M+Na]⁺.
実施例２２−１
ｔｅｒｔ−ブチル ４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシレート

To a suspension of the compound (150 mg) obtained in Example 21-1 in methanol (1 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (3 ml), and the mixture was stirred at room temperature overnight. Thereafter, the reaction solution was concentrated under reduced pressure.
A suspension of the obtained residue, 2-chloro-5-ethylpyrimidine (100 mg), cesium carbonate (570 mg) in dimethyl sulfoxide (3.5 ml) was added to a microwave reactor (Initiator Sixty ^™ (Biotage) The mixture was stirred at 180 ° C. for 20 minutes under microwave irradiation. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: chloroform = 8: 2-5: 5) and crystallized from hexane-ethyl acetate to give the title compound (60.2 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.23-2.34 (m, 2 H) 2.35-2.46 (m, 2 H) 2.51 (q, J = 7.6 Hz, 2 H) 2.71 (s, 3 H) 3.14-3.26 (m, 2 H) 4.03 (s, 3 H) 4.92-5.05 (m, 3 H) 6.99 (s, 1 H) 7.65 (d, J = (8.9 Hz, 1 H) 8.19-8.26 (m, 3 H) 8.69 (s, 1 H).
MS ESI / APCI Dual posi: 431 [M + H] ⁺ , 453 [M + Na] ⁺ .
Example 22-1
tert-Butyl 4- {5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例１５（３）で得られた化合物（１５５ｍｇ）を用いて実施例１−１と同様の操作を行った。得られた残渣をシリカゲルクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（７４ｍｇ）を無色粉末として得た。
¹H NMR (300MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.06 - 2.17 (m, 2 H) 2.19 - 2.37 (m, 2 H) 2.95 - 3.09 (m, 2 H) 3.11 (s, 3 H) 4.25 - 4.42 (m, 2 H) 4.66 - 4.83 (m, 1 H) 8.01 - 8.08 (m, 2 H) 8.11 - 8.15 (m, 2 H) 8.21 - 8.27 (m, 2 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 457[M+H]⁺.
実施例２３−１
１−｛１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル｝−５−｛４−（メチルスルホニル）フェニル｝−１Ｈ−ピラゾロ［３，４―ｃ］ピリジン

The same operation as in Example 1-1 was performed using the compound (155 mg) obtained in Reference Example 15 (3). The obtained residue was purified by silica gel chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1) to give the title compound (74 mg) as a colorless powder.
¹ H NMR (300MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.06-2.17 (m, 2 H) 2.19-2.37 (m, 2 H) 2.95-3.09 (m, 2 H) 3.11 (s, 3 H) 4.25-4.42 (m, 2 H) 4.66-4.83 (m, 1 H) 8.01-8.08 (m, 2 H) 8.11-8.15 (m, 2 H) 8.21-8.27 (m, 2 H) 9.11 ( s, 1 H).
MS ESI / APCI Dual posi: 457 [M + H] ⁺ .
Example 23-1
1- {1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl} -5- {4- (methylsulfonyl) phenyl} -1H-pyrazolo [3,4-c] pyridine

実施例２２−１で得られた化合物（７０ｍｇ）のメタノール（２．０ｍｌ）溶液に４Ｍ塩化水素・１，４−ジオキサン溶液（５００μｌ）を加え、室温で終夜攪拌した。反応溶液を濃縮して５−｛４−（メチルスルホニル）フェニル｝−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン 塩酸塩を得た。得られた５−｛４−（メチルスルホニル）フェニル｝−１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン 塩酸塩と５−エチル−２−クロロピリミジン（４４ｍｇ）、炭酸セシウム（２４９ｍｇ）のジメチルスルホキシド（１．５ｍｌ）懸濁液をマイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェ−ブ照射下１１０℃にて２０分攪拌した。反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を飽和食塩水にて洗浄した。無水硫酸マグネシウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１：０〜９５：５）、次いでシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：０〜１：１）にて精製し、表題化合物（４４ｍｇ）を無色粉末として得た。
¹H NMR (300MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.5 Hz, 3 H) 2.14 - 2.25 (m, 2 H) 2.26 - 2.45 (m, 2 H) 2.50 (q, J=7.5 Hz, 2 H) 3.10 (s, 3 H) 3.13 - 3.25 (m, 2 H) 4.81 - 4.93 (m, 1 H) 4.93 - 5.03 (m, 2 H) 8.02 - 8.08 (m, 2 H) 8.11 - 8.14 (m, 2 H) 8.20 - 8.27 (m, 4 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 463[M+H]⁺.
実施例２４−１
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［３−フルオロ−４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound obtained in Example 22-1 (70 mg) in methanol (2.0 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (500 μl), and the mixture was stirred at room temperature overnight. The reaction solution was concentrated to give 5- {4- (methylsulfonyl) phenyl} -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine hydrochloride. Obtained 5- {4- (methylsulfonyl) phenyl} -1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridine hydrochloride and 5-ethyl-2-chloropyrimidine (44 mg) Then, a suspension of cesium carbonate (249 mg) in dimethyl sulfoxide (1.5 ml) was used at 110 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). Stir for 20 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue is purified by silica gel column chromatography (developing solvent chloroform: methanol = 1: 0 to 95: 5) and then silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 0 to 1: 1). The title compound (44 mg) was obtained as a colorless powder.
¹ H NMR (300MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.5 Hz, 3 H) 2.14-2.25 (m, 2 H) 2.26-2.45 (m, 2 H) 2.50 (q, J = 7.5 Hz , 2 H) 3.10 (s, 3 H) 3.13-3.25 (m, 2 H) 4.81-4.93 (m, 1 H) 4.93-5.03 (m, 2 H) 8.02-8.08 (m, 2 H) 8.11-8.14 (m, 2 H) 8.20-8.27 (m, 4 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 463 [M + H] ⁺ .
Example 24-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [3-fluoro-4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例１６で得られた化合物（１００ｍｇ）と３−フルオロ−４−（メチルスルホニル）フェニルボロン酸（８５ｍｇ）を用いて実施例４−１と同様の操作にて反応及び精製を行い、表題化合物（１６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.8 Hz, 3 H) 2.15 - 2.23 (m, 2 H) 2.30 - 2.39 (m, 2 H) 2.50 (q, J=7.8 Hz, 2 H) 3.14 - 3.22 (m, 2 H) 3.27 (s, 3 H) 4.84 - 4.91 (m, 1 H) 4.95 - 5.02 (m, 2 H) 7.95 - 8.06 (m, 3 H) 8.13 (s, 2 H) 8.22 (s, 2 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 481[M+H]⁺.
MS ESI/APCI Dual nega: 479[M-H]^-.

The title compound was obtained by reacting and purifying the compound (100 mg) obtained in Reference Example 16 and 3-fluoro-4- (methylsulfonyl) phenylboronic acid (85 mg) in the same manner as in Example 4-1. (16 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.8 Hz, 3 H) 2.15-2.23 (m, 2 H) 2.30-2.39 (m, 2 H) 2.50 (q, J = 7.8 Hz, 2 H) 3.14-3.22 (m, 2 H) 3.27 (s, 3 H) 4.84-4.91 (m, 1 H) 4.95-5.02 (m, 2 H) 7.95-8.06 (m, 3 H) 8.13 ( s, 2 H) 8.22 (s, 2 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 481 [M + H] ⁺ .
MS ESI / APCI Dual nega: 479 [MH] ^- .

  The following Examples 24-2 to 24-5 were also synthesized according to the method described in Example 4-1 using the boronic acid corresponding to the compound obtained in Reference Example 16. The structures, NMR data, and MS data of these compounds are shown in Table 18-1.

Example 25-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} benzamide

参考例１７で得られた化合物（１００ｍｇ）と２８％アンモニア水溶液（２２ｍｇ）を用いて、参考例５−１と同様の操作にて反応及び精製を行い、表題化合物（４３．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.5 Hz, 3 H) 2.14 - 2.25 (m, 2 H) 2.26 - 2.43 (m, 2 H) 2.50 (q, J=7.5 Hz, 2 H) 3.11 - 3.25 (m, 2 H) 4.80 - 4.92 (m, 1 H) 4.97 (br. d, J=13.5 Hz, 2 H) 5.63 (br. s., 1 H) 6.12 (br. s., 1 H) 7.89 - 7.97 (m, 2 H) 8.07 - 8.16 (m, 4 H) 8.22 (s, 2 H) 9.10 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 428[M+H]⁺.
MS ESI/APCI Dual nega: 426[M-H]^-.

Using the compound (100 mg) obtained in Reference Example 17 and 28% aqueous ammonia solution (22 mg), the reaction and purification were conducted in the same manner as in Reference Example 5-1, and the title compound (43.9 mg) was obtained as a colorless powder. Got as.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.5 Hz, 3 H) 2.14-2.25 (m, 2 H) 2.26-2.43 (m, 2 H) 2.50 (q, J = 7.5 Hz, 2 H) 3.11-3.25 (m, 2 H) 4.80-4.92 (m, 1 H) 4.97 (br.d, J = 13.5 Hz, 2 H) 5.63 (br. S., 1 H) 6.12 (br s., 1 H) 7.89-7.97 (m, 2 H) 8.07-8.16 (m, 4 H) 8.22 (s, 2 H) 9.10-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 428 [M + H] ⁺ .
MS ESI / APCI Dual nega: 426 [MH] ^- .

  The following Examples 25-2 to 25-7 were also synthesized using the amine compound corresponding to the compound obtained in Reference Example 17 according to the method described in Example 5-1. The structures, NMR data, and MS data of these compounds are shown in Table 19-1.

Example 26-1
1- [1- (5-Methylpyrimidin-2-yl) piperidin-4-yl] -5- (2-fluoro-4-carbamoylphenyl] -1H-benzotriazole

実施例１３−１２で得られた化合物（５３ｍｇ）のジメチルスルホキシド（１．０ｍｌ）溶液に、１Ｍ水酸化ナトリウム水溶液（０．１９ｍｌ）を加え、１１５℃にて１５分攪拌した。反応溶液を室温まで冷却後、酢酸エチルで希釈した。有機層を水で３回、次いで飽和食塩水で洗浄し、無水硫酸マグネシウム乾燥後、減圧下に濃縮した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９９：１）にて精製を行い、表題化合物（５２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.17 (s, 3 H) 2.27 - 2.33 (m, 2 H) 2.39 - 2.48 (m, 2 H) 3.18 - 3.25 (m, 2 H) 4.92 - 4.98 (m, 2 H) 4.98 - 5.05 (m, 1 H) 7.60 (t, J=7.8 Hz, 1 H) 7.66 - 7.73 (m, 4 H) 8.21 (s, 2 H) 8.24 (s, 1 H).
MS ESI posi: 432[M+H]⁺.

To a solution of the compound obtained in Example 13-12 (53 mg) in dimethyl sulfoxide (1.0 ml) was added 1M aqueous sodium hydroxide solution (0.19 ml), and the mixture was stirred at 115 ° C. for 15 minutes. The reaction solution was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed 3 times with water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent: chloroform: methanol = 99: 1) to obtain the title compound (52 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.17 (s, 3 H) 2.27-2.33 (m, 2 H) 2.39-2.48 (m, 2 H) 3.18-3.25 (m, 2 H) 4.92-4.98 (m, 2 H) 4.98-5.05 (m, 1 H) 7.60 (t, J = 7.8 Hz, 1 H) 7.66-7.73 (m, 4 H) 8.21 (s, 2 H) 8.24 (s, 1 H) .
MS ESI posi: 432 [M + H] ⁺ .

  Example 26-2 was also synthesized according to the method described in Example 26-1 using the compound obtained in Example 14-12. The structures, NMR data, and MS data of these compounds are shown in Table 20-1.

Example 27-1
3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6- [4- (methylsulfonyl) phenyl] -3H- [1,2,3] triazolo [4,5-c ] Pyridine

参考例１８（７）で得られた化合物（３５ｍｌ）を用いて、実施例１−１と同様の操作にて反応及び精製を行い、表題化合物（２０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J=7.6 Hz, 3 H) 2.34 - 2.41 (m, 2 H) 2.41 - 2.50 (m, 2 H) 2.53 (q, J=7.6 Hz, 2 H) 3.11 (s, 3 H) 3.21 - 3.34 (m, 2 H) 5.03 (d, J=13.6 Hz, 2 H) 5.13 - 5.21 (m, 1 H) 8.08 (d, J=8.7 Hz, 2 H) 8.23 - 8.31 (m, 4 H) 8.43 (s, 1 H) 9.26 (s, 1 H).
MS ESI/APCI Dual posi: 464[M+H]⁺, 486[M+Na]⁺.
MS ESI/APCI Dual nega: 498[M+Cl]^-.
実施例２７−２〜２７−３も参考例１８（７）で得られた化合物を用いて、実施例２７−１に記載されている方法に準拠して合成した。それらの化合物の構造、ＮＭＲデータ、ＭＳデータを表２１−１に示す。

Using the compound (35 ml) obtained in Reference Example 18 (7), the reaction and purification were carried out in the same manner as in Example 1-1 to obtain the title compound (20 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J = 7.6 Hz, 3 H) 2.34-2.41 (m, 2 H) 2.41-2.50 (m, 2 H) 2.53 (q, J = 7.6 Hz, 2 H) 3.11 (s, 3 H) 3.21-3.34 (m, 2 H) 5.03 (d, J = 13.6 Hz, 2 H) 5.13-5.21 (m, 1 H) 8.08 (d, J = 8.7 Hz , 2 H) 8.23-8.31 (m, 4 H) 8.43 (s, 1 H) 9.26 (s, 1 H).
MS ESI / APCI Dual posi: 464 [M + H] ⁺ , 486 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 498 [M + Cl] ^- .
Examples 27-2 to 27-3 were also synthesized according to the method described in Example 27-1 using the compound obtained in Reference Example 18 (7). The structures, NMR data and MS data of these compounds are shown in Table 21-1.

Example 28-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenoxy] -1H-benzotriazole (1) tert-butyl 4- {5- [ 4- (Methylsulfonyl) phenoxy] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例９で得られた化合物（１５３ｍｇ）をテトラヒドロフラン（４．０ｍｌ）−水（１．０ｍｌ）の混合溶液に溶解し、過ヨウ素酸ナトリウム（１５３ｍｇ）、酢酸（０．０１４ｍｌ）を加え、室温にて１２時間攪拌した。反応液を酢酸エチルで抽出し、有機層を水、飽和食塩水で洗浄、無水硫酸マグネシウムで乾燥後、減圧下に濃縮した。得られた残渣をクロロホルム（１．５ｍｌ）に溶解し、４−メチルスルホニルフェノール（９２ｍｇ）、酢酸銅（II）（６５ｍｇ）、及びトリエチルアミン（０．２５ｍｌ）を加え、室温にて２４時間攪拌した。反応液を減圧下で濃縮し、残渣を酢酸エチルで抽出した。有機層をアンモニア水、水、飽和食塩水で洗浄し、無水硫酸マグネシウムで乾燥後、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝９０：１０）にて精製を行い、表題化合物（３７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.17 - 2.24 (m, 2 H) 2.30 - 2.42 (m, 2 H) 2.99 - 3.12 (m, 2 H) 3.06 (s, 3 H) 4.25 - 4.45 (m, 2 H) 4.82 - 4.89 (m, 1 H) 7.09 - 7.12 (m, 2 H) 7.26 - 7.29 (m, 1 H) 7.62 (d, J=9.1 Hz, 1 H) 7.74 (d, J=2.1 Hz, 1 H) 7.89 - 7.93 (m, 2 H).
（２）１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［（４−メチルスルホニル）フェノキシ］−１Ｈ−ベンゾトリアゾール

The compound (153 mg) obtained in Reference Example 9 was dissolved in a mixed solution of tetrahydrofuran (4.0 ml) -water (1.0 ml), sodium periodate (153 mg) and acetic acid (0.014 ml) were added, For 12 hours. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in chloroform (1.5 ml), 4-methylsulfonylphenol (92 mg), copper (II) acetate (65 mg), and triethylamine (0.25 ml) were added, and the mixture was stirred at room temperature for 24 hours. . The reaction mixture was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with aqueous ammonia, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 90: 10) to give the title compound (37 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.17-2.24 (m, 2 H) 2.30-2.42 (m, 2 H) 2.99-3.12 (m, 2 H) 3.06 (s , 3 H) 4.25-4.45 (m, 2 H) 4.82-4.89 (m, 1 H) 7.09-7.12 (m, 2 H) 7.26-7.29 (m, 1 H) 7.62 (d, J = 9.1 Hz, 1 H) 7.74 (d, J = 2.1 Hz, 1 H) 7.89-7.93 (m, 2 H).
(2) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5-[(4-methylsulfonyl) phenoxy] -1H-benzotriazole

実施例２８−１（１）で得られた化合物（３７ｍｇ）を用いて実施例３−１、３−２と同様の操作にて反応及び精製を行い、表題化合物（２２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δppm 1.22 (t, J=7.4 Hz, 3 H) 2.26 - 2.32 (m, 2 H) 2.38 - 2.47 (m, 2 H) 2.51 (q, J=7.4 Hz, 2 H) 3.06 (s, 3 H) 3.16 - 3.23 (m, 2 H) 4.94 - 5.02 (m, 3 H) 7.08 - 7.13 (m, 2 H) 7.24 - 7.28 (m, 1 H) 7.63 (d, J=9.1 Hz, 1 H) 7.73 (d, J=1.7 Hz, 1 H) 7.89 - 7.93 (m, 2 H) 8.23 (s, 2 H).
MS ESI posi: 479[M+H]⁺.
実施例２９−１
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The compound (37 mg) obtained in Example 28-1 (1) was used for the reaction and purification in the same manner as in Examples 3-1 and 3-2 to obtain the title compound (22 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δppm 1.22 (t, J = 7.4 Hz, 3 H) 2.26-2.32 (m, 2 H) 2.38-2.47 (m, 2 H) 2.51 (q, J = 7.4 Hz , 2 H) 3.06 (s, 3 H) 3.16-3.23 (m, 2 H) 4.94-5.02 (m, 3 H) 7.08-7.13 (m, 2 H) 7.24-7.28 (m, 1 H) 7.63 (d , J = 9.1 Hz, 1 H) 7.73 (d, J = 1.7 Hz, 1 H) 7.89-7.93 (m, 2 H) 8.23 (s, 2 H).
MS ESI posi: 479 [M + H] ⁺ .
Example 29-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridine

参考例１６で得られた化合物（１００ｍｇ）に４−（メチルスルホニル）フェノール（５３．４ｍｇ）、ヨウ化銅（４．９１ｍｇ）、ピコリン酸（６．３５ｍｇ）、リン酸三カリウム（１０９ｍｇ）を加えた。反応系内をアルゴンで置換し、ジメチルスルホキシド（０．５１６ｍｌ）を加え、１００℃にて１５時間攪拌した。反応液に水を加え、酢酸エチルにて抽出した。有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２〜１：４）にて精製し、表題化合物（８７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.14 - 2.21 (m, 2 H) 2.27 - 2.36 (m, 2 H) 2.50 (q, J=7.6 Hz, 2 H) 3.05 (s, 3 H) 3.13 - 3.20 (m, 2 H) 4.77 - 4.84 (m, 1 H) 4.93 - 5.00 (m, 2 H) 7.14 - 7.19 (m, 2 H) 7.33 (d, J=0.8 Hz, 1 H) 7.90 - 7.94 (m, 2 H) 8.04 (s, 1 H) 8.22 (s, 2 H) 8.74 (s, 1 H).
MS ESI/APCI Dual posi: 479[M+H]⁺.
MS ESI/APCI Dual nega: 477[M-H]^-, 513[M+Cl]^-.

4- (methylsulfonyl) phenol (53.4 mg), copper iodide (4.91 mg), picolinic acid (6.35 mg), tripotassium phosphate (109 mg) were added to the compound (100 mg) obtained in Reference Example 16. added. The reaction system was replaced with argon, dimethyl sulfoxide (0.516 ml) was added, and the mixture was stirred at 100 ° C. for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2 to 1: 4) to give the title compound (87 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.14-2.21 (m, 2 H) 2.27-2.36 (m, 2 H) 2.50 (q, J = 7.6 Hz, 2 H) 3.05 (s, 3 H) 3.13-3.20 (m, 2 H) 4.77-4.84 (m, 1 H) 4.93-5.00 (m, 2 H) 7.14-7.19 (m, 2 H) 7.33 ( d, J = 0.8 Hz, 1 H) 7.90-7.94 (m, 2 H) 8.04 (s, 1 H) 8.22 (s, 2 H) 8.74 (s, 1 H).
MS ESI / APCI Dual posi: 479 [M + H] ⁺ .
MS ESI / APCI Dual nega: 477 [MH] ^- , 513 [M + Cl] ^- .

  Example 29-2 was also synthesized according to the method described in Example 29-1 using the compound synthesized in Reference Example 16 and the corresponding phenol. The structure, NMR data, and MS data of these compounds are shown in Table 22-1.

Example 30-1
3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6- [4- (methylsulfonyl) phenoxy] -3H- [1,2,3] triazolo [4,5-c ] Pyridine

参考例１８（７）で得られた化合物（９０ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（７０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.30 - 2.36 (m, 2 H) 2.36 - 2.44 (m, 2 H) 2.51 (q, J=7.6 Hz, 2 H) 3.07 (s, 3 H) 3.17 - 3.26 (m, 2 H) 5.00 (d, J=13.6 Hz, 2 H) 5.06 - 5.14 (m, 1 H) 7.20 - 7.24 (m, 2 H) 7.62 (d, J=1.2 Hz, 1 H) 7.94 - 7.98 (m, 2 H) 8.23 (s, 2 H) 8.83 (d, J=1.2 Hz, 1 H).
MS ESI/APCI Dual posi: 480[M+H]⁺, 502[M+Na]⁺.
MS ESI/APCI Dual nega: 514[M+Cl]^-.
実施例３１−１
２−［（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−インダゾル−５−イル｝フェニル）スルホニル］エタノール

The compound (90 mg) obtained in Reference Example 18 (7) was used for the reaction and purification in the same manner as in Example 29-1, and the title compound (70 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.30-2.36 (m, 2 H) 2.36-2.44 (m, 2 H) 2.51 (q, J = 7.6 Hz, 2 H) 3.07 (s, 3 H) 3.17-3.26 (m, 2 H) 5.00 (d, J = 13.6 Hz, 2 H) 5.06-5.14 (m, 1 H) 7.20-7.24 (m, 2 H ) 7.62 (d, J = 1.2 Hz, 1 H) 7.94-7.98 (m, 2 H) 8.23 (s, 2 H) 8.83 (d, J = 1.2 Hz, 1 H).
MS ESI / APCI Dual posi: 480 [M + H] ⁺ , 502 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 514 [M + Cl] ^- .
Example 31-1
2-[(4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-indazol-5-yl} phenyl) sulfonyl] ethanol

参考例１９で得られた化合物（１００ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（２．３ｍｌ）溶液へ、参考例Ｄ−２で得られた化合物（８０ｍｇ）、［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（II）ジクロリド ジクロロメタン錯体（１０ｍｇ）、２Ｍ炭酸ナトリウム水溶液（３５０μｌ）を加え、１００℃にて１時間攪拌した。室温へ冷却後、反応液へ水を加え、酢酸エチルにて抽出し、得られた有機層を水、飽和食塩水にて順次洗浄した。無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９８：２〜９３：７）にて精製後、酢酸エチル−クロロホルム−ヘキサン混合液で再結晶を行い、表題化合物（６７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.08 - 2.20 (m, 2 H) 2.24 - 2.42 (m, 2 H) 2.50 (q, J=7.6 Hz, 2 H) 2.78 (t, J=6.5 Hz, 1 H) 3.07 - 3.22 (m, 2 H) 3.36 - 3.45 (m, 2 H) 4.01 - 4.11 (m, 2 H) 4.67 - 4.81 (m, 1 H) 4.90 - 5.03 (m, 2 H) 7.57 - 7.68 (m, 2 H) 7.80 - 7.87 (m, 2 H) 7.96 - 8.04 (m, 3 H) 8.08 (s, 1 H) 8.21 (s, 2 H).
MS ESI/APCI Dual posi: 492[M+H]⁺，514[M+Na]⁺．
実施例３２−１
プロパン−２−イル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

To a solution of the compound obtained in Reference Example 19 (100 mg) in N, N-dimethylformamide (2.3 ml), the compound obtained in Reference Example D-2 (80 mg), [1,1′-bis (diphenylphosphine). Fino) ferrocene] palladium (II) dichloride dichloromethane complex (10 mg), 2M aqueous sodium carbonate solution (350 μl) were added, and the mixture was stirred at 100 ° C. for 1 hour. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed successively with water and saturated brine. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 98: 2-93: 7), and recrystallized with a mixed solution of ethyl acetate-chloroform-hexane to give the title compound (67 mg) as colorless. Obtained as a powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.08-2.20 (m, 2 H) 2.24-2.42 (m, 2 H) 2.50 (q, J = 7.6 Hz, 2 H) 2.78 (t, J = 6.5 Hz, 1 H) 3.07-3.22 (m, 2 H) 3.36-3.45 (m, 2 H) 4.01-4.11 (m, 2 H) 4.67-4.81 (m, 1 H) 4.90-5.03 (m, 2 H) 7.57-7.68 (m, 2 H) 7.80-7.87 (m, 2 H) 7.96-8.04 (m, 3 H) 8.08 (s, 1 H) 8.21 (s, 2 H).
MS ESI / APCI Dual posi: 492 [M + H] ⁺ , 514 [M + Na] ⁺ .
Example 32-1
Propan-2-yl 4- [5- (2-methylpyridin-3-yl) -1H-indazol-1-yl] piperidin-1-carboxylate

参考例２０で得られた化合物（８０．０ｍｇ）のクロロホルム（２ｍｌ）溶液へ、トリエチルアミン（７６．１μｌ）、クロロぎ酸イソプロピル（４７．０μｌ）を加え室温にて１時間半攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝６：４〜２：８）にて精製後、ヘキサン−ジエチルエーテル混合液で粉末化し、表題化合物（６１．２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J=6.4 Hz, 6 H) 2.01 - 2.13 (m, 2 H) 2.21 - 2.39 (m, 2 H) 2.53 (s, 3 H) 2.95 - 3.12 (m, 2 H) 4.28 - 4.51 (m, 2 H) 4.56 - 4.70 (m, 1 H) 4.91 - 5.03 (m, 1 H) 7.17 - 7.24 (m, 1 H) 7.31 - 7.38 (m, 1 H) 7.49 - 7.60 (m, 2 H) 7.66 - 7.69 (m, 1 H) 8.05 (s, 1 H) 8.50 - 8.55 (m, 1 H).
MS ESI/APCI Dual posi: 379[M+H], 401[M+Na]+.
実施例３２−２
プロピル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

Triethylamine (76.1 μl) and isopropyl chloroformate (47.0 μl) were added to a chloroform (2 ml) solution of the compound (80.0 mg) obtained in Reference Example 20, and the mixture was stirred at room temperature for 1.5 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 6: 4-2: 8) and then pulverized with a hexane-diethyl ether mixture to give the title compound (61.2 mg) as a colorless powder. Got as.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J = 6.4 Hz, 6 H) 2.01-2.13 (m, 2 H) 2.21-2.39 (m, 2 H) 2.53 (s, 3 H) 2.95-3.12 (m, 2 H) 4.28-4.51 (m, 2 H) 4.56-4.70 (m, 1 H) 4.91-5.03 (m, 1 H) 7.17-7.24 (m, 1 H) 7.31-7.38 (m , 1 H) 7.49-7.60 (m, 2 H) 7.66-7.69 (m, 1 H) 8.05 (s, 1 H) 8.50-8.55 (m, 1 H).
MS ESI / APCI Dual posi: 379 [M + H], 401 [M + Na] +.
Example 32-2
Propyl 4- [5- (2-methylpyridin-3-yl) -1H-indazol-1-yl] piperidine-1-carboxylate

参考例２０で得られた化合物（８０．０ｍｇ）とクロロぎ酸プロピル（４６．１μｌ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（６９．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (t, J=7.5 Hz, 3 H) 1.65 - 1.77 (m, 2 H) 2.02 - 2.14 (m, 2 H) 2.30 (qd, J=12.2, 4.1 Hz, 2 H) 2.53 (s, 3 H) 2.95 - 3.14 (m, 2 H) 4.09 (t, J=6.7 Hz, 2 H) 4.29 - 4.49 (m, 2 H) 4.63 (tt, J=11.4, 4.4 Hz, 1 H) 7.16 - 7.24 (m, 1 H) 7.35 (dd, J=8.6, 1.6 Hz, 1 H) 7.48 - 7.59 (m, 2 H) 7.67 (dd, J=1.6, 0.9 Hz, 1 H) 8.05 (s, 1 H) 8.52 (dd, J=4.9, 1.6 Hz, 1 H).
MS ESI/APCI Dual posi: 379[M+H]⁺, 401[M+Na]⁺.
実施例３２−３
（メチルシクロプロピル）メチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

The compound (80.0 mg) obtained in Reference Example 20 and propyl chloroformate (46.1 μl) were used for reaction and purification in the same manner as in Example 32-1, and the title compound (69.8 mg) ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (t, J = 7.5 Hz, 3 H) 1.65-1.77 (m, 2 H) 2.02-2.14 (m, 2 H) 2.30 (qd, J = 12.2 , 4.1 Hz, 2 H) 2.53 (s, 3 H) 2.95-3.14 (m, 2 H) 4.09 (t, J = 6.7 Hz, 2 H) 4.29-4.49 (m, 2 H) 4.63 (tt, J = 11.4, 4.4 Hz, 1 H) 7.16-7.24 (m, 1 H) 7.35 (dd, J = 8.6, 1.6 Hz, 1 H) 7.48-7.59 (m, 2 H) 7.67 (dd, J = 1.6, 0.9 Hz , 1 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.9, 1.6 Hz, 1 H).
MS ESI / APCI Dual posi: 379 [M + H] ⁺ , 401 [M + Na] ⁺ .
Example 32-3
(Methylcyclopropyl) methyl 4- [5- (2-methylpyridin-3-yl) -1H-indazol-1-yl] piperidine-1-carboxylate

１−メチルシクロプロパンメタノール（１１８ｍｇ）のテトラヒドロフラン（１ｍｌ）溶液へ、トリホスゲン（１３８ｍｇ）のテトラヒドロフラン（１ｍｌ）溶液を加え、室温で１時間攪拌した。反応液を氷冷し、トリエチルアミン（３８０μｌ）を加えた。室温で２０分攪拌した後に、参考例２０で得られた化合物（８０．０ｍｇ）を反応溶液の中に加え、更に室温で２時間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝６：４〜２：８）にて精製後、ヘキサン−ジエチルエーテル混合液で粉末化し、表題化合物（７５．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.33 - 0.42 (m, 2 H) 0.48 - 0.55 (m, 2 H) 1.16 (s, 3 H) 2.03 - 2.17 (m, 2 H) 2.23 - 2.40 (m, 2 H) 2.53 (s, 3 H) 2.95 - 3.17 (m, 2 H) 3.93 (s, 2 H) 4.34 - 4.47 (m, 2 H) 4.58 - 4.72 (m, 1 H) 7.21 (dd, J=7.6, 4.8 Hz, 1 H) 7.35 (dd, J=8.6, 1.6 Hz, 1 H) 7.48 - 7.60 (m, 2 H) 8.05 (s, 1 H) 8.52 (dd, J=4.8, 1.7 Hz, 1 H).
MS ESI/APCI Dual posi: 405[M+H]⁺.
実施例３２−４
シクロブチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

To a solution of 1-methylcyclopropanemethanol (118 mg) in tetrahydrofuran (1 ml) was added a solution of triphosgene (138 mg) in tetrahydrofuran (1 ml), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was ice-cooled and triethylamine (380 μl) was added. After stirring at room temperature for 20 minutes, the compound obtained in Reference Example 20 (80.0 mg) was added to the reaction solution, and the mixture was further stirred at room temperature for 2 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 6: 4-2: 8), and then powdered with a hexane-diethyl ether mixture to give the title compound (75.6 mg) as a colorless powder. Got as.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.33-0.42 (m, 2 H) 0.48-0.55 (m, 2 H) 1.16 (s, 3 H) 2.03-2.17 (m, 2 H) 2.23-2.40 (m, 2 H) 2.53 (s, 3 H) 2.95-3.17 (m, 2 H) 3.93 (s, 2 H) 4.34-4.47 (m, 2 H) 4.58-4.72 (m, 1 H) 7.21 (dd , J = 7.6, 4.8 Hz, 1 H) 7.35 (dd, J = 8.6, 1.6 Hz, 1 H) 7.48-7.60 (m, 2 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.8, 1.7 Hz, 1 H).
MS ESI / APCI Dual posi: 405 [M + H] ⁺ .
Example 32-4
Cyclobutyl 4- [5- (2-methylpyridin-3-yl) -1H-indazol-1-yl] piperidine-1-carboxylate

参考例２０で得られた化合物（８０．０ｍｇ）とシクロブタノール（９８．７ｍｇ）を用いて、実施例３２−３と同様の操作にて反応及び精製を行い、表題化合物（３８．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61 - 1.88 (m, 2 H) 2.01 - 2.18 (m, 4 H) 2.19 - 2.45 (m, 4 H) 2.53 (s, 3 H) 2.94 - 3.13 (m, 2 H) 4.27 - 4.45 (m, 2 H) 4.56 - 4.69 (m, 1 H) 4.90 - 5.06 (m, 1 H) 7.17 - 7.25 (m, 1 H) 7.30 - 7.40 (m, 1 H) 7.47 - 7.59 (m, 2 H) 7.67 (dd, J=1.6, 0.9 Hz, 1 H) 8.05 (s, 1 H) 8.52 (dd, J=4.9, 1.8 Hz, 1 H).
MS ESI/APCI Dual posi: 391[M+H]⁺.
実施例３２−５
１，１−ジフルオロ−２−メチルプロパン−２−イル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−インダゾル−１−イル］ピペリジン−１−カルボキシラート

Using the compound (80.0 mg) obtained in Reference Example 20 and cyclobutanol (98.7 mg), the reaction and purification were conducted in the same manner as in Example 32-3, and the title compound (38.6 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61-1.88 (m, 2 H) 2.01-2.18 (m, 4 H) 2.19-2.45 (m, 4 H) 2.53 (s, 3 H) 2.94-3.13 (m, 2 H) 4.27-4.45 (m, 2 H) 4.56-4.69 (m, 1 H) 4.90-5.06 (m, 1 H) 7.17-7.25 (m, 1 H) 7.30-7.40 (m, 1 H ) 7.47-7.59 (m, 2 H) 7.67 (dd, J = 1.6, 0.9 Hz, 1 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.9, 1.8 Hz, 1 H).
MS ESI / APCI Dual posi: 391 [M + H] ⁺ .
Example 32-5
1,1-difluoro-2-methylpropan-2-yl 4- [5- (2-methylpyridin-3-yl) -1H-indazol-1-yl] piperidine-1-carboxylate

参考例２０で得られた化合物（８０．０ｍｇ）のクロロホルム（２ｍｌ）溶液へ、トリエチルアミン（７６．１μｌ）、参考例Ｉ−１で得られた化合物（１４２ｍｇ）を加え室温にて３０分間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出した。得られた有機層をフェーズセパレーターに通して、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝６：４〜２：８）にて精製後、ヘキサン−ジエチルエーテル混合液で粉末化し、表題化合物（１０１ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53 - 1.58 (m, 6 H) 2.04 - 2.13 (m, 2 H) 2.21 - 2.38 (m, 2 H) 2.53 (s, 3 H) 2.96 - 3.18 (m, 2 H) 4.19 - 4.47 (m, 2 H) 4.56 - 4.72 (m, 1 H) 5.93 - 6.42 (m, 1 H) 7.21 (dd, J=7.6, 4.8 Hz, 1 H) 7.35 (dd, J=8.7, 1.6 Hz, 1 H) 7.46 - 7.59 (m, 2 H) 7.67 (s, 1 H) 8.05 (s, 1 H) 8.52 (dd, J=4.8, 1.9 Hz, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺.
実施例３３−１
プロパン−２−イル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

To a solution of the compound obtained in Reference Example 20 (80.0 mg) in chloroform (2 ml), triethylamine (76.1 μl) and the compound obtained in Reference Example I-1 (142 mg) were added and stirred at room temperature for 30 minutes. . A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 6: 4-2: 8) and then pulverized with a hexane-diethyl ether mixture to give the title compound (101 mg) as a colorless powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.53-1.58 (m, 6 H) 2.04-2.13 (m, 2 H) 2.21-2.38 (m, 2 H) 2.53 (s, 3 H) 2.96-3.18 (m, 2 H) 4.19-4.47 (m, 2 H) 4.56-4.72 (m, 1 H) 5.93-6.42 (m, 1 H) 7.21 (dd, J = 7.6, 4.8 Hz, 1 H) 7.35 (dd , J = 8.7, 1.6 Hz, 1 H) 7.46-7.59 (m, 2 H) 7.67 (s, 1 H) 8.05 (s, 1 H) 8.52 (dd, J = 4.8, 1.9 Hz, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ .
Example 33-1
Propan-2-yl 4- [5- (2-methylpyridin-3-yl) -1H-benzotriazol-1-yl] piperidin-1-carboxylate

参考例２１で得られた化合物（８０．０ｍｇ）とクロロぎ酸イソプロピル（４６．８μｌ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（８３．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.2 Hz, 6 H) 2.18 - 2.29 (m, 2 H) 2.31 - 2.46 (m, 2 H) 2.52 (s, 3 H) 3.03 - 3.17 (m, 2 H) 4.31 - 4.51 (m, 2 H) 4.82 - 5.06 (m, 2 H) 7.21 - 7.26 (m, 1 H) 7.43 - 7.48 (m, 1 H) 7.54 - 7.60 (m, 1 H) 7.61 - 7.67 (m, 1 H) 8.02 (s, 1 H) 8.53 - 8.59 (m, 1 H).
MS ESI/APCI Dual posi: 380[M+H]⁺, 402[M+Na]⁺.
MS ESI/APCI Dual nega: 414[M+Cl]^-.
実施例３３−２
プロピル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

The compound (80.0 mg) obtained in Reference Example 21 and isopropyl chloroformate (46.8 μl) were used for reaction and purification in the same manner as in Example 32-1, and the title compound (83.6 mg) ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.2 Hz, 6 H) 2.18-2.29 (m, 2 H) 2.31-2.46 (m, 2 H) 2.52 (s, 3 H) 3.03-3.17 (m, 2 H) 4.31-4.51 (m, 2 H) 4.82-5.06 (m, 2 H) 7.21-7.26 (m, 1 H) 7.43-7.48 (m, 1 H) 7.54-7.60 (m , 1 H) 7.61-7.67 (m, 1 H) 8.02 (s, 1 H) 8.53-8.59 (m, 1 H).
MS ESI / APCI Dual posi: 380 [M + H] ⁺ , 402 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 414 [M + Cl] ^- .
Example 33-2
Propyl 4- [5- (2-methylpyridin-3-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例２１で得られた化合物（８０．０ｍｇ）とクロロぎ酸プロピル（４６．０μｌ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（６１．４ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.99 (t, J=7.4 Hz, 3 H) 1.71 (sxt, J=7.1 Hz, 2 H) 2.17 - 2.30 (m, 2 H) 2.32 - 2.49 (m, 2 H) 2.52 (s, 3 H) 3.04 - 3.22 (m, 2 H) 4.11 (t, J=6.7 Hz, 2 H) 4.35 - 4.48 (m, 2 H) 4.84 - 4.98 (m, 1 H) 7.24 (dd, J=7.5, 5.0 Hz, 1 H) 7.40 - 7.51 (m, 1 H) 7.54 - 7.67 (m, 2 H) 8.02 (s, 1 H) 8.56 (dd, J=4.9, 1.8 Hz, 1 H).
MS ESI/APCI Dual posi: 380[M+H]⁺, 402[M+Na]⁺.
MS ESI/APCI Dual nega: 414[M+Cl]^-.
実施例３３−３
（１−メチルシクロプロピル）メチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

