WO2010101973A1 - Fungicidal pyrazoles - Google Patents

Fungicidal pyrazoles Download PDF

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Publication number
WO2010101973A1
WO2010101973A1 PCT/US2010/026003 US2010026003W WO2010101973A1 WO 2010101973 A1 WO2010101973 A1 WO 2010101973A1 US 2010026003 W US2010026003 W US 2010026003W WO 2010101973 A1 WO2010101973 A1 WO 2010101973A1
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WO
WIPO (PCT)
Prior art keywords
dimethyl
independently selected
alkyl
pyrazol
ring
Prior art date
Application number
PCT/US2010/026003
Other languages
French (fr)
Inventor
Jeffrey Keith Long
Wonpyo Hong
Andrew Edmund Taggi
Original Assignee
E. I. Du Pont De Nemours And Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=42139982&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2010101973(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to MEP-2016-26A priority Critical patent/ME02349B/en
Priority to CA2750862A priority patent/CA2750862C/en
Priority to CN2010800198065A priority patent/CN102421756A/en
Priority to AU2010221440A priority patent/AU2010221440B2/en
Priority to KR1020117023011A priority patent/KR101752925B1/en
Priority to RS20160051A priority patent/RS54531B1/en
Priority to PL10707187T priority patent/PL2403834T3/en
Priority to US13/254,205 priority patent/US9062005B2/en
Priority to RU2011139893/04A priority patent/RU2577247C2/en
Priority to UAA201109619A priority patent/UA124518C2/en
Priority to DK10707187.0T priority patent/DK2403834T3/en
Priority to SI201031129T priority patent/SI2403834T1/en
Priority to ES10707187.0T priority patent/ES2562178T3/en
Priority to BRPI1005812A priority patent/BRPI1005812B8/en
Application filed by E. I. Du Pont De Nemours And Company filed Critical E. I. Du Pont De Nemours And Company
Priority to JP2011553063A priority patent/JP6285090B2/en
Priority to NZ594181A priority patent/NZ594181A/en
Priority to EP10707187.0A priority patent/EP2403834B1/en
Priority to MX2011008900A priority patent/MX2011008900A/en
Publication of WO2010101973A1 publication Critical patent/WO2010101973A1/en
Priority to IL214184A priority patent/IL214184A/en
Priority to ZA2011/05391A priority patent/ZA201105391B/en
Priority to US14/695,689 priority patent/US9655361B2/en
Priority to HRP20160111T priority patent/HRP20160111T1/en
Priority to US15/496,048 priority patent/US20170223959A1/en
Priority to US16/173,167 priority patent/US10448639B2/en
Priority to US16/572,759 priority patent/US20200008425A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to certain pyrazoles, their //-oxides, salts and compositions, and methods of their use as fungicides.
  • JP09208620 discloses JV-phenylpyrazolylamine and JV-pyridylpyrazolylamine derivatives as insecticides, herbicides and fungicides; however the fungicides of the present invention are not disclosed in this publication.
  • This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -
  • C 7 cycloalkyl CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl; or
  • R 1 is phenyl optionally substituted with up to 3 R 8 ; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R 9a on carbon atom ring members and
  • R la is H
  • R la and R 1 are taken together with the carbon atom to which they are attached to form a cyclopropyl ring optionally substituted with up to 2 substituents independently selected from halogen and methyl;
  • R 2 is CH 3 , CH 2 CH 3 , halogen, cyano, cyanomethyl, halomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl; each R 3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C 2 -C 3 alkylcarbonylamino, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 1 -C 3 alkylthio, C 1 -C 3 haloalkylthio, C 1 -C 3 alkylsulf ⁇ nyl, C 1 -C 3 haloalkylsulfmyl, C 1 -C 3 alkylsulfonyl, C 1 -C
  • R 4 is H, formyl, C 2 -C 5 alkenyl, C 3 -C 5 alkynyl, C 3 -C 7 cycloalkyl, -SO 3 -M + ,
  • R 10 is H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl;
  • R 6 and R 7 are independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, C 4 -Cg cycloalkylalkyl and C 4 -Cg alkylcycloalkyl; or
  • R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O) n and NR 13 ; each R 8 , R 9a and R 9b is independently selected from halogen, C ⁇ C 2 alkyl, C ⁇ C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano, nitro, SCH 3 , S(O)CH 3 and
  • R 10 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; each R 11 is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 7 alkoxyalkyl, C 2 -C 7 alkylaminoalkyl, C 2 -Cg dialkylaminoalkyl, C 1 -C 6 alkylthio or C 2 -C 7 alkylthioalkyl; each R 12 is independently C 3 -C 7 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfmyl, C 1 -C 4 alkylsulfonyl or cyano; R 13 is H, C 1 -C 3 alkyl or C 2 -C 3 haloalkyl; each R 14 is independently H, cyano, C 1 -C 3
  • R 15 is H, C 1 -C 4 alkyl or OR 18 ;
  • R 16 is C 1 -C 4 alkyl or OR 18 ; or R 15 and R 16 are taken together as -OCH 2 CH 2 O-;
  • each R 19 and R 20 is independently H or CH 3 ;
  • each R 22 is independently H, C 1 -C 6 alkyl, C 1 -C 6
  • each R 23a and R 23b is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 (alkylthio)carbonyl, C 2 -C 6 alkoxy(thiocarbonyl),
  • each R 24 and R 25 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 (alkylthi
  • this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an JV-oxide or a salt thereof.
  • This invention also relates to a fungicidal composition comprising a compound of Formula 1, an JV-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising: (a) a compound of Formula 1, an JV-oxide, or a salt thereof, and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).
  • This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
  • This invention also relates to a composition
  • a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.
  • the invention also relates to compounds of Formula 2 (including all geometric and stereoisomers) and salts thereof
  • X is NH
  • the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated.
  • a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
  • the phrase “consisting of appears in a clause of the body of a claim, rather than immediately following the preamble it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
  • transitional phrase consisting essentially of is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention.
  • plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds).
  • Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
  • the term “seedling”, used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • the term “alkylating agent” refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term “alkylating” does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified for R 1 .
  • a molecular fragment i.e. radical
  • a series of atom symbols e.g., C, H, N, O, S
  • the point or points of attachment may be explicitly indicated by a hyphen ("-").
  • -SCN indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers.
  • alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl isomers.
  • Alkenyl also includes polyenes such as 1,2-propadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl isomers.
  • Alkynylene denotes a straight-chain or branched alkynediyl containing one triple bond.
  • alkynylene examples include CH 2 C ⁇ C, C ⁇ CCH 2 and the different butynylene, pentynylene and hexynylene isomers.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • Alkoxyalkyl denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
  • Alkylsulfmyl includes both enantiomers of an alkylsulf ⁇ nyl group. Examples of “alkylsulfmyl” include CH 3 S(O)-, CH 3 CH 2 S(O)-, CH 3 CH 2 CH 2 S(O)-, (CH 3 ) 2 CHS(O)- and the different butylsulfinyl isomers.
  • alkylsulfonyl examples include CH 3 S(O) 2 -, CH 3 CH 2 S(O) 2 -, CH 3 CH 2 CH 2 S(O) 2 -, (CH 3 ) 2 CHS(O) 2 -, and the different butylsulfonyl isomers.
  • Alkylthioalkyl denotes alkylthio substitution on alkyl.
  • alkylthioalkyl include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 .
  • Alkylaminoalkyl denotes a straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety.
  • alkylaminoalkyl examples include CH 3 NHCH 2 -, (CH 3 ) 2 CHNHCH 2 - and CH 3 NHCH(CH 3 )-.
  • Dialkylaminoalkyl denotes two independent straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino (straight-chain or branched)alkyl moiety.
  • dialkylaminoalkyl examples include (CH 3 ) 2 NCH r , (CH 3 ) 2 CH(CH 3 )NCH 2 - and (CH 3 ) 2 NCH(CH 3 )-.
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl moiety.
  • cycloalkylalkyl examples include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
  • cycloalkoxy denotes cycloalkyl linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy.
  • Cycloalkenyl includes carbocyclic rings that contain only one double bond such as cyclopentenyl and cyclohexenyl, as well as carbocyclic rings with more than one double bond such as 1,3- and 1 ,4-cyclohexadienyl, but are not aromatic.
  • cycloalkylene denotes a cycloalkanediyl ring.
  • cycloalkylene examples include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene.
  • cycloalkenylene denotes a cycloalkenediyl ring containing one olefmic bond.
  • Examples of “cycloalkenylene” include cylopropenediyl and cyclpentenediyl.
  • halogen either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F 3 C-, ClCH 2 -, CF 3 CH 2 - and CF 3 CCl 2 -.
  • halocycloalkyl examples include CH 2 FO-, CHF 2 O-, CF 3 O-, CCl 3 CH 2 O-, HCF 2 CH 2 CH 2 O- and CF 3 CH 2 O-.
  • fluoroalkoxy examples include CH 2 FO-, CHF 2 O-, CF 3 O- HCF 2 CH 2 CH 2 O- and CF 3 CH 2 O-.
  • fluoromethoxy examples include CH 2 FO-, CHF 2 O- and CF 3 O-.
  • haloalkylthio examples include CCl 3 S-, CF 3 S-, CCl 3 CH 2 S- and ClCH 2 CH 2 CH 2 S-.
  • haloalkylsulfmyl examples include CF 3 S(O)-, CCl 3 S(O)-, CF 3 CH 2 S(O)- and CF 3 CF 2 S(O)-.
  • haloalkylsulfonyl include CF 3 S(O) 2 -, CCl 3 S(O) 2 -, CF 3 CH 2 S(O) 2 - and CF 3 CF 2 S(O) 2 -.
  • Cj-C The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 12.
  • C 1 -C 4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2 -
  • C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 )-, CH 3 OCH 2 CH 2 - or CH 3 CH 2 OCH 2 -
  • C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 - and CH 3 CH 2 OCH 2 CH 2 -.
  • an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
  • unsubstituted in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1.
  • optionally substituted means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. The number of optional substituents may be restricted by an expressed limitation. For example, the phrase “optionally substituted with up to 3 substituents selected from R 9a on carbon ring members" means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows).
  • the phrase "optionally substituted with up to 5 substituents selected from R 3 on carbon ring members” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows.
  • a range specified for the number of substituents e.g., r being an integer from 0 to 4 or from 0 to 3 for 5- and 6-membered nitrogen-containing heterocycles in Exhibit A
  • the number of positions available for substituents on a ring e.g., 2 positions available for (R a ) r on U-27 in Exhibit A
  • the actual higher end of the range is recognized to be the number of available positions.
  • said substituents are independently selected from the group of defined substituents, e.g., (R 3 ) p in Table 1 where p is 0, 1, 2, 3, 4 or 5.
  • substituents which can be hydrogen, for example R 1 , R 4 , R 5 , R 6 , R 7 or R 13 , then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
  • variable group When a variable group is shown to be optionally attached to a position, for example (R a ) r in H-23 of Exhibit 1 , wherein r may be 0, then hydrogen may be at the position even if not recited in the variable group definition.
  • hydrogen atoms When one or more positions on a group are said to be "not substituted” or “unsubstituted”, then hydrogen atoms are attached to take up any free valency.
  • a "ring” as a component of Formula 1 is carbocyclic or heterocyclic.
  • the term “ring system” as a component of Formula 1 denotes two fused rings (e.g., a phenyl ring fused to a pyridinyl ring to form quinolinyl).
  • carbocyclic ring denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. "Saturated carbocyclic” refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
  • heterocyclic ring or “heterocycle” denote a ring or ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring.
  • saturated heterocyclic ring refers to a heterocyclic ring containing only single bonds between ring members.
  • a partially unsaturated heterocyclic ring is intermediate between a saturated heterocyclic ring and a fully unsaturated heterocyclic ring (which may be aromatic). Therefore, as referred to in the present disclosure and claims, the term “partially unsaturated heterocyclic ring” denotes a heterocyclic ring comprising at least one ring member bonded to an adjacent ring member through a double bond and which conceptually potentially accommodates a number of non-cumulated double bonds between adjacent ring members (i.e. in its fully unsaturated counterpart form) greater than the number of double bonds present (i.e. in its partially unsaturated form).
  • heterocyclic ring When a fully unsaturated heterocyclic ring satisfies H ⁇ ckel's rule, then said ring is also called a "heteroaromatic ring” or “aromatic heterocyclic ring".
  • the terms “heteroaromatic ring system” and “heteroaromatic bicyclic ring system” denote a ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur, and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • Aromatic indicates that each of the ring atoms is essentially in the same plane and has a /?-orbital perpendicular to the ring plane, and that (4n + T) ⁇ electrons, where n is a positive integer, are associated with the ring to comply with H ⁇ ckel's rule.
  • aromatic heterocyclic ring system denotes a heterocyclic ring system in which at least one ring of the ring system is aromatic.
  • nonaromatic ring system denotes a carbocyclic or heterocyclic ring system that may be fully saturated, as well as partially or fully unsaturated, provided that none of the rings in the ring system are aromatic.
  • four- to seven-membered nonaromatic heterocyclic ring refers to rings containing four to seven ring members and which do not satisfy H ⁇ ckel's rule. This term (as used where R 6 and R 7 are taken together) is not limited by carbon atoms only and can include ring members selected from O, S(O) n and NR 13 .
  • Q 1 , Q 2 or R 1 comprises a phenyl or a 6-membered fully unsaturated heterocyclic ring
  • the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1.
  • Q 1 , Q 2 and R 1 can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of the Invention.
  • An example of phenyl optionally substituted with one to five substituents is the ring illustrated as U-57 in Exhibit A, wherein R 8 is as defined in the Summary of the Invention for R 8 and q is an integer from 0 to 5.
  • substituents on the ring or ring system of Q 1 or Q 2 are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment.
  • the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S).
  • the nitrogen atom ring members may be oxidized as //-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives.
  • R 1 can be (among others) 5- or 6-membered nitrogen-containing aromatic heterocycle, which may be optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention.
  • R 1 is phenyl or a 5- or 6- membered nitrogen-containing aromatic heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described.
  • the ring or ring system of Q 1 or Q 2 may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described.
  • Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings H-I through H-39 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems B-I through B-39 illustrated in Exhibit 2.
  • variable R a is any substituent as defined in the Summary of the Invention for Q 1 , Q 2 or R 1 (e.g., a Q 1 ring or ring system is optionally substituted with R 3 on carbon ring members and cyano, C j -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 ⁇ C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 ⁇ C 6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5 for Q 1 and Q 2 or from 0 to 3 for R 1 , limited by the number of available positions on each depicted ring or ring system.
  • R a is any substituent as defined in the Summary of the Invention for Q 2 (e.g., a Q 2 ring is optionally substituted with R 3 on carbon ring members and cyano, C ⁇ -Cg alkyl, C 2 - C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring
  • Examples of a 5- or 6-membered nitrogen-containing heterocycle optionally substituted with from one or more substituents of particular note for Q 1 , Q 2 and R 1 include the rings U-I through U-56 illustrated in Exhibit A wherein R a is any substituent as defined in the Summary of the Invention for Q 1 Q 2 and R 1 , respectively (i.e.
  • R 3 on carbon atom ring members, and the recited list of possible substituents on nitrogen atom ring members; and for R 1 , R 9a on carbon ring members and R 9 ⁇ on nitrogen ring members) and r is an integer ranging from 0 to 4 for Q 1 and Q 2 and from 0 to 3 for R 1 , limited by the number of available positions on each U group. Note that some U groups can only be substituted with less than 4 R a groups (e.g., U-4 through U-43 and U-47 through U-56).
  • r is limited to the integers 0 or 1 , and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (R a ) r .
  • R a groups are shown in the structures H-I through H-39, B-I through B-39, P-I through P-40, and U-I through U-57 in Exhibits 1 through 3 and Exhibit A, it is noted that they do not need to be present since they are optional substituents.
  • the nitrogen atoms that require substitution to fill their valence are substituted with H or R a . Note that when the attachment point between (R a ) r and the H, B, P or U group in Exhibits 1 through 3 and Exhibit A is illustrated as floating, (R a ) r can be attached to any available carbon atom or nitrogen atom of the H, B, P or U group.
  • R 6 and R 7 are taken together to form a four- to seven-membered nonaromatic heterocyclic ring
  • examples of where R 6 and R 7 are taken together to form a four- to seven-membered nonaromatic heterocyclic ring include the rings G-I through G-28 as illustrated in Exhibit 4. Note that when R 6 and R 7 are taken together to form a ring comprising a ring selected from G-25 through G-28, G 2 is selected from O, S(O) n or NR 13 . Note that when G 2 is N, the nitrogen atom can complete its valence by substitution with either H or the substituents corresponding to R 13 as defined in the Summary of Invention.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
  • nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form TV-oxides.
  • tertiary amines can form iV-oxides.
  • Synthetic methods for the preparation of iV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as t-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane
  • salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1.
  • Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • Embodiments of the present invention as described in the Summary of the Invention include (where Formula 1 as used in the following Embodiments includes //-oxides and salts, geometric isomers, stereoisomers and atropisomers thereof ):
  • Embodiment 1 A compound of Formula 1 wherein X is O, S(O) m , NR 4 , CR 15 R 16 or
  • Embodiment 2 A compound of Formula 1 wherein X is O, S(0) m , NR 4 or CR 15 R 16 .
  • Embodiment 4 A compound of Formula 1 wherein X is O, NR 4 or CR 15 R 16 .
  • Embodiment 5. A compound of Formula 1 wherein X is O, S(0) m or NR 4 .
  • Embodiment 6. A compound of Formula 1 wherein X is O or S(0) m .
  • Embodiment 7. A compound of Formula 1 wherein X is O.
  • Embodiment 8. A compound of Formula 1 wherein X is NR 4 .
  • Embodiment 9 A compound of Formula 1 wherein X is O or NR 4 .
  • Embodiment 11. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q 1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R 3 substituent is located at a meta position
  • R 3 substituent is selected from F, Cl, Br and cyano (-CN).
  • Embodiment 11a A compound of Formula 1 or any one of Embodiments 1 through 11 wherein when Q 1 is a six-membered ring and an R 3 substituent is located at a meta position (relative to the connection of the Q 1 ring to the remainder of
  • R 3 substituent is F.
  • R 3 substituent is F.
  • Q 1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R 3 substituent, then said R 3 substituent is attached at an ortho position (relative to the connection of the Q 1 ring to the remainder of Formula 1).
  • Embodiment 14 A compound of Embodiment 13 wherein Q 1 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R 3 .
  • Embodiment 15 A compound of Embodiment 14 wherein Q 1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R 3 .
  • Embodiment 16 A compound of Embodiment 15 wherein Q 1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R 3 .
  • a compound of Embodiment 16 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q 1 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q * .
  • Embodiment 18 A compound of Embodiment 16 or 17 wherein Q 1 is phenyl or pyridinyl, each substituted with 1 , 2 or 3 substituents independently selected from R 3 .
  • Embodiment 19 A compound of Embodiment 18 wherein Q 1 is phenyl or pyridinyl, each substituted with 2 or 3 substituents independently selected from R 3 .
  • Embodiment 20 A compound of Embodiment 18 wherein Q 1 is phenyl or pyridinyl, each substituted with 2 or 3 substituents independently selected from R 3 .
  • Embodiment 21 wherein Q 1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 .
  • Embodiment 23 A compound of Embodiment 21 wherein Q 1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 .
  • Embodiment 24 A compound of Embodiment 21 wherein Q 1 is phenyl substituted at the 2- and 6-positions with substituents independently selected from R 3 .
  • Embodiment 25 A compound of Embodiment 18 wherein Q 1 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R 3 .
  • Embodiment 26 A compound of Embodiment 25 wherein Q 1 is pyridinyl substituted with 1 or 2 substituents independently selected from R 3 .
  • Embodiment 27 A compound of Embodiment 26 wherein Q 1 is pyridinyl substituted with 1 substituent independently selected from R 3 .
  • Embodiment 28 A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when Q 2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R 3 substituent is located at a meta position
  • Q 2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R 3 substituent is located at a meta position
  • R 3 substituent is selected from F, Cl, Br and cyano (-CN).
  • Embodiment 29 A compound of Formula 1 or any one of Embodiments 1 through 28 wherein when Q 2 is a six-membered ring and an R 3 substituent is located at a meta position (relative to the connection of the Q 2 ring to the remainder of
  • Embodiment 30 A compound of Formula 1 or any one of Embodiments 1 through 29 wherein when Q 2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R 3 substituent, then said R 3 substituent is attached at an ortho position (relative to the connection of the Q 2 ring to the remainder of Formula 1).
  • Q 2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R 3 substituent, then said R 3 substituent is attached at an ortho position (relative to the connection of the Q 2 ring to the remainder of Formula 1).
  • Embodiment 31 A compound of Formula 1 or any one of Embodiments 1 through 30 wherein Q 2 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R 3 .
  • Embodiment 32 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R 3 .
  • Embodiment 32 Embodiment 32.
  • Embodiment 33 A compound of Embodiment 32 wherein Q 2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R 3 .
  • Embodiment 34 A compound of any one of Embodiments 31 through 33 wherein Q 2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 ,
  • Embodiment 35 A compound of Embodiment 34 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q 2 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q 2 .
  • Embodiment 36 A compound of any one of Embodiments 34 or 35 wherein Q 2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R 3 .
  • Embodiment 37 A compound of Embodiment 36 wherein Q 2 is phenyl substituted with
  • Embodiment 38 A compound of Embodiment 37 wherein Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R 3 .
  • Embodiment 39 A compound of Embodiment 38 wherein Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 .
  • Embodiment 40 A compound of Embodiment 40 wherein Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 .
  • Embodiment 42. A compound of Embodiment 36 wherein Q 2 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R 3 .
  • Embodiment 43 A compound of Embodiment 42 wherein Q 2 is pyridinyl substituted with 1 or 2 subsituents independently selected from R 3 .
  • Embodiment 44 A compound of Embodiment 43 wherein Q 2 is pyridinyl substituted with 1 substituent selected from R 3 .
  • Embodiment 45 A compound of Formula 1 or any one of Embodiments 1 through 44 wherein at least one of Q 1 and Q 2 is phenyl optionally substituted with R 3 (e.g., optionally substituted with up to 5 substituents independently selected from R 3 ).
  • Embodiment 46 Embodiment 46.
  • Embodiment 45 wherein at least one of Q 1 and Q 2 is phenyl substituted with 2, 3 or 4 substituents independently selected from R 3 .
  • Embodiment 47 A compound of Embodiment 46 wherein at least one Q 1 and Q 2 is phenyl substituted with 2 or 3 substituents independently selected from R 3 .
  • Embodiment 48 A compound of Embodiment 47 wherein each of Q 1 and Q 2 is phenyl substituted with 2 or 3 substituents independently selected from R 3 .
  • Embodiment 49 Embodiment 49.
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl; or
  • R 1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R 9a on carbon atom ring members and R 9 ⁇ on nitrogen atom ring members.
  • Embodiment 50 A compound of Embodiment 49 wherein R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cyano, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy; or
  • R 1 is pyridinyl, pyrimidinyl, pyrazolyl or oxazolyl, each optionally substituted with up to 3 substituents independently selected from R 9a on carbon atom ring members and R 9 ⁇ on nitrogen atom ring members.
