JP2011001354A - Amide compound, and use thereof in controlling plant disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new compound exhibiting an excellent effect on controlling plant diseases, and an agent for controlling plant diseases comprising the compound.SOLUTION: There are disclosed an amide compound represented by the formula or a salt thereof, and an agent of controlling plant diseases comprising the compound (in the formula, p represents an integer of 1 to 5; and Rrepresents a 1-5C linear hydrocarbon group that may be substituted, a 3-10C cycloalkyl group that may be substituted, a phenyl group that may be substituted, a halogen, a cyano group, a nitro group or the like).

Description

  The present invention relates to an amide compound and its use for controlling plant diseases.

  Conventionally, many compounds have been developed and used for controlling plant diseases.

  An object of the present invention is to provide a compound having an excellent plant disease control effect.

  As a result of intensive studies to find a compound having an excellent plant disease control effect, the present inventors have found that the amide compound represented by the following formula (1) has an excellent plant disease control effect and completed the present invention. did. That is, the present invention is as follows.

〔式中、
ｐは１から５の整数のいずれかを表し、
Ｒ²は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１〜Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３〜Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ⁵基、−Ｓ−Ｒ⁵基、−Ｃ（＝Ｏ）−Ｒ⁵基、−Ｃ（＝Ｏ）−ＯＲ⁵基、−ＯＣ（＝Ｏ）−Ｒ⁵基、−ＮＲ⁵Ｒ⁶基、−Ｃ（＝Ｏ）−ＮＲ⁵Ｒ⁶基又は−ＮＲ⁵−Ｃ（＝Ｏ）−Ｒ⁶基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ²がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ²が結合して、群Ｅより選ばれる１以上の基で置換されていてもよいＣ２〜Ｃ５ポリメチレン基、群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基、群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基を表し、
Ｒ⁵及びＲ⁶は独立して、水素、群Cより選ばれる１以上の基で置換されていてもよいＣ１〜Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３〜Ｃ１０シクロアルキル基又は群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基を表す。
但し、ｐが２から５の整数のいずれかである場合、Ｒ²は相互に同一又は相異なる。
なお、群Ｃは群Ｄより選ばれる１以上の基で置換されていてもよいＣ３〜Ｃ１０シクロアルキル基、ハロゲン、シアノ基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルコキシ）カルボニル基及びハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルキル）カルボニルオキシ基からなる群を表し、
群ＤはＣ１〜Ｃ５アルキル基及びハロゲンからなる群を表し、
群Ｅはハロゲン、シアノ基、ニトロ基、ハロゲンで置換されていてもよいＣ１〜Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３〜Ｃ１０シクロアルキル基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１〜Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルコキシ）カルボニル基及びハロゲンで置換されていてもよい（Ｃ１〜Ｃ４アルキル）カルボニルオキシ基からなる群を表す。〕
で示されるアミド化合物（以下、本発明化合物と記す）又はその塩。 [1] Formula (1)

[Where,
p represents any integer from 1 to 5;
R ² is a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D. , Phenyl group, halogen, cyano group, nitro group, —O—R ⁵ group, —S—R ⁵ group, —C (═O) —R optionally substituted with one or more groups selected from group E ⁵ groups, —C (═O) —OR ⁵ group, —OC (═O) —R ⁵ group, —NR ⁵ R ⁶ group, —C (═O) —NR ⁵ R ⁶ group or —NR ⁵ —C Represents the (= O) -R ⁶ group,
Alternatively, when p is 2 or more and two R ² are bonded to adjacent carbons of the benzene ring, the two R ² are bonded and substituted with one or more groups selected from group E. An optionally substituted C2-C5 polymethylene group, a propene-1,3-diyl group which may be substituted with one or more groups selected from group E, and one or more groups selected from group E. Represents a 1,3-butadiene-1,4-diyl group or a methylenedioxy group,
R ⁵ and R ⁶ are independently hydrogen, a C1-C10 chain hydrocarbon group optionally substituted with one or more groups selected from group C, or one or more groups selected from group D. Represents a phenyl group which may be substituted with one or more groups selected from C3 to C10 cycloalkyl groups which may be substituted or group E.
However, when p is any integer of 2 to 5, R ² is the same or different from each other.
Group C is a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from Group D, a halogen, a cyano group, a C1-C4 alkoxy group which may be substituted with halogen, or a halogen. An optionally substituted C1-C4 alkylthio group, an optionally substituted C1-C4 alkylsulfinyl group, an optionally substituted C1-C4 alkylsulfonyl group, and an optionally substituted halogen ( A group consisting of a (C1-C4 alkyl) carbonyl group, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen and a (C1-C4 alkyl) carbonyloxy group optionally substituted with halogen;
Group D represents a group consisting of a C1-C5 alkyl group and halogen,
Group E is halogen, cyano group, nitro group, C1-C10 chain hydrocarbon group which may be substituted with halogen, C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D C1-C4 alkoxy group optionally substituted with halogen, C1-C4 alkylthio group optionally substituted with halogen, C1-C4 alkylsulfinyl group optionally substituted with halogen, halogen-substituted May be a C1-C4 alkylsulfonyl group, a (C1-C4 alkyl) carbonyl group optionally substituted with halogen, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a halogen-substituted A good (C1-C4 alkyl) carbonyloxy group is represented. ]
Or an salt thereof (hereinafter referred to as the present compound).

[2] The amide compound or a salt thereof according to [1], wherein R ² is halogen.

[3] The amide compound or a salt thereof according to [1], wherein R ² is fluorine or chlorine.

[4] The amide compound or a salt thereof according to [1], wherein R ² is fluorine or bromine.

[5] The amide compound or a salt thereof according to [1], wherein p is 3, and R ² are the same or different from each other and are halogen.

[6] The amide compound or a salt thereof according to [1], wherein p is 3, and R ² are the same or different from each other and are fluorine or chlorine.

[7] The amide compound or a salt thereof according to claim 1, wherein p is 3, and R ² are the same or different from each other and are fluorine or bromine.

[8] A plant disease control agent comprising the amide compound or salt thereof according to any one of [1] to [7] and an inert carrier.

[9] A method for controlling plant diseases comprising a step of applying an effective amount of the amide compound or salt thereof according to any one of [1] to [7] to a plant or a soil in which the plant grows.

[10] Use of the amide compound or salt thereof according to any one of [1] to [7] for controlling plant diseases.

  Since the compound of the present invention has an excellent plant disease control effect, it is useful as an active ingredient of a plant disease control agent.

Various substituents used in the description of the present specification will be described below with examples.
“Halogen” means fluorine, chlorine, bromine and iodine.

Examples of the “C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group,
Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group, 5-iodo Pentyl group,
Cyanomethyl group, dicyanomethyl group, 2-cyanoethyl group, 2,2-dicyanoethyl group, 3-cyanopropyl group, 3,3-dicyanopropyl group, 4-cyanobutyl group, 4,4-dicyanobutyl group, 5-cyano Pentyl group, 5,5-dicyanopentyl group,
Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, 2-methoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, 5-methoxypentyl group, 2-ethoxyethyl group, 3-ethoxypropyl group, 4-ethoxybutyl group, 5-ethoxypentyl group, 2-propoxyethyl group, 3-propoxypropyl group, 4-propoxybutyl group, 5- Propoxypentyl group, 2-butoxyethyl group, 3-butoxypropyl group, 4-butoxybutyl group, 5-butoxypentyl group,
Methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group, butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, 2-methylthioethyl group, 3-methylthiopropyl group, 4- Methylthiobutyl group, 5-methylthiopentyl group, 2-ethylthioethyl group, 3-ethylthiopropyl group, 4-ethylthiobutyl group, 5-ethylthiopentyl group, 2-propylthioethyl group, 3-propylthiopropyl group Group, 4-propylthiobutyl group, 5-propylthiopentyl group, 2-butylthioethyl group, 3-butylthiopropyl group, 4-butylthiobutyl group, 5-butylthiopentyl group,
Methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfinylmethyl group, isopropanesulfinylmethyl group, butanesulfinylmethyl group, isobutanesulfinylmethyl group, t-butanesulfinylmethyl group, 2-methanesulfinylethyl group, 3-methanesulfinylpropyl group Group, 4-methanesulfinylbutyl group, 5-methanesulfinylpentyl group, 2-ethanesulfinylethyl group, 3-ethanesulfinylpropyl group, 4-ethanesulfinylbutyl group, 5-ethanesulfinylpentyl group, 2-propanesulfinylethyl group 3-propanesulfinylpropyl group, 4-propanesulfinylbutyl group, 5-propanesulfinylpentyl group, 2-butanesulfinylethyl group, 3-butanesulfy group Rupuropiru group, 4-Bed ethanesulfinyl butyl group, 5- butane sulfinyl point pen butyl group,
Methanesulfonylmethyl group, ethanesulfonylmethyl group, propanesulfonylmethyl group, isopropanesulfonylmethyl group, butanesulfonylmethyl group, isobutanesulfonylmethyl group, t-butanesulfonylmethyl group, 2-methanesulfonylethyl group, 3-methanesulfonylpropyl group Group, 4-methanesulfonylbutyl group, 5-methanesulfonylpentyl group, 2-ethanesulfonylethyl group, 3-ethanesulfonylpropyl group, 4-ethanesulfonylbutyl group, 5-ethanesulfonylpentyl group, 2-propanesulfonylethyl group 3-propanesulfonylpropyl group, 4-propanesulfonylbutyl group, 5-propanesulfonylpentyl group, 2-butanesulfonylethyl group, 3-butanesulfonylpropyl group, 4-butanesulfonylbutyl group And it includes 5-butane sulfonyl pentyl group.

  Examples of the “C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D” include, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl. Group, cyclodecyl group, methylcyclopropyl group, 1,1-dimethylcyclopropyl group, ethylcyclopropyl group, propylcyclopropyl group, butylcyclopropyl group, pentylcyclopropyl group, 2-methylcyclohexyl group, 2-ethylcyclohexyl group 2-propylcyclohexyl group, 2-butylcyclohexyl group, 2-pentylcyclohexyl group, 3-methylcyclohexyl group, 3-ethylcyclohexyl group, 3-propylcyclohexyl group, 3-butylcyclohexyl group, 3-pentylcycle Hexyl group, 4-methylcyclohexyl group, 4-ethylcyclohexyl group, 4-propylcyclohexyl group, 4-butylcyclohexyl group, 4-pentylcyclohexyl group, fluorocyclopropyl group, chlorocyclopropyl group, 1,1-difluorocyclopropyl Group, 1,1-dichlorocyclopropyl group, 2-fluorocyclohexyl group, 3-fluorocyclohexyl group, 4-fluorocyclohexyl group, 2-chlorocyclohexyl group, 3-chlorocyclohexyl group and 4-chlorocyclohexyl group.

Examples of the “phenyl group optionally substituted with one or more groups selected from group E” include, for example, phenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-iodophenyl group, 3-iodophenyl group, 4-iodophenyl group,
2-cyanophenyl group, 3-cyanophenyl group, 4-cyanophenyl group, 2-nitrophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4- Methylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2-propylphenyl group, 3-propylphenyl group, 4-propylphenyl group, 2-isopropylphenyl group, 3-isopropylphenyl Group, 4-isopropylphenyl group, 2-butylphenyl group, 3-butylphenyl group, 4-butylphenyl group, 2-isobutylphenyl group, 3-isobutylphenyl group, 4-isobutylphenyl group, 2-t-butylphenyl Group, 3-t-butylphenyl group, 4-t-butylphenyl group, 2-pentylphenyl group, -Hexylphenyl group, 4-heptylphenyl group, 2-octylphenyl group, 3-nonylphenyl group, 4-decylphenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethyl Phenyl group, 2- (2,2,2-trifluoroethyl) phenyl group, 3- (3,3,3-trifluoropropyl) phenyl group, 4- (4,4,4-trifluorobutyl) phenyl group 2- (5,5,5-trifluoropentyl) phenyl group, 3- (6,6,6-trifluorohexyl) phenyl group, 4- (7,7,7-trifluoroheptyl) phenyl group, 2 -(8,8,8-trifluorooctyl) phenyl group, 3- (9,9,9-trifluorononyl) phenyl group, 4- (10,10,10-trifluorode) ) Phenyl group,
2-cyclopropylphenyl group, 3-cyclopropylphenyl group, 4-cyclopropylphenyl group, 2-cyclobutylphenyl group, 3-cyclopentylphenyl group, 4-cyclohexylphenyl group, 2-cycloheptylphenyl group, 3-cyclo Octylphenyl group, 4-cyclononylphenyl group, 2-cyclodecylphenyl group, 3- (methylcyclopropyl) phenyl group, 4- (1,1-dimethylcyclopropyl) phenyl group, 3- (fluorocyclopropyl) phenyl Group, 4- (chlorocyclopropyl) phenyl group, 2- (1,1-difluorocyclopropyl) phenyl group, 3- (1,1-dichlorocyclopropyl) phenyl group, 4- (2-fluorocyclohexyl) phenyl group 4- (2-chlorocyclohexyl) phenyl group,
2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-trifluoromethoxyphenyl group, 3-trifluoromethoxyphenyl group, 4-trifluoromethoxyphenyl group, 2-ethoxyphenyl group, 3- Propoxyphenyl group, 4-butoxyphenyl group,
2-methylthiophenyl group, 3-methylthiophenyl group, 4-methylthiophenyl group, 2-trifluoromethylthiophenyl group, 3-trifluoromethylthiophenyl group, 4-trifluoromethylthiophenyl group, 2-ethylthiophenyl group, 3 -Propylthiophenyl group, 4-butylthiophenyl group,
2-methanesulfinylphenyl group, 3-methanesulfinylphenyl group, 4-methanesulfinylphenyl group, 2-methanesulfinylphenyl group, 3-methanesulfinylphenyl group, 4-methanesulfinylphenyl group, 2-ethylsulfinylphenyl group, 3 -Propylsulfinylphenyl group, 4-butylsulfinylphenyl group,
2-methanesulfonylphenyl group, 3-methanesulfonylphenyl group, 4-methanesulfonylphenyl group, 2-methanesulfonylphenyl group, 3-methanesulfonylphenyl group, 4-methanesulfonylphenyl group, 2-ethylsulfonylphenyl group, 3 -Propylsulfonylphenyl group, 4-butylsulfonylphenyl group,
2-acetylphenyl group, 3-acetylphenyl group, 4-acetylphenyl group, 2-difluoroacetylphenyl group, 3-trifluoroacetylphenyl group, 4-dichloroacetylphenyl group, 2-trichloroacetylphenyl group, 3-propa Noylphenyl group, 4-butanoylphenyl group, 2-isobutanoylphenyl group, 3-pentanoylphenyl group, 4-pivaloylphenyl group,
2- (methoxycarbonyl) phenyl group, 3- (methoxycarbonyl) phenyl group, 4- (methoxycarbonyl) phenyl group, 2- (trifluoromethoxycarbonyl) phenyl group, 3- (trichloromethoxycarbonyl) phenyl group, 4- (Ethoxycarbonyl) phenyl group, 2- (propoxycarbonyl) phenyl group, 3- (isopropoxycarbonyl) phenyl group, 4- (butoxycarbonyl) phenyl group,
2-acetoxyphenyl group, 3-acetoxyphenyl group, 4-acetoxyphenyl group, 2-difluoroacetoxyphenyl group, 3-trifluoroacetoxyphenyl group, 4-trichloroacetoxyphenyl group, 2-propanoyloxyphenyl group, 3- Examples include butanoyloxyphenyl group, 4-isobutanoyloxyphenyl group, 2-pentanoyloxyphenyl group and 3-pivaloyloxyphenyl group.

  Examples of the “C2-C5 polymethylene group optionally substituted with one or more groups selected from group E” include, for example, ethylene group, 1,3-propylene group, 1,4-butylene group, 1,5-pentylene group , Fluoroethylene group, chloroethylene group, bromoethylene group, cyanoethylene group, nitroethylene group, 1,2-propylene group, 3,3,3-trifluoro-1,2-propylene group, cyclopropylethylene group, methoxy Ethylene group, trifluoromethoxyethylene group, methylthioethylene group, trifluoromethylthioethylene group, methanesulfinylethylene group, trifluoromethanesulfinylethylene group, methanesulfonylethylene group, trifluoromethanesulfonylethylene group, acetylethylene group, trifluoroacetylethylene group , Methoxyca Boniruechiren group, a trifluoromethoxy carbonyl ethylene group include acetoxy ethylene group and trifluoroacetoxy ethylene group.

  Examples of the “propene-1,3-diyl group optionally substituted with one or more groups selected from group E” include propene-1,3-diyl group, 2-fluoropropene-1,3-diyl group 3-fluoropropene-1,3-diyl group, 3,3-difluoropropene-1,3-diyl group, 2-chloropropene-1,3-diyl group, 2-bromopropene-1,3-diyl group 2-cyanopropene-1,3-diyl group, 2-nitropropene-1,3-diyl group, 2-methylpropene-1,3-diyl group, 3-methylpropene-1,3-diyl group, 3 , 3-Dimethylpropene-1,3-diyl group, 2-trifluoromethylpropene-1,3-diyl group, 2-cyclopropylpropene-1,3-diyl group, 2-methoxypropene-1,3-diyl Group, 2-trif Olomethoxypropene-1,3-diyl group, 2-methylthiopropene-1,3-diyl group, 2-trifluoromethylthiopropene-1,3-diyl group, 2-methanesulfinylpropene-1,3-diyl group, 2-trifluoromethanesulfinylpropene-1,3-diyl group, 2-acetylpropene-1,3-diyl group, 2-trifluoroacetylpropene-1,3-diyl group, 2-methoxycarbonylpropene-1,3- Examples include a diyl group, a 2-trifluoromethoxycarbonylpropene-1,3-diyl group, a 2-acetoxypropene-1,3-diyl group, and a 2-trifluoroacetoxypropene-1,3-diyl group.