The compound obtained in Reference Example 21 (80.0 mg) and propyl chloroformate (46.0 μl) were used for reaction and purification in the same manner as in Example 32-1, and the title compound (61.4 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.99 (t, J = 7.4 Hz, 3 H) 1.71 (sxt, J = 7.1 Hz, 2 H) 2.17-2.30 (m, 2 H) 2.32-2.49 ( m, 2 H) 2.52 (s, 3 H) 3.04-3.22 (m, 2 H) 4.11 (t, J = 6.7 Hz, 2 H) 4.35-4.48 (m, 2 H) 4.84-4.98 (m, 1 H ) 7.24 (dd, J = 7.5, 5.0 Hz, 1 H) 7.40-7.51 (m, 1 H) 7.54-7.67 (m, 2 H) 8.02 (s, 1 H) 8.56 (dd, J = 4.9, 1.8 Hz , 1 H).
MS ESI / APCI Dual posi: 380 [M + H] ⁺ , 402 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 414 [M + Cl] ^- .
Example 33-3
(1-Methylcyclopropyl) methyl 4- [5- (2-methylpyridin-3-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例２１で得られた化合物（８０．０ｍｇ）と１−メチルシクロプロパンメタノール（１１７ｍｇ）を用いて、実施例３２−３と同様の操作にて反応及び精製を行い、表題化合物（２２．１ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.34 - 0.43 (m, 2 H) 0.49 - 0.56 (m, 2 H) 1.17 (s, 3 H) 2.15 - 2.32 (m, 2 H) 2.33 - 2.50 (m, 2 H) 2.53 (s, 3 H) 3.05 - 3.24 (m, 2 H) 3.95 (s, 2 H) 4.36 - 4.51 (m, 2 H) 4.85 - 5.01 (m, 1 H) 7.18 - 7.25 (m, 1 H) 7.46 (dd, J=8.5, 1.6 Hz, 1 H) 7.53 - 7.68 (m, 3 H) 8.02 (s, 1 H) 8.56 (dd, J=4.7, 1.9 Hz, 1 H).
MS ESI/APCI Dual posi: 406[M+H]⁺.
実施例３３−４
シクロブチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

Using the compound (80.0 mg) obtained in Reference Example 21 and 1-methylcyclopropanemethanol (117 mg), the reaction and purification were conducted in the same manner as in Example 32-3, and the title compound (22.1 mg) ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.34-0.43 (m, 2 H) 0.49-0.56 (m, 2 H) 1.17 (s, 3 H) 2.15-2.32 (m, 2 H) 2.33-2.50 (m, 2 H) 2.53 (s, 3 H) 3.05-3.24 (m, 2 H) 3.95 (s, 2 H) 4.36-4.51 (m, 2 H) 4.85-5.01 (m, 1 H) 7.18-7.25 (m, 1 H) 7.46 (dd, J = 8.5, 1.6 Hz, 1 H) 7.53-7.68 (m, 3 H) 8.02 (s, 1 H) 8.56 (dd, J = 4.7, 1.9 Hz, 1 H) .
MS ESI / APCI Dual posi: 406 [M + H] ⁺ .
Example 33-4
Cyclobutyl 4- [5- (2-methylpyridin-3-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例２１で得られた化合物（８０．０ｍｇ）とシクロブタノール（９８．３ｍｇ）を用いて、実施例３２−３と同様の操作にて反応及び精製を行い、表題化合物（６０．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.60 - 1.86 (m, 2 H) 2.02 - 2.16 (m, 2 H) 2.19 - 2.29 (m, 2 H) 2.31 - 2.49 (m, 4 H) 2.52 (s, 3 H) 3.02 - 3.19 (m, 2 H) 4.34 - 4.47 (m, 2 H) 4.84 - 5.07 (m, 2 H) 7.20 - 7.26 (m, 1 H) 7.46 (dd, J=8.5, 1.4 Hz, 1 H) 7.53 - 7.66 (m, 2 H) 8.02 (s, 1 H) 8.56 (dd, J=4.8, 1.7 Hz, 1 H).
MS ESI/APCI Dual posi: 392[M+H]⁺, 414[M+Na]⁺.
実施例３３−５
１，１−ジフルオロ−２−メチルプロパン−２−イル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ベンゾトリアゾル−１−イル］ピペリジン−１−カルボキシラート

Using the compound (80.0 mg) obtained in Reference Example 21 and cyclobutanol (98.3 mg), the reaction and purification were carried out in the same manner as in Example 32-3, and the title compound (60.6 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.60-1.86 (m, 2 H) 2.02-2.16 (m, 2 H) 2.19-2.29 (m, 2 H) 2.31-2.49 (m, 4 H) 2.52 (s, 3 H) 3.02-3.19 (m, 2 H) 4.34-4.47 (m, 2 H) 4.84-5.07 (m, 2 H) 7.20-7.26 (m, 1 H) 7.46 (dd, J = 8.5, 1.4 Hz, 1 H) 7.53-7.66 (m, 2 H) 8.02 (s, 1 H) 8.56 (dd, J = 4.8, 1.7 Hz, 1 H).
MS ESI / APCI Dual posi: 392 [M + H] ⁺ , 414 [M + Na] ⁺ .
Example 33-5
1,1-difluoro-2-methylpropan-2-yl 4- [5- (2-methylpyridin-3-yl) -1H-benzotriazol-1-yl] piperidine-1-carboxylate

参考例２１で得られた化合物（８０．０ｍｇ）を用いて、実施例３２−５と同様の操作にて反応及び精製を行い、表題化合物（７８．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.56 (t, J=1.5 Hz, 6 H) 2.17 - 2.31 (m, 2 H) 2.32 - 2.50 (m, 2 H) 2.53 (s, 3 H) 3.01 - 3.25 (m, 2 H) 4.21 - 4.43 (m, 2 H) 4.84 - 4.97 (m, 1 H) 5.97 - 6.43 (m, 1 H) 7.21 - 7.25 (m, 1 H) 7.47 (dd, J=8.5, 1.4 Hz, 1 H) 7.51 - 7.68 (m, 2 H) 8.02 (d, J=1.2 Hz, 1 H) 8.56 (dd, J=4.9, 1.2 Hz, 1 H).
MS ESI/APCI Dual posi: 430[M+H]⁺, 452[M+Na]⁺.
MS ESI/APCI Dual nega: 464[M+Cl]^-.
実施例３４−１
２−（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝フェニル）プロパン−２−オール

The compound (80.0 mg) obtained in Reference Example 21 was used for reaction and purification in the same manner as in Example 32-5 to obtain the title compound (78.9 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.56 (t, J = 1.5 Hz, 6 H) 2.17-2.31 (m, 2 H) 2.32-2.50 (m, 2 H) 2.53 (s, 3 H) 3.01-3.25 (m, 2 H) 4.21-4.43 (m, 2 H) 4.84-4.97 (m, 1 H) 5.97-6.43 (m, 1 H) 7.21-7.25 (m, 1 H) 7.47 (dd, J = 8.5, 1.4 Hz, 1 H) 7.51-7.68 (m, 2 H) 8.02 (d, J = 1.2 Hz, 1 H) 8.56 (dd, J = 4.9, 1.2 Hz, 1 H).
MS ESI / APCI Dual posi: 430 [M + H] ⁺ , 452 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 464 [M + Cl] ^- .
Example 34-1
2- (4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} phenyl) propan-2-ol

参考例１０で得られた化合物（１００ｍｇ）と参考例Ｅ−８で得られた化合物（１０１ｍｇ）を用いて、実施例２−１と同様の操作にて反応及び精製を行い、表題化合物（６６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.4 Hz, 3 H) 1.65 (s, 6 H) 2.25 - 2.33 (m, 2 H) 2.39 - 2.48 (m, 2 H) 2.51 (q, J=7.4 Hz, 2 H) 3.16 - 3.25 (m, 2 H) 4.95 - 5.03 (m, 3 H) 7.58 - 7.66 (m, 5 H) 7.71 - 7.76 (m, 1 H) 8.21 - 8.26 (m, 3 H).
MS ESI/APCI Dual posi: 443[M+H]⁺, 465[M+Na]⁺.
実施例３４−２
２−（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝フェニル）アセトアミド

Using the compound (100 mg) obtained in Reference Example 10 and the compound (101 mg) obtained in Reference Example E-8, the reaction and purification were carried out in the same manner as in Example 2-1, to obtain the title compound (66 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.4 Hz, 3 H) 1.65 (s, 6 H) 2.25-2.33 (m, 2 H) 2.39-2.48 (m, 2 H) 2.51 (q, J = 7.4 Hz, 2 H) 3.16-3.25 (m, 2 H) 4.95-5.03 (m, 3 H) 7.58-7.66 (m, 5 H) 7.71-7.76 (m, 1 H) 8.21- 8.26 (m, 3 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ , 465 [M + Na] ⁺ .
Example 34-2
2- (4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} phenyl) acetamide

参考例１０で得られた化合物（１００ｍｇ）と参考例Ｅ−９で得られた化合物（１０１ｍｇ）を用いて、実施例２−１と同様の操作にて反応及び精製を行い、表題化合物（６５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.4 Hz, 3 H) 2.25 - 2.33 (m, 2 H) 2.39 - 2.48 (m, 2 H) 2.51 (q, J=7.4 Hz, 2 H) 3.16 - 3.24 (m, 2 H) 3.66 (s, 2 H) 4.95 - 5.03 (m, 3 H) 5.49 (br. s., 2 H) 7.37 - 7.43 (m, 2 H) 7.62 - 7.68 (m, 3 H) 7.69 - 7.75 (m, 1 H) 8.21 - 8.27 (m, 3 H).
MS ESI/APCI Dual posi: 442[M+H]⁺.
MS ESI/APCI Dual nega: 440[M-H]^-.
実施例３５−１
２−［（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−２−フルオロフェニル）スルホニル］エタノール

Using the compound (100 mg) obtained in Reference Example 10 and the compound (101 mg) obtained in Reference Example E-9, the reaction and purification were carried out in the same manner as in Example 2-1, and the title compound (65 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.4 Hz, 3 H) 2.25-2.33 (m, 2 H) 2.39-2.48 (m, 2 H) 2.51 (q, J = 7.4 Hz, 2 H) 3.16-3.24 (m, 2 H) 3.66 (s, 2 H) 4.95-5.03 (m, 3 H) 5.49 (br. S., 2 H) 7.37-7.43 (m, 2 H) 7.62 -7.68 (m, 3 H) 7.69-7.75 (m, 1 H) 8.21-8.27 (m, 3 H).
MS ESI / APCI Dual posi: 442 [M + H] ⁺ .
MS ESI / APCI Dual nega: 440 [MH] ^- .
Example 35-1
2-[(4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -2-fluorophenyl) sulfonyl] ethanol

参考例１１で得られた化合物（６７ｍｇ）と参考例Ｄ−５で得られた化合物（６６ｍｇ）を用いて、実施例２−１と同様の操作にて反応及び精製を行い、表題化合物（４３ｍｇ）を淡褐色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19 - 1.27 (m, 3 H) 2.22 - 2.56 (m, 6 H) 2.61 (t, J=6.5 Hz, 1 H) 3.14 - 3.28 (m, 2 H) 3.58 - 3.64 (m, 2 H) 4.05 - 4.14 (m, 2 H) 4.94 - 5.08 (m, 3 H) 7.49 - 7.56 (m, 1 H) 7.60 - 7.65 (m, 1 H) 7.70 - 7.73 (m, 2 H) 8.01 - 8.09 (m, 1 H) 8.23 (s, 2 H) 8.27 - 8.32 (m, 1 H).
MS ESI/APCI Dual posi: 511[M+H], 533[M+Na]⁺.

Using the compound (67 mg) obtained in Reference Example 11 and the compound (66 mg) obtained in Reference Example D-5, the reaction and purification were carried out in the same manner as in Example 2-1, to obtain the title compound (43 mg ) Was obtained as a light brown solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19-1.27 (m, 3 H) 2.22-2.56 (m, 6 H) 2.61 (t, J = 6.5 Hz, 1 H) 3.14-3.28 (m, 2 H) 3.58-3.64 (m, 2 H) 4.05-4.14 (m, 2 H) 4.94-5.08 (m, 3 H) 7.49-7.56 (m, 1 H) 7.60-7.65 (m, 1 H) 7.70-7.73 (m, 2 H) 8.01-8.09 (m, 1 H) 8.23 (s, 2 H) 8.27-8.32 (m, 1 H).
MS ESI / APCI Dual posi: 511 [M + H], 533 [M + Na] ⁺ .

  The following Examples 35-2 to 35-4 are also based on the method described in Example 2-1 using the compound obtained in Reference Example 11 and the compound obtained in Reference Examples D-6 to D-8. And synthesized. The structure, NMR data, and MS data of these compounds are shown in Table 23-1.

Example 36-1
5- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -N- (propan-2-yl) pyrimidine-2-carboxamide (1) tert-Butyl 4- {5- [2- (propan-2-ylcarbamoyl) pyrimidin-5-yl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例９で得られた化合物（５０ｍｇ）、参考例Ｆ−６で得られた化合物（３４ｍｇ）、［１，１´−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（ＩＩ）ジクロリド ジクロロメタン錯体（１０ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．１８ｍｌ）のＮ，Ｎ−ジメチルホルムアミド溶液（０．５０ｍｌ）をアルゴン雰囲気下、１００℃で９時間攪拌した。反応を室温まで冷やした後、セライト（登録商標）濾過し濾液を濃縮、得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１：０〜１：４）にて精製し、表題化合物（９０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 - 1.37 (m, 6 H) 1.46 - 1.58 (m, 9 H) 2.16 - 2.48 (m, 4 H) 3.00 - 3.18 (m, 2 H) 4.28 - 4.47 (m, 3 H) 4.83 - 5.02 (m, 1 H) 7.67 - 7.83 (m, 2 H) 8.28 - 8.37 (m, 1 H) 9.10 - 9.16 (m, 2 H).
（２）５−［１−（ピペリジン−４−イル）−１Ｈ−ベンゾトリアゾル−５−イル］−Ｎ−（プロパン−２−イル）ピリミジン−２−カルボキサミド 塩酸塩

Compound (50 mg) obtained in Reference Example 9, compound (34 mg) obtained in Reference Example F-6, [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (10 mg) A 2M aqueous sodium carbonate solution (0.18 ml) in N, N-dimethylformamide (0.50 ml) was stirred at 100 ° C. for 9 hours under an argon atmosphere. The reaction was cooled to room temperature, filtered through Celite (registered trademark), and the filtrate was concentrated. The obtained residue was purified by NH silica gel column chromatography (developing solvent: chloroform: methanol = 1: 0 to 1: 4) to give the title Compound (90 mg) was obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30-1.37 (m, 6 H) 1.46-1.58 (m, 9 H) 2.16-2.48 (m, 4 H) 3.00-3.18 (m, 2 H) 4.28 -4.47 (m, 3 H) 4.83-5.02 (m, 1 H) 7.67-7.83 (m, 2 H) 8.28-8.37 (m, 1 H) 9.10-9.16 (m, 2 H).
(2) 5- [1- (Piperidin-4-yl) -1H-benzotriazol-5-yl] -N- (propan-2-yl) pyrimidine-2-carboxamide hydrochloride

実施例３６−１（１）で得られた化合物（９０ｍｇ）のメタノール（２．０ｍｌ）溶液へ４Ｍ塩酸ジオキサン溶液（０．５０ｍｌ）を加え、室温で一晩攪拌した。反応溶液を濃縮して表題化合物（５８ｍｇ）を得た。
¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.22 (d, J=6.5 Hz, 6 H) 2.24 - 2.39 (m, 2 H) 2.46 - 2.64 (m, 2 H) 3.10 - 3.29 (m, 2 H) 3.45 - 3.60 (m, 2 H) 4.07 - 4.22 (m, 1 H) 5.19 - 5.74 (m, 3 H) 8.11 - 8.26 (m, 2 H) 8.69 (s, 1 H) 9.40 (s, 2 H).
（３）５−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ベンゾトリアゾル−５−イル｝−Ｎ−（プロパン−２−イル）ピリミジン−２−カルボキサミド

To a solution of the compound (90 mg) obtained in Example 36-1 (1) in methanol (2.0 ml) was added 4M hydrochloric acid dioxane solution (0.50 ml), and the mixture was stirred overnight at room temperature. The reaction solution was concentrated to give the title compound (58 mg).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ ppm 1.22 (d, J = 6.5 Hz, 6 H) 2.24-2.39 (m, 2 H) 2.46-2.64 (m, 2 H) 3.10-3.29 (m, 2 H) 3.45-3.60 (m, 2 H) 4.07-4.22 (m, 1 H) 5.19-5.74 (m, 3 H) 8.11-8.26 (m, 2 H) 8.69 (s, 1 H) 9.40 (s, 2 H).
(3) 5- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazol-5-yl} -N- (propan-2-yl) pyrimidine- 2-carboxamide

参考例３６−１（２）で得られた化合物（５５ｍｇ）のジメチルスルホキシド（１．３ｍｌ）溶液へ、２−クロロ−５−エチルピリミジン（３０ｍｇ）、炭酸セシウム（１３４ｍｇ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１８０℃にて２０分撹拌した。室温へ放冷後水を加え、酢酸エチルで抽出した。得られた有機層を飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥し、乾燥剤を濾別した。溶媒を減圧留去し、得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１０：０〜０：１０）にて精製し、表題化合物（２９ｍｇ）を白色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 1.33 (d, J=6.5 Hz, 6 H) 2.23 - 2.58 (m, 6 H) 3.14 - 3.29 (m, 2 H) 4.31 - 4.48 (m, 1 H) 4.94 -5.11 (m, 3 H) 7.69 - 7.80 (m, 2 H) 7.84 - 7.93 (m, 1 H) 8.24 (s, 2 H) 8.31 - 8.34 (m, 1 H) 9.12 (s, 2 H).
MS ESI/APCI Dual posi: 472[M+H]⁺.
実施例３７−１
プロパン−２−イル ４−｛５−［４−（エチルカルバモイル）−２，５−ジフルオロフェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−カルボキシラート

To a solution of the compound obtained in Reference Example 36-1 (2) (55 mg) in dimethyl sulfoxide (1.3 ml), 2-chloro-5-ethylpyrimidine (30 mg) and cesium carbonate (134 mg) were added, and The mixture was stirred at 180 ° C. for 20 minutes under microwave irradiation using a reaction apparatus (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling to room temperature, water was added and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the desiccant was filtered off. The solvent was distilled off under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 10: 0 to 0:10) to obtain the title compound (29 mg) as a white solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 1.33 (d, J = 6.5 Hz, 6 H) 2.23-2.58 (m, 6 H) 3.14-3.29 ( m, 2 H) 4.31-4.48 (m, 1 H) 4.94 -5.11 (m, 3 H) 7.69-7.80 (m, 2 H) 7.84-7.93 (m, 1 H) 8.24 (s, 2 H) 8.31- 8.34 (m, 1 H) 9.12 (s, 2 H).
MS ESI / APCI Dual posi: 472 [M + H] ⁺ .
Example 37-1
Propan-2-yl 4- {5- [4- (ethylcarbamoyl) -2,5-difluorophenyl] -1H-benzotriazol-1-yl} piperidine-1-carboxylate

参考例２２で得られた化合物（７０．０ｍｇ）と７０％エタノールアミン水溶液（１５．２ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（５４．０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 - 1.34 (m, 9 H) 2.16 - 2.48 (m, 4 H) 3.03 - 3.17 (m, 2 H) 3.48 - 3.63 (m, 2 H) 4.30 - 4.50 (m, 2 H) 4.81 - 5.07 (m, 2 H) 6.70 - 6.86 (m, 1 H) 7.25 - 7.33 (m, 1 H) 7.61 - 7.74 (m, 2 H) 7.91 - 8.00 (m, 1 H) 8.25 (s, 1 H).
MS ESI/APCI Dual posi: 472[M+H]⁺.
MS ESI/APCI Dual nega: 506[M+Cl]^-.

Using the compound (70.0 mg) obtained in Reference Example 22 and a 70% aqueous ethanolamine solution (15.2 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (54. 0 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24-1.34 (m, 9 H) 2.16-2.48 (m, 4 H) 3.03-3.17 (m, 2 H) 3.48-3.63 (m, 2 H) 4.30 -4.50 (m, 2 H) 4.81-5.07 (m, 2 H) 6.70-6.86 (m, 1 H) 7.25-7.33 (m, 1 H) 7.61-7.74 (m, 2 H) 7.91-8.00 (m, 1 H) 8.25 (s, 1 H).
MS ESI / APCI Dual posi: 472 [M + H] ⁺ .
MS ESI / APCI Dual nega: 506 [M + Cl] ^- .

  The following Examples 37-2 to 37-4 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 22 and the corresponding amine. Table 24-1 shows the structures, NMR data, and MS data of these compounds.

Example 38-1
1- [1- (2,2-Dimethylpropyl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（５０ｍｇ）のジメチルスルホキシド（０．５ｍｌ）−テトラヒドロフラン（０．５ｍｌ）混合溶液へ、ピバルアルデヒド（１５ｍｇ）、酢酸（２０μｌ）、ナトリウムトリアセトキシボロヒドリド（７４ｍｇ）を加え、室温にて一晩、５０℃にて３時間攪拌した。反応液を濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１０：０〜９：１）にて精製し、表題化合物（４０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (s, 9 H) 2.03 - 2.15 (m, 2 H) 2.18 (s, 2 H) 2.44 - 2.61 (m, 4 H) 3.02 - 3.08 (m, 2 H) 3.12 (s, 3 H) 4.60 - 4.78 (m, 1 H) 7.73 (m, J=1.1 Hz, 2 H) 7.81 - 7.87 (m, 2 H) 8.02 - 8.09 (m, 2 H) 8.27 - 8.30 (m, 1 H).
MS ESI/APCI Dual posi: 427[M+H]⁺.
実施例３８−２
１−［１−（２−エチルブチル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾール

To a mixed solution of the compound (50 mg) obtained in Reference Example 12 in dimethylsulfoxide (0.5 ml) -tetrahydrofuran (0.5 ml), pivalaldehyde (15 mg), acetic acid (20 μl), sodium triacetoxyborohydride (74 mg) And stirred at room temperature overnight and at 50 ° C. for 3 hours. The reaction mixture was concentrated, and the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 10: 0-9: 1) to give the title compound (40 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (s, 9 H) 2.03-2.15 (m, 2 H) 2.18 (s, 2 H) 2.44-2.61 (m, 4 H) 3.02-3.08 (m , 2 H) 3.12 (s, 3 H) 4.60-4.78 (m, 1 H) 7.73 (m, J = 1.1 Hz, 2 H) 7.81-7.87 (m, 2 H) 8.02-8.09 (m, 2 H) 8.27-8.30 (m, 1 H).
MS ESI / APCI Dual posi: 427 [M + H] ⁺ .
Example 38-2
1- [1- (2-Ethylbutyl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-benzotriazole

参考例１２で得られた化合物（５０ｍｇ）と１−ブロモ−２−エチルブタン（３３ｍｇ）を用いて、実施例１６−１と同様の操作にて反応及び精製を行い、表題化合物（５１ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.85 - 0.94 (m, 6 H) 1.28 - 1.53 (m, 5 H) 2.10 - 2.30 (m, 6 H) 2.42 - 2.60 (m, 2 H) 3.04 - 3.16 (m, 5 H) 4.67 - 4.81 (m, 1 H) 7.72 - 7.74 (m, 2 H) 7.81 - 7.87 (m, 2 H) 8.03 - 8.10 (m, 2 H) 8.27 - 8.30 (m, 1 H).
MS ESI/APCI Dual posi: 441[M+H]⁺.
MS ESI/APCI Dual nega: 475[M+Cl]^-.

Using the compound (50 mg) obtained in Reference Example 12 and 1-bromo-2-ethylbutane (33 mg), the reaction and purification were carried out in the same manner as in Example 16-1, and the title compound (51 mg) was purified colorless. Obtained as a powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.85-0.94 (m, 6 H) 1.28-1.53 (m, 5 H) 2.10-2.30 (m, 6 H) 2.42-2.60 (m, 2 H) 3.04 -3.16 (m, 5 H) 4.67-4.81 (m, 1 H) 7.72-7.74 (m, 2 H) 7.81-7.87 (m, 2 H) 8.03-8.10 (m, 2 H) 8.27-8.30 (m, 1 H).
MS ESI / APCI Dual posi: 441 [M + H] ⁺ .
MS ESI / APCI Dual nega: 475 [M + Cl] ^- .

  The following Examples 38-3 to 38-5 were also synthesized according to the method described in Example 16-1 using the compound obtained in Reference Example 12 and the corresponding alkyl halide. The structure, NMR data, and MS data of these compounds are shown in Table 25-1.

Example 39-1
N, N-dimethyl-2- (4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidin-5-amine (1) 5- [4- (Methylsulfonyl) phenyl] -1- [1- (5-nitropyrimidin-2-yl) piperidin-4-yl] -1H-benzotriazole

参考例１２で得られた化合物（２００ｍｇ）と２−クロロ−５−ニトロピリミジン（１３４ｍｇ）を用いて実施例３６−１（３）と同様の反応及び精製を行い、表題化合物（３９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.33 - 2.59 (m, 4 H) 3.12 (s, 3 H) 3.43 - 3.59 (m, 2 H) 5.00 - 5.20 (m, 3 H) 7.65 - 7.80 (m, 2 H) 7.84 (d, J=8.4 Hz, 2 H) 8.07 (d, J=8.4 Hz, 2 H) 8.31 (s, 1 H) 9.13 (s, 2 H).
（２）２−（４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−イル）ピリミジン−５−アミン

Using the compound (200 mg) obtained in Reference Example 12 and 2-chloro-5-nitropyrimidine (134 mg), the same reaction and purification as in Example 36-1 (3) were carried out, and the title compound (39 mg) was purified colorless. Obtained as a powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.33-2.59 (m, 4 H) 3.12 (s, 3 H) 3.43-3.59 (m, 2 H) 5.00-5.20 (m, 3 H) 7.65-7.80 (m, 2 H) 7.84 (d, J = 8.4 Hz, 2 H) 8.07 (d, J = 8.4 Hz, 2 H) 8.31 (s, 1 H) 9.13 (s, 2 H).
(2) 2- (4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidin-5-amine

参考例３９−１（１）で得られた化合物（３９ｍｇ）、鉄（２３ｍｇ）の飽和塩化アンモニウム水溶液（１．０ｍｌ）−エタノール（１．０ｍｌ）混合溶液を５０℃で３日間攪拌した。反応液をセライト（登録商標）濾過し、濾液を濃縮して表題化合物を含む粗生成物を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17 - 2.59 (m, 4 H) 3.04 - 3.24 (m, 5 H) 4.80 - 4.92 (m, 2 H) 4.93 - 5.06 (m, 1 H) 7.66 - 7.77 (m, 2 H) 7.81 - 7.87 (m, 2 H) 8.01 - 8.09 (m, 4 H) 8.28 - 8.30 (m, 1 H).
（３）Ｎ，Ｎ−ジメチル−２−（４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ベンゾトリアゾル−１−イル｝ピペリジン−１−イル）ピリミジン−５−アミン

A mixed solution of the compound obtained in Reference Example 39-1 (1) (39 mg) and iron (23 mg) in saturated aqueous ammonium chloride (1.0 ml) -ethanol (1.0 ml) was stirred at 50 ° C. for 3 days. The reaction solution was filtered through Celite (registered trademark), and the filtrate was concentrated to obtain a crude product containing the title compound.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.17-2.59 (m, 4 H) 3.04-3.24 (m, 5 H) 4.80-4.92 (m, 2 H) 4.93-5.06 (m, 1 H) 7.66 -7.77 (m, 2 H) 7.81-7.87 (m, 2 H) 8.01-8.09 (m, 4 H) 8.28-8.30 (m, 1 H).
(3) N, N-dimethyl-2- (4- {5- [4- (methylsulfonyl) phenyl] -1H-benzotriazol-1-yl} piperidin-1-yl) pyrimidin-5-amine

参考例３９−１（２）で得られた粗生成物、ホルムアルデヒド（７２ｍｇ）、ナトリウムトリアセトキシボロヒドリド（６９ｍｇ）、酢酸（２０μｌ）のクロロホルム（２．０ｍｌ）溶液を室温で一晩攪拌した。反応液を濃縮した後、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１０：０〜１９：１）、ＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１０：０〜９７：３）、ＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 酢酸エチル：ヘキサン＝０：１０〜１０：０）で精製し、表題化合物（１１ｍｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.22 - 2.34 (m, 2 H) 2.38 - 2.56 (m, 2 H) 2.87 (s, 6 H) 3.09 - 3.23 (m, 5 H) 4.83 - 4.93 (m, 2 H) 4.93 - 5.07 (m, 1 H) 7.70 - 7.73 (m, 2 H) 7.81 - 7.86 (m, 2 H) 8.03 - 8.07 (m, 2 H) 8.09 (s, 2 H) 8.28 - 8.31 (m, 1 H).
MS ESI/APCI Dual posi: 478[M+H]⁺.
実施例４０−１
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−｛４−［（メチルスルホニル）メチル］フェニル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

A solution of the crude product obtained in Reference Example 39-1 (2), formaldehyde (72 mg), sodium triacetoxyborohydride (69 mg), and acetic acid (20 μl) in chloroform (2.0 ml) was stirred at room temperature overnight. After concentrating the reaction solution, the obtained residue was subjected to silica gel column chromatography (developing solvent chloroform: methanol = 10: 0 to 19: 1), NH silica gel column chromatography (developing solvent chloroform: methanol = 10: 0 to 97: 3) and purification by NH silica gel column chromatography (developing solvent: ethyl acetate: hexane = 0: 10 to 10: 0) to obtain the title compound (11 mg) as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.22-2.34 (m, 2 H) 2.38-2.56 (m, 2 H) 2.87 (s, 6 H) 3.09-3.23 (m, 5 H) 4.83-4.93 (m, 2 H) 4.93-5.07 (m, 1 H) 7.70-7.73 (m, 2 H) 7.81-7.86 (m, 2 H) 8.03-8.07 (m, 2 H) 8.09 (s, 2 H) 8.28 -8.31 (m, 1 H).
MS ESI / APCI Dual posi: 478 [M + H] ⁺ .
Example 40-1
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- {4-[(methylsulfonyl) methyl] phenyl} -1H-pyrazolo [3,4-c] pyridine

参考例１６で得られた化合物（１００ｍｇ）、参考例Ｅ−７で得られた化合物（９３．６ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（１５ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．２ｍｌ）のエタノール（２ｍｌ）懸濁液を、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１６０℃にて３０分間撹拌した。冷却後反応液をセライト（登録商標）ろ過し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝７：３〜０：１０）にて精製後、ヘキサン／２−プロパノールから再結晶し、表題化合物（１０３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19 - 1.26 (m, 3 H) 2.12 - 2.24 (m, 2 H) 2.25 - 2.43 (m, 2 H) 2.45 - 2.56 (m, 2 H) 2.79 (s, 3 H) 3.11 - 3.26 (m, 2 H) 4.32 (s, 2 H) 4.80 - 5.04 (m, 3 H) 7.50 - 7.57 (m, 2 H) 8.03 - 8.11 (m, 4 H) 8.22 (s, 2 H) 9.09 - 9.13 (m, 1 H).
MS ESI/APCI Dual posi: 477[M+H]⁺, 499[M+Na]⁺.
MS ESI/APCI Dual nega: 475[M-H]^-.
実施例４０−２
５−［２，５−ジフルオロ−４−（メチルスルホニル）フェニル］−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）５−［２，５−ジフルオロ−４−（メチルスルファニル）フェニル］−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Ethanol of the compound obtained in Reference Example 16 (100 mg), the compound obtained in Reference Example E-7 (93.6 mg), tetrakis (triphenisphosphine) palladium (15 mg), 2M aqueous sodium carbonate solution (0.2 ml) The suspension (2 ml) was stirred for 30 minutes at 160 ° C. under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage). After cooling, the reaction solution was filtered through Celite (registered trademark), and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 7: 3-0: 10) and recrystallized from hexane / 2-propanol to give the title compound (103 mg) as a colorless powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.19-1.26 (m, 3 H) 2.12-2.24 (m, 2 H) 2.25-2.43 (m, 2 H) 2.45-2.56 (m, 2 H) 2.79 (s, 3 H) 3.11-3.26 (m, 2 H) 4.32 (s, 2 H) 4.80-5.04 (m, 3 H) 7.50-7.57 (m, 2 H) 8.03-8.11 (m, 4 H) 8.22 (s, 2 H) 9.09-9.13 (m, 1 H).
MS ESI / APCI Dual posi: 477 [M + H] ⁺ , 499 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 475 [MH] ^- .
Example 40-2
5- [2,5-Difluoro-4- (methylsulfonyl) phenyl] -1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] Pyridine (1) 5- [2,5-difluoro-4- (methylsulfanyl) phenyl] -1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3 4-c] pyridine

参考例１６で得られた化合物（１５５ｍｇ）と参考例Ｅ−１１で得られた化合物（１３８ｍｇ）を用いて、実施例２−１と同様の操作にて反応及び精製を行い、表題化合物（５４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.15 - 2.21 (m, 2 H) 2.29 - 2.38 (m, 2 H) 2.47 - 2.53 (m, 5 H) 3.13 - 3.22 (m, 2 H) 4.81 - 4.89 (m, 1 H) 4.94 - 5.00 (m, 2 H) 7.03 (dd, J=11.4, 6.0 Hz, 1 H) 7.84 (dd, J=10.7, 6.6 Hz, 1 H) 8.08 (s, 1 H) 8.15 (s, 1 H) 8.22 (s, 2 H) 9.09 (s, 1 H).
MS ESI/APCI Dual posi: 467[M+H]⁺.
（２）５−［２，５−ジフルオロ−４−（メチルスルホニル）フェニル］−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (155 mg) obtained in Reference Example 16 and the compound (138 mg) obtained in Reference Example E-11, the reaction and purification were carried out in the same manner as in Example 2-1, and the title compound (54 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.15-2.21 (m, 2 H) 2.29-2.38 (m, 2 H) 2.47-2.53 (m, 5 H) 3.13-3.22 (m, 2 H) 4.81-4.89 (m, 1 H) 4.94-5.00 (m, 2 H) 7.03 (dd, J = 11.4, 6.0 Hz, 1 H) 7.84 (dd, J = 10.7 , 6.6 Hz, 1 H) 8.08 (s, 1 H) 8.15 (s, 1 H) 8.22 (s, 2 H) 9.09 (s, 1 H).
MS ESI / APCI Dual posi: 467 [M + H] ⁺ .
(2) 5- [2,5-Difluoro-4- (methylsulfonyl) phenyl] -1- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4 -C] pyridine

実施例４０−２（１）で得られた化合物（５４ｍｇ）のアセトン（３ｍｌ）溶液へ、オキソン（登録商標）（２２１ｍｇ）の水（１ｍｌ）懸濁液を加え室温で６時間半攪拌した。反応液へ水、飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１９：１〜１：４）にて精製後、ヘキサンで粉末化し、表題化合物（３２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.7 Hz, 3 H) 2.16 - 2.23 (m, 2 H) 2.31 - 2.39 (m, 2 H) 2.50 (q, J=7.7 Hz, 2 H) 3.15 - 3.21 (m, 2 H) 3.28 (s, 3 H) 4.84 - 4.91 (m, 1 H) 4.95 - 5.01 (m, 2 H) 7.79 (dd, J=10.1, 5.6 Hz, 1 H) 8.13 - 8.18 (m, 2 H) 8.22 (s, 2 H) 8.31 (s, 1 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 499[M+H]⁺.
実施例４０−３
２−［（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝フェニル）スルホニル］エタノール
（１）５−｛４−［（２−｛［ｔｅｒｔ−ブチル（ジメチル）シリル］オキシ｝エチル）スルファニル］フェニル｝−１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

A suspension of Oxone (registered trademark) (221 mg) in water (1 ml) was added to a solution of the compound (54 mg) obtained in Example 40-2 (1) in acetone (3 ml), and the mixture was stirred at room temperature for 6 and a half hours. Water and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 19: 1 to 1: 4) and pulverized with hexane to give the title compound (32 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.7 Hz, 3 H) 2.16-2.23 (m, 2 H) 2.31-2.39 (m, 2 H) 2.50 (q, J = 7.7 Hz, 2 H) 3.15-3.21 (m, 2 H) 3.28 (s, 3 H) 4.84-4.91 (m, 1 H) 4.95-5.01 (m, 2 H) 7.79 (dd, J = 10.1, 5.6 Hz, 1 H) 8.13-8.18 (m, 2 H) 8.22 (s, 2 H) 8.31 (s, 1 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 499 [M + H] ⁺ .
Example 40-3
2-[(4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} phenyl) sulfonyl] ethanol (1) 5- {4-[(2-{[tert-butyl (dimethyl) silyl] oxy} ethyl) sulfanyl] phenyl} -1- [1- (5-ethylpyrimidin-2-yl) piperidine-4- Yl] -1H-pyrazolo [3,4-c] pyridine

参考例１６で得られた化合物（１５０ｍｇ）と参考例Ｅ−１２で得られた化合物（１９９ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（１９９ｍｇ）を無色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.06 (s, 6 H) 0.87 - 0.91 (m, 9 H) 1.22 (t, J=7.6 Hz, 3 H) 2.12 - 2.24 (m, 2 H) 2.25 - 2.42 (m, 2 H) 2.50 (d, J=7.6 Hz, 2 H) 3.06 - 3.26 (m, 4 H) 3.83 (s, 2 H) 4.78 - 4.90 (m, 1 H) 4.91 - 5.02 (m, 2 H) 7.42 - 7.48 (m, 2 H) 7.91 - 7.97 (m, 2 H) 7.98 - 8.00 (m, 1 H) 8.06 (s, 1 H) 8.22 (s, 2 H) 9.07 - 9.10 (m, 1 H).
MS ESI/APCI Dual posi: 575[M+H]⁺, 597[M+Na]⁺.
（２）２−［（４−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝フェニル）スルホニル］エタノール

Using the compound (150 mg) obtained in Reference Example 16 and the compound (199 mg) obtained in Reference Example E-12, the reaction and purification were carried out in the same manner as in Example 40-1, to obtain the title compound (199 mg). ) Was obtained as a colorless solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.06 (s, 6 H) 0.87-0.91 (m, 9 H) 1.22 (t, J = 7.6 Hz, 3 H) 2.12-2.24 (m, 2 H) 2.25-2.42 (m, 2 H) 2.50 (d, J = 7.6 Hz, 2 H) 3.06-3.26 (m, 4 H) 3.83 (s, 2 H) 4.78-4.90 (m, 1 H) 4.91-5.02 ( m, 2 H) 7.42-7.48 (m, 2 H) 7.91-7.97 (m, 2 H) 7.98-8.00 (m, 1 H) 8.06 (s, 1 H) 8.22 (s, 2 H) 9.07-9.10 ( m, 1 H).
MS ESI / APCI Dual posi: 575 [M + H] ⁺ , 597 [M + Na] ⁺ .
(2) 2-[(4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} phenyl) Sulfonyl] ethanol

実施例４０−３（１）で得られた化合物（１９２ｍｇ）を用いて、実施例４０−２（２）と同様の操作にて反応及び精製を行い、表題化合物（４２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.13 - 2.26 (m, 2 H) 2.26 - 2.43 (m, 2 H) 2.50 (q, J=7.6 Hz, 2 H) 2.82 (s, 1 H) 3.11 - 3.25 (m, 2 H) 3.36 - 3.44 (m, 2 H) 4.00 - 4.09 (m, 2 H) 4.81 - 5.05 (m, 3 H) 7.99 - 8.07 (m, 2 H) 8.13 (s, 2 H) 8.21 - 8.30 (m, 4 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 493[M+H]⁺, 515[M+Na]⁺.
実施例４０−４
３−｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−２−カルボニトリル

Using the compound (192 mg) obtained in Example 40-3 (1), the reaction and purification were conducted in the same manner as in Example 40-2 (2) to obtain the title compound (42 mg) as a colorless powder. It was.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.13-2.26 (m, 2 H) 2.26-2.43 (m, 2 H) 2.50 (q, J = 7.6 Hz, 2 H) 2.82 (s, 1 H) 3.11-3.25 (m, 2 H) 3.36-3.44 (m, 2 H) 4.00-4.09 (m, 2 H) 4.81-5.05 (m, 3 H) 7.99- 8.07 (m, 2 H) 8.13 (s, 2 H) 8.21-8.30 (m, 4 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 493 [M + H] ⁺ , 515 [M + Na] ⁺ .
Example 40-4
3- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridine-2-carbonitrile

参考例１６で得られた化合物（１５０ｍｇ）の１，４−ジオキサン（１ｍｌ）溶液に、参考例Ｅ−１３で得られた化合物（１３６ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（２３ｍｇ）、フッ化セシウム（１１８ｍｇ）、ヨウ化銅（７．４ｍｇ）を加え、８０℃にて４．５時間、１１０℃にて１時間、１２０℃にて３０分攪拌した。反応液に水を加え、酢酸エチルにて抽出した。有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝８：１〜１：１〜１：９〜クロロホルム：メタノール＝９：１）にて精製後、得られた残渣を再度シリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝４：１〜２：３〜１：９）にて精製した。得られた残渣をジエチルエーテルにて粉末化し、表題化合物（９２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.8 Hz, 3 H) 2.18 - 2.24 (m, 2 H) 2.32 - 2.40 (m, 2 H) 2.50 (q, J=7.8 Hz, 2 H) 3.15 - 3.22 (m, 2 H) 4.86 - 4.93 (m, 1 H) 4.96 - 5.02 (m, 2 H) 7.61 - 7.64 (m, 1 H) 8.17 (s, 1 H) 8.21 (d, J=1.2 Hz, 1 H) 8.22 (s, 2 H) 8.25 - 8.28 (m, 1 H) 8.71 - 8.76 (m, 1 H) 9.19 (s, 1 H).
MS ESI/APCI Dual posi: 411[M+H]⁺, 433[M+Na]⁺.