  • Embodiment 51 A compound of Embodiment 50 wherein R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl.
  • Embodiment 52 Embodiment 52.
  • Embodiment 53 A compound of Embodiment 52 wherein R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl.
  • Embodiment 54 A compound of Embodiment 53 wherein R 1 is H, halogen or C 1 -C 6 alkyl.
  • Embodiment 55 A compound of Embodiment 54 wherein R 1 is H or CH 3 .
  • Embodiment 56 A compound of Embodiment 55 wherein R 1 is H.
  • Embodiment 57 A compound of Formula 1 or any one of Embodiments 1 through 56 wherein R 1 is other than an optionally substituted phenyl or an optionally substituted five- or six-membered nitrogen-containing aromatic heterocycle.
  • R la is H.
  • Embodiment 60 A compound of Formula 1 or any one of Embodiments 1 through 59 wherein R 2 is CH 3 , CH 2 CH 3 , halogen, cyano, cyanomethyl, monohalomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl.
  • Embodiment 61 A compound of Embodiment 60 wherein R 2 is CH 3 , CH 2 CH 3 , Cl, Br or I.
  • Embodiment 62. A compound of Embodiment 61 wherein R 2 is CH 3 , CH 2 CH 3 , Cl or
  • Embodiment 63 A compound of Embodiment 62 wherein R 2 is CH 3 , Cl or Br.
  • Embodiment 64 A compound of Embodiment 63 wherein R 2 is CH 3 or Cl.
  • Embodiment 65 A compound of Embodiment 64 wherein R 2 is CH 3 .
  • Embodiment 66 A compound of Embodiment 62 wherein R 2 is Cl or Br.
  • Embodiment 67 A compound of Embodiment 66 wherein R 2 is Cl.
  • Embodiment 68 A compound of Formula 1 or any one of Embodiments 1 through 67 wherein R 5 is H or C 1 -C 6 alkyl.
  • Embodiment 69 A compound of Embodiment 68 wherein R 5 is H, CH 3 or CH 2 CH 3 .
  • Embodiment 70 A compound of Embodiment 68 wherein R 5 is C 1 -C 6 alkyl.
  • Embodiment 71 A compound of Embodiment 69 or 70 wherein R 5 is CH 3 or CH 2 CH 3 .
  • Embodiment 72 A compound of Formula 1 or any one of Embodiments 1 through 71 wherein when R 6 is separate (i.e. not taken together with R 7 to form a ring), then
  • R 6 is H or C 1 -C 6 alkyl.
  • Embodiment 73 A compound of Embodiment 72 wherein R 6 is H.
  • Embodiment 74. A compound of Formula 1 or any one of Embodiments 1 through 73 wherein when R 7 is separate (i.e. not taken together with R 6 to form a ring), then
  • R 7 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 4 -C 8 alkylcycloalkyl.
  • Embodiment 75 A compound of Embodiment 74 wherein R 7 is H or C 1 -C 6 alkyl.
  • Embodiment 76 A compound of Embodiment 75 wherein R 7 is H.
  • Embodiment 77 A compound of Embodiment 75 wherein R 7 is H.
  • Embodiment 78 A compound of Embodiment 77 wherein when R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring is six-membered and contains one ring member selected from O and NR 13 in addition to the connecting nitrogen atom and ring members selected from carbon atoms.
  • Embodiment 79 A compound of Embodiment 77 wherein R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a piperidine ring.
  • Embodiment 80 A compound of Embodiment 78 wherein R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a piperazine or morpholine ring.
  • Embodiment 81. A compound of Formula 1 or any one of Embodiments 1 through 80 wherein each R 8 is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro.
  • Embodiment 82 A compound of Embodiment 81 wherein each R 8 is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, cyano and nitro.
  • Embodiment 83 A compound of Embodiment 82 wherein each R 8 is independently Cl or F.
  • Embodiment 84. A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R 9a is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro.
  • Embodiment 85 A compound of Embodiment 84 wherein each R 9a is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, cyano and nitro.
  • Embodiment 86. A compound of Embodiment 85 wherein each R 9a is independently selected from Cl, F, CH 3 , -OCH 3 and cyano.
  • Embodiment 87. A compound of Embodiment 86 wherein each R 9a is independently Cl or F.
  • Embodiment 88. A compound of Formula 1 or any one of Embodiments 1 through 87 wherein each R 9 ⁇ is independently C 1 -C 2 alkyl.
  • Embodiment 89 A compound of Formula 1 or any one of Embodiments 1 through 88 wherein each R 3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy,
  • Embodiment 90 A compound of Embodiment 89 wherein each R 3 is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy and -U-V-T.
  • Embodiment 91 A compound of Embodiment 89 wherein each R 3 is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy and -U-V-T.
  • each R 3 is independently selected from F, Cl, Br, cyano, nitro, CH 3 , CF 3 , -OCH 3 , -OCHF 2 and -U-V-T.
  • Embodiment 92 A compound of Formula 1 or any one of Embodiments 1 through 91 wherein at least one R 3 substituent on the ring or ring system of Q 1 or Q 2 is
  • Embodiment 93 A compound of Formula 1 or any one of Embodiments 1 through 91 wherein each R 3 is other than -U-V-T.
  • Embodiment 94 A compound of Embodiment 89 wherein each R 3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C 1 -
  • Embodiment 95 Embodiment 95.
  • each R 3 is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy and C 1 -C 3 haloalkoxy.
  • Embodiment 96 A compound of Embodiment 95 wherein each R 3 is independently selected from halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy and
  • Embodiment 97 A compound of Embodiment 96 wherein each R 3 is independently selected from F, Cl, Br, cyano, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy and
  • Embodiment 98 A compound of Embodiment 97 wherein each R 3 is independently selected from F, Cl, Br, cyano, methyl, C 1 -C 2 alkoxy and fluoromethoxy.
  • Embodiment 99 A compound of Embodiment 98 wherein each R 3 is independently selected from F, Cl, cyano, methyl, C 1 -C 2 alkoxy and fluoromethoxy.
  • Embodiment 100 A compound of Embodiment 95 wherein each R 3 is independently selected from F, Cl, Br, cyano, nitro, CH 3 , CF 3 , -OCH 3 and -OCHF 2 .
  • Embodiment 101 A compound of any one of Embodiments 89 through 98 or 100 wherein each R 3 is independently selected from F, Cl, Br, cyano and methoxy.
  • Embodiment 102 A compound of Embodiment 101 wherein each R 3 is independently selected from F, Cl, Br and cyano.
  • Embodiment 103 A compound of Embodiment 101 wherein each R 3 is independently selected from F, Cl, cyano and -OCH 3 .
  • Embodiment 104 A compound of Formula 1 or any one of Embodiments 1 through 92 wherein each U is independently O or NR 22 .
  • Embodiment 105 A compound of Embodiment 104 wherein each U is independently O or NH.
  • Embodiment 106. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 105 wherein each V is C 2 -C 4 alkylene.
  • Embodiment 107. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 106 wherein each T is independently NR 23a R 23b or OR 24 .
  • Embodiment 108 A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 107 wherein each R 23a and R 23b is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
  • Embodiment 109. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 108 wherein each R 24 is independently H, C 1 -C 6 alkyl or C 1 -
  • Embodiment 110 A compound of Formula 1 or any one of Embodiments 1 through 109 wherein when an R 3 substituent attached to phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl Of Q 1 Or Q 2 is other than F, Cl, Br, cyano, methyl, C 1 -
  • R 3 substituent is attached at the para position (of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl ring).
  • Embodiment 111 A compound of Formula 1 or any one of Embodiments 1 through 110 wherein R 4 is H, formyl, C 3 -C 7 cycloalkyl or -SR 10 ; or C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each optionally substituted with up to 2 R 12 .
  • Embodiment 112 A compound of Embodiment 111 wherein R 4 is H, formyl, C 3 -C 7 cycloalkyl or -SR 10 ; or C 1 -C 6 alkyl substituted with one R 12 .
  • Embodiment 113 A compound of Embodiment 112 wherein R 4 is H, formyl,
  • Embodiment 114 A compound of Embodiment 113 wherein R 4 is H, formyl, cyclopropyl or -CH 2 CN.
  • Embodiment 115 A compound of Embodiment 113 wherein R 4 is H, formyl,
  • Embodiment 116 A compound of Embodiment 115 wherein R 4 is H, formyl or cyclopropyl.
  • Embodiment 117 A compound of Embodiment 114 or 116 wherein R 4 is H.
  • Embodiment 118 A compound of Formula 1 or any one of Embodiments 1 through 117 wherein R 13 is H or CH 3 .
  • Embodiment 119 A compound of Embodiment 118 wherein R 13 is CH 3 .
  • Embodiment 120 A compound of Formula 1 or any one of Embodiments 1 through 119 wherein each R 12 is independently C 3 -C 7 cycloalkyl, Q-C 4 alkoxy or cyano.
  • Embodiment 121 A compound of Embodiment 120 wherein each R 12 is independently cyclopropyl, -OCH 3 or cyano.
  • Embodiment 122 A compound of Embodiment 120 wherein each R 12 is independently
  • Embodiment 123 A compound of Embodiment 122 wherein each R 12 is independently cyclopropyl or -OCH 3 .
  • Embodiment 124 A compound of Formula 1 or any one of Embodiments 1 through 123 wherein R 10 is CH 3 , CH 2 CH 3 , CF 3 or CF 2 CF 3 .
  • Embodiment 125 A compound of Embodiment 124 wherein R 10 is CH 3 .
  • Embodiment 126. A compound of Formula 1 or any one of Embodiments 1 through 125 wherein R 11 is C 1 -C 6 alkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkylthio.
  • Embodiment 127 A compound of Embodiment 126 wherein R 11 is CH 3 , CH 2 CH 3 ,
  • Embodiment 128 A compound of Embodiment 127 wherein R 11 is CH 3 , -OCH 3 or
  • Embodiment 129 A compound of Formula 1 or any one of Embodiments 1 through 128 wherein R 15 is H or CH 3 .
  • Embodiment 130 A compound of Embodiment 129 wherein R 15 is H.
  • Embodiment 131 A compound of Formula 1 or any one of Embodiments 1 through 130 wherein R 16 is CH 3 or OR 18 .
  • Embodiment 132 A compound of Embodiment 131 wherein R 16 is OR 18 .
  • Embodiment 133 A compound of Formula 1 or any one of Embodiments 1 through 132 wherein R 18 is H.
  • Embodiment 134 A compound of Formula 1 or any one of Embodiments 1 through 133 wherein W is O.
  • Embodiment 135. A compound of Formula 1 or any one of Embodiments 1 through 134 wherein M + is a cation selected from sodium, potassium and lithium ions.
  • Embodiment 136. A compound of Embodiment 135 wherein M + is a cation selected from sodium and potassium ions.
  • Embodiment 137 A compound of Embodiment 136 wherein M + is a sodium ion.
  • Embodiment 138. A compound of Formula 1 or any one of Embodiments 1 through 137 wherein m is 0.
  • Embodiment 139. A compound of Formula 1 or any one of Embodiments 1 through 138 wherein n is 0.
  • Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds (e.g. compounds of Formula 2) useful for preparing the compounds of Formula 1.
  • embodiments of this invention including Embodiments 1-139 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention. Combinations of Embodiments 1-139 are illustrated by:
  • Embodiment A A compound of Formula 1 wherein
  • Q 1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R 3 ; provided that when an R 3 substituent is located at a meta position, then said R 3 substituent is selected from F, Cl, Br and cyano;
  • Q 2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R 3 , provided that when an R 3 substituent is located at a meta position, then said R 3 substituent is selected from F, Cl, Br and cyano;
  • X is O, NR 4 , C(O) or CR 15 R 16 ;
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl;
  • R la is H
  • R 6 is H or C 1 -C 6 alkyl
  • R 7 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 4 -C 8 alkylcycloalkyl; or
  • R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR 13 ; each R 12 is independently C 3 -C 7 cycloalkyl, C 1 -C 4 alkoxy or cyano; R 13 is H or CH 3 ; R 15 is H or CH 3 ; and R 16 is OR 18 .
  • Embodiment B A compound of Embodiment A wherein
  • Q 1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R 3 ;
  • Q 2 is phenyl or pyridinyl, each substituted with 1 , 2 or 3 substituents independently selected from R 3 ;
  • R 1 is H, halogen or C 1 -C 6 alkyl
  • R 2 is CH 3 , Cl or Br; each R 3 is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy and -U-V-T; R 4 is H, formyl, C 3 -C 7 cycloalkyl or -SR 10 ; or C 1 -C 6 alkyl substituted with one R 12 ; each R 12 is independently cyclopropyl, -OCH 3 or cyano; R 15 is H; each U is independently O or NH; each V is C 2 -C 4 alkylene; each T is independently NR 23a R 23b or OR 24 ; each R 23a and R 23b is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and each R 24 is independently H, C 1 -C 6 alkyl or C 1 -C 6
  • Embodiment C A compound of Embodiment B wherein at least one of Q 1 and Q 2 is phenyl substituted with 2 or 3 substituents independently selected from R 3 ;
  • R 1 is H or CH 3 ;
  • R 2 is CH 3 ;
  • R 4 is H;
  • each R 3 is independently selected from halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl,
  • Embodiment D A compound of Embodiment C wherein Q 1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R 3 ;
  • Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R 3 ;
  • X is O, NR 4 or CR 15 R 16 ;
  • R 1 is H; each R 3 is independently selected from F, Cl, Br, cyano, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl,
  • Embodiment E A compound of Embodiment D wherein each R 3 is independently selected from F, Cl, Br, cyano, methyl, C 1 -C 2 alkoxy and fluoromethoxy.
  • Embodiment F A compound of Embodiment E wherein X is O or NH; and each R 3 is independently selected from F, Cl, Br, cyano and methoxy.
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of:
  • This invention provides a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one other fungicide.
  • a fungicidal composition comprising a compound corresponding to any of the compound embodiments described above.
  • This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • compositions comprising a compound corresponding to any of the compound embodiments described above.
  • This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof).
  • a compound of Formula 1 including all geometric and stereoisomers, iV-oxides, and salts thereof.
  • methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above.
  • the compounds are applied as compositions of this invention.
  • compounds of Formula 1 that are compounds of Formula IP (including all geometric and stereoisomers), iV-oxides, and salts thereof, and also agricultural compositions containing them and their use as fungicides:
  • Q 1 and Q 2 are independently phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R 3 ;
  • X is O, S(O) m or NR 4 ;
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 - C 7 cycloalkyl, CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or
  • R 1 is phenyl optionally substituted with up to 3 R 8 ; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R 9a on carbon atom ring members and R 9 ⁇ on nitrogen atom ring members;
  • R 2 is CH 3 , CH 2 CH 3 , cyclopropyl or halogen; each R 3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 1 -C 3 alkylthio, C 1 -C 3 haloalkylthio, C 1 -C 3 alkylsulfmyl, C 1 -C 3 haloalkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 1 -C 3 haloalkylsulfonyl, C 3 -C 4 cycloalkyl, C 3 -C 7 cycloalkoxy, C 4 -C 6 alkylcycloalkyl, C 4 -C 6 cycloalkylalkyl
  • R 5 is H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl;
  • R 6 and R 7 are independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, C 4 -C 8 cycloalkylalkyl and C 4 -C 8 alkylcycloalkyl; or
  • R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O) n and NR 13 ; each R 8 , R 9a and R 915 is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano, nitro, SCH 3 , S(O)CH 3 and S(O) 2 CH 3 ;
  • R 10 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl
  • R 11 is C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 7 alkoxyalkyl, C 2 -C 7 alkylaminoalkyl, C 2 -C 8 dialkylaminoalkyl, C 1 -C 6 alkylthio or C 2 -C 7 alkylthioalkyl; each R 12 is independently C 3 -C 7 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulf ⁇ nyl or C 1 -C 4 alkylsulfonyl; R 13 is H, C 1 -C 3 alkyl or C 2 -C 3 haloalkyl; W is O or S; M + is a cation; m is 0, 1 or 2; and n is 0, 1 or 2.
  • Q 1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R 3 ;
  • Q 2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R 3
  • X is O or NR 4 ;
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, CO 2 R 5 , C(O)NR 6 R 7 , cyano, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or C 2 -C 5 alkoxyalkyl; or R 1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R 9a on carbon atom ring members and R 9 ⁇ on nitrogen atom ring members; R 2 is CH 3 , CH 2 CH 3 , Cl or Br; each R 3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy C 1 -C 3 alkylthio, C 1
  • R 7 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 4 -C 8 alkylcycloalkyl; or R 6 and R 7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR 13 ; each R 8 is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro; each R 9a is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro; each R9b
  • R 13 is H or CH 3 .
  • Embodiment BP A compound of Embodiment AP wherein
  • Q 1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R 3 ;
  • Q 2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R 3 ;
  • X is NR 4 ;
  • R 1 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, cyano, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy;
  • R 2 is CH 3 ; each R 3 is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkoxy and C 1 -C 3 haloalkoxy;
  • R 4 is H, formyl, C 3 -C 7 cycloalkyl or -SR 10 ; or C 1 -C 6 alkyl substituted
  • Q 1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; or
  • Q 1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ;
  • Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ;
  • X is O;
  • R 2 is CH 3 ; each R 3 is independently selected from F, Cl, Br, cyano, nitro, CH 3 , CF 3 , -OCH 3 , and
  • R 4 is H, formyl or cyclopropyl.
  • Embodiment DP A compound of Embodiment CP wherein
  • Q 1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ;
  • Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; each R 3 is independently selected from F, Cl, cyano and -OCH 3 ;
  • R 4 is H.
  • Embodiment EP A compound of Embodiment BP wherein
  • Q 1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R 3 ;
  • Q 2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R 3 ; each R 3 is independently selected from F, Cl, CN and -OCH 3 ; and
  • R 4 is H.
  • fungicidal composition comprising a fungicidally effective amount of a compound of Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof) or any one of counterpart embodiments that are embodiment counterparts to
  • Embodiments 1 through 139 and Embodiments A through F e.g., Embodiment AP, BP, CP,
  • DP or EP DP or EP
  • additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula IP
  • sulfoxides and sulfones of Formula Ib can be made via oxidation of the linking sulfur atom on sulfides of Formula Ia (i.e. Formula 1 wherein X is S(O) m and m is 0).
  • a compound of Formula Ib wherein m is 1 (i.e. sulfoxides) or m is 2 (i.e. sulfones) is prepared by oxidizing a corresponding sulfide of Formula Ia with a suitable oxidizing agent.
  • an oxidizing agent in an amount from 1 to 4 equivalents depending on the oxidation state of the product desired is added to a solution of the compound of Formula Ia in a solvent.
  • Useful oxidizing agents include Oxone® (potassium peroxymonosulfate), hydrogen peroxide, sodium periodate, peracetic acid and 3-chloroperbenzoic acid.
  • the solvent is selected with regard to the oxidizing agent employed.
  • Aqueous ethanol or aqueous acetone is preferably used with potassium peroxymonosulfate, and dichloromethane is generally preferable with 3-chloroperbenzoic acid.
  • Useful reaction temperatures typically range from -78 to 90 0 C. Particular procedures useful for oxidizing sulfides to sulfoxides and sulfones are described by Brand et al., J. Agric. Food Chem. 1984, 32, 221-226 and references cited therein.
  • compounds of Formula 1 in which X is NH and R la is H can be prepared by the reaction of lH-pyrazole compounds of Formula 2 with various alkylating agents (e.g., Formula 3), such as iodoalkanes, alkylsulfonates (e.g., mesylate (OMs) or tosylate (OTs)) or trialkyl phosphates, preferably in the presence of an organic or inorganic base such as l,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate or potassium hydroxide, and in a solvent such as N, ⁇ /-dimethylformamide, tetrahydrofuran, toluene or water.
  • alkylating agents e.g., Formula 3
  • alkylating agents e.g., Formula 3
  • alkylating agents e.g., Formula 3
  • alkylsulfonates e.g., mesylate (OMs)
  • Compounds of Formula 1 wherein CHR 1 R ⁇ forms an optionally substituted cyclopropyl ring can likewise be prepared by reaction of a pyrazole of Formula 2 with an organometallic reagent, such as tricyclopropylbismuth, in the presence of a catalyst, such as copper acetate, under conditions known in the art. See, for example, J. Am. Chem. Soc. 2007, 129(1), 44-45. Of note as starting materials in the method of Scheme 2 are compounds of Formula 2 specifically disclosed in Tables 588 through 671 below.
  • compounds of Formula 1 can be prepared by the reaction of compounds of Formula 4 (i.e. 5-aminopyrazoles for X being NR 4 , 5-hydroxypyrazoles (5 -pyrazolones) for X being O, or 5-mercaptopyrazoles for X being S) with aromatic compounds of Formula 5 containing a leaving group G (i.e. halogen or (halo)alkylsulfonate), optionally in the presence of a metal catalyst, and generally in the presence of a base and a polar aprotic solvent such as ⁇ /, ⁇ /-dimethylformamide or dimethyl sulfoxide.
  • a leaving group G i.e. halogen or (halo)alkylsulfonate
  • compounds of Formula 5 in which Q 2 is an electron-deficient heteroaromatic ring, or a benzene ring with electron-withdrawing substituents react by direct displacement of the leaving group G from the ring to provide compounds of Formula 1.
  • G is typically Cl, Br, I or a sulfonate (e.g., OS(O) 2 CH 3 ).
  • Compounds of Formula 5 are commercially available or their preparation is known in the art. Of note are embodiments of the method of Scheme 3 wherein a compound of Formula 4 is used to prepare a corresponding compound of Formula 1 specifically disclosed in Tables 85 through 252 below.
  • a metal catalyst e.g., metal or metal salt
  • G is Br or I or a sulfonate such as OS(O) 2 CF 3 or OS(O) 2 (CF 2 ) 3 CF 3 .
  • copper salt complexes e.g., CuI with JV. ⁇ /'-dimethyl- ethylenediamine, proline or bipyridyl
  • palladium complexes e.g., tris(dibenzylidene- acetone)dipalladium(O)
  • palladium salts e.g., palladium acetate
  • ligands such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (i.e. "Xantphos"), 2-dicyclohexyl- phosphino-2',4',6'-triisopropylbiphenyl (i.e.
  • Xphos 2,2'-bis(diphenylphosphino)- l,l'-binaphthalene
  • BINAP 2,2'-bis(diphenylphosphino)- l,l'-binaphthalene
  • a base such as potassium carbonate, cesium carbonate, sodium phenoxide or sodium tert-butoxide
  • solvent such as ⁇ /, ⁇ /-dimethylformamide, 1 ,2-dimethoxy ethane, dimethyl sulfoxide, 1,4-dioxane or toluene, optionally mixed with alcohols such as ethanol, can be used.
  • compounds of Formula Ic i.e.
  • Formula 1 in which X is NR 4 and R 4 is H can be prepared by reaction of compounds of Formula 6 (i.e. 5-bromopyrazoles or other pyrazoles substituted at the 5 -position with a leaving group) with compounds of Formula 7 under metal-catalyzed conditions similar to those described above for Scheme 3.