  Examples of the “1,3-butadiene-1,4-diyl group optionally substituted with one or more groups selected from group E” include 1,3-butadiene-1,4-diyl group, 1-fluoro -1,3-butadiene-1,4-diyl group, 2-fluoro-1,3-butadiene-1,4-diyl group, 1-chloro-1,3-butadiene-1,4-diyl group, 2- Chloro-1,3-butadiene-1,4-diyl group, 1-bromo-1,3-butadiene-1,4-diyl group, 2-bromo-1,3-butadiene-1,4-diyl group, 1 -Cyano-1,3-butadiene-1,4-diyl group, 1-nitro-1,3-butadiene-1,4-diyl group, 1-methyl-1,3-butadiene-1,4-diyl group, 2-methyl-1,3-butadiene-1,4-diyl group, 1-trifluoromethyl -1,3-butadiene-1,4-diyl group, 1-cyclopropyl-1,3-butadiene-1,4-diyl group, 1-methoxy-1,3-butadiene-1,4-diyl group, 1 -Trifluoromethoxy-1,3-butadiene-1,4-diyl group, 1-methylthio-1,3-butadiene-1,4-diyl group, 1-trifluoromethylthio-1,3-butadiene-1, 4-diyl group, 1-methanesulfinyl-1,3-butadiene-1,4-diyl group, 1-trifluoromethanesulfinyl-1,3-butadiene-1,4-diyl group, 1-acetyl-1,3- Butadiene-1,4-diyl group, 1-trifluoroacetyl-1,3-butadiene-1,4-diyl group, 1-methoxycarbonyl-1,3-butadiene-1,4-diyl group, 1-trifluoro Methoxycarbonyl-1,3-butadiene-1,4-diyl group, 1-acetoxy-1,3-butadiene-1,4-diyl group and 1-trifluoroacetoxy-1,3-butadiene-1,4-diyl Groups.

  Examples of the “C1-C4 chain hydrocarbon group” include a methyl group, an ethyl group, an ethynyl group, a propyl group, an isopropyl group, an allyl group, a propargyl group, a butyl group, an isobutyl group, and a t-butyl group.

Examples of the “C1-C10 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group,
Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group, 5-iodo Pentyl group,
Hexyl group, 6,6,6-trifluorohexyl group, 6-chlorohexyl group,
Heptyl group, 7,7,7-trifluoroheptyl group, 7-chloroheptyl group,
Octyl group, 8,8,8, -trifluorooctyl group, 8-chlorooctyl group,
Nonyl group, 9,9,9-trifluorononyl group, 9-chlorononyl group,
Decyl group, 10,10,10-trifluorodecyl group, 10-chlorodecyl group,
Cyanomethyl group, dicyanomethyl group, 2-cyanoethyl group, 2,2-dicyanoethyl group, 3-cyanopropyl group, 3,3-dicyanopropyl group, 4-cyanobutyl group, 4,4-dicyanobutyl group, 5-cyano Pentyl group, 5,5-dicyanopentyl group,
Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, 2-methoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, 5-methoxypentyl group, 2-ethoxyethyl group, 3-ethoxypropyl group, 4-ethoxybutyl group, 5-ethoxypentyl group, 2-propoxyethyl group, 3-propoxypropyl group, 4-propoxybutyl group, 5- Propoxypentyl group, 2-butoxyethyl group, 3-butoxypropyl group, 4-butoxybutyl group, 5-butoxypentyl group,
Methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group, butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, 2-methylthioethyl group, 3-methylthiopropyl group, 4- Methylthiobutyl group, 5-methylthiopentyl group, 2-ethylthioethyl group, 3-ethylthiopropyl group, 4-ethylthiobutyl group, 5-ethylthiopentyl group, 2-propylthioethyl group, 3-propylthiopropyl group Group, 4-propylthiobutyl group, 5-propylthiopentyl group, 2-butylthioethyl group, 3-butylthiopropyl group, 4-butylthiobutyl group, 5-butylthiopentyl group,
Methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfinylmethyl group, isopropanesulfinylmethyl group, butanesulfinylmethyl group, isobutanesulfinylmethyl group, t-butanesulfinylmethyl group, 2-methanesulfinylethyl group, 3-methanesulfinylpropyl group Group, 4-methanesulfinylbutyl group, 5-methanesulfinylpentyl group, 2-ethanesulfinylethyl group, 3-ethanesulfinylpropyl group, 4-ethanesulfinylbutyl group, 5-ethanesulfinylpentyl group, 2-propanesulfinylethyl group 3-propanesulfinylpropyl group, 4-propanesulfinylbutyl group, 5-propanesulfinylpentyl group, 2-butanesulfinylethyl group, 3-butanesulfy group Rupuropiru group, 4-Bed ethanesulfinyl butyl group, 5- butane sulfinyl point pen butyl group,
Methanesulfonylmethyl group, ethanesulfonylmethyl group, propanesulfonylmethyl group, isopropanesulfonylmethyl group, butanesulfonylmethyl group, isobutanesulfonylmethyl group, t-butanesulfonylmethyl group, 2-methanesulfonylethyl group, 3-methanesulfonylpropyl group Group, 4-methanesulfonylbutyl group, 5-methanesulfonylpentyl group, 2-ethanesulfonylethyl group, 3-ethanesulfonylpropyl group, 4-ethanesulfonylbutyl group, 5-ethanesulfonylpentyl group, 2-propanesulfonylethyl group 3-propanesulfonylpropyl group, 4-propanesulfonylbutyl group, 5-propanesulfonylpentyl group, 2-butanesulfonylethyl group, 3-butanesulfonylpropyl group, 4-butanesulfonylbutyl group And it includes 5-butane sulfonyl pentyl group.

Examples of the “C1-C4 alkoxy group optionally substituted with halogen” include a methoxy group, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a chloromethoxy group, a dichloromethoxy group, a trichloromethoxy group, a bromomethoxy group, Dibromomethoxy group, iodomethoxy group, chlorodifluoromethoxy group,
Ethoxy group, 2-fluoroethoxy group, 2,2,2-trifluoroethoxy group, perfluoroethoxy group, 2-chloroethoxy group, 2,2,2-trichloroethoxy group, 2-bromoethoxy group, 2-iodo An ethoxy group,
Propoxy group, 3-fluoropropoxy group, 3,3,3-trifluoropropoxy group, perfluoropropoxy group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropoxy group, perfluoroisopropoxy group Group, 3-chloropropoxy group, 3,3,3-trichloropropoxy group, 3-bromopropoxy group, 3-iodopropoxy group,
Butoxy group, 4-fluorobutoxy group, 4,4,4-trifluorobutoxy group, perfluorobutoxy group, 4-chlorobutoxy group, 4,4,4-trichlorobutoxy group, 4-bromobutoxy group and 4-iodo A butoxy group is mentioned.

Examples of the “C1-C4 alkylthio group optionally substituted with halogen” include methylthio group, fluoromethylthio group, difluoromethylthio group, trifluoromethylthio group, chloromethylthio group, dichloromethylthio group, trichloromethylthio group, bromomethylthio group, Dibromomethylthio group, iodomethylthio group, chlorodifluoromethylthio group,
Ethylthio group, 2-fluoroethylthio group, 2,2,2-trifluoroethylthio group, perfluoroethylthio group, 2-chloroethylthio group, 2,2,2-trichloroethylthio group, 2-bromoethyl A thio group, a 2-iodoethylthio group,
Propylthio group, 3-fluoropropylthio group, 3,3,3-trifluoropropylthio group, perfluoropropylthio group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropylthio group, Fluoroisopropylthio group, 3-chloropropylthio group, 3,3,3-trichloropropylthio group, 3-bromopropylthio group, 3-iodopropylthio group,
Butylthio group, 4-fluorobutylthio group, 4,4,4-trifluorobutylthio group, perfluorobutylthio group, 4-chlorobutylthio group, 4,4,4-trichlorobutylthio group, 4-bromobutyl A thio group and a 4-iodobutylthio group are mentioned.

Examples of the “C1-C4 alkylsulfinyl group optionally substituted with halogen” include methanesulfinyl group, fluoromethanesulfinyl group, difluoromethanesulfinyl group, trifluoromethanesulfinyl group, chloromethanesulfinyl group, dichloromethanesulfinyl group, trichloromethanesulfinyl group. Group, bromomethanesulfinyl group, dibromomethanesulfinyl group, iodomethanesulfinyl group, chlorodifluoromethanesulfinyl group,
Ethanesulfinyl group, 2-fluoroethanesulfinyl group, 2,2,2-trifluoroethanesulfinyl group, perfluoroethanesulfinyl group, 2-chloroethanesulfinyl group, 2,2,2-trichloroethanesulfinyl group, 2-bromoethanesulfinyl group Group, 2-iodoethanesulfinyl group,
Propanesulfinyl group, 3-fluoropropanesulfinyl group, 3,3,3-trifluoropropanesulfinyl group, perfluoropropanesulfinyl group, isopropanesulfinyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropanesulfinyl group, perfluoroisopropanesulfinyl group, 3-chloropropanesulfinyl group, 3,3,3-trichloropropanesulfinyl group, 3-bromopropanesulfinyl group, 3-iodopropanesulfinyl group,
Butanesulfinyl group, 4-fluorobutanesulfinyl group, 4,4,4-trifluorobutanesulfinyl group, perfluorobutanesulfinyl group, 4-chlorobutanesulfinyl group, 4,4,4-trichlorobutanesulfinyl group, 4-bromo Examples include butanesulfinyl group and 4-iodobutanesulfinyl group.

Examples of the “C1-C4 alkylsulfonyl group optionally substituted with halogen” include methanesulfonyl group, fluoromethanesulfonyl group, difluoromethanesulfonyl group, trifluoromethanesulfonyl group, chloromethanesulfonyl group, dichloromethanesulfonyl group, trichloromethanesulfonyl. Group, bromomethanesulfonyl group, dibromomethanesulfonyl group, iodomethanesulfonyl group, chlorodifluoromethanesulfonyl group,
Ethanesulfonyl group, 2-fluoroethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group, perfluoroethanesulfonyl group, 2-chloroethanesulfonyl group, 2,2,2-trichloroethanesulfonyl group, 2-bromoethanesulfonyl Group, 2-iodoethanesulfonyl group,
Propanesulfonyl group, 3-fluoropropanesulfonyl group, 3,3,3-trifluoropropanesulfonyl group, perfluoropropanesulfonyl group, isopropanesulfonyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropanesulfonyl group, perfluoroisopropanesulfonyl group, 3-chloropropanesulfonyl group, 3,3,3-trichloropropanesulfonyl group, 3-bromopropanesulfonyl group, 3-iodopropanesulfonyl group,
Butanesulfonyl group, 4-fluorobutanesulfonyl group, 4,4,4-trifluorobutanesulfonyl group, perfluorobutanesulfonyl group, 4-chlorobutanesulfonyl group, 4,4,4-trichlorobutanesulfonyl group, 4-bromo A butanesulfonyl group and a 4-iodobutanesulfonyl group are mentioned.

Examples of the “(C1-C4 alkyl) carbonyl group optionally substituted with halogen” include acetyl group, fluoroacetyl group, difluoroacetyl group, trifluoroacetyl group, chloroacetyl group, dichloroacetyl group, trichloroacetyl group, bromo group. Acetyl group, dibromoacetyl group, iodoacetyl group, chlorodifluoroacetyl group,
Propanoyl group, 3-fluoropropanoyl group, 3,3,3-trifluoropropanoyl group, perfluoropropanoyl group, 3-chloropropanoyl group, 3,3,3-trichloropropanoyl group, 3-bromopropanoyl group Noyl group, 3-iodopropanoyl group,
Butanoyl group, 4-fluorobutanoyl group, 4,4,4-trifluorobutanoyl group, perfluorobutanoyl group, 3,3,3,3 ′, 3 ′, 3′-hexafluoroisobutanoyl group, Perfluoroisobutanoyl group, 4-chlorobutanoyl group, 4,4,4-trichlorobutanoyl group, 4-bromobutanoyl group, 4-iodobutanoyl group, isobutanoyl group, 2,2,2,2 ′ , 2 ′, 2′-hexafluoroisobutanoyl group, perfluoroisobutanoyl group,
Pentanoyl group, 5-fluoropentanoyl group, 5,5,5-trifluoropentanoyl group, perfluoropentanoyl group, 5-chloropentanoyl group, 5,5,5-trichloropentanoyl group, 5-bromopenta Examples include a noyl group, a 5-iodopentanoyl group, and a pivaloyl group.

Examples of the “(C1-C4 alkoxy) carbonyl group optionally substituted with halogen” include a methoxycarbonyl group, a fluoromethoxycarbonyl group, a difluoromethoxycarbonyl group, a trifluoromethoxycarbonyl group, a chloromethoxycarbonyl group, and a dichloromethoxycarbonyl group. , Trichloromethoxycarbonyl group, bromomethoxycarbonyl group, dibromomethoxycarbonyl group, iodomethoxycarbonyl group, chlorodifluoromethoxycarbonyl group,
Ethoxycarbonyl group, 2-fluoroethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, perfluoroethoxycarbonyl group, 2-chloroethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, 2-bromo Ethoxycarbonyl group, 2-iodoethoxycarbonyl group,
Propoxycarbonyl group, 3-fluoropropoxycarbonyl group, 3,3,3-trifluoropropoxycarbonyl group, perfluoropropoxycarbonyl group, isopropoxycarbonyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropoxycarbonyl group, perfluoroisopropoxycarbonyl group, 3-chloropropoxycarbonyl group, 3,3,3-trichloropropoxycarbonyl group, 3-bromopropoxycarbonyl group, 3-iodopropoxycarbonyl group,
Butoxycarbonyl group, 4-fluorobutoxycarbonyl group, 4,4,4-trifluorobutoxycarbonyl group, perfluorobutoxycarbonyl group, 4-chlorobutoxycarbonyl group, 4,4,4-trichlorobutoxycarbonyl group, 4-bromo A butoxycarbonyl group, a 4-iodobutoxycarbonyl group, and a t-butoxycarbonyl group are mentioned.

Examples of the “(C1-C4 alkyl) carbonyloxy group optionally substituted with halogen” include, for example, an acetoxy group, a fluoroacetoxy group, a difluoroacetoxy group, a trifluoroacetoxy group, a chloroacetoxy group, a dichloroacetoxy group, and a trichloroacetoxy group Bromoacetoxy group, dibromoacetoxy group, iodoacetoxy group, chlorodifluoroacetoxy group,
Propanoyloxy group, 3-fluoropropanoyloxy group, 3,3,3-trifluoropropanoyloxy group, perfluoropropanoyloxy group, 3-chloropropanoyloxy group, 3,3,3-trichloropropanoyl An oxy group, a 3-bromopropanoyloxy group, a 3-iodopropanoyloxy group,
Butanoyloxy group, 4-fluorobutanoyloxy group, 4,4,4-trifluorobutanoyloxy group, perfluorobutanoyloxy group, isobutanoyloxy group, 3,3,3,3 ′, 3 ′ , 3′-hexafluoroisobutanoyloxy group, perfluoroisobutanoyloxy group, 4-chlorobutanoyloxy group, 4,4,4-trichlorobutanoyloxy group, 4-bromobutanoyloxy group, 4- Iodobutanoyloxy group, pentanoyloxy group, 5-fluoropentanoyloxy group, 5,5,5-trifluoropentanoyloxy group, perfluoropentanoyloxy group, 5-chloropentanoyloxy group, 5,5 , 5-trichloropentanoyloxy group, 5-bromopentanoyloxy group, 5-iodopentanoyloxy group and piva Yloxy group, and the like.

  Examples of the “C1-C5 alkyl group” include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a t-butyl group, and a pentyl group.

Examples of the “C1-C10 chain hydrocarbon group optionally substituted with halogen” include, for example, methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, Bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group and 5-iodo A pentyl group is mentioned.

As an aspect of this invention compound, the following amide compounds are mentioned, for example.
In the formula (1), R ² may be substituted with one or more groups selected from a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, or group D. Represents a C3-C10 cycloalkyl group, a phenyl group optionally substituted with one or more groups selected from group E, a halogen or a cyano group,
Alternatively, when p is 2 or more and two R ² are bonded to adjacent carbons of the benzene ring, the two R ² are bonded and substituted with one or more groups selected from group E. A C2-C5 polymethylene group which may be substituted, a propene-1,3-diyl group which may be substituted with one or more groups selected from group E, and one or more groups selected from group E. An amide compound which is a 1,3-butadiene-1,4-diyl group or a methylenedioxy group;
An amide compound in which R ² is a C1-C5 chain hydrocarbon group or halogen which may be substituted with one or more groups selected from group C in formula (1);
An amide compound represented by formula (1), wherein R ² is a C1-C5 chain hydrocarbon group which may be substituted with halogen or halogen;
An amide compound in which R ² in formula (1) is a methyl group or halogen optionally substituted with halogen;
An amide compound in which R ² is a methyl group or halogen in formula (1);
An amide compound in which R ² is halogen in formula (1);
An amide compound in which R ² is a fluorine atom in formula (1);
An amide compound in which R ² is chlorine in formula (1);
An amide compound in which p is 1 and R ² is a methyl group in formula (1);
An amide compound in which p is 1 and R ² is fluorine in formula (1);
An amide compound in which p is 1 and R ² is chlorine in formula (1);
as well as,
An amide compound represented by the formula (1), wherein p is 2 and two R ² are fluorine and chlorine, respectively.