To a 1,4-dioxane (1 ml) solution of the compound obtained in Reference Example 16 (150 mg), the compound obtained in Reference Example E-13 (136 mg), tetrakis (triphenisphosphine) palladium (23 mg), fluoride Cesium (118 mg) and copper iodide (7.4 mg) were added, and the mixture was stirred at 80 ° C. for 4.5 hours, 110 ° C. for 1 hour, and 120 ° C. for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue is purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 8: 1 to 1: 1 to 1: 9 to chloroform: methanol = 9: 1), and the obtained residue is again purified on a silica gel column. The product was purified by chromatography (developing solvent hexane: ethyl acetate = 4: 1 to 2: 3 to 1: 9). The obtained residue was triturated with diethyl ether to give the title compound (92 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.8 Hz, 3 H) 2.18-2.24 (m, 2 H) 2.32-2.40 (m, 2 H) 2.50 (q, J = 7.8 (Hz, 2 H) 3.15-3.22 (m, 2 H) 4.86-4.93 (m, 1 H) 4.96-5.02 (m, 2 H) 7.61-7.64 (m, 1 H) 8.17 (s, 1 H) 8.21 ( d, J = 1.2 Hz, 1 H) 8.22 (s, 2 H) 8.25-8.28 (m, 1 H) 8.71-8.76 (m, 1 H) 9.19 (s, 1 H).
MS ESI / APCI Dual posi: 411 [M + H] ⁺ , 433 [M + Na] ⁺ .

  The following Examples 40-5 to 40-19 were also synthesized according to the method described in Example 40-1 using the boronic acid or boronic acid ester corresponding to the compound obtained in Reference Example 16. The structures, NMR data, and MS data of these compounds are shown in Tables 26-1 to 26-2.

Example 41-1
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- [3-fluoro-4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２３−Ａで得られた化合物（１００ｍｇ）と３−フルオロ−４−（メチルスルホニル）フェニルボロン酸（８１．９ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（９５．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57 - 0.66 (m, 2 H) 0.88 - 0.97 (m, 2 H) 1.69 - 1.81 (m, 1 H) 2.13 - 2.24 (m, 2 H) 2.26 - 2.43 (m, 2 H) 3.10 - 3.24 (m, 2 H) 3.27 (s, 3 H) 4.81 - 4.92 (m, 1 H) 4.92 - 5.01 (m, 2 H) 7.95 - 8.08 (m, 3 H) 8.12 - 8.14 (m, 2 H) 8.17 (s, 2 H) 9.11 - 9.14 (m, 1 H).
MS ESI/APCI Dual posi: 493[M+H]⁺.

Reaction and purification were carried out in the same manner as in Example 40-1, using the compound (100 mg) obtained in Reference Example 23-A and 3-fluoro-4- (methylsulfonyl) phenylboronic acid (81.9 mg). To give the title compound (95.6 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.66 (m, 2 H) 0.88-0.97 (m, 2 H) 1.69-1.81 (m, 1 H) 2.13-2.24 (m, 2 H) 2.26 -2.43 (m, 2 H) 3.10-3.24 (m, 2 H) 3.27 (s, 3 H) 4.81-4.92 (m, 1 H) 4.92-5.01 (m, 2 H) 7.95-8.08 (m, 3 H ) 8.12-8.14 (m, 2 H) 8.17 (s, 2 H) 9.11-9.14 (m, 1 H).
MS ESI / APCI Dual posi: 493 [M + H] ⁺ .

  The following Examples 41-2 to 41-13 are also the compounds obtained in Reference Example 23-A and the compounds obtained in Reference Examples E-13 to E-15, 2-chloro-4-fluoro-pyridine-3- Synthesized according to the method described in Example 40-1 using boronic acid or the corresponding boronic acid or boronic ester. The structures, NMR data, and MS data of these compounds are shown in Tables 27-1 to 27-3.

Examples 41-14
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- (2-ethylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridine

実施例４１−８で得られた化合物（５０ｍｇ）のテトラヒドロフラン（１．１６ｍｌ）溶液へ、０℃にてトリス（２，４−ペンタンジオナト）鉄（２．０４ｍｇ）、Ｎ−メチルピロリドン（０．１６６ｍｌ）、０．９０Ｍ エチルマグネシウムブロミド・テトラヒドロフラン溶液（０．１５４ｍｌ）を加え、同温にて１０分撹拌した。反応液に水を加え、テトラヒドロフランを減圧留去し、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。残渣にジエチルエーテルを加え、水で洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１）にて精製後、ヘキサン−酢酸エチル混合溶液にて再結晶し、表題化合物（２０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.65 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.23 (t, J=7.4 Hz, 3 H) 1.71 - 1.78 (m, 1 H) 2.17 - 2.24 (m, 2 H) 2.30 - 2.40 (m, 2 H) 2.90 (q, J=7.4 Hz, 2 H) 3.14 - 3.22 (m, 2 H) 4.84 - 4.92 (m, 1 H) 4.94 - 5.01 (m, 2 H) 7.20 - 7.24 (m, 1 H) 7.67 - 7.71 (m, 2 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.59 - 8.63 (m, 1 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 426[M+H]⁺, 448[M+Na]⁺.
実施例４１−１５
５−（２−シクロプロピルピリジン−３−イル）−１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound (50 mg) obtained in Example 41-8 in tetrahydrofuran (1.16 ml) at 0 ° C., tris (2,4-pentandionato) iron (2.04 mg), N-methylpyrrolidone (0 .166 ml) and 0.90 M ethylmagnesium bromide / tetrahydrofuran solution (0.154 ml) were added, and the mixture was stirred at the same temperature for 10 minutes. Water was added to the reaction solution, and tetrahydrofuran was distilled off under reduced pressure, followed by extraction with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. Diethyl ether was added to the residue and washed with water. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (20 mg) as a colorless powder. .
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.65 (m, 2 H) 0.90-0.96 (m, 2 H) 1.23 (t, J = 7.4 Hz, 3 H) 1.71-1.78 (m, 1 H) 2.17-2.24 (m, 2 H) 2.30-2.40 (m, 2 H) 2.90 (q, J = 7.4 Hz, 2 H) 3.14-3.22 (m, 2 H) 4.84-4.92 (m, 1 H) 4.94-5.01 (m, 2 H) 7.20-7.24 (m, 1 H) 7.67-7.71 (m, 2 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.59-8.63 (m, 1 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 426 [M + H] ⁺ , 448 [M + Na] ⁺ .
Examples 41-15
5- (2-Cyclopropylpyridin-3-yl) -1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

実施例４１−８で得られた化合物（７０ｍｇ）と０．７Ｍ シクロプロピル・マグネシウムブロミド・テトラヒドロフラン溶液（０．２７８ｍｌ）を用いて、実施例４１−１４と同様の操作にて反応及び精製を行い、表題化合物（４１ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.65 (m, 2 H) 0.86 - 0.96 (m, 4 H) 1.17 - 1.22 (m, 2 H) 1.71 - 1.79 (m, 1 H) 2.16 - 2.23 (m, 3 H) 2.30 - 2.39 (m, 2 H) 3.14 - 3.22 (m, 2 H) 4.84 - 4.92 (m, 1 H) 4.93 - 5.00 (m, 2 H) 7.12 - 7.16 (m, 1 H) 7.69 - 7.74 (m, 1 H) 7.84 - 7.87 (m, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.47 - 8.51 (m, 1 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 438[M+H]⁺.
実施例４１−１６
１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−（６−エチル−２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）５−（６−クロロ−２−メチルピリジン−３−イル）−１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The reaction and purification were conducted in the same manner as in Example 41-14 using the compound (70 mg) obtained in Example 41-8 and 0.7M cyclopropyl / magnesium bromide / tetrahydrofuran solution (0.278 ml). The title compound (41 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.65 (m, 2 H) 0.86-0.96 (m, 4 H) 1.17-1.22 (m, 2 H) 1.71-1.79 (m, 1 H) 2.16 -2.23 (m, 3 H) 2.30-2.39 (m, 2 H) 3.14-3.22 (m, 2 H) 4.84-4.92 (m, 1 H) 4.93-5.00 (m, 2 H) 7.12-7.16 (m, 1 H) 7.69-7.74 (m, 1 H) 7.84-7.87 (m, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.47-8.51 (m, 1 H) 9.14 (s, 1 H ).
MS ESI / APCI Dual posi: 438 [M + H] ⁺ .
Examples 41-16
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- (6-ethyl-2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] Pyridine (1) 5- (6-chloro-2-methylpyridin-3-yl) -1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3 4-c] pyridine

参考例２３−Ａで得られた化合物（１００ｍｇ）、６−クロロ−２−メチルピリジン−３−ボロン酸（５１．５ｍｇ）、テトラキス（トリフェニスホスフィン）パラジウム（１４．４ｍｇ）、２Ｍ炭酸ナトリウム水溶液（０．２５０ｍｌ）のエタノール（２．５ｍｌ）懸濁液を、アルゴン雰囲気下、１５時間加熱還流した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１）にて精製し、表題化合物（７６ｍｇ）を淡黄色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 0.56 - 0.69 (m, 2 H) 0.83 - 1.00 (m, 2 H) 1.65 - 1.83 (m, 1 H) 2.10 - 2.51 (m, 4 H) 2.60 (s, 3 H) 3.08 - 3.30 (m, 2 H) 4.76 - 5.07 (m, 3 H) 7.21 - 7.33 (m, 1 H) 7.68 - 7.78 (m, 2 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 446[M+H]⁺, 468[M+Na]⁺.
MS ESI/APCI Dual nega: 444[M-H]^-.
（２）１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−（６−エチル−２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Compound (100 mg) obtained in Reference Example 23-A, 6-chloro-2-methylpyridine-3-boronic acid (51.5 mg), tetrakis (triphenisphosphine) palladium (14.4 mg), 2M aqueous sodium carbonate solution A suspension of (0.250 ml) in ethanol (2.5 ml) was heated to reflux for 15 hours under an argon atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1) to obtain the title compound (76 mg) as a pale yellow oily substance.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 0.56-0.69 (m, 2 H) 0.83-1.00 (m, 2 H) 1.65-1.83 (m, 1 H) 2.10-2.51 (m, 4 H) 2.60 (s, 3 H) 3.08-3.30 (m, 2 H) 4.76-5.07 (m, 3 H) 7.21-7.33 (m, 1 H) 7.68-7.78 (m, 2 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 446 [M + H] ⁺ , 468 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 444 [MH] ^- .
(2) 1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- (6-ethyl-2-methylpyridin-3-yl) -1H-pyrazolo [3,4 -C] pyridine

実施例４１−１６（１）で得られた化合物（７６ｍｇ）を用いて、実施例４１−１４と同様の操作にて反応及び精製を行い、表題化合物（３３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.65 (m, 2 H) 0.89 - 0.96 (m, 2 H) 1.34 (t, J=7.6 Hz, 3 H) 1.70 - 1.79 (m, 1 H) 2.15 - 2.25 (m, 2 H) 2.29 - 2.41 (m, 2 H) 2.59 (s, 3 H) 2.86 (q, J=7.6 Hz, 2 H) 3.13 - 3.23 (m, 2 H) 4.82 - 4.91 (m, 1 H) 4.93 - 5.01 (m, 2 H) 7.11 (d, J=7.8 Hz, 1 H) 7.64 - 7.72 (m, 2 H) 8.07 (s, 1 H) 8.16 (s, 2 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 440[M+H]⁺.
実施例４１−１７
５−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−６−メチルピリジン−２−カルボニトリル

Using the compound (76 mg) obtained in Example 41-16 (1), the reaction and purification were carried out in the same manner as in Example 41-14 to obtain the title compound (33 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.65 (m, 2 H) 0.89-0.96 (m, 2 H) 1.34 (t, J = 7.6 Hz, 3 H) 1.70-1.79 (m, 1 H) 2.15-2.25 (m, 2 H) 2.29-2.41 (m, 2 H) 2.59 (s, 3 H) 2.86 (q, J = 7.6 Hz, 2 H) 3.13-3.23 (m, 2 H) 4.82- 4.91 (m, 1 H) 4.93-5.01 (m, 2 H) 7.11 (d, J = 7.8 Hz, 1 H) 7.64-7.72 (m, 2 H) 8.07 (s, 1 H) 8.16 (s, 2 H ) 9.11 (s, 1 H).
MS ESI / APCI Dual posi: 440 [M + H] ⁺ .
Examples 41-17
5- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -6-methylpyridin-2- Carbonitrile

実施例４１−１６（１）で得られた化合物（５０ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１．１２ｍｌ）溶液へ、テトラキス（トリフェニスホスフィン）パラジウム（１３．０ｍｇ）、シアン化亜鉛（１５．８ｍｇ）を加え、アルゴン雰囲気下、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１００℃にて３０分間撹拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜２：３）にて精製後、ヘキサン−酢酸エチル混合溶液にて再結晶し、表題化合物（１８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.65 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.72 - 1.78 (m, 1 H) 2.16 - 2.24 (m, 2 H) 2.30 - 2.40 (m, 2 H) 2.67 (s, 3 H) 3.14 - 3.21 (m, 2 H) 4.85 - 4.93 (m, 1 H) 4.94 - 5.02 (m, 2 H) 7.65 (d, J=7.8 Hz, 1 H) 7.75 - 7.78 (m, 1 H) 7.89 (d, J=7.8 Hz, 1 H) 8.12 (s, 1 H) 8.17 (s, 2 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 437[M+H]⁺.
実施例４１−１８
５−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−６−メチルピリジン−２−カルボキサミド

To a solution of the compound (50 mg) obtained in Example 41-16 (1) in N, N-dimethylformamide (1.12 ml), tetrakis (triphenisphosphine) palladium (13.0 mg), zinc cyanide (15. 8 mg) was added, and the mixture was stirred at 100 ° C. for 30 minutes under microwave irradiation using a microwave reactor (Initiator Sixty ^™ (trade name) manufactured by Biotage) under an argon atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 2: 3) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (18 mg) as a colorless powder. Got as.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.65 (m, 2 H) 0.90-0.96 (m, 2 H) 1.72-1.78 (m, 1 H) 2.16-2.24 (m, 2 H) 2.30 -2.40 (m, 2 H) 2.67 (s, 3 H) 3.14-3.21 (m, 2 H) 4.85-4.93 (m, 1 H) 4.94-5.02 (m, 2 H) 7.65 (d, J = 7.8 Hz , 1 H) 7.75-7.78 (m, 1 H) 7.89 (d, J = 7.8 Hz, 1 H) 8.12 (s, 1 H) 8.17 (s, 2 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 437 [M + H] ⁺ .
Examples 41-18
5- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -6-methylpyridin-2- Carboxamide

実施例４１−１７で得られた化合物（４０ｍｇ）のジメチルスルホキシド（０．９１６ｍｌ）溶液へ、３０％過酸化水素水（１８．３μｌ）、炭酸カリウム（２５．３ｍｇ）を加え、室温にて３時間撹拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２〜０：１）にて精製後、ヘキサン−クロロホルム混合溶液にて再結晶し、表題化合物（３４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.65 (m, 2 H) 0.91 - 0.96 (m, 2 H) 1.72 - 1.78 (m, 1 H) 2.17 - 2.24 (m, 2 H) 2.31 - 2.40 (m, 2 H) 2.65 (s, 3 H) 3.15 - 3.24 (m, 2 H) 4.85 - 4.93 (m, 1 H) 4.94 - 5.01 (m, 2 H) 5.52 - 5.61 (m, 1 H) 7.76 (s, 1 H) 7.91 (d, J=7.8 Hz, 1 H) 7.95 - 8.03 (m, 1 H) 8.11 (s, 1 H) 8.14 (d, J=7.8 Hz, 1 H) 8.17 (s, 2 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 455[M+H]⁺.
実施例４１−１９
（５−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−６−メチルピリジン−２−イル）メタノール
（１）エチル ５−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−６−メチルピリジン−２−カルボキシラート

To a solution of the compound obtained in Example 41-17 (40 mg) in dimethyl sulfoxide (0.916 ml), 30% aqueous hydrogen peroxide (18.3 μl) and potassium carbonate (25.3 mg) were added. Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2 to 0: 1) and recrystallized from a hexane-chloroform mixed solution to give the titled compound (34 mg) as a colorless powder. Obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.65 (m, 2 H) 0.91-0.96 (m, 2 H) 1.72-1.78 (m, 1 H) 2.17-2.24 (m, 2 H) 2.31 -2.40 (m, 2 H) 2.65 (s, 3 H) 3.15-3.24 (m, 2 H) 4.85-4.93 (m, 1 H) 4.94-5.01 (m, 2 H) 5.52-5.61 (m, 1 H ) 7.76 (s, 1 H) 7.91 (d, J = 7.8 Hz, 1 H) 7.95-8.03 (m, 1 H) 8.11 (s, 1 H) 8.14 (d, J = 7.8 Hz, 1 H) 8.17 ( s, 2 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 455 [M + H] ⁺ .
Examples 41-19
(5- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -6-methylpyridine-2 -Yl) methanol (1) ethyl 5- {1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -6-methylpyridine-2-carboxylate

実施例４１−１７で得られた化合物（１００ｍｇ）のエタノール（２．２９ｍｌ）溶液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（２．２９ｍｌ）を加え、８０℃にて１５時間撹拌した。反応液へ飽和食塩水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２〜０：１）にて精製し、表題化合物（１０３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.64 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.46 (t, J=7.2 Hz, 3 H) 1.72 - 1.78 (m, 1 H) 2.17 - 2.23 (m, 2 H) 2.31 - 2.39 (m, 2 H) 2.72 (s, 3 H) 3.15 - 3.22 (m, 2 H) 4.51 (q, J=7.2 Hz, 2 H) 4.85 - 4.92 (m, 1 H) 4.94 - 5.01 (m, 2 H) 7.76 (s, 1 H) 7.90 (d, J=7.8 Hz, 1 H) 8.06 (d, J=7.8 Hz, 1 H) 8.10 (s, 1 H) 8.17 (s, 2 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 484[M+H]⁺.
（２）（５−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝−６−メチルピリジン−２−イル）メタノール

To a solution of the compound obtained in Example 41-17 (100 mg) in ethanol (2.29 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (2.29 ml), and the mixture was stirred at 80 ° C. for 15 hours. Saturated saline was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2 to 0: 1) to give the title compound (103 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.64 (m, 2 H) 0.90-0.96 (m, 2 H) 1.46 (t, J = 7.2 Hz, 3 H) 1.72-1.78 (m, 1 H) 2.17-2.23 (m, 2 H) 2.31-2.39 (m, 2 H) 2.72 (s, 3 H) 3.15-3.22 (m, 2 H) 4.51 (q, J = 7.2 Hz, 2 H) 4.85- 4.92 (m, 1 H) 4.94-5.01 (m, 2 H) 7.76 (s, 1 H) 7.90 (d, J = 7.8 Hz, 1 H) 8.06 (d, J = 7.8 Hz, 1 H) 8.10 (s , 1 H) 8.17 (s, 2 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 484 [M + H] ⁺ .
(2) (5- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -6-methyl Pyridin-2-yl) methanol

実施例４１−１９（１）で得られた化合物（１０３ｍｇ）のテトラヒドロフラン（２．１３ｍｌ）溶液へ、０℃にて１．０１Ｍ 水素化ジイソブチルアルミニウム・トルエン溶液（０．６３３ｍｌ）を加え、同温にて１時間攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 酢酸エチル）にて精製後、ヘキサン−酢酸エチル混合溶液にて再結晶し、表題化合物（７５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.65 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.71 - 1.78 (m, 1 H) 2.17 - 2.23 (m, 2 H) 2.31 - 2.40 (m, 2 H) 2.62 (s, 3 H) 3.14 - 3.21 (m, 2 H) 3.91 - 4.02 (m, 1 H) 4.79 (s, 2 H) 4.84 - 4.91 (m, 1 H) 4.94 - 5.00 (m, 2 H) 7.17 (d, J=7.8 Hz, 1 H) 7.71 (s, 1 H) 7.76 (d, J=7.8 Hz, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 442[M+H]⁺, 464[M+Na]⁺.
MS ESI/APCI Dual nega: 440[M-H]^-.
実施例４１−２０
１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−［６−（メトキシメチル）−２−メチルピリジン−３−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound (103 mg) obtained in Example 41-19 (1) in tetrahydrofuran (2.13 ml) was added 1.01 M diisobutylaluminum hydride / toluene solution (0.633 ml) at 0 ° C., and the same temperature. For 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent: ethyl acetate) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (75 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.65 (m, 2 H) 0.90-0.96 (m, 2 H) 1.71-1.78 (m, 1 H) 2.17-2.23 (m, 2 H) 2.31 -2.40 (m, 2 H) 2.62 (s, 3 H) 3.14-3.21 (m, 2 H) 3.91-4.02 (m, 1 H) 4.79 (s, 2 H) 4.84-4.91 (m, 1 H) 4.94 -5.00 (m, 2 H) 7.17 (d, J = 7.8 Hz, 1 H) 7.71 (s, 1 H) 7.76 (d, J = 7.8 Hz, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 442 [M + H] ⁺ , 464 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 440 [MH] ^- .
Examples 41-20
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- [6- (methoxymethyl) -2-methylpyridin-3-yl] -1H-pyrazolo [3,4 -C] pyridine

実施例４１−１９で得られた化合物（５０ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（１．１３ｍｌ）溶液へ、０℃にて水素化ナトリウム（６０％オイル懸濁、５．４４ｍｇ）を加え、１０分撹拌した。ヨードメタン（１９．３ｍｇ）を加え、同温にて２時間撹拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１）にて精製後、ヘキサン−酢酸エチル混合溶液にて再結晶し、表題化合物（３７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.65 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.71 - 1.78 (m, 1 H) 2.16 - 2.23 (m, 2 H) 2.30 - 2.39 (m, 2 H) 2.61 (s, 3 H) 3.14 - 3.22 (m, 2 H) 3.51 (s, 3 H) 4.63 (s, 2 H) 4.84 - 4.91 (m, 1 H) 4.93 - 5.00 (m, 2 H) 7.36 (d, J=7.8 Hz, 1 H) 7.70 (s, 1 H) 7.77 (d, J=7.8 Hz, 1 H) 8.08 (s, 1 H) 8.16 (s, 2 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 456[M+H]⁺.
実施例４１−２１
３−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−２−カルボキサミド

To a solution of the compound (50 mg) obtained in Example 41-19 in N, N-dimethylformamide (1.13 ml), sodium hydride (60% oil suspension, 5.44 mg) was added at 0 ° C. Stir for minutes. Iodomethane (19.3 mg) was added and stirred at the same temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1) and recrystallized from a hexane-ethyl acetate mixed solution to give the title compound (37 mg) as a colorless powder. .
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.65 (m, 2 H) 0.90-0.96 (m, 2 H) 1.71-1.78 (m, 1 H) 2.16-2.23 (m, 2 H) 2.30 -2.39 (m, 2 H) 2.61 (s, 3 H) 3.14-3.22 (m, 2 H) 3.51 (s, 3 H) 4.63 (s, 2 H) 4.84-4.91 (m, 1 H) 4.93-5.00 (m, 2 H) 7.36 (d, J = 7.8 Hz, 1 H) 7.70 (s, 1 H) 7.77 (d, J = 7.8 Hz, 1 H) 8.08 (s, 1 H) 8.16 (s, 2 H ) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 456 [M + H] ⁺ .
Example 41-21
3- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridine-2-carboxamide

実施例４１−９で得られた化合物（５１ｍｇ）を用いて、実施例４１−１８と同様の操作にて反応及び精製を行い、表題化合物（３８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.65 (m, 2 H) 0.89 - 0.96 (m, 2 H) 1.71 - 1.79 (m, 1 H) 2.14 - 2.21 (m, 2 H) 2.28 - 2.37 (m, 2 H) 3.12 - 3.20 (m, 2 H) 4.81 - 4.88 (m, 1 H) 4.92 - 4.99 (m, 2 H) 5.38 - 5.51 (m, 1 H) 7.49 - 7.59 (m, 2 H) 7.78 (d, J=1.2 Hz, 1 H) 7.89 - 7.93 (m, 1 H) 8.06 (s, 1 H) 8.16 (s, 2 H) 8.60 - 8.63 (m, 1 H) 9.06 (s, 1 H).
MS ESI/APCI Dual posi: 441[M+H]⁺, 463[M+Na]⁺.
実施例４１−２２
（３−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−２−イル）メタノール
（１）メチル ３−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−２−カルボキシラート

The compound (51 mg) obtained in Example 41-9 was used for the reaction and purification in the same manner as in Example 41-18 to obtain the title compound (38 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.65 (m, 2 H) 0.89-0.96 (m, 2 H) 1.71-1.79 (m, 1 H) 2.14-2.21 (m, 2 H) 2.28 -2.37 (m, 2 H) 3.12-3.20 (m, 2 H) 4.81-4.88 (m, 1 H) 4.92-4.99 (m, 2 H) 5.38-5.51 (m, 1 H) 7.49-7.59 (m, 2 H) 7.78 (d, J = 1.2 Hz, 1 H) 7.89-7.93 (m, 1 H) 8.06 (s, 1 H) 8.16 (s, 2 H) 8.60-8.63 (m, 1 H) 9.06 (s , 1 H).
MS ESI / APCI Dual posi: 441 [M + H] ⁺ , 463 [M + Na] ⁺ .
Examples 41-22
(3- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridin-2-yl) methanol (1) Methyl 3- {1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridin-2- Carboxylate

実施例４１−９で得られた化合物（１４０ｍｇ）のメタノール（２ｍｌ）溶液へ、４Ｍ塩化水素・１，４−ジオキサン溶液（２ｍｌ）を加え、室温にて１時間撹拌した。反応液へ２Ｍ水酸化ナトリウム水溶液を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９５：５〜９０：１０）にて精製後、ヘキサン−ジエチルエーテル混合溶液にて粉末化し、表題化合物（１３１ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.64 (m, 2 H) 0.90 - 0.95 (m, 2 H) 1.71 - 1.78 (m, 1 H) 2.15 - 2.21 (m, 2 H) 2.29 - 2.37 (m, 2 H) 3.12 - 3.20 (m, 2 H) 3.87 (s, 3 H) 4.81 - 4.88 (m, 1 H) 4.93 - 4.99 (m, 2 H) 7.51 (dd, J=7.8, 4.8 Hz, 1 H) 7.86 (d, J=1.2 Hz, 1 H) 8.02 (dd, J=7.8, 1.7 Hz, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.69 (dd, J=4.8, 1.7 Hz, 1 H) 9.06 (s, 1 H).
MS ESI/APCI Dual posi: 456[M+H]⁺.
（２）（３−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−２−イル）メタノール

To a solution of the compound obtained in Example 41-9 (140 mg) in methanol (2 ml) was added 4M hydrogen chloride / 1,4-dioxane solution (2 ml), and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 2M aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 95: 5-90: 10) and then powdered with a mixed solution of hexane-diethyl ether to give the title compound (131 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.64 (m, 2 H) 0.90-0.95 (m, 2 H) 1.71-1.78 (m, 1 H) 2.15-2.21 (m, 2 H) 2.29 -2.37 (m, 2 H) 3.12-3.20 (m, 2 H) 3.87 (s, 3 H) 4.81-4.88 (m, 1 H) 4.93-4.99 (m, 2 H) 7.51 (dd, J = 7.8, 4.8 Hz, 1 H) 7.86 (d, J = 1.2 Hz, 1 H) 8.02 (dd, J = 7.8, 1.7 Hz, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 8.69 (dd, J = 4.8, 1.7 Hz, 1 H) 9.06 (s, 1 H).
MS ESI / APCI Dual posi: 456 [M + H] ⁺ .
(2) (3- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridin-2- Il) Methanol

実施例４１−２２（１）で得られた化合物（５０ｍｇ）のメタノール（２ｍｌ）−テトラヒドロフラン（１ｍｌ）混合溶液へ、水素化ホウ素ナトリウム（１２ｍｇ）を加え、室温で３時間攪拌した。水素化ホウ素ナトリウム（３６ｍｇ）を追加し、５０℃で４時間攪拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９：１〜１：９）にて精製後、ジエチルエーテル−ヘキサン混合溶液で粉末化し、表題化合物（１３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.64 (m, 2 H) 0.90 - 0.95 (m, 2 H) 1.71 - 1.78 (m, 1 H) 2.17 - 2.23 (m, 2 H) 2.29 - 2.39 (m, 2 H) 3.13 - 3.21 (m, 2 H) 4.75 - 4.80 (m, 2 H) 4.84 - 4.92 (m, 1 H) 4.94 - 5.01 (m, 2 H) 5.33 - 5.38 (m, 1 H) 7.36 (dd, J=7.4, 4.8 Hz, 1 H) 7.82 (d, J=1.2 Hz, 1 H) 7.86 - 7.89 (m, 1 H) 8.12 (s, 1 H) 8.17 (s, 2 H) 8.64 (dd, J=4.8, 1.4 Hz, 1 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 428[M+H]⁺.
実施例４１−２３
１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−［２−（メトキシメチル）ピリジン−３−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Sodium borohydride (12 mg) was added to a mixed solution of the compound (50 mg) obtained in Example 41-22 (1) in methanol (2 ml) -tetrahydrofuran (1 ml), and the mixture was stirred at room temperature for 3 hours. Sodium borohydride (36 mg) was added, and the mixture was stirred at 50 ° C. for 4 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 9: 1 to 1: 9) and then powdered with a mixed solution of diethyl ether-hexane to give the title compound (13 mg) as a colorless powder. Obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.64 (m, 2 H) 0.90-0.95 (m, 2 H) 1.71-1.78 (m, 1 H) 2.17-2.23 (m, 2 H) 2.29 -2.39 (m, 2 H) 3.13-3.21 (m, 2 H) 4.75-4.80 (m, 2 H) 4.84-4.92 (m, 1 H) 4.94-5.01 (m, 2 H) 5.33-5.38 (m, 1 H) 7.36 (dd, J = 7.4, 4.8 Hz, 1 H) 7.82 (d, J = 1.2 Hz, 1 H) 7.86-7.89 (m, 1 H) 8.12 (s, 1 H) 8.17 (s, 2 H) 8.64 (dd, J = 4.8, 1.4 Hz, 1 H) 9.11 (s, 1 H).
MS ESI / APCI Dual posi: 428 [M + H] ⁺ .
Examples 41-23
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- [2- (methoxymethyl) pyridin-3-yl] -1H-pyrazolo [3,4-c] pyridine

実施例４１−２２で得られた化合物（７ｍｇ）を用いて、実施例４１−２０と同様の操作にて反応及び精製を行い、表題化合物（４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.64 (m, 2 H) 0.91 - 0.95 (m, 2 H) 1.72 - 1.78 (m, 1 H) 2.18 - 2.23 (m, 2 H) 2.31 - 2.39 (m, 2 H) 3.15 - 3.21 (m, 2 H) 3.42 (s, 3 H) 4.65 (s, 2 H) 4.84 - 4.91 (m, 1 H) 4.94 - 5.00 (m, 2 H) 7.34 - 7.38 (m, 1 H) 7.90 - 7.93 (m, 1 H) 7.94 - 7.95 (m, 1 H) 8.10 - 8.12 (m, 1 H) 8.16 (s, 2 H) 8.67 - 8.70 (m, 1 H) 9.11 - 9.13 (m, 1 H).
MS ESI/APCI Dual posi: 442[M+H]⁺.
実施例４１−２４
４−｛１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝ピリジン−３−カルボニトリル

Using the compound (7 mg) obtained in Example 41-22, the reaction and purification were conducted in the same manner as in Example 41-20 to obtain the title compound (4 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.64 (m, 2 H) 0.91-0.95 (m, 2 H) 1.72-1.78 (m, 1 H) 2.18-2.23 (m, 2 H) 2.31 -2.39 (m, 2 H) 3.15-3.21 (m, 2 H) 3.42 (s, 3 H) 4.65 (s, 2 H) 4.84-4.91 (m, 1 H) 4.94-5.00 (m, 2 H) 7.34 -7.38 (m, 1 H) 7.90-7.93 (m, 1 H) 7.94-7.95 (m, 1 H) 8.10-8.12 (m, 1 H) 8.16 (s, 2 H) 8.67-8.70 (m, 1 H ) 9.11-9.13 (m, 1 H).
MS ESI / APCI Dual posi: 442 [M + H] ⁺ .
Examples 41-24
4- {1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} pyridine-3-carbonitrile

参考例２３−Ａで得られた化合物（７０ｍｇ）と参考例Ｅ−１６で得られた化合物（６０．５ｍｇ）を用いて、実施例４０−４と同様の操作にて反応及び精製を行い、表題化合物（２０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.65 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.71 - 1.79 (m, 1 H) 2.16 - 2.23 (m, 2 H) 2.30 - 2.39 (m, 2 H) 3.14 - 3.21 (m, 2 H) 4.85 - 4.94 (m, 1 H) 4.94 - 5.01 (m, 2 H) 7.90 (d, J=5.4 Hz, 1 H) 8.17 (s, 2 H) 8.18 (s, 1 H) 8.29 (s, 1 H) 8.85 (d, J=5.4 Hz, 1 H) 9.00 (s, 1 H) 9.20 (s, 1 H).
MS ESI/APCI Dual posi: 423[M+H]⁺.
実施例４１−２５
５−（２−クロロ−４−フルオロピリジン−３−イル）−１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (70 mg) obtained in Reference Example 23-A and the compound (60.5 mg) obtained in Reference Example E-16, the reaction and purification were carried out in the same manner as in Example 40-4. The title compound (20 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.65 (m, 2 H) 0.90-0.96 (m, 2 H) 1.71-1.79 (m, 1 H) 2.16-2.23 (m, 2 H) 2.30 -2.39 (m, 2 H) 3.14-3.21 (m, 2 H) 4.85-4.94 (m, 1 H) 4.94-5.01 (m, 2 H) 7.90 (d, J = 5.4 Hz, 1 H) 8.17 (s , 2 H) 8.18 (s, 1 H) 8.29 (s, 1 H) 8.85 (d, J = 5.4 Hz, 1 H) 9.00 (s, 1 H) 9.20 (s, 1 H).
MS ESI / APCI Dual posi: 423 [M + H] ⁺ .
Examples 41-25
5- (2-Chloro-4-fluoropyridin-3-yl) -1- [1- (5-cyclopropylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] Pyridine

参考例２３−Ａで得られた化合物（５０ｍｇ）と２−クロロ−４−フルオロピリジン-３−ボロン酸（３５ｍｇ）を用いて、実施例４０−４と同様の操作にて反応及び精製を行い、表題化合物（２２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.64 (m, 2 H) 0.90 - 0.96 (m, 2 H) 1.72 - 1.78 (m, 1 H) 2.16 - 2.22 (m, 2 H) 2.29 - 2.38 (m, 2 H) 3.14 - 3.21 (m, 2 H) 4.83 - 4.90 (m, 1 H) 4.93 - 5.00 (m, 2 H) 7.22 (d, J=10.5 Hz, 1 H) 8.08 - 8.12 (m, 2 H) 8.17 (s, 2 H) 9.09 (d, J=10.5 Hz, 1 H) 9.14 (s, 1 H).
MS ESI/APCI Dual posi: 450[M+H]⁺.
実施例４１−２６
１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−（４−フルオロ−２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The reaction and purification were conducted in the same manner as in Example 40-4 using the compound (50 mg) obtained in Reference Example 23-A and 2-chloro-4-fluoropyridine-3-boronic acid (35 mg). The title compound (22 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.64 (m, 2 H) 0.90-0.96 (m, 2 H) 1.72-1.78 (m, 1 H) 2.16-2.22 (m, 2 H) 2.29 -2.38 (m, 2 H) 3.14-3.21 (m, 2 H) 4.83-4.90 (m, 1 H) 4.93-5.00 (m, 2 H) 7.22 (d, J = 10.5 Hz, 1 H) 8.08-8.12 (m, 2 H) 8.17 (s, 2 H) 9.09 (d, J = 10.5 Hz, 1 H) 9.14 (s, 1 H).
MS ESI / APCI Dual posi: 450 [M + H] ⁺ .
Examples 41-26
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- (4-fluoro-2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] Pyridine

実施例４１−２５で得られた化合物（２０ｍｇ）と３Ｍ メチルマグネシウムブロミド・ジエチルエーテル溶液（１８μｌ）を用いて、実施例４１−１４と同様の操作にて反応及び精製を行い、表題化合物（３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59 - 0.64 (m, 2 H) 0.90 - 0.95 (m, 2 H) 1.71 - 1.78 (m, 1 H) 2.15 - 2.21 (m, 2 H) 2.28 - 2.38 (m, 2 H) 2.62 (s, 3 H) 3.14 - 3.21 (m, 2 H) 4.83 - 4.90 (m, 1 H) 4.92 - 4.99 (m, 2 H) 6.98 - 7.03 (m, 1 H) 8.06 (s, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.10 - 9.16 (m, 2 H).
MS ESI posi: 430[M+H]⁺.
実施例４１−２７
１−［１−（５−シクロプロピルピリミジン−２−イル）ピペリジン−４−イル］−５−（２−エチル−５−フルオロピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (20 mg) obtained in Example 41-25 and 3M methylmagnesium bromide / diethyl ether solution (18 μl), the reaction and purification were carried out in the same manner as in Example 41-14 to give the title compound (3 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.59-0.64 (m, 2 H) 0.90-0.95 (m, 2 H) 1.71-1.78 (m, 1 H) 2.15-2.21 (m, 2 H) 2.28 -2.38 (m, 2 H) 2.62 (s, 3 H) 3.14-3.21 (m, 2 H) 4.83-4.90 (m, 1 H) 4.92-4.99 (m, 2 H) 6.98-7.03 (m, 1 H ) 8.06 (s, 1 H) 8.09 (s, 1 H) 8.16 (s, 2 H) 9.10-9.16 (m, 2 H).
MS ESI posi: 430 [M + H] ⁺ .
Examples 41-27
1- [1- (5-Cyclopropylpyrimidin-2-yl) piperidin-4-yl] -5- (2-ethyl-5-fluoropyridin-3-yl) -1H-pyrazolo [3,4-c] Pyridine

実施例４１−１２で得られた化合物（７０ｍｇ）と３Ｍ エチルマグネシウムブロミド・ジエチルエーテル溶液（４２μｌ）を用いて、実施例４１−１４と同様の操作にて反応及び精製を行い、表題化合物（８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60 - 0.64 (m, 2 H) 0.90 - 0.95 (m, 2 H) 1.21 (t, J=7.4 Hz, 3 H) 1.72 - 1.78 (m, 1 H) 2.17 - 2.23 (m, 2 H) 2.31 - 2.39 (m, 2 H) 2.88 (q, J=7.4 Hz, 2 H) 3.14 - 3.21 (m, 2 H) 4.85 - 4.91 (m, 1 H) 4.94 - 5.00 (m, 2 H) 7.46 (dd, J=8.7, 2.9 Hz, 1 H) 7.71 (d, J=0.8 Hz, 1 H) 8.10 (s, 1 H) 8.17 (s, 2 H) 8.46 (d, J=2.9 Hz, 1 H) 9.12 (s, 1 H).
MS ESI posi: 444[M+H]⁺.
実施例４２−１
５−［３−フルオロ−４−（メチルスルホニル）フェニル］−１−｛１−［５−（プロパン−２−イル）ピリミジン−２−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (70 mg) obtained in Example 41-12 and 3M ethylmagnesium bromide / diethyl ether solution (42 μl), the reaction and purification were carried out in the same manner as in Example 41-14 to give the title compound (8 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.64 (m, 2 H) 0.90-0.95 (m, 2 H) 1.21 (t, J = 7.4 Hz, 3 H) 1.72-1.78 (m, 1 H) 2.17-2.23 (m, 2 H) 2.31-2.39 (m, 2 H) 2.88 (q, J = 7.4 Hz, 2 H) 3.14-3.21 (m, 2 H) 4.85-4.91 (m, 1 H) 4.94-5.00 (m, 2 H) 7.46 (dd, J = 8.7, 2.9 Hz, 1 H) 7.71 (d, J = 0.8 Hz, 1 H) 8.10 (s, 1 H) 8.17 (s, 2 H) 8.46 (d, J = 2.9 Hz, 1 H) 9.12 (s, 1 H).
MS ESI posi: 444 [M + H] ⁺ .
Example 42-1
5- [3-Fluoro-4- (methylsulfonyl) phenyl] -1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-pyrazolo [3 4-c] pyridine

参考例２３−Ｂで得られた化合物（１００ｍｇ）と３−フルオロ−４−（メチルスルホニル）フェニルボロン酸（８１．６ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（９６．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (d, J=7.0 Hz, 6 H) 2.13 - 2.25 (m, 2 H) 2.27 - 2.43 (m, 2 H) 2.74 - 2.87 (m, 1 H) 3.11 - 3.24 (m, 2 H) 3.27 (s, 3 H) 4.81 - 4.94 (m, 1 H) 4.94 - 5.03 (m, 2 H) 7.95 - 8.08 (m, 3 H) 8.12 - 8.14 (m, 2 H) 8.24 - 8.26 (m, 2 H) 9.12 - 9.14 (m, 1 H).
MS ESI/APCI Dual posi: 495[M+H]⁺.