  • compounds of Formula 7 are commercially available or their preparation is known in the art.
  • compounds of Formula 6 wherein G is Br or I can be prepared by reaction of 5-aminopyrazoles of Formula 4a (i.e. Formula 4 wherein X is NH) under diazotization conditions either in the presence of, or followed by combination with, copper salts containing bromide or iodide.
  • 5-aminopyrazoles of Formula 4a i.e. Formula 4 wherein X is NH
  • diazotization conditions either in the presence of, or followed by combination with, copper salts containing bromide or iodide.
  • tert-butyl nitrite to a solution of a 5-aminopyrazole of Formula 4a in the presence of CuBr 2 in a solvent such as acetonitrile provides the corresponding 5-bromopyrazole of Formula 6.
  • a 5-aminopyrazole of Formula 4a can be converted to a diazonium salt and then to a corresponding 5-halopyrazole of Formula 6 by treatment with sodium nitrite in solvents such as water, acetic acid or trifluoroacetic acid, in the presence of a mineral acid typically containing the same halide atom (such as aqueous HI solution for G being I), followed by treatment with the corresponding copper(I) or copper(II) salt according to general procedures well known to those skilled in the art.
  • solvents such as water, acetic acid or trifluoroacetic acid
  • G is Br or I.
  • 5-bromopyrazoles of Formula 6a i.e. Formula 6 wherein G is Br
  • 5-hydroxypyrazoles of Formula 4b i.e. Formula 4 wherein X is O
  • phosphorus tribromide as described in Tetrahedron Lett. 2000, 47(24), 4713.
  • 5-hydroxypyrazoles of Formula 4b can also be used to prepare 5-fluoroalkylsulfonyl (e.g, 5-trifluoromethanesulfonyl, 5-nonafluorobutylsulfonyl) pyrazoles of Formula 6b (i.e. Formula 6 wherein G is fluoroalkylsulfonyl) as described in Synlett 2004, 5, 795.
  • 5-fluoroalkylsulfonyl e.g, 5-trifluoromethanesulfonyl, 5-nonafluorobutylsulfonyl
  • Formula 6b i.e. Formula 6 wherein G is fluoroalkylsulfonyl
  • Rf is fluoroalkyl such as CF3 or (CF 2 ) 2 CF3
  • a 4-bromo or iodo pyrazole of Formula 10 Reaction of a 4-bromo or iodo pyrazole of Formula 10 with a boronic acid, trialkyltin, zinc or organomagnesium reagent of Formula 11 in the presence of a palladium or nickel catalyst having appropriate ligands (e.g., triphenylphosphine (PPI1 3 ), dibenzylideneacetone (dba), dicyclohexyl(2',6'-dimethoxy- [l,l'-biphenyl]-2-yl)phosphine (SPhos)) and a base, if needed, affords the corresponding compound of Formula 1.
  • PPI1 3 triphenylphosphine
  • dba dibenzylideneacetone
  • SPhos dicyclohexyl(2',6'-dimethoxy- [l,l'-biphenyl]-2-yl)phosphin
  • a substituted aryl boronic acid or derivative e.g., Formula 11 wherein Q 1 is optionally substituted phenyl or heterocyclyl and M is B(OH) 2 , B(OC(CH 3 ) 2 C(CH 3 ) 2 ⁇ )) or B(O-Z-Pr) 3 / Li - reacts with a 4-bromo- or 4-iodopyrazole of Formula 10 in the presence of dichlorobis(triphenylphosphine) palladium(II) and aqueous base such as sodium carbonate or potassium hydroxide, in solvents such as 1,4-dioxane, 1 ,2-dimethoxyethane, toluene or ethyl alcohol, or under anhydrous conditions with a ligand such as phosphine oxide or phosphite ligand (e.g., diphenylphosphine oxide) and potassium fluoride in a solvent such as 1,4-dio
  • Sn(Me) 3 , Sn(Bu) 3 , ZnCl, MgBr, 10 G is Br, I MgCl or MgCl-LiCl.
  • compounds of Formula 4a i.e. Formula 4 wherein X is NH
  • compounds of Formula 11 such as Q i -B(OH) 2 (Formula Ha)
  • transition-metal-catalyzed cross-coupling reaction conditions as described for the method of Scheme 8.
  • halogenating reagents such as bromine, sodium bromite, ⁇ /-bromosuccinimide (NBS) or JV-iodosuccinimide (NIS)
  • solvents such as acetic
  • compounds of Formula 13 wherein A is H or a protecting group can be converted into intermediates corresponding to Formula 10 wherein Q 2 is replaced by A or a protecting group, respectively, which are useful for preparing compounds of Formula 1.
  • Compounds of Formula 13 wherein A is H can be be prepared by methods known in the art; see, for example, Synlett 2004, 5, 795-798, US 4256902 and references cited therein.
  • some compounds of Formula 13 wherein A is H, particularly those in which R 2 is methyl, ethyl or halogen, are commercially available.
  • compounds of Formula 13 wherein X is O, S(O ) m or NR 4 , m is 0, and A is Q 2 can be prepared from corresponding compounds of Formula 13a (i.e. Formula 13 wherein A is H) by procedures analogous those used for the method of Scheme 3.
  • Compounds of Formula 13 wherein X is S i.e. S(O ) m wherein m is 0
  • Compounds of Formula 13a are commercially available or can be prepared by methods known in the art.
  • CHR 1 R ⁇ G is F, Cl, Br, I, NO 2 , OS(O) 2 CF 3 , etc.
  • Formula Id i.e. Formula 1 wherein X is CR 15 R 16 , R 15 is H, R 16 is OR 18 and R 18 is H
  • an organometallic reagent i.e. Formula 26
  • an alkyllithium preferably n-butyllithium, or an alkylmagnesium reagent, preferably isopropylmagnesium chloride (optionally complexed with lithium chloride
  • a sulfur electrophile i.e. Formula 27
  • carbonyl electrophile i.e. Formula 28, 29 or 30
  • Reaction temperatures can range from -90 0 C to the boiling point of the reaction solvent; temperatures of -78 0 C to ambient temperature are generally preferred, with temperatures of -78 to -10 0 C preferred when an alkyllithium reagent is used, and -20 0 C to ambient temperature preferred with use of alkylmagnesium reagents.
  • solvents are useful, such as toluene, ethyl ether, tetrahydrofuran or dimethoxymethane; anhydrous tetrahydrofuran is preferred.
  • a second metallic component such as zinc chloride, zinc bromide or a monovalent copper salt, such as copper(I) iodide or copper(I) cyanide, can advantageously be added before the electrophile in cases in which the electrophile is Q 2 C(O)Cl (i.e. Formula 30).
  • the Q 2 -containing sulfur and carbonyl intermediates of Formulae 27, 28, 29 and 30 are commercially available or can be prepared by methods known in the art.
  • 5-thiopyrazole compounds of Formula 4c can be prepared by reaction of corresponding 5-hydroxypyrazole compounds of Formula 4b with P 2 S 5 (see, for example, Justus Liebigs Annalen der Chemie 1908, 361, 251) or with Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane 2,4-disulfide; see, for example, International Patent Publication WO 2005/118575) in solvents such as toluene, xylene or tetrahydrofuran.
  • P 2 S 5 see, for example, Justus Liebigs Annalen der Chemie 1908, 361, 251
  • Lawesson's Reagent 2,4-bis-(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane 2,4-disulfide
  • solvents such as toluene, x
  • compounds of Formula Ic i.e. Formula 1 wherein X is NR 4 and R 4 is H
  • a solvent such as ethanol or methanol
  • an acid or base catalyst such as acetic acid, piperidine or sodium methoxide
  • R 32 is H or lower alkyl (e.g., CH 3 , CH 2 CH 3 or (CH 2 ) 2 CH 3 )
  • compounds of Formula 2 wherein X is NH can be similarly prepared by condensing compounds of Formula 17 with hydrazine. This method is described in Chemistry of Heterocyclic Compounds 2005, 41(1), 105-110.
  • compounds of Formula 17 (wherein, e.g., R 2 is methyl, ethyl or optionally substituted cyclopropyl and R 33 is H or lower alkyl such as CH 3 , CH 2 CH 3 or (CH 2 ) 2 CH 3 ) can be prepared by reaction of corresponding ketene dithioacetal compounds of Formula 18 with compounds of formula Q 2 -NH 2 (i.e.
  • Formula 7) optionally in the presence of a base, such as sodium hydride or ethylmagnesium chloride, in solvents such as toluene, tetrahydrofuran or dimethoxymethane, at temperatures ranging from -10 0 C to the boiling point of the solvent.
  • a base such as sodium hydride or ethylmagnesium chloride
  • solvents such as toluene, tetrahydrofuran or dimethoxymethane, at temperatures ranging from -10 0 C to the boiling point of the solvent.
  • R 33 is H or lower alkyl (e.g., CH 3 , CH 2 CH 3 or (CH 2 ) 2 CH 3 )
  • compounds of Formula 17a i.e. tautomer of Formula 17 wherein R 33 is H
  • compounds of Formula 19a can be prepared by reaction of corresponding isothiocyanate compounds of Formula 19 with arylacetone compounds of Formula 20 wherein R 2 is methyl, ethyl or optionally substituted cyclopropyl; see, for example, Zhurnal Organicheskoi Khimii 1982, 0 18(12), 2501.
  • Bases useful for this reaction include sodium hydride, alkoxide bases (e.g., potassium te/t-butoxide or sodium ethoxide), potassium hydroxide, sodium hydroxide, potassium carbonate, or amine bases (e.g., triethylamine or JV,jV-diisopropylethylamine).
  • alkoxide bases e.g., potassium te/t-butoxide or sodium ethoxide
  • potassium hydroxide sodium hydroxide
  • potassium carbonate e.g., triethylamine or JV,jV-diisopropylethylamine
  • amine bases e.g., triethylamine or JV,jV-diisopropylethylamine.
  • solvents such as tetrahydrofuran, ether, toluene, ⁇ f,iV-dimethyl- formamide, alcohols (e.g., ethanol), esters (e
  • Solvents are chosen for compatibility with the base selected, as is well- known in the art. Reaction temperatures can range from -78 0 C to the boiling point of the solvent.
  • One useful mixture of base and solvent is potassium tert-butoxide in tetrahydrofuran, to which at -70 to 0 0 C is added a combined solution of an isothiocyanate of Formula 19 and a carbonyl compound of Formula 20.
  • Ketothioamides of Formula 17 can be also be prepared by allowing the corresponding ketoamides to react with sulfurizing agents such as Lawesson's reagent or P 2 S 5 ; see, for example, HeIv. Chim. Act. 1998, 57(7), 1207.
  • sulfurizing agents such as Lawesson's reagent or P 2 S 5 ; see, for example, HeIv. Chim. Act. 1998, 57(7), 1207.
  • R la are H and R 2 is OCH 3 ) can be prepared by reacting corresponding compounds of
  • compounds of Formula 31 wherein X is NH can be prepared by condensation of corresponding isothiocyanates of Formula 19 with esters of Formula 33 wherein R 33 is lower alkyl (e.g., methyl, ethyl, propyl) in the presence of a strong, non- nucleophilic base such as sodium hydride or lithium hexamethyldisilazide, in an inert solvent such as tetrahydrofuran (analogous to the method of Scheme 18), followed by reaction of the intermediate with hydrazine or an acid salt of hydrazine, such as, for example, an acetate or hydrochloride salt (analogous to the method of Scheme 16).
  • a strong, non- nucleophilic base such as sodium hydride or lithium hexamethyldisilazide
  • an inert solvent such as tetrahydrofuran
  • R 33 is lower alkyl
  • the methylating agent can be included in the reaction mixture with the compounds of Formulae 21 and 22 without isolation of the cyano ketoamide intermediate.
  • compounds of Formula 23 can also be prepared by a method analogous to Scheme 17 wherein the C(O)R 2 of the compound of Formula 18 is replaced by cyano.
  • the resultant compound of Formula 23 is then reacted with an alkylhydrazine of Formula 15 to form the corresponding 3-aminopyrazole compound of Formula 24 using general procedures known in the art; see, for example, J. Chem. Soc. Perkin 1 1988, 2, 169-173 and J. Med. Chem. 2003, 46(7), 1229-1241.
  • the amino group of the compound of Formula 24 can then be converted to R 2 being halogen in Formula Ic by a diazotization reaction using conditions known in the art, such as those previously described for Scheme 5.
  • R is halogen
  • compounds of Formula 2 wherein X is NH and R 2 is halogen can be similarly prepared by condensing compounds of Formula 23 with hydrazine instead of an alkylhydrazine of Formula 15.
  • compounds of Formula Ih i.e. Formula 1 wherein X in NR 4
  • compounds of Formula Ic i.e. Formula 1 wherein X is NH
  • an electrophile comprising R 4 (i.e. Formula 25) typically in the presence of a base such as NaH and a polar solvent such as ⁇ f, ⁇ /-dimethylformamide.
  • electrophile comprising R 4 means a chemical compound capable of transferring an R 4 moiety to a nucleophile (such as the nitrogen atom attached to Q 2 in Formula Ic).
  • electrophiles comprising R 4 have the formula R 4 Lg wherein Lg is a nucleofuge (i.e. leaving group in nucleophilic reactions).
  • Typical nucleofuges include halogens (e.g., Cl, Br, I) and sulfonates (e.g., OS(O) 2 CH 3 , OS(O) 2 CF 3 , OS(O) 2 -(4-CH 3 -Ph)).
  • electrophiles comprising R 4 do not comprise a nucleofuge; an example is sulfur trioxide (SO 3 ), which after deprotonation (such as by a base of the formulae M + H ⁇ wherein M + is a cation) of the nitrogen atom attached to Q 2 in Formula Ic, can bond to the nitrogen atom as a -SO 3 ⁇ M + substituent.
  • SO 3 sulfur trioxide
  • aromatic amines anilines
  • aromatic halides such as bromides or iodides prepared via the Sandmeyer reaction can react with alcohols under copper-catalyzed conditions, such as the Ullmann reaction or known modifications thereof, to provide compounds of Formula 1 that contain alkoxy substituents.
  • some halogen groups such as fluorine or chlorine, can be displaced with alcohols under basic conditions to provide compounds of Formula 1 containing the corresponding alkoxy substituents.
  • the resultant alkoxy compounds can themselves be used in further reactions to prepare compounds of Formula 1 wherein R 3 is -U-V-T (see, for example, PCT Publication WO 2007/149448 A2).
  • Compounds of Formula 1 or precursors thereof in which R 2 or R 3 is halide, preferably bromide or iodide, are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1.
  • sulfide groups can be oxidized to the corresponding sulfoxides or sulfones by conditions well-known in the art.
  • ketones can be readily converted to ketals using general methods known in the art, thus providing compounds of Formula 1 wherein X is CR 15 R 16 and R 15 and R 16 are taken together as -OCH 2 CH 2 O-.
  • compounds of Formula 1 wherein X is CR 15 R 16 , R 15 is C 1 -C 4 alkyl, R 16 is OR 18 , and R 18 is H can be prepared by adding an alkyl Grignard reagent to the corresponding compounds of Formula 1 wherein X is C(O).
  • the reaction mixture was heated to 70 0 C, and a solution of 2,4-difluorophenylacetonitrile (3.9 g, 25 mmol), ethyl acetate (3.8 mL, 38 mmol) and xylenes (1 mL) was added dropwise over 15 min. Additional xylenes (5 mL) was added to aid stirring.
  • the reaction mixture was heated for 2 h, then allowed to cool. Water (50 mL) was added, and the mixture was extracted with hexanes (50 mL). The aqueous phase was then acidified to p ⁇ 3-4 with 1 N aqueous HCl solution.
  • Step B Preparation of 4-(2,4-Difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
  • 9,9-dimethylxanthene (460 mg, 0.80 mmol) and powdered potassium carbonate (5.5 g, 40 mmol) were combined in anhydrous 1,4-dioxane (20 mL), and the mixture was sparged with a subsurface stream of N 2 gas for 10 min.
  • 4-(2,4-Difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine i.e. the product of Step B) (0.89 g, 4.0 mmol) was added in one portion, and l-bromo-3-chlorobenzene (0.47 mL, 4.0 mmol) was added via a syringe.
  • the reaction mixture was heated at reflux under a nitrogen atmosphere for 3 h. Additional l-bromo-3-chlorobenzene (0.09 mL, 0.8 mmol) was added, and heating was continued for
  • Example 1 (2.4 g, 10 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyi nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous HCl solution (20 mL) was added, and then ethyl acetate was added
  • the filter pad was washed with ethyl acetate (20 mL), and the phases were separated.
  • the organic phase was washed with 1.0 N aqueous hydrochloric acid solution and brine, dried over MgSO ⁇ and concentrated to leave the title compound as an orange-brown semisolid (2.8 g).
  • Step A) (0.20 g, 0.66 mmol), palladium(II) acetate (15 mg, 0.066 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.13 mmol) and powdered potassium carbonate (1.8 g, 13 mmol) were combined in anhydrous 1,4-dioxane (3 mL), and the mixture was sparged with a subsurface stream of N 2 gas for 10 min. 2,6-Difluoro-
  • Step B Preparation of ⁇ -Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile Solid sodium ethoxide (4.7 g, 66 mmol) was stirred in a mixture of xylene (20 mL) and ethanol (10 mL) and heated to 50 0 C.
  • Step C Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazole- 5 -amine ⁇ -Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step B) (8.03 g, 35.7 mmol) and acetic acid (5 mL) were stirred in ethanol (35 mL), and methylhydrazine (1.91 mL, 35.7 mmol) was added. The reaction mixture was heated at reflux for 16 h, cooled, and then poured into water (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL).
  • Step D Preparation of 5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl- lH-pyrazole
  • Aqueous hydrochloric acid solution (25 mL) was added, then ethyl acetate (25 mL) was added, and the resulting mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid.
  • the filter pad was washed with ethyl acetate (50 mL), and the phases were separated.
  • the organic phase was washed with 1 N aqueous HCl solution (25 mL) and brine (25 mL), dried over MgSO 4 , and concentrated.
  • 2,4,6-Trifluoroaniline (0.28 g, 1.9 mmol) was added in one portion, and the reaction mixture was heated at reflux under nitrogen for 22 h. The reaction mixture was cooled, then filtered through Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (2O mL), and the filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO ⁇ and concentrated to leave a semisolid residue.
  • Step B Preparation of 3,5-Difluoro-4-[(4-iodo-l,3-dimethyl-lH-pyrazol-
  • Step A Preparation of ⁇ -Acetyl-2,4-dichloro-iV-(2,4-difiuorophenyl)benzene- ethanethioamide
  • 2,4-Difluorophenyl isothiocyanate (0.27 mL, 2.0 mmol) was added to a stirred suspension of sodium hydride (60% in mineral oil) (112 mg, 2.8 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice-water bath under a nitrogen atmosphere.
  • a solution of (2,4-dichlorophenyl)-2-propanone (570 mg, 2.8 mmol) in tetrahydrofuran (4 mL) was added dropwise over 5 min. The resultant yellow solution was stirred at 5-10 0 C for 1 h. Water (10 mL) was carefully added, and the reaction mixture was extracted with ethyl acetate (10 mL).
  • reaction mixture was quenched by the addition of saturated aqueous
  • Step B Preparation of Methyl ⁇ -acetyl-2,4,6-trifluorobenzeneacetate
  • reaction mixture was stirred for an additional 30 minutes, and then while maintaining the -65 0 C temperature, a solution of freshly distilled acetyl chloride (0.80 mL, 11 mmol) in dry tetrahydrofuran (3 mL) was added dropwise.
  • the reaction mixture was allowed to warm slowly to ambient temperature, and then water (30 mL) was added.
  • the resultant mixture was extracted with ethyl acetate (60 mL).
  • the aqueous phase was acidified with 1 N hydrochloric acid and extracted with ethyl acetate (60 mL). Only the first extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product.
  • This solid was suspended in a small volume of ethyl acetate (about 5 mL), an equal volume of hexanes was gradually added, and the suspension was stirred for 30 minutes.
  • the solid component was collected on a glass frit, washed with small portions of ethyl acetate/ hexanes (1 :1 and 1 :2 v:v), and allowed to dry in air to provide a white solid (1.02 g). Evaporation of the mother liquor and treatment of the resultant residue with small volumes of ethyl acetate and hexanes as already described provided an additional 0.13 g of solid containing the title product (1.15 g total).
  • Step D Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-l,3-dimethyl-4-(2,4,6- trifluorophenyl)-lH-pyrazole l,3-Dimethyl-4-(2,4,6-trifluorophenyl)-lH-pyrazol-5-ol (i.e. the product of Step C) (0.310 g, 1.28 mmol), was combined with 3,4,5-trifluoronitrobenzene (157 ⁇ L, 1.35 mmol) and potassium carbonate powder (0.27 g, 2 mmol) in dry ⁇ f, ⁇ /-dimethylformamide (4 mL). This mixture was stirred and heated at 80 0 C for 45 minutes and then allowed to cool.
  • reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The organic phase was washed with water and with brine, dried over MgSO ⁇ and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate (30% to 100%) in hexane to give the title product, a compound of the present invention, as an off- white solid (209 mg).
  • Q 1 is 2,6-di-F-Ph, and R 2 is Me.
  • 2-C1-4-F 2-F-4-C1 2,4-di-Cl 2,6-di-Cl 2,4,6-tri-Cl
  • the present disclosure also includes Tables 2 through 84, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. "Q 1 is 2,6-di-F-Ph, and R 2 is Me.") is replaced with the respective row heading shown below.
  • Table 2 the row heading is "Q 1 is 2,6-di-F-Ph, and R 2 is CL", and (R 3 ) p is as defined in Table 1 above.
  • the first entry in Table 2 specifically discloses 2-chloro-4-(2,6- difluorophenyl)- ⁇ /-(2-fluorophenyl)-l -methyl- lH-pyrazol-5-amine.
  • Tables 3 through 84 are constructed similarly.
  • Q 1 is 2,6-di-F -Ph, and R 2 is Cl.
  • 47 Q 1 is 2-Br-Ph, and R 2 is Cl.
  • J Q 1 is 2,6-di-F -Ph, and R 2 is Br.
  • Q 1 is 2-Br-Ph, and R 2 is Br.
  • Q 1 is 2,4,6-tri -F-Ph, and R 2 is Me.
  • Q 1 is 2,4-di-Cl-Ph, and R 2 is Me.
  • Q 1 is 2,4,6-tri -F-Ph, and R 2 is Cl.
  • Q 1 is 2,4,6-tri -F-Ph, and R 2 is Br.
  • Q 1 is 2,4-di-Cl-Ph, and R 2 is Br.
  • Q 1 is 2,6-di-F -4-OMe-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-Cl-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-F 4-OMe-Ph, and R 2 is Cl.
  • 56 Q 1 is 2,6-di-Cl-Ph, and R 2 is Cl.
  • 12 Q 1 is 2,6-di-F -4-OMe-Ph, and R 2 is Br.
  • 57 Q 1 is 2,6-di-Cl-Ph, and R 2 is Br.