〔式中、Ｒ²及びｐは前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばテトラヒドロフラン（以下、ＴＨＦと記す場合がある。）、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル（以下、ＭＴＢＥと記す場合がある。）等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド（以下、ＤＭＦと記す場合がある。）等の酸アミド類、ジメチルスルホキシド（以下、ＤＭＳＯと記す場合がある。）等のスルホキシド類及びこれらの混合物が挙げられる。
該反応に用いられる脱水縮合剤としては、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（以下、ＷＳＣと記す。）、ベンゾトリアゾール−１−イルオキシ）トリス（ジメチルアミノ）ホスホニウムヘキサフルオロホスフェート（以下、ＢＯＰ試薬と記す。）及び１，３−ジシクロヘキシルカルボジイミド等が挙げられる。
該反応には化合物（２）１モルに対して、化合物（３）が通常１〜３モルの割合、脱水縮合剤が通常１〜５モルの割合で用いられる。
該反応の反応温度は、通常０〜２００℃の範囲である。該反応の反応時間は通常１〜２４時間の範囲である。
該反応において、ＢＯＰ試薬を使用する場合は、必要に応じて塩基の存在下で反応を行う。かかる塩基としては、例えばトリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
該反応には化合物（２）１モルに対して、塩基が通常１〜１０モルの割合で用いられる。
反応終了後は、反応混合物に水を加えた後、有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 1)
The compound of the present invention or a salt thereof can be produced by reacting the compound (3) or a salt thereof with the compound (2) in the presence of a dehydration condensing agent.

[Wherein, R ² and p represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as tetrahydrofuran (hereinafter sometimes referred to as THF), ethylene glycol dimethyl ether, tert-butyl methyl ether (hereinafter sometimes referred to as MTBE), hexane, Aliphatic hydrocarbons such as heptane and octane, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, Examples thereof include acid amides such as N-dimethylformamide (hereinafter sometimes referred to as DMF), sulfoxides such as dimethyl sulfoxide (hereinafter sometimes referred to as DMSO), and mixtures thereof.
Examples of the dehydrating condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC), benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexa Examples thereof include fluorophosphate (hereinafter referred to as BOP reagent) and 1,3-dicyclohexylcarbodiimide.
In the reaction, with respect to 1 mol of the compound (2), the compound (3) is usually used in a proportion of 1 to 3 mol, and the dehydrating condensing agent is usually used in a proportion of 1 to 5 mol.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
In the reaction, when a BOP reagent is used, the reaction is performed in the presence of a base as necessary. Examples of such bases include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
In the reaction, the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (2).
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

〔式中、Ｒ²及びｐは前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類及びこれらの混合物が挙げられる。
該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
該反応には化合物（４）１モルに対して、化合物（３）が通常１〜３モルの割合、塩基が通常１〜１０モルの割合で用いられる。
該反応の反応温度は通常−２０〜１４０℃の範囲である。該反応の反応時間は通常０．１〜２４時間の範囲である。
反応終了後は、反応混合物を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 2)
The compound of the present invention can be produced by reacting compound (3) or a salt thereof with compound (4) or a salt thereof in the presence of a base.

[Wherein, R ² and p represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
In the reaction, with respect to 1 mol of the compound (4), the compound (3) is usually used in a proportion of 1 to 3 mol, and the base is usually used in a proportion of 1 to 10 mol.
The reaction temperature is usually in the range of -20 to 140 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

〔式中、Ｒ²及びｐは前記と同じ意味を表す。〕 (Production method 3)
The compound of the present invention can be produced, for example, from compound (5) according to the following scheme.

[Wherein, R ² and p represent the same meaning as described above. ]

Step (I-1)
Compound (6) can be produced by reacting compound (5) with compound (3) or a salt thereof in the presence of a dehydration condensing agent.
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
Examples of the dehydrating condensing agent used in the reaction include WSC, BOP reagent, and 1,3-dicyclohexylcarbodiimide.
In the reaction, with respect to 1 mol of the compound (5), the compound (3) is usually used in a proportion of 1 to 3 mol, and the dehydrating condensing agent is usually used in a proportion of 1 to 5 mol.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
In the reaction, when a BOP reagent is used, the reaction is performed in the presence of a base as necessary. Examples of such bases include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
In the reaction, the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (5).
After completion of the reaction, the compound (6) can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. The isolated compound (6) can be further purified by chromatography, recrystallization and the like.

Step (I-2)
The compound of the present invention can be produced by reacting compound (6) with an acid.
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene, sulfoxides such as DMSO, methanol, ethanol, 2-methylethanol and the like. Alcohols, acetones, ketones such as methyl ethyl ketone and methyl isobutyl ketone, water, and mixtures thereof.
Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as trifluoroacetic acid, p-toluenesulfonic acid, and methanesulfonic acid.
In the reaction, the acid is usually used in an amount of 1 mol to excess with respect to 1 mol of the compound (6).
The reaction temperature of the reaction is usually in the range of 0 to 150 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

  The compound of the present invention can form an agriculturally acceptable salt. Such a salt of the compound of the present invention is usually a salt of the compound of the present invention and an acid. Examples of the salt with an acid include inorganic acid salts such as hydrochloride, hydrobromide, and sulfate, and organic acid salts such as methanesulfonate, formate, acetate, and trifluoroacetate.

〔式中、Ｒ²及びｐは前記と同じ意味を表し、ＨＸは酸を表す。〕
該反応は、溶媒の存在下又は溶媒の非存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、水及びこれらの混合物が挙げられる。
該反応に用いられる酸としては、例えば塩酸、臭化水素酸、ヨウ化水素酸、硫酸等の無機酸、酢酸、トリフルオロ酢酸、ギ酸、ｐ−トルエンスルホン酸、メタンスルホン酸等の有機酸が挙げられる。
該反応には本発明化合物１モルに対して、酸が通常１〜１００モルの割合で用いられる。
該反応の反応温度は、通常０〜２００℃の範囲である。該反応の反応時間は通常１〜２４時間の範囲である。
反応終了後は、未反応の酸を除去して本発明化合物と酸との塩を単離することができる。 The salt of this invention compound and an acid can be manufactured by making this invention compound react with an acid.

[Wherein R ² and p represent the same meaning as described above, and HX represents an acid. ]
The reaction is performed in the presence of a solvent or in the absence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, water, and the like. Of the mixture.
Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, and sulfuric acid, and organic acids such as acetic acid, trifluoroacetic acid, formic acid, p-toluenesulfonic acid, and methanesulfonic acid. Can be mentioned.
In the reaction, an acid is usually used at a ratio of 1 to 100 mol with respect to 1 mol of the compound of the present invention.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
After completion of the reaction, the salt of the compound of the present invention and the acid can be isolated by removing the unreacted acid.

  The plant disease control agent of the present invention contains the compound of the present invention or a salt thereof and an inert carrier (solid carrier, liquid carrier or gas carrier). The plant disease control agent of the present invention is further mixed with a surfactant and other formulation adjuvants, wettable powder, granular wettable powder, flowable powder, granules, dry flowable powder, emulsion, aqueous liquid, oil, Formulated into smoking agents, aerosols, microcapsules and the like. These preparations contain the compound of the present invention or a salt thereof in a weight ratio of usually 0.1 to 99%, preferably 0.2 to 90%.

  Examples of the solid support include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, wax clay, bentonite, acid clay, talc), and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon). , Calcium carbonate, hydrated silica) and the like. Examples of the liquid carrier include water, alcohols (eg, methanol, ethanol), ketones (eg, acetone, methyl ethyl ketone), aromatic hydrocarbons (eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene), fat Group hydrocarbons (eg, hexane, cyclohexanone, kerosene), esters (eg, ethyl acetate, butyl acetate), nitriles (eg, acetonitrile, isobutyronitrile), ethers (eg, dioxane, diisopropyl ether), Acid amides (for example, dimethylformamide, dimethylacetamide), halogenated hydrocarbons (for example, dichloroethane, trichloroethylene, carbon tetrachloride) and the like can be mentioned. Examples of the gaseous carrier include dimethyl ether and carbon dioxide.

  Examples of the surfactant include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylene compounds thereof, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.

  Other formulation adjuvants include, for example, fixing agents, dispersants, thickeners, wetting agents, extenders and antioxidants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, Alginic acid), lignin derivatives, bentonite, saccharides, synthetic water-soluble polymers (eg, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4) -Methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, fatty acid or ester thereof, and the like.

The compound of the present invention or a salt thereof is used for controlling plant diseases by applying to plants or soil where plants grow. Examples of the method of applying the compound of the present invention or a salt thereof to the plant or the soil where the plant grows include, for example, a method of spraying foliage on the plant, a method of applying to the soil where the plant is cultivated, and a method of applying to the plant seed. It is done.
In the plant disease control method of the present invention, the plant disease control agent of the present invention is usually used.
In the case where the plant disease control agent of the present invention is used in a method of spraying foliage on a plant or a method of applying to a soil where plants are cultivated, the application amount of the plant disease control agent of the present invention is 1,000 m ^{2 at the} application site. The ratio of the present compound or its salt is usually 1 to 500 g, preferably 2 to 200 g. When the plant disease control agent of the present invention is formulated into an emulsion, wettable powder, suspension, etc., the concentration of the compound of the present invention or a salt thereof is usually 0.0005 to 2% by weight, preferably It is diluted with water so as to be 0.005 to 1% by weight. When the plant disease control agent of the present invention is formulated into a powder, granule or the like, the formulation is applied as it is without dilution.
When used in the method of applying the plant disease control agent of the present invention to plant seeds, the application amount of the plant disease control agent of the present invention is usually 0.001 to 1 kg of the compound of the present invention or a salt thereof per 1 kg of seed. The ratio is 100 g, preferably 0.01 to 50 g.

The plant disease control agent of the present invention can be mixed and / or used in combination with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers or soil conditioners.
Examples of the active ingredient of such a bactericide include the following.

(1) Azole bactericidal active compounds propiconazole, prothioconazole, triadimenol, prochloraz, penconazole, zebolazole, tebuconazole diconazole, bromuconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, metconazole, metconazole ), Tetraconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, triticonazole. (Imazalil), flutriafol, simeconazole, ipconazole, etc .;

(2) Amine bactericidal active compounds fenpropimorph, tridemorph, fenpropidin, spiroxamine and the like;

(3) benzimidazole bactericidal active compounds carbendazim, benomyl, thiabendazole, thiophanate-methyl and the like;

(4) Dicarboximide bactericidal active compound procymidone, iprodione, vinclozolin and the like;

(5) Anilinopyrimidine bactericidal active compounds cyprodinil, pyrimethanil, mepanipyrim and the like;

(6) Phenylpyrrole bactericidal active compound fenpiclonil, fludioxonil and the like;

(7) strobilurin bactericidal active compounds cresoxim-methyl, azoxystrobin, trifloxystrobin, floxastrobin, picoxystrobin (picoxystrobibin) pyraclostrobin, dimoxystrobin, pyribencarb, methinostrobin, oryzatrobin, enestrobin, etc .;

(8) Phenylamide bactericidal active compounds metalaxyl, metalaxyl M or mefenoxam, benalaxyl, benalaxyl M or kiraxyl-ra

(9) Carboxylic acid amide bactericidal active compounds dimethomorph, iprovarialcarb, benchavaricarb-isopropyl, mandipropamide, varifenal

(10) Carboxylic acid bactericidal active compounds carboxin, mepronil, flutolanil, tifluzamide, furamethpyr, boscalid, penthipyrofylpentylpyrpentyl Bixafen,

(11) Other bactericidal active compounds dietophane carb; thiuram; fluazinam; mancozeb; chlorothalonil; captan; diclofluuride; folpette; Flusulfamide; fluorpicolide; focetyl; simoxanil; penclone; tolcrofosmethyl; carpropamide; diclocimet; phenoxanil; tricyclazole; pyroxilone; probenazole; ;I Oxolinic acid; oxytetracycline; streptomycin; basic copper chloride; cupric hydroxide; basic copper sulfate; organic copper;

〔式中、Ｘ¹は水素、またはハロゲンを表し、Ｘ²はメチル基、ジフルオロメチル基、又はトリフルオロメチル基を表し、Ｑは下記のいずれかの基

を表す。〕
で示されるピラゾールカルボキサミド化合物； Formula (8)

[Wherein, X ¹ represents hydrogen or halogen, X ² represents a methyl group, a difluoromethyl group, or a trifluoromethyl group, and Q represents any of the following groups:

Represents. ]
A pyrazole carboxamide compound represented by:

〔式中、Ｘ³はメチル基、ジフルオロメチル基、またはエチル基を表し、Ｘ⁴はメトキシ基、またはメチルアミノ基を表し、Ｘ⁵はフェニル基、２−メチルフェニル基、または２，５−ジメチルフェニル基を表す。〕
で示されるα−アルコキシフェニル酢酸化合物； Formula (9)

[Wherein, X ³ represents a methyl group, a difluoromethyl group or an ethyl group, X ⁴ represents a methoxy group or a methylamino group, X ⁵ represents a phenyl group, a 2-methylphenyl group, or 2,5- Represents a dimethylphenyl group. ]
An α-alkoxyphenylacetic acid compound represented by:

〔式中、Ｘ⁶はメトキシ基、エトキシ基、プロポキシ基、２−プロペニルオキシ基、２−プロピニルオキシ基、３−ブテニルオキシ基、３−ブチニルオキシ基、メチルチオ基、エチルチオ基、または２−プロペニルチオ基を表し、Ｘ⁷は１−メチルエチル基、または１−メチルプロピル基を表し、Ｘ⁸は２−メチルフェニル基、または２，６−ジクロロフェニル基を表す。〕
で示されるピラゾリノン化合物。 Formula (10)

[Wherein, X ⁶ is a methoxy group, an ethoxy group, a propoxy group, a 2-propenyloxy group, a 2-propynyloxy group, a 3-butenyloxy group, a 3-butynyloxy group, a methylthio group, an ethylthio group, or a 2-propenylthio group. X ⁷ represents a 1-methylethyl group or a 1-methylpropyl group, and X ⁸ represents a 2-methylphenyl group or a 2,6-dichlorophenyl group. ]
A pyrazolinone compound represented by:

Examples of the active ingredient of such an insecticide include the following.
(1) Organophosphorus insecticidal active compounds: acephate, aluminum phosphide, butathiofos, cadusafos, chlorethoxyphos, chlorfenvinphos, chlorfenvinphos , Chlorpyrifos-methyl, Cyanophos (CYAP), Diazinon, DCIP (Dichlorodipropionether), Dichlorfenthion (ECP), Dichlorvos (DchloV) Dimethoate, dimethylvinphos, disulfoton, EPN, etion, ethoprofos, etrimfos, fentione: MPP, fenitrothion, EP fothiazate, formothion (formulation), hydrogen phosphide (isofenphos), isoxathion (isoxathion), malathion (mesulfenfos), DM thiothion , Monocrotophos, nared (BRP), oxydeprofos (ESP), parathion, fosarone, phosmet (PMP), pirimiphosentyl (pyrimimiphosentythiophene) ), Quinalphos, phentoate (PAP), profenofos, propopafos, prothiofos, pyrachlorfos, salithion, sulfilos ebupirimfos), temephos (temephos), tetrachlorvinphos bottle phosphite (tetrachlorvinphos), terbufos (terbufos), thiometon (thiometon), trichlorfon (trichlorphon: DEP), vamidothion (vamidothion), folate (phorate), cadusafos (cadusafos), and the like;

(2) Carbamate insecticidal active compounds alaniccarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbofuran, carbosulfane, carbosulfane, carbosulfane Ethiofencarb, fenobucarb, phenothiocarb, phenoxycarb, furathiocarb, isoprocarb (MIPC), metholcarb, MIPC, etolcarb (Methiocarb), NAC, oxamyl (oxamyl), pirimicarb (pirimicarb), propoxur (propoxur: PHC), XMC, thiodicarb (thiodicarb), xylylcarb (xylylcarb), aldicarb (aldicarb) or the like;

(3) Synthetic Pyrethroid Insecticidal Compounds Acrinathrin, Allethrin, Benfluthrin, Beta-Cyfluthrin, Bifenthrin, Cycloprothrin, Cycloprothrin (Cyhalothrin), cypermethrin, deltamethrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, fenvalerate Flunate, flufenprox, flumethrin, fluvalinate, halfenprox, imiprothrin, perthrin, threthrin, pelmethrin Resmethrin, sigma-cypermethrin, silafluofen, tefluthrin, tralomethrin, transfluthrin, transfluthrin, transfluthrin eteramethrin), phenothrin, cyphenothrin, alpha-cypermethrin, zeta-cypermethrin, lambda cithalthrin (lambda-thylmethrin) (Tau-flavinate), 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3-prop-1- Enylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4-methylbenzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2- Methyl-3-prop-1-enylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylate and the like;

(4) Nereistoxin insecticidal active compound cartap, bensultap, thiocyclam, monosultap, bisultap, etc .;

(5) Neonicotinoid insecticidal active compound imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloani, dinotefur, intefurandin

(6) Benzoylurea insecticidal active compound chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucyclolon, flucyclofluron Phenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron, etc.