Using the compound (100 mg) obtained in Reference Example 23-B and 3-fluoro-4- (methylsulfonyl) phenylboronic acid (81.6 mg), the reaction and purification were carried out in the same manner as in Example 40-1. To give the title compound (96.9 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (d, J = 7.0 Hz, 6 H) 2.13-2.25 (m, 2 H) 2.27-2.43 (m, 2 H) 2.74-2.87 (m, 1 H) 3.11-3.24 (m, 2 H) 3.27 (s, 3 H) 4.81-4.94 (m, 1 H) 4.94-5.03 (m, 2 H) 7.95-8.08 (m, 3 H) 8.12-8.14 (m , 2 H) 8.24-8.26 (m, 2 H) 9.12-9.14 (m, 1 H).
MS ESI / APCI Dual posi: 495 [M + H] ⁺ .

  Examples 42-2 to 42-5 below also conform to the method described in Example 40-1 using the boronic acid corresponding to the compound obtained in Reference Example 23-B or Reference Example 23-C. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Table 28-1.

Example 43-1
Propan-2-yl 4- {5- [3-fluoro-4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２３−Ｄで得られた化合物（１００ｍｇ）と３−フルオロ−４−（メチルスルホニル）フェニルボロン酸（８９ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（９２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.05 - 2.18 (m, 2 H) 2.21 - 2.38 (m, 2 H) 2.99 - 3.15 (m, 2 H) 3.27 (s, 3 H) 4.30 - 4.49 (m, 2 H) 4.69 - 4.84 (m, 1 H) 4.98 (quin, J=6.3 Hz, 1 H) 7.94 - 8.09 (m, 3 H) 8.12 - 8.17 (m, 2 H) 9.10 (s, 1 H).
MS ESI/APCI Dual posi: 461[M+H]⁺, 483[M+Na]⁺.

Using the compound (100 mg) obtained in Reference Example 23-D and 3-fluoro-4- (methylsulfonyl) phenylboronic acid (89 mg), the reaction and purification were carried out in the same manner as in Example 40-1. The title compound (92 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.05-2.18 (m, 2 H) 2.21-2.38 (m, 2 H) 2.99-3.15 (m, 2 H) 3.27 (s, 3 H) 4.30-4.49 (m, 2 H) 4.69-4.84 (m, 1 H) 4.98 (quin, J = 6.3 Hz, 1 H) 7.94-8.09 (m, 3 H) 8.12- 8.17 (m, 2 H) 9.10 (s, 1 H).
MS ESI / APCI Dual posi: 461 [M + H] ⁺ , 483 [M + Na] ⁺ .

  The following Examples 43-2 to 43-13 are also based on the method described in Example 40-1 using the boronic acid corresponding to the compounds obtained in Reference Examples 23-D to 23-G. Synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 29-1 to 29-2.

Example 44-1
1- [1- (5-Fluoropyrimidin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ａで得られた化合物（１００ｍｇ）のジメチルスルホキシド（１ｍｌ）溶液へ、２−クロロ−５−フルオロピリミジン（７４ｍｇ）、炭酸セシウム（４５８ｍｇ）を加え、マイクロウェ−ブ反応装置（Ｂｉｏｔａｇｅ社製 Ｉｎｉｔｉａｔｏｒ Ｓｉｘｔｙ^TM（商品名））を用いて、マイクロウェーブ照射下１８０℃にて２０分撹拌した。室温へ放冷後、水とクロロホルムを加えてセライト（登録商標）ろ過を行った。得られた有機層を水で洗浄後、無水硫酸ナトリウムで乾燥し、乾燥剤を濾別した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝９：１〜５：５）にて精製した後、得られた固体をクロロホルム−ヘキサンより再結晶させ表題化合物（６５ｍｇ）を白色固体として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.14 - 2.43 (m, 4 H) 3.10 (s, 3 H) 3.15 - 3.28 (m, 2 H) 4.81 - 5.00 (m, 3 H) 8.03 - 8.07 (m, 2 H) 8.12 - 8.14 (m, 2 H) 8.22 - 8.26 (m, 4 H) 9.12 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 453[M+H]⁺.

To a solution of the compound obtained in Reference Example 24-A (100 mg) in dimethyl sulfoxide (1 ml), 2-chloro-5-fluoropyrimidine (74 mg) and cesium carbonate (458 mg) were added, and a microwave reactor (Biotage The mixture was stirred at 180 ° C. for 20 minutes under microwave irradiation using an Initiator Sixty ^™ (trade name) manufactured by the company. After allowing to cool to room temperature, water and chloroform were added, and Celite (registered trademark) filtration was performed. The obtained organic layer was washed with water and then dried over anhydrous sodium sulfate, and the desiccant was filtered off. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 9: 1 to 5: 5), and then the resulting solid was recrystallized from chloroform-hexane to give the title Compound (65 mg) was obtained as a white solid.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.14-2.43 (m, 4 H) 3.10 (s, 3 H) 3.15-3.28 (m, 2 H) 4.81-5.00 (m, 3 H) 8.03-8.07 (m, 2 H) 8.12-8.14 (m, 2 H) 8.22-8.26 (m, 4 H) 9.12-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 453 [M + H] ⁺ .

  The following Examples 44-2 to 44-7 were also prepared using the compound obtained in Reference Example 24-A and the compound obtained in Reference Examples G-2 to G-4 or the corresponding halide. Synthesis was performed in accordance with the method described in -1. The structures, NMR data, and MS data of these compounds are shown in Table 30-1.

Example 44-8
1- {1- [5- (2-methylpropyl) pyrimidin-2-yl] piperidin-4-yl} -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

実施例４４−５で得られた化合物（１００ｍｇ）を用いて、実施例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (d, J=6.7 Hz, 6 H) 1.70 - 1.88 (m, 1 H) 2.14 - 2.46 (m, 6 H) 3.10 (s, 3 H) 3.13 - 3.25 (m, 2 H) 4.82 - 4.94 (m, 1 H) 4.94 - 5.04 (m, 2 H) 8.02 - 8.08 (m, 2 H) 8.11 - 8.13 (m, 2 H) 8.17 (s, 2 H) 8.21 - 8.27 (m, 2 H) 9.12 - 9.16 (m, 1 H).
MS ESI/APCI Dual posi: 491[M+H]⁺.
実施例４４−９
５−［４−（メチルスルホニル）フェニル］−１−｛１−［５−（プロパン−２−イル）ピリミジン−２−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The compound (100 mg) obtained in Example 44-5 was used for the reaction and purification in the same manner as in Example 20-1 (3) to give the title compound (3 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (d, J = 6.7 Hz, 6 H) 1.70-1.88 (m, 1 H) 2.14-2.46 (m, 6 H) 3.10 (s, 3 H) 3.13-3.25 (m, 2 H) 4.82-4.94 (m, 1 H) 4.94-5.04 (m, 2 H) 8.02-8.08 (m, 2 H) 8.11-8.13 (m, 2 H) 8.17 (s, 2 H) 8.21-8.27 (m, 2 H) 9.12-9.16 (m, 1 H).
MS ESI / APCI Dual posi: 491 [M + H] ⁺ .
Example 44-9
5- [4- (Methylsulfonyl) phenyl] -1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-pyrazolo [3,4-c] Pyridine

実施例４４−６で得られた化合物（１００ｍｇ）を用いて、実施例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（１．４３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58 - 0.66 (m, 2 H) 0.89 - 0.97 (m, 2 H) 1.69 - 1.81 (m, 1 H) 2.13 - 2.24 (m, 2 H) 2.26 - 2.42 (m, 2 H) 3.10 (s, 3 H) 3.12 - 3.24 (m, 2 H) 4.81 - 4.92 (m, 1 H) 4.92 - 5.01 (m, 2 H) 8.02 - 8.07 (m, 2 H) 8.11 - 8.14 (m, 2 H) 8.16 (s, 2 H) 8.21 - 8.27 (m, 2 H) 9.12 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 475[M+H]⁺.
実施例４４−１０
１−［１−（５−シクロプロピルピリジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）１−［１−（５−ヨードピリジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

The compound (100 mg) obtained in Example 44-6 was used for the reaction and purification in the same manner as in Example 20-1 (3) to give the title compound (1.43 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.66 (m, 2 H) 0.89-0.97 (m, 2 H) 1.69-1.81 (m, 1 H) 2.13-2.24 (m, 2 H) 2.26 -2.42 (m, 2 H) 3.10 (s, 3 H) 3.12-3.24 (m, 2 H) 4.81-4.92 (m, 1 H) 4.92-5.01 (m, 2 H) 8.02-8.07 (m, 2 H ) 8.11-8.14 (m, 2 H) 8.16 (s, 2 H) 8.21-8.27 (m, 2 H) 9.12-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 475 [M + H] ⁺ .
Example 44-10
1- [1- (5-Cyclopropylpyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine (1) 1 -[1- (5-Iodopyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ａで得られた化合物（１４０ｍｇ）と２−クロロ−５−ヨードピリジン（１４１ｍｇ）を用いて、実施例４４−１と同様の操作にて反応及び精製を行い、表題化合物（９０ｍｇ）を黄色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15 - 2.26 (m, 2 H) 2.30 - 2.48 (m, 2 H) 3.07 - 3.24 (m, 5 H) 4.44 - 4.56 (m, 2 H) 4.79 - 4.92 (m, 1 H) 6.58 - 6.65 (m, 1 H) 7.68 - 7.75 (m, 1 H) 8.01 - 8.09 (m, 2 H) 8.13 (s, 2 H) 8.21 - 8.27 (m, 2 H) 8.33 - 8.38 (m, 1 H) 9.10 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 560[M+H]⁺.
（２）１−［１−（５−シクロプロピルピリジン−２−イル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (140 mg) obtained in Reference Example 24-A and 2-chloro-5-iodopyridine (141 mg), the reaction and purification were carried out in the same manner as in Example 44-1, and the title compound (90 mg ) Was obtained as a yellow powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15-2.26 (m, 2 H) 2.30-2.48 (m, 2 H) 3.07-3.24 (m, 5 H) 4.44-4.56 (m, 2 H) 4.79 -4.92 (m, 1 H) 6.58-6.65 (m, 1 H) 7.68-7.75 (m, 1 H) 8.01-8.09 (m, 2 H) 8.13 (s, 2 H) 8.21-8.27 (m, 2 H ) 8.33-8.38 (m, 1 H) 9.10-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 560 [M + H] ⁺ .
(2) 1- [1- (5-Cyclopropylpyridin-2-yl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

実施例４４−１０（１）で得られた化合物（８４ｍｇ）とシクロプロピルボロン酸（１７ｍｇ）を用いて、参考例G−２と同様の操作にて反応及び精製を行い、表題化合物（７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58 - 0.65 (m, 2 H) 0.86 - 0.97 (m, 2 H) 1.76 - 1.89 (m, 1 H) 2.14 - 2.26 (m, 2 H) 2.33 - 2.51 (m, 2 H) 3.05 - 3.19 (m, 5 H) 4.43 - 4.55 (m, 2 H) 4.76 - 4.89 (m, 1 H) 6.67 - 6.74 (m, 1 H) 7.19 - 7.25 (m, 1 H) 8.02 - 8.09 (m, 3 H) 8.11 - 8.14 (m, 2 H) 8.21 - 8.27 (m, 2 H) 9.11 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 474[M+H]⁺.
実施例４５−１
５−［２−フルオロ−４−（メチルスルホニル）フェニル］−１−［１−（５−メチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (84 mg) obtained in Example 44-10 (1) and cyclopropylboronic acid (17 mg), the reaction and purification were carried out in the same manner as in Reference Example G-2, and the title compound (7 mg) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.65 (m, 2 H) 0.86-0.97 (m, 2 H) 1.76-1.89 (m, 1 H) 2.14-2.26 (m, 2 H) 2.33 -2.51 (m, 2 H) 3.05-3.19 (m, 5 H) 4.43-4.55 (m, 2 H) 4.76-4.89 (m, 1 H) 6.67-6.74 (m, 1 H) 7.19-7.25 (m, 1 H) 8.02-8.09 (m, 3 H) 8.11-8.14 (m, 2 H) 8.21-8.27 (m, 2 H) 9.11-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 474 [M + H] ⁺ .
Example 45-1
5- [2-Fluoro-4- (methylsulfonyl) phenyl] -1- [1- (5-methylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ｂで得られた化合物（６０ｍｇ）と２−クロロ−５−メチルピリミジン（４１．１ｍｇ）を用いて、実施例４４−１と同様の操作にて反応及び精製を行い、表題化合物（４９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13 - 2.25 (m, 5 H) 2.27 - 2.43 (m, 2 H) 3.11 (s, 3 H) 3.12 - 3.24 (m, 2 H) 4.82 - 5.02 (m, 3 H) 7.74 - 7.88 (m, 2 H) 8.13 (s, 1 H) 8.19 - 8.22 (m, 2 H) 8.23 - 8.25 (m, 1 H) 8.30 - 8.38 (m, 1 H) 9.13 - 9.16 (m, 1 H).
MS ESI/APCI Dual posi: 467[M+H]⁺.

Using the compound (60 mg) obtained in Reference Example 24-B and 2-chloro-5-methylpyrimidine (41.1 mg), the reaction and purification were carried out in the same manner as in Example 44-1 to obtain the title compound. (49 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.13-2.25 (m, 5 H) 2.27-2.43 (m, 2 H) 3.11 (s, 3 H) 3.12-3.24 (m, 2 H) 4.82-5.02 (m, 3 H) 7.74-7.88 (m, 2 H) 8.13 (s, 1 H) 8.19-8.22 (m, 2 H) 8.23-8.25 (m, 1 H) 8.30-8.38 (m, 1 H) 9.13 -9.16 (m, 1 H).
MS ESI / APCI Dual posi: 467 [M + H] ⁺ .

  The following Examples 45-2 to 45-3 were also synthesized according to the method described in Example 44-1 using the compound obtained in Reference Example 24-B and the corresponding halide. The structure, NMR data and MS data of these compounds are shown in Table 31-1.

Example 45-4
5- [2-Fluoro-4- (methylsulfonyl) phenyl] -1- [1- (5-methoxypyridin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ｂで得られた化合物（２５ｍｇ）のジメトキシエタン（１ｍｌ）溶液へ、２−クロロ−５−メトキシピリジン（１１．５ｍｇ）、トリス（ジベンジリデンアセトン）ジパラジウム（１．２ｍｇ）、２，２’−ビス（ジフェニルホスフィノ）−１，１’−ビナフチル（１．７ｍｇ）、ナトリウム ｔ−ブトキシド（１２．８ｍｇ）を加え、アルゴン雰囲気下８０℃にて２０時間攪拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層の溶媒を減圧留去後、得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１００：０〜９５：５）にて精製し、表題化合物（７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15 - 2.27 (m, 2 H) 2.37 - 2.55 (m, 2 H) 3.03 - 3.18 (m, 5 H) 3.82 (s, 3 H) 4.33 - 4.45 (m, 2 H) 4.75 - 4.88 (m, 1 H) 6.73 - 6.79 (m, 1 H) 7.16 - 7.23 (m, 1 H) 7.75 - 7.88 (m, 2 H) 7.95 - 7.99 (m, 1 H) 8.14 (s, 1 H) 8.22 - 8.25 (m, 1 H) 8.34 (t, J=7.9 Hz, 1 H) 9.15 (s, 1 H).
MS ESI/APCI Dual posi: 482[M+H]⁺.

To a solution of the compound (25 mg) obtained in Reference Example 24-B in dimethoxyethane (1 ml), 2-chloro-5-methoxypyridine (11.5 mg), tris (dibenzylideneacetone) dipalladium (1.2 mg), 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl (1.7 mg) and sodium t-butoxide (12.8 mg) were added, and the mixture was stirred at 80 ° C. for 20 hours under an argon atmosphere. Water was added to the reaction solution, and the mixture was extracted with chloroform. After the solvent of the obtained organic layer was distilled off under reduced pressure, the obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: ethyl acetate = 100: 0 to 95: 5) to give the title compound (7 mg) as colorless. Obtained as a powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.15-2.27 (m, 2 H) 2.37-2.55 (m, 2 H) 3.03-3.18 (m, 5 H) 3.82 (s, 3 H) 4.33-4.45 (m, 2 H) 4.75-4.88 (m, 1 H) 6.73-6.79 (m, 1 H) 7.16-7.23 (m, 1 H) 7.75-7.88 (m, 2 H) 7.95-7.99 (m, 1 H ) 8.14 (s, 1 H) 8.22-8.25 (m, 1 H) 8.34 (t, J = 7.9 Hz, 1 H) 9.15 (s, 1 H).
MS ESI / APCI Dual posi: 482 [M + H] ⁺ .

  The following Examples 45-5 to 45-6 were also described in Example 45-4 using the compound obtained in Reference Example 24-B and the compound obtained in Reference Example G-6 or G-7. Synthesized according to the method. The structures, NMR data, and MS data of these compounds are shown in Table 31-2.

Example 46-1
5- (2-Methylpyridin-3-yl) -1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-pyrazolo [3,4-c ] Pyridine

参考例２４−Ｃで得られた化合物（１００ｍｇ）と参考例Ｇ−５で得られた化合物（１０７ｍｇ）を用いて、実施例４４−１と同様の操作にて反応及び精製を行い、表題化合物（２３．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (d, J=6.8 Hz, 6 H) 2.15 - 2.26 (m, 2 H) 2.28 - 2.46 (m, 2 H) 2.62 (s, 3 H) 2.75 - 2.87 (m, 1 H) 3.12 - 3.26 (m, 2 H) 4.82 - 4.94 (m, 1 H) 4.95 - 5.04 (m, 2 H) 7.21 - 7.27 (m, 1 H) 7.71 - 7.72 (m, 1 H) 7.73 - 7.77 (m, 1 H) 8.09 (s, 1 H) 8.25 (s, 2 H) 8.53 - 8.58 (m, 1 H) 9.12 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 414[M+H]⁺.

Using the compound (100 mg) obtained in Reference Example 24-C and the compound (107 mg) obtained in Reference Example G-5, the reaction and purification were carried out in the same manner as in Example 44-1, and the title compound was obtained. (23.6 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26 (d, J = 6.8 Hz, 6 H) 2.15-2.26 (m, 2 H) 2.28-2.46 (m, 2 H) 2.62 (s, 3 H) 2.75-2.87 (m, 1 H) 3.12-3.26 (m, 2 H) 4.82-4.94 (m, 1 H) 4.95-5.04 (m, 2 H) 7.21-7.27 (m, 1 H) 7.71-7.72 (m , 1 H) 7.73-7.77 (m, 1 H) 8.09 (s, 1 H) 8.25 (s, 2 H) 8.53-8.58 (m, 1 H) 9.12-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 414 [M + H] ⁺ .

  Examples 46-2 to 46-6 below are also the same as those in Example 44 using the compound obtained in Reference Example 24-C and the compound obtained in Reference Example G-8 to G-10 or the corresponding halide. Synthesis was performed in accordance with the method described in -1. The structure, NMR data, and MS data of these compounds are shown in Table 32-1.

Example 46-7
5- (2-Methylpyridin-3-yl) -1- [1- (5-methylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine (1) methyl 2- {4- [5- (2-Methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidin-1-yl} pyrimidine-5-carboxylate

参考例２４−Ｃで得られた化合物（３００ｍｇ）とメチル ２−クロロピリミジン−５−カルボキシラート（２１２ｍｇ）を用いて、実施例４４−１と同様の操作にて反応及び精製を行い、表題化合物（４３７ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.17 - 2.51 (m, 4 H) 2.62 (s, 3 H) 3.22 - 3.40 (m, 2 H) 3.90 (s, 3 H) 4.82 - 5.03 (m, 1 H) 5.06 - 5.21 (m, 2 H) 7.19 - 7.29 (m, 1 H) 7.71 - 7.78 (m, 2 H) 8.10 (s, 1 H) 8.53 - 8.59 (m, 1 H) 8.88 (s, 2 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 430[M+H]⁺, 452[M+Na]⁺.
（２）５−（２−メチルピリジン−３−イル）−１−［１−（５−メチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (300 mg) obtained in Reference Example 24-C and methyl 2-chloropyrimidine-5-carboxylate (212 mg), the reaction and purification were carried out in the same manner as in Example 44-1, and the title compound (437 mg) was obtained as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.17-2.51 (m, 4 H) 2.62 (s, 3 H) 3.22-3.40 (m, 2 H) 3.90 (s, 3 H) 4.82-5.03 (m , 1 H) 5.06-5.21 (m, 2 H) 7.19-7.29 (m, 1 H) 7.71-7.78 (m, 2 H) 8.10 (s, 1 H) 8.53-8.59 (m, 1 H) 8.88 (s , 2 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 430 [M + H] ⁺ , 452 [M + Na] ⁺ .
(2) 5- (2-Methylpyridin-3-yl) -1- [1- (5-methylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

実施例４６−７（１）で得られた化合物（４３７ｍｇ）のテトラヒドロフラン（１０．２ｍｌ）溶液へ、０℃にて水素化リチウムアルミニウム（７７．２ｍｇ）を加え、同温にて１時間攪拌した。酢酸エチル、水、１０％クエン酸水溶液を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜０：１〜クロロホルム：メタノール＝１０：１）にて精製し、表題化合物（６０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.16 (s, 3 H) 2.18 - 2.49 (m, 4 H) 2.62 (s, 3 H) 3.08 - 3.27 (m, 2 H) 4.76 - 5.06 (m, 3 H) 7.19 - 7.30 (m, 1 H) 7.70 - 7.80 (m, 2 H) 8.09 (s, 1 H) 8.20 (s, 2 H) 8.52 - 8.59 (m, 1 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 386[M+H]⁺, 408[M+Na]⁺.
実施例４６−８
１−｛１−［５−（フルオロメチル）ピリミジン−２−イル］ピペリジン−４−イル｝−５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）（２−｛４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル］ピペリジン−１−イル｝ピリミジン−５−イル）メタノール

To a solution of the compound (437 mg) obtained in Example 46-7 (1) in tetrahydrofuran (10.2 ml) was added lithium aluminum hydride (77.2 mg) at 0 ° C., and the mixture was stirred at the same temperature for 1 hour. . Ethyl acetate, water and 10% aqueous citric acid solution were added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 0: 1 to chloroform: methanol = 10: 1) to obtain the title compound (60 mg) as a colorless powder. .
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.16 (s, 3 H) 2.18-2.49 (m, 4 H) 2.62 (s, 3 H) 3.08-3.27 (m, 2 H) 4.76-5.06 (m , 3 H) 7.19-7.30 (m, 1 H) 7.70-7.80 (m, 2 H) 8.09 (s, 1 H) 8.20 (s, 2 H) 8.52-8.59 (m, 1 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 386 [M + H] ⁺ , 408 [M + Na] ⁺ .
Example 46-8
1- {1- [5- (fluoromethyl) pyrimidin-2-yl] piperidin-4-yl} -5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridine ( 1) (2- {4- [5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidin-1-yl} pyrimidin-5-yl) methanol

実施例４６−７（１）で得られた化合物（４３７ｍｇ）のテトラヒドロフラン（１０．２ｍｌ）溶液へ、０℃にて水素化リチウムアルミニウム（７７．２ｍｇ）を加え、同温にて１時間攪拌した。酢酸エチル、水、１０％クエン酸水溶液を加え、酢酸エチルにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜０：１〜クロロホルム：メタノール＝１０：１）にて精製し、表題化合物（９０ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.11 - 2.53 (m, 4 H) 2.62 (s, 3 H) 3.13 - 3.34 (m, 2 H) 4.56 (s, 2 H) 4.80 - 5.13 (m, 3 H) 7.18 - 7.29 (m, 1 H) 7.70 - 7.80 (m, 2 H) 8.09 (s, 1 H) 8.38 (s, 2 H) 8.52 - 8.58 (m, 1 H) 9.12 (s, 1 H).
MS ESI/APCI Dual posi: 402[M+H]⁺, 424[M+Na]⁺.
MS ESI/APCI Dual nega: 400[M-H]^-.
（２）１−｛１−［５−（フルオロメチル）ピリミジン−２−イル］ピペリジン−４−イル｝−５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound (437 mg) obtained in Example 46-7 (1) in tetrahydrofuran (10.2 ml) was added lithium aluminum hydride (77.2 mg) at 0 ° C., and the mixture was stirred at the same temperature for 1 hour. . Ethyl acetate, water and 10% aqueous citric acid solution were added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 0: 1 to chloroform: methanol = 10: 1) to obtain the title compound (90 mg) as a colorless oily substance. It was.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.11-2.53 (m, 4 H) 2.62 (s, 3 H) 3.13-3.34 (m, 2 H) 4.56 (s, 2 H) 4.80-5.13 (m , 3 H) 7.18-7.29 (m, 1 H) 7.70-7.80 (m, 2 H) 8.09 (s, 1 H) 8.38 (s, 2 H) 8.52-8.58 (m, 1 H) 9.12 (s, 1 H).
MS ESI / APCI Dual posi: 402 [M + H] ⁺ , 424 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 400 [MH] ^- .
(2) 1- {1- [5- (Fluoromethyl) pyrimidin-2-yl] piperidin-4-yl} -5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c ] Pyridine

実施例４６−８（１）で得られた化合物（４０ｍｇ）を用いて、参考例Ｅ−１４（１）と同様の操作にて反応及び精製を行い、表題化合物（１７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.20 - 2.27 (m, 2 H) 2.32 - 2.41 (m, 2 H) 2.62 (s, 3 H) 3.22 - 3.30 (m, 2 H) 4.88 - 4.95 (m, 1 H) 5.02 - 5.10 (m, 2 H) 5.17 - 5.30 (m, 2 H) 7.22 - 7.27 (m, 1 H) 7.72 (d, J=1.2 Hz, 1 H) 7.74 - 7.77 (m, 1 H) 8.10 (s, 1 H) 8.40 (d, J=2.1 Hz, 2 H) 8.54 - 8.59 (m, 1 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 404[M+H]⁺.
実施例４６−９
１−｛１−［５−（ジフルオロメチル）ピリミジン−２−イル］ピペリジン−４−イル｝−５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）２−｛４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル］ピペリジン−１−イル｝ピリミジン−５−カルバルデヒド

The compound (40 mg) obtained in Example 46-8 (1) was subjected to reaction and purification in the same manner as in Reference Example E-14 (1) to give the title compound (17 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.20-2.27 (m, 2 H) 2.32-2.41 (m, 2 H) 2.62 (s, 3 H) 3.22-3.30 (m, 2 H) 4.88-4.95 (m, 1 H) 5.02-5.10 (m, 2 H) 5.17-5.30 (m, 2 H) 7.22-7.27 (m, 1 H) 7.72 (d, J = 1.2 Hz, 1 H) 7.74-7.77 (m , 1 H) 8.10 (s, 1 H) 8.40 (d, J = 2.1 Hz, 2 H) 8.54-8.59 (m, 1 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 404 [M + H] ⁺ .
Example 46-9
1- {1- [5- (Difluoromethyl) pyrimidin-2-yl] piperidin-4-yl} -5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridine ( 1) 2- {4- [5- (2-Methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidin-1-yl} pyrimidine-5-carbaldehyde

実施例４６−８（１）で得られた化合物（５０ｍｇ）のクロロホルム（１．２５ｍｌ）溶液へ、二酸化マンガン（５４．１ｍｇ）を加え、室温にて１５時間撹拌した。反応系をセライト（登録商標）ろ過後、ろ液を減圧濃縮し、表題化合物（４８ｍｇ）を無色油状物質として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.18 - 2.55 (m, 4 H) 2.62 (s, 3 H) 3.28 - 3.47 (m, 2 H) 4.86 - 5.07 (m, 1 H) 5.11 - 5.25 (m, 2 H) 7.20 - 7.30 (m, 1 H) 7.70 - 7.79 (m, 2 H) 8.11 (s, 1 H) 8.52 - 8.60 (m, 1 H) 8.77 (s, 2 H) 9.13 (s, 1 H) 9.82 (s, 1 H).
MS ESI/APCI Dual posi: 400[M+H]⁺.
MS ESI/APCI Dual nega: 434[M+Cl]^-.
（２）１−｛１−［５−（ジフルオロメチル）ピリミジン−２−イル］ピペリジン−４−イル｝−５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Manganese dioxide (54.1 mg) was added to a chloroform (1.25 ml) solution of the compound (50 mg) obtained in Example 46-8 (1), and the mixture was stirred at room temperature for 15 hours. The reaction system was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure to give the title compound (48 mg) as a colorless oil.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.18-2.55 (m, 4 H) 2.62 (s, 3 H) 3.28-3.47 (m, 2 H) 4.86-5.07 (m, 1 H) 5.11-5.25 (m, 2 H) 7.20-7.30 (m, 1 H) 7.70-7.79 (m, 2 H) 8.11 (s, 1 H) 8.52-8.60 (m, 1 H) 8.77 (s, 2 H) 9.13 (s , 1 H) 9.82 (s, 1 H).
MS ESI / APCI Dual posi: 400 [M + H] ⁺ .
MS ESI / APCI Dual nega: 434 [M + Cl] ^- .
(2) 1- {1- [5- (Difluoromethyl) pyrimidin-2-yl] piperidin-4-yl} -5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c ] Pyridine

実施例４６−９（１）で得られた化合物（４８ｍｇ）を用いて、参考例Ｅ−１４（１）と同様の操作にて反応及び精製を行い、表題化合物（８ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.21 - 2.27 (m, 2 H) 2.32 - 2.41 (m, 2 H) 2.62 (s, 3 H) 3.24 - 3.33 (m, 2 H) 4.88 - 4.96 (m, 1 H) 5.04 - 5.11 (m, 2 H) 6.49 - 6.71 (m, 1 H) 7.21 - 7.28 (m, 1 H) 7.71 - 7.77 (m, 2 H) 8.10 (s, 1 H) 8.46 (s, 2 H) 8.54 - 8.59 (m, 1 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 422[M+H]⁺.
実施例４７−１
５−［２−フルオロ−４−（メチルスルホニル）フェニル］−１−｛１−［３−（プロパン−２−イル）−１，２，４−オキサジアゾル−５−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）４−（５−ブロモ−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル）ピペリジン−１−カルボニトリル

The compound (48 mg) obtained in Example 46-9 (1) was subjected to reaction and purification in the same manner as in Reference Example E-14 (1) to give the title compound (8 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.21-2.27 (m, 2 H) 2.32-2.41 (m, 2 H) 2.62 (s, 3 H) 3.24-3.33 (m, 2 H) 4.88-4.96 (m, 1 H) 5.04-5.11 (m, 2 H) 6.49-6.71 (m, 1 H) 7.21-7.28 (m, 1 H) 7.71-7.77 (m, 2 H) 8.10 (s, 1 H) 8.46 (s, 2 H) 8.54-8.59 (m, 1 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 422 [M + H] ⁺ .
Example 47-1
5- [2-Fluoro-4- (methylsulfonyl) phenyl] -1- {1- [3- (propan-2-yl) -1,2,4-oxadiazol-5-yl] piperidin-4-yl} -1H-pyrazolo [3,4-c] pyridine (1) 4- (5-bromo-1H-pyrazolo [3,4-c] pyridin-1-yl) piperidine-1-carbonitrile

参考例２５で得られた化合物（５００ｍｇ）のクロロホルム（１．７８ｍｌ）溶液へ、０℃にて炭酸水素ナトリウム（２９９ｍｇ）の水（１．７８ｍｌ）懸濁液を加え、同温にて５分撹拌した。同温にて臭化シアン（２０７ｍｇ）のクロロホルム（１．７８ｍｌ）溶液を加え、室温にて５時間撹拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜１：２）にて精製し、表題化合物（５５８ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.05 - 2.24 (m, 2 H) 2.33 - 2.58 (m, 2 H) 3.22 - 3.41 (m, 2 H) 3.62 - 3.78 (m, 2 H) 4.55 - 4.73 (m, 1 H) 7.81 - 7.87 (m, 1 H) 8.03 (s, 1 H) 8.72 - 8.78 (m, 1 H).
MS ESI/APCI Dual posi: 306[M+H]⁺, 328[M+Na]⁺.
MS ESI/APCI Dual nega: 304[M-H]^-.
（２）５−ブロモ−１−｛１−［３−（プロパン−２−イル）−１，２，４−オキサジアゾル−５−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound (500 mg) obtained in Reference Example 25 in chloroform (1.78 ml) was added a sodium hydrogencarbonate (299 mg) suspension in water (1.78 ml) at 0 ° C., and the same temperature was maintained for 5 minutes. Stir. A solution of cyanogen bromide (207 mg) in chloroform (1.78 ml) was added at the same temperature, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 1: 2) to give the title compound (558 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 2.05-2.24 (m, 2 H) 2.33-2.58 (m, 2 H) 3.22-3.41 (m, 2 H) 3.62-3.78 (m, 2 H) 4.55 -4.73 (m, 1 H) 7.81-7.87 (m, 1 H) 8.03 (s, 1 H) 8.72-8.78 (m, 1 H).
MS ESI / APCI Dual posi: 306 [M + H] ⁺ , 328 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 304 [MH] ^- .
(2) 5-Bromo-1- {1- [3- (propan-2-yl) -1,2,4-oxadiazol-5-yl] piperidin-4-yl} -1H-pyrazolo [3,4 c] pyridine