  • 12A Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Me.
  • 58 Q 1 is 2-F-4-MeO-Ph, and R 2 is Me.
  • 12B Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Cl.
  • 59 Q 1 is 2-F-4-MeO-Ph, and R 2 is Cl.
  • 12C Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Br.
  • 60 Q 1 is 2-F-4-MeO-Ph, and R 2 is Br.
  • Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Me.
  • 6OA Q 1 is 2-F-4-EtO-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Cl.
  • 6OB Q 1 is 2-F-4-EtO-Ph, and R 2 is Cl.
  • Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Br.
  • 6OC Q 1 is 2-F-4-EtO-Ph, and R 2 is Br.
  • Q 1 is 2-Cl-4-F-Ph, and R 2 is Me.
  • 61 Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Me.
  • Q 1 is 2-Cl-4-F-Ph, and R 2 is Cl.
  • 62 Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Cl.
  • Q 1 is 2-Cl-4-F-Ph, and R 2 is Br.
  • Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Br.
  • Q 1 is 2-Cl-6-F-Ph, and R 2 is Me.
  • 63A Q 1 is 2-Cl-4-EtO-Ph, and R 2 is Me.
  • Q 1 is 2-Cl-6-F-Ph, and R 2 is Cl.
  • 63B Q 1 is 2-Cl-4-EtO-Ph, and R 2 is Cl.
  • Q 1 is 4-Cl-2,6-di-F-Ph, and R 2 is Cl.
  • 66B Q 1 is 2-Br-4-EtO-Ph, and R 2 is Cl.
  • 27 Q 1 is 4-Cl-2,6-di-F-Ph, and R 2 is Br.
  • 66C Q 1 is 2-Br-4-EtO-Ph, and R 2 is Br.
  • 28 Q 1 is 2-Br-4-F-Ph, and R 2 is Me.
  • 67 Q 1 is 2-F-4-CN-Ph, and R 2 is Me.
  • 29 Q 1 is 2-Br-4-F-Ph, and R 2 is Cl.
  • 68 Q 1 is 2-F-4-CN-Ph, and R 2 is Cl.
  • Q 1 is 2-Cl-Ph, and R 2 is Me.
  • 82 Q 1 is 2,5-di-Cl-3-thienyl, and R 2 is Me.
  • 44 Q 1 is 2-Cl-Ph, and R 2 is Cl.
  • 83 Q 1 is 2,5-di-Cl-3-thienyl, and R 2 is Cl.
  • 45 Q 1 is 2-Cl-Ph, and R 2 is Br.
  • 84 Q 1 is 2,5-di-Cl-3-thienyl, and R 2 is Br.
  • 46 is 2-Br-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-F-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • 2-F-4-Br 2-Br-6-F 2-Cl-4-Br 2-Br-4-Cl 2-I-4-F
  • the present disclosure also includes Tables 86 through 280, each of which is constructed the same as Table 85 above, except that the row heading in Table 85 (i.e. "pi is 2,6-di-F-Ph, X is O, RI and R ⁇ a are both H, and R ⁇ is Me.") is replaced with the respective row heading shown below.
  • Table 86 the row heading is "Q 1 is 2,6-di-F-Ph, X is O, R 1 and R la are both H, and R 2 is Cl.” and (R 3 ) p is as defined in Table 85 above.
  • Table 87 through 280 are constructed similarly.
  • Q 1 is 2,6-di-F-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2,6-di-F-4-CN-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2,6-di-F-4-CN-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • 100 Q 1 is 2-Cl-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 101 Q 1 is 2-Cl-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 102 Q 1 is 2-Cl-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 103 Q 1 is 2-Cl-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 104 Q 1 is 2-Cl-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 105 Q 1 is 2-Cl-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 106 Q 1 is 2-Cl-4,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 107 Q 1 is 2-Cl-4,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 108 Q 1 is 2-Cl-4,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 109 Q 1 is 4-Cl-2,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 110 Q 1 is 4-Cl-2,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 111 Q 1 is 4-Cl-2,6-di-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 112 Q 1 is 2-Br-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 113 Q 1 is 2-Br-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 114 Q 1 is 2-Br-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 115 Q 1 is 2-Br-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 116 Q 1 is 2-Br-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 117 Q 1 is 2-Br-6-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 118 Q 1 is 2-Me-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 119 Q 1 is 2-Me-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 120 Q 1 is 2-Me-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 121 Q 1 is 2-1-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 122 QI is 2-1-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 123 Q 1 is 2-1-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 124 Q 1 is 2-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 126 Q 1 is 2-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 127 Q 1 is 2-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 128 Q 1 is 2-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 129 Q 1 is 2-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 130 Q 1 is 2-Br-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 131 Q 1 is 2-Br-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 132 Q 1 is 2-Br-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 133 Q 1 is 2-F-4-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 134 Q 1 is 2-F-4-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 135 Q 1 is 2-F-4-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • 136 Q 1 is 2,4-di-Cl-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • Q 1 is 2,6-di-Cl-Ph, X is O, R 1 and R la are both H, and R 2 is Br.
  • 142 Q 1 is 2-F-4-MeO-Ph, X is O, R 1 and R l a are both H, and R 2 is Me.
  • 143 Q 1 is 2-F-4-MeO-Ph, X is O, R 1 and R l a are both H, and R 2 is Cl.
  • 144 Q 1 is 2-F-4-MeO-Ph, X is O, R 1 and R l a are both H, and R 2 is Br.
  • Q 1 is 2-F-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Br-4-MeO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Br-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • 150B Q 1 is 2-Br-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-Br-4-EtO-Ph
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is O
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Cl-3-thienyl
  • X is O
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-Cl-3-thienyl
  • X is O
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2,5-di-Cl-3-thienyl
  • X is O
  • R 1 and R la are both H
  • R 2 is Cl.
  • Q 1 is 2,6-di-F-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2,6-di-F-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • 180A Q 1 is 2,6-di-F-4-OEt-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 180B Q 1 is 2,6-di-F-4-OEt-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 180C Q 1 is 2,6-di-F-4-OEt-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 181 Q 1 is 2,6-di-F-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 182 Q 1 is 2,6-di-F-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 183 Q 1 is 2,6-di-F-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 184 Q 1 is 2-Cl-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 185 Q 1 is 2-Cl-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • Q 1 is 2-Cl-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • Q 1 is 2-Cl-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 188 is 2-Cl-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • Q 1 is 2-Cl-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 196 Q 1 is 2-Br-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • Q 1 is 2-Br-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 198 Q 1 is 2-Br-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 199 Q 1 is 2-Br-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 200 Q 1 is 2-Br-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 201 Q 1 is 2-Br-6-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 202 Q 1 is 2-Me-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 203 Q 1 is 2-Me-4-F-Ph, X is S, R 1 and R la are both H, and R 2 is Cl.
  • 204 Q 1 is 2-Me-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 205 Q 1 is 2-1-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 206 QI is 2-1-4-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 207 Q 1 is 2-1-4-F-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-F-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Br-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-F-4-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-F-4-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-F-4-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2,4-di-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2,4-di-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2,4-di-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2,6-di-Cl-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-F-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-F-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-F-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-F-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-F-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-F-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • 230 Q 1 is 2-Cl-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Cl.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Br-4-MeO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • Q 1 is 2-Br-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Me.
  • Q 1 is 2-Br-4-EtO-Ph
  • X is S
  • R 1 and R l a are both H
  • R 2 is Br.
  • 240 Q 1 is 2-Cl-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 241 Q 1 is 2-Br-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Me.
  • 242 Q 1 is 2-Br-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Cl.
  • 243 Q 1 is 2-Br-4-CN-Ph, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 252 Q 1 is 2,5-di-Cl-3-thienyl, X is S, R 1 and R l a are both H, and R 2 is Br.
  • 253 Q 1 is 2,6-di-F-Ph, X is NH, R 1 and R l a form c-Pr, and R 2 is Me.
  • 254 Q 1 is 2,4-di-F-Ph, X is O, R 1 is Et, R l a is H, and R 2 is Cl.
  • 255 Q 1 is 2,4,6-tri-F-Ph, X is S, R 1 and R l a are both H, and R 2 is Et.
  • 256 Q 1 is 2,6-di-F-4-OMe-Ph, X is CHOH, R 1 and R l a are both H, and R 2 is CF 3 .
  • 258 Q 1 is 2-Cl-4-F-Ph, X is CHOH, X is O, R 1 is c-Pr, R l a is H, and R 2 is Br.
  • 259 Q 1 is 2-Cl-6-F-Ph, X is S, R 1 and R l a form c-Pr, and R 2 is Me.
  • 260 Q 1 is 2-Cl-4,6-di-F-Ph, X is CHOH, R 1 is c-Pr, R l a is H, and R 2 is Cl.
  • 261 Q 1 is 4-Cl-2,6-di-F-Ph, X is NH, X is NH, R 1 is Et, R l a is H, and R 2 is Br.
  • 262 Q 1 is 2-Br-4-F-Ph, X is O, R 1 and R l a are both H, and R 2 is Et.
  • 264 Q 1 is 2-Me-4-F-Ph, X is CHOH, R 1 and R l a are both H, and R 2 is c-Pr.
  • 265 Q 1 is 2-1-4-F-Ph, X is NH, R 1 is CH 2 CF 3 , R l a is H, and R 2 is Me.
  • 266 Q 1 is 2-F-Ph, X is O, R 1 is CH 2 F, R l a is H, and R 2 is Cl.
  • 267 Q 1 is 2-Cl-Ph, X is S, R 1 and R l a are both H, and R 2 is CH 2 Cl.
  • Q 1 is 2-F-4-MeO-Ph
  • X is CHOCH 3
  • R 1 and R l a are both H
  • R 2 is Cl
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is NH
  • R 1 and R l a form c-Pr
  • R 2 is Br
  • Q 1 is 2-Br-4-MeO-Ph
  • X is O
  • R 1 is «-Pr
  • R l a is H
  • R 2 is Me.
  • Q 1 is 2-F-4-CN-Ph
  • X is NH
  • R 1 is CH 2 C ⁇ CH
  • R l a is H
  • R 2 is Cl.
  • Q 1 is 2,6-di-F-Ph
  • X is CHOH
  • R 2 is Me
  • the present disclosure also includes Tables 282 through 448, each of which is constructed the same as Table 281 above, except that the row heading in Table 281 (i.e. "Q 1 is 2,6-di-F-Ph, X is CHOH, and R ⁇ is Me.") is replaced with the respective row heading shown below.
  • Table 282 the row heading is "Q 1 is 2,6-di-F-Ph, X is CHOH, and R 2 is Cl.” and (R 3 ) p is as defined in Table 281 above.
  • Table 282 specifically discloses 3-chloro-4-(2,6-difluorophenyl)- ⁇ -(4-fluorophenyl)- 1 -methyl- lH-pyrazole-5-methanol.
  • Tables 283 through 448 are constructed similarly.
  • Q 1 is 2,4-di-F-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2,6-di-F-4-OEt-Ph
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2,6-di-F-4-OEt-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2,6-di-F-4-OEt-Ph
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2,6-di-F-4-CN-Ph
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2,6-di-F-4-CN-Ph
  • X is CHOH
  • R 2 is Br
  • Q 1 is 2-Cl-4-F-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-Cl-6-F-Ph
  • X is CHOH
  • R 2 is Me
  • 301 Q 1 is 2-Cl-6-F-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Cl-4,6-di-F-Ph
  • X is CHOH
  • R 2 is Me.
  • 304 Q 1 is 2-Cl-4,6-di-F-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Br-4-F-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2-Br-4-F-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2-Br-6-F-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Me-4-F-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-Me-4-F-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-1-4-F-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-1-4-F-Ph
  • X is CHOH
  • R 2 is Cl.
  • Q 1 is 2-1-4-F-Ph, X is CHOH, and R 2 is Br.
  • 320 Q 1 is 2-F-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-F-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-F-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Cl-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-Cl-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-Cl-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Br-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-Br-Ph, X is CHOH, and R 2 is Cl.
  • 328 Q 1 is 2-Br-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-F-4-Cl-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-F-4-Cl-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2,4-di-Cl-Ph
  • X is CHOH
  • R 2 is Me
  • 333 Q 1 is 2,4-di-Cl-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2,4-di-Cl-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2,6-di-Cl-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2,6-di-Cl-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2,6-di-Cl-Ph
  • X is CHOH
  • R 2 is Br
  • Q 1 is 2-F-4-MeO-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2-F-4-MeO-Ph
  • X is CHOH
  • R 2 is Cl
  • 340 Q 1 is 2-F-4-MeO-Ph, X is CHOH, and R 2 is Br.
  • 340A Q 1 is 2-F-4-EtO-Ph, X is CHOH, and R 2 is Me.
  • 340B Q 1 is 2-F-4-EtO-Ph, X is CHOH, and R 2 is Cl.
  • 340C Q 1 is 2-F-4-EtO-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2-Br-4-MeO-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2-Br-4-MeO-Ph
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2-Br-4-MeO-Ph
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2-Br-4-EtO-Ph
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2-F-4-CN-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-F-4-CN-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-F-4-CN-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Cl-4-CN-Ph
  • X is CHOH
  • R 2 is Me
  • Q 1 is 2-Cl-4-CN-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-Cl-4-CN-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2-Br-4-CN-Ph, X is CHOH, and R 2 is Me.
  • Q 1 is 2-Br-4-CN-Ph, X is CHOH, and R 2 is Cl.
  • Q 1 is 2-Br-4-CN-Ph, X is CHOH, and R 2 is Br.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2-Cl-3-thienyl
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2-Cl-3-thienyl
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2,5-di-Cl-3-thienyl
  • X is CHOH
  • R 2 is Me.
  • Q 1 is 2,5-di-Cl-3-thienyl
  • X is CHOH
  • R 2 is Cl
  • Q 1 is 2,5-di-Cl-3-thienyl
  • X is CHOH
  • R 2 is Br.
  • Q 1 is 2,6-di-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2,6-di-F-Ph
  • X is C(O)
  • R 2 is Br.
  • Q 1 is 2,4-di-F-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,4-di-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2,4,6-tri-F-Ph
  • X is C(O)
  • R 2 is Me.
  • Q 1 is 2,4,6-tri-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2,6-di-F-4-OMe-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,6-di-F-4-OMe-Ph, X is C(O), and R 2 is Br.
  • a Q 1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2,6-di-F-4-CN-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,6-di-F-4-CN-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2,6-di-F-4-CN-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Cl-4-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Cl-6-F-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Cl-6-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-6-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Br-4-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Br-4-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Br-6-F-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Br-6-F-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Me-4-F-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-F-4-Cl-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-F-4-Cl-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-F-4-Cl-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2,4-di-Cl-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,4-di-Cl-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2,6-di-Cl-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2,6-di-Cl-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-F-4-MeO-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-F-4-MeO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-F-4-EtO-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-F-4-EtO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-F-4-EtO-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Cl-4-MeO-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Cl-4-MeO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-4-MeO-Ph
  • X is C(O)
  • R 2 is Br.
  • Q 1 is 2-Cl-4-EtO-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Cl-4-EtO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-4-EtO-Ph
  • X is C(O)
  • R 2 is Br.
  • Q 1 is 2-Br-4-MeO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Br-4-EtO-Ph, X is C(O), and R 2 is Me.
  • 430B Q 1 is 2-Br-4-EtO-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-F-4-CN-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-F-4-CN-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Cl-4-CN-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Cl-4-CN-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Cl-4-CN-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2-Br-4-CN-Ph, X is C(O), and R 2 is Me.
  • Q 1 is 2-Br-4-CN-Ph, X is C(O), and R 2 is Cl.
  • Q 1 is 2-Br-4-CN-Ph, X is C(O), and R 2 is Br.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is C(O)
  • R 2 is Cl.
  • Q 1 is 2,5-di-Cl-3-pyridinyl
  • X is C(O)
  • R 2 is Br.
  • Q 1 is 2-Cl-3-thienyl
  • X is C(O)
  • R 2 is Me.
  • Q 1 is 2-Cl-3-thienyl
  • X is C(O)
  • R 2 is Cl
  • Q 1 is 2-Cl-3-thienyl
  • X is C(O)
  • R 2 is Br.
  • Q 1 is 2,6-di-F-Ph, and X is NH.
  • the present disclosure also includes Tables 450 through 587, each of which is constructed the same as Table 449 above, except that the row heading in Table 449 (i.e. "Q is 2,6-di-F-Ph, and X is NH.") is replaced with the respective row heading shown below.
  • Table 450 the row heading is "Q 1 is 2,4-di-F-Ph, and X is NH.”
  • Q 2 is as defined in Table 449 above.
  • the first entry in Table 450 specifically discloses 2-chloro- ⁇ /-[4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]-3-pyridinamine.
  • Tables 451 through 587 are constructed similarly.
  • 450 Q 1 is 2,4-di-F-Ph, and X is NH.
  • 519 Q 1 is 2-Cl-Ph, and X is S.
  • 451 Q 1 is 2,4,6-tri-F-Ph, and X is NH.
  • 520 Q 1 is 2-Br-Ph, and X is S.
  • Q 1 is 2,6-di-F-4-OMe-Ph, and X is NH.
  • Q 1 is 2-F-4-Cl-Ph, and X is S.
  • Q 1 is 2,6-di-F-4-CN-Ph, and X is NH.
  • Q 1 is 2,4-di-Cl-Ph, and X is S.
  • Q 1 is 2-Cl-4-F-Ph, and X is NH. 523 Q 1 is 2,6-di-Cl-Ph, and X is S.
  • Q 1 is 2-Cl-6-F-Ph, and X is NH.
  • Q 1 is 2-F-4-MeO-Ph, and X is S.
  • Q 1 is 2-Cl-4,6-di-F-Ph, and X is NH.
  • Q 1 is 2-Cl-4-MeO-Ph, and X is S.
  • Q 1 is 4-Cl-2,6-di-F-Ph, and X is NH.
  • 526 Q 1 is 2-Br-4-MeO-Ph, and X is S.
  • Q 1 is 2-Br-4-F-Ph, and X is NH.
  • 527 Q 1 is 2-F-4-CN-Ph, and X is S.
  • Q 1 is 2-Br-6-F-Ph, and X is NH.
  • 528 Q 1 is 2-Cl-4-CN-Ph, and X is S.
  • 461 Q 1 is 2-1-4-F-Ph, and X is NH.
  • 530 Q 1 is 2,5-di-Cl-3-pyridinyl, and X is S.
  • Table Row Heading Table Row Heading
  • 462 Q 1 is 2-F-Ph, and X is NH.
  • 531 Q 1 is 2-Cl-3-thienyl, and X is S.
  • Q 1 is 2-Cl-Ph, and X is NH.
  • 532 Q 1 is 2,5-di-Cl-3-thienyl, and X is S.
  • Q 1 is 2-Br-Ph, and X is NH.
  • Q 1 is 2,6-di-F-Ph, and X is CHOH.
  • Q 1 is 2-F-4-Cl-Ph, and X is NH.
  • 534 Q 1 is 2,4-di-F-Ph, and X is CHOH.
  • Q 1 is 2,4-di-Cl-Ph, and X is NH.
  • Q 1 is 2,4,6-tri-F-Ph, and X is CHOH.
  • Q 1 is 2,6-di-Cl-Ph, and X is NH.
  • Q 1 is 2,6-di-F-4-OMe-Ph, and X is CHOH.
  • Q 1 is 2-F-4-MeO-Ph, and X is NH.
  • Q 1 is 2,6-di-F-4-CN-Ph, and X is CHOH.
  • Q 1 is 2-Cl-4-MeO-Ph, and X is NH.
  • Q 1 is 2-Cl-4-F-Ph, and X is CHOH.
  • Q 1 is 2-Br-4-MeO-Ph, and X is NH.
  • Q 1 is 2-Cl-6-F-Ph, and X is CHOH.
  • Q 1 is 2-F-4-CN-Ph, and X is NH.
  • 540 Q 1 is 2-Cl-4,6-di-F-Ph, and X is CHOH.
  • Q 1 is 2-Cl-4-CN-Ph, and X is NH.
  • Q 1 is 4-Cl-2,6-di-F-Ph, and X is CHOH.
  • Q 1 is 2-Br-4-CN-Ph, and X is NH.
  • Q 1 is 2-Br-4-F-Ph, and X is CHOH.
  • Q 1 is 2,5-di-Cl-3-pyridinyl, and X is NH.
  • 543 Q 1 is 2-Br-6-F-Ph, and X is CHOH.
  • Q 1 is 2-Cl-3-thienyl, and X is NH.
  • Q 1 is 2-Me-4-F-Ph, and X is CHOH.
  • Q 1 is 2,5-di-Cl-3-thienyl, and X is NH.
  • Q 1 is 2-1-4-F-Ph, and X is CHOH.
  • Q 1 is 2,6-di-F-Ph, and X is O.
  • Q 1 is 2-F-Ph, and X is CHOH.
  • Q 1 is 2,4-di-F-Ph, and X is O.
  • Q 1 is 2-Cl-Ph, and X is CHOH.
  • Q 1 is 2,4,6-tri-F-Ph, and X is O.
  • Q 1 is 2-Br-Ph, and X is CHOH.
  • Q 1 is 2,6-di-F-4-OMe-Ph, and X is O.
  • Q 1 is 2-F-4-Cl-Ph, and X is CHOH.
  • 481 Q 1 is 2,6-di-F-4-CN-Ph, and X is O.
  • 550 Q 1 is 2,4-di-Cl-Ph, and X is CHOH.
  • Q 1 is 2-Cl-4-F-Ph, and X is O.
  • Q 1 is 2,6-di-Cl-Ph, and X is CHOH.
  • Q 1 is 2-Cl-6-F-Ph, and X is O.
  • Q 1 is 2-F-4-MeO-Ph, and X is CHOH.
  • Q 1 is 2-Cl-4,6-di-F-Ph, and X is O.
  • Q 1 is 2-Cl-4-MeO-Ph, and X is CHOH.
  • Q 1 is 4-Cl-2,6-di-F-Ph, and X is O.
  • Q 1 is 2-Br-4-MeO-Ph, and X is CHOH.
  • Q 1 is 2-Br-6-F-Ph, and X is O.
  • Q 1 is 2-Cl-4-CN-Ph, and X is CHOH.
  • Q 1 is 2-Me-4-F-Ph, and X is O.
  • Q 1 is 2-Br-4-CN-Ph, and X is CHOH.
  • 489 Q 1 is 2-1-4-F-Ph, and X is O.
  • 558 Q 1 is 2,5-di-Cl-pyridin-3-yl, and X is CHOH.
  • Q 1 is 2-F-Ph, and X is O.
  • Q 1 is 2,5-di-Cl-thien-3-yl, and X is CHOH.
  • 492 Q 1 is 2-Br-Ph, and X is O.
  • 561 Q 1 is 2,4-di-F-Ph, and X is C(O).
  • Q 1 is 2-F-4-Cl-Ph, and X is O.
  • 562 Q 1 is 2,4,6-tri-F-Ph, and X is C(O).
  • Q 1 is 2,6-di-Cl-Ph, and X is O.
  • Q 1 is 2,6-di-F-4-CN-Ph, and X is C(O).