(7) Phenylpyrazole insecticidal active compounds acetoprole, etiprole, fipronil, vaniliprole, pyriprole, pyrafluprole, etc .;

(8) Bt toxin Live spores and produced crystal toxins derived from Bacillus thuringiensis, and mixtures thereof;

(9) Hydrazine insecticidal active compounds Chromafenozide, halofenozide, methoxyphenozide, tebufenozide and the like;

(10) Organochlorine compounds Aldrin, dieldrin, dienochlor, endosulfan, methoxychlor and the like;

(11) Other insecticidal active ingredients machine oil, nicotine sulfate (nicotine-sulfate);
Avermectin (avermectin-B), bromopropyrate, buprofezin, chlorphenapyr, cyromazine, D-D (1,3-Dichloropropene), D-D (1,3-Dichloropropene) fenazaquin, flupyrazofos, hydroprene, methoprene, indoxacarb, methoxadiazone, milbemyropymetropine, milbemycine Pyridalyl, pyriproxyfen, spinosad, sulfuramide, tolfenpyrad, triazemate, flubendiametic, flubendiamide , Benclothiaz, Calcium cyanamide, Calcium polysulfide, Chlordane, DDT, DSP, flufenerim, flurifammid , Formatenate, metham-ammonium, metham-sodium, methyl bromide, ninototefuran, potassium oleate, protastoleate profibutene, spiromesifen, sulfur, metaflumizone, spirotetramat, pyrifluinole, spinet tram, spinet tram

［式中、
Ｒ₁₀は、Ｍｅ、Ｃｌ、ＢｒまたはＦ、
Ｒ₂₀は、Ｆ、Ｃｌ、Ｂｒ、Ｃ１−Ｃ４ハロアルキル、またはＣ１−Ｃ４ハロアルコキシ、
Ｒ₃₀は、Ｆ、ＣｌまたはＢｒ、
Ｒ₄₀は、Ｈ、１以上のハロゲン；ＣＮ；ＳＭｅ；Ｓ（Ｏ）Ｍｅ；Ｓ（０）₂ＭｅおよびＯＭｅで置換されていてもよいＣ１−Ｃ４アルキル、Ｃ３−Ｃ４アルケニル、Ｃ３−Ｃ４アルキニル、または、Ｃ３−Ｃ５シクロアルキルアルキル、
Ｒ₅₀は、ＨまたはＭｅ、
Ｒ₆₀は、Ｈ、ＦまたはＣｌ、
Ｒ₇₀は、Ｈ、ＦまたはＣｌを表す。］で示される化合物、 Formula (11)

[Where:
R ₁₀ is Me, Cl, Br or F,
R ₂₀ is F, Cl, Br, C1-C4 haloalkyl, or C1-C4 haloalkoxy,
R ₃₀ is F, Cl or Br,
R ₄₀ is H, one or more halogen; CN; SMe; S (O) Me; C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl optionally substituted with S (0) ₂ Me and OMe Or C3-C5 cycloalkylalkyl,
R ₅₀ is H or Me,
R ₆₀ is H, F or Cl,
R ₇₀ represents H, F or Cl. A compound represented by

［式中、Ｘは、Ｃｌ、ＢｒまたはＩを表す。］
で示される化合物。 Formula (12)

[Wherein X represents Cl, Br, or I. ]
A compound represented by

  Examples of the active ingredient of such an acaricide include, for example, acequinocyl, amitraz, benzoximate, bifenate, phenisobromolate, quinomethionate, chinomethionate, chlorobenzilate, CPCBS (chlorfenson), clofentezine, cyflumetofen, quercene, dioxol, etoxazole, fenbutatin phenothiophene Fenpyroximate, fluacrylpyrim, fluproxyfen, penthiridinepirpene, fenpyridine , Tetradiphon, spirodiclofen, spiromesifen, spirotetramat, amidoflumet, cienopyrafene ), And the like.

  Examples of the active ingredient of such a nematicide include DCIP, fostiazate, levamisole hydrochloride, methylisothiocyanate, morantartrate tartrate, and imiciafos.

  Examples of the active ingredient of such a plant growth regulator include ethephon, chlormequat-chloride, mepiquat-chloride, and the like.

  The plant disease control agent of the present invention can be used, for example, in agricultural lands such as fields, paddy fields, lawns, orchards. Examples of the “crop” in which the plant disease control agent of the present invention can be used include the following.

Agricultural crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplant, tomato, pepper, pepper, potato Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, Jatropha, etc.,
Bridegroom,
Foliage plant,
Fruit trees; pears (apples, pears, Japanese pears, quince, quince, etc.), nuclear fruits (peaches, plums, nectarines, ume, sweet cherry, apricots, prunes, etc.), citrus (satsuma mandarin, orange, lemon, lime, grapefruit) ), Nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, oyster, olive, loquat, banana, coffee, Date palm, coconut palm, etc.
Trees other than fruit trees: Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.

  The “crop” includes crops to which traits such as resistance to herbicides, pest resistance, and disease resistance have been imparted by classical breeding methods or genetic recombination techniques.

  Examples of plant diseases in which the compound of the present invention or a salt thereof is effective include plant diseases caused by filamentous fungi, and specific examples include the following plant diseases.

Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuroi);
Wheat diseases: powdery mildew (Erysiphe graminis), red mold (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale), rust (Puccinia striiformis, P. graminis, P. recondita), red snow rot (Micronectriella nivale), Snowy rot granule nuclei (Typhula sp.), Bare scab (Ustilago tritici), Tuna scab (Tilletia caries), Eye rot (Pseudocercosporella herpotrichoides), Leaf blight (Mycosphaerella graminicola), Fu Blight (Stagonospora nodorum), macular disease (Pyrenophora tritici-repentis);
Barley diseases: powdery mildew (Erysiphe graminis), mildew (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale), rust (Puccinia striiformis, P. graminis, P. hordei), naked scab ( Ustilago nuda), cloud disease (Rhynchosporium secalis), reticulum disease (Pyrenophora teres), spot disease (Cochliobolus sativus), leafy leaf disease (Pyrenophora graminea), Rhizoctonia solani (Rhizoctonia solani);
Citrus spot disease (Diaporthe citri), common scab (Elsinoe fawcetti), fruit rot (Penicillium digitatum, P. italicum), phytophthora disease (Phytophthora parasitica, Phytophthora citrophthora);
Monilinia mali, rot (Valsa ceratosperma), powdery mildew (Podosphaera leucotricha), spotted leaf (Alternaria alternata apple pathotype), black rot (Venturia inaequalis), anthracnose (Glomerella cingulata), plague (Phytophtora cactorum);
Pear black spot disease (Venturia nashicola, V. pirina), black spot disease (Alternaria alternata Japanese pear pathotype), red star disease (Gymnosporangium haraeanum);
Peach ash scab (Monilinia fructicola), black scab (Cladosporium carpophilum), Phomopsis sp. (Phomopsis sp.);

Grapes black rot (Elsinoe ampelina), late rot (Glomerella cingulata), powdery mildew (Uncinula necator), rust (Phakopsora ampelopsidis), black lot disease (Guignardia bidwellii), downy mildew (Plasmopara viticola);
Oyster anthracnose (Gloeosporium kaki), deciduous leaf disease (Cercospora kaki, Mycosphaerella nawae);
Colletotrichum lagenarium, powdery mildew (Sphaerotheca fuliginea), vine blight (Mycosphaerella melonis), vine split (Fusarium oxysporum), downy mildew (Pseudoperonospora cubensis), plague (Phytophthora sp.) Seedling blight (Pythium sp.);
Tomato ring disease (Alternaria solani), leaf mold (Cladosporium fulvum), plague (Phytophthora infestans);
Eggplant brown spot (Phomopsis vexans), powdery mildew (Erysiphe cichoracearum);
Brassicaceae vegetable black spot (Alternaria japonica), white spot (Cercosporella brassicae);
Leek rust (Puccinia allii), soybean purpura (Cercospora kikuchii), black scab (Elsinoe glycines), sunspot (Diaporthe phaseolorum var. Sojae), rust (Phakopsora pachyrhizi), stem rot (Phytophthora sojae)
Green Bean Anthracnose (Colletotrichum lindemthianum)
Groundnut black rot (Cercospora personata), brown spot (Cercospora arachidicola), silkworm (Sclerotium rolfsii);
Pea powdery mildew (Erysiphe pisi);
Potato summer plague (Alternaria solani), plague (Phytophthora infestans), scarlet rot (Phytophthora erythroseptica), half body wilt (Verticillium albo-atrum, V. dahliae, V. nigrescens);
Strawberry powdery mildew (Sphaerotheca humuli);
Tea net blast (Exobasidium reticulatum); white spot (Elsinoe leucospila), ring spot (Pestalotiopsis sp.), Anthracnose (Colletotrichum theae-sinensis)
Tobacco red blight (Alternaria longipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), plague (Phytophthora nicotianae);

Sugar beet brown spot (Cercospora beticola), leaf rot (Thanatephorus cucumeris), root rot (Thanatephorus cucumeris), black root (Aphanomyces cochlioides);
Rose scab (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa);
Chrysanthemum brown spot (Septoria chrysanthemi-indici), white rust (Puccinia horiana);
Sunflower downy mildew (Plasmopara halstedii);
Onion white spot blight (Botrytis cinerea, B. byssoidea, B. squamosa), gray rot (Botrytis alli), sclerotia rot (Botrytis squamosa);
Various crops of gray mold (Botrytis cinerea), sclerotia (Sclerotinia sclerotiorum), seedling blight (Pythium aphanidermatum, P. debarianum, P. graminicola, P. irregulare, P. ultimum); Black soot disease (Alternaria brassicicola);
Shirah's dollar spot disease (Sclerotinia homeocarpa), Shiva brown patch disease and large patch disease (Rhizoctonia solani);
Viral diseases of various plants mediated by banana sigatoka disease (Mycosphaerella fijiensis, Mycosphaerella musicola, Pseudocercospora musae); and Polymixa spp. Or Olpidium spp.

  Hereinafter, although this invention is demonstrated in more detail by a manufacture example, a reference manufacture example, a formulation example, a test example, etc., this invention is not limited only to these examples.

  First, the manufacture example of this invention compound is shown.

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．２１ｇ、ＤＭＦ２ｍｌ、トリエチルアミン０．４２ｇ及び２−クロロ−４−フルオロベンジルアミン０．３２ｇの混合物にＢＯＰ試薬０．５３ｇを加え、室温で終夜撹拌した。反応混合物に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た。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、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に付して２−アミノ−Ｎ−（２−クロロ−４−フルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（１）と記す。）０．３１ｇを得た。
¹H-NMR (DMSO-d₆) δ［ppm］:4.40(2H, d, J=5.6Hz), 7.22-7.27(1H, m), 7.34-7.38(1H, m), 7.44-7.47(1H, m), 7.78(2H, brs), 8.90(1H, t, J=5.6Hz) Production Example 1

To a mixture of 0.21 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 ml of DMF, 0.42 g of triethylamine and 0.32 g of 2-chloro-4-fluorobenzylamine, 0.53 g of BOP reagent was added at room temperature. And stirred overnight. 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 water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-4-fluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (1). ) 0.31 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ [ppm]: 4.40 (2H, d, J = 5.6Hz), 7.22-7.27 (1H, m), 7.34-7.38 (1H, m), 7.44-7.47 (1H , m), 7.78 (2H, brs), 8.90 (1H, t, J = 5.6Hz)

窒素雰囲気下にて、ＢＯＰ試薬０．４９ｇ、２−クロロベンジルアミン０．１３ｇ、ＤＭＦ１ｍＬ、トリエチルアミン０．１５ｇの混合物に、窒素雰囲気下かつ氷冷下にて２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．２１ｇを加え、室温で８時間攪拌した。室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、水、飽和食塩水で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−クロロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（２）と記す。）を０．１５ｇ得た。
¹H-NMR (DMSO-d₆) δ［ppm］:4.43(2H, d, J=5.6Hz), 7.28-7.37(3H, m), 7.45(1H, d, J=7.8Hz,), 7.77(2H, brs, ), 8.90(1H, t, J=5.6Hz) Production Example 2

Under a nitrogen atmosphere, a mixture of 0.49 g of BOP reagent, 0.13 g of 2-chlorobenzylamine, 1 mL of DMF, and 0.15 g of triethylamine was added to 2-amino-4-trifluoromethylthiazole under a nitrogen atmosphere and ice cooling. 0.21 g of -5-carboxylic acid was added and stirred at room temperature for 8 hours. The reaction mixture was allowed to stand at room temperature overnight and poured into a saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with water and saturated brine. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained solid was washed with chloroform, and 2-amino-N- (2-chlorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (2)) was 0. .15 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ [ppm]: 4.43 (2H, d, J = 5.6Hz), 7.28-7.37 (3H, m), 7.45 (1H, d, J = 7.8Hz,), 7.77 (2H, brs,), 8.90 (1H, t, J = 5.6Hz)

ＢＯＰ試薬０．７３ｇ、２−メチルベンジルアミン０．２０ｇ、ＤＭＦ１．５ｍＬ、トリエチルアミン０．１７ｇの混合物に、氷冷下にて２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．３２ｇを加え、室温で２．５時間攪拌した。室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、水、飽和食塩水で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−メチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（３）と記す。）を０．４１ｇ得た。
¹H-NMR (DMSO-d₆) δ［ppm］:2.28(3H, s), 4.34(2H, d, J=5.6Hz), 7.14-7.21(4H, m), 7.73(2H, brs), 8.81(1H, t, J=5.6Hz) Production Example 3

A mixture of 0.73 g of BOP reagent, 0.20 g of 2-methylbenzylamine, 1.5 mL of DMF, and 0.17 g of triethylamine was added to 0.32 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid under ice cooling. And stirred at room temperature for 2.5 hours. The reaction mixture was allowed to stand at room temperature overnight and poured into a saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with water and saturated brine. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained solid was washed with chloroform, and 2-amino-N- (2-methylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (3)) was 0. .41 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ [ppm]: 2.28 (3H, s), 4.34 (2H, d, J = 5.6Hz), 7.14-7.21 (4H, m), 7.73 (2H, brs), 8.81 (1H, t, J = 5.6Hz)

ＢＯＰ試薬０．７３ｇ、２−フルオロベンジルアミン０．２１ｇ、ＤＭＦ１．５ｍＬ、トリエチルアミン０．１７ｇの混合物に、氷冷下にて２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．３２ｇを加え、室温で５時間攪拌した。室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、水、飽和食塩水で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−フルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４）と記す。）を０．３８ｇ得た。
¹H-NMR (DMSO-d₆) δ［ppm］:4.40(2H, d, J=5.6Hz), 7.16-7.20(2H, m), 7.30-7.34(2H, m), 7.76(2H, brs), 8.89(1H, t, J=5.6Hz) Production Example 4

A mixture of 0.73 g of BOP reagent, 0.21 g of 2-fluorobenzylamine, 1.5 mL of DMF, and 0.17 g of triethylamine was added to 0.32 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid under ice cooling. And stirred at room temperature for 5 hours. The reaction mixture was allowed to stand at room temperature overnight and poured into a saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with water and saturated brine. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained solid was washed with chloroform, and 2-amino-N- (2-fluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (4)) was 0. .38 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ [ppm]: 4.40 (2H, d, J = 5.6Hz), 7.16-7.20 (2H, m), 7.30-7.34 (2H, m), 7.76 (2H, brs ), 8.89 (1H, t, J = 5.6Hz)

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−メチルベンジルアミン０．２４ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−メチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２９ （３Ｈ， ｓ）， ４．３３ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．０１−７．１０ （３Ｈ， ｍ）， ７．１７−７．２５ （１Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．８７ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 5

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.24 g of 3-methylbenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (3-methylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (5)). 0.49 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.29 (3H, s), 4.33 (2H, d, J = 5.8 Hz), 7.01-7.10 (3H, m), 7.17-7.25 (1H, m), 7.73 (2H, brs), 8.87 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−メチルベンジルアミン０．２４ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−メチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６）と記す。）を０．５１ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２８ （３Ｈ， ｓ）， ４．３１ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．０８−７．１９ （６Ｈ， ｍ）， ８．８７ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 6

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.24 g of 4-methylbenzylamine was added, and 6 hours at room temperature. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (4-methylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (6)). 0.51 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.28 (3H, s), 4.31 (2H, d, J = 6.0 Hz), 7.08-7.19 (6H, m), 8.87 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−トリフルオロメチルベンジルアミン０．３９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−４−トリフルオロメチル−Ｎ−（２−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７）と記す。）を０．５５ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．５５ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．４５−７．５５ （２Ｈ， ｍ）， ７．６４−７．７７ （２Ｈ， ｍ）， ７．８０ （２Ｈ， ｂｒｓ）， ８．９６ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 7