実施例４７−１（１）で得られた化合物（５５８ｍｇ）のテトラヒドロフラン（９．１１ｍｌ）溶液へ、Ｎ´−ヒドロキシ−２−メチルプロパンイミドアミド（２２３ｍｇ）、１Ｍ 塩化亜鉛・ジエチルエーテル溶液（２．１９ｍｌ）を加え、室温にて３０分撹拌した。反応系に生じた粉末をろ取した。得られた粉末にエタノール（９．１１ｍｌ）、濃塩酸（４．５６ｍｌ）を加え、８０℃にて１時間攪拌した。反応系を減圧濃縮し、得られた残渣に飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１）にて精製し、表題化合物（４６７ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.31 (d, J=7.0 Hz, 6 H) 2.08 - 2.26 (m, 2 H) 2.28 - 2.54 (m, 2 H) 2.81 - 3.02 (m, 1 H) 3.29 - 3.47 (m, 2 H) 4.28 - 4.44 (m, 2 H) 4.65 - 4.84 (m, 1 H) 7.81 - 7.86 (m, 1 H) 8.02 (s, 1 H) 8.76 - 8.81 (m, 1 H).
MS ESI/APCI Dual posi: 391[M+H]⁺, 413[M+Na]⁺.
（３）５−［２−フルオロ−４−（メチルスルホニル）フェニル］−１−｛１−［３−（プロパン−２−イル）−１，２，４−オキサジアゾル−５−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound (558 mg) obtained in Example 47-1 (1) in tetrahydrofuran (9.11 ml), N′-hydroxy-2-methylpropanimidamide (223 mg), 1M zinc chloride / diethyl ether solution (2 19 ml) and stirred at room temperature for 30 minutes. The powder generated in the reaction system was collected by filtration. Ethanol (9.11 ml) and concentrated hydrochloric acid (4.56 ml) were added to the obtained powder and stirred at 80 ° C. for 1 hour. The reaction system was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the resulting residue, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1) to obtain the title compound (467 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.31 (d, J = 7.0 Hz, 6 H) 2.08-2.26 (m, 2 H) 2.28-2.54 (m, 2 H) 2.81-3.02 (m, 1 H) 3.29-3.47 (m, 2 H) 4.28-4.44 (m, 2 H) 4.65-4.84 (m, 1 H) 7.81-7.86 (m, 1 H) 8.02 (s, 1 H) 8.76-8.81 (m , 1 H).
MS ESI / APCI Dual posi: 391 [M + H] ⁺ , 413 [M + Na] ⁺ .
(3) 5- [2-Fluoro-4- (methylsulfonyl) phenyl] -1- {1- [3- (propan-2-yl) -1,2,4-oxadiazol-5-yl] piperidine-4 -Yl} -1H-pyrazolo [3,4-c] pyridine

実施例４７−１（２）で得られた化合物（７０ｍｇ）と２−フルオロ−４−（メチルスルホニル）フェニルボロン酸（５８．５ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（９ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J=7.0 Hz, 6 H) 2.13 - 2.67 (m, 4 H) 2.81 - 3.05 (m, 1 H) 3.12 (s, 3 H) 3.31 - 3.52 (m, 2 H) 4.31 - 4.50 (m, 2 H) 4.74 - 4.96 (m, 1 H) 7.75 - 7.91 (m, 2 H) 8.14 - 8.40 (m, 3 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 485[M+H]⁺, 507[M+Na]⁺.
MS ESI/APCI Dual nega: 519[M+Cl]^-.
実施例４７−２
５−（２−メチルピリジン−３−イル）−１−｛１−［３−（プロパン−２−イル）−１，２，４−オキサジアゾル−５−イル］ピペリジン−４−イル｝−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (70 mg) obtained in Example 47-1 (2) and 2-fluoro-4- (methylsulfonyl) phenylboronic acid (58.5 mg), the same operation as in Example 40-1 was carried out. Reaction and purification were performed to give the title compound (9 mg) as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J = 7.0 Hz, 6 H) 2.13-2.67 (m, 4 H) 2.81-3.05 (m, 1 H) 3.12 (s, 3 H) 3.31-3.52 (m, 2 H) 4.31-4.50 (m, 2 H) 4.74-4.96 (m, 1 H) 7.75-7.91 (m, 2 H) 8.14-8.40 (m, 3 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 485 [M + H] ⁺ , 507 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 519 [M + Cl] ^- .
Example 47-2
5- (2-Methylpyridin-3-yl) -1- {1- [3- (propan-2-yl) -1,2,4-oxadiazol-5-yl] piperidin-4-yl} -1H- Pyrazolo [3,4-c] pyridine

実施例４７−１（２）で得られた化合物（７０ｍｇ）と２−メチルピリジン−３−ボロン酸ピナコールエステル（５８．７ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（１０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J=7.0 Hz, 6 H) 2.20 - 2.29 (m, 2 H) 2.41 - 2.51 (m, 2 H) 2.62 (s, 3 H) 2.89 - 2.98 (m, 1 H) 3.37 - 3.45 (m, 2 H) 4.35 - 4.44 (m, 2 H) 4.81 - 4.89 (m, 1 H) 7.22 - 7.28 (m, 2 H) 7.72 - 7.77 (m, 2 H) 8.12 (s, 1 H) 8.54 - 8.58 (m, 1 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 404[M+H]⁺.
MS ESI/APCI Dual nega: 438[M+Cl]^-.
実施例４８−１
プロパン−２−イル ４−｛５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (70 mg) obtained in Example 47-1 (2) and 2-methylpyridine-3-boronic acid pinacol ester (58.7 mg), the reaction and reaction were carried out in the same manner as in Example 40-1. Purification was performed to give the title compound (10 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.32 (d, J = 7.0 Hz, 6 H) 2.20-2.29 (m, 2 H) 2.41-2.51 (m, 2 H) 2.62 (s, 3 H) 2.89-2.98 (m, 1 H) 3.37-3.45 (m, 2 H) 4.35-4.44 (m, 2 H) 4.81-4.89 (m, 1 H) 7.22-7.28 (m, 2 H) 7.72-7.77 (m , 2 H) 8.12 (s, 1 H) 8.54-8.58 (m, 1 H) 9.11 (s, 1 H).
MS ESI / APCI Dual posi: 404 [M + H] ⁺ .
MS ESI / APCI Dual nega: 438 [M + Cl] ^- .
Example 48-1
Propan-2-yl 4- {5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２４−Ａで得られた化合物（５０ｍｇ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（３５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.4 Hz, 6 H) 2.06 - 2.19 (m, 2 H) 2.21 - 2.39 (m, 2 H) 2.98 - 3.15 (m, 5 H) 4.31 - 4.48 (m, 2 H) 4.68 - 4.84 (m, 1 H) 4.90 - 5.04 (m, 1 H) 8.01 - 8.09 (m, 2 H) 8.11 - 8.15 (m, 2 H) 8.21 - 8.27 (m, 2 H) 9.09 - 9.13 (m, 1 H).
MS ESI/APCI Dual posi: 443[M+H]⁺, 465[M+Na]⁺.

The compound (50 mg) obtained in Reference Example 24-A was subjected to reaction and purification in the same manner as in Example 32-1, to obtain the title compound (35 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.4 Hz, 6 H) 2.06-2.19 (m, 2 H) 2.21-2.39 (m, 2 H) 2.98-3.15 (m, 5 H) 4.31-4.48 (m, 2 H) 4.68-4.84 (m, 1 H) 4.90-5.04 (m, 1 H) 8.01-8.09 (m, 2 H) 8.11-8.15 (m, 2 H) 8.21-8.27 (m, 2 H) 9.09-9.13 (m, 1 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ , 465 [M + Na] ⁺ .

  The following Examples 48-2 to 48-6 also conformed to the method described in Example 32-1 or 32-5 using the carbamate reagent corresponding to the compound obtained in Reference Example 24-A. And synthesized. Table 33-1 shows the structures, NMR data, and MS data of these compounds.

Example 49-1
Ethyl 4- {5- [2-fluoro-4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２４−Ｂで得られた化合物（６０ｍｇ）とクロロぎ酸エチル（２２．９μｌ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（５２．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3 H) 2.06 - 2.19 (m, 2 H) 2.22 - 2.40 (m, 2 H) 3.00 - 3.18 (m, 5 H) 4.20 (q, J=7.2 Hz, 2 H) 4.29 - 4.51 (m, 2 H) 4.69 - 4.84 (m, 1 H) 7.74 - 7.89 (m, 2 H) 8.15 (s, 1 H) 8.21 - 8.27 (m, 1 H) 8.30 - 8.38 (m, 1 H) 9.13 (s, 1 H).
MS ESI/APCI Dual posi: 447[M+H]⁺, 469[M+Na]⁺.
MS ESI/APCI Dual nega: 481[M+Cl]^-.

Using the compound (60 mg) obtained in Reference Example 24-B and ethyl chloroformate (22.9 μl), the reaction and purification were carried out in the same manner as in Example 32-1, to obtain the title compound (52.9 mg). ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J = 7.1 Hz, 3 H) 2.06-2.19 (m, 2 H) 2.22-2.40 (m, 2 H) 3.00-3.18 (m, 5 H) 4.20 (q, J = 7.2 Hz, 2 H) 4.29-4.51 (m, 2 H) 4.69-4.84 (m, 1 H) 7.74-7.89 (m, 2 H) 8.15 (s, 1 H) 8.21- 8.27 (m, 1 H) 8.30-8.38 (m, 1 H) 9.13 (s, 1 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ , 469 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 481 [M + Cl] ^- .

  The following Examples 49-2 to 49-18 were also prepared according to the method described in Examples 32-1 to 32-5 using the compound obtained in Reference Example 24-B and the corresponding alcohol or carbamate reagent. Synthesized in compliance. The structures, NMR data, and MS data of these compounds are shown in Tables 34-1 to 34-3.

Examples 49-19
1-methylcyclopropyl 4- {5- [2-fluoro-4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２４−Ｂで得られた化合物（６０ｍｇ）のクロロホルム（６００μｌ）溶液へ、トリエチルアミン（１５０μｌ）、１−メチルシクロプロピル ４−ニトロフェニルカーボネート（４２ｍｇ；Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，２０１１，５２，３１７１に記載）を加え室温にて二日間攪拌した。反応液へクロロホルムを加え、１M水酸化ナトリウム水溶液にて２回、１M塩酸にて１回洗浄した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１００：０〜９５：５）にて精製後、ヘキサン−クロロホルム混合液で再結晶し、表題化合物（５９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64 - 0.71 (m, 2 H) 0.88 - 0.96 (m, 2 H) 1.55 (s, 3 H) 2.05 - 2.18 (m, 2 H) 2.20 - 2.38 (m, 2 H) 3.11 (s, 5 H) 4.10 - 4.56 (m, 2 H) 4.65 - 4.82 (m, 1 H) 7.76 - 7.88 (m, 2 H) 8.15 (s, 1 H) 8.23 - 8.25 (m, 1 H) 8.30 - 8.38 (m, 1 H) 9.09 - 9.14 (m, 1 H).
MS ESI/APCI Dual posi: 473[M+H]⁺, 495[M+Na]⁺.
実施例５０−１
ｔｅｒｔ−ブチル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル］ピペリジン−１−カルボキシラート

To a solution of the compound (60 mg) obtained in Reference Example 24-B in chloroform (600 μl), triethylamine (150 μl), 1-methylcyclopropyl 4-nitrophenyl carbonate (42 mg; described in Tetrahedron Letters, 2011, 52, 3171) And stirred at room temperature for 2 days. Chloroform was added to the reaction solution, and the mixture was washed twice with 1M aqueous sodium hydroxide solution and once with 1M hydrochloric acid. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 100: 0 to 95: 5) and then recrystallized from a hexane-chloroform mixed solution to obtain the title compound (59 mg) as a colorless powder. .
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.71 (m, 2 H) 0.88-0.96 (m, 2 H) 1.55 (s, 3 H) 2.05-2.18 (m, 2 H) 2.20-2.38 (m, 2 H) 3.11 (s, 5 H) 4.10-4.56 (m, 2 H) 4.65-4.82 (m, 1 H) 7.76-7.88 (m, 2 H) 8.15 (s, 1 H) 8.23-8.25 (m, 1 H) 8.30-8.38 (m, 1 H) 9.09-9.14 (m, 1 H).
MS ESI / APCI Dual posi: 473 [M + H] ⁺ , 495 [M + Na] ⁺ .
Example 50-1
tert-Butyl 4- [5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidine-1-carboxylate

参考例１５で得られた化合物（１００ｍｇ）と２−メチルピリジン−３−ボロン酸 ピナコールエステル（８６．２ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（６８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.06 - 2.18 (m, 2 H) 2.22 - 2.38 (m, 2 H) 2.61 (s, 3 H) 2.95 - 3.13 (m, 2 H) 4.24 - 4.48 (m, 2 H) 4.68 - 4.83 (m, 1 H) 7.24 (s, 1 H) 7.70 - 7.78 (m, 2 H) 8.11 (s, 1 H) 8.53 - 8.58 (m, 1 H) 9.10 (s, 1 H).
MS ESI/APCI Dual posi: 394[M+H]⁺, 416[M+Na]⁺.
実施例５０−２
プロパン−２−イル ４−［５−（２−メチルピリジン−３−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル］ピペリジン−１−カルボキシラート

Using the compound (100 mg) obtained in Reference Example 15 and 2-methylpyridine-3-boronic acid pinacol ester (86.2 mg), the reaction and purification were carried out in the same manner as in Example 40-1, and the title Compound (68 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.51 (s, 9 H) 2.06-2.18 (m, 2 H) 2.22-2.38 (m, 2 H) 2.61 (s, 3 H) 2.95-3.13 (m , 2 H) 4.24-4.48 (m, 2 H) 4.68-4.83 (m, 1 H) 7.24 (s, 1 H) 7.70-7.78 (m, 2 H) 8.11 (s, 1 H) 8.53-8.58 (m , 1 H) 9.10 (s, 1 H).
MS ESI / APCI Dual posi: 394 [M + H] ⁺ , 416 [M + Na] ⁺ .
Example 50-2
Propan-2-yl 4- [5- (2-methylpyridin-3-yl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidine-1-carboxylate

参考例２４−Cで得られた化合物（１００ｍｇ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（７８．５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.3 Hz, 6 H) 2.07 - 2.19 (m, 2 H) 2.22 - 2.39 (m, 2 H) 2.61 (s, 3 H) 2.98 - 3.17 (m, 2 H) 4.39 (br. s., 2 H) 4.68 - 4.84 (m, 1 H) 4.98 (quin, J=6.3 Hz, 1 H) 7.21 - 7.27 (m, 1 H) 7.69 - 7.77 (m, 2 H) 8.11 (s, 1 H) 8.53 - 8.59 (m, 1 H) 9.10 (s, 1 H).
MS ESI/APCI Dual posi: 380[M+H]⁺, 402[M+Na]⁺.

The compound (100 mg) obtained in Reference Example 24-C was subjected to reaction and purification in the same manner as in Example 32-1, and the title compound (78.5 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.3 Hz, 6 H) 2.07-2.19 (m, 2 H) 2.22-2.39 (m, 2 H) 2.61 (s, 3 H) 2.98-3.17 (m, 2 H) 4.39 (br. S., 2 H) 4.68-4.84 (m, 1 H) 4.98 (quin, J = 6.3 Hz, 1 H) 7.21-7.27 (m, 1 H) 7.69 -7.77 (m, 2 H) 8.11 (s, 1 H) 8.53-8.59 (m, 1 H) 9.10 (s, 1 H).
MS ESI / APCI Dual posi: 380 [M + H] ⁺ , 402 [M + Na] ⁺ .

  The following Examples 50-3 to 50-8 are also described in Examples 32-1 to 32-5 or 49-19 using the alcohol obtained in Reference Example 24-C and the corresponding alcohol or carbamate reagent. Synthesized according to the published method. The structure, NMR data, and MS data of these compounds are shown in Table 35-1.

Example 51-1
1- [1- (2,2-Dimethylpropyl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ａで得られた化合物（５０ｍｇ）を用いて、実施例３８−１と同様の操作にて反応及び精製を行い、表題化合物（１９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.91 (s, 9 H) 1.94 - 2.06 (m, 2 H) 2.17 (s, 2 H) 2.35 - 2.60 (m, 4 H) 2.96 - 3.06 (m, 2 H) 3.10 (s, 3 H) 4.47 - 4.63 (m, 1 H) 8.02 - 8.08 (m, 2 H) 8.10 - 8.15 (m, 2 H) 8.21 - 8.27 (m, 2 H) 9.09 - 9.18 (m, 1 H).
MS ESI/APCI Dual posi: 427[M+H]⁺.
実施例５１−２
１−｛１−［（３−メチルオキセタン−３−イル）メチル］ピペリジン−４−イル｝−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (50 mg) obtained in Reference Example 24-A, the reaction and purification were carried out in the same manner as in Example 38-1, and the title compound (19 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.91 (s, 9 H) 1.94-2.06 (m, 2 H) 2.17 (s, 2 H) 2.35-2.60 (m, 4 H) 2.96-3.06 (m , 2 H) 3.10 (s, 3 H) 4.47-4.63 (m, 1 H) 8.02-8.08 (m, 2 H) 8.10-8.15 (m, 2 H) 8.21-8.27 (m, 2 H) 9.09-9.18 (m, 1 H).
MS ESI / APCI Dual posi: 427 [M + H] ⁺ .
Example 51-2
1- {1-[(3-Methyloxetan-3-yl) methyl] piperidin-4-yl} -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ａで得られた化合物（５０ｍｇ）と３−メチル−３−オキセタンメタノール（４２ｍｇ）を用いて、実施例３８−１と同様の操作にて反応及び精製を行い、表題化合物（４４ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 3 H) 2.05 - 2.15 (m, 2 H) 2.31 - 2.51 (m, 4 H) 2.69 (s, 2 H) 2.83 - 2.92 (m, 2 H) 3.10 (s, 3 H) 4.35 - 4.40 (m, 2 H) 4.51 - 4.66 (m, 3 H) 8.02 - 8.08 (m, 2 H) 8.11 - 8.15 (m, 2 H) 8.20 - 8.26 (m, 2 H) 9.11 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 441[M+H]⁺.
実施例５１−３
１−［１−（２−メチルプロピル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (50 mg) obtained in Reference Example 24-A and 3-methyl-3-oxetanemethanol (42 mg), the reaction and purification were carried out in the same manner as in Example 38-1, and the title compound (44 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 3 H) 2.05-2.15 (m, 2 H) 2.31-2.51 (m, 4 H) 2.69 (s, 2 H) 2.83-2.92 (m , 2 H) 3.10 (s, 3 H) 4.35-4.40 (m, 2 H) 4.51-4.66 (m, 3 H) 8.02-8.08 (m, 2 H) 8.11-8.15 (m, 2 H) 8.20-8.26 (m, 2 H) 9.11-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 441 [M + H] ⁺ .
Example 51-3
1- [1- (2-Methylpropyl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridine

参考例２４−Ａで得られた化合物（５０ｍｇ）と１−ヨード−２−メチルプロパン（３９ｍｇ）を用いて、実施例１６−１と同様の操作にて反応及び精製を行い、表題化合物（５３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.94 (d, J=6.5 Hz, 6 H) 1.74 - 1.90 (m, 1 H) 2.03 - 2.26 (m, 6 H) 2.34 - 2.52 (m, 2 H) 3.02 - 3.15 (m, 5 H) 4.49 - 4.65 (m, 1 H) 8.02 - 8.07 (m, 2 H) 8.11 - 8.15 (m, 2 H) 8.21 - 8.28 (m, 2 H) 9.12 - 9.15 (m, 1 H).
MS ESI/APCI Dual posi: 413[M+H]⁺.

Using the compound (50 mg) obtained in Reference Example 24-A and 1-iodo-2-methylpropane (39 mg), the reaction and purification were conducted in the same manner as in Example 16-1, and the title compound (53 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.94 (d, J = 6.5 Hz, 6 H) 1.74-1.90 (m, 1 H) 2.03-2.26 (m, 6 H) 2.34-2.52 (m, 2 H) 3.02-3.15 (m, 5 H) 4.49-4.65 (m, 1 H) 8.02-8.07 (m, 2 H) 8.11-8.15 (m, 2 H) 8.21-8.28 (m, 2 H) 9.12-9.15 (m, 1 H).
MS ESI / APCI Dual posi: 413 [M + H] ⁺ .

  The following Examples 51-4 to 51-8 were also synthesized according to the method described in Example 16-1 using the compound obtained in Reference Example 24-A and the corresponding alkyl halide. The structure, NMR data, and MS data of these compounds are shown in Table 36-1.

Example 52-1
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -2-fluorobenzamide

参考例２６−Ａで得られた化合物（８２．０ｍｇ）と２８％アンモニア水（１７ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（２５．３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.13 - 2.26 (m, 2 H) 2.28 - 2.45 (m, 2 H) 2.51 (q, J=7.5 Hz, 2 H) 3.13 - 3.26 (m, 2 H) 4.81 - 5.04 (m, 3 H) 5.74 - 5.85 (m, 1 H) 6.67 - 6.83 (m, 1 H) 7.89 - 7.97 (m, 2 H) 8.12 (s, 2 H) 8.20 - 8.28 (m, 3 H) 9.11 - 9.14 (m, 1 H).
MS ESI/APCI Dual posi: 446[M+H]⁺.
MS ESI/APCI Dual nega: 444[M-H]^-.

Using the compound (82.0 mg) obtained in Reference Example 26-A and 28% aqueous ammonia (17 mg), the reaction and purification were conducted in the same manner as in Example 5-1, to obtain the title compound (25.3 mg). ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.13-2.26 (m, 2 H) 2.28-2.45 (m, 2 H) 2.51 (q, J = 7.5 Hz, 2 H) 3.13-3.26 (m, 2 H) 4.81-5.04 (m, 3 H) 5.74-5.85 (m, 1 H) 6.67-6.83 (m, 1 H) 7.89-7.97 (m, 2 H) 8.12 (s, 2 H) 8.20-8.28 (m, 3 H) 9.11-9.14 (m, 1 H).
MS ESI / APCI Dual posi: 446 [M + H] ⁺ .
MS ESI / APCI Dual nega: 444 [MH] ^- .

  The following Examples 52-2 to 52-3 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 26-A and the corresponding amine. The structure, NMR data, and MS data of these compounds are shown in Table 37-1.

Example 53-1.
4- {1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} -2,5-difluorobenzamide

参考例２６−Ｂで得られた化合物（７５．０ｍｇ）と２８％アンモニア水（１６ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（２３．２ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.5 Hz, 3 H) 2.13 - 2.25 (m, 2 H) 2.27 - 2.44 (m, 2 H) 2.50 (q, J=7.7 Hz, 2 H) 3.11 - 3.25 (m, 2 H) 4.80 - 5.03 (m, 3 H) 5.85 (br. s., 1 H) 6.70 - 6.82 (m, 1 H) 7.90 - 8.07 (m, 2 H) 8.12 (s, 1 H) 8.22 (s, 2 H) 8.29 - 8.31 (m, 1 H) 9.11 - 9.14 (m, 1 H).
MS ESI/APCI Dual posi: 464[M+H]⁺.

Using the compound (75.0 mg) obtained in Reference Example 26-B and 28% aqueous ammonia (16 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (23.2 mg) was obtained. ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.5 Hz, 3 H) 2.13-2.25 (m, 2 H) 2.27-2.44 (m, 2 H) 2.50 (q, J = 7.7 Hz, 2 H) 3.11-3.25 (m, 2 H) 4.80-5.03 (m, 3 H) 5.85 (br. S., 1 H) 6.70-6.82 (m, 1 H) 7.90-8.07 (m, 2 H ) 8.12 (s, 1 H) 8.22 (s, 2 H) 8.29-8.31 (m, 1 H) 9.11-9.14 (m, 1 H).
MS ESI / APCI Dual posi: 464 [M + H] ⁺ .

  The following Examples 53-2 to 53-4 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 26-B and the corresponding amine. The structures, NMR data, and MS data of these compounds are shown in Table 38-1.

Example 54-1
Propan-2-yl 4- [5- (4-carbamoyl-3-fluorophenyl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidin-1-carboxylate

参考例２６−Ｃで得られた化合物（７０．０ｍｇ）と２８％アンモニア水（１６．８ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４４．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.06 - 2.18 (m, 2 H) 2.21 - 2.38 (m, 2 H) 2.99 - 3.15 (m, 2 H) 4.29 - 4.49 (m, 2 H) 4.68 - 4.83 (m, 1 H) 4.91 - 5.05 (m, 1 H) 5.82 (br. s., 1 H) 6.70 - 6.83 (m, 1 H) 7.87 - 7.96 (m, 2 H) 8.09 - 8.15 (m, 2 H) 8.19 - 8.28 (m, 1 H) 9.07 - 9.11 (m, 1 H).
MS ESI/APCI Dual posi: 426[M+H]⁺, 448[M+Na]⁺.

Using the compound (70.0 mg) obtained in Reference Example 26-C and 28% aqueous ammonia (16.8 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (44 .8 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.06-2.18 (m, 2 H) 2.21-2.38 (m, 2 H) 2.99-3.15 (m, 2 H) 4.29-4.49 (m, 2 H) 4.68-4.83 (m, 1 H) 4.91-5.05 (m, 1 H) 5.82 (br. S., 1 H) 6.70-6.83 (m, 1 H) 7.87- 7.96 (m, 2 H) 8.09-8.15 (m, 2 H) 8.19-8.28 (m, 1 H) 9.07-9.11 (m, 1 H).
MS ESI / APCI Dual posi: 426 [M + H] ⁺ , 448 [M + Na] ⁺ .

  The following Examples 54-2 to 54-7 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 26-C and the corresponding amine. The structure, NMR data, and MS data of these compounds are shown in Table 39-1.

Example 55-1
Propan-2-yl 4- [5- (4-carbamoyl-2-fluorophenyl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidine-1-carboxylate

参考例２６−Ｄで得られた化合物（８０．０ｍｇ）と２８％アンモニア水（１９．２ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４６．５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.2 Hz, 6 H) 2.07 - 2.16 (m, 2 H) 2.24 - 2.36 (m, 2 H) 3.00 - 3.14 (m, 2 H) 4.28 - 4.50 (m, 2 H) 4.70 - 4.79 (m, 1 H) 4.94 - 5.02 (m, 1 H) 5.47 - 5.77 (m, 1 H) 5.97 - 6.23 (m, 1 H) 7.66 - 7.72 (m, 2 H) 8.13 (s, 1 H) 8.16 - 8.20 (m, 1 H) 8.21 (s, 1 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 426[M+H]⁺, 448[M+Na]⁺.

Using the compound (80.0 mg) obtained in Reference Example 26-D and 28% aqueous ammonia (19.2 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (46 0.5 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.2 Hz, 6 H) 2.07-2.16 (m, 2 H) 2.24-2.36 (m, 2 H) 3.00-3.14 (m, 2 H) 4.28-4.50 (m, 2 H) 4.70-4.79 (m, 1 H) 4.94-5.02 (m, 1 H) 5.47-5.77 (m, 1 H) 5.97-6.23 (m, 1 H) 7.66-7.72 (m, 2 H) 8.13 (s, 1 H) 8.16-8.20 (m, 1 H) 8.21 (s, 1 H) 9.11 (s, 1 H).
MS ESI / APCI Dual posi: 426 [M + H] ⁺ , 448 [M + Na] ⁺ .

  The following Examples 55-2 to 55-6 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 26-D and the corresponding amine. The structures, NMR data, and MS data of these compounds are shown in Tables 40-1 to 40-2.

Example 56-1
Propan-2-yl 4- [5- (4-carbamoyl-2,5-difluorophenyl) -1H-pyrazolo [3,4-c] pyridin-1-yl] piperidine-1-carboxylate

参考例２６−Ｅで得られた化合物（６０．０ｍｇ）と２８％アンモニア水（１３．８ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４５．６ｍｇ）を無色粉末として得た。
¹H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.1 Hz, 6 H) 2.06 - 2.17 (m, 2 H) 2.23 - 2.36 (m, 2 H) 2.98 - 3.15 (m, 2 H) 4.27 - 4.53 (m, 2 H) 4.70 - 4.81 (m, 1 H) 4.93 - 5.03 (m, 1 H) 5.83 (br. s, 1 H) 6.71 - 6.82 (m, 1 H) 7.91 - 8.07 (m, 2 H) 8.14 (s, 1 H) 8.31 (s, 1 H) 9.10 (s, 1 H).
MS ESI/APCI Dual posi: 444[M+H]⁺, 466[M+Na]⁺.

Using the compound (60.0 mg) obtained in Reference Example 26-E and 28% aqueous ammonia (13.8 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (45 .6 mg) was obtained as a colorless powder.
¹ H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J = 6.1 Hz, 6 H) 2.06-2.17 (m, 2 H) 2.23-2.36 (m, 2 H) 2.98-3.15 (m, 2 H) 4.27-4.53 (m, 2 H) 4.70-4.81 (m, 1 H) 4.93-5.03 (m, 1 H) 5.83 (br. S, 1 H) 6.71-6.82 (m, 1 H) 7.91-8.07 (m, 2 H) 8.14 (s, 1 H) 8.31 (s, 1 H) 9.10 (s, 1 H).
MS ESI / APCI Dual posi: 444 [M + H] ⁺ , 466 [M + Na] ⁺ .

  The following Examples 56-2 to 56-23 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 26-E and the corresponding amine. The structures, NMR data, and MS data of these compounds are shown in Tables 41-1 to 41-4.

Example 57-1
2,2-dimethylpropyl 4- {5- [2,5-difluoro-4- (methylcarbamoyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２６−Ｆで得られた化合物（７０．０ｍｇ）と４０％メチルアミン水溶液（１７．３ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（５３．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (s, 9 H) 2.08 - 2.20 (m, 2 H) 2.23 - 2.40 (m, 2 H) 3.01 - 3.22 (m, 5 H) 3.84 (s, 2 H) 4.29 - 4.53 (m, 2 H) 4.69 - 4.85 (m, 1 H) 6.78 - 6.92 (m, 1 H) 7.90 - 8.04 (m, 2 H) 8.14 (s, 1 H) 8.28 - 8.32 (m, 1 H) 9.07 - 9.13 (m, 1 H).
MS ESI/APCI Dual posi: 486[M+H]⁺, 508[M+Na]⁺.
MS ESI/APCI Dual nega: 520[M+Cl]^-.

Using the compound (70.0 mg) obtained in Reference Example 26-F and a 40% aqueous methylamine solution (17.3 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound ( 53.9 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.98 (s, 9 H) 2.08-2.20 (m, 2 H) 2.23-2.40 (m, 2 H) 3.01-3.22 (m, 5 H) 3.84 (s , 2 H) 4.29-4.53 (m, 2 H) 4.69-4.85 (m, 1 H) 6.78-6.92 (m, 1 H) 7.90-8.04 (m, 2 H) 8.14 (s, 1 H) 8.28-8.32 (m, 1 H) 9.07-9.13 (m, 1 H).
MS ESI / APCI Dual posi: 486 [M + H] ⁺ , 508 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 520 [M + Cl] ^- .

  The following Examples 57-2 to 57-23 were also synthesized in accordance with the method described in Example 5-1 using the compounds obtained in Reference Examples 26-F to 26-J and the corresponding amines. The structures, NMR data, and MS data of these compounds are shown in Tables 42-1 to 42-4.

Example 58-1
1-methylcyclopropyl 4- {5- [4- (azetidin-1-ylcarbonyl) -2,5-difluorophenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1- Carboxylate (1) Azetidin-1-yl [2,5-difluoro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanone

参考例Ｅ−１０で得られた化合物（２６０ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（５ｍｌ）溶液へ、アゼチジン（７８ｍｇ）、１−ヒドロキシベンゾトリアゾ−ル一水和物（２１０ｍｇ）、Ｎ−エチル−Ｎ’−３−ジメチルアミノプロピルカルボジイミド塩酸塩（２６３ｍｇ）を加え、室温にて一晩攪拌した。反応液へ水を加え、酢酸エチルにて抽出した。得られた有機層を水、飽和食塩水で洗浄後、フェーズセパレーターを通し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１００：０〜９５：５）にて精製し、表題化合物（１３８ｍｇ）を無色油状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.33 - 1.38 (m, 12 H) 2.25 - 2.42 (m, 2 H) 4.03 - 4.26 (m, 4 H) 7.15 - 7.22 (m, 1 H) 7.39 - 7.48 (m, 1 H).
MS ESI/APCI Dual posi: 324[M+H]⁺.
（２）ｔｅｒｔ−ブチル ４−｛５−［４−（アゼチジン−１−イルカルボニル）−２，５−ジフルオロフェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

To a solution of the compound obtained in Reference Example E-10 (260 mg) in N, N-dimethylformamide (5 ml), azetidine (78 mg), 1-hydroxybenzotriazole monohydrate (210 mg), N-ethyl. -N'-3-dimethylaminopropylcarbodiimide hydrochloride (263 mg) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine, passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform: methanol = 100: 0 to 95: 5) to obtain the title compound (138 mg) as a colorless oily substance.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.33-1.38 (m, 12 H) 2.25-2.42 (m, 2 H) 4.03-4.26 (m, 4 H) 7.15-7.22 (m, 1 H) 7.39 -7.48 (m, 1 H).
MS ESI / APCI Dual posi: 324 [M + H] ⁺ .
(2) tert-butyl 4- {5- [4- (azetidin-1-ylcarbonyl) -2,5-difluorophenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1 -Carboxylate

参考例１５で得られた化合物（１００ｍｇ）と実施例５８−１（１）で得られた化合物（１２７ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（１３０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62 - 0.70 (m, 2 H) 0.91 (m, J=6.1 Hz, 2 H) 1.59 (s, 3 H) 1.99 - 2.45 (m, 6 H) 2.93 - 3.13 (m, 2 H) 4.07 - 4.51 (m, 6 H) 4.60 - 4.83 (m, 1 H) 7.33 - 7.44 (m, 1 H) 7.76 - 7.94 (m, 1 H) 8.07 - 8.15 (m, 1 H) 8.17 - 8.25 (m, 1 H) 8.99 - 9.10 (m, 1 H).
MS ESI/APCI Dual posi: 498[M+H]⁺.
MS ESI/APCI Dual nega: 532[M+Cl]^-.
（３）アゼチジン−１−イル｛２，５−ジフルオロ−４−［１−（ピペリジン−４−イル）−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル］フェニル｝メタノン

Using the compound (100 mg) obtained in Reference Example 15 and the compound (127 mg) obtained in Example 58-1 (1), the reaction and purification were carried out in the same manner as in Example 40-1, and the title Compound (130 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.70 (m, 2 H) 0.91 (m, J = 6.1 Hz, 2 H) 1.59 (s, 3 H) 1.99-2.45 (m, 6 H) 2.93-3.13 (m, 2 H) 4.07-4.51 (m, 6 H) 4.60-4.83 (m, 1 H) 7.33-7.44 (m, 1 H) 7.76-7.94 (m, 1 H) 8.07-8.15 (m , 1 H) 8.17-8.25 (m, 1 H) 8.99-9.10 (m, 1 H).
MS ESI / APCI Dual posi: 498 [M + H] ⁺ .
MS ESI / APCI Dual nega: 532 [M + Cl] ^- .
(3) Azetidin-1-yl {2,5-difluoro-4- [1- (piperidin-4-yl) -1H-pyrazolo [3,4-c] pyridin-5-yl] phenyl} methanone

実施例５８−１（２）で得られた化合物（１３０ｍｇ）のクロロホルム（２ｍｌ）溶液へ、氷冷下トリフルオロ酢酸（０．２ｍｌ）を加え、氷冷で１時間、室温で４時間攪拌した。反応液へ飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層を水、飽和食塩水で洗浄後、フェーズセパレーターを通した。溶媒を減圧留去し、表題化合物（１００ｍｇ）を無色ガム状物質として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06 - 2.44 (m, 6 H) 2.81 - 2.96 (m, 2 H) 3.28 - 3.41 (m, 2 H) 4.15 - 4.29 (m, 4 H) 4.60 - 4.77 (m, 1 H) 7.34 - 7.44 (m, 1 H) 7.85 - 7.95 (m, 1 H) 8.12 (s, 1 H) 8.19 - 8.24 (m, 1 H) 9.11 (s, 1 H).
MS ESI/APCI Dual posi: 398[M+H]⁺.
（４）１−メチルシクロプロピル ４−｛５−［４−（アゼチジン−１−イルカルボニル）−２，５−ジフルオロフェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

To a solution of the compound (130 mg) obtained in Example 58-1 (2) in chloroform (2 ml) was added trifluoroacetic acid (0.2 ml) under ice cooling, and the mixture was stirred for 1 hour with ice cooling and 4 hours at room temperature. . A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was washed with water and saturated brine, and then passed through a phase separator. The solvent was distilled off under reduced pressure to obtain the title compound (100 mg) as a colorless gum.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.06-2.44 (m, 6 H) 2.81-2.96 (m, 2 H) 3.28-3.41 (m, 2 H) 4.15-4.29 (m, 4 H) 4.60 -4.77 (m, 1 H) 7.34-7.44 (m, 1 H) 7.85-7.95 (m, 1 H) 8.12 (s, 1 H) 8.19-8.24 (m, 1 H) 9.11 (s, 1 H).
MS ESI / APCI Dual posi: 398 [M + H] ⁺ .
(4) 1-methylcyclopropyl 4- {5- [4- (azetidin-1-ylcarbonyl) -2,5-difluorophenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine -1-carboxylate

実施例５８−１（３）で得られた化合物（５０．０ｍｇ）を用いて、実施例４９−１９と同様の操作にて反応及び精製を行い、表題化合物（３０．７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62 - 0.70 (m, 2 H) 0.80 - 1.00 (m, 2 H) 1.59 (s, 3 H) 1.99 - 2.45 (m, 6 H) 2.93 - 3.13 (m, 2 H) 4.07 - 4.51 (m, 6 H) 4.60 - 4.83 (m, 1 H) 7.33 - 7.44 (m, 1 H) 7.76 - 7.94 (m, 1 H) 8.07 - 8.15 (m, 1 H) 8.17 - 8.25 (m, 1 H) 8.99 - 9.10 (m, 1 H).
MS ESI/APCI Dual posi: 496[M+H]⁺, 518[M+Na]⁺.
MS ESI/APCI Dual nega: 530[M+Cl]^-.
実施例５８−２
シクロプロピルメチル ４−｛５−［４−（アゼチジン−１−イルカルボニル）−２，５−ジフルオロフェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (50.0 mg) obtained in Example 58-1 (3), the reaction and purification were conducted in the same manner as in Example 49-19 to give the title compound (30.7 mg) as a colorless powder. Obtained.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.70 (m, 2 H) 0.80-1.00 (m, 2 H) 1.59 (s, 3 H) 1.99-2.45 (m, 6 H) 2.93-3.13 (m, 2 H) 4.07-4.51 (m, 6 H) 4.60-4.83 (m, 1 H) 7.33-7.44 (m, 1 H) 7.76-7.94 (m, 1 H) 8.07-8.15 (m, 1 H ) 8.17-8.25 (m, 1 H) 8.99-9.10 (m, 1 H).
MS ESI / APCI Dual posi: 496 [M + H] ⁺ , 518 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 530 [M + Cl] ^- .
Example 58-2
Cyclopropylmethyl 4- {5- [4- (azetidin-1-ylcarbonyl) -2,5-difluorophenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