  • 496 Q 1 is 2-F-4-MeO-Ph, and X is O.
  • 565 Q 1 is 2-Cl-4-F-Ph, and X is C(O).
  • Q 1 is 2-Cl-4-MeO-Ph, and X is O.
  • 566 Q 1 is 2-Cl-6-F-Ph, and X is C(O).
  • 570 Q 1 is 2-Br-6-F-Ph, and X is C(O).
  • 502 Q 1 is 2,5-di-Cl-pyridin-3-yl, and X is O.
  • 571 Q 1 is 2-Me-4-F-Ph, and X is C(O).
  • 503 Q 1 is 2-Cl-thien-3-yl, and X is O.
  • 572 Q 1 is 2-1-4-F-Ph, and X is C(O).
  • 504 Q 1 is 2,5-di-Cl-thien-3-yl, and X is O.
  • 573 Q 1 is 2-F-Ph, and X is C(O).
  • 505 Q 1 is 2,6-di-F-Ph, and X is S.
  • 578 Q 1 is 2,6-di-Cl-Ph, and X is C(O).
  • 510 Q 1 is 2-Cl-4-F-Ph, and X is S.
  • 579 Q 1 is 2-F-4-MeO-Ph, and X is C(O).
  • 511 Q 1 is 2-Cl-6-F-Ph, and X is S.
  • 580 Q 1 is 2-Cl-4-MeO-Ph, and X is C(O).
  • 512 Q 1 is 2-Cl-4,6-di-F-Ph, and X is S.
  • 581 Q 1 is 2-Br-4-MeO-Ph, and X is C(O).
  • Q 1 is 4-Cl-2,6-di-F-Ph, and X is S.
  • Q 1 is 2-F-4-CN-Ph, and X is C(O).
  • 514 Q 1 is 2-Br-4-F-Ph, and X is S.
  • 583 Q 1 is 2-Cl-4-CN-Ph, and X is C(O).
  • 515 Q 1 is 2-Br-6-F-Ph, and X is S.
  • Q 1 is 2-Br-4-CN-Ph, and X is C(O).
  • 516 Q 1 is 2-Me-4-F-Ph, and X is S. 585 Q 1 is 2,5-di-Cl-3-pyridinyl, and X is C(O).
  • 517 Q 1 is 2-1-4-F-Ph, and X is S. 586 Q 1 is 2-Cl-3-thienyl, and X is C(O). 518 Q 1 is 2-F-Ph, and X is S. 587 Q 1 is 2,5-di-Cl-3-thienyl, and X is C(O).
  • Q 1 is 2,6-di-F-Ph, and R 2 is Me.
  • the present disclosure also includes Tables 589 through 671, each of which is constructed the same as Table 588 above, except that the row heading in Table 588 (i.e. "Q 1 is 2,6-di-F-Ph, and R 2 is Me.") is replaced with the respective row heading shown below.
  • Table 589 the row heading is "Q 1 is 2,6-di-F-Ph, and R 2 is CL", and (R 3 ) p is as defined in Table 588 above.
  • the first entry in Table 589 specifically discloses 5-chloro-4-(2,6-difluorophenyl)- ⁇ /-(2-fluorophenyl)-lH-pyrazol-3-amine.
  • Tables 589 through 671 are constructed similarly.
  • Q 1 is 2,6-di-F-Ph, and R 2 is Br.
  • 635 Q 1 is 2-Br-Ph, and R 2 is Br.
  • Q 1 is 2,4-di-F-Ph, and R 2 is Me.
  • Q 1 is 2-F-4-Cl-Ph, and R 2 is Me.
  • Q 1 is 2,4-di-F-Ph, and R 2 is Cl.
  • Q 1 is 2-F-4-Cl-Ph, and R 2 is Cl.
  • Q 1 is 2,4-di-F-Ph, and R 2 is Br.
  • Q 1 is 2-F-4-Cl-Ph, and R 2 is Br.
  • Q 1 is 2,4,6-tri-F-Ph, and R 2 is Me.
  • Q 1 is 2,4-di-Cl-Ph, and R 2 is Me.
  • Q 1 is 2,4,6-tri-F-Ph, and R 2 is Cl.
  • 640 Q 1 is 2,4-di-Cl-Ph, and R 2 is Cl.
  • Q 1 is 2,6-di-F-4-OMe-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-Cl-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-F-4-OMe-Ph, and R 2 is Br.
  • Q 1 is 2,6-di-Cl-Ph, and R 2 is Br.
  • Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Me.
  • Q 1 is 2-F-4-MeO-Ph, and R 2 is Me.
  • Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Cl.
  • 646 Q 1 is 2-F-4-MeO-Ph, and R 2 is Cl.
  • Q 1 is 2,6-di-F-4-OEt-Ph, and R 2 is Br. 647 Q 1 is 2-F-4-MeO-Ph, and R 2 is Br.
  • 600 Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Me.
  • 647A Q 1 is 2-F-4-EtO-Ph, and R 2 is Me.
  • 601 Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Cl.
  • 647B Q 1 is 2-F-4-EtO-Ph, and R 2 is Cl.
  • 602 Q 1 is 2,6-di-F-4-CN-Ph, and R 2 is Br.
  • 647C Q 1 is 2-F-4-EtO-Ph, and R 2 is Br.
  • Q 1 is 2-Cl-4-F-Ph, and R 2 is Me.
  • 648 Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Me.
  • 604 Q 1 is 2-Cl-4-F-Ph, and R 2 is Cl.
  • 649 Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Cl.
  • Q 1 is 2-Cl-4-F-Ph, and R 2 is Br.
  • 650 Q 1 is 2-Cl-4-MeO-Ph, and R 2 is Br.
  • 606 Q 1 is 2-Cl-6-F-Ph, and R 2 is Me.
  • 650A Q 1 is 2-Cl-4-EtO-Ph, and R 2 is Me.
  • 607 Q 1 is 2-Cl-6-F-Ph, and R 2 is Cl.
  • 650B Q 1 is 2-Cl-4-EtO-Ph, and R 2 is Cl.
  • 608 Q 1 is 2-Cl-6-F-Ph, and R 2 is Br.
  • 650C Q 1 is 2-Cl-4-EtO-Ph, and R 2 is Br.
  • 609 Q 1 is 2-Cl-4,6-di-F-Ph, and R 2 is Me.
  • 651 Q 1 is 2-Br-4-MeO-Ph, and R 2 is Me.
  • 610 Q 1 is 2-Cl-4,6-di-F-Ph, and R 2 is Cl.
  • 652 Q 1 is 2-Br-4-MeO-Ph, and R 2 is Cl.
  • 611 Q 1 is 2-Cl-4,6-di-F-Ph, and R 2 is Br.
  • 653 Q 1 is 2-Br-4-MeO-Ph, and R 2 is Br.
  • 612 Q 1 is 4-Cl-2,6-di-F-Ph, and R 2 is Me.
  • 653A Q 1 is 2-Br-4-EtO-Ph, and R 2 is Me.

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Abstract

Disclosed are compounds of Formula (1), including all geometric and stereoisomers, JV-oxides, and salts thereof, wherein Q1 is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; Q2 is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; X is O, S(O)m, NR4, CR15R16, C(O) or C(=S); and R1, R1a, R2, R4, R15, R16 and m are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula (1) and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention. Also disclosed are compounds of Formula (2), including all geometric and stereoisomers, and salts thereof, wherein X is NH; and Q1, Q2 and R2 are as defined for Formula (1); which are useful as intermediates for preparing compounds of Formula (1).

Description

TITLE FUNGICIDAL PYRAZOLES
FIELD OF THE INVENTION
This invention relates to certain pyrazoles, their //-oxides, salts and compositions, and methods of their use as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action. JP09208620 discloses JV-phenylpyrazolylamine and JV-pyridylpyrazolylamine derivatives as insecticides, herbicides and fungicides; however the fungicides of the present invention are not disclosed in this publication.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
Figure imgf000002_0001
wherein
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, Cj-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6- membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C3-C12 cycloalkyl or C3-C12 cycloalkenyl, each optionally substituted with up to 5 substituents independently selected from R3;
X is O, S(O)m, NR4, CR15R16, C(O) or C(=S); R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-
C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or
R1 is phenyl optionally substituted with up to 3 R8; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and
R9b on nitrogen atom ring members;
Rla is H; or
Rla and R1 are taken together with the carbon atom to which they are attached to form a cyclopropyl ring optionally substituted with up to 2 substituents independently selected from halogen and methyl;
R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, halomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C2-C3 alkylcarbonylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfϊnyl, C1-C3 haloalkylsulfmyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C1-C2 alkylsulfonyloxy, C1-C2 haloalkylsulfonyloxy, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl,
C2-C4 alkynyl, hydroxy, formyl, C2-C3 alkylcarbonyl, C2-C3 alkylcarbonyloxy,
-SF5, -SCN, C(=S)NR19R20 or -U-V-T; R4 is H, formyl, C2-C5 alkenyl, C3-C5 alkynyl, C3-C7 cycloalkyl, -SO3-M+,
-S(=O)tR10, -(C=W)R11, NH2 or OR21; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
R6 and R7 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C4-Cg cycloalkylalkyl and C4-Cg alkylcycloalkyl; or
R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O)n and NR13; each R8, R9a and R9b is independently selected from halogen, C ^C2 alkyl, C ^C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano, nitro, SCH3, S(O)CH3 and
S(O)2CH3;
R10 is C1-C6 alkyl or C1-C6 haloalkyl; each R11 is independently C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxyalkyl, C2-C7 alkylaminoalkyl, C2-Cg dialkylaminoalkyl, C1-C6 alkylthio or C2-C7 alkylthioalkyl; each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfmyl, C1-C4 alkylsulfonyl or cyano; R13 is H, C1-C3 alkyl or C2-C3 haloalkyl; each R14 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl;
R15 is H, C1-C4 alkyl or OR18; R16 is C1-C4 alkyl or OR18; or R15 and R16 are taken together as -OCH2CH2O-; each R18 is independently H, formyl, C3-C7 cycloalkyl, -SO3-M+ or -(C=W)R11; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; each R19 and R20 is independently H or CH3; R21 is H, formyl, C3-C7 cycloalkyl, -SO3-M+ or -(C=W)R11; or C1-C6 alkyl or C1-
C6 haloalkyl, each optionally substituted with up to 2 R12; each U is independently O, S(=O)W, NR22 or a direct bond; each V is independently C1-C6 alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy; each T is independently cyano, NR23aR23b, OR24 or S(=O)yR25 each R22 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2- C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl),
C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R23a and R23b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl),
C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or a pair of R23a and R23b attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R26; each R24 and R25 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R26 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; each W is independently O or S; each M+ is independently a cation; m is 0, 1 or 2; n is 0, 1 or 2; t is 0, 1 or 2; each u and v are independently 0, 1 or 2 in each instance of S(=O)U(=NR14)V, provided that the sum of u and v is 0, 1 or 2; each w is independently 0, 1 or 2; and each y is independently 0, 1 or 2; provided that: when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from -U-V-T wherein U is a direct bond, V is C(=O) and T is NR23aR23b or OR24, then X is other than NR4. More particularly, this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an JV-oxide or a salt thereof. This invention also relates to a fungicidal composition comprising a compound of Formula 1, an JV-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
This invention also relates to a fungicidal composition comprising: (a) a compound of Formula 1, an JV-oxide, or a salt thereof, and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).
This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
This invention also relates to a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.
The invention also relates to compounds of Formula 2 (including all geometric and stereoisomers) and salts thereof
Figure imgf000006_0001
z wherein
X is NH; and
Q1, Q2 and R2 are as defined above for Formula 1; provided that: (a) when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from -U-V-T wherein U is a direct bond and T is NR23 aR23^ or OR24, then V is other than C(=O); and (b) when Q1 is phenyl and Q2 is 4-(trifluoromethyl)phenyl, then R2 is other than methyl; and to use of said compounds as intermediates for preparing compounds of Formula 1. More particularly, the present invention pertains to a compound of Formula 2 or a salt thereof.
DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains", "containing," "characterized by" or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method. The transitional phrase "consisting of excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
The transitional phrase "consisting essentially of is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of occupies a middle ground between "comprising" and "consisting of.
Where applicants have defined an invention or a portion thereof with an open-ended term such as "comprising," it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms "consisting essentially of or "consisting of."
Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
As referred to in the present disclosure and claims, "plant" includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
As referred to herein, the term "seedling", used either alone or in a combination of words means a young plant developing from the embryo of a seed. As used herein, the term "alkylating agent" refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term "alkylating" does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified for R1.
Generally when a molecular fragment (i.e. radical) is denoted by a series of atom symbols (e.g., C, H, N, O, S) the implicit point or points of attachment will be easily recognized by those skilled in the art. In some instances herein, particularly when alternative points of attachment are possible, the point or points of attachment may be explicitly indicated by a hyphen ("-"). For example, "-SCN" indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).
In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl isomers. "Alkenylene" denotes a straight-chain or branched alkenediyl containing one olefmic bond. Examples of "alkenylene" include CH=CH, CH2CH=CH, CH=C(CH3). "Alkynylene" denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of "alkynylene" include CH2C≡C, C≡CCH2 and the different butynylene, pentynylene and hexynylene isomers. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfmyl" includes both enantiomers of an alkylsulfϊnyl group. Examples of "alkylsulfmyl" include CH3S(O)-, CH3CH2S(O)-, CH3CH2CH2S(O)-, (CH3)2CHS(O)- and the different butylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2-, CH3CH2S(O)2-, CH3CH2CH2S(O)2-, (CH3)2CHS(O)2-, and the different butylsulfonyl isomers. "Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2. "(Alkylthio)carbonyl" denotes a straight-chain or branched alkylthio group bonded to a C(=0) moiety. Examples of "(alkylthio)carbonyl" include CH3SC(=O), CH3CH2CH2SC(=O) and (CH3)2CHSC(=O). "Alkoxy(thiocarbonyl)" denotes a straight-chain or branched alkoxy group bonded to a C(=S) moiety. Examples of "alkoxy(thiocarbonyl)" include CH3OC(=S),
CH3CH2CH2OC(=S) and (CH3)2CHOC(=S). "Alkylaminoalkyl" denotes a straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety. Examples of "alkylaminoalkyl" include CH3NHCH2-, (CH3)2CHNHCH2- and CH3NHCH(CH3)-. "Dialkylaminoalkyl" denotes two independent straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino (straight-chain or branched)alkyl moiety. Examples of "dialkylaminoalkyl" include (CH3)2NCHr, (CH3)2CH(CH3)NCH2- and (CH3)2NCH(CH3)-. The term "alkylcarbonylamino" denotes alkyl bonded to a C(=O)NH moiety. Examples of "alkylcarbonylamino" include CH3CH2C(=O)NH and CH3CH2CH2C(=O)NH.
"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. The term "cycloalkoxy" denotes cycloalkyl linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy. "Cycloalkenyl" includes carbocyclic rings that contain only one double bond such as cyclopentenyl and cyclohexenyl, as well as carbocyclic rings with more than one double bond such as 1,3- and 1 ,4-cyclohexadienyl, but are not aromatic. "Cycloalkylcarbonyl" denotes cycloalkyl bonded to a C(=O) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl. The term "cycloalkoxycarbonyl" means cycloalkoxy bonded to a C(=O) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl. The term"cycloalkylene" denotes a cycloalkanediyl ring.
Examples of "cycloalkylene" include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene. The term"cycloalkenylene" denotes a cycloalkenediyl ring containing one olefmic bond. Examples of "cycloalkenylene" include cylopropenediyl and cyclpentenediyl.
The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C-, ClCH2-, CF3CH2- and CF3CCl2-. The terms "halocycloalkyl", "haloalkoxy", "haloalkylthio", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkoxy" include CH2FO-, CHF2O-, CF3O-, CCl3CH2O-, HCF2CH2CH2O- and CF3CH2O-. Examples of "fluoroalkoxy" include CH2FO-, CHF2O-, CF3O- HCF2CH2CH2O- and CF3CH2O-. Examples of "fluoromethoxy" include CH2FO-, CHF2O- and CF3O-. Examples of "haloalkylthio" include CCl3S-, CF3S-, CCl3CH2S- and ClCH2CH2CH2S-. Examples of "haloalkylsulfmyl" include CF3S(O)-, CCl3S(O)-, CF3CH2S(O)- and CF3CF2S(O)-. Examples of "haloalkylsulfonyl" include CF3S(O)2-, CCl3S(O)2-, CF3CH2S(O)2- and CF3CF2S(O)2-. The total number of carbon atoms in a substituent group is indicated by the "Cj-C;" prefix where i and j are numbers from 1 to 12. For example, C1-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2-; C3 alkoxyalkyl designates, for example, CH3CH(OCH3)-, CH3OCH2CH2- or CH3CH2OCH2-; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2- and CH3CH2OCH2CH2-.
As used herein, the following definitions shall apply unless otherwise indicated. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted." Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
The term "unsubstituted" in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term "optionally substituted" means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. The number of optional substituents may be restricted by an expressed limitation. For example, the phrase "optionally substituted with up to 3 substituents selected from R9a on carbon ring members" means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). Similarly, the phrase "optionally substituted with up to 5 substituents selected from R3 on carbon ring members" means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows. When a range specified for the number of substituents (e.g., r being an integer from 0 to 4 or from 0 to 3 for 5- and 6-membered nitrogen-containing heterocycles in Exhibit A) exceeds the number of positions available for substituents on a ring (e.g., 2 positions available for (Ra)r on U-27 in Exhibit A), the actual higher end of the range is recognized to be the number of available positions. When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., (R3)p in Table 1 where p is 0, 1, 2, 3, 4 or 5. When a group contains a substituent which can be hydrogen, for example R1, R4, R5, R6, R7 or R13, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example (Ra)r in H-23 of Exhibit 1 , wherein r may be 0, then hydrogen may be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be "not substituted" or "unsubstituted", then hydrogen atoms are attached to take up any free valency.
The variables "m", "n", "t", "u", "v", "w" and "y" in the Summary of the Invention and corresponding parts of the patent specification relate to subscripts appearing to the right of atoms or other molecular fragments within parentheses and denote the integral number of instances present of the atoms or other molecular fragments within the parentheses, "m" relates to "S(O)1n", "n" relates to "S(O)n", "t" relates to "-S(=O)tR10", "u" and "v" relate to "S(=O)U(=NR14)V", "w" relates to "S(=O)W", and "y" relates to "S(=O)yR25. For example, "m" being 0, 1 or 2 means that "S(O)m" can be "S", "S(O)" or "S(O)2". Unless otherwise indicated, a "ring" as a component of Formula 1 is carbocyclic or heterocyclic. The term "ring system" as a component of Formula 1 denotes two fused rings (e.g., a phenyl ring fused to a pyridinyl ring to form quinolinyl). The term "ring member" refers to an atom or other moiety (e.g., O, S(O), S(O)2 or S(=O)U(=NR14)V) forming the backbone of a ring or ring system. The term "carbocyclic ring" denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. "Saturated carbocyclic" refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
The terms "heterocyclic ring" or "heterocycle" denote a ring or ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. The term "saturated heterocyclic ring" refers to a heterocyclic ring containing only single bonds between ring members. In regards to degree of saturation, "a partially unsaturated heterocyclic ring" is intermediate between a saturated heterocyclic ring and a fully unsaturated heterocyclic ring (which may be aromatic). Therefore, as referred to in the present disclosure and claims, the term "partially unsaturated heterocyclic ring" denotes a heterocyclic ring comprising at least one ring member bonded to an adjacent ring member through a double bond and which conceptually potentially accommodates a number of non-cumulated double bonds between adjacent ring members (i.e. in its fully unsaturated counterpart form) greater than the number of double bonds present (i.e. in its partially unsaturated form). When a fully unsaturated heterocyclic ring satisfies Hϋckel's rule, then said ring is also called a "heteroaromatic ring" or "aromatic heterocyclic ring". The terms "heteroaromatic ring system" and "heteroaromatic bicyclic ring system" denote a ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur, and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
"Aromatic" indicates that each of the ring atoms is essentially in the same plane and has a /?-orbital perpendicular to the ring plane, and that (4n + T) π electrons, where n is a positive integer, are associated with the ring to comply with Hϋckel's rule. The term "aromatic heterocyclic ring system" denotes a heterocyclic ring system in which at least one ring of the ring system is aromatic. The term "nonaromatic ring system" denotes a carbocyclic or heterocyclic ring system that may be fully saturated, as well as partially or fully unsaturated, provided that none of the rings in the ring system are aromatic. The term "four- to seven-membered nonaromatic heterocyclic ring" refers to rings containing four to seven ring members and which do not satisfy Hϋckel's rule. This term (as used where R6 and R7 are taken together) is not limited by carbon atoms only and can include ring members selected from O, S(O)n and NR13.
In the context of the present invention when an instance of Q1, Q2 or R1 comprises a phenyl or a 6-membered fully unsaturated heterocyclic ring, the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1.
As noted above, Q1, Q2 and R1 can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of the Invention. An example of phenyl optionally substituted with one to five substituents is the ring illustrated as U-57 in Exhibit A, wherein R8 is as defined in the Summary of the Invention for R8 and q is an integer from 0 to 5.
As noted above, Q1 is, inter alia, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q1 (e.g., a Q1 ring or ring system is optionally substituted with R3 on carbon ring members and cyano, Cj-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members). Similarly, Q2 is, inter alia, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q2. As the substituents on the ring or ring system of Q1 or Q2 are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment. In these definitions of heterocyclic ring and heteroaromatic ring system, the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S). The definition of S(=O)U(=NR14)V allows the up to 2 sulfur ring members, to be oxidized sulfur moieties (e.g., S(=O) or S(=O)2) or unoxidized sulfur atoms (i.e. when u and v are both zero). The nitrogen atom ring members may be oxidized as //-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives. The up to 3 carbon atom ring members selected from C(=O) and C(=S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms.
Also as noted above, R1 can be (among others) 5- or 6-membered nitrogen-containing aromatic heterocycle, which may be optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention.
When R1 is phenyl or a 5- or 6- membered nitrogen-containing aromatic heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described. Likewise, the ring or ring system of Q1 or Q2 may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described.
Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings H-I through H-39 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems B-I through B-39 illustrated in Exhibit 2. In Exhibits 1 and 2 the variable Ra is any substituent as defined in the Summary of the Invention for Q1, Q2 or R1 (e.g., a Q1 ring or ring system is optionally substituted with R3 on carbon ring members and cyano, Cj-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3~C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3~C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5 for Q1 and Q2 or from 0 to 3 for R1, limited by the number of available positions on each depicted ring or ring system.