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g and BOP reagent 0.93 g, add 0.39 g of 2-trifluoromethylbenzylamine at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-4-trifluoromethyl-N- (2-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (7)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.55 (2H, d, J = 5.6 Hz), 7.45-7.55 (2H, m), 7.64-7.77 (2H M), 7.80 (2H, brs), 8.96 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−トリフルオロメチルベンジルアミン０．３９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−４−トリフルオロメチル−Ｎ−（３−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（８）と記す。）を０．４２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４６ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．５３−７．６５ （４Ｈ， ｍ）， ７．７７ （２Ｈ， ｂｒｓ）， ９．００ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 8

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g and BOP reagent 0.93 g was added 3-trifluoromethylbenzylamine 0.39 g at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-4-trifluoromethyl-N- (3-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (8)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.46 (2H, d, J = 6.0 Hz), 7.53-7.65 (4H, m), 7.77 (2H, brs), 9.00 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−メトキシベンジルアミン０．３０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−メトキシベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（９）と記す。）を０．３４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ３．８０ （３Ｈ， ｓ）， ４．３３ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ６．８８−６．９５ （１Ｈ， ｍ）， ６．９８ （１Ｈ， ｄ， Ｊ ＝ ８．２ Ｈｚ）， ７．１５ （１Ｈ， ｄ， Ｊ ＝ ７．５ Ｈｚ）， ７．２１−７．２９ （１Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．７０ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 9

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g, and BOP reagent 0.93 g, 0.30 g of 2-methoxybenzylamine was added, and the mixture was at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-methoxybenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (9)). 0.34 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 3.80 (3H, s), 4.33 (2H, d, J = 5.8 Hz), 6.88-6.95 (1H, m), 6.98 (1H, d, J = 8.2 Hz), 7.15 (1H, d, J = 7.5 Hz), 7.21-7.29 (1H, m), 7.73 (2H , Brs), 8.70 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−フルオロベンジルアミン０．２８ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−フルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０）と記す。）を０．４０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３８ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．０１−７．１５ （３Ｈ， ｍ）， ７．３３−７．４３ （１Ｈ， ｍ）， ７．７６ （２Ｈ， ｂｒｓ）， ８．９３ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 10

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.28 g of 3-fluorobenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (3-fluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (10)). 0.40 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (2H, d, J = 5.8 Hz), 7.01-7.15 (3H, m), 7.33-7.43 (1H M), 7.76 (2H, brs), 8.93 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−フルオロベンジルアミン０．２８ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−フルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１１）と記す。）を０．４７ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３４ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．１０−７．２２ （２Ｈ， ｍ）， ７．２４−７．３６ （２Ｈ， ｍ）， ７．７５ （２Ｈ， ｂｒｓ）， ８．９０ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 11

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.28 g of 4-fluorobenzylamine was added, and the mixture was at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (4-fluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (11)). 0.47 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.34 (2H, d, J = 6.0 Hz), 7.10-7.22 (2H, m), 7.24-7.36 (2H , M), 7.75 (2H, brs), 8.90 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４４ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−ニトロベンジルアミン塩酸塩０．４２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−ニトロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１２）と記す。）を０．５１ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．６６ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．４７−７．５９ （２Ｈ， ｍ）， ７．７１−７．７８ （１Ｈ， ｍ）， ７．８０ （２Ｈ， ｂｒｓ）， ８．０１−８．１０ （１Ｈ， ｍ）， ８．９２ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 12

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.44 g, and BOP reagent 0.93 g was added 2-nitrobenzylamine hydrochloride 0.42 g at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-nitrobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (12)). 0.51 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.66 (2H, d, J = 5.6 Hz), 7.47-7.59 (2H, m), 7.71-7.78 (1H M), 7.80 (2H, brs), 8.01-8.10 (1H, m), 8.92 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−トリフルオロメチルベンジルアミン０．３９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−４−トリフルオロメチル−Ｎ−（４−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１３）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４５ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．４９ （２Ｈ， ｄ， Ｊ ＝ ８．０ Ｈｚ）， ７．７１ （２Ｈ， ｄ， Ｊ ＝ ８．２ Ｈｚ）， ７．７８ （２Ｈ， ｂｒｓ）， ８．９８ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 13

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.39 g of 4-trifluoromethylbenzylamine was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-4-trifluoromethyl-N- (4-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (13)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.45 (2H, d, J = 5.8 Hz), 7.49 (2H, d, J = 8.0 Hz), 7.71 (2H, d, J = 8.2 Hz), 7.78 (2H, brs), 8.98 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４４ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−ニトロベンジルアミン塩酸塩０．４２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−ニトロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１４）と記す。）を０．５３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．５０ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．６１−７．６８ （１Ｈ， ｍ）， ７．６９−７．８６ （３Ｈ， ｍ）， ８．０６−８．１７ （２Ｈ， ｍ）， ９．０４ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 14

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.44 g and BOP reagent 0.93 g was added 3-nitrobenzylamine hydrochloride 0.42 g at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (3-nitrobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (14)). 0.53 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.50 (2H, d, J = 5.8 Hz), 7.61-7.68 (1H, m), 7.69-7.86 (3H M), 8.06-8.17 (2H, m), 9.04 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−ｔｅｒｔ−ブチルベンジルアミン０．３６ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−ｔｅｒｔ−ブチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１５）と記す。）を０．１８ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： １．２７ （９Ｈ， ｓ）， ４．３２ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．１４−７．２４ （２Ｈ， ｍ）， ７．３２−７．４０ （２Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．８４ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 15

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g, and BOP reagent 0.93 g was added 0.36 g of 4-tert-butylbenzylamine at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (4-tert-butylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (15)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 1.27 (9H, s), 4.32 (2H, d, J = 5.8 Hz), 7.14-7.24 (2H, m), 7.32-7.40 (2H, m), 7.73 (2H, brs), 8.84 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３，４−ジフルオロベンジルアミン０．３２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３，４−ジフルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１６）と記す。）を０．５３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３５ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．０７−７．１５ （１Ｈ， ｍ）， ７．２５−７．３４ （１Ｈ， ｍ）， ７．３５−７．４６ （１Ｈ， ｍ）， ７．７７ （２Ｈ， ｂｒｓ）， ８．９３ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 16

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, add 0.32 g of 3,4-difluorobenzylamine at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (3,4-difluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (16)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (2H, d, J = 5.8 Hz), 7.07-7.15 (1H, m), 7.25-7.34 (1H , M), 7.35-7.46 (1H, m), 7.77 (2H, brs), 8.93 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３，５−ジフルオロベンジルアミン０．３２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３，５−ジフルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１７）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３９ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ６．９１−７．０３ （２Ｈ， ｍ）， ７．０６−７．１７ （１Ｈ， ｍ）， ７．７９ （２Ｈ， ｂｒｓ）， ８．９６ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 17

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.32 g of 3,5-difluorobenzylamine was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (3,5-difluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (17)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.39 (2H, d, J = 6.0 Hz), 6.91-7.03 (2H, m), 7.06-7.17 (1H M), 7.79 (2H, brs), 8.96 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−クロロベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−クロロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１８）と記す。）を０．５０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３７ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．２１−７．２８ （１Ｈ， ｍ）， ７．２８−７．３４ （２Ｈ， ｍ）， ７．３４−７．４２ （１Ｈ， ｍ）， ７．７７ （２Ｈ， ｂｒｓ）， ８．９４ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 18

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.31 g of 3-chlorobenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (3-chlorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (18)). 0.50 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.37 (2H, d, J = 6.0 Hz), 7.21-7.28 (1H, m), 7.28-7.34 (2H , M), 7.34-7.42 (1H, m), 7.77 (2H, brs), 8.94 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４４ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−ブロモベンジルアミン塩酸塩０．４９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−ブロモベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１９）と記す。）を０．５８ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３６ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．２２−７．３７ （２Ｈ， ｍ）， ７．３９−７．５３ （２Ｈ， ｍ）， ７．７７ （２Ｈ， ｂｒｓ）， ８．９４ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 19

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.44 g of triethylamine and 0.93 g of BOP reagent, 0.49 g of 3-bromobenzylamine hydrochloride was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (3-bromobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (19)). 0.58 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.36 (2H, d, J = 6.0 Hz), 7.22-7.37 (2H, m), 7.39-7.53 (2H M), 7.77 (2H, brs), 8.94 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２，５−ジフルオロベンジルアミン０．３２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２，５−ジフルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２０）と記す。）を０．５０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３９ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．０６−７．１３ （１Ｈ， ｍ）， ７．１３−７．２１ （１Ｈ， ｍ）， ７．２２−７．３０ （１Ｈ， ｍ）， ７．７８ （２Ｈ， ｂｒｓ）， ８．９３ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 20

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g and BOP reagent 0.93 g was added 0.35 g of 2,5-difluorobenzylamine at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (2,5-difluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (20)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.39 (2H, d, J = 5.8 Hz), 7.06-7.13 (1H, m), 7.13-7.21 (1H M), 7.2-2.30 (1H, m), 7.78 (2H, brs), 8.93 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２，４−ジフルオロベンジルアミン０．３２ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２，４−ジフルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２１）と記す。）を０．４６ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３６ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．０３−７．１４ （１Ｈ， ｍ）， ７．１７−７．２９ （１Ｈ， ｍ）， ７．３１−７．４２ （１Ｈ， ｍ）， ７．７６ （２Ｈ， ｂｒｓ）， ８．８９ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 21

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g, and BOP reagent 0.93 g was added 0.34 g of 2,4-difluorobenzylamine at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (2,4-difluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (21)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.36 (2H, d, J = 5.8 Hz), 7.03-7.14 (1H, m), 7.17-7.29 (1H , M), 7.31-7.42 (1H, m), 7.76 (2H, brs), 8.89 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−フルオロ−４−メチルベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−フルオロ−４−メチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２２）と記す。）を０．４３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２９ （３Ｈ， ｓ）， ４．３５ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ６．８９−７．０７ （２Ｈ， ｍ）， ７．１３−７．２８ （１Ｈ， ｍ）， ７．７４ （２Ｈ， ｂｒｓ）， ８．８４ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 22

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.31 g of 2-fluoro-4-methylbenzylamine was added, Stir at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (2-fluoro-4-methylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (22)). 0.43 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.29 (3H, s), 4.35 (2H, d, J = 5.8 Hz), 6.89-7.07 (2H, m), 7.13-7.28 (1H, m), 7.74 (2H, brs), 8.84 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−フルオロ−２−メチルベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−フルオロ−２−メチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２３）と記す。）を０．４２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２９ （３Ｈ， ｓ）， ４．３１ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ６．９４−７．１０ （２Ｈ， ｍ）， ７．１６−７．２９ （１Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．８１ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 23

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.21 g and BOP reagent 0.93 g, 0.31 g of 4-fluoro-2-methylbenzylamine was added, Stir at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (4-fluoro-2-methylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (23)). 0.42 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.29 (3H, s), 4.31 (2H, d, J = 5.6 Hz), 6.94-7.10 (2H, m), 7.16-7.29 (1H, m), 7.73 (2H, brs), 8.81 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−エチルベンジルアミン０．３０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−エチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２４）と記す。）を０．４２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： １．１６ （３Ｈ， ｔ， Ｊ ＝ ７．５ Ｈｚ）， ２．５７ （２Ｈ， ｑ， Ｊ ＝ ７．５ Ｈｚ）， ４．３２ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．１２−７．２３ （４Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．８６ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 24

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.30 g of 4-ethylbenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (4-ethylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (24)). 0.42 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 1.16 (3H, t, J = 7.5 Hz), 2.57 (2H, q, J = 7.5 Hz), 4.32 (2H, d, J = 5.8 Hz), 7.12-7.23 (4H, m), 7.73 (2H, brs), 8.86 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−クロロベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−クロロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２５）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３５ （２Ｈ， ｄ， Ｊ ＝ ６．０ Ｈｚ）， ７．２５−７．３５ （２Ｈ， ｍ）， ７．３６−７．４５ （２Ｈ， ｍ）， ７．７６ （２Ｈ， ｂｒｓ）， ８．９１ （１Ｈ， ｔ， Ｊ ＝ ６．０ Ｈｚ）． Production Example 25

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.31 g of 4-chlorobenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (4-chlorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (25)). 0.49 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (2H, d, J = 6.0 Hz), 7.25-7.35 (2H, m), 7.36-7.45 (2H , M), 7.76 (2H, brs), 8.91 (1H, t, J = 6.0 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−アミノベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−アミノベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２６）と記す。）を０．４７ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．１７ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ４．９７ （２Ｈ， ｂｒｓ）， ６．３７−６．７３ （２Ｈ， ｍ）， ６．８１−７．２４ （２Ｈ， ｍ）， ７．６９ （２Ｈ， ｂｒｓ）， ８．７０ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 26

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 4-aminobenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (4-aminobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (26)). 0.47 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.17 (2H, d, J = 5.8 Hz), 4.97 (2H, brs), 6.37-6.73 (2H, m), 6.81-7.24 (2H, m), 7.69 (2H, brs), 8.70 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４４ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−ブロモベンジルアミン塩酸塩０．４９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−ブロモベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２７）と記す。）を０．５４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４０ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．１６−７．２７ （１Ｈ， ｍ）， ７．２７−７．３５ （１Ｈ， ｍ）， ７．３５−７．４５ （１Ｈ， ｍ）， ７．５５−７．６８ （１Ｈ， ｍ）， ７．７８ （２Ｈ， ｂｒｓ）， ８．９１ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 27

To a mixture of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 2 mL, triethylamine 0.44 g, and BOP reagent 0.93 g, add 0.49 g of 2-bromobenzylamine hydrochloride at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-bromobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (27)). 0.54 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.40 (2H, d, J = 5.8 Hz), 7.16-7.27 (1H, m), 7.27-7.35 (1H M), 7.35-7.45 (1H, m), 7.55-7.68 (1H, m), 7.78 (2H, brs), 8.91 (1H, t, J = 5 .8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−フェニルベンジルアミン０．４０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−フェニルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２８）と記す。）を０．５２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３０ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．１７−７．２９ （１Ｈ， ｍ）， ７．２９−７．４３ （６Ｈ， ｍ）， ７．４３−７．５１ （２Ｈ， ｍ）， ７．７２ （２Ｈ， ｂｒｓ）， ８． ８２ （１Ｈ， ｔ， Ｊ ＝ ５．８ Ｈｚ）． Production Example 28

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.40 g of 2-phenylbenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-phenylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (28)). 0.52 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.30 (2H, d, J = 5.8 Hz), 7.17-7.29 (1H, m), 7.29-7.43 (6H , M), 7.43-7.51 (2H, m), 7.72 (2H, brs), 8. 82 (1H, t, J = 5.8 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−エチルベンジルアミン０．３０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−４−トリフルオロメチル−Ｎ−（２−エチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２９）と記す。）を０．３７ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： １．１７ （３Ｈ， ｔ， Ｊ ＝ ７．５ Ｈｚ）， ２．６４ （２Ｈ， ｑ， Ｊ ＝ ７．５ Ｈｚ）， ４．３９ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．１６−７．２２ （４Ｈ， ｍ）， ７．７３ （２Ｈ， ｂｒｓ）， ８．８２ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 29

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.30 g of 2-ethylbenzylamine was added, and the mixture was stirred at room temperature for 6 hours. Stir. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-4-trifluoromethyl-N- (2-ethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (29)). 0.37 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 1.17 (3H, t, J = 7.5 Hz), 2.64 (2H, q, J = 7.5 Hz), 4.39 (2H, d, J = 5.6 Hz), 7.16-7.22 (4H, m), 7.73 (2H, brs), 8.82 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−ブロモ−４−フルオロベンジルアミン０．４５ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−ブロモ−４−フルオロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３０）と記す。）を０．５９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３８ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．２６−７．４１ （２Ｈ， ｍ）， ７．５７−７．６４ （１Ｈ， ｍ）， ７．７９ （２Ｈ， ｂｒｓ）， ８．８１ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 30

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.45 g of 2-bromo-4-fluorobenzylamine was added, Stir at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (2-bromo-4-fluorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (30)). 0.59 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (2H, d, J = 5.6 Hz), 7.26-7.41 (2H, m), 7.57-7.64 (1H , M), 7.79 (2H, brs), 8.81 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２，４−ジクロロベンジルアミン０．３９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２，４−ジクロロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３１）と記す。）を０．６２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４１ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．２９−７．３８ （１Ｈ， ｍ）， ７．４２−７．５０ （１Ｈ， ｍ）， ７．５９−７．６６ （１Ｈ， ｍ）， ７．７９ （２Ｈ， ｂｒｓ）， ８．９１ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 31

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.39 g of 2,4-dichlorobenzylamine was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and described as 2-amino-N- (2,4-dichlorobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (31)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.41 (2H, d, J = 5.6 Hz), 7.29-7.38 (1H, m), 7.42-7.50 (1H M), 7.59-7.66 (1H, m), 7.79 (2H, brs), 8.91 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−ヨードベンジルアミン塩酸塩０．５９ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−ヨードベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３２）と記す。）を０．６２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３２ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ６．９９−７．０９ （１Ｈ， ｍ）， ７．２１−７．３０ （１Ｈ， ｍ）， ７．３６−７．４７ （１Ｈ， ｍ）， ７．７８ （２Ｈ， ｂｒｓ）， ７．８４−７．９２ （１Ｈ， ｍ）， ８．９０ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 32