実施例５８−１（３）で得られた化合物（５０．０ｍｇ）とシクロプロパンメタノール（５９．７ｍｇ）を用いて、実施例３２−３と同様の操作にて反応及び精製を行い、表題化合物（２１．３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.27 - 0.35 (m, 2 H) 0.53 - 0.63 (m, 2 H) 1.21 - 1.32 (m, 1 H) 2.06 - 2.45 (m, 6 H) 3.00 - 3.20 (m, 2 H) 3.97 (d, J=7.3 Hz, 2 H) 4.13 - 4.29 (m, 4 H) 4.33 - 4.50 (m, 2 H) 4.69 - 4.83 (m, 1 H) 7.35 - 7.42 (m, 1 H) 7.85 - 7.94 (m, 1 H) 8.13 (s, 1 H) 8.21 - 8.24 (m, 1 H) 9.07 - 9.11 (m, 1 H).
MS ESI/APCI Dual posi: 496[M+H]⁺, 518[M+Na]⁺.
MS ESI/APCI Dual nega: 530[M+Cl]^-.
実施例５８−３
１−メチルシクロプロピル ４−｛５−［２，５−ジフルオロ−４−（ピロリジン−１−イルカルボニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

The title compound was obtained by carrying out the reaction and purification in the same manner as in Example 32-3 using the compound (50.0 mg) obtained in Example 58-1 (3) and cyclopropanemethanol (59.7 mg). (21.3 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.27-0.35 (m, 2 H) 0.53-0.63 (m, 2 H) 1.21-1.32 (m, 1 H) 2.06-2.45 (m, 6 H) 3.00 -3.20 (m, 2 H) 3.97 (d, J = 7.3 Hz, 2 H) 4.13-4.29 (m, 4 H) 4.33-4.50 (m, 2 H) 4.69-4.83 (m, 1 H) 7.35-7.42 (m, 1 H) 7.85-7.94 (m, 1 H) 8.13 (s, 1 H) 8.21-8.24 (m, 1 H) 9.07-9.11 (m, 1 H).
MS ESI / APCI Dual posi: 496 [M + H] ⁺ , 518 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 530 [M + Cl] ^- .
Example 58-3
1-methylcyclopropyl 4- {5- [2,5-difluoro-4- (pyrrolidin-1-ylcarbonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1- Carboxylate

参考例Ｅ−１０で得られた化合物（５００ｍｇ）、ピロリジン（１８８ｍｇ）、参考例１５で得られた化合物（１８０ｍｇ）を用いて、実施例５８−１（１）〜５８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（２２．６ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63 - 0.71 (m, 2 H) 0.86 - 0.96 (m, 2 H) 1.56 (s, 3 H) 1.84 - 2.38 (m, 8 H) 2.95 - 3.13 (m, 2 H) 3.36 - 3.45 (m, 2 H) 3.63 - 3.71 (m, 2 H) 4.13 - 4.59 (m, 2 H) 4.65 - 4.83 (m, 1 H) 7.22 - 7.31 (m, 1 H) 7.85 - 7.94 (m, 1 H) 8.12 (s, 1 H) 8.19 - 8.23 (m, 1 H) 9.08 (s, 1 H).
MS ESI/APCI Dual posi: 510[M+H]⁺, 532[M+Na]⁺.
MS ESI/APCI Dual nega: 544[M+Cl]^-.
実施例５８−４
１−メチルシクロプロピル ４−｛５−［２，５−ジフルオロ−４−（ピロリジン−１−イルカルボニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (500 mg) obtained in Reference Example E-10, pyrrolidine (188 mg) and the compound (180 mg) obtained in Reference Example 15, Examples 58-1 (1) to 58-1 (4) and The reaction and purification were carried out in the same manner to obtain the title compound (22.6 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.71 (m, 2 H) 0.86-0.96 (m, 2 H) 1.56 (s, 3 H) 1.84-2.38 (m, 8 H) 2.95-3.13 (m, 2 H) 3.36-3.45 (m, 2 H) 3.63-3.71 (m, 2 H) 4.13-4.59 (m, 2 H) 4.65-4.83 (m, 1 H) 7.22-7.31 (m, 1 H ) 7.85-7.94 (m, 1 H) 8.12 (s, 1 H) 8.19-8.23 (m, 1 H) 9.08 (s, 1 H).
MS ESI / APCI Dual posi: 510 [M + H] ⁺ , 532 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 544 [M + Cl] ^- .
Example 58-4
1-methylcyclopropyl 4- {5- [2,5-difluoro-4- (pyrrolidin-1-ylcarbonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1- Carboxylate

参考例Ｅ−１０で得られた化合物（５００ｍｇ）、ピロリジン（１８８ｍｇ）、参考例１５で得られた化合物（１８０ｍｇ）を用いて、実施例５８−１（１）〜５８−１（３）、５８−２と同様の操作にて反応及び精製を行い、表題化合物（１８．０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29 - 0.36 (m, 2 H) 0.55 - 0.62 (m, 2 H) 1.08 - 1.24 (m, 1 H) 1.86 - 2.07 (m, 4 H) 2.08 - 2.46 (m, 4 H) 3.01 - 3.23 (m, 2 H) 3.36 - 3.46 (m, 2 H) 3.62 - 3.74 (m, 2 H) 3.98 (d, J=7.3 Hz, 2 H) 4.36 - 4.50 (m, 2 H) 4.69 - 4.89 (m, 1 H) 7.24 - 7.33 (m, 1 H) 7.86 - 7.96 (m, 1 H) 8.13 - 8.16 (m, 1 H) 8.21 - 8.25 (m, 1 H) 9.09 - 9.12 (m, 1 H).
MS ESI/APCI Dual posi: 510[M+H]⁺, 532[M+Na]⁺.
MS ESI/APCI Dual nega: 508[M-H]^-.
実施例５９−１
４−（｛１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−イル｝オキシ）ベンズアミド

Using the compound (500 mg) obtained in Reference Example E-10, pyrrolidine (188 mg), and the compound (180 mg) obtained in Reference Example 15, Examples 58-1 (1) to 58-1 (3), Reaction and purification were carried out in the same manner as in 58-2 to obtain the title compound (18.0 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29-0.36 (m, 2 H) 0.55-0.62 (m, 2 H) 1.08-1.24 (m, 1 H) 1.86-2.07 (m, 4 H) 2.08 -2.46 (m, 4 H) 3.01-3.23 (m, 2 H) 3.36-3.46 (m, 2 H) 3.62-3.74 (m, 2 H) 3.98 (d, J = 7.3 Hz, 2 H) 4.36-4.50 (m, 2 H) 4.69-4.89 (m, 1 H) 7.24-7.33 (m, 1 H) 7.86-7.96 (m, 1 H) 8.13-8.16 (m, 1 H) 8.21-8.25 (m, 1 H ) 9.09-9.12 (m, 1 H).
MS ESI / APCI Dual posi: 510 [M + H] ⁺ , 532 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 508 [MH] ^- .
Example 59-1
4-({1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridin-5-yl} oxy) benzamide

参考例１６で得られた化合物（１００ｍｇ）と４−ヒドロキシベンズアミド（４２．５ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（９２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.09 (t, J=7.6 Hz, 3 H) 1.89 - 1.99 (m, 2 H) 1.99 - 2.05 (m, 2 H) 2.37 - 2.43 (m, 2 H) 3.03 - 3.12 (m, 2 H) 4.69 - 4.77 (m, 2 H) 5.05 - 5.13 (m, 1 H) 6.92 - 6.98 (m, 2 H) 7.17 - 7.24 (m, 1 H) 7.34 - 7.38 (m, 1 H) 7.78 - 7.89 (m, 3 H) 8.12 (s, 1 H) 8.23 (s, 2 H) 8.98 (s, 1 H).
MS ESI/APCI Dual posi: 444[M+H]⁺.
MS ESI/APCI Dual nega: 442[M-H]^-

Using the compound (100 mg) obtained in Reference Example 16 and 4-hydroxybenzamide (42.5 mg), the reaction and purification were carried out in the same manner as in Example 29-1, and the title compound (92 mg) was obtained as a colorless powder. Got as.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.09 (t, J = 7.6 Hz, 3 H) 1.89-1.99 (m, 2 H) 1.99-2.05 (m, 2 H) 2.37-2.43 (m, 2 H) 3.03-3.12 (m, 2 H) 4.69-4.77 (m, 2 H) 5.05-5.13 (m, 1 H) 6.92-6.98 (m, 2 H) 7.17-7.24 (m, 1 H) 7.34- 7.38 (m, 1 H) 7.78-7.89 (m, 3 H) 8.12 (s, 1 H) 8.23 (s, 2 H) 8.98 (s, 1 H).
MS ESI / APCI Dual posi: 444 [M + H] ⁺ .
MS ESI / APCI Dual nega: 442 [MH] ^-

  The following Examples 59-2 to 59-3 and 59-5 to 59-9 are also the compounds obtained in Reference Example 16 or Reference Example 23-C and the compounds obtained in Reference Examples H-1 to H-3. Or it synthesize | combined based on the method described in Example 29-1 using the corresponding phenol. The structure, NMR data, and MS data of these compounds are shown in Table 43-1.

Example 59-10
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [3-fluoro-4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridine ( 1) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [3-fluoro-4- (methylsulfanyl) phenoxy] -1H-pyrazolo [3,4-c] Pyridine

参考例１６で得られた化合物（１００ｍｇ）と参考例Ｈ−４で得られた化合物（４９０ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（１１６ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.16 - 1.28 (m, 3 H) 2.07 - 2.57 (m, 6 H) 2.45 (s, 3 H) 3.05 - 3.24 (m, 2 H) 4.68 - 5.03 (m, 3 H) 6.74 - 6.87 (m, 2 H) 7.22 (d, J=1.3 Hz, 1 H) 7.27 - 7.38 (m, 1 H) 8.00 (s, 1 H) 8.21 (s, 2 H) 8.69 - 8.73 (m, 1 H).
MS ESI/APCI Dual posi: 465[M+H]⁺.
（２）１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［３−フルオロ−４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (100 mg) obtained in Reference Example 16 and the compound (490 mg) obtained in Reference Example H-4, the reaction and purification were carried out in the same manner as in Example 29-1, and the title compound (116 mg) was obtained. ) Was obtained as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.16-1.28 (m, 3 H) 2.07-2.57 (m, 6 H) 2.45 (s, 3 H) 3.05-3.24 (m, 2 H) 4.68-5.03 (m, 3 H) 6.74-6.87 (m, 2 H) 7.22 (d, J = 1.3 Hz, 1 H) 7.27-7.38 (m, 1 H) 8.00 (s, 1 H) 8.21 (s, 2 H) 8.69-8.73 (m, 1 H).
MS ESI / APCI Dual posi: 465 [M + H] ⁺ .
(2) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [3-fluoro-4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c ] Pyridine

実施例５９−１０（１）で得られた化合物（１１６ｍｇ）のテトラヒドロフラン（０．４７８ｍｌ）−メタノール（０．４７８ｍｌ）溶液へ、オキソン（登録商標）（４４１ｍｇ）の水（１．１９ｍｌ）溶液を加え、室温にて５時間撹拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：１〜１：２）にて精製後、ヘキサン−酢酸エチル混合溶液で再結晶し、表題化合物（３０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.18 - 1.23 (m, 3 H) 2.13 - 2.20 (m, 2 H) 2.26 - 2.36 (m, 2 H) 2.45 - 2.52 (m, 2 H) 3.12 - 3.18 (m, 2 H) 3.19 (s, 3 H) 4.76 - 4.85 (m, 1 H) 4.92 - 4.99 (m, 2 H) 6.84 - 6.89 (m, 1 H) 6.90 - 6.95 (m, 1 H) 7.34 (s, 1 H) 7.87 - 7.93 (m, 1 H) 8.05 (s, 1 H) 8.20 (s, 2 H) 8.74 (s, 1 H).
MS ESI/APCI Dual posi: 497[M+H]⁺, 519[M+Na]⁺.
MS ESI/APCI Dual nega: 495[M+Cl]^-.
実施例５９−１１
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［２−フルオロ−４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン
（１）１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［２−フルオロ−４−（メチルスルファニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a solution of the compound obtained in Example 59-10 (1) (116 mg) in tetrahydrofuran (0.478 ml) -methanol (0.478 ml), a solution of Oxone (441) (441 mg) in water (1.19 ml) was added. The mixture was further stirred at room temperature for 5 hours. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 1 to 1: 2) and recrystallized from a hexane-ethyl acetate mixed solution to give the titled compound (30 mg) as a colorless powder. Obtained.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.18-1.23 (m, 3 H) 2.13-2.20 (m, 2 H) 2.26-2.36 (m, 2 H) 2.45-2.52 (m, 2 H) 3.12 -3.18 (m, 2 H) 3.19 (s, 3 H) 4.76-4.85 (m, 1 H) 4.92-4.99 (m, 2 H) 6.84-6.89 (m, 1 H) 6.90-6.95 (m, 1 H ) 7.34 (s, 1 H) 7.87-7.93 (m, 1 H) 8.05 (s, 1 H) 8.20 (s, 2 H) 8.74 (s, 1 H).
MS ESI / APCI Dual posi: 497 [M + H] ⁺ , 519 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 495 [M + Cl] ^- .
Example 59-11
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [2-fluoro-4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridine ( 1) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [2-fluoro-4- (methylsulfanyl) phenoxy] -1H-pyrazolo [3,4-c] Pyridine

参考例１６で得られた化合物（１００ｍｇ）と参考例Ｈ−５で得られた化合物（４９０ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（１１１ｍｇ）を無色粉末として得た。
¹H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.5 Hz, 3 H) 2.03 - 2.39 (m, 4 H) 2.40 - 2.59 (m, 5 H) 3.03 - 3.24 (m, 2 H) 4.63 - 4.84 (m, 1 H) 4.85 - 5.02 (m, 2 H) 7.01 - 7.19 (m, 4 H) 7.96 (s, 1 H) 8.20 (s, 2 H) 8.57 - 8.64 (m, 1 H).
MS ESI/APCI Dual posi: 465[M+H]⁺, 487[M+Na]⁺.
MS ESI/APCI Dual nega: 463[M-H]^-.
（２）１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−５−［２−フルオロ−４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (100 mg) obtained in Reference Example 16 and the compound (490 mg) obtained in Reference Example H-5, the reaction and purification were carried out in the same manner as in Example 29-1, and the title compound (111 mg ) Was obtained as a colorless powder.
¹ H NMR (200 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.5 Hz, 3 H) 2.03-2.39 (m, 4 H) 2.40-2.59 (m, 5 H) 3.03-3.24 (m, 2 H) 4.63-4.84 (m, 1 H) 4.85-5.02 (m, 2 H) 7.01-7.19 (m, 4 H) 7.96 (s, 1 H) 8.20 (s, 2 H) 8.57-8.64 (m, 1 H).
MS ESI / APCI Dual posi: 465 [M + H] ⁺ , 487 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 463 [MH] ^- .
(2) 1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -5- [2-fluoro-4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c ] Pyridine

実施例５９−１１（１）で得られた化合物（１１１ｍｇ）を用いて、実施例５９−１０（２）と同様の操作にて反応及び精製を行い、表題化合物（５５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J=7.4 Hz, 3 H) 2.13 - 2.19 (m, 2 H) 2.25 - 2.34 (m, 2 H) 2.49 (q, J=7.4 Hz, 2 H) 3.09 (s, 3 H) 3.11 - 3.18 (m, 2 H) 4.74 - 4.81 (m, 1 H) 4.92 - 4.99 (m, 2 H) 7.27 - 7.31 (m, 1 H) 7.33 - 7.34 (m, 1 H) 7.71 - 7.74 (m, 1 H) 7.76 - 7.80 (m, 1 H) 8.04 (s, 1 H) 8.21 (s, 2 H) 8.63 (s, 1 H).
MS ESI/APCI Dual posi: 497[M+H]⁺, 519[M+Na]⁺.
実施例５９−１２
１−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−Ｎ−［４−（メチルスルホニル）フェニル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−５−アミン

Using the compound (111 mg) obtained in Example 59-11 (1), the reaction and purification were conducted in the same manner as in Example 59-10 (2) to obtain the title compound (55 mg) as a colorless powder. It was.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.21 (t, J = 7.4 Hz, 3 H) 2.13-2.19 (m, 2 H) 2.25-2.34 (m, 2 H) 2.49 (q, J = 7.4 Hz, 2 H) 3.09 (s, 3 H) 3.11-3.18 (m, 2 H) 4.74-4.81 (m, 1 H) 4.92-4.99 (m, 2 H) 7.27-7.31 (m, 1 H) 7.33- 7.34 (m, 1 H) 7.71-7.74 (m, 1 H) 7.76-7.80 (m, 1 H) 8.04 (s, 1 H) 8.21 (s, 2 H) 8.63 (s, 1 H).
MS ESI / APCI Dual posi: 497 [M + H] ⁺ , 519 [M + Na] ⁺ .
Example 59-12
1- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -N- [4- (methylsulfonyl) phenyl] -1H-pyrazolo [3,4-c] pyridin-5-amine

参考例１６で得られた化合物（１００ｍｇ）のトルエン（２．５８ｍｌ）溶液へ、４−（メチルスルホニル）アニリン（５３．１ｍｇ）、トリス（ジベンジリデンアセトン）ジパラジウム（２３．６ｍｇ）、１，３−ビス（ジフェニルホスフィノ）プロパン（２１．３ｍｇ）、ナトリウム ｔｅｒｔ−ブトキシド（３４．７ｍｇ）を加え、アルゴン雰囲気下、６０℃にて１５時間、１００℃にて１５時間撹拌した。反応液へ水を加え、クロロホルムにて抽出した。得られた有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝１：２〜１：４）、次いでＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：酢酸エチル＝１：１）にて精製し、表題化合物（１７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.14 - 2.21 (m, 2 H) 2.26 - 2.35 (m, 2 H) 2.50 (q, J=7.6 Hz, 2 H) 3.04 (s, 3 H) 3.12 - 3.20 (m, 2 H) 4.74 - 4.82 (m, 1 H) 4.92 - 5.00 (m, 2 H) 6.75 (s, 1 H) 7.30 - 7.33 (m, 1 H) 7.35 - 7.38 (m, 2 H) 7.80 - 7.85 (m, 2 H) 7.95 (s, 1 H) 8.22 (s, 2 H) 8.80 (s, 1 H).
MS ESI/APCI Dual posi: 478[M+H]⁺, 500[M+Na]⁺.
実施例６０−１
５−［４−（メチルスルホニル）フェノキシ］−１−［１−（５−プロピルピリミジン−２−イル）ピペリジン−４−イル］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

To a toluene (2.58 ml) solution of the compound (100 mg) obtained in Reference Example 16, 4- (methylsulfonyl) aniline (53.1 mg), tris (dibenzylideneacetone) dipalladium (23.6 mg), 1, 3-bis (diphenylphosphino) propane (21.3 mg) and sodium tert-butoxide (34.7 mg) were added, and the mixture was stirred at 60 ° C. for 15 hours and at 100 ° C. for 15 hours under an argon atmosphere. Water was added to the reaction solution, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 1: 2 to 1: 4) and then NH silica gel column chromatography (developing solvent chloroform: ethyl acetate = 1: 1). Compound (17 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.14-2.21 (m, 2 H) 2.26-2.35 (m, 2 H) 2.50 (q, J = 7.6 Hz, 2 H) 3.04 (s, 3 H) 3.12-3.20 (m, 2 H) 4.74-4.82 (m, 1 H) 4.92-5.00 (m, 2 H) 6.75 (s, 1 H) 7.30-7.33 ( m, 1 H) 7.35-7.38 (m, 2 H) 7.80-7.85 (m, 2 H) 7.95 (s, 1 H) 8.22 (s, 2 H) 8.80 (s, 1 H).
MS ESI / APCI Dual posi: 478 [M + H] ⁺ , 500 [M + Na] ⁺ .
Example 60-1
5- [4- (Methylsulfonyl) phenoxy] -1- [1- (5-propylpyrimidin-2-yl) piperidin-4-yl] -1H-pyrazolo [3,4-c] pyridine

参考例２７で得られた化合物（７０ｍｇ）と２−クロロ−５−プロピルピリミジン（５７ｍｇ）を用いて、実施例４４−１と同様の操作にて反応及び精製を行い、表題化合物（２７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.96 (t, J=7.3 Hz, 3 H) 1.50 - 1.67 (m, 2 H) 2.12 - 2.23 (m, 2 H) 2.24 - 2.38 (m, 2 H) 2.43 (t, J=7.3 Hz, 2 H) 3.05 (s, 3 H) 3.16 (s, 2 H) 4.74 - 4.88 (m, 1 H) 4.91 - 5.02 (m, 2 H) 7.13 - 7.19 (m, 2 H) 7.32 - 7.34 (m, 1 H) 7.89 - 7.95 (m, 2 H) 8.04 - 8.06 (m, 1 H) 8.19 (s, 2 H) 8.73 - 8.75 (m, 1 H).
MS ESI/APCI Dual posi: 493[M+H]⁺.

Using the compound (70 mg) obtained in Reference Example 27 and 2-chloro-5-propylpyrimidine (57 mg), the reaction and purification were conducted in the same manner as in Example 44-1 to obtain the title compound (27 mg). Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.96 (t, J = 7.3 Hz, 3 H) 1.50-1.67 (m, 2 H) 2.12-2.23 (m, 2 H) 2.24-2.38 (m, 2 H) 2.43 (t, J = 7.3 Hz, 2 H) 3.05 (s, 3 H) 3.16 (s, 2 H) 4.74-4.88 (m, 1 H) 4.91-5.02 (m, 2 H) 7.13-7.19 ( m, 2 H) 7.32-7.34 (m, 1 H) 7.89-7.95 (m, 2 H) 8.04-8.06 (m, 1 H) 8.19 (s, 2 H) 8.73-8.75 (m, 1 H).
MS ESI / APCI Dual posi: 493 [M + H] ⁺ .

  The following Examples 60-2 to 60-7 were also prepared in Example 44-1 using the compound obtained in Reference Example 27 and the compound obtained in Reference Example G-2 or G-4 or the corresponding halogen compound. It was synthesized according to the method described in 1. The structure, NMR data, and MS data of these compounds are shown in Table 44-1.

Example 60-8
5- [4- (Methylsulfonyl) phenoxy] -1- {1- [5- (propan-2-yl) pyrimidin-2-yl] piperidin-4-yl} -1H-pyrazolo [3,4-c] Pyridine

実施例６０−４で得られた化合物（３２ｍｇ）を用いて、実施例２０−１（３）と同様の操作にて反応及び精製を行い、表題化合物（４ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 - 1.29 (m, 6 H) 2.13 - 2.24 (m, 2 H) 2.25 - 2.41 (m, 2 H) 2.74 - 2.87 (m, 1 H) 3.05 (s, 3 H) 3.10 - 3.23 (m, 2 H) 4.73 - 4.88 (m, 1 H) 4.91 - 5.03 (m, 2 H) 7.13 - 7.20 (m, 2 H) 7.32 - 7.34 (m, 1 H) 7.88 - 7.96 (m, 2 H) 8.03 - 8.05 (m, 1 H) 8.22 - 8.26 (m, 2 H) 8.73 - 8.76 (m, 1 H).
MS ESI/APCI Dual posi: 493[M+H]⁺.
実施例６１−１
ｔｅｒｔ−ブチル ４−｛５−［４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (32 mg) obtained in Example 60-4, the reaction and purification were carried out in the same manner as in Example 20-1 (3) to obtain the title compound (4 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23-1.29 (m, 6 H) 2.13-2.24 (m, 2 H) 2.25-2.41 (m, 2 H) 2.74-2.87 (m, 1 H) 3.05 (s, 3 H) 3.10-3.23 (m, 2 H) 4.73-4.88 (m, 1 H) 4.91-5.03 (m, 2 H) 7.13-7.20 (m, 2 H) 7.32-7.34 (m, 1 H ) 7.88-7.96 (m, 2 H) 8.03-8.05 (m, 1 H) 8.22-8.26 (m, 2 H) 8.73-8.76 (m, 1 H).
MS ESI / APCI Dual posi: 493 [M + H] ⁺ .
Example 61-1
tert-Butyl 4- {5- [4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例１５で得られた化合物（３．０ｇ）と４−（メチルスルホニル）フェノール（１．６ｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（１．５８ｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 2.02 - 2.15 (m, 2 H) 2.17 - 2.33 (m, 2 H) 3.05 (s, 5 H) 4.24 - 4.44 (m, 2 H) 4.59 - 4.75 (m, 1 H) 7.13 - 7.19 (m, 2 H) 7.33 - 7.34 (m, 1 H) 7.89 - 7.95 (m, 2 H) 8.05 - 8.07 (m, 1 H) 8.71 - 8.72 (m, 1 H).
MS ESI/APCI Dual posi: 473[M+H]⁺, 495[M+Na]⁺.
実施例６１−２
プロパン−２−イル ４−｛５−［４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン−１−イル｝ピペリジン−１−カルボキシラート

Using the compound (3.0 g) obtained in Reference Example 15 and 4- (methylsulfonyl) phenol (1.6 g), the reaction and purification were carried out in the same manner as in Example 29-1, and the title compound ( 1.58 g) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 2.02-2.15 (m, 2 H) 2.17-2.33 (m, 2 H) 3.05 (s, 5 H) 4.24-4.44 (m , 2 H) 4.59-4.75 (m, 1 H) 7.13-7.19 (m, 2 H) 7.33-7.34 (m, 1 H) 7.89-7.95 (m, 2 H) 8.05-8.07 (m, 1 H) 8.71 -8.72 (m, 1 H).
MS ESI / APCI Dual posi: 473 [M + H] ⁺ , 495 [M + Na] ⁺ .
Example 61-2
Propan-2-yl 4- {5- [4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２７で得られた化合物（５０ｍｇ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（４９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J=6.4 Hz, 6 H) 2.04 - 2.16 (m, 2 H) 2.18 - 2.35 (m, 2 H) 2.97 - 3.13 (m, 5 H) 4.29 - 4.48 (m, 2 H) 4.62 - 4.77 (m, 1 H) 4.91 - 5.03 (m, 1 H) 7.13 - 7.20 (m, 2 H) 7.31 - 7.35 (m, 1 H) 7.88 - 7.96 (m, 2 H) 8.06 (s, 1 H) 8.70 - 8.73 (m, 1 H).
MS ESI/APCI Dual posi: 459[M+H]⁺, 481[M+Na]⁺.

The compound (50 mg) obtained in Reference Example 27 was used for reaction and purification in the same manner as in Example 32-1, to obtain the title compound (49 mg) as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J = 6.4 Hz, 6 H) 2.04-2.16 (m, 2 H) 2.18-2.35 (m, 2 H) 2.97-3.13 (m, 5 H) 4.29-4.48 (m, 2 H) 4.62-4.77 (m, 1 H) 4.91-5.03 (m, 1 H) 7.13-7.20 (m, 2 H) 7.31-7.35 (m, 1 H) 7.88-7.96 (m, 2 H) 8.06 (s, 1 H) 8.70-8.73 (m, 1 H).
MS ESI / APCI Dual posi: 459 [M + H] ⁺ , 481 [M + Na] ⁺ .

  Examples 61-3 to 61-10 below were also described in Examples 32-1 to 32-5 or 49-19 using the compound obtained in Reference Example 27 and the corresponding alcohol or carbamate reagent. Synthesized according to the method. The structures, NMR data, and MS data of these compounds are shown in Tables 45-1 to 45-2.

Example 62-1
Propan-2-yl 4- {5- [3- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridin-1-yl} piperidine-1-carboxylate

参考例２３−Ｄで得られた化合物（１００ｍｇ）と３−メタンスルホニルフェノール（５６．３ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（１０７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J=6.2 Hz, 6 H) 2.07 - 2.14 (m, 2 H) 2.21 - 2.31 (m, 2 H) 2.99 - 3.11 (m, 5 H) 4.25 - 4.49 (m, 2 H) 4.63 - 4.71 (m, 1 H) 4.97 (quin, J=6.2 Hz, 1 H) 7.29 - 7.30 (m, 1 H) 7.35 - 7.38 (m, 1 H) 7.53 - 7.59 (m, 2 H) 7.67 - 7.70 (m, 1 H) 8.04 (s, 1 H) 8.68 (s, 1 H).
MS ESI/APCI Dual posi: 459[M+H]⁺, 481[M+Na]⁺.
実施例６３−１
１−［１−（２−メチルプロピル）ピペリジン−４−イル］−５−［４−（メチルスルホニル）フェノキシ］−１Ｈ−ピラゾロ［３，４−ｃ］ピリジン

Using the compound (100 mg) obtained in Reference Example 23-D and 3-methanesulfonylphenol (56.3 mg), the reaction and purification were performed in the same manner as in Example 29-1, and the title compound (107 mg) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.28 (d, J = 6.2 Hz, 6 H) 2.07-2.14 (m, 2 H) 2.21-2.31 (m, 2 H) 2.99-3.11 (m, 5 H) 4.25-4.49 (m, 2 H) 4.63-4.71 (m, 1 H) 4.97 (quin, J = 6.2 Hz, 1 H) 7.29-7.30 (m, 1 H) 7.35-7.38 (m, 1 H) 7.53-7.59 (m, 2 H) 7.67-7.70 (m, 1 H) 8.04 (s, 1 H) 8.68 (s, 1 H).
MS ESI / APCI Dual posi: 459 [M + H] ⁺ , 481 [M + Na] ⁺ .
Example 63-1
1- [1- (2-Methylpropyl) piperidin-4-yl] -5- [4- (methylsulfonyl) phenoxy] -1H-pyrazolo [3,4-c] pyridine

参考例２７で得られた化合物（５０ｍｇ）と１−ヨード−２−メチルプロパン（３０ｍｇ）を用いて、実施例１６−１と同様の操作にて反応及び精製を行い、表題化合物（４０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (d, J=6.4 Hz, 6 H) 1.72 - 1.90 (m, 1 H) 1.99 - 2.25 (m, 6 H) 2.30 - 2.51 (m, 2 H) 3.00 - 3.13 (m, 5 H) 4.42 - 4.60 (m, 1 H) 7.12 - 7.19 (m, 2 H) 7.31 - 7.33 (m, 1 H) 7.88 - 7.95 (m, 2 H) 8.05 (s, 1 H) 8.74 (s, 1 H).
MS ESI/APCI Dual posi: 429[M+H]⁺.

Using the compound (50 mg) obtained in Reference Example 27 and 1-iodo-2-methylpropane (30 mg), the reaction and purification were carried out in the same manner as in Example 16-1, and the title compound (40 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (d, J = 6.4 Hz, 6 H) 1.72-1.90 (m, 1 H) 1.99-2.25 (m, 6 H) 2.30-2.51 (m, 2 H) 3.00-3.13 (m, 5 H) 4.42-4.60 (m, 1 H) 7.12-7.19 (m, 2 H) 7.31-7.33 (m, 1 H) 7.88-7.95 (m, 2 H) 8.05 (s , 1 H) 8.74 (s, 1 H).
MS ESI / APCI Dual posi: 429 [M + H] ⁺ .

  The following Examples 63-2 to 63-5 were also synthesized according to the method described in Example 16-1 using the compound obtained in Reference Example 27 and the corresponding alkyl halide. The structure, NMR data, and MS data of these compounds are shown in Table 46-1.

Example 64-1
3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6- (2-methylpyridin-3-yl) -3H- [1,2,3] triazolo [4,5- c] pyridine

参考例１８で得られた化合物（１００ｍｇ）と２−メチルピリジン−３−ボロン酸 ピナコールエステル（８４．８ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（８３．７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 2.31 - 2.58 (m, 6 H) 2.63 (s, 3 H) 3.16 - 3.32 (m, 2 H) 4.97 - 5.09 (m, 2 H) 5.10 - 5.24 (m, 1 H) 7.23 - 7.31 (m, 1 H) 7.74 - 7.81 (m, 1 H) 8.07 (s, 1 H) 8.24 (s, 2 H) 8.56 - 8.62 (m, 1 H) 9.21 - 9.28 (m, 1 H).
MS ESI/APCI Dual posi: 401[M+H]⁺, 423[M+Na]⁺.
MS ESI/APCI Dual nega: 435[M+Cl]^-.
実施例６５−１
プロパン−２−イル ４−｛６−［２−フルオロ−４−（メチルスルホニル）フェニル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−３−イル｝ピペリジン−１−カルボキシラート

Using the compound (100 mg) obtained in Reference Example 18 and 2-methylpyridine-3-boronic acid pinacol ester (84.8 mg), the reaction and purification were carried out in the same manner as in Example 40-1, and the title Compound (83.7 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 2.31-2.58 (m, 6 H) 2.63 (s, 3 H) 3.16-3.32 (m, 2 H) 4.97-5.09 (m, 2 H) 5.10-5.24 (m, 1 H) 7.23-7.31 (m, 1 H) 7.74-7.81 (m, 1 H) 8.07 (s, 1 H) 8.24 (s, 2 H) 8.56-8.62 (m, 1 H) 9.21-9.28 (m, 1 H).
MS ESI / APCI Dual posi: 401 [M + H] ⁺ , 423 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 435 [M + Cl] ^- .
Example 65-1
Propan-2-yl 4- {6- [2-fluoro-4- (methylsulfonyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl} piperidine-1 -Carboxylate

参考例２８で得られた化合物（１００ｍｇ）と２−フルオロ−４−（メチルスルホニル）フェニルボロン酸（８９．０ｍｇ）を用いて、実施例４０−１と同様の操作にて反応及び精製を行い、表題化合物（５２．９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.2 Hz, 6 H) 2.23 - 2.48 (m, 4 H) 3.04 - 3.20 (m, 5 H) 4.36 - 4.51 (m, 2 H) 4.92 - 5.12 (m, 2 H) 7.78 - 7.91 (m, 2 H) 8.30 - 8.39 (m, 1 H) 8.55 - 8.57 (m, 1 H) 9.26 - 9.28 (m, 1 H).
MS ESI posi: 462[M+H]⁺.
実施例６６−１
［２，３−ジフルオロ−４−（３−｛１−［５−（トリフルオロメチル）ピリミジン−２−イル］ピペリジン−４−イル｝−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル）フェニル］［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］メタノン

The reaction and purification were carried out in the same manner as in Example 40-1, using the compound (100 mg) obtained in Reference Example 28 and 2-fluoro-4- (methylsulfonyl) phenylboronic acid (89.0 mg). The title compound (52.9 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.2 Hz, 6 H) 2.23-2.48 (m, 4 H) 3.04-3.20 (m, 5 H) 4.36-4.51 (m, 2 H) 4.92-5.12 (m, 2 H) 7.78-7.91 (m, 2 H) 8.30-8.39 (m, 1 H) 8.55-8.57 (m, 1 H) 9.26-9.28 (m, 1 H).
MS ESI posi: 462 [M + H] ⁺ .
Example 66-1
[2,3-difluoro-4- (3- {1- [5- (trifluoromethyl) pyrimidin-2-yl] piperidin-4-yl} -3H- [1,2,3] triazolo [4,5 -C] pyridin-6-yl) phenyl] [(3R) -3-hydroxypyrrolidin-1-yl] methanone

参考例３２−Ａで得られた化合物（４０ｍｇ）と２−クロロ−５−（トリフルオロメチル）ピリミジン（１７ｍｇ）を用いて、実施例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（３０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.99 - 2.21 (m, 2 H) 2.35 - 2.52 (m, 4 H) 3.30 - 3.91 (m, 6 H) 4.48 - 4.67 (m, 1 H) 5.07 - 5.15 (m, 2 H) 5.16 - 5.24 (m, 1 H) 7.30 - 7.36 (m, 1 H) 7.85 - 7.95 (m, 1 H) 8.48 (s, 1 H) 8.56 (s, 2 H) 9.26 (s, 1 H).
MS ESI posi: 575[M+H]⁺.

Using the compound (40 mg) obtained in Reference Example 32-A and 2-chloro-5- (trifluoromethyl) pyrimidine (17 mg), the reaction and purification were carried out in the same manner as in Example 8-1 (4). To give the title compound (30 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.99-2.21 (m, 2 H) 2.35-2.52 (m, 4 H) 3.30-3.91 (m, 6 H) 4.48-4.67 (m, 1 H) 5.07 -5.15 (m, 2 H) 5.16-5.24 (m, 1 H) 7.30-7.36 (m, 1 H) 7.85-7.95 (m, 1 H) 8.48 (s, 1 H) 8.56 (s, 2 H) 9.26 (s, 1 H).
MS ESI posi: 575 [M + H] ⁺ .

  The following Examples 66-2 to 66-9 were also prepared in the same manner as in Example 8 using the compound obtained in Reference Example 32-A and the compound obtained in Reference Examples G-2 to G-15 or the corresponding halogen compound. -1 (4) was synthesized according to the method described. The structures, NMR data, and MS data of these compounds are shown in Tables 47-1 to 47-2.