Exhibit 1
Figure imgf000013_0001
H-I H-2 H-3 H-4
Figure imgf000014_0001
H-5 H-6 H-7 H-S H-9
Figure imgf000014_0002
H-IO H-I l H-12 H-13 H-14
Figure imgf000014_0003
H-15 H-16 H-17 H-18 H-19
Figure imgf000014_0004
H-20 H-21 H-22 H-23 H-24
Figure imgf000014_0005
H-25 H-26 H-27 H-28 H-29
Figure imgf000014_0006
H-30 H-31 H-32 H-33 H-34
Figure imgf000014_0007
H-35 H-36 H-37 H-38 H-39 Exhibit 2
Figure imgf000015_0001
B-I B-2 B-3
Figure imgf000015_0002
B-4 B-5 B-6
Figure imgf000015_0003
B-IO B-I l B-12
Figure imgf000015_0004
B-13 B-14 B-15
Figure imgf000015_0005
B-19 B-20 B-21
Figure imgf000016_0001
B-22 B-23 B-24
Figure imgf000016_0002
B-28 B-29 B-30
Figure imgf000016_0003
B-31 B-32 B-3
Figure imgf000016_0004
B-34 B-35 B-36
Figure imgf000016_0005
or
B-37 B-38 B-39
Examples of a saturated or partially unsaturated 5- to 6-membered fully unsaturated heterocyclic ring include the rings P-I through P-40 illustrated in Exhibit 3. In Exhibit 3 the variable Ra is any substituent as defined in the Summary of the Invention for Q2 (e.g., a Q2 ring is optionally substituted with R3 on carbon ring members and cyano, C^-Cg alkyl, C2- C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring system.
Exhibit 3
Figure imgf000017_0001
P-I P-2 P-3 P-4 P-5
Figure imgf000017_0002
P-6 P-7 P-8 P-9 P-IO
Figure imgf000017_0003
P-I l P-12 P-13 P-14 P-15
Figure imgf000017_0004
P-16 P-17 P-18 P-19 P-20
Figure imgf000017_0005
P-21 P-22 P-23 P-24 P-25
Figure imgf000017_0006
Figure imgf000018_0001
P-31 P-32 P-33 P-34 P-35
Figure imgf000018_0002
P-36 P-37 P-38 P-39 P-40
Examples of a 5- or 6-membered nitrogen-containing heterocycle optionally substituted with from one or more substituents of particular note for Q1, Q2 and R1 include the rings U-I through U-56 illustrated in Exhibit A wherein Ra is any substituent as defined in the Summary of the Invention for Q1 Q2 and R1, respectively (i.e. for Q1 and Q2: R3 on carbon atom ring members, and the recited list of possible substituents on nitrogen atom ring members; and for R1, R9a on carbon ring members and R9^ on nitrogen ring members) and r is an integer ranging from 0 to 4 for Q1 and Q2 and from 0 to 3 for R1, limited by the number of available positions on each U group. Note that some U groups can only be substituted with less than 4 Ra groups (e.g., U-4 through U-43 and U-47 through U-56). As U-24, U-25, U-31, U-32, U-33, U-34, U-35, U-36, U-37 and U-38 have only one available position, for these U groups, r is limited to the integers 0 or 1 , and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (Ra)r.
Exhibit A
Figure imgf000018_0003
U-I U-2 U-3 U-4 U-5 r
Figure imgf000018_0004
U-6 U-7 U-8 U-9 U-IO
Figure imgf000019_0001
U-I l U-12 U-13 U-14 U-15
Figure imgf000019_0002
U-21 U-22 U-23 U-24 U-25
Figure imgf000019_0003
U-26 U-27 U-28 U-29 U-30
Figure imgf000019_0004
U-31 U-32 U-33 U-34 U-35
Figure imgf000019_0005
Figure imgf000020_0001
Although Ra groups are shown in the structures H-I through H-39, B-I through B-39, P-I through P-40, and U-I through U-57 in Exhibits 1 through 3 and Exhibit A, it is noted that they do not need to be present since they are optional substituents. The nitrogen atoms that require substitution to fill their valence are substituted with H or Ra. Note that when the attachment point between (Ra)r and the H, B, P or U group in Exhibits 1 through 3 and Exhibit A is illustrated as floating, (Ra)r can be attached to any available carbon atom or nitrogen atom of the H, B, P or U group. Note that when the attachment point on the H, B or P group in Exhibits 1 through 3 is illustrated as floating, the H, B or P group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the H, B or P group by replacement of a hydrogen atom. Of note are alternative depictions of the chemical structures shown in Exhibits 1 through 3 and Exhibit A in which the "Ra" variable substituent is replaced by "Rv", wherein the "v" superscript in "Rv" does not refer to the subscript variable "v" defined in the Summary of the Invention but instead differentiates "Rv" from other substituent variables beginning with "R". Examples of where R6 and R7 are taken together to form a four- to seven-membered nonaromatic heterocyclic ring include the rings G-I through G-28 as illustrated in Exhibit 4. Note that when R6 and R7 are taken together to form a ring comprising a ring selected from G-25 through G-28, G2 is selected from O, S(O)n or NR13. Note that when G2 is N, the nitrogen atom can complete its valence by substitution with either H or the substituents corresponding to R13 as defined in the Summary of Invention.
Exhibit 4
Figure imgf000020_0002
G-I G-2 G-3 G-4 G-5
Figure imgf000021_0001
-I l G-12 G-13 G-14 G-15
Figure imgf000021_0002
G-16 G-17 G-18 G-19 G-20
Figure imgf000021_0003
G-26 G-27 G-28
A wide variety of synthetic methods are known in the art to enable preparation of aromatic and nonaromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form TV-oxides. One skilled in the art will also recognize that tertiary amines can form iV-oxides. Synthetic methods for the preparation of iV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of iV-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
One skilled in the art recognizes that some of the compounds disclosed herein can exist in equilibrium with one or more of their respective tautomeric counterparts. Unless otherwise indicated, reference to a compound by one tautomer description is to be considered to include all tautomers. For example, reference to the tautomeric form depicted by Formula 2* also includes the tautomic form depicted by Formula 22.
Figure imgf000022_0001
21
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
Compounds selected from Formula 1, geometric and stereoisomers, tautomers, TV-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
Embodiments of the present invention as described in the Summary of the Invention include (where Formula 1 as used in the following Embodiments includes //-oxides and salts, geometric isomers, stereoisomers and atropisomers thereof ):
Embodiment 1. A compound of Formula 1 wherein X is O, S(O)m, NR4, CR15R16 or
C(O).
Embodiment 2. A compound of Formula 1 wherein X is O, S(0)m, NR4 or CR15R16. Embodiment 3. A compound of Formula 1 wherein X is O, NR4, CR15R16 or C(=0).
Embodiment 4. A compound of Formula 1 wherein X is O, NR4 or CR15R16. Embodiment 5. A compound of Formula 1 wherein X is O, S(0)m or NR4. Embodiment 6. A compound of Formula 1 wherein X is O or S(0)m. Embodiment 7. A compound of Formula 1 wherein X is O. Embodiment 8. A compound of Formula 1 wherein X is NR4.
Embodiment 9. A compound of Formula 1 wherein X is O or NR4. Embodiment 10. A compound of Formula 1 wherein X is CR15R16, C(=0) or C(=S). Embodiment 11. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R3 substituent is located at a meta position
(relative to the connection of the Q1 ring to the remainder of Formula 1), then said R3 substituent is selected from F, Cl, Br and cyano (-CN). Embodiment 11a. A compound of Formula 1 or any one of Embodiments 1 through 11 wherein when Q1 is a six-membered ring and an R3 substituent is located at a meta position (relative to the connection of the Q1 ring to the remainder of
Formula 1), then said R3 substituent is F. Embodiment 12. A compound of Formula 1 or any one of Embodiments 1 through 11a wherein when Q1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R3 substituent, then said R3 substituent is attached at an ortho position (relative to the connection of the Q1 ring to the remainder of Formula 1). Embodiment 13. A compound of Formula 1 or any one of Embodiments 1 through 12 wherein Q1 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R3. Embodiment 14. A compound of Embodiment 13 wherein Q1 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3. Embodiment 15. A compound of Embodiment 14 wherein Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3. Embodiment 16. A compound of Embodiment 15 wherein Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3. Embodiment 17. A compound of Embodiment 16 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q1 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q * . Embodiment 18. A compound of Embodiment 16 or 17 wherein Q1 is phenyl or pyridinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3. Embodiment 19. A compound of Embodiment 18 wherein Q1 is phenyl or pyridinyl, each substituted with 2 or 3 substituents independently selected from R3. Embodiment 20. A compound of Embodiment 19 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3. Embodiment 21. A compound of Embodiment 20 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3. Embodiment 22. A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3. Embodiment 23. A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3. Embodiment 24. A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2- and 6-positions with substituents independently selected from R3. Embodiment 25. A compound of Embodiment 18 wherein Q1 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 26. A compound of Embodiment 25 wherein Q1 is pyridinyl substituted with 1 or 2 substituents independently selected from R3. Embodiment 27. A compound of Embodiment 26 wherein Q1 is pyridinyl substituted with 1 substituent independently selected from R3. Embodiment 28. A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when Q2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R3 substituent is located at a meta position
(relative to the connection of the Q2 ring to the remainder of Formula 1), then said R3 substituent is selected from F, Cl, Br and cyano (-CN). Embodiment 29. A compound of Formula 1 or any one of Embodiments 1 through 28 wherein when Q2 is a six-membered ring and an R3 substituent is located at a meta position (relative to the connection of the Q2 ring to the remainder of
Formula 1), then said R3 substituent is F.
Embodiment 30. A compound of Formula 1 or any one of Embodiments 1 through 29 wherein when Q2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R3 substituent, then said R3 substituent is attached at an ortho position (relative to the connection of the Q2 ring to the remainder of Formula 1).
Embodiment 31. A compound of Formula 1 or any one of Embodiments 1 through 30 wherein Q2 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R3. Embodiment 32. A compound of Embodiment 31 wherein Q2 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3.
Embodiment 33. A compound of Embodiment 32 wherein Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3. Embodiment 34. A compound of any one of Embodiments 31 through 33 wherein Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 ,
2 or 3 substituents independently selected from R3.
Embodiment 35. A compound of Embodiment 34 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q2 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q2. Embodiment 36. A compound of any one of Embodiments 34 or 35 wherein Q2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 37. A compound of Embodiment 36 wherein Q2 is phenyl substituted with
1, 2 or 3 substituents independently selected from R3. Embodiment 38. A compound of Embodiment 37 wherein Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3. Embodiment 39. A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3. Embodiment 40. A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3. Embodiment 41. A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2- and 6-positions with substituents independently selected from R3. Embodiment 42. A compound of Embodiment 36 wherein Q2 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 43. A compound of Embodiment 42 wherein Q2 is pyridinyl substituted with 1 or 2 subsituents independently selected from R3. Embodiment 44. A compound of Embodiment 43 wherein Q2 is pyridinyl substituted with 1 substituent selected from R3. Embodiment 45. A compound of Formula 1 or any one of Embodiments 1 through 44 wherein at least one of Q1 and Q2 is phenyl optionally substituted with R3 (e.g., optionally substituted with up to 5 substituents independently selected from R3). Embodiment 46. A compound of Embodiment 45 wherein at least one of Q1 and Q2 is phenyl substituted with 2, 3 or 4 substituents independently selected from R3. Embodiment 47. A compound of Embodiment 46 wherein at least one Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3. Embodiment 48. A compound of Embodiment 47 wherein each of Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3. Embodiment 49. A compound of Formula 1 or any one of Embodiments 1 through 48 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or
R1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9^ on nitrogen atom ring members. Embodiment 50. A compound of Embodiment 49 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy or C1-C6 haloalkoxy; or
R1 is pyridinyl, pyrimidinyl, pyrazolyl or oxazolyl, each optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9^ on nitrogen atom ring members. Embodiment 51. A compound of Embodiment 50 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl. Embodiment 52. A compound of Embodiment 51 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or
C2-C5 alkoxyalkyl. Embodiment 53. A compound of Embodiment 52 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl.
Embodiment 54. A compound of Embodiment 53 wherein R1 is H, halogen or C1-C6 alkyl.
Embodiment 55. A compound of Embodiment 54 wherein R1 is H or CH3. Embodiment 56. A compound of Embodiment 55 wherein R1 is H. Embodiment 57. A compound of Formula 1 or any one of Embodiments 1 through 56 wherein R1 is other than an optionally substituted phenyl or an optionally substituted five- or six-membered nitrogen-containing aromatic heterocycle. Embodiment 58. A compound of Formula 1 or any one of Embodiments 1 through 50 wherein R1 is other than H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl. Embodiment 59. A compound of Formula 1 or any one of Embodiments 1 through 58 wherein Rla is H.
Embodiment 60. A compound of Formula 1 or any one of Embodiments 1 through 59 wherein R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, monohalomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl. Embodiment 61. A compound of Embodiment 60 wherein R2 is CH3, CH2CH3, Cl, Br or I. Embodiment 62. A compound of Embodiment 61 wherein R2 is CH3, CH2CH3, Cl or
Br. Embodiment 63. A compound of Embodiment 62 wherein R2 is CH3, Cl or Br.
Embodiment 64. A compound of Embodiment 63 wherein R2 is CH3 or Cl. Embodiment 65. A compound of Embodiment 64 wherein R2 is CH3. Embodiment 66. A compound of Embodiment 62 wherein R2 is Cl or Br. Embodiment 67. A compound of Embodiment 66 wherein R2 is Cl. Embodiment 68. A compound of Formula 1 or any one of Embodiments 1 through 67 wherein R5 is H or C1-C6 alkyl.
Embodiment 69. A compound of Embodiment 68 wherein R5 is H, CH3 or CH2CH3. Embodiment 70. A compound of Embodiment 68 wherein R5 is C1-C6 alkyl. Embodiment 71. A compound of Embodiment 69 or 70 wherein R5 is CH3 or CH2CH3. Embodiment 72. A compound of Formula 1 or any one of Embodiments 1 through 71 wherein when R6 is separate (i.e. not taken together with R7 to form a ring), then
R6 is H or C1-C6 alkyl.
Embodiment 73. A compound of Embodiment 72 wherein R6 is H. Embodiment 74. A compound of Formula 1 or any one of Embodiments 1 through 73 wherein when R7 is separate (i.e. not taken together with R6 to form a ring), then
R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl. Embodiment 75. A compound of Embodiment 74 wherein R7 is H or C1-C6 alkyl. Embodiment 76. A compound of Embodiment 75 wherein R7 is H. Embodiment 77. A compound of Formula 1 or any one Embodiments 1 through 76 wherein when R6 and R7 are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring contains ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13.
Embodiment 78. A compound of Embodiment 77 wherein when R6 and R7 are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring is six-membered and contains one ring member selected from O and NR13 in addition to the connecting nitrogen atom and ring members selected from carbon atoms.
Embodiment 79. A compound of Embodiment 77 wherein R6 and R7 are taken together with the nitrogen atom to which they are connected to form a piperidine ring.
Embodiment 80. A compound of Embodiment 78 wherein R6 and R7 are taken together with the nitrogen atom to which they are connected to form a piperazine or morpholine ring. Embodiment 81. A compound of Formula 1 or any one of Embodiments 1 through 80 wherein each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro. Embodiment 82. A compound of Embodiment 81 wherein each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 alkoxy, cyano and nitro.
Embodiment 83. A compound of Embodiment 82 wherein each R8 is independently Cl or F. Embodiment 84. A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro.
Embodiment 85. A compound of Embodiment 84 wherein each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 alkoxy, cyano and nitro. Embodiment 86. A compound of Embodiment 85 wherein each R9a is independently selected from Cl, F, CH3, -OCH3 and cyano. Embodiment 87. A compound of Embodiment 86 wherein each R9a is independently Cl or F. Embodiment 88. A compound of Formula 1 or any one of Embodiments 1 through 87 wherein each R9^ is independently C1-C2 alkyl.
Embodiment 89. A compound of Formula 1 or any one of Embodiments 1 through 88 wherein each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy,
C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfmyl,
C1-C3 haloalkylsulfϊnyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(=S)NH2 and -U-V-T. Embodiment 90. A compound of Embodiment 89 wherein each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and -U-V-T. Embodiment 91. A compound of Embodiment 90 wherein each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, -OCH3, -OCHF2 and -U-V-T. Embodiment 92. A compound of Formula 1 or any one of Embodiments 1 through 91 wherein at least one R3 substituent on the ring or ring system of Q1 or Q2 is
-U-V-T. Embodiment 93. A compound of Formula 1 or any one of Embodiments 1 through 91 wherein each R3 is other than -U-V-T. Embodiment 94. A compound of Embodiment 89 wherein each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-
C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfϊnyl, C1-C3 haloalkylsulfmyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl and C3-C4 cycloalkyl. Embodiment 95. A compound of Embodiment 94 wherein each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy.
Embodiment 96. A compound of Embodiment 95 wherein each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and
C1-C3 haloalkoxy.
Embodiment 97. A compound of Embodiment 96 wherein each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and
C1-C2 haloalkoxy. Embodiment 98. A compound of Embodiment 97 wherein each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy. Embodiment 99. A compound of Embodiment 98 wherein each R3 is independently selected from F, Cl, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
Embodiment 100. A compound of Embodiment 95 wherein each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, -OCH3 and -OCHF2. Embodiment 101. A compound of any one of Embodiments 89 through 98 or 100 wherein each R3 is independently selected from F, Cl, Br, cyano and methoxy. Embodiment 102. A compound of Embodiment 101 wherein each R3 is independently selected from F, Cl, Br and cyano. Embodiment 103. A compound of Embodiment 101 wherein each R3 is independently selected from F, Cl, cyano and -OCH3.
Embodiment 104. A compound of Formula 1 or any one of Embodiments 1 through 92 wherein each U is independently O or NR22.
Embodiment 105. A compound of Embodiment 104 wherein each U is independently O or NH. Embodiment 106. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 105 wherein each V is C2-C4 alkylene. Embodiment 107. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 106 wherein each T is independently NR23aR23b or OR24. Embodiment 108. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 107 wherein each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl. Embodiment 109. A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 108 wherein each R24 is independently H, C1-C6 alkyl or C1-
C6 haloalkyl. Embodiment 110. A compound of Formula 1 or any one of Embodiments 1 through 109 wherein when an R3 substituent attached to phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl Of Q1Or Q2 is other than F, Cl, Br, cyano, methyl, C1-
C2 alkoxy and fluoromethoxy, then said R3 substituent is attached at the para position (of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl ring).
Embodiment 111. A compound of Formula 1 or any one of Embodiments 1 through 110 wherein R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12.
Embodiment 112. A compound of Embodiment 111 wherein R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl substituted with one R12.
Embodiment 113. A compound of Embodiment 112 wherein R4 is H, formyl,
-CH2OCH3, cyclopropyl, -SCH3, -SCF3 or -CH2CN. Embodiment 114. A compound of Embodiment 113 wherein R4 is H, formyl, cyclopropyl or -CH2CN. Embodiment 115. A compound of Embodiment 113 wherein R4 is H, formyl,
-CH2OCH3, cyclopropyl, -SCH3 or -SCF3. Embodiment 116. A compound of Embodiment 115 wherein R4 is H, formyl or cyclopropyl.
Embodiment 117. A compound of Embodiment 114 or 116 wherein R4 is H. Embodiment 118. A compound of Formula 1 or any one of Embodiments 1 through 117 wherein R13 is H or CH3.
Embodiment 119. A compound of Embodiment 118 wherein R13 is CH3. Embodiment 120. A compound of Formula 1 or any one of Embodiments 1 through 119 wherein each R12 is independently C3-C7 cycloalkyl, Q-C4 alkoxy or cyano. Embodiment 121. A compound of Embodiment 120 wherein each R12 is independently cyclopropyl, -OCH3 or cyano. Embodiment 122. A compound of Embodiment 120 wherein each R12 is independently
C3-C7 cycloalkyl or Q-C4 alkoxy.
Embodiment 123. A compound of Embodiment 122 wherein each R12 is independently cyclopropyl or -OCH3.
Embodiment 124. A compound of Formula 1 or any one of Embodiments 1 through 123 wherein R10 is CH3, CH2CH3, CF3 or CF2CF3.
Embodiment 125. A compound of Embodiment 124 wherein R10 is CH3. Embodiment 126. A compound of Formula 1 or any one of Embodiments 1 through 125 wherein R11 is C1-C6 alkyl, C1-C6 alkoxy or C1-C6 alkylthio.
Embodiment 127. A compound of Embodiment 126 wherein R11 is CH3, CH2CH3,
-OCH3, -OCH2CH3, -SCH3 or -SCH2CH3. Embodiment 128. A compound of Embodiment 127 wherein R11 is CH3, -OCH3 or
-SCH3. Embodiment 129. A compound of Formula 1 or any one of Embodiments 1 through 128 wherein R15 is H or CH3. Embodiment 130. A compound of Embodiment 129 wherein R15 is H.
Embodiment 131. A compound of Formula 1 or any one of Embodiments 1 through 130 wherein R16 is CH3 or OR18.
Embodiment 132. A compound of Embodiment 131 wherein R16 is OR18. Embodiment 133. A compound of Formula 1 or any one of Embodiments 1 through 132 wherein R18 is H.
Embodiment 134. A compound of Formula 1 or any one of Embodiments 1 through 133 wherein W is O. Embodiment 135. A compound of Formula 1 or any one of Embodiments 1 through 134 wherein M+ is a cation selected from sodium, potassium and lithium ions. Embodiment 136. A compound of Embodiment 135 wherein M+ is a cation selected from sodium and potassium ions.
Embodiment 137. A compound of Embodiment 136 wherein M+ is a sodium ion. Embodiment 138. A compound of Formula 1 or any one of Embodiments 1 through 137 wherein m is 0. Embodiment 139. A compound of Formula 1 or any one of Embodiments 1 through 138 wherein n is 0.
Embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds (e.g. compounds of Formula 2) useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention. Combinations of Embodiments 1-139 are illustrated by:
Embodiment A. A compound of Formula 1 wherein
Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3; provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano;
Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3, provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano; X is O, NR4, C(O) or CR15R16;
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl;
Rla is H;
R2 is CH3, CH2CH3, Cl or Br; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfϊnyl, C1-C3 haloalkylsulfϊnyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(=S)NH2 and -U-V-T; R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; R5 is C1-C6 alkyl;
R6 is H or C1-C6 alkyl;
R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl; or
R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13; each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy or cyano; R13 is H or CH3; R15 is H or CH3; and R16 is OR18.
Embodiment B. A compound of Embodiment A wherein
Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
Q2 is phenyl or pyridinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3;
R1 is H, halogen or C1-C6 alkyl;
R2 is CH3, Cl or Br; each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and -U-V-T; R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl substituted with one R12; each R12 is independently cyclopropyl, -OCH3 or cyano; R15 is H; each U is independently O or NH; each V is C2-C4 alkylene; each T is independently NR23aR23b or OR24; each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and each R24 is independently H, C1-C6 alkyl or C1-C6 haloalkyl. Embodiment C. A compound of Embodiment B wherein at least one of Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3; R1 is H or CH3; R2 is CH3; R4 is H; each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl,
C1-C3 alkoxy and C1-C3 haloalkoxy; and R18 is H.
Embodiment D. A compound of Embodiment C wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3; X is O, NR4 or CR15R16; R1 is H; each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl,
C1-C2 alkoxy and C1-C2 haloalkoxy; and R4 is H. Embodiment E. A compound of Embodiment D wherein each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
Embodiment F. A compound of Embodiment E wherein X is O or NH; and each R3 is independently selected from F, Cl, Br, cyano and methoxy.