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.59 g of 2-iodobenzylamine hydrochloride was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-iodobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (32)). 0.62 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.32 (2H, d, J = 5.6 Hz), 6.99-7.09 (1H, m), 7.21-7.30 (1H M), 7.36-7.47 (1H, m), 7.78 (2H, brs), 7.84-7.92 (1H, m), 8.90 (1H, t, J = 5 .6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２，５−ジメチルベンジルアミン０．３０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２，５−ジメチルベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３３）と記す。）を０．５３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２２ （３Ｈ， ｓ）， ２．２４ （３Ｈ， ｓ）， ４．３０ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ６．９６−７．０６ （３Ｈ， ｍ）， ７．７２ （２Ｈ， ｂｒｓ）， ８．７８ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 33

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.30 g of 2,5-dimethylbenzylamine was added at room temperature. Stir for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (2,5-dimethylbenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (33)). ) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.22 (3H, s), 2.24 (3H, s), 4.30 (2H, d, J = 5.6 Hz), 6.96- 7.06 (3H, m), 7.72 (2H, brs), 8.78 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−フルオロ−２−ヨードベンジルアミン塩酸塩０．６３ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−フルオロ−２−ヨードベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３４）と記す。）を０．７４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３１ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．１５−７．４０ （２Ｈ， ｍ）， ７．６７−７．９１ （３Ｈ， ｍ）， ８．８８ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 34

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.63 g of 4-fluoro-2-iodobenzylamine hydrochloride was added. The mixture was further stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (4-fluoro-2-iodobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (34)). 0.74 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.31 (2H, d, J = 5.6 Hz), 7.15-7.40 (2H, m), 7.67-7.91 (3H , M), 8.88 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−フルオロ−２−ニトロベンジルアミン塩酸塩０．３５ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、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で精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−フルオロ−２−ニトロベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３５）と記す。）を０．４５ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．６２ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．５４−７．６１ （１Ｈ， ｍ）， ７．６３−７．７２ （１Ｈ， ｍ）， ７．８０ （２Ｈ， ｂｒｓ）， ７．９４−８．０２ （１Ｈ， ｍ）， ８．９１ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 35

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.35 g of 4-fluoro-2-nitrobenzylamine hydrochloride was added. The mixture was further stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (4-fluoro-2-nitrobenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (35)). 0.45 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.62 (2H, d, J = 5.6 Hz), 7.54-7.61 (1H, m), 7.63-7.72 (1H M), 7.80 (2H, brs), 7.94-8.02 (1H, m), 8.91 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３−フルオロ−２−メチルベンジルアミン０．２８ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（３−フルオロ−２−メチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（３６）と記す。）を０．４０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．１８ （３Ｈ， ｄ， Ｊ ＝ ２．０ Ｈｚ）， ４．３７ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．０３−７．０９ （２Ｈ， ｍ）， ７．２０ （１Ｈ， ｄｄ， Ｊ ＝ １３．９， ７．８ Ｈｚ）， ７．７５ （２Ｈ， ｓ）， ８．８６ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 36

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 3-fluoro-2-methylbenzylamine 0.28 g were mixed. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-fluoro-2-methylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 36) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.18 (3H, d, J = 2.0 Hz), 4.37 (2H, d, J = 5.6 Hz), 7.03-7. 09 (2H, m), 7.20 (1H, dd, J = 13.9, 7.8 Hz), 7.75 (2H, s), 8.86 (1H, t, J = 5.6 Hz) ).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および５−フルオロ−２−メチルベンジルアミン０．２８ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（５−フルオロ−２−メチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（３７）と記す。）を０．３８ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２５ （３Ｈ， ｓ）， ４．３３ （２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ６．９４−７．０２ （２Ｈ， ｍ）， ７．１８−７．２３ （１Ｈ， ｍ）， ７．７７ （２Ｈ， ｓ）， ８．８９ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 37

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 5-fluoro-2-methylbenzylamine 0.28 g were mixed, The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (5-fluoro-2-methylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 37).) Was obtained in an amount of 0.38 g.
¹ H-NMR (DMSO-d ₆ ) δ: 2.25 (3H, s), 4.33 (2H, d, J = 5.9 Hz), 6.94-7.02 (2H, m), 7.18-7.23 (1H, m), 7.77 (2H, s), 8.89 (1H, t, J = 5.9 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および４−フルオロ−２−トリフルオロメチルベンジルアミン０．３９ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（４−フルオロ−２−トリフルオロメチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（３８）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．５１ （２Ｈ， ｄ， Ｊ ＝ ５．４ Ｈｚ）， ７．５０−７．６５ （３Ｈ， ｍ）， ７．８０ （２Ｈ， ｓ）， ８．９７ （１Ｈ， ｔ， Ｊ ＝ ５．４ Ｈｚ）． Production Example 38

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 4-fluoro-2-trifluoromethylbenzylamine 0.39 g were mixed. The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-fluoro-2-trifluoromethylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.49 g of compound (38) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.51 (2H, d, J = 5.4 Hz), 7.50-7.65 (3H, m), 7.80 (2H, s), 8.97 (1H, t, J = 5.4 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−５−ニトロベンジルアミン塩酸塩０．４５ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−クロロ−５−ニトロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（３９）と記す。）を０．４０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．５２ （２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ７．７９ （１Ｈ， ｄ， Ｊ ＝ ８．８ Ｈｚ）， ７．８４ （２Ｈ， ｓ）， ８．１５−８．２０ （２Ｈ， ｍ）， ９．１１ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 39

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-chloro-5-nitrobenzylamine hydrochloride 0.45 g were mixed. The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-5-nitrobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 39)) was obtained in an amount of 0.40 g.
¹ H-NMR (DMSO-d ₆ ) δ: 4.52 (2H, d, J = 5.9 Hz), 7.79 (1H, d, J = 8.8 Hz), 7.84 (2H, s), 8.15-8.20 (2H, m), 9.11 (1H, t, J = 5.9 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−５−フルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−４−トリフルオロメチル−Ｎ−（２−クロロ−５−フルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（４０）と記す。）を０．４３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４１ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．１０ （１Ｈ， ｄｄ， Ｊ ＝ ９．６， ３．０ Ｈｚ）， ７．１７−７．２２ （１Ｈ， ｍ）， ７．５２ （１Ｈ， ｄｄ， Ｊ ＝ ８．８， ５．１ Ｈｚ）， ７．８０ （２Ｈ， ｓ）， ８．９５ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 40

0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.32 g of 2-chloro-5-fluorobenzylamine were mixed. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-trifluoromethyl-N- (2-chloro-5-fluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 40).) Was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.41 (2H, d, J = 5.6 Hz), 7.10 (1H, dd, J = 9.6, 3.0 Hz), 7. 17-7.22 (1H, m), 7.52 (1H, dd, J = 8.8, 5.1 Hz), 7.80 (2H, s), 8.95 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−３−フルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−クロロ−３−フルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４１）と記す。）を０．１４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４６ （２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ７．１７ （１Ｈ， ｄ， Ｊ ＝ ７．１ Ｈｚ）， ７．３１−７．４３ （２Ｈ， ｍ）， ７．７９ （２Ｈ， ｓ）， ８．９５ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 41

0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.32 g of 2-chloro-3-fluorobenzylamine were mixed. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-3-fluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 41)) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.46 (2H, d, J = 5.9 Hz), 7.17 (1H, d, J = 7.1 Hz), 7.31-7. 43 (2H, m), 7.79 (2H, s), 8.95 (1H, t, J = 5.9 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−５−フルオロベンジルアミン塩酸塩０．４８ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−ブロモ−５−フルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４２）と記す。）を０．４５ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３８ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．０６−７．１６ （２Ｈ， ｍ）， ７．６７ （１Ｈ， ｄｄ， Ｊ ＝ ８．８， ５．４ Ｈｚ）， ７．７９ （２Ｈ， ｓ）， ８．９５ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 42

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-bromo-5-fluorobenzylamine hydrochloride 0.48 g were mixed. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-5-fluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 42) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (2H, d, J = 5.6 Hz), 7.06-7.16 (2H, m), 7.67 (1H, dd, J = 8.8, 5.4 Hz), 7.79 (2H, s), 8.95 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３，４，５−トリフルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（３，４，５−トリフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４３）と記す。）を０．３４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３５ （２Ｈ， ｄ， Ｊ ＝ ６．１ Ｈｚ）， ７．１７−７．２２ （２Ｈ， ｍ）， ７．８０ （２Ｈ， ｓ）， ８．９５ （１Ｈ， ｔ， Ｊ ＝ ６．１ Ｈｚ）． Production Example 43

Mixing 0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.24 g triethylamine, 1.06 g BOP reagent, and 0.32 g 3,4,5-trifluorobenzylamine, The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4,5-trifluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.34 g of (43) is obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (2H, d, J = 6.1 Hz), 7.17-7.22 (2H, m), 7.80 (2H, s), 8.95 (1H, t, J = 6.1 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２，４，５−トリフルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２，４，５−トリフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４４）と記す。）を０．４５ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３５ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．３２−７．３９ （１Ｈ， ｍ）， ７．５２−７．５９ （１Ｈ， ｍ）， ７．７８ （２Ｈ， ｓ）， ８．９２ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 44

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 2,4,5-trifluorobenzylamine 0.32 g were mixed, The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,4,5-trifluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.45 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (2H, d, J = 5.6 Hz), 7.32-7.39 (1H, m), 7.52-759 (1H , M), 7.78 (2H, s), 8.92 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２，３，５−トリフルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２，３，５−トリフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４５）と記す。）を０．３４ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４３ （２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ６．９５−７．００ （１Ｈ， ｍ）， ７．４２−７．５０ （１Ｈ， ｍ）， ７．８０ （２Ｈ， ｓ）， ８．９７ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 45

Mixing 0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.24 g triethylamine, 1.06 g BOP reagent, and 0.32 g 2,3,5-trifluorobenzylamine, The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,3,5-trifluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.34 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.43 (2H, d, J = 5.9 Hz), 6.95-7.00 (1H, m), 7.42-7.50 (1H M), 7.80 (2H, s), 8.97 (1H, t, J = 5.9 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−４，５−ジフルオロベンジルアミン塩酸塩０．４３ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−クロロ−４，５−ジフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４６）と記す。）を０．５２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３８ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．３４ （１Ｈ， ｄｄ， Ｊ ＝ １１．５， ８．５ Ｈｚ）， ７．７６ （１Ｈ， ｄｄ， Ｊ ＝ １０．４， ７．４ Ｈｚ）， ７．８０ （２Ｈ， ｓ）， ８．９４ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 46

0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.49 g triethylamine, 1.06 g BOP reagent, and 0.43 g 2-chloro-4,5-difluorobenzylamine hydrochloride Mix and stir the mixture for 1 hour at room temperature. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-4,5-difluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.52 g of compound (46) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (2H, d, J = 5.6 Hz), 7.34 (1H, dd, J = 11.5, 8.5 Hz), 7. 76 (1H, dd, J = 10.4, 7.4 Hz), 7.80 (2H, s), 8.94 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．７１ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−４，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−ブロモ−４，５−ジフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４７）と記す。）を０．５２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３５ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．３２ （１Ｈ， ｄｄ， Ｊ ＝ １１．６， ８．４ Ｈｚ）， ７．７９ （２Ｈ， ｓ）， ７．８８ （１Ｈ， ｄｄ， Ｊ ＝ １０．２， ７．６ Ｈｚ）， ８．９４ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 47

0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.71 g triethylamine, 1.06 g BOP reagent, and 0.52 g 2-bromo-4,5-difluorobenzylamine hydrochloride Mix and stir the mixture for 1 hour at room temperature. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-4,5-difluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.52 g of compound (47) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.35 (2H, d, J = 5.6 Hz), 7.32 (1H, dd, J = 11.6, 8.4 Hz), 7. 79 (2H, s), 7.88 (1H, dd, J = 10.2, 7.6 Hz), 8.94 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３，４−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（３，４−ジフルオロ−２−メチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４８）と記す。）を０．２１ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２４ （３Ｈ， ｓ）， ４．３４ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．０４−７．０８ （１Ｈ， ｍ）， ７．２０−７．２７ （１Ｈ， ｍ）， ７．７５ （２Ｈ， ｓ）， ８．８５ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 48

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 3,4-difluoro-2-methylbenzylamine 0.31 g were mixed. The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4-difluoro-2-methylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.21 g of compound (48) is obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.24 (3H, s), 4.34 (2H, d, J = 5.6 Hz), 7.04-7.08 (1H, m), 7.20-7.27 (1H, m), 7.75 (2H, s), 8.85 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−ブロモ−３，５−ジフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（４９）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４３ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ６．９９ （１Ｈ， ｄ， Ｊ ＝ ９．５ Ｈｚ）， ７．４０−７．４６ （１Ｈ， ｍ）， ７．８１ （２Ｈ， ｓ）， ８．９８ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 49

0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.49 g triethylamine, 1.06 g BOP reagent, and 0.52 g 2-bromo-3,5-difluorobenzylamine hydrochloride Mix and stir the mixture for 1 hour at room temperature. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,5-difluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.49 g of compound (49) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.43 (2H, d, J = 5.6 Hz), 6.99 (1H, d, J = 9.5 Hz), 7.40-7. 46 (1H, m), 7.81 (2H, s), 8.98 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．５１ｇ、ＢＯＰ試薬１．０６ｇ、および４−フェニルベンジルアミン０．３７ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（４−フェニルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（５０）と記す。）を０．２０ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４１ （２Ｈ， ｄ， Ｊ ＝ ６．１ Ｈｚ）， ７．３４−７．３８ （３Ｈ， ｍ）， ７．４３−７．４８ （２Ｈ， ｍ）， ７．６２−７．６７ （４Ｈ， ｍ）， ７．７５ （２Ｈ， ｓ）， ８．９３ （１Ｈ， ｔ， Ｊ ＝ ６．１ Ｈｚ）． Production Example 50

0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.51 g of triethylamine, 1.06 g of BOP reagent, and 0.37 g of 4-phenylbenzylamine were mixed, and the mixture was mixed at room temperature. Stir for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-phenylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (50)). 0.20 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.41 (2H, d, J = 6.1 Hz), 7.34-7.38 (3H, m), 7.43-7.48 (2H M), 7.62-7.67 (4H, m), 7.75 (2H, s), 8.93 (1H, t, J = 6.1 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および４−トリフルオロメトキシベンジルアミン０．３８ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（４−トリフルオロメトキシベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（５１）と記す。）を０．５７ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．３８ （２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ７．３４ （２Ｈ， ｄ， Ｊ ＝ ８．３ Ｈｚ）， ７．３９ （２Ｈ， ｄ， Ｊ ＝ ８．３ Ｈｚ）， ７．７７ （２Ｈ， ｓ）， ８．９３ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 51

0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.38 g of 4-trifluoromethoxybenzylamine were mixed, and the mixture was mixed. Stir at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-trifluoromethoxybenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (51)). 0.57 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.38 (2H, d, J = 5.9 Hz), 7.34 (2H, d, J = 8.3 Hz), 7.39 (2H, d, J = 8.3 Hz), 7.77 (2H, s), 8.93 (1H, t, J = 5.9 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３，４，５−トリフルオロ−２−メチルベンジルアミン０．３５ｇを混合し、その混合物を室温で７時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（３，４，５−トリフルオロ−２−メチルベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（５２）と記す。）を０．４８ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２０ （３Ｈ， ｓ）， ４．３４ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．０５−７．１１ （１Ｈ， ｍ）， ７．７８ （２Ｈ， ｓ）， ８．８９ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 52

0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.24 g triethylamine, 1.06 g BOP reagent, and 0.35 g 3,4,5-trifluoro-2-methylbenzylamine And the mixture was stirred at room temperature for 7 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4,5-trifluoro-2-methylbenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as “amide”). And 0.48 g of the present compound (52).
¹ H-NMR (DMSO-d ₆ ) δ: 2.20 (3H, s), 4.34 (2H, d, J = 5.6 Hz), 7.05-7.11 (1H, m), 7.78 (2H, s), 8.89 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−３，４，５−トリフルオロベンジルアミン塩酸塩０．５５ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２−ブロモ−３，４，５−トリフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（５３）と記す。）を０．６３ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４０ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．２１−７．２７ （１Ｈ， ｍ）， ７．８２ （２Ｈ， ｓ）， ８．９６ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 53

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-bromo-3,4,5-trifluorobenzylamine hydrochloride 0 0.55 g was mixed and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,4,5-trifluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as “amide”). And 0.63 g of the present compound (53).
¹ H-NMR (DMSO-d ₆ ) δ: 4.40 (2H, d, J = 5.6 Hz), 7.21-7.27 (1H, m), 7.82 (2H, s), 8.96 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２，３，４，５−テトラフルオロベンジルアミン塩酸塩０．４３ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（２，３，４，５−テトラフルオロベンジル）−４−トリフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（５４）と記す。）を０．４９ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４１ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．２２−７．２９ （１Ｈ， ｍ）， ７．８０ （２Ｈ， ｓ）， ８．９４ （１Ｈ， ｔ， Ｊ ＝ ５．６ Ｈｚ）． Production Example 54

0.42 g 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.49 g triethylamine, 1.06 g BOP reagent, and 0.43 g 2,3,4,5-tetrafluorobenzylamine hydrochloride And the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,3,4,5-tetrafluorobenzyl) -4-trifluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as “this”). 0.49 g of Inventive Compound (54) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.41 (2H, d, J = 5.6 Hz), 7.22-7.29 (1H, m), 7.80 (2H, s), 8.94 (1H, t, J = 5.6 Hz).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および４，５−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−４−トリフルオロメチル−Ｎ−（４，５−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（５５）と記す。）を０．４２ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ２．２５ （３Ｈ， ｓ）， ４．２９ （２Ｈ， ｄ， Ｊ ＝ ５．６ Ｈｚ）， ７．１６ （１Ｈ， ｄｄ， Ｊ ＝ １１．８， ８．４ Ｈｚ）， ７．２７ （１Ｈ， ｄｄ， Ｊ ＝ １１．６， ８．４ Ｈｚ）， ７．７６ （２Ｈ， ｓ）， ８．８６ （１Ｈ， ｔ， Ｊ ＝ ５．５ Ｈｚ）． Production Example 55

2-amino-4-trifluoromethylthiazole-5-carboxylic acid 0.42 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 4,5-difluoro-2-methylbenzylamine 0.31 g were mixed. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-trifluoromethyl-N- (4,5-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). 0.42g of compound (55) was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 2.25 (3H, s), 4.29 (2H, d, J = 5.6 Hz), 7.16 (1H, dd, J = 11.8) , 8.4 Hz), 7.27 (1H, dd, J = 11.6, 8.4 Hz), 7.76 (2H, s), 8.86 (1H, t, J = 5.5 Hz). ).