Example 67-1
(2,3-Difluoro-4- {3- [1- (5-methoxypyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine -6-yl} phenyl) [(3R) -3-hydroxypyrrolidin-1-yl] methanone (1) 6-chloro-3- [1- (5-methoxypyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine

参考例３０で得られた化合物（１００ｍｇ）と２−クロロ−５−メトキシピリミジン（１２２ｍｇ）を用いて、実施例８−１（４）と同様の操作にて反応及び精製を行い、表題化合物（５４ｍｇ）を淡黄色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.26 - 2.33 (m, 2 H) 2.34 - 2.43 (m, 2 H) 3.14 - 3.21 (m, 2 H) 3.83 (s, 3 H) 4.86 - 4.93 (m, 2 H) 5.02 - 5.10 (m, 1 H) 7.98 (s, 1 H) 8.13 (s, 2 H) 8.93 (s, 1 H).
MS ESI posi: 346[M+H]⁺.
（２）２，３−ジフルオロ−４−｛３−［１−（５−メトキシピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝安息香酸

Using the compound (100 mg) obtained in Reference Example 30 and 2-chloro-5-methoxypyrimidine (122 mg), the reaction and purification were carried out in the same manner as in Example 8-1 (4), and the title compound ( 54 mg) was obtained as a pale yellow powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.26-2.33 (m, 2 H) 2.34-2.43 (m, 2 H) 3.14-3.21 (m, 2 H) 3.83 (s, 3 H) 4.86-4.93 (m, 2 H) 5.02-5.10 (m, 1 H) 7.98 (s, 1 H) 8.13 (s, 2 H) 8.93 (s, 1 H).
MS ESI posi: 346 [M + H] ⁺ .
(2) 2,3-difluoro-4- {3- [1- (5-methoxypyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c ] Pyridin-6-yl} benzoic acid

実施例６７−１（１）で得られた化合物（３０ｍｇ）と４−（ジヒドロキシボラニル）−２，３−ジフルオロ安息香酸（３５．０ｍｇ）を用いて、参考例３１と同様の操作にて反応及び精製を行い、表題化合物（１０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 2.13 - 2.23 (m, 2 H) 2.29 - 2.35 (m, 2 H) 3.17 - 3.24 (m, 2 H) 3.80 (s, 3 H) 4.72 - 4.78 (m, 2 H) 5.41 - 5.49 (m, 1 H) 7.58 - 7.68 (m, 1 H) 7.74 - 7.82 (m, 1 H) 8.27 (s, 2 H) 8.45 - 8.49 (m, 1 H) 9.63 - 9.65 (m, 1 H).
MS ESI posi: 468[M+H]⁺.
MS ESI nega: 466[M-H]^-.
（３）（２，３−ジフルオロ−４−｛３−［１−（５−メトキシピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝フェニル）［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］メタノン

The compound (30 mg) obtained in Example 67-1 (1) and 4- (dihydroxyboranyl) -2,3-difluorobenzoic acid (35.0 mg) were used in the same manner as in Reference Example 31. Reaction and purification were performed to obtain the title compound (10 mg) as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 2.13-2.23 (m, 2 H) 2.29-2.35 (m, 2 H) 3.17-3.24 (m, 2 H) 3.80 (s, 3 H) 4.72- 4.78 (m, 2 H) 5.41-5.49 (m, 1 H) 7.58-7.68 (m, 1 H) 7.74-7.82 (m, 1 H) 8.27 (s, 2 H) 8.45-8.49 (m, 1 H) 9.63-9.65 (m, 1 H).
MS ESI posi: 468 [M + H] ⁺ .
MS ESI nega: 466 [MH] ^- .
(3) (2,3-Difluoro-4- {3- [1- (5-methoxypyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5- c] Pyridin-6-yl} phenyl) [(3R) -3-hydroxypyrrolidin-1-yl] methanone

実施例６７−１（２）で得られた化合物（１０ｍｇ）と（Ｒ）−３−ピロリジノール（２．８０ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.97 - 2.23 (m, 2 H) 2.35 (d, J=9.9 Hz, 2 H) 2.41 - 2.50 (m, 2 H) 3.18 - 3.26 (m, 2 H) 3.35 - 3.90 (m, 5 H) 3.83 - 3.87 (m, 3 H) 4.50 - 4.67 (m, 1 H) 4.90 - 4.97 (m, 2 H) 5.11 - 5.18 (m, 1 H) 7.31 - 7.36 (m, 1 H) 7.86 - 7.91 (m, 1 H) 8.15 (s, 2 H) 8.48 (s, 1 H) 9.25 (d, J=0.8 Hz, 1 H).
MS ESI posi: 537[M+H]⁺.
実施例６８−１
（２，３−ジフルオロ−４−｛３−［１−（５−メチルピリジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝フェニル）［（３Ｒ）−３−ヒドロキシピロリジン−１−イル］メタノン

Using the compound (10 mg) obtained in Example 67-1 (2) and (R) -3-pyrrolidinol (2.80 mg), the reaction and purification were carried out in the same manner as in Example 5-1, The title compound (3 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.97-2.23 (m, 2 H) 2.35 (d, J = 9.9 Hz, 2 H) 2.41-2.50 (m, 2 H) 3.18-3.26 (m, 2 H) 3.35-3.90 (m, 5 H) 3.83-3.87 (m, 3 H) 4.50-4.67 (m, 1 H) 4.90-4.97 (m, 2 H) 5.11-5.18 (m, 1 H) 7.31-7.36 (m, 1 H) 7.86-7.91 (m, 1 H) 8.15 (s, 2 H) 8.48 (s, 1 H) 9.25 (d, J = 0.8 Hz, 1 H).
MS ESI posi: 537 [M + H] ⁺ .
Example 68-1
(2,3-Difluoro-4- {3- [1- (5-methylpyridin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine -6-yl} phenyl) [(3R) -3-hydroxypyrrolidin-1-yl] methanone

参考例３２−Ａで得られた化合物（６０ｍｇ）と２−ブロモ−５−メチルピリジン（５０ｍｇ）を用いて、実施例４５−４と同様の操作にて反応及び精製を行い、表題化合物（２０ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.91 - 2.16 (m, 2 H) 2.24 (s, 3 H) 2.32 - 2.65 (m, 4 H) 3.07 - 3.24 (m, 2 H) 3.31 - 3.93 (m, 4 H) 4.45 - 4.72 (m, 3 H) 5.03 - 5.20 (m, 1 H) 6.70 - 6.77 (m, 1 H) 7.29 - 7.44 (m, 2 H) 7.84 - 7.93 (m, 1 H) 8.05 - 8.10 (m, 1 H) 8.44 - 8.51 (m, 1 H) 9.23 - 9.28 (m, 1 H).
MS ESI posi: 520[M+H]⁺.

Using the compound (60 mg) obtained in Reference Example 32-A and 2-bromo-5-methylpyridine (50 mg), the reaction and purification were conducted in the same manner as in Example 45-4, and the title compound (20 mg ) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.91-2.16 (m, 2 H) 2.24 (s, 3 H) 2.32-2.65 (m, 4 H) 3.07-3.24 (m, 2 H) 3.31-3.93 (m, 4 H) 4.45-4.72 (m, 3 H) 5.03-5.20 (m, 1 H) 6.70-6.77 (m, 1 H) 7.29-7.44 (m, 2 H) 7.84-7.93 (m, 1 H ) 8.05-8.10 (m, 1 H) 8.44-8.51 (m, 1 H) 9.23-9.28 (m, 1 H).
MS ESI posi: 520 [M + H] ⁺ .

  The following Examples 68-2 to 68-13 were also prepared in the same manner as in Example 45 using the compound obtained in Reference Example 32-A and the compound obtained in Reference Examples G-16 to G-18 or the corresponding halogen compound. -4 was synthesized according to the method described in -4. The structures, NMR data, and MS data of these compounds are shown in Tables 48-1 to 48-2.

Example 69-1
2,2-dimethylpropyl 4- {6- [4- (ethylcarbamoyl) -2,3-difluorophenyl] -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl} Piperidine-1-carboxylate

参考例３２−Bで得られた化合物（３０．０ｍｇ）とネオペンチルクロロホルメート（１７．５ｍｇ）を用いて、実施例３２−１と同様の操作にて反応及び精製を行い、表題化合物（３０．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.99 (s, 9 H) 1.30 (t, J=7.3 Hz, 3 H) 2.24 - 2.52 (m, 4 H) 3.05 - 3.30 (m, 2 H) 3.51 - 3.65 (m, 2 H) 3.86 (s, 2 H) 4.37 - 4.54 (m, 2 H) 4.98 - 5.13 (m, 1 H) 6.60 - 6.74 (m, 1 H) 7.92 - 8.02 (m, 2 H) 8.49 - 8.55 (m, 1 H) 9.24 - 9.27 (m, 1 H).
MS ESI posi: 501[M+H]⁺.

The compound (30.0 mg) obtained in Reference Example 32-B and neopentyl chloroformate (17.5 mg) were used for reaction and purification in the same manner as in Example 32-1, and the title compound ( 30.8 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.99 (s, 9 H) 1.30 (t, J = 7.3 Hz, 3 H) 2.24-2.52 (m, 4 H) 3.05-3.30 (m, 2 H) 3.51-3.65 (m, 2 H) 3.86 (s, 2 H) 4.37-4.54 (m, 2 H) 4.98-5.13 (m, 1 H) 6.60-6.74 (m, 1 H) 7.92-8.02 (m, 2 H) 8.49-8.55 (m, 1 H) 9.24-9.27 (m, 1 H).
MS ESI posi: 501 [M + H] ⁺ .

  Examples 69-2 to 69-46 below are also described in Examples 32-1 to 32-5 or 49-19 using the alcohol obtained in Reference Example 32-B and the corresponding alcohol or carbamate reagent. Synthesized according to the published method. The structures, NMR data, and MS data of these compounds are shown in Tables 49-1 to 49-7.

Examples 69-47
1-piperidinecarboxylic acid 4- [6- [4-[(ethylamino) carbonyl] -2,3-difluorophenyl] -3H-1,2,3-triazolo [4,5-c] pyridin-3-yl ]-(5-Ethyl-2-pyridinyl) methyl ester

（５−エチルピリジン−２−イル）メタノール（２１．３ｍｇ）のクロロホルム溶液（１ｍｌ）にクロロぎ酸４−ニトロフェニル（３１．３ｍｇ）とトリエチルアミン（４５μｌ）を加え、室温で３時間攪拌した。その中へ参考例３２−Ｂで得られた化合物（１５ｍｇ）とトリエチルアミン（４５μｌ）を加え、室温でさらに一晩攪拌した。反応液に飽和炭酸水素ナトリウム水溶液を加え、クロロホルムにて抽出した。得られた有機層をフェーズセパレーターへ通して、溶媒を減圧留去した。得られた残渣を分取ＨＰＬＣで精製した後、得られた固体をヘキサン−２−プロパノールで再結晶し、表題化合物（１３．４ｍｇ）を得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 - 1.33 (m, 6 H) 2.27 - 2.35 (m, 2 H) 2.38 - 2.50 (m, 2 H) 2.68 (q, J=7.8 Hz, 2 H) 3.11 - 3.32 (m, 2 H) 3.54 - 3.61 (m, 2 H) 4.44 - 4.53 (m, 2 H) 5.02 - 5.10 (m, 1 H) 5.28 (s, 2 H) 6.64 - 6.71 (m, 1 H) 7.30 - 7.34 (m, 1 H) 7.54 - 7.58 (m, 1 H) 7.94 - 7.99 (m, 2 H) 8.47 - 8.49 (m, 1 H) 8.52 (s, 1 H) 9.25 - 9.26 (m, 1 H).
MS ESI/APCI Dual posi: 550[M+H]⁺, 572[M+Na]⁺.

To a chloroform solution (1 ml) of (5-ethylpyridin-2-yl) methanol (21.3 mg) were added 4-nitrophenyl chloroformate (31.3 mg) and triethylamine (45 μl), and the mixture was stirred at room temperature for 3 hours. The compound (15 mg) obtained in Reference Example 32-B and triethylamine (45 μl) were added thereto, and the mixture was further stirred overnight at room temperature. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was passed through a phase separator, and the solvent was distilled off under reduced pressure. The obtained residue was purified by preparative HPLC, and the obtained solid was recrystallized from hexane-2-propanol to obtain the title compound (13.4 mg).
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23-1.33 (m, 6 H) 2.27-2.35 (m, 2 H) 2.38-2.50 (m, 2 H) 2.68 (q, J = 7.8 Hz, 2 H) 3.11-3.32 (m, 2 H) 3.54-3.61 (m, 2 H) 4.44-4.53 (m, 2 H) 5.02-5.10 (m, 1 H) 5.28 (s, 2 H) 6.64-6.71 (m , 1 H) 7.30-7.34 (m, 1 H) 7.54-7.58 (m, 1 H) 7.94-7.99 (m, 2 H) 8.47-8.49 (m, 1 H) 8.52 (s, 1 H) 9.25-9.26 (m, 1 H).
MS ESI / APCI Dual posi: 550 [M + H] ⁺ , 572 [M + Na] ⁺ .

  The following Examples 69-48 to 69-64 were also synthesized according to the method described in Examples 69-47 using the compound obtained in Reference Example 32-B and the corresponding alcohol. The structures, NMR data, and MS data of these compounds are shown in Tables 49-8 to 49-10.

Example 70-1
4- {3- [1- (cyclopropylmethyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -N-ethyl-2, 3-difluorobenzamide

参考例３２−Ｂで得られた化合物（２０ｍｇ）と（ブロモメチル）シクロプロパン（１０．５ｍｇ）を用いて、実施例１６−１と同様の操作にて反応及び精製を行い、表題化合物（４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 0.45 - 0.55 (m, 2 H) 0.77 - 0.89 (m, 2 H) 1.17 - 1.32 (m, 4 H) 2.59 - 2.80 (m, 4 H) 3.12 - 3.25 (m, 2 H) 3.34 - 3.50 (m, 4 H) 3.86 - 4.04 (m, 2 H) 5.33 - 5.53 (m, 1 H) 7.53 - 7.63 (m, 1 H) 7.83 - 7.97 (m, 1 H) 8.48 (s, 1 H) 9.48 (s, 1 H).
MS ESI posi: 441[M+H]⁺.

Using the compound (20 mg) obtained in Reference Example 32-B and (bromomethyl) cyclopropane (10.5 mg), the reaction and purification were conducted in the same manner as in Example 16-1, and the title compound (4 mg) Was obtained as a colorless powder.
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 0.45-0.55 (m, 2 H) 0.77-0.89 (m, 2 H) 1.17-1.32 (m, 4 H) 2.59-2.80 (m, 4 H) 3.12-3.25 (m, 2 H) 3.34-3.50 (m, 4 H) 3.86-4.04 (m, 2 H) 5.33-5.53 (m, 1 H) 7.53-7.63 (m, 1 H) 7.83-7.97 (m , 1 H) 8.48 (s, 1 H) 9.48 (s, 1 H).
MS ESI posi: 441 [M + H] ⁺ .

  The following Examples 70-2 to 70-4 were also synthesized according to the method described in Example 16-1 using the compound obtained in Reference Example 32-B and the corresponding alkyl halide. The structures, NMR data, and MS data of these compounds are shown in Table 50-1.

Example 70-5
4- [3- (1-Benzylpiperidin-4-yl) -3H- [1,2,3] triazolo [4,5-C] pyridin-6-yl] -N-ethyl-2,3-difluorobenzamide

参考例３２−Ｂで得られた化合物（２０ｍｇ）とベンズアルデヒド（１１ｍｇ）を用いて、実施例３８−１と同様の操作にて反応及び精製を行い、表題化合物（１３ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 1.18 - 1.31 (m, 3 H) 2.46 - 2.74 (m, 4 H) 3.20 - 3.38 (m, 2 H) 3.40 - 3.53 (m, 2 H) 3.56 - 3.84 (m, 2 H) 4.22 - 4.53 (m, 2 H) 5.30 - 5.48 (m, 1 H) 7.45 - 7.63 (m, 6 H) 7.83 - 7.94 (m, 1 H) 8.42 - 8.52 (m, 1 H) 9.39 - 9.52 (m, 1 H).
MS ESI/APCI Dual posi: 478[M+H]⁺.
実施例７０−６
４−｛３−［１−（２，２−ジメチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−Ｎ−エチル−２，３−ジフルオロベンズアミド

Using the compound (20 mg) obtained in Reference Example 32-B and benzaldehyde (11 mg), the reaction and purification were carried out in the same manner as in Example 38-1, to obtain the title compound (13 mg) as a colorless powder. .
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 1.18-1.31 (m, 3 H) 2.46-2.74 (m, 4 H) 3.20-3.38 (m, 2 H) 3.40-3.53 (m, 2 H) 3.56-3.84 (m, 2 H) 4.22-4.53 (m, 2 H) 5.30-5.48 (m, 1 H) 7.45-7.63 (m, 6 H) 7.83-7.94 (m, 1 H) 8.42-8.52 (m , 1 H) 9.39-9.52 (m, 1 H).
MS ESI / APCI Dual posi: 478 [M + H] ⁺ .
Example 70-6
4- {3- [1- (2,2-dimethylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -N-ethyl -2,3-difluorobenzamide

参考例３２−Ｂで得られた化合物（２０．０ｍｇ）とピバルアルデヒド（１１．４ｍｇ）を用いて、実施例３８−１と同様の操作にて反応及び精製を行い、表題化合物（４．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (s, 9 H) 1.30 (t, J=7.3 Hz, 3 H) 2.15 - 2.23 (m, 4 H) 2.49 - 2.61 (m, 4 H) 3.01 - 3.12 (m, 2 H) 3.50 - 3.63 (m, 2 H) 4.76 - 4.89 (m, 1 H) 7.94 - 7.99 (m, 2 H) 8.48 - 8.52 (m, 1 H) 9.31 (d, J=1.4 Hz, 1 H).
MS ESI/APCI Dual posi: 457[M+H]⁺.
実施例７０−７
４−｛３−［１−（２，２−ジフルオロプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−Ｎ−エチル−２，３−ジフルオロベンズアミド

Using the compound (20.0 mg) obtained in Reference Example 32-B and pivalaldehyde (11.4 mg), the reaction and purification were carried out in the same manner as in Example 38-1, and the title compound (4. 8 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.93 (s, 9 H) 1.30 (t, J = 7.3 Hz, 3 H) 2.15-2.23 (m, 4 H) 2.49-2.61 (m, 4 H) 3.01-3.12 (m, 2 H) 3.50-3.63 (m, 2 H) 4.76-4.89 (m, 1 H) 7.94-7.99 (m, 2 H) 8.48-8.52 (m, 1 H) 9.31 (d, J = 1.4 Hz, 1 H).
MS ESI / APCI Dual posi: 457 [M + H] ⁺ .
Example 70-7
4- {3- [1- (2,2-difluoropropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -N-ethyl -2,3-difluorobenzamide

２，２−ジフルオロプロパノール（０．４２ｇ）、ｐ−トルエンスルホニルクロリド（１．０ｇ）、トリメチルアミン塩酸塩（４１ｍｇ）のクロロホルム（２ｍｌ）溶液へトリエチルアミン（０．９ｍｌ）を加え、室温で１時間撹拌した。反応液に水を加えた後、酢酸エチルで２回抽出した。有機層を無水硫酸ナトリウムで乾燥後、乾燥剤を濾別し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開溶媒 ヘキサン：酢酸エチル＝９６：４〜８５：１５）で精製し、２，２−ジフルオロプロピル ４-メチルフェニルスルホナート（１．１ｇ）を得た。
上記で得られた２，２−ジフルオロプロピル ４-メチルフェニルスルホナート（６５ｍｇ）、参考例３２−Ｂで得られた化合物（２０ｍｇ）のジメチルスルホキシド（０．６ｍｌ）溶液を１８０℃で２時間撹拌した。反応液を室温に冷却、分取ＨＰＬＣ精製後、ＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１００：０〜９５：５）で精製し、表題化合物（１．５ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J=7.3 Hz, 3 H) 1.63 - 1.79 (m, 3 H) 2.19 - 2.32 (m, 2 H) 2.47 - 2.70 (m, 4 H) 2.75 - 2.87 (m, 2 H) 3.18 - 3.28 (m, 2 H) 3.49 - 3.64 (m, 2 H) 4.80 - 4.95 (m, 1 H) 7.93 - 7.99 (m, 2 H) 8.48 - 8.55 (m, 1 H) 9.26 - 9.31 (m, 1 H).
MS ESI/APCI Dual posi: 465[M+H]⁺.
実施例７０−８
Ｎ−エチル−２，３−ジフルオロ−４−｛３−［１−（２−ヒドロキシ−２−メチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝ベンズアミド

Triethylamine (0.9 ml) was added to a chloroform (2 ml) solution of 2,2-difluoropropanol (0.42 g), p-toluenesulfonyl chloride (1.0 g) and trimethylamine hydrochloride (41 mg), and the mixture was stirred at room temperature for 1 hour. did. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent hexane: ethyl acetate = 96: 4-85: 15) to obtain 2,2-difluoropropyl 4-methylphenylsulfonate (1.1 g).
The 2,2-difluoropropyl 4-methylphenylsulfonate (65 mg) obtained above and the dimethyl sulfoxide (0.6 ml) solution of the compound (20 mg) obtained in Reference Example 32-B were stirred at 180 ° C. for 2 hours. did. The reaction solution was cooled to room temperature, purified by preparative HPLC, and then purified by NH silica gel column chromatography (developing solvent: chloroform: methanol = 100: 0 to 95: 5) to obtain the title compound (1.5 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J = 7.3 Hz, 3 H) 1.63-1.79 (m, 3 H) 2.19-2.32 (m, 2 H) 2.47-2.70 (m, 4 H) 2.75-2.87 (m, 2 H) 3.18-3.28 (m, 2 H) 3.49-3.64 (m, 2 H) 4.80-4.95 (m, 1 H) 7.93-7.99 (m, 2 H) 8.48-8.55 (m, 1 H) 9.26-9.31 (m, 1 H).
MS ESI / APCI Dual posi: 465 [M + H] ⁺ .
Example 70-8
N-ethyl-2,3-difluoro-4- {3- [1- (2-hydroxy-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5- c] Pyridin-6-yl} benzamide

参考例３２−Ｂで得られた化合物（４０ｍｇ）を用いて参考例３５−Ｈ（１）と同様の操作にて反応及び精製を行い、表題化合物（４０ｍｇ）を得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 (s, 6 H) 1.30 (t, J=7.3 Hz, 3 H) 2.16 - 2.33 (m, 2 H) 2.40 - 2.76 (m, 6 H) 3.14 - 3.30 (m, 2 H) 3.49 - 3.64 (m, 2 H) 4.79 - 4.97 (m, 1 H) 7.97 (d, J=4.8 Hz, 2 H) 8.47 - 8.55 (m, 1 H) 9.23 - 9.34 (m, 1 H).
MS ESI/APCI Dual posi: 459[M+H]⁺.
実施例７０−９
Ｎ−エチル−２，３−ジフルオロ−４−｛３−［１−（２−フルオロ−２−メチルプロピル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝ベンズアミド

Using the compound (40 mg) obtained in Reference Example 32-B, the reaction and purification were performed in the same manner as in Reference Example 35-H (1) to obtain the title compound (40 mg).
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 (s, 6 H) 1.30 (t, J = 7.3 Hz, 3 H) 2.16-2.33 (m, 2 H) 2.40-2.76 (m, 6 H) 3.14-3.30 (m, 2 H) 3.49-3.64 (m, 2 H) 4.79-4.97 (m, 1 H) 7.97 (d, J = 4.8 Hz, 2 H) 8.47-8.55 (m, 1 H) 9.23- 9.34 (m, 1 H).
MS ESI / APCI Dual posi: 459 [M + H] ⁺ .
Example 70-9
N-ethyl-2,3-difluoro-4- {3- [1- (2-fluoro-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5- c] Pyridin-6-yl} benzamide

実施例７０−８で得られた化合物（２０ｍｇ）を用いて参考例３５−Ｈ（２）と同様の操作にて反応及び精製を行い、表題化合物（１６ｍｇ）を得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 1.26 (t, J=7.2 Hz, 3 H) 1.52 - 1.64 (m, 6 H) 2.56 - 2.90 (ｍ, 4 H) 3.39 - 3.73 (m, 6 H) 3.79 - 4.08 (m, 2 H) 5.42 - 5.53 (m, 1 H) 7.58 (t, J=6.8 Hz, 1 H) 7.85 - 7.95 (m, 1 H) 8.47 (s, 1 H) 9.49 (s, 1 H).
MS ESI/APCI Dual posi: 461[M+H]⁺.
実施例７１−１
４−｛３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン−６−イル｝−２−フルオロベンズアミド

Using the compound (20 mg) obtained in Example 70-8, the reaction and purification were conducted in the same manner as in Reference Example 35-H (2) to obtain the title compound (16 mg).
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 1.26 (t, J = 7.2 Hz, 3 H) 1.52-1.64 (m, 6 H) 2.56-2.90 (m, 4 H) 3.39-3.73 (m, 6 H) 3.79-4.08 (m, 2 H) 5.42-5.53 (m, 1 H) 7.58 (t, J = 6.8 Hz, 1 H) 7.85-7.95 (m, 1 H) 8.47 (s, 1 H) 9.49 (s, 1 H).
MS ESI / APCI Dual posi: 461 [M + H] ⁺ .
Example 71-1
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluorobenzamide

参考例３３−Ａで得られた化合物（８０ｍｇ）と２８％アンモニア水（１６ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（６９ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J=7.6 Hz, 3 H) 2.29 - 2.59 (m, 6 H) 3.18 - 3.30 (m, 2 H) 4.97 - 5.08 (m, 2 H) 5.09 - 5.24 (m, 1 H) 5.75 - 5.86 (m, 1 H) 6.69 - 6.82 (m, 1 H) 7.89 - 8.00 (m, 2 H) 8.22 - 8.31 (m, 3 H) 8.39 - 8.43 (m, 1 H) 9.22 - 9.26 (m, 1 H).
MS ESI/APCI Dual posi: 447[M+H]⁺.
MS ESI/APCI Dual nega: 481[M+Cl]^-.

Using the compound (80 mg) obtained in Reference Example 33-A and 28% aqueous ammonia (16 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (69 mg) was obtained as a colorless powder. Got as.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 (t, J = 7.6 Hz, 3 H) 2.29-2.59 (m, 6 H) 3.18-3.30 (m, 2 H) 4.97-5.08 (m, 2 H) 5.09-5.24 (m, 1 H) 5.75-5.86 (m, 1 H) 6.69-6.82 (m, 1 H) 7.89-8.00 (m, 2 H) 8.22-8.31 (m, 3 H) 8.39-8.43 (m, 1 H) 9.22-9.26 (m, 1 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ .
MS ESI / APCI Dual nega: 481 [M + Cl] ^- .

  The following Examples 71-2 to 71-9 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 33-A and the corresponding amine. The structures, NMR data, and MS data of these compounds are shown in Tables 51-1 to 51-2.

Example 72-1
N-ethyl-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il} -3-fluorobenzamide

参考例３３−Ｂで得られた化合物（５０ｍｇ）と７０％エチルアミン水溶液（１０．８ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 1.29 (t, J=7.2 Hz, 3 H) 2.32 - 2.38 (m, 2 H) 2.40 - 2.49 (m, 2 H) 2.52 (q, J=7.6 Hz, 2 H) 3.19 - 3.28 (m, 2 H) 3.49 - 3.58 (m, 2 H) 4.98 - 5.05 (m, 2 H) 5.12 - 5.20 (m, 1 H) 6.08 - 6.15 (m, 1 H) 7.62 - 7.68 (m, 2 H) 8.12 - 8.18 (m, 1 H) 8.24 (s, 2 H) 8.51 (s, 1 H) 9.25 (s, 1 H).
MS ESI posi: 475[M+H]⁺.

Using the compound (50 mg) obtained in Reference Example 33-B and a 70% aqueous ethylamine solution (10.8 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (46 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 1.29 (t, J = 7.2 Hz, 3 H) 2.32-2.38 (m, 2 H) 2.40-2.49 ( m, 2 H) 2.52 (q, J = 7.6 Hz, 2 H) 3.19-3.28 (m, 2 H) 3.49-3.58 (m, 2 H) 4.98-5.05 (m, 2 H) 5.12-5.20 (m, 1 H) 6.08-6.15 (m, 1 H) 7.62-7.68 (m, 2 H) 8.12-8.18 (m, 1 H) 8.24 (s, 2 H) 8.51 (s, 1 H) 9.25 (s, 1 H ).
MS ESI posi: 475 [M + H] ⁺ .

  The following Examples 72-2 to 72-6 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 33-B and the corresponding amine. The structure, NMR data, and MS data of these compounds are shown in Table 52-1.

Example 73-1
N-ethyl-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il} -2,5-difluorobenzamide

参考例３３−Ｃで得られた化合物（５０ｍｇ）と７０％エチルアミン水溶液（１０．４ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（３０ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J=7.6 Hz, 3 H) 1.29 (t, J=7.2 Hz, 3 H) 2.32 - 2.39 (m, 2 H) 2.40 - 2.48 (m, 2 H) 2.52 (d, J=7.2 Hz, 2 H) 3.19 - 3.27 (m, 2 H) 3.51 - 3.59 (m, 2 H) 4.99 - 5.05 (m, 2 H) 5.11 - 5.20 (m, 1 H) 6.75 - 6.84 (m, 1 H) 7.92 - 8.02 (m, 2 H) 8.24 (s, 2 H) 8.60 (s, 1 H) 9.22 - 9.25 (m, 1 H).
MS ESI posi: 493[M+H]⁺.

Using the compound (50 mg) obtained in Reference Example 33-C and a 70% aqueous ethylamine solution (10.4 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (30 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.23 (t, J = 7.6 Hz, 3 H) 1.29 (t, J = 7.2 Hz, 3 H) 2.32-2.39 (m, 2 H) 2.40-2.48 ( m, 2 H) 2.52 (d, J = 7.2 Hz, 2 H) 3.19-3.27 (m, 2 H) 3.51-3.59 (m, 2 H) 4.99-5.05 (m, 2 H) 5.11-5.20 (m, 1 H) 6.75-6.84 (m, 1 H) 7.92-8.02 (m, 2 H) 8.24 (s, 2 H) 8.60 (s, 1 H) 9.22-9.25 (m, 1 H).
MS ESI posi: 493 [M + H] ⁺ .

  The following Examples 73-2 to 73-5 were also synthesized according to the method described in Example 5-1 using the compound obtained in Reference Example 33-C and the corresponding amine. The structure, NMR data, and MS data of these compounds are shown in Table 53-1.

Example 74-1
4- {3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluoro-N- (2-methoxyethyl) -5-methylbenzamide

参考例３３−Ｄで得られた化合物（１５ｍｇ）のＮ，Ｎ−ジメチルホルムアミド（０．３２５ｍｌ）溶液へ、０℃にて２−メトキシエチルアミン（３．６７ｍｇ）、トリエチルアミン（９．８８ｍｇ）、４８％プロピルホスホニックアンハイドライド・Ｎ，Ｎ−ジメチルホルムアミド溶液（３２．３ｍｇ）を加え、室温にて１時間攪拌した。反応系をＮＨシリカゲルカラムクロマトグラフィー（展開溶媒 クロロホルム：メタノール＝１０：１）に通し、濃縮して得られた残渣を分取ＨＰＬＣにて精製し、表題化合物（６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.6 Hz, 3 H) 2.30 - 2.54 (m, 6 H) 2.38 (s, 3 H) 3.18 - 3.27 (m, 2 H) 3.40 (s, 3 H) 3.55 - 3.61 (m, 2 H) 3.68 - 3.74 (m, 2 H) 4.98 - 5.05 (m, 2 H) 5.11 - 5.19 (m, 1 H) 7.08 - 7.15 (m, 1 H) 7.25 (s, 1 H) 7.99 - 8.08 (m, 2 H) 8.23 (s, 2 H) 9.20 - 9.25 (m, 1 H).
MS ESI posi: 519[M+H]⁺.

To a solution of the compound (15 mg) obtained in Reference Example 33-D in N, N-dimethylformamide (0.325 ml) at 0 ° C., 2-methoxyethylamine (3.67 mg), triethylamine (9.88 mg), 48 % Propylphosphonic anhydride / N, N-dimethylformamide solution (32.3 mg) was added and stirred at room temperature for 1 hour. The reaction system was passed through NH silica gel column chromatography (developing solvent: chloroform: methanol = 10: 1), and the residue obtained by concentration was purified by preparative HPLC to obtain the title compound (6 mg) as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.6 Hz, 3 H) 2.30-2.54 (m, 6 H) 2.38 (s, 3 H) 3.18-3.27 (m, 2 H) 3.40 (s, 3 H) 3.55-3.61 (m, 2 H) 3.68-3.74 (m, 2 H) 4.98-5.05 (m, 2 H) 5.11-5.19 (m, 1 H) 7.08-7.15 (m, 1 H) 7.25 (s, 1 H) 7.99-8.08 (m, 2 H) 8.23 (s, 2 H) 9.20-9.25 (m, 1 H).
MS ESI posi: 519 [M + H] ⁺ .

  The following Examples 74-2 to 74-15 are also based on the method described in Example 5-1 or Example 74-1, using the compound obtained in Reference Example 33-D and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 54-1 to 54-3.

Example 75-1
N-ethyl-4- {3- [1- (5-ethylpyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine-6- Il} -2-methylbenzamide

参考例３３−Ｅで得られた化合物（８０．０ｍｇ）と７０％エタノールアミン水溶液（１７．４ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（７４．８ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.18 - 1.34 (m, 6 H) 2.27 - 2.58 (m, 9 H) 3.15 - 3.30 (m, 2 H) 3.47 - 3.58 (m, 2 H) 4.94 - 5.06 (m, 2 H) 5.07 - 5.23 (m, 1 H) 5.79 - 5.89 (m, 1 H) 7.43 - 7.53 (m, 1 H) 7.83 - 7.89 (m, 1 H) 7.91 - 7.96 (m, 1 H) 8.24 (s, 2 H) 8.30 - 8.34 (m, 1 H) 9.18 - 9.24 (m, 1 H).
MS ESI posi: 471[M+H]⁺.

Using the compound (80.0 mg) obtained in Reference Example 33-E and a 70% aqueous ethanolamine solution (17.4 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound ( 74.8 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.18-1.34 (m, 6 H) 2.27-2.58 (m, 9 H) 3.15-3.30 (m, 2 H) 3.47-3.58 (m, 2 H) 4.94 -5.06 (m, 2 H) 5.07-5.23 (m, 1 H) 5.79-5.89 (m, 1 H) 7.43-7.53 (m, 1 H) 7.83-7.89 (m, 1 H) 7.91-7.96 (m, 1 H) 8.24 (s, 2 H) 8.30-8.34 (m, 1 H) 9.18-9.24 (m, 1 H).
MS ESI posi: 471 [M + H] ⁺ .

  Examples 75-2 to 75-60 below were also synthesized according to the method described in Example 5-1 using the compounds obtained in Reference Examples 33-E to 33-T and the corresponding amines. did. The structures, NMR data, and MS data of these compounds are shown in Tables 55-1 to 55-9.

Example 76-1
Propan-2-yl 4- {6- [2,3-difluoro-4- (methylcarbamoyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl} piperidine -1-carboxylate

参考例３４−Ａで得られた化合物（１５ｍｇ）とメチルアミン塩酸塩（４．５ｍｇ）を用いて、実施例７４−１と同様の操作にて反応及び精製を行い、表題化合物（１２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J=6.2 Hz, 6 H) 2.26 - 2.33 (m, 2 H) 2.35 - 2.44 (m, 2 H) 3.05 - 3.19 (m, 5 H) 4.30 - 4.56 (m, 2 H) 4.96 - 5.07 (m, 2 H) 6.66 - 6.76 (m, 1 H) 7.93 - 8.01 (m, 2 H) 8.52 (s, 1 H) 9.25 - 9.28 (m, 1 H).
MS ESI/APCI Dual posi: 459[M+H]⁺.

Using the compound (15 mg) obtained in Reference Example 34-A and methylamine hydrochloride (4.5 mg), the reaction and purification were carried out in the same manner as in Example 74-1 to obtain the title compound (12 mg). Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.30 (d, J = 6.2 Hz, 6 H) 2.26-2.33 (m, 2 H) 2.35-2.44 (m, 2 H) 3.05-3.19 (m, 5 H) 4.30-4.56 (m, 2 H) 4.96-5.07 (m, 2 H) 6.66-6.76 (m, 1 H) 7.93-8.01 (m, 2 H) 8.52 (s, 1 H) 9.25-9.28 (m , 1 H).
MS ESI / APCI Dual posi: 459 [M + H] ⁺ .

  The following Examples 76-2 to 76-14 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 34-A and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 56-1 to 56-2.

Example 77-1
Propan-2-yl 4- {6- [4- (ethylcarbamoyl) -3-fluorophenyl] -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl} piperidine-1 -Carboxylate

参考例３４−Ｂで得られた化合物（８０．０ｍｇ）と７０％エタノールアミン水溶液（１８．１ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（６２．３ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 - 1.34 (m, 9 H) 2.22 - 2.48 (m, 4 H) 3.05 - 3.22 (m, 2 H) 3.49 - 3.64 (m, 2 H) 4.34 - 4.54 (m, 2 H) 4.93 - 5.12 (m, 2 H) 6.73 - 6.86 (m, 1 H) 7.87 - 7.98 (m, 2 H) 8.21 - 8.29 (m, 1 H) 8.40 (d, J=1.2 Hz, 1 H) 9.23 (d, J=1.2 Hz, 1 H).
MS ESI/APCI Dual posi: 455[M+H]⁺, 477[M+Na]⁺.
MS ESI/APCI Dual nega: 489[M+Cl]^-.

The compound (80.0 mg) obtained in Reference Example 34-B and a 70% aqueous ethanolamine solution (18.1 mg) were used for reaction and purification in the same manner as in Example 5-1, and the title compound ( 62.3 mg) was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24-1.34 (m, 9 H) 2.22-2.48 (m, 4 H) 3.05-3.22 (m, 2 H) 3.49-3.64 (m, 2 H) 4.34 -4.54 (m, 2 H) 4.93-5.12 (m, 2 H) 6.73-6.86 (m, 1 H) 7.87-7.98 (m, 2 H) 8.21-8.29 (m, 1 H) 8.40 (d, J = 1.2 Hz, 1 H) 9.23 (d, J = 1.2 Hz, 1 H).
MS ESI / APCI Dual posi: 455 [M + H] ⁺ , 477 [M + Na] ⁺ .
MS ESI / APCI Dual nega: 489 [M + Cl] ^- .

  Examples 77-2 to 77-16 below were also synthesized according to the method described in Example 5-1 using the compounds obtained in Reference Examples 34-B to 34-E and the corresponding amines. did. The structures, NMR data, and MS data of these compounds are shown in Tables 57-1 to 57-3.

Example 78-1
4- {3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -N -Ethyl-2,3-difluorobenzamide

参考例３５−Ａで得られた化合物（３０ｍｇ）と７０％エチルアミン水溶液（６．１４ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（７ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, DMSO-d₆) δ ppm 1.15 (t, J=7.2 Hz, 3 H) 2.15 - 2.25 (m, 2 H) 2.32 - 2.40 (m, 2 H) 3.26 - 3.32 (m, 4 H) 4.77 - 4.84 (m, 2 H) 5.45 - 5.54 (m, 1 H) 7.51 - 7.55 (m, 1 H) 7.83 - 7.88 (m, 1 H) 8.46 - 8.51 (m, 3 H) 8.53 - 8.58 (m, 1 H) 9.65 - 9.68 (m, 1 H).
MS ESI posi: 499[M+H]⁺.

Using the compound (30 mg) obtained in Reference Example 35-A and a 70% aqueous ethylamine solution (6.14 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (7 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (600 MHz, DMSO-d ₆ ) δ ppm 1.15 (t, J = 7.2 Hz, 3 H) 2.15-2.25 (m, 2 H) 2.32-2.40 (m, 2 H) 3.26-3.32 (m, 4 H) 4.77-4.84 (m, 2 H) 5.45-5.54 (m, 1 H) 7.51-7.55 (m, 1 H) 7.83-7.88 (m, 1 H) 8.46-8.51 (m, 3 H) 8.53- 8.58 (m, 1 H) 9.65-9.68 (m, 1 H).
MS ESI posi: 499 [M + H] ⁺ .

  The following Examples 78-2 to 78-13 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-A and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 58-1 to 58-2.

Example 79-1
Azetidin-1-yl (2,3-difluoro-4- {3- [1- (5-methylpyridin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4 5-c] pyridin-6-yl} phenyl) methanone

参考例３５−Ｂで得られた化合物（１０．０ｍｇ）とアゼチジン（２．５１ｍｇ）を用いて、実施例７４−１と同様の操作にて反応及び精製を行い、表題化合物（１．０７ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.24 (s, 3 H) 2.31 - 2.62 (m, 6 H) 3.10 - 3.23 (m, 2 H) 4.14 - 4.30 (m, 4 H) 4.46 - 4.57 (m, 2 H) 5.06 - 5.20 (m, 1 H) 6.73
(d, J=8.7 Hz, 1 H) 7.35 - 7.45 (m, 2 H) 7.84 - 7.92 (m, 1 H) 8.06 - 8.09 (m, 1 H) 8.46 - 8.49 (m, 1 H) 9.23 - 9.26 (m, 1 H).
MS ESI/APCI Dual posi: 490[M+H]⁺.