Specific embodiments include compounds of Formula 1 selected from the group consisting of:
4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl-Λ/-(2,4,6-trifluorophenyl)- lH-pyrazol-5-amine (Compound 18), N-(4-chlorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 22), 4-(2,6-difluoro-4-methoxyphenyl)-Λ/-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-
5-amine (Compound 23), 4-(2,6-difluoro-4-methoxyphenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-
5-amine (Compound 24), N-(2,6-difluoro-4-methoxyphenyl)-4-(3,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-
5-amine (Compound 36),
4-(2,4-difluorophenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-5-amine (Compound 41),
4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-
3,5-difluorobenzonitrile (Compound 45), 4-[[4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-3-fluorobenzonitrile
(Compound 361), 4-(2-chloro-4-fluorophenyl)-Λ/-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 172), 4- [ [4-(2-chloro-4-fluorophenyl)- 1 ,3 -dimethyl- 1 H-pyrazol-5 -yl]oxy] -3 -fluorobenzonitrile
(Compound 118),
3-chloro-4-[[4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile (Compound 358),
4-(2-chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazole-5-methanol
(Compound 351),
N,4-bis(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine (Compound 175), N-(2-chloro-4-fluorophenyl)-4-(2-chloro-6-fluorophenyl)-l,3-dimethyl-lH-pyrazol- 5-amine (Compound 193),
N-(2-chloro-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 297), N-(2-chloro-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 343), N-(4-chloro-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 349), N-(4-chloro-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 357),
3-chloro-4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile (Compound 139),
4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]amino]-3,5-difluoro- benzonitrile (Compound 91), 4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-2,5-difluoro- benzonitrile (Compound 148), N-(2-chloro-4-fluorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazol-
5-amine (Compound 87), α,4-bis(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole-5-methanol (Compound 352), N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole-
5-amine (Compound 286), N-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-
5-amine (Compound 287), N-(2,6-dichloro-4-fluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 368), 3-chloro-4-[5-[(2-chloro-4,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]- benzonitrile (Compound 332),
3-chloro-4-[5-[(4-chloro-2,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]- benzonitrile (Compound 336),
N-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 346), 4-(2-chloro-4-fluorophenyl)-Λ/-(2,4-dichloro-6-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 367), 4-(2-chloro-4-fluorophenyl)-Λ/-(2,6-dichloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 369), 4-[[4-(2-bromo-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-3-fluorobenzonitrile
(Compound 284),
Λ/-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol- 5-amine (Compound 265),
4-(2-bromo-4-fluorophenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-5-amine
(Compound 266), N-(4-bromo-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 364), 4-[[4-(2-bromo-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-3,5-difluoro- benzonitrile (Compound 232), 4-(2-bromo-4-fluorophenyl)-Λ/-(2-chloro-4,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 292),
4-(2-bromo-4-fluorophenyl)-Λ/-(4-chloro-2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol- 5-amine (Compound 360),
N-(4-bromo-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 365), 3-bromo-4-[[4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-5-yl]oxy]benzonitrile
(Compound 372), 3-chloro-4-[[4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile
(Compound 373), N-(2,4-dichloro-6-fluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 374), N-(2,6-dichloro-4-fluorophenyl)-4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 375),
N-(2-bromo-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine (Compound 376),
N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 377), N-(4-bromo-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 378), N-(2-bromo-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 379), N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-6-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine (Compound 380), α-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazole- 5-methanol (Compound 381),
4-[5-[(2-chloro-4,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]-
3-fluorobenzonitrile (Compound 382), 4-[5-[(4-chloro-2,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]-
3-fluorobenzonitrile (Compound 383), α-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazole-
5-methanol (Compound 384), α-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazole-5-methanol
(Compound 385), and α-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole- 5-methanol (Compound 386).
This invention provides a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above. This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof). Of note as embodiment of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above. Of particular note are embodiments where the compounds are applied as compositions of this invention. Of note are compounds of Formula 1 that are compounds of Formula IP (including all geometric and stereoisomers), iV-oxides, and salts thereof, and also agricultural compositions containing them and their use as fungicides:
Figure imgf000038_0001
IP wherein Q1 and Q2 are independently phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3; X is O, S(O)m or NR4;
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3- C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or
C2-C5 alkoxyalkyl; or
R1 is phenyl optionally substituted with up to 3 R8; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9^ on nitrogen atom ring members;
R2 is CH3, CH2CH3, cyclopropyl or halogen; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfmyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl and C2-C4 alkynyl; R4 is H, foπnyl, C3-C7 cycloalkyl, -SO3-M+, -SR10 or -(C=W)R11; or C1-C6 alkyl or
C1-C6 haloalkyl, each optionally substituted with up to 2 R12; R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
R6 and R7 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C4-C8 cycloalkylalkyl and C4-C8 alkylcycloalkyl; or
R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O)n and NR13; each R8, R9a and R915 is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano, nitro, SCH3, S(O)CH3 and S(O)2CH3;
R10 is C1-C6 alkyl or C1-C6 haloalkyl;
R11 is C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxyalkyl, C2-C7 alkylaminoalkyl, C2-C8 dialkylaminoalkyl, C1-C6 alkylthio or C2-C7 alkylthioalkyl; each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfϊnyl or C1-C4 alkylsulfonyl; R13 is H, C1-C3 alkyl or C2-C3 haloalkyl; W is O or S; M+ is a cation; m is 0, 1 or 2; and n is 0, 1 or 2.
Accordingly of note is a compound selected from Formula IP (including all geometric and stereoisomers), //-oxides, and salts thereof, as defined above. Also of note are counterpart embodiments that are embodiment counterparts to Embodiments 1 through 139 and Embodiments A through F wherein in said counterpart embodiments "Formula 1" is replaced by "Formula IP" and the scope of said counterpart embodiments does not exceed the scope defined above for Formula IP. Examples of combinations of Embodiments 1 through 139 as applied to Formula IP are Embodiments AP, BP, CP, DP and EP: Embodiment AP. A compound of Formula IP wherein
Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3; Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3 X is O or NR4;
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or R1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9^ on nitrogen atom ring members; R2 is CH3, CH2CH3, Cl or Br; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfmyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl and C3-C4 cycloalkyl; R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; R5 is H or C1-C6 alkyl; R6 is H or C1-C6 alkyl;
R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl; or R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13; each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro; each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro; each R9b is C1-C2 alkyl; R10 is CH3, CH2CH3, CF3 or CF2CF3; each R12 is independently C3-C7 cycloalkyl or C1-C4 alkoxy; and
R13 is H or CH3. Embodiment BP. A compound of Embodiment AP wherein
Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3; Q2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3; X is NR4; R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy or C1-C6 haloalkoxy; R2 is CH3; each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; R4 is H, formyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl substituted with one R12; R10 is CH3; and each R12 is independently cyclopropyl or -OCH3. Embodiment CP. A compound of Embodiment AP wherein
Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or
Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; X is O;
R2 is CH3; each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, -OCH3, and
-OCHF2; and
R4 is H, formyl or cyclopropyl. Embodiment DP. A compound of Embodiment CP wherein
Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; each R3 is independently selected from F, Cl, cyano and -OCH3; and
R4 is H. Embodiment EP. A compound of Embodiment BP wherein
Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; each R3 is independently selected from F, Cl, CN and -OCH3; and R4 is H.
Also of note is a fungicidal composition comprising a fungicidally effective amount of a compound of Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof) or any one of counterpart embodiments that are embodiment counterparts to
Embodiments 1 through 139 and Embodiments A through F (e.g., Embodiment AP, BP, CP,
DP or EP), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Also of note is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula IP
(including all geometric and stereoisomers, //-oxides, and salts thereof) or any one of said counterpart embodiments. Of particular note are embodiments where the compounds of Formula IP are applied as compositions of this invention.
One or more of the following methods and variations as described in Schemes 1-24 can be used to prepare the compounds of Formula 1 (including Formula IP). The definitions of Q1, Q2, R1, R2 and m in the compounds of Formulae 1-33 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae Ia, Ib, Ic, Id, Ie, If, Ig and Ih are various subsets of Formula 1; Formulae 4a, 4b and 4c are various subsets of Formula 4; Formulae 6a and 6b are various subsets of Formula 6; Formula 11a is a subset of Formula 11; Formula 13a is a subset or analog of Formula 13; and Formula 17a is a subset of Formula 17. Substituents for each subset formula are as defined for its parent formula unless otherwise noted.
As illustrated in Scheme 1, sulfoxides and sulfones of Formula Ib (i.e. Formula 1 wherein X is S(O)m and m is 1 or 2) can be made via oxidation of the linking sulfur atom on sulfides of Formula Ia (i.e. Formula 1 wherein X is S(O)m and m is 0). In this method a compound of Formula Ib wherein m is 1 (i.e. sulfoxides) or m is 2 (i.e. sulfones) is prepared by oxidizing a corresponding sulfide of Formula Ia with a suitable oxidizing agent. In a typical procedure, an oxidizing agent in an amount from 1 to 4 equivalents depending on the oxidation state of the product desired is added to a solution of the compound of Formula Ia in a solvent. Useful oxidizing agents include Oxone® (potassium peroxymonosulfate), hydrogen peroxide, sodium periodate, peracetic acid and 3-chloroperbenzoic acid. The solvent is selected with regard to the oxidizing agent employed. Aqueous ethanol or aqueous acetone is preferably used with potassium peroxymonosulfate, and dichloromethane is generally preferable with 3-chloroperbenzoic acid. Useful reaction temperatures typically range from -78 to 90 0C. Particular procedures useful for oxidizing sulfides to sulfoxides and sulfones are described by Brand et al., J. Agric. Food Chem. 1984, 32, 221-226 and references cited therein.
Scheme 1
Figure imgf000042_0001
As shown in Scheme 2, compounds of Formula 1 in which X is NH and Rla is H can be prepared by the reaction of lH-pyrazole compounds of Formula 2 with various alkylating agents (e.g., Formula 3), such as iodoalkanes, alkylsulfonates (e.g., mesylate (OMs) or tosylate (OTs)) or trialkyl phosphates, preferably in the presence of an organic or inorganic base such as l,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate or potassium hydroxide, and in a solvent such as N,Λ/-dimethylformamide, tetrahydrofuran, toluene or water.
Scheme 2
i „
Figure imgf000043_0001
Rla is H
X is NH
Compounds of Formula 1 wherein CHR1R^ forms an optionally substituted cyclopropyl ring can likewise be prepared by reaction of a pyrazole of Formula 2 with an organometallic reagent, such as tricyclopropylbismuth, in the presence of a catalyst, such as copper acetate, under conditions known in the art. See, for example, J. Am. Chem. Soc. 2007, 129(1), 44-45. Of note as starting materials in the method of Scheme 2 are compounds of Formula 2 specifically disclosed in Tables 588 through 671 below.
As is shown in Scheme 3, compounds of Formula 1 can be prepared by the reaction of compounds of Formula 4 (i.e. 5-aminopyrazoles for X being NR4, 5-hydroxypyrazoles (5 -pyrazolones) for X being O, or 5-mercaptopyrazoles for X being S) with aromatic compounds of Formula 5 containing a leaving group G (i.e. halogen or (halo)alkylsulfonate), optionally in the presence of a metal catalyst, and generally in the presence of a base and a polar aprotic solvent such as Λ/,Λ/-dimethylformamide or dimethyl sulfoxide. For example, compounds of Formula 5 in which Q2 is an electron-deficient heteroaromatic ring, or a benzene ring with electron-withdrawing substituents, react by direct displacement of the leaving group G from the ring to provide compounds of Formula 1. For compounds of Formula 5 wherein Q2 is attached through a sp3 -hybridized carbon atom, G is typically Cl, Br, I or a sulfonate (e.g., OS(O)2CH3). Compounds of Formula 5 are commercially available or their preparation is known in the art. Of note are embodiments of the method of Scheme 3 wherein a compound of Formula 4 is used to prepare a corresponding compound of Formula 1 specifically disclosed in Tables 85 through 252 below. Scheme 3
OSO2CF3, etc.
Figure imgf000044_0001
4
For reactions according to the method of Scheme 3 of a compound of Formula 4 wherein X is O or NR4 with a compound of Formula 5 (Q2-G) wherein Q is an aromatic or heteroaromatic ring Q lacking sufficiently electron-withdrawing substituents, or to improve reaction rate, yield or product purity, the use of a metal catalyst (e.g., metal or metal salt) in amounts ranging from catalytic up to superstoichiometric can facilitate the desired reaction. Typically for these conditions, G is Br or I or a sulfonate such as OS(O)2CF3 or OS(O)2(CF2)3CF3. For example, copper salt complexes (e.g., CuI with JV.Λ/'-dimethyl- ethylenediamine, proline or bipyridyl), palladium complexes (e.g., tris(dibenzylidene- acetone)dipalladium(O)) or palladium salts (e.g., palladium acetate) with ligands such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (i.e. "Xantphos"), 2-dicyclohexyl- phosphino-2',4',6'-triisopropylbiphenyl (i.e. "Xphos") or 2,2'-bis(diphenylphosphino)- l,l'-binaphthalene (i.e. "BINAP"), in the presence of a base such as potassium carbonate, cesium carbonate, sodium phenoxide or sodium tert-butoxide, in a solvent such as Λ/,Λ/-dimethylformamide, 1 ,2-dimethoxy ethane, dimethyl sulfoxide, 1,4-dioxane or toluene, optionally mixed with alcohols such as ethanol, can be used. Alternatively as illustrated in Scheme 4, compounds of Formula Ic (i.e. Formula 1 in which X is NR4 and R4 is H) can be prepared by reaction of compounds of Formula 6 (i.e. 5-bromopyrazoles or other pyrazoles substituted at the 5 -position with a leaving group) with compounds of Formula 7 under metal-catalyzed conditions similar to those described above for Scheme 3. Compounds of Formula 7 are commercially available or their preparation is known in the art.
Scheme 4
Figure imgf000044_0002
6 G is Br, I, OSO2C4F9, etc. lc
As shown in Scheme 5, compounds of Formula 6 wherein G is Br or I can be prepared by reaction of 5-aminopyrazoles of Formula 4a (i.e. Formula 4 wherein X is NH) under diazotization conditions either in the presence of, or followed by combination with, copper salts containing bromide or iodide. For example, addition of tert-butyl nitrite to a solution of a 5-aminopyrazole of Formula 4a in the presence of CuBr2 in a solvent such as acetonitrile provides the corresponding 5-bromopyrazole of Formula 6. Likewise, a 5-aminopyrazole of Formula 4a can be converted to a diazonium salt and then to a corresponding 5-halopyrazole of Formula 6 by treatment with sodium nitrite in solvents such as water, acetic acid or trifluoroacetic acid, in the presence of a mineral acid typically containing the same halide atom (such as aqueous HI solution for G being I), followed by treatment with the corresponding copper(I) or copper(II) salt according to general procedures well known to those skilled in the art. Scheme 5
raattiioonn
Figure imgf000045_0003
Figure imgf000045_0002
Figure imgf000045_0001
4a 6
G is Br or I.
As shown in Scheme 6, 5-bromopyrazoles of Formula 6a (i.e. Formula 6 wherein G is Br) can be prepared by reacting 5-hydroxypyrazoles of Formula 4b (i.e. Formula 4 wherein X is O) with phosphorus tribromide as described in Tetrahedron Lett. 2000, 47(24), 4713. Scheme 6
Figure imgf000045_0004
4b 6a
As shown in Scheme 7, 5-hydroxypyrazoles of Formula 4b can also be used to prepare 5-fluoroalkylsulfonyl (e.g, 5-trifluoromethanesulfonyl, 5-nonafluorobutylsulfonyl) pyrazoles of Formula 6b (i.e. Formula 6 wherein G is fluoroalkylsulfonyl) as described in Synlett 2004, 5, 795. Scheme 7
Figure imgf000046_0001
6b wherein Rf is fluoroalkyl such as CF3 or (CF2)2CF3
As shown in Scheme 8, compounds of Formula 1 can be prepared by reaction of 4-bromo or iodo pyrazoles of Formula 10 wherein X is O, NR4, C(=O) or S(O)m in which m is 2 with organometallic compounds of formula Qi-M (Formula 11) under transition-metal- catalyzed cross-coupling reaction conditions. Reaction of a 4-bromo or iodo pyrazole of Formula 10 with a boronic acid, trialkyltin, zinc or organomagnesium reagent of Formula 11 in the presence of a palladium or nickel catalyst having appropriate ligands (e.g., triphenylphosphine (PPI13), dibenzylideneacetone (dba), dicyclohexyl(2',6'-dimethoxy- [l,l'-biphenyl]-2-yl)phosphine (SPhos)) and a base, if needed, affords the corresponding compound of Formula 1. For example, a substituted aryl boronic acid or derivative (e.g., Formula 11 wherein Q1 is optionally substituted phenyl or heterocyclyl and M is B(OH)2, B(OC(CH3)2C(CH3)2θ)) or B(O-Z-Pr)3/ Li - reacts with a 4-bromo- or 4-iodopyrazole of Formula 10 in the presence of dichlorobis(triphenylphosphine) palladium(II) and aqueous base such as sodium carbonate or potassium hydroxide, in solvents such as 1,4-dioxane, 1 ,2-dimethoxyethane, toluene or ethyl alcohol, or under anhydrous conditions with a ligand such as phosphine oxide or phosphite ligand (e.g., diphenylphosphine oxide) and potassium fluoride in a solvent such as 1,4-dioxane (see Angewandte Chemie, International Edition 2008, 47(25), 4695-4698) to provide the corresponding compound of Formula 1. Scheme 8
Figure imgf000046_0002
(CH3)2O),
Sn(Me)3, Sn(Bu)3, ZnCl, MgBr, 10 G is Br, I MgCl or MgCl-LiCl.
As illustrated in Scheme 9, compounds of Formula 4a (i.e. Formula 4 wherein X is NH) can be prepared by reacting compounds of Formula 12 with compounds of Formula 11 (such as Qi-B(OH)2 (Formula Ha)) using transition-metal-catalyzed cross-coupling reaction conditions as described for the method of Scheme 8. Scheme 9
Figure imgf000047_0001
12 G is Br, I 4a
As illustrated in Scheme 10, pyrazoles of Formula 10 wherein X is O, S(O)2, NR4 or C(=O) and G is Br or I are readily prepared by the reaction of pyrazoles unsubstituted at the 4-position (Formula 13) with halogenating reagents such as bromine, sodium bromite, Λ/-bromosuccinimide (NBS) or JV-iodosuccinimide (NIS), in solvents such as acetic acid, acetonitrile, Λ/,Λ/-dimethylformamide, JV,iV-dimethylacetamide or 1,4-dioxane, or a mixture of water with the aforementioned solvents, at temperatures ranging from ambient to the boiling point of the solvent. Scheme 10
I
Figure imgf000047_0002
Furthermore, using reaction conditions similar to those for the method of Scheme 10, compounds of Formula 13 wherein A is H or a protecting group can be converted into intermediates corresponding to Formula 10 wherein Q2 is replaced by A or a protecting group, respectively, which are useful for preparing compounds of Formula 1. Compounds of Formula 13 wherein A is H can be be prepared by methods known in the art; see, for example, Synlett 2004, 5, 795-798, US 4256902 and references cited therein. Furthermore, some compounds of Formula 13 wherein A is H, particularly those in which R2 is methyl, ethyl or halogen, are commercially available. As shown in Scheme 11, compounds of Formula 13 wherein X is O, S(O )m or NR4, m is 0, and A is Q2 can be prepared from corresponding compounds of Formula 13a (i.e. Formula 13 wherein A is H) by procedures analogous those used for the method of Scheme 3. Compounds of Formula 13 wherein X is S (i.e. S(O )m wherein m is 0) can then be oxidized using procedures such as those used for the method of Scheme 1 to provide corresponding compounds of Formula 13 wherein X is S(O)2 for use in the method of Scheme 10. Compounds of Formula 13a are commercially available or can be prepared by methods known in the art.
Scheme 11
R2
Q2-G
5
I 1 1 a CHR1R^ G is F, Cl, Br, I, NO2, OS(O)2CF3 , etc. CHR1R^
13a 13
X is O, S or NR4 A is Q2 As shown in Scheme 12, compounds of Formula Ia (i.e. Formula 1 wherein X is
S(O)1n and m is O), Formula Id (i.e. Formula 1 wherein X is CR15R16, R15 is H, R16 is OR18 and R18 is H,) and Formula Ie (i.e. Formula 1 wherein X is C(=0)) can be prepared by treatment of compounds of Formula 6 with an organometallic reagent (i.e. Formula 26) such as an alkyllithium, preferably n-butyllithium, or an alkylmagnesium reagent, preferably isopropylmagnesium chloride (optionally complexed with lithium chloride), followed by the addition of a sulfur electrophile (i.e. Formula 27) or carbonyl electrophile (i.e. Formula 28, 29 or 30). Reaction temperatures can range from -90 0C to the boiling point of the reaction solvent; temperatures of -78 0C to ambient temperature are generally preferred, with temperatures of -78 to -10 0C preferred when an alkyllithium reagent is used, and -20 0C to ambient temperature preferred with use of alkylmagnesium reagents. A variety of solvents are useful, such as toluene, ethyl ether, tetrahydrofuran or dimethoxymethane; anhydrous tetrahydrofuran is preferred. A second metallic component, such as zinc chloride, zinc bromide or a monovalent copper salt, such as copper(I) iodide or copper(I) cyanide, can advantageously be added before the electrophile in cases in which the electrophile is Q2C(O)Cl (i.e. Formula 30). The Q2-containing sulfur and carbonyl intermediates of Formulae 27, 28, 29 and 30 are commercially available or can be prepared by methods known in the art. Scheme 12
Figure imgf000049_0001
It will be recognized by one skilled in the art that reactions analogous to those shown in Scheme 12 can also be utilized with pyrazoles lacking a Q1 substituent, thus affording certain compounds of Formula 13 that are useful in the method outlined in Scheme 10.
General methods useful for preparing 5-aminopyrazoles of Formula 4a are well known in the art; see, for example, Journal fiir Praktische Chemie (Leipzig) 1911, 83, 111 and J. Am. Chem. Soc. 1954, 76, 501. Such a method is illustrated in Scheme 13 in which R2 is alkyl or cycloalkyl.
Scheme 13
Figure imgf000049_0002
Similarly, general methods useful for preparing 5-hydroxypyrazoles of Formula 4b are well known in the art; see, for example, Annalen der Chemie 1924, 436, 88. Such a method is illustrated in Scheme 14 in which R2 is alkyl or cycloalkyl. Scheme 14
Figure imgf000050_0001
1 6 B1 is alkyl, aryl, benzyl, etc
As shown in Scheme 15, 5-thiopyrazole compounds of Formula 4c (i.e. Formula 4 wherein X is S) can be prepared by reaction of corresponding 5-hydroxypyrazole compounds of Formula 4b with P2S5 (see, for example, Justus Liebigs Annalen der Chemie 1908, 361, 251) or with Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane 2,4-disulfide; see, for example, International Patent Publication WO 2005/118575) in solvents such as toluene, xylene or tetrahydrofuran.