２−アミノ−４−トリフルオロメチルチアゾール−５−カルボン酸０．４２ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−トリフルオロメトキシベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、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に付して、２−アミノ−Ｎ−（３−トリフルオロメトキシベンジル）−４−トリフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５６）と記す。）を０．２８ｇ得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．４０ （２Ｈ， ｄ， Ｊ ＝ ５．８ Ｈｚ）， ７．２２−７．３０ （３Ｈ， ｍ）， ７．４６ （１Ｈ， ｔ， Ｊ ＝ ７．７ Ｈｚ）， ７．７６ （２Ｈ， ｓ）， ８．９８ （１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）． Production Example 56

To a mixture of 0.42 g of 2-amino-4-trifluoromethylthiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.38 g of 3-trifluoromethoxybenzylamine was added at room temperature. Stir for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-trifluoromethoxybenzyl) -4-trifluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (56). 0.28 g was obtained.
¹ H-NMR (DMSO-d ₆ ) δ: 4.40 (2H, d, J = 5.8 Hz), 7.22-7.30 (3H, m), 7.46 (1H, t, J = 7.7 Hz), 7.76 (2H, s), 8.98 (1H, t, J = 5.9 Hz).

２−ブロモ−４，５−ジフルオロベンジルアジド３．３５ｇのＴＨＦ溶液（４０ｍＬ）に、氷冷下にてトリフェニルホスフィン３．９１ｇを加えた。その混合物を室温で６時間攪拌した。反応混合物を終夜室温で放置し、ここにアンモニア水（２８％）を１５ｍＬ加えた。その混合物を室温で３時間攪拌した後、４Ｎ水酸化ナトリウム水溶液４６．４ｍＬを加えた。その混合物を室温で１時間攪拌した後、１Ｎ塩酸を８７．５ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸１．５ｍＬを加え、トルエンを加えて水を共沸させた。残渣をＴＨＦで洗浄し、得られた結晶を乾燥して、２−ブロモ−４，５−ジフルオロベンジルアミン塩酸塩１．９４ｇを得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．１０ （２Ｈ， ｓ） ， ７．８２（１Ｈ， ｄｄ， Ｊ₁ ＝ １１．７ Ｈｚ， Ｊ₂ ＝ ８．３ Ｈｚ）， ７．９３（１Ｈ， ｄｄ， Ｊ₁ ＝ １０．１ Ｈｚ， Ｊ₂ ＝ ７．７ Ｈｚ）， ８．５５（３Ｈ， ｂｒｓ） Reference production examples are shown below.
Reference production example 1

To a THF solution (40 mL) of 2.35 g of 2-bromo-4,5-difluorobenzyl azide, 3.91 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 6 hours. The reaction mixture was left overnight at room temperature, and 15 mL of aqueous ammonia (28%) was added thereto. The mixture was stirred at room temperature for 3 hours, and 46.4 mL of 4N aqueous sodium hydroxide solution was added. The mixture was stirred at room temperature for 1 hour, and 87.5 mL of 1N hydrochloric acid was added. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Under ice-cooling, 1.5 mL of concentrated hydrochloric acid was added, and toluene was added to azeotrope water. The residue was washed with THF, and the obtained crystal was dried to obtain 1.94 g of 2-bromo-4,5-difluorobenzylamine hydrochloride.
¹ H-NMR (DMSO-d ₆ ) δ: 4.10 (2H, s), 7.82 (1H, dd, J ₁ = 11.7 Hz, J ₂ = 8.3 Hz), 7.93 ( 1H, dd, J ₁ = 10.1 Hz, J ₂ = 7.7 Hz), 8.55 (3H, brs)

２−ブロモ−４，５−ジフルオロベンジルクロリド３．２８ｇのＤＭＳＯ溶液（３０ｍＬ）にアジ化ナトリウム１．０８ｇを加えた。その混合物を室温で１．５時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水５０ｍＬに注加した。ｔ−ブチルメチルエーテルで抽出し、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−ブロモ−４，５−ジフルオロベンジルアジド３．３５ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．４５ （２Ｈ， ｓ） ， ７．２８（１Ｈ， ｄｄ， Ｊ₁ ＝ １０．０ Ｈｚ， Ｊ₂ ＝ ７．６ Ｈｚ）， ７．４４（１Ｈ， ｄｄ， Ｊ₁ ＝ ９．５ Ｈｚ， Ｊ₂ ＝ ７．３ Ｈｚ） Reference production example 2

To a solution of 2-bromo-4,5-difluorobenzyl chloride (3.28 g) in DMSO (30 mL) was added 1.08 g of sodium azide. The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was left overnight at room temperature and the reaction mixture was poured into 50 mL of water. The mixture was extracted with t-butyl methyl ether, washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure yielded 3.35 g of 2-bromo-4,5-difluorobenzyl azide.
¹ H-NMR (CDCl ₃ ) δ: 4.45 (2H, s), 7.28 (1H, dd, J ₁ = 10.0 Hz, J ₂ = 7.6 Hz), 7.44 (1H, dd, J ₁ = 9.5 Hz, J ₂ = 7.3 Hz)

２−ブロモ−４，５−ジフルオロベンジルアルコール４．０２ｇのトルエン溶液（１５ｍＬ）に塩化チオニル１．４５ｍＬとＤＭＦ２滴を加えた。その混合物を８０℃にて１時間攪拌した。反応混合物を減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−４，５−ジフルオロベンジルクロリド３．２８ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．６２ （２Ｈ， ｓ） ， ７．３６（１Ｈ， ｄｄ， Ｊ₁ ＝ １０．５ Ｈｚ， Ｊ₂ ＝ ８．１ Ｈｚ）， ７．４３（１Ｈ， ｄｄ， Ｊ₁ ＝ ９．５ Ｈｚ， Ｊ₂ ＝ ７．４ Ｈｚ） Reference production example 3

To a toluene solution (15 mL) of 4.02 g of 2-bromo-4,5-difluorobenzyl alcohol, 1.45 mL of thionyl chloride and 2 drops of DMF were added. The mixture was stirred at 80 ° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 3.28 g of 2-bromo-4,5-difluorobenzyl chloride.
¹ H-NMR (CDCl ₃ ) δ: 4.62 (2H, s), 7.36 (1H, dd, J ₁ = 10.5 Hz, J ₂ = 8.1 Hz), 7.43 (1H, dd, J ₁ = 9.5 Hz, J ₂ = 7.4 Hz)

２−ブロモ−３，５−ジフルオロベンジルアジド６．９０ｇのＴＨＦ溶液（１００ｍＬ）に、氷冷下にてトリフェニルホスフィン７．９１ｇを加えた。その混合物を室温で９時間攪拌した。反応混合物を終夜室温で放置し、アンモニア水（２８％）を３０ｍＬ加えた。室温で３時間攪拌した後、４Ｎ水酸化ナトリウム水溶液９４ｍＬを加えた。室温で１時間攪拌した後、１Ｎ塩酸を１７７ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ１０ｍＬを加えた。氷冷下にて濃塩酸３ｍＬを加え、生じた結晶を濾過により集めた。得られた結晶をＴＨＦで洗浄した後、乾燥して、２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩２．８９ｇを得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．１７ （２Ｈ， ｓ） ， ７．４８−７．５３（２Ｈ， ｍ）， ８．７１（３Ｈ， ｂｒｓ） Reference production example 4

To a THF solution (100 mL) of 6.90 g of 2-bromo-3,5-difluorobenzyl azide, 7.91 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 9 hours. The reaction mixture was left overnight at room temperature, and 30 mL of aqueous ammonia (28%) was added. After stirring at room temperature for 3 hours, 94 mL of 4N aqueous sodium hydroxide solution was added. After stirring at room temperature for 1 hour, 177 mL of 1N hydrochloric acid was added. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 10 mL of THF was added to the residue. Under ice-cooling, 3 mL of concentrated hydrochloric acid was added, and the resulting crystals were collected by filtration. The obtained crystals were washed with THF and dried to obtain 2.89 g of 2-bromo-3,5-difluorobenzylamine hydrochloride.
¹ H-NMR (DMSO-d ₆ ) δ: 4.17 (2H, s), 7.48-7.53 (2H, m), 8.71 (3H, brs)

２−ブロモ−３，５−ジフルオロベンジルクロリド７．００ｇのＤＭＳＯ溶液（５５ｍＬ）にアジ化ナトリウム２．１８ｇを加えた。その混合物を室温で２．５時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水２００ｍＬに注加した。ｔ−ブチルメチルエーテルで抽出し、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−ブロモ−３，５−ジフルオロベンジルアジド６．９０ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．５２ （２Ｈ， ｓ） ， ６．８７−６．９２（１Ｈ， ｍ）， ７．０２−７．０５（１Ｈ， ｍ） Reference production example 5

2.18 g of sodium azide was added to a DMSO solution (55 mL) of 7.00 g of 2-bromo-3,5-difluorobenzyl chloride. The mixture was stirred at room temperature for 2.5 hours. The reaction mixture was left at room temperature overnight and the reaction mixture was poured into 200 mL of water. The mixture was extracted with t-butyl methyl ether, washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure gave 6.90 g of 2-bromo-3,5-difluorobenzyl azide.
¹ H-NMR (CDCl ₃ ) δ: 4.52 (2H, s), 6.87-6.92 (1H, m), 7.02-7.05 (1H, m)

２−ブロモ−３，５−ジフルオロベンジルアルコール６．１２ｇのトルエン溶液（２００ｍＬ）に塩化チオニル２．４０ｍＬとＤＭＦ４滴を加えた。その混合物を８０℃にて１時間攪拌した。反応混合物を減圧下で濃縮し２−ブロモ−３，５−ジフルオロベンジルクロリド７．００ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．６８ （２Ｈ， ｓ） ， ６．８７−７．１８（２Ｈ， ｍ） Reference production example 6

To a toluene solution (200 mL) of 6.12 g of 2-bromo-3,5-difluorobenzyl alcohol, 2.40 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 80 ° C. for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain 7.00 g of 2-bromo-3,5-difluorobenzyl chloride.
¹ H-NMR (CDCl ₃ ) δ: 4.68 (2H, s), 6.87-7.18 (2H, m)

２−ブロモ−３，５−ジフルオロ安息香酸１９．５１ｇのＴＨＦ溶液（３００ｍＬ）に１，１’−カルボニルジイミダゾール２０．０１ｇを加え、３時間４０分加熱還流した。反応混合物を室温まで放冷し、水素化ホウ素ナトリウム５．０７ｇの水溶液（１６０ｍＬ）に４時間かけて滴下した。水素化ホウ素ナトリウム２．５ｇを追加し、３時間攪拌した後、室温で一晩放置した。反応混合物を濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，５−ジフルオロベンジルアルコール７．４１４ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ２．０１（１Ｈ， ｂｒｓ）， ４．７６（２Ｈ， ｓ）， ６．８４（１Ｈ， ｄｄｄ， Ｊ₁ ＝ ８．３ Ｈｚ， Ｊ₂ ＝ ８．３ Ｈｚ， Ｊ₃ ＝ ２．９ Ｈｚ）， ７．１３−７．１６（１Ｈ， ｍ） Reference production example 7

20.01 g of 1,1′-carbonyldiimidazole was added to a THF solution (300 mL) of 19.51 g of 2-bromo-3,5-difluorobenzoic acid, and the mixture was heated to reflux for 3 hours and 40 minutes. The reaction mixture was allowed to cool to room temperature and dropped into an aqueous solution (160 mL) of 5.07 g of sodium borohydride over 4 hours. After adding 2.5 g of sodium borohydride and stirring for 3 hours, the mixture was allowed to stand overnight at room temperature. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography to obtain 7.414 g of 2-bromo-3,5-difluorobenzyl alcohol.
¹ H-NMR (CDCl ₃ ) δ: 2.01 (1H, brs), 4.76 (2H, s), 6.84 (1H, ddd, J ₁ = 8.3 Hz, J ₂ = 8.3) Hz, J ₃ = 2.9 Hz), 7.13-7.16 (1H, m)

２−ブロモ−３，４，５−トリフルオロベンジルクロリド６．５４ｇのＤＭＳＯ溶液（５５ｍＬ）にアジ化ナトリウム２．１８ｇを加えた。その混合物を室温で３０分間攪拌した。反応混合物を室温で一晩放置した後、反応混合物を水８０ｍＬに注加した。ｔ−ブチルメチルエーテルで抽出した後、水、飽和食塩水の順で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。残渣にＴＨＦ１００ｍＬを加え、氷冷下にてトリフェニルホスフィン７．２７ｇを加え、室温で１．５時間攪拌した。室温で３日間放置した後、アンモニア水（２８％）２８ｍＬを加え、３時間攪拌した。４Ｎ水酸化ナトリウム水溶液９４ｍＬを加え、１時間攪拌した。１Ｎ塩酸を１５０ｍＬ加えた後、反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。飽和食塩水で洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸５ｍＬを加え、トルエンを加えて水を共沸させた。残渣をクロロホルムで洗浄し、得られた結晶を乾燥して、２−ブロモ−３，４，５−トリフルオロベンジルアミン塩酸塩３．３６ｇを得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．１５ （２Ｈ， ｓ） ， ７．７５−７．８０（１Ｈ， ｍ）， ８．６９（３Ｈ， ｂｒｓ） Reference production example 8

2.18 g of sodium azide was added to a DMSO solution (55 mL) of 6.54 g of 2-bromo-3,4,5-trifluorobenzyl chloride. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was left at room temperature overnight and then poured into 80 mL of water. After extraction with t-butyl methyl ether, water and saturated brine were washed in this order. Dried over magnesium sulfate and concentrated under reduced pressure. To the residue was added 100 mL of THF, 7.27 g of triphenylphosphine was added under ice cooling, and the mixture was stirred at room temperature for 1.5 hours. After standing at room temperature for 3 days, 28 mL of aqueous ammonia (28%) was added and stirred for 3 hours. 94 mL of 4N aqueous sodium hydroxide solution was added and stirred for 1 hour. After adding 150 mL of 1N hydrochloric acid, the reaction mixture was allowed to stand, and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with saturated brine and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Under ice-cooling, 5 mL of concentrated hydrochloric acid was added, and toluene was added to azeotrope water. The residue was washed with chloroform, and the obtained crystals were dried to obtain 3.36 g of 2-bromo-3,4,5-trifluorobenzylamine hydrochloride.
¹ H-NMR (DMSO-d ₆ ) δ: 4.15 (2H, s), 7.75-7.80 (1H, m), 8.69 (3H, brs)

２−ブロモ−３，４，５−トリフルオロベンジルアルコール１６．６５ｇのトルエン溶液（２００ｍＬ）に塩化チオニル７．５６ｍＬとＤＭＦ４滴を加えた。その混合物を１１０℃にて３時間攪拌した。反応混合物を減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，４，５−トリフルオロベンジルクロリド６．５３７ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．６４ （２Ｈ， ｓ）， ７．２１−７．２６（１Ｈ， ｍ） Reference production example 9

To a toluene solution (200 mL) of 16.65 g of 2-bromo-3,4,5-trifluorobenzyl alcohol, 7.56 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 110 ° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 6.537 g of 2-bromo-3,4,5-trifluorobenzyl chloride.
¹ H-NMR (CDCl ₃ ) δ: 4.64 (2H, s), 7.21-7.26 (1H, m)

２−ブロモ−３，４，５−トリフルオロ安息香酸１６．９１ｇのトルエン溶液（２００ｍＬ）に塩化チオニル７．２６ｍＬとＤＭＦ４滴を加えた。その混合物を１１０℃で６時間攪拌した。反応混合物を減圧下で濃縮し、残渣をＴＨＦ１５０ｍＬに溶解させた。このＴＨＦ溶液を氷冷した水素化ホウ素ナトリウム４．０９ｇのエタノール溶液（３００ｍＬ）に１．５時間かけて滴下し、その後室温で１時間攪拌した。反応混合物を室温で一晩放置した後、減圧下で濃縮した。残渣に水と酢酸エチルを加え、酢酸エチル層を分取した。水層は酢酸エチルで抽出し、先の酢酸エチル層と合わせた。飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，４，５−トリフルオロベンジルアルコール６．６０３ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ２．０８（１Ｈ， ｔ， Ｊ ＝ ５．９ Ｈｚ）， ４．７２（２Ｈ， ｄ， Ｊ ＝ ５．９ Ｈｚ）， ７．２４−７．２９（１Ｈ， ｍ） Reference production example 10