Using the compound (10.0 mg) obtained in Reference Example 35-B and azetidine (2.51 mg), the reaction and purification were conducted in the same manner as in Example 74-1 to obtain the title compound (1.07 mg). Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.24 (s, 3 H) 2.31-2.62 (m, 6 H) 3.10-3.23 (m, 2 H) 4.14-4.30 (m, 4 H) 4.46-4.57 (m, 2 H) 5.06-5.20 (m, 1 H) 6.73
(d, J = 8.7 Hz, 1 H) 7.35-7.45 (m, 2 H) 7.84-7.92 (m, 1 H) 8.06-8.09 (m, 1 H) 8.46-8.49 (m, 1 H) 9.23-9.26 (m, 1 H).
MS ESI / APCI Dual posi: 490 [M + H] ⁺ .

  The following Examples 79-2 to 79-9 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-B and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 59-1 to 59-2.

Example 80-1
(1-Methylcyclopropyl) methyl 4- {6- [2,3-difluoro-4- (methylcarbamoyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridine-3- Il} piperidine-1-carboxylate

参考例３５−Ｃで得られた化合物（２０ｍｇ）と４０％メチルアミン水溶液（４．９４ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（１６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.36 - 0.42 (m, 2 H) 0.50 - 0.55 (m, 2 H) 1.17 (s, 3 H) 2.28 - 2.37 (m, 2 H) 2.37 - 2.47 (m, 2 H) 3.09 (d, J=4.5 Hz, 3 H) 3.12 - 3.27 (m, 2 H) 3.96 (s, 2 H) 4.42 - 4.51 (m, 2 H) 5.01 - 5.10 (m, 1 H) 6.68 - 6.74 (m, 1 H) 7.94 - 8.01 (m, 2 H) 8.52 (s, 1 H) 9.26 - 9.27 (m, 1 H).
MS ESI posi: 485[M+H]⁺.

Using the compound (20 mg) obtained in Reference Example 35-C and 40% aqueous methylamine solution (4.94 mg), the reaction and purification were conducted in the same manner as in Example 5-1, and the title compound (16 mg) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.36-0.42 (m, 2 H) 0.50-0.55 (m, 2 H) 1.17 (s, 3 H) 2.28-2.37 (m, 2 H) 2.37-2.47 (m, 2 H) 3.09 (d, J = 4.5 Hz, 3 H) 3.12-3.27 (m, 2 H) 3.96 (s, 2 H) 4.42-4.51 (m, 2 H) 5.01-5.10 (m, 1 H) 6.68-6.74 (m, 1 H) 7.94-8.01 (m, 2 H) 8.52 (s, 1 H) 9.26-9.27 (m, 1 H).
MS ESI posi: 485 [M + H] ⁺ .

The following Examples 80-2 to 80-22 also conformed to the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-C and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 60-1 to 60-4.

Example 81-1
(2R) -butan-2-yl 4- {6- [2,3-difluoro-4- (methylcarbamoyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridine-3 -Yl} piperidine-1-carboxylate

参考例３５−Ｄで得られた化合物（１５ｍｇ）とメチルアミン塩酸塩（３．３ｍｇ）を用いて、実施例７４−１と同様の操作にて反応及び精製を行い、表題化合物（４．２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.95 (t, J=7.4 Hz, 3 H) 1.28 (d, J=6.6 Hz, 3 H) 1.57 - 1.71 (m, 2 H) 2.26 - 2.33 (m, 2 H) 2.36 - 2.45 (m, 2 H) 3.04 - 3.22 (m, 5 H) 4.36 - 4.52 (m, 2 H) 4.77 - 4.86 (m, 1 H) 4.99 - 5.08 (m, 1 H) 6.65 - 6.80 (m, 1 H) 7.92 - 8.04 (m, 2 H) 8.52 (s, 1 H) 9.26 (d, J=1.2 Hz, 1 H).
MS ESI/APCI Dual posi: 473[M+H]⁺.

Using the compound (15 mg) obtained in Reference Example 35-D and methylamine hydrochloride (3.3 mg), the reaction and purification were carried out in the same manner as in Example 74-1 to give the title compound (4.2 mg ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.95 (t, J = 7.4 Hz, 3 H) 1.28 (d, J = 6.6 Hz, 3 H) 1.57-1.71 (m, 2 H) 2.26-2.33 ( m, 2 H) 2.36-2.45 (m, 2 H) 3.04-3.22 (m, 5 H) 4.36-4.52 (m, 2 H) 4.77-4.86 (m, 1 H) 4.99-5.08 (m, 1 H) 6.65-6.80 (m, 1 H) 7.92-8.04 (m, 2 H) 8.52 (s, 1 H) 9.26 (d, J = 1.2 Hz, 1 H).
MS ESI / APCI Dual posi: 473 [M + H] ⁺ .

  The following Examples 81-2 to 81-17 were also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-D and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 61-1 to 61-3.

Example 82-1
(1S) -1-phenylethyl 4- {6- [2,3-difluoro-4- (methylcarbamoyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridine-3- Il} piperidine-1-carboxylate

参考例３５−Ｅで得られた化合物（１５ｍｇ）と４０％メチルアミン水溶液（５ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４．５ｍｇ）を無色粉末として得た。
¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61 (d, J=6.7 Hz, 3 H) 2.24 - 2.51 (m, 4 H) 3.05 - 3.28 (m, 5 H) 4.40 - 4.52 (m, 2 H) 4.97 - 5.11 (m, 1 H) 5.88 (q, J=6.5 Hz, 1 H) 6.65 - 6.80 (m, 1 H) 7.30 - 7.41 (m, 5 H) 7.95 - 7.99 (m, 2 H) 8.50 - 8.52 (m, 1 H) 9.23 (s, 1 H).
MS ESI/APCI Dual posi: 521[M+H]⁺.

Using the compound (15 mg) obtained in Reference Example 35-E and 40% aqueous methylamine solution (5 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (4.5 mg) Was obtained as a colorless powder.
¹ H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.61 (d, J = 6.7 Hz, 3 H) 2.24-2.51 (m, 4 H) 3.05-3.28 (m, 5 H) 4.40-4.52 (m, 2 H) 4.97-5.11 (m, 1 H) 5.88 (q, J = 6.5 Hz, 1 H) 6.65-6.80 (m, 1 H) 7.30-7.41 (m, 5 H) 7.95-7.99 (m, 2 H) 8.50-8.52 (m, 1 H) 9.23 (s, 1 H).
MS ESI / APCI Dual posi: 521 [M + H] ⁺ .

  The following Examples 82-2 to 82-16 also conformed to the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-E and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 62-1 to 62-2.

Example 83-1
(5-Fluoropyridin-2-yl) methyl 4- {6- [2,3-difluoro-4- (methylcarbamoyl) phenyl] -3H- [1,2,3] triazolo [4,5-c] pyridine -3-yl} piperidine-1-carboxylate

参考例３５−Ｆで得られた化合物（１５ｍｇ）と４０％メチルアミン水溶液（３．４ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（２．５ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.26 - 2.37 (m, 2 H) 2.39 - 2.49 (m, 2 H) 3.09 (d, J=5.0 Hz, 3 H) 3.13 - 3.33 (m, 2 H) 4.42 - 4.53 (m, 2 H) 5.02 - 5.11 (m, 1 H) 5.29 (s, 2 H) 6.67 - 6.74 (m, 1 H) 7.40 - 7.48 (m, 2 H) 7.94 - 8.02 (m, 2 H) 8.47 - 8.50 (m, 1 H) 8.52 (s, 1 H) 9.23 - 9.28 (m, 1 H).
MS ESI/APCI Dual posi: 526[M+H]⁺.

Using the compound (15 mg) obtained in Reference Example 35-F and 40% aqueous methylamine solution (3.4 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (2. 5 mg) was obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.26-2.37 (m, 2 H) 2.39-2.49 (m, 2 H) 3.09 (d, J = 5.0 Hz, 3 H) 3.13-3.33 (m, 2 H) 4.42-4.53 (m, 2 H) 5.02-5.11 (m, 1 H) 5.29 (s, 2 H) 6.67-6.74 (m, 1 H) 7.40-7.48 (m, 2 H) 7.94-8.02 (m , 2 H) 8.47-8.50 (m, 1 H) 8.52 (s, 1 H) 9.23-9.28 (m, 1 H).
MS ESI / APCI Dual posi: 526 [M + H] ⁺ .

  The following Examples 83-2 to 83-6 also conform to the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-F and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 63-1 to 63-2.

Example 84-1
4- {3- [1- (2,2-dimethylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3 -Difluoro-N-methylbenzamide

参考例３５−Ｇで得られた化合物（２１ｍｇ）とメチルアミン塩酸塩（９．９ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（４．２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₃) δ ppm 1.18 (s, 9 H) 2.47 - 2.87 (m, 4 H) 2.97 (s, 3 H) 3.10 - 4.03 (m, 6 H) 5.31 - 5.59 (m, 1 H) 7.57 - 7.65 (m, 1 H) 7.88 - 7.94 (m, 1 H) 8.45 - 8.50 (m, 1 H) 9.48 (s, 1 H).
MS ESI/APCI Dual posi: 443[M+H]⁺.

Using the compound (21 mg) obtained in Reference Example 35-G and methylamine hydrochloride (9.9 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (4.2 mg) ) Was obtained as a colorless powder.
¹ H NMR (600 MHz, METHANOL-d ₃ ) δ ppm 1.18 (s, 9 H) 2.47-2.87 (m, 4 H) 2.97 (s, 3 H) 3.10-4.03 (m, 6 H) 5.31-5.59 ( m, 1 H) 7.57-7.65 (m, 1 H) 7.88-7.94 (m, 1 H) 8.45-8.50 (m, 1 H) 9.48 (s, 1 H).
MS ESI / APCI Dual posi: 443 [M + H] ⁺ .

  The following Examples 84-2 to 84-13 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-G and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 64-1 to 64-2.

Example 85-1
2,3-difluoro-4- {3- [1- (2-fluoro-2-methylpropyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridine- 6-yl} -N-methylbenzamide

参考例３５−Ｈで得られた化合物（０．１Ｍ Ｎ，Ｎ−ジメチルホルムアミド溶液、１ｍｌ）とメチルアミン塩酸塩（２０ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（１２．６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 1.53 - 1.66 (m, 6 H) 2.54 - 2.88 (m, 4 H) 2.97 (s, 3 H) 3.42 - 4.14 (m, 6 H) 5.38 - 5.53 (m, 1 H) 7.59 - 7.63 (m, 1 H) 7.87 - 7.95 (m, 1 H) 8.47 (s, 1 H) 9.44 - 9.51 (m, 1 H).
MS ESI/APCI Dual posi: 447[M+H]⁺.

Using the compound obtained in Reference Example 35-H (0.1 M N, N-dimethylformamide solution, 1 ml) and methylamine hydrochloride (20 mg), the reaction and purification were carried out in the same manner as in Example 5-1. To give the title compound (12.6 mg) as a colorless powder.
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 1.53-1.66 (m, 6 H) 2.54-2.88 (m, 4 H) 2.97 (s, 3 H) 3.42-4.14 (m, 6 H) 5.38- 5.53 (m, 1 H) 7.59-7.63 (m, 1 H) 7.87-7.95 (m, 1 H) 8.47 (s, 1 H) 9.44-9.51 (m, 1 H).
MS ESI / APCI Dual posi: 447 [M + H] ⁺ .

  The following Examples 85-2 to 85-9 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-H and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 65-1 to 65-2.

Example 86-1
4- {3- [1- (cyclopropylmethyl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2,3-difluoro- N-methylbenzamide

参考例３５−Ｉで得られた化合物（０．０６Ｍ Ｎ，Ｎ−ジメチルホルムアミド溶液、０．８３ｍｌ）とメチルアミン塩酸塩（１０ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（３．６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, METHANOL-d₄) δ ppm 0.46 - 0.54 (m, 2 H) 0.77 - 0.88 (m, 2 H) 1.17 - 1.25 (m, 1 H) 2.59 - 2.79 (m, 4 H) 2.92 - 3.00 (m, 3 H) 3.15 - 3.24 (m, 2 H) 3.33 - 3.43 (m, 2 H) 3.92 - 4.02 (m, 2 H) 5.39 - 5.49 (m, 1 H) 7.59 - 7.64 (m, 1 H) 7.87 - 7.94 (m, 1 H) 8.48 (s, 1 H) 9.46 - 9.50 (m, 1 H).
MS ESI/APCI Dual posi: 427[M+H]⁺.

Using the compound (0.06M N, N-dimethylformamide solution, 0.83 ml) obtained in Reference Example 35-I and methylamine hydrochloride (10 mg), the reaction was carried out in the same manner as in Example 5-1. And purification was performed to obtain the title compound (3.6 mg) as a colorless powder.
¹ H NMR (600 MHz, METHANOL-d ₄ ) δ ppm 0.46-0.54 (m, 2 H) 0.77-0.88 (m, 2 H) 1.17-1.25 (m, 1 H) 2.59-2.79 (m, 4 H) 2.92-3.00 (m, 3 H) 3.15-3.24 (m, 2 H) 3.33-3.43 (m, 2 H) 3.92-4.02 (m, 2 H) 5.39-5.49 (m, 1 H) 7.59-7.64 (m , 1 H) 7.87-7.94 (m, 1 H) 8.48 (s, 1 H) 9.46-9.50 (m, 1 H).
MS ESI / APCI Dual posi: 427 [M + H] ⁺ .

  The following Examples 86-2 to 86-10 also conform to the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-I and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 66-1 to 66-2.

Example 87-1
4- {3- [1- (5-chloropyrimidin-2-yl) piperidin-4-yl] -3H- [1,2,3] triazolo [4,5-c] pyridin-6-yl} -2 -Fluoro-5-methylbenzamide

参考例３５−Ｊで得られた化合物（１０ｍｇ）と２８％アンモニア水溶液（１．９５ｍｇ）を用いて、実施例５−１と同様の操作にて反応及び精製を行い、表題化合物（２ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.33 - 2.53 (m, 7 H) 3.23 - 3.32 (m, 2 H) 4.96 - 5.03 (m, 2 H) 5.12 - 5.20 (m, 1 H) 5.81 (br. s., 1 H) 6.70 - 6.78 (m, 1 H) 7.28 - 7.32 (m, 1 H) 8.07 - 8.10 (m, 2 H) 8.30 (s, 2 H) 9.22 - 9.26 (m, 1 H).
MS ESI posi: 467[M+H]⁺.

Using the compound (10 mg) obtained in Reference Example 35-J and 28% aqueous ammonia solution (1.95 mg), the reaction and purification were carried out in the same manner as in Example 5-1, and the title compound (2 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.33-2.53 (m, 7 H) 3.23-3.32 (m, 2 H) 4.96-5.03 (m, 2 H) 5.12-5.20 (m, 1 H) 5.81 (br. s., 1 H) 6.70-6.78 (m, 1 H) 7.28-7.32 (m, 1 H) 8.07-8.10 (m, 2 H) 8.30 (s, 2 H) 9.22-9.26 (m, 1 H).
MS ESI posi: 467 [M + H] ⁺ .

  The following Examples 87-2 to 87-10 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-J and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 67-1 to 67-2.

Example 88-1
(1-Methylcyclopropyl) methyl 4- [6- (4-carbamoyl-5-fluoro-2-methylphenyl) -3H- [1,2,3] triazolo [4,5-c] pyridin-3-yl ] Piperidine-1-carboxylate

参考例３５−Ｋで得られた化合物（１０ｍｇ）と塩化アンモニウム（３．４ｍｇ）を用いて、実施例７４−１と同様の操作にて反応及び精製を行い、表題化合物（０．９ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.34 - 0.43 (m, 2 H) 0.49 - 0.56 (m, 2 H) 1.17 (s, 3 H) 2.27 - 2.51 (m, 7 H) 3.07 - 3.29 (m, 2 H) 3.96 (s, 2 H) 4.42 - 4.51 (m, 2 H) 5.01 - 5.12 (m, 1 H) 6.11 - 6.20 (m, 1 H) 6.76 - 6.85 (m, 1 H) 7.29 - 7.33 (m, 1 H) 8.06 - 8.11 (m, 2 H) 9.28 (s, 1 H).
MS ESI/APCI Dual posi: 467[M+H]⁺.

Using the compound (10 mg) obtained in Reference Example 35-K and ammonium chloride (3.4 mg), the reaction and purification were carried out in the same manner as in Example 74-1 to obtain the title compound (0.9 mg). Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.34-0.43 (m, 2 H) 0.49-0.56 (m, 2 H) 1.17 (s, 3 H) 2.27-2.51 (m, 7 H) 3.07-3.29 (m, 2 H) 3.96 (s, 2 H) 4.42-4.51 (m, 2 H) 5.01-5.12 (m, 1 H) 6.11-6.20 (m, 1 H) 6.76-6.85 (m, 1 H) 7.29 -7.33 (m, 1 H) 8.06-8.11 (m, 2 H) 9.28 (s, 1 H).
MS ESI / APCI Dual posi: 467 [M + H] ⁺ .

  The following Examples 88-2 to 88-15 are also based on the method described in Example 5-1 or Example 74-1 using the compound obtained in Reference Example 35-K and the corresponding amine. And synthesized. The structures, NMR data, and MS data of these compounds are shown in Tables 68-1 to 68-2.

Example 89-1
3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6-{[4- (methylsulfonyl) benzyl] oxy} -3H- [1,2,3] triazolo [4 5-c] pyridine

参考例１８で得られた化合物（１００ｍｇ）と４−（メチルスルホニル）ベンジルアルコール（２４２ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（２４ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.5 Hz, 3 H) 2.27 - 2.32 (m, 2 H) 2.33 - 2.41 (m, 2 H) 2.51 (q, J=7.5 Hz, 2 H) 3.05 (s, 3 H) 3.15 - 3.22 (m, 2 H) 4.95 - 5.00 (m, 2 H) 5.01 - 5.07 (m, 1 H) 5.55 (s, 2 H) 7.38 (d, J=1.2 Hz, 1 H) 7.67 (d, J=8.3 Hz, 2 H) 7.94 (d, J=8.3 Hz, 2 H) 8.22 (s, 2 H) 8.72 (d, J=1.2 Hz, 1 H).
MS ESI/APCI Dual posi: 494[M+H]⁺.
実施例８９−２
３−［１−（５−エチルピリミジン−２−イル）ピペリジン−４−イル］−６−［３−（メチルスルホニル）フェノキシ］−３Ｈ−［１，２，３］トリアゾロ［４，５−ｃ］ピリジン

Using the compound (100 mg) obtained in Reference Example 18 and 4- (methylsulfonyl) benzyl alcohol (242 mg), the reaction and purification were conducted in the same manner as in Example 29-1, and the title compound (24 mg) was obtained. Obtained as a colorless powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.5 Hz, 3 H) 2.27-2.32 (m, 2 H) 2.33-2.41 (m, 2 H) 2.51 (q, J = 7.5 Hz, 2 H) 3.05 (s, 3 H) 3.15-3.22 (m, 2 H) 4.95-5.00 (m, 2 H) 5.01-5.07 (m, 1 H) 5.55 (s, 2 H) 7.38 (d, J = 1.2 Hz, 1 H) 7.67 (d, J = 8.3 Hz, 2 H) 7.94 (d, J = 8.3 Hz, 2 H) 8.22 (s, 2 H) 8.72 (d, J = 1.2 Hz, 1 H ).
MS ESI / APCI Dual posi: 494 [M + H] ⁺ .
Example 89-2
3- [1- (5-Ethylpyrimidin-2-yl) piperidin-4-yl] -6- [3- (methylsulfonyl) phenoxy] -3H- [1,2,3] triazolo [4,5-c ] Pyridine

参考例１８で得られた化合物（１００ｍｇ）と３−メタンスルホニルフェノール（５３．４ｍｇ）を用いて、実施例２９−１と同様の操作にて反応及び精製を行い、表題化合物（１０６ｍｇ）を無色粉末として得た。
¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.7 Hz, 3 H) 2.30 - 2.44 (m, 4 H) 2.51 (q, J=7.7 Hz, 2 H) 3.06 (s, 3 H) 3.17 - 3.25 (m, 2 H) 4.96 - 5.02 (m, 2 H) 5.05 - 5.13 (m, 1 H) 7.38 - 7.43 (m, 1 H) 7.56 - 7.66 (m, 3 H) 7.72 - 7.77 (m, 1 H) 8.23 (s, 2 H) 8.77 - 8.81 (m, 1 H).
MS ESI/APCI Dual posi: 480[M+H]⁺, 502[M+Na]⁺.

Using the compound (100 mg) obtained in Reference Example 18 and 3-methanesulfonylphenol (53.4 mg), the reaction and purification were conducted in the same manner as in Example 29-1, and the title compound (106 mg) was purified colorless. Obtained as a powder.
¹ H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J = 7.7 Hz, 3 H) 2.30-2.44 (m, 4 H) 2.51 (q, J = 7.7 Hz, 2 H) 3.06 (s, 3 H) 3.17-3.25 (m, 2 H) 4.96-5.02 (m, 2 H) 5.05-5.13 (m, 1 H) 7.38-7.43 (m, 1 H) 7.56-7.66 (m, 3 H) 7.72- 7.77 (m, 1 H) 8.23 (s, 2 H) 8.77-8.81 (m, 1 H).
MS ESI / APCI Dual posi: 480 [M + H] ⁺ , 502 [M + Na] ⁺ .

Test example 1
The compound according to the present invention was added to human GPR119-expressing cells, and GPR119 agonist activity was evaluated using the amount of cAMP produced by the cells as an index.

(1) Construction of human GPR119-expressing cells Human GPR119 (NM — 178471) was amplified by polymerase chain reaction (PCR) using KOD-plus polymerase using human MTC multi-tissue cDNA panel (Clontech) as a template. A human GPR119 amplification product was inserted into pcDNA5 / FRT / TO (Invitrogen) as an insert, and a cell line capable of inducing expression of the human GPR119 gene in a tetracycline dose-dependent manner using the Flp-In T-Rex system was prepared.

(2) Measurement method for enhancement of intracellular cAMP production Tetracycline having a final concentration of 10 ng / ml was added to the cell line to induce expression of human GPR119. Cells were collected 24 hours after stimulation of expression induction and suspended in assay buffer (D-MEM (Invitrogen), 1 mM 3-Isobutyl-1-methylxantine (Sigma), 0.01% bovine serum albumin (Sigma)). Later, it was seeded on a 96-well half area plate (Corning) at 5000 cells / 15 μl. 15 μl of a test compound solution dissolved in assay buffer was added to each well, incubated at 37 ° C. for 30 minutes, and then time-resolved fluorescence (Ex: 320 nm, Em: 665 nm, 620 nm) with EnVision according to the protocol of cAMP HiRange kit (Cisbio). ) Was measured. Ratio values of anti-cAMP-Cryptate and cAMP-d2 were calculated from the measured fluorescence intensity. For analysis of the ratio value, XLfit was used, and after preparing a cAMP standard curve, the cAMP concentration in each well in the presence of the test compound was calculated. The compound concentration that activates 50% of the maximum activated GPR119 activity as 100% from the value obtained by subtracting the cAMP concentration in the presence of DMSO from the maximum cAMP concentration (Emax) under the high dose of the test compound (EC ₅₀ ) Was calculated. When the maximum activation rate (Emax) of the test compound could not be calculated, the cAMP concentration increase rate (% stimulation) in the presence of the test compound was calculated with the cAMP concentration in the presence of DMSO as 100%.

(3) Results Tables 69-1 to 69-10 show the GPR119 agonist activities calculated based on the measurement results obtained by conducting the above tests on the compounds of the present invention.

Formulation examples of the compound of the present invention are shown below.
Formulation Example 1
A granule containing the following ingredients is produced.
Component Compound represented by formula (I) 10mg
Lactose 700mg
Corn starch 274mg
HPC-L 16mg
1000mg
The compound of formula (I) and lactose are passed through a 60 mesh sieve. Pass corn starch through a 120 mesh sieve. These are mixed in a V-type mixer. A low-viscosity hydroxypropylcellulose (HPC-L) aqueous solution is added to the mixed powder, kneaded and granulated (extruded granulation, pore diameter: 0.5 to 1 mm), and then dried. The obtained dried granules are sieved with a vibrating sieve (12/60 mesh) to obtain granules.

Formulation Example 2
A powder for capsule filling containing the following components is produced.
Component Compound represented by formula (I) 10mg
Lactose 79mg
Corn starch 10mg
Magnesium stearate 1mg
100mg
The compound of formula (I) and lactose are passed through a 60 mesh sieve. Pass corn starch through a 120 mesh sieve. These and magnesium stearate are mixed in a V-type mixer. 100 mg of 10 times powder is filled into a No. 5 hard gelatin capsule.

Formulation Example 3
A capsule filling granule containing the following ingredients is produced.
Ingredient Compound represented by formula (I) 15mg
Lactose 90mg
Cornstarch 42mg
HPC-L 3mg
150mg
The compound of formula (I) and lactose are passed through a 60 mesh sieve. Pass corn starch through a 120 mesh sieve. These are mixed in a V-type mixer. A low-viscosity hydroxypropylcellulose (HPC-L) aqueous solution is added to the mixed powder, kneaded and granulated, and then dried. The obtained dried granule is sieved with a vibrating sieve (12/60 mesh) and sized, and 150 mg thereof is filled into a No. 4 hard gelatin capsule.

Formulation Example 4
A tablet containing the following ingredients is produced.
Component Compound represented by formula (I) 10mg
Lactose 90mg
Microcrystalline cellulose 30mg
Magnesium stearate 5mg
CMC-Na 15mg
150mg
The compound represented by the formula (I), lactose, microcrystalline cellulose, and CMC-Na (carboxymethylcellulose sodium salt) are passed through a 60 mesh sieve and mixed. Magnesium stearate is added to the mixed powder to obtain a mixed powder for preparation. The mixed powder is directly hit to obtain a 150 mg tablet.

Formulation Example 5
The intravenous formulation is produced as follows.
100 mg of the compound represented by formula (I)
Saturated fatty acid glyceride 1000ml
Solutions of the above components are usually administered intravenously to the patient at a rate of 1 ml per minute.

  The present invention is expected to contribute to the development of the pharmaceutical industry by reducing the burden on patients by providing a pharmaceutical having an excellent GPR119 agonistic action and effective in preventing or treating diseases derived from diabetes. Is done.

Claims (10)

The following general formula (I)

(In the formula (I),
Substituent A is phenyl or 5- or 6-membered heteroaryl (the phenyl and 5- or 6-membered heteroaryl are either unsubstituted or selected from the following substituent group Z1 in the same or different manner: 1 to 3 Substituted with 1 group.)
Indicate
Substituent group Z1 is a halogen atom, carbamoyl, sulfamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or halogen atom, hydroxy, carbamoyl, sulfamoyl, C _3-8 Cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl, saturated heterocyclyl, C _1-6 alkoxy, C _1-6 alkoxycarbonyl, mono C _1-6 alkylaminocarbonyl, diC _1-6 alkylamino carbonyl, heterocyclylcarbonyl saturated, substituted with C _1-6 alkylcarbonylamino, C _1-6 alkylsulfonylamino and C _1-6 1 to 3 groups which are identical to or different selected from the group consisting of alkylsulfonyl have.), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated hetero Reels, saturated heterocyclyl (said C _3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl partially saturated heteroaryl and saturated, unsubstituted or substituted, is substituted with 1 to 3 halogen atoms C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylaminocarbonyl is unsubstituted or from the group consisting of hydroxy, carbamoyl, C _3-8 cycloalkyl, C _1-6 alkoxy, diC _1-6 alkylamino and C _1-6 alkylsulfonyl substituted with 1 to 3 groups which are the same or different and selected.), mono-C _3-8 cycloalkyl-aminocarbonyl, heterocyclylcarbonyl aminocarbonyl mono saturated ( Heterocyclylcarbonyl aminocarbonyl mono saturation, unsubstituted or substituted, is substituted with one to two oxo.), Di-C _1-6 alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, substituted Or substituted with one or two groups selected from the group consisting of hydroxy, cyano and C _1-6 alkoxy, the same or different.), A saturated heterocyclylcarbonyl [the saturated heterocyclylcarbonyl is Unsubstituted, hydroxy, C _1-6 alkyl (wherein the C _1-6 alkyl is unsubstituted or substituted with 1 hydroxy), mono C _1-6 alkylamino, di-C substituted with _1-6 1-2 groups identical to or different selected from alkyl amino and the group consisting of C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl, the mono-C _1-6 alkylaminosulfonyl being unsubstituted or substituted with one hydroxy. Show
W represents a single bond, —O—, —NH—, —OCH ₂ — or —CH ₂ O—,
X represents a nitrogen atom or CR ²¹ ;
Y ¹ represents a nitrogen atom or CR ²² ;
Y ² represents a nitrogen atom or CR ²³ ,
Y ³ represents a nitrogen atom or CR ²⁴ ,
R ²¹ , R ²² , R ²³ and R ²⁴ are the same or different and each represents a hydrogen atom or C _1-6 alkyl;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with 1 C _1-6 alkyl). ), Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) ,
(B) -COOR ³¹ (wherein R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), C _1-6 alkoxy (the C _1-6 alkoxy is Unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (the heteroaryl is and is not substituted, it halogen atom and C _1-6 alkyl Substituted with one group selected from the group.), Heterocyclyl saturated heterocyclyl (saturated are unsubstituted or substituted, is substituted with one C _1-6 alkyl.), Mono C Substituted with 1 to 6 groups selected from the group consisting of _1-6 alkylamino, di-C _1-6 alkylamino, C _1-6 alkylsulfanyl and C _1-6 alkylsulfonyl}, C _{3- 8} cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl), aryl or saturated Of the heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted with one C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with one aryl). Is replaced.),
(C) The following formula (β)

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1- Same or different from the group consisting of ₆ alkoxycarbonyl, mono C _1-6 alkylaminocarbonyl, di C _1-6 alkylaminocarbonyl, saturated heterocyclylcarbonyl, mono C _1-6 alkylamino and di C _1-6 alkylamino 1 chosen Substituted with three groups. ]
Indicates.
However, the structure represented by the following formula (A) is excluded.

Or a pharmaceutically acceptable salt thereof as an active ingredient. In the general formula (I),
Substituent A is phenyl or 5- or 6-membered heteroaryl (the phenyl and 5- or 6-membered heteroaryl are unsubstituted or selected from the following substituent group Z2 in the same or different manner: 1 to 3 Substituted with 1 group.)
Indicate
Substituent group Z2 is a halogen atom, carbamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted, halogen atom, hydroxy, carbamoyl, C _1-6 alkoxy, and C Substituted with 1 to 3 groups identically or differently selected from the group consisting of _1-6 alkylsulfonyl.), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl , C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), mono C _1-6 alkylaminocarbonyl (the mono C _{1- 6} alkylaminocarbonyl is unsubstituted or consists of hydroxy, carbamoyl, C _3-8 cycloalkyl, C _1-6 alkoxy, diC _1-6 alkylamino and C _1-6 alkylsulfonyl. A mono-C _3-8 cycloalkylaminocarbonyl, a mono-saturated heterocyclylaminocarbonyl (the mono-saturated heterocyclylaminocarbonyl is: Unsubstituted or substituted with 1 to 2 oxo), di-C _1-6 alkylaminocarbonyl (the di-C _1-6 alkylaminocarbonyl is unsubstituted, hydroxy, cyano and Substituted with one or two groups selected from the group consisting of C _1-6 alkoxy identically or differently.), Saturated heterocyclylcarbonyl [wherein the saturated heterocyclylcarbonyl is unsubstituted, hydroxy, C _1-6 alkyl (said C _1-6 alkyl is unsubstituted or substituted with substituted with one hydroxy.), mono-C _1-6 alkylamino Is substituted with one to two groups the same or different and selected from the group consisting of di-C _1-6 alkylamino and C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl, the mono-C _1-6 alkylaminosulfonyl being unsubstituted or substituted with one hydroxy. Show
W represents a single bond, —O—, —OCH ₂ — or —CH ₂ O—,
X represents a nitrogen atom or CR ²¹ ;
Y ¹ represents CR ²²
Y ² represents a nitrogen atom or CR ²³ ,
Y ³ represents CR ²⁴ ,
R ²¹ , R ²² , R ²³ and R ²⁴ are the same or different and each represents a hydrogen atom or C _1-6 alkyl;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (wherein the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with 1 C _1-6 alkyl). ), Aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) ,
(B) -COOR ³¹ (wherein R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), C _1-6 alkoxy (the C _1-6 alkoxy is Unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl is substituted) Or substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (the heteroaryl is and is not substituted, it halogen atom and C _1-6 alkyl Substituted with one group selected from the group.), Heterocyclyl saturated heterocyclyl (saturated are unsubstituted or substituted, is substituted with one C _1-6 alkyl.), Di-C _1-6 alkylamino, and C _1-6 substituted with 1-6 substituents selected from the group consisting of alkylsulfonyl.}, C _3-8 cycloalkyl (said C _3-8 cycloalkyl, substituted Or substituted with 1 to 3 groups selected from the group consisting of a halogen atom and C _1-6 alkyl.), Aryl or saturated heterocyclyl [the saturated heterocyclyl is unsubstituted or substituted] 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl)].
(C) The following formula (β)

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1-6 alkoxycarbonyl, saturated It is substituted with 1 to 3 groups selected from the group consisting of heterocyclylcarbonyl and diC _1-6 alkylamino, the same or different. ]
Indicates.
However, the structure represented by the following formula (A) is excluded.

A hypoglycemic agent comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In the general formula (I),
Substituent A is phenyl or 6-membered heteroaryl (the phenyl and 6-membered heteroaryl are 1 to 3 groups that are not substituted or are the same or different from the following substituent group Z3: Has been replaced.)
Indicate
Substituent group Z3 is a halogen atom, carbamoyl, cyano, cyanamide, C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkylsulfonyl). ), C _3-8 cycloalkyl, aryl, heteroaryl, partially saturated heteroaryl, saturated heterocyclyl, C _1-6 alkoxy, mono C _1-6 alkylaminocarbonyl (the mono C _1-6 alkylamino) The carbonyl is unsubstituted or substituted with 1 to 3 groups selected identically or differently from the group consisting of hydroxy, C _1-6 alkoxy and diC _1-6 alkylamino), di. C _1-6 alkylaminocarbonyl (the di C _1-6 alkylaminocarbonyl, unsubstituted or substituted, is substituted with one hydroxy.), heterocyclylcarbonyl saturated [ Heterocyclylcarbonyl Saturated, unsubstituted or substituted with hydroxy, C _1-6 alkyl (said C _1-6 alkyl is unsubstituted or substituted with substituted with one hydroxy.), Di C _1- Substituted with one group selected from the group consisting of ₆ alkylamino and C _1-6 alkylsulfonyl. ], C _1-6 alkylsulfonylamino, C _1-6 alkylsulfonyl (wherein the C _1-6 alkylsulfonyl is one which is unsubstituted or selected from the group consisting of hydroxy, carbamoyl and C _1-6 alkoxy) And a mono-C _1-6 alkylaminosulfonyl (wherein the C _1-6 alkylsulfonyl is unsubstituted or substituted with one hydroxy), and
W represents a single bond, —O— or —OCH ₂ —;
Substituent B is
(A) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy), C _{3- 8} cycloalkyl or C _3-8 cycloalkyl C _1-6 alkyl,
(B) -COOR ³¹ [wherein R ³¹ is C _1-6 alkyl or C _3-8 cycloalkyl (the C _1-6 alkyl and C _3-8 cycloalkyl are unsubstituted or substituted by 1 to 3 Substituted with a halogen atom)]
(C) The following formula (β)

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is a non-substituted or halogen atom, C _1-6 alkyl (the C _1-6 Alkyl is unsubstituted or substituted with one hydroxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy and C _1-6 alkoxycarbonyl It is substituted with 1 to 3 groups selected identically or differently. ]
A hypoglycemic agent comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The substituent B is (a) C _2-6 alkyl (the C _2-6 alkyl is unsubstituted or substituted with 1 to 6 groups selected from the group consisting of a halogen atom and hydroxy). ), C _3-8 cycloalkyl, C _3-8 cycloalkyl C _1-6 alkyl (the C _3-8 cycloalkyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl Substituted), aryl C _1-6 alkyl or saturated heterocyclyl C _1-6 alkyl (the saturated heterocyclyl C _1-6 alkyl is unsubstituted or substituted with one C _1-6 alkyl) Has been.)
A hypoglycemic agent comprising the compound according to any one of claims 1 and 2 or a pharmaceutically acceptable salt thereof as an active ingredient. Substituent B is (b) -COOR ³¹ (R ³¹ is C _1-6 alkyl {the C _1-6 alkyl is not substituted or is a halogen atom, cyano, C _3-8 cycloalkyl (the C _3-8 cycloalkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl.), C _1-6 alkoxy (the C _{1 -6} alkoxy is unsubstituted or substituted with 1 aryl), aryl [the aryl is unsubstituted or halogen atom, C _1-6 alkyl (the C _1-6 alkyl And is substituted with 1 to 3 groups selected from the group consisting of C _1-6 alkoxy.], Heteroaryl (said heteroaryl is unsubstituted or substituted with a halogen atom and a C _1-6 a Substituted with one group selected from the group consisting of kill.), Heterocyclyl saturated (heterocyclyl saturation is unsubstituted or substituted, it is substituted with one C _1-6 alkyl.) Substituted with 1 to 6 groups selected from the group consisting of di-C _1-6 alkylamino, and C _1-6 alkylsulfonyl}, C _3-8 cycloalkyl (the C _3-8 cycloalkyl Is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen atoms and C _1-6 alkyl.), Aryl or saturated heterocyclyl [the saturated heterocyclyl is substituted Or 1 C _1-6 alkyl (the C _1-6 alkyl is unsubstituted or substituted with 1 aryl).],
A hypoglycemic agent comprising the compound according to any one of claims 1 and 2 or a pharmaceutically acceptable salt thereof as an active ingredient. Substituent B is (c) the following formula (β)

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is not substituted, is a halogen atom, carbamoyl, cyano, C _1-6 alkyl C _1-6 alkyl is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of a halogen atom, hydroxy and C _1-6 alkoxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy (the C _1-6 alkoxy is unsubstituted or substituted with 1 to 3 halogen atoms), C _1-6 alkoxycarbonyl, saturated It is substituted with 1 to 3 groups selected from the group consisting of heterocyclylcarbonyl and diC _1-6 alkylamino, the same or different. ]
A hypoglycemic agent comprising the compound according to any one of claims 1 and 2 or a pharmaceutically acceptable salt thereof as an active ingredient. Substituent B is (c) the following formula (β)

A 5- or 6-membered heteroaryl represented by the above [5 or 6-membered heteroaryl represented by the formula (β) is a non-substituted or halogen atom, C _1-6 alkyl (the C _1-6 Alkyl is unsubstituted or substituted with one hydroxy.), C _2-6 alkenyl, C _3-8 cycloalkyl, C _1-6 alkoxy and C _1-6 alkoxycarbonyl It is substituted with 1 to 3 groups selected identically or differently. ]
A hypoglycemic agent comprising the compound according to any one of claims 1, 2, 3, and 6 or a pharmaceutically acceptable salt thereof as an active ingredient. A hypoglycemic agent comprising the compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof as an active ingredient, wherein Y ¹ represents CH and Y ³ represents CH. The hypoglycemic agent which contains as an active ingredient the compound of any one of Claims 1-8 whose Y < ² > shows a nitrogen atom, or its pharmaceutically acceptable salt.   A hypoglycemic agent comprising the compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof as an active ingredient, wherein X represents a nitrogen atom.