To a toluene solution (200 mL) of 16.91 g of 2-bromo-3,4,5-trifluorobenzoic acid, 7.26 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 110 ° C. for 6 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 150 mL of THF. This THF solution was added dropwise to ice-cooled sodium borohydride 4.09 g ethanol solution (300 mL) over 1.5 hours, and then stirred at room temperature for 1 hour. The reaction mixture was left at room temperature overnight and then concentrated under reduced pressure. Water and ethyl acetate were added to the residue, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the previous ethyl acetate layer. The extract was washed with saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography to obtain 6.603 g of 2-bromo-3,4,5-trifluorobenzyl alcohol.
¹ H-NMR (CDCl ₃ ) δ: 2.08 (1H, t, J = 5.9 Hz), 4.72 (2H, d, J = 5.9 Hz), 7.24-7.29 ( 1H, m)

２−クロロ−４，５−ジフルオロ−ベンジルアジド２．６３ｇのＴＨＦ溶液（５０ｍＬ）に、氷冷下にてトリフェニルホスフィン３．７２ｇを加えた。その混合物を室温で７．５時間攪拌した。反応混合物を１日間室温で放置し、アンモニア水（２８％）を１４ｍＬ加えた。室温で３．５時間攪拌した後、４Ｎ水酸化ナトリウム水溶液４５ｍＬを加えた。室温で２時間攪拌した後、１Ｎ塩酸を８５ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸１．５ｍＬを加え、生じた結晶を濾過により集めた。得られた結晶をＴＨＦで洗浄した後、乾燥して、２−クロロ−４，５−ジフルオロ−ベンジルアミン塩酸塩１．４１ｇを得た。
¹Ｈ−ＮＭＲ （ＤＭＳＯ−ｄ₆） δ： ４．１０ （２Ｈ， ｓ） ， ７．７９（１Ｈ， ｄｄ， Ｊ₁ ＝ １０．４ Ｈｚ， Ｊ₁ ＝ ７．４ Ｈｚ）， ７．８８（１Ｈ， ｄｄ， Ｊ₁ ＝ １１．５ Ｈｚ， Ｊ₁ ＝ ８．５ Ｈｚ）， ８．７２（３Ｈ， ｂｒｓ） Reference production example 11

To a THF solution (50 mL) of 2.63 g of 2-chloro-4,5-difluoro-benzyl azide, 3.72 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 7.5 hours. The reaction mixture was allowed to stand at room temperature for 1 day, and 14 mL of aqueous ammonia (28%) was added. After stirring at room temperature for 3.5 hours, 45 mL of 4N aqueous sodium hydroxide solution was added. After stirring at room temperature for 2 hours, 85 mL of 1N hydrochloric acid was added. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Concentrated hydrochloric acid (1.5 mL) was added under ice cooling, and the resulting crystals were collected by filtration. The obtained crystals were washed with THF and dried to obtain 1.41 g of 2-chloro-4,5-difluoro-benzylamine hydrochloride.
¹ H-NMR (DMSO-d ₆ ) δ: 4.10 (2H, s), 7.79 (1H, dd, J ₁ = 10.4 Hz, J ₁ = 7.4 Hz), 7.88 ( 1H, dd, J ₁ = 11.5 Hz, J ₁ = 8.5 Hz), 8.72 (3H, brs)

２−クロロ−４，５−ジフルオロ−ベンジルブロミド３．１５ｇのＤＭＳＯ溶液（２５ｍＬ）にアジ化ナトリウム１．０３ｇを加えた。その混合物を室温で１時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水１００ｍＬに注加した。ｔ−ブチルメチルエーテルで抽出し、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−クロロ−４，５−ジフルオロ−ベンジルアジド２．６３ｇを得た。
¹Ｈ−ＮＭＲ （ＣＤＣｌ₃） δ： ４．４６（２Ｈ， ｓ） ， ７．２５−７．２９（２Ｈ， ｍ） Reference production example 12

To a solution (25 mL) of 3.15 g of 2-chloro-4,5-difluoro-benzyl bromide, 1.03 g of sodium azide was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was left at room temperature overnight and the reaction mixture was poured into 100 mL of water. The mixture was extracted with t-butyl methyl ether, washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure gave 2.63 g of 2-chloro-4,5-difluoro-benzyl azide.
¹ H-NMR (CDCl ₃ ) δ: 4.46 (2H, s), 7.25-7.29 (2H, m)

  Next, formulation examples are shown. In addition, a part shows a weight part.

Formulation Example 1
Each wettable powder is obtained by thoroughly grinding and mixing 50 parts of any one of the compounds (1) to (56) of the present invention, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate and 45 parts of synthetic silicon hydroxide. Get.

Formulation Example 2
20 parts of any one of the compounds (1) to (56) of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol. After pulverization, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and stirred to obtain each flowable preparation.

Formulation Example 3
Each powder agent is obtained by pulverizing and mixing well 2 parts of any one of the compounds (1) to (56) of the present invention, 88 parts of kaolin clay and 10 parts of talc.

Formulation Example 4
Each emulsion is obtained by thoroughly mixing 5 parts of any one of the compounds (1) to (56) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene. Get.

Formulation Example 5
After thoroughly mixing 2 parts of any one of the present compounds (1) to (56), 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay, water is added. Kneaded well and granulated and dried to obtain each granule.

Formulation Example 6
10 parts of any one of the compounds (1) to (56) of the present invention; 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water are mixed and pulverized by a wet pulverization method. Thus, each flowable preparation is obtained.

Formulation Example 7
40 parts of any one of the present compounds (1) to (56), 5 parts of propylene glycol (manufactured by Nacalai Tesque), 5 parts of Soprophor FLK (manufactured by Rhodia Nikka), and 0.2 part of anti-form C emulsion (Dow Corning), 0.3 part of Proxel GXL (manufactured by Arch Chemical) and 49.5 parts of ion-exchanged water are mixed to prepare a raw material slurry. 150 parts of glass beads (Φ = 1 mm) are put into 100 parts of the slurry, and pulverized for 2 hours while cooling with cooling water. After grinding, the glass beads are removed by filtration to obtain each flowable formulation.

Formulation Example 8
50 parts of any one of the compounds (1) to (56) of the present invention, 38.5 parts of NN kaolin clay (manufactured by Takehara Chemical Industries), 10 parts of Morwet D425, 1.5 parts of Morwer EFW (Akzo Nobel) And the mixture is pulverized with a jet mill to obtain each powder.

Next, test examples show that the compounds of the present invention are useful for controlling plant diseases.
The control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.

Test example 1
A plastic pot was filled with soil, rice (cultivar; Nipponbare) was sown, and grown in a greenhouse for 20 days. Then, the present compound (5), (8), (9), (15), (16), (17), (18), (19), (22), (23), (24), (25 ) And (51) were each made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed on the foliage so as to adhere well to the rice leaf surface. After spraying, the plants were air-dried and placed for 6 days in contact with rice seedlings (variety: Nihonbare) afflicted with Magnaporthe oryzae at 24 ° C in the daytime and 20 ° C in the nighttime. did. As a result, the present compounds (5), (8), (9), (15), (16), (17), (18), (19), (22), (23), (24), The lesion area in the plant which processed (25) and (51) was 30% or less of the lesion area in an untreated plant.

Test example 2
A plastic pot was filled with soil, seeded with wheat (variety: Shirogane), grown in a greenhouse for 9 days, and then sprinkled with spores of wheat red rust fungus (Puccinia redondita f. Sp. Tritici). After inoculation, it was placed in a dark and humid place at 23 ° C. for 1 day, and then air-dried to obtain a wheat rust-infected seedling. Each of the compounds (29), (41) and (48) of the present invention was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm) so as to adhere well to the leaves of the wheat. The foliage was sprayed on the ground. After spraying, the plants were air-dried and placed under illumination for 6 days, and then the lesion area was examined. As a result, the lesion area on the plant treated with the compounds (29), (41) and (48) of the present invention was 30% or less of the lesion area on the untreated plant.

Test example 3
A plastic pot was filled with soil, seeded with wheat (variety: Apogee), and grown in a greenhouse for 10 days. Each of the compounds (15), (21), (22) and (46) of the present invention was made into a flowable formulation according to Formulation Example 6, and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed to ensure sufficient adhesion. After spraying, the plants were air-dried and spray-inoculated with a water suspension of Septoria tritici spores after 3 or 4 days. After the inoculation, the area was first placed under a high humidity of 18 ° C. for 3 days and further under illumination for 14 to 18 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compounds (15), (21), (22) and (46) of the present invention was 30% or less of the lesion area in the untreated plant.

Test example 4
The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. The above-mentioned pot was spray-inoculated with a water suspension of Pseudoperonospola cubensis zoosporangium, placed at 23 ° C. under high humidity for 1 day, and then air-dried to obtain a cucumber downy mildew-infected seedling. Compound (6), (8), (10), (11), (12), (14), (16), (17), (18), (19), (22), (23) , (25), (30), (35), (36), (37), (38), (40), (42), (45), (46), (47), (48), ( 49), (52), (53) and (55) were each made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm) so that it sufficiently adheres to the cucumber leaf surface. The foliage was sprayed. After spraying, the plants were air-dried and placed in a greenhouse at 23 ° C. for 5 days, and then the lesion area was examined. As a result, the present compounds (6), (8), (10), (11), (12), (14), (16), (17), (18), (19), (22), (23), (25), (30), (35), (36), (37), (38), (40), (42), (45), (46), (47), (48 ), (49), (52), (53) and the lesion area in the plant treated with (55) was 30% or less of the lesion area in the untreated plant.

Test Example 5
The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. The compound (44) of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed on the foliage so that it adhered sufficiently to the cucumber leaf surface. After spraying, the plants were air-dried, and a spore-containing PDA medium of cucumber gray mold fungus (Botrytis cinerea) was placed on the cucumber leaf surface. After inoculation, the lesion area was examined after 4 days in a humid environment at 12 ° C. As a result, the lesion area in the plant treated with the compound (44) of the present invention was 30% or less of the lesion area in the untreated plant.

Test Example 6
A plastic pot was stuffed with soil, seeded with green beans (variety; Nagahama peas) and grown in a greenhouse for 8 days. Each of the compounds (11), (15), (52), (54) and (55) of the present invention was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed so as to adhere well to the leaf surface. After spraying, the plants were air-dried, and a mycelia-containing PDA medium of Sclerotinia sclerotiorum was placed on the kidney leaf surface. After inoculation, the lesion area was investigated after 23 days at 23 ° C. and high humidity. As a result, the lesion area in the plant treated with the compounds (11), (15), (52), (54) and (55) of the present invention was 30% or less of the lesion area in the untreated plant. .

Test Example 7
The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. The above-mentioned pot was spray-inoculated with a water suspension of Pseudoperonospola cubensis zoosporangium, placed at 23 ° C. under high humidity for 1 day, and then air-dried to obtain a cucumber downy mildew-infected seedling. Each of the compounds (1), (2), (3) and (4) of the present invention was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface. The foliage was sprayed to adhere. After spraying, the plants were air-dried and placed in a greenhouse at 23 ° C. for 5 days, and then the lesion area was examined. As a result, the lesion area in the plant which processed this invention compound (1), (2), (3) and (4) was 30% or less of the lesion area in an untreated plant.

Test Example 8
The plastic pot was filled with soil, tomato (variety: patio) was sown and grown in a greenhouse for 20 days. Compounds of the present invention (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12) , (13), (14), (16), (17), (18), (19), (20), (23), (25), (27), (29), (30), ( 31), (32), (34), (35), (36), (37), (38), (39), (40), (41), (42), (45), (46) , (47), (48), (49), (52), (53) and (55) are each made into a flowable formulation according to Formulation Example 6, and then diluted with water to a predetermined concentration (500 ppm), The foliage was sprayed so as to adhere well to the leaf surface of the tomato seedling. After air-drying the diluted solution on the leaf surface to dryness, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, followed by cultivation in an artificial weather room at 20 ° C. for 4 days, and then the lesion area was examined.
Compounds of the present invention (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12) , (13), (14), (16), (17), (18), (19), (20), (23), (25), (27), (29), (30), ( 31), (32), (34), (35), (36), (37), (38), (39), (40), (41), (42), (45), (46) , (47), (48), (49), (52), (53) and (55), the lesion area in the plant was 30% or less of the lesion area in the untreated plant.

Test Example 9
Tomato (variety: patio) was sown on a plastic sponge piece and hydroponically cultivated in a plastic cup for about 20 days. Compound (1), (2), (3), (4), (5), (6), (7), (10), (14), (16), (17), (19) , (22), (23), (25), (27), (29), (30), (36), (37), (38), (40), (41), (42), ( 45), (46), (47), (48), (49), (52) and (53) are each made into a flowable formulation according to Formulation Example 6, and then 1 mg per plant in terms of weight is converted to the above. The tomato hydroponic seedling was put into a cup. Further, after 7 days of hydroponics, spray inoculation with an aqueous suspension of Phytophthora infestans spores. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, followed by cultivation in an artificial weather room at 20 ° C. for 4 days, and then the lesion area was examined.
Compound (1), (2), (3), (4), (5), (6), (7), (10), (14), (16), (17), (19) , (22), (23), (25), (27), (29), (30), (36), (37), (38), (40), (41), (42), ( 45), (46), (47), (48), (49), (52), and the lesion area in the plant treated with (53) was 30% or less of the lesion area in the untreated plant. It was.

Claims (10)

Formula (1)

[Where,
p represents any integer from 1 to 5;
R ² is a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D. , Phenyl group, halogen, cyano group, nitro group, —O—R ⁵ group, —S—R ⁵ group, —C (═O) —R optionally substituted with one or more groups selected from group E ⁵ groups, —C (═O) —OR ⁵ group, —OC (═O) —R ⁵ group, —NR ⁵ R ⁶ group, —C (═O) —NR ⁵ R ⁶ group or —NR ⁵ —C Represents the (= O) -R ⁶ group,
Alternatively, when p is 2 or more and two R ² are bonded to adjacent carbons of the benzene ring, the two R ² are bonded and substituted with one or more groups selected from group E. An optionally substituted C2-C5 polymethylene group, a propene-1,3-diyl group which may be substituted with one or more groups selected from group E, and one or more groups selected from group E. Represents a 1,3-butadiene-1,4-diyl group or a methylenedioxy group,
R ⁵ and R ⁶ are independently hydrogen, a C1-C10 chain hydrocarbon group optionally substituted with one or more groups selected from group C, or one or more groups selected from group D. Represents a phenyl group which may be substituted with one or more groups selected from C3 to C10 cycloalkyl groups which may be substituted or group E.
However, when p is any integer of 2 to 5, R ² is the same or different from each other.
Group C is a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from Group D, a halogen, a cyano group, a C1-C4 alkoxy group which may be substituted with halogen, or a halogen. An optionally substituted C1-C4 alkylthio group, an optionally substituted C1-C4 alkylsulfinyl group, an optionally substituted C1-C4 alkylsulfonyl group, and an optionally substituted halogen ( A group consisting of a (C1-C4 alkyl) carbonyl group, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen and a (C1-C4 alkyl) carbonyloxy group optionally substituted with halogen;
Group D represents a group consisting of a C1-C5 alkyl group and halogen,
Group E is halogen, cyano group, nitro group, C1-C10 chain hydrocarbon group which may be substituted with halogen, C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D C1-C4 alkoxy group optionally substituted with halogen, C1-C4 alkylthio group optionally substituted with halogen, C1-C4 alkylsulfinyl group optionally substituted with halogen, halogen-substituted May be a C1-C4 alkylsulfonyl group, a (C1-C4 alkyl) carbonyl group optionally substituted with halogen, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a halogen-substituted A good (C1-C4 alkyl) carbonyloxy group is represented. ]
Or an salt thereof. The amide compound or a salt thereof according to claim 1, wherein R ² is halogen. The amide compound or a salt thereof according to claim 1, wherein R ² is fluorine or chlorine. The amide compound or a salt thereof according to claim 1, wherein R ² is fluorine or bromine. The amide compound or a salt thereof according to claim 1, wherein p is 3, and R ² are the same or different from each other and are halogen. The amide compound or a salt thereof according to claim 1, wherein p is 3, and R ² are the same or different from each other and are fluorine or chlorine. The amide compound or a salt thereof according to claim 1, wherein p is 3, and R ² are the same or different from each other and are fluorine or bromine.   A plant disease control agent comprising the amide compound or a salt thereof according to any one of claims 1 to 7, and an inert carrier.   A method for controlling plant diseases, comprising a step of applying an effective amount of the amide compound or a salt thereof according to any one of claims 1 to 7 to a plant or soil in which the plant grows.   Use of the amide compound or a salt thereof according to any one of claims 1 to 7, for controlling plant diseases.