Scheme 15
Figure imgf000050_0002
4C
As shown in Scheme 16, compounds of Formula Ic (i.e. Formula 1 wherein X is NR4 and R4 is H) can be prepared by condensing compounds of Formula 17 with alkylhydrazines of Formula 15 in a solvent such as ethanol or methanol and optionally in the presence of an acid or base catalyst such as acetic acid, piperidine or sodium methoxide, according to general procedures known in the art.
Scheme 16
Figure imgf000050_0003
17 wherein R32 is H or lower alkyl (e.g., CH3, CH2CH3 or (CH2)2CH3)
In a manner analogous to the method of Scheme 16, compounds of Formula 2 wherein X is NH can be similarly prepared by condensing compounds of Formula 17 with hydrazine. This method is described in Chemistry of Heterocyclic Compounds 2005, 41(1), 105-110. As shown in Scheme 17, compounds of Formula 17 (wherein, e.g., R2 is methyl, ethyl or optionally substituted cyclopropyl and R33 is H or lower alkyl such as CH3, CH2CH3 or (CH2)2CH3) can be prepared by reaction of corresponding ketene dithioacetal compounds of Formula 18 with compounds of formula Q2-NH2 (i.e. Formula 7) optionally in the presence of a base, such as sodium hydride or ethylmagnesium chloride, in solvents such as toluene, tetrahydrofuran or dimethoxymethane, at temperatures ranging from -10 0C to the boiling point of the solvent. See, for example, J. Heterocycl. Chem. 1975, /2(1), 139. Methods useful for preparing compounds of Formula 18 are known in the art.
Scheme 17
Figure imgf000051_0001
1 β 17 γ Q wherein R33 is H or lower alkyl (e.g., CH3, CH2CH3 or (CH2)2CH3)
It is also known in the art (see, for example, Synthesis 1989, 398) that compounds of Formula 18 in which the two R33 groups are taken together as a single CH2 group (thus forming a dithietane ring) react with an stoichiometric excess amount of hydrazines of Formula 15 to afford compounds of Formula 4c, which are useful for preparation of
15 compounds of Formula 1 in which X is S according to the method of Scheme 3.
As shown in Scheme 18, compounds of Formula 17a (i.e. tautomer of Formula 17 wherein R33 is H) can be prepared by reaction of corresponding isothiocyanate compounds of Formula 19 with arylacetone compounds of Formula 20 wherein R2 is methyl, ethyl or optionally substituted cyclopropyl; see, for example, Zhurnal Organicheskoi Khimii 1982, 0 18(12), 2501. Bases useful for this reaction include sodium hydride, alkoxide bases (e.g., potassium te/t-butoxide or sodium ethoxide), potassium hydroxide, sodium hydroxide, potassium carbonate, or amine bases (e.g., triethylamine or JV,jV-diisopropylethylamine). A variety of solvents are useful, such as tetrahydrofuran, ether, toluene, Λf,iV-dimethyl- formamide, alcohols (e.g., ethanol), esters (e.g., ethyl acetate or isopropyl acetate), or 5 mixtures thereof. Solvents are chosen for compatibility with the base selected, as is well- known in the art. Reaction temperatures can range from -78 0C to the boiling point of the solvent. One useful mixture of base and solvent is potassium tert-butoxide in tetrahydrofuran, to which at -70 to 0 0C is added a combined solution of an isothiocyanate of Formula 19 and a carbonyl compound of Formula 20. Scheme 18
Figure imgf000052_0001
Ketothioamides of Formula 17 can be also be prepared by allowing the corresponding ketoamides to react with sulfurizing agents such as Lawesson's reagent or P2S5; see, for example, HeIv. Chim. Act. 1998, 57(7), 1207.
Compounds of Formula 2 wherein X is NH and R2 is Cl or Br, which are useful for preparing compounds of Formula 1 according to the method of Scheme 2, can be prepared by reaction of corresponding compounds of Formula 31 with POCI3 or POBr3 using general procedures known in the art, as shown in Scheme 19. Scheme 19
Figure imgf000052_0002
31 X is NH 2
As shown in Scheme 20, compounds of Formula If (i.e. Formula 1 wherein R1 and
Rla are H and R2 is OCH3) can be prepared by reacting corresponding compounds of
Formula 31 with diazomethane or iodomethane in the presence of base using general procedures known in the art, such as those described in J. Heterocyclic Chem. 1988, 1307-
1310.
Scheme 20
Figure imgf000052_0003
If
Compounds of Formula Ig (i.e. Formula 1 wherein R1 and Rla are H and R2 is SCH3) can be prepared by treating corresponding compounds of Formula 31 with P2S5 or
Lawesson's Reagent to prepare compounds of Formula 32, which are then reacted with diazomethane or iodomethane in the presence of base using general procedures known in the art, as shown in Scheme 21.
Scheme 21
Figure imgf000053_0001
As shown in Scheme 22, compounds of Formula 31 wherein X is NH can be prepared by condensation of corresponding isothiocyanates of Formula 19 with esters of Formula 33 wherein R33 is lower alkyl (e.g., methyl, ethyl, propyl) in the presence of a strong, non- nucleophilic base such as sodium hydride or lithium hexamethyldisilazide, in an inert solvent such as tetrahydrofuran (analogous to the method of Scheme 18), followed by reaction of the intermediate with hydrazine or an acid salt of hydrazine, such as, for example, an acetate or hydrochloride salt (analogous to the method of Scheme 16).
Scheme 22
Figure imgf000053_0002
19 33 31
X is NH
R33 is lower alkyl
One skilled in the art will recognize that use of a substituted hydrazine of formula H2NNHCHR1R^ instead of unsubstituted hydrazine in the method of Scheme 22, followed by the further manipulations described for Schemes 19, 20 and 21 will also afford compounds of Formula 1.
Compounds of Formula Ic (i.e. Formula 1 wherein X is NR4 and R4 is H) in which R2 is halogen can also be prepared as shown in Scheme 23. In this method an acetonitrile compound of Formula 21 is condensed with an isothiocyanate compound of Formula 22 in the presence of a base such as sodium hydride or potassium tert-butoxide, in a solvent such as Λ/,Λ/-dimethylformamide or tetrahydrofuran, to afford a cyano ketoamide intermediate compound, which is then reacted with a methylating agent such as iodomethane or dimethyl sulfate, in the presence of a base to provide the corresponding compound of Formula 23. Alternatively, the methylating agent can be included in the reaction mixture with the compounds of Formulae 21 and 22 without isolation of the cyano ketoamide intermediate. One skilled in the art will recognize that compounds of Formula 23 can also be prepared by a method analogous to Scheme 17 wherein the C(O)R2 of the compound of Formula 18 is replaced by cyano. According to the method of Scheme 23, the resultant compound of Formula 23 is then reacted with an alkylhydrazine of Formula 15 to form the corresponding 3-aminopyrazole compound of Formula 24 using general procedures known in the art; see, for example, J. Chem. Soc. Perkin 1 1988, 2, 169-173 and J. Med. Chem. 2003, 46(7), 1229-1241. The amino group of the compound of Formula 24 can then be converted to R2 being halogen in Formula Ic by a diazotization reaction using conditions known in the art, such as those previously described for Scheme 5. Scheme 23
Figure imgf000054_0001
R is halogen.
Analogous to the method of Scheme 23, compounds of Formula 2 wherein X is NH and R2 is halogen can be similarly prepared by condensing compounds of Formula 23 with hydrazine instead of an alkylhydrazine of Formula 15. As shown in Scheme 24, compounds of Formula Ih (i.e. Formula 1 wherein X in NR4) can be prepared by reacting corresponding compounds of Formula Ic (i.e. Formula 1 wherein X is NH) with an electrophile comprising R4 (i.e. Formula 25) typically in the presence of a base such as NaH and a polar solvent such as Λf,Λ/-dimethylformamide. In this context the expression "electrophile comprising R4" means a chemical compound capable of transferring an R4 moiety to a nucleophile (such as the nitrogen atom attached to Q2 in Formula Ic). Often electrophiles comprising R4 have the formula R4Lg wherein Lg is a nucleofuge (i.e. leaving group in nucleophilic reactions). Typical nucleofuges include halogens (e.g., Cl, Br, I) and sulfonates (e.g., OS(O)2CH3, OS(O)2CF3, OS(O)2-(4-CH3-Ph)). However, some electrophiles comprising R4 do not comprise a nucleofuge; an example is sulfur trioxide (SO3), which after deprotonation (such as by a base of the formulae M+H~ wherein M+ is a cation) of the nitrogen atom attached to Q2 in Formula Ic, can bond to the nitrogen atom as a -SO3 ^M+ substituent. Scheme 24
Figure imgf000055_0001
H Ih
Figure imgf000055_0002
It is recognized by one skilled in the art that various functional groups can be converted into others to provide different compounds of Formula 1. For example, compounds of Formula 1 in which R2 is methyl, ethyl or cyclopropyl can be modified by free-radical halogenation to form compounds of Formula 1 wherein R2 is halomethyl, haloethyl or halocyclopropyl. The halomethyl compounds can be used as intermediates to prepare compounds of Formula 1 wherein R2 is hydroxymethyl or cyanomethyl. Compounds of Formula 1 or intermediates for their preparation may contain aromatic nitro groups, which can be reduced to amino groups, and then be converted via reactions well known in the art such as the Sandmeyer reaction, to various halides, providing other compounds of Formula 1. By similar known reactions, aromatic amines (anilines) can be converted via diazonium salts to phenols, which can then be alkylated to prepare compounds of Formula 1 with alkoxy substituents. Likewise, aromatic halides such as bromides or iodides prepared via the Sandmeyer reaction can react with alcohols under copper-catalyzed conditions, such as the Ullmann reaction or known modifications thereof, to provide compounds of Formula 1 that contain alkoxy substituents. Additionally, some halogen groups, such as fluorine or chlorine, can be displaced with alcohols under basic conditions to provide compounds of Formula 1 containing the corresponding alkoxy substituents. The resultant alkoxy compounds can themselves be used in further reactions to prepare compounds of Formula 1 wherein R3 is -U-V-T (see, for example, PCT Publication WO 2007/149448 A2). Compounds of Formula 1 or precursors thereof in which R2 or R3 is halide, preferably bromide or iodide, are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1. These types of reactions are well documented in the literature; see, for example, Tsuji in Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley and Sons, Chichester, 2002; Tsuji in Palladium in Organic Synthesis, Springer, 2005; and Miyaura and Buchwald in Cross Coupling Reactions: A Practical Guide, 2002; and references cited therein.
One skilled in the art will recognize that sulfide groups can be oxidized to the corresponding sulfoxides or sulfones by conditions well-known in the art. Likewise, compounds of Formula 1 wherein X is CR15R16, R15 is H, R16 is OR18 and R18 is H can be readily interconverted with corresponding compounds of Formula 1 wherein X is C(=O) by alcohol oxidation and ketone reduction reactions well known in the art. Compounds of Formula 1 wherein X is C(=O) (i.e. ketones) can be readily converted to ketals using general methods known in the art, thus providing compounds of Formula 1 wherein X is CR15R16 and R15 and R16 are taken together as -OCH2CH2O-. Compounds of Formula 1 wherein X is C(=O) can also be converted by the use of Lawesson's Reagent to prepare corresponding compounds of Formula 1 wherein X is C(=S). Furthermore, compounds of Formula 1 wherein X is CR15R16, R15 is C1-C4 alkyl, R16 is OR18, and R18 is H can be prepared by adding an alkyl Grignard reagent to the corresponding compounds of Formula 1 wherein X is C(O). The above reactions can also in many cases be performed in alternate sequence, such as the preparation of lHpyrazoles for use in the reaction in Scheme 2 by reactions illustrated later for the general preparation of substituted pyrazoles. The presence of certain functional groups may not be compatible with all of these reaction conditions, and the use of protecting groups may be desirable for obtaining the desired products with improved yields and or purity.
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1. One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfield from tetramethylsilane in CDCI3 unless otherwise noted; "s" means singlet, "m" means multiplet, "br s" means broad singlet. Mass spectra are reported as the molecular weight of the highest isotopic abundance parent ion (M+ 1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP+) where "amu" stands for atomic mass units.
SYNTHESIS EXAMPLE 1 Preparation of N-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
(Compound 1) Step A: Preparation of α-Acetyl-2,4-difluorobenzeneacetonitrile (alternatively named methyl α-cyano-2,4-difluorobenzeneacetate) Sodium hydride (60 % in mineral oil) (1.5 g, 38 mmol) was stirred in xylenes (7 mL) under a nitrogen atmosphere at ambient temperature. A solution of anhydrous ethanol (6.3 mL, 64 mmol) in xylenes (2 mL) was added dropwise over about 20 minutes at a temperature of about 40 0C. The reaction mixture was heated to 70 0C, and a solution of 2,4-difluorophenylacetonitrile (3.9 g, 25 mmol), ethyl acetate (3.8 mL, 38 mmol) and xylenes (1 mL) was added dropwise over 15 min. Additional xylenes (5 mL) was added to aid stirring. The reaction mixture was heated for 2 h, then allowed to cool. Water (50 mL) was added, and the mixture was extracted with hexanes (50 mL). The aqueous phase was then acidified to pΗ 3-4 with 1 N aqueous HCl solution. The aqueous phase was extracted with ether (50 mL), and the ethereal extract was washed with water (25 mL) and brine, then dried over MgSO4, and concentrated to give the title compound as a viscous residue (3.3 g). 1H NMR δ 7.42 (m, IH), 6.8-7.0 (m, 2H), 4.95 (s, IH), 2.36 (s, 3H).
Step B: Preparation of 4-(2,4-Difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
Acetic acid (0.5 mL, 8.3 mmol) and methylhydrazine (534 μL, 10.0 mmol) were added to a solution of the residue obtained in Step A (1.6 g, 8.5 mmol) in ethyl alcohol (8 mL). The reaction mixture was then heated at reflux for 16 h under a nitrogen atmosphere. While the reaction mixture was still warm, water was added in small portions (1 mL at a time) until a precipitate formed (about 12 mL of water total). The mixture was reheated to dissolve the solids and then allowed cooled to room temperature. The resulting precipitate was collected on a glass frit, washed with 2 to 3 mL of 50% aqueous ethyl alcohol, and dried under vacuum to obtain the compound as a white solid (0.99 g). 1H NMR δ 7.20 (m, IH), 6.92 (m, 2H), 3.68 (s, 3H), 3.47 (br s, 2H), 2.14 (s, 3H). Step C: Preparation of Λ/-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine
Palladium(II) acetate (90 mg, 0.40 mmol), 4,5-bis(diphenylphosphino)-
9,9-dimethylxanthene (460 mg, 0.80 mmol) and powdered potassium carbonate (5.5 g, 40 mmol) were combined in anhydrous 1,4-dioxane (20 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 4-(2,4-Difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine (i.e. the product of Step B) (0.89 g, 4.0 mmol) was added in one portion, and l-bromo-3-chlorobenzene (0.47 mL, 4.0 mmol) was added via a syringe. The reaction mixture was heated at reflux under a nitrogen atmosphere for 3 h. Additional l-bromo-3-chlorobenzene (0.09 mL, 0.8 mmol) was added, and heating was continued for
1 h. The reaction mixture was allowed to cool to room temperature, and then partitioned between water (40 mL) and ethyl acetate (40 mL). The organic phase was washed with additional water (40 mL), brine (40 mL), dried over MgSθ4 and concentrated under reduced pressure. The residue was purified by column chromatography through 10 g of silica gel eluted with hexanes/ethyl acetate (1 : 1) to give the title compound, a compound of the present invention, as a solid (0.41 g).
1H NMR δ 7.2-7.3 (m, 2H), 7.10 (m, IH), 6.9-7.0 (m, 2H), 6.70 (m, IH), 6.58 (m, IH), 6.52 (m, IH), 3.64 (s, 3H), 2.14 (s, 3H). MS: 334 amu.
SYNTHESIS EXAMPLE 2 Preparation of 4-(2-Chloro-4-fluorophenyl)-Λ/-(2,6-difluoro-4-methoxyphenyl)- l,3-dimethyl-lH-pyrazol-5-amine (Compound 17) Step A: Preparation of 5-Bromo-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazole
Copper(II) bromide (3.94 g, 17.7 mmol) was added to a solution of 4-[2-chloro- 4-fluorophenyl]-l,3-dimethyl-lH-pyrazol-5-amine (prepared similarly to the preparation of
4-(2,4-Difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine in Steps A and B of Synthesis
Example 1) (2.4 g, 10 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyi nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous HCl solution (20 mL) was added, and then ethyl acetate was added
(20 mL). This mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid.
The filter pad was washed with ethyl acetate (20 mL), and the phases were separated. The organic phase was washed with 1.0 N aqueous hydrochloric acid solution and brine, dried over MgSOφ and concentrated to leave the title compound as an orange-brown semisolid (2.8 g).
1H NMR δ 7.18-7.25 (m, 2H), 7.04 (m, IH), 3.89 (s, 3H), 2.14 (s, 3H). Step B: Preparation of 4-(2-Chloro-4-fluorophenyl)-Λ/-(2,6-difluoro-
4-methoxyphenyl)-l,3-dimethyl-lH-pyrazol-5-amine
5-Bromo-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole (i.e. the product of
Step A) (0.20 g, 0.66 mmol), palladium(II) acetate (15 mg, 0.066 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.13 mmol) and powdered potassium carbonate (1.8 g, 13 mmol) were combined in anhydrous 1,4-dioxane (3 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,6-Difluoro-
4-methoxyaniline (0.22 g, 1.3 mmol) was added in one portion, and the reaction mixture was heated at reflux for 22 h. The reaction mixture was filtered through Celite® diatomaceous filter aid, and the filter pad was washed with ethyl acetate (20 mL). The filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSOφ and concentrated to leave a semisolid residue. This residue was purified by column chromatography through 5 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1 :3) to give the title compound, a compound of the present invention, as a light-brown solid (48 mg). 1H NMR δ 7.0-7.1 (m, 2H), 6.85 (m, IH), 6.26 (m, 2H), 4.84 (br s, IH), 3.78 (s, 3H), 3.66
(s, 3H), 2.08 (s 3H). MS: 382 amu.
SYNTHESIS EXAMPLE 3
Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-l,3-dimethyl-Λ/-(2,4,6-trifluorophenyl)- lH-pyrazol-5-amine (Compound 24) Step A: Preparation of 2,6-Difluoro-4-methoxybenzeneacetonitrile
A solution of KCN (0.88 g, 13 mmol) dissolved in water (2 mL) was added dropwise to a water-bath-cooled solution of 2,6-difluoro-4-methoxybenzyl bromide (2.50 g, 10.5 mmol) in Λ/,Λ/-dimethylformamide (10 mL). The reaction mixture was stirred for 20 min. Water was added (20 mL) and then the reaction mixture was poured into saturated aqueous NaΗCC>3 solution (20 mL) and extracted with ether (50 mL). The organic phase was washed with water (5 x 25 mL), dried over MgSOφ and concentrated to give an oil, which crystallized on standing to provide the title compound as a white solid (1.9 g). 1H NMR δ 6.50 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H). Step B: Preparation of α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile Solid sodium ethoxide (4.7 g, 66 mmol) was stirred in a mixture of xylene (20 mL) and ethanol (10 mL) and heated to 50 0C. A solution of 2,6-difluoro-4-methoxybenzene- acetonitrile (i.e. the product of Step A) (8.0 g, 44 mmol) in ethyl acetate (10.4 mL) was added dropwise. The reaction mixture was heated at 50 0C for 4 h and then allowed to cool to ambient temperature. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (25 mL). The aqueous phase was acidified with 3 N aqueous HCl to pH 4 and extracted with ethyl acetate (100 mL). This organic phase was washed with water (50 mL), brine (50 rnL), then dried over MgSO4, and concentrated to leave the title compound as a tan semisolid (8.0 g).
1H NMR δ 6.56 (m, 2H), 4.86 (s, IH), 3.83 (s, 3H), 2.40 (s, 3H).
Step C: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazole- 5 -amine α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step B) (8.03 g, 35.7 mmol) and acetic acid (5 mL) were stirred in ethanol (35 mL), and methylhydrazine (1.91 mL, 35.7 mmol) was added. The reaction mixture was heated at reflux for 16 h, cooled, and then poured into water (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with 1 N aqueous NaOH (50 mL) and then brine (50 mL), dried over MgSO4, and concentrated to leave a solid. The solid was dissolved in methanol, and the resulting solution was warmed to 45 0C. Water (25 mL) was added dropwise, and the mixture was allowed to cool. The precipitate was collected on a glass frit to give the title compound as a white solid (3.88 g). 1H NMR δ 6.55 (m, 2H), 3.81 (s, 3H), 3.67 (s, 3H), 3.43 (br s, 2H), 2.09 (s, 3H).
Step D: Preparation of 5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl- lH-pyrazole
Copper(II) bromide (3.81 g, 16.9 mmol) was added to a solution of 4-(2,6-difluoro- 4-methoxyphenyl)-l,3-dimethyl-lH-pyrazole (i.e. the product of Step C) (3.88 g, 15.4 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyi nitrite (90% technical grade, 3.54 mL, 26.9 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous hydrochloric acid solution (25 mL) was added, then ethyl acetate (25 mL) was added, and the resulting mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (50 mL), and the phases were separated. The organic phase was washed with 1 N aqueous HCl solution (25 mL) and brine (25 mL), dried over MgSO4, and concentrated. The residue was purified by column chromatography through 24 g of silica gel eluted with a gradient of hexanes/ethyl acetate (9:1 to 1 :1) to give the title compound as a white solid (3.25 g). 1H NMR δ 6.54 (m, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 2.16 (s, 3H).
Step E: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-l,3-dimethyl-
Λ/-(2,4,6-trifluorophenyl)-lH-pyrazol-5-amine
5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazole (i.e. the product of Step D) (0.30 g, 0.94 mmol), palladium(II) acetate (20 mg, 0.090 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.11 g, 0.19 mmol) and powdered potassium carbonate (2.6 g, 19 mmol) were combined in anhydrous 1,4-dioxane (4 mL), and the resulting mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,4,6-Trifluoroaniline (0.28 g, 1.9 mmol) was added in one portion, and the reaction mixture was heated at reflux under nitrogen for 22 h. The reaction mixture was cooled, then filtered through Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (2O mL), and the filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSOφ and concentrated to leave a semisolid residue. The residue was purified by column chromatography through 12 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1 :3) to give the title compound, a compound of the present invention, as a semisolid (73 mg).
1H NMR (acetone-^) δ 6.84 (br s, IH), 6.68 (m, 2H), 6.43 (m, 2H), 3.77 (s, 3H), 3.75 (s, 3H), 1.99 (s, 3H). MS: 384 amu (AP+). SYNTHESIS EXAMPLE 4
Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]- 3,5-difluorobenzonitrile (Compound 45)
Step A: Preparation of 4-[(l,3-Dimethyl-lH-pyrazol-5-yl)oxy]-
3 ,5 -difluorobenzonitrile Potassium carbonate (1.38 g, 10 mmol) was added to a solution of 2,4-dihydro-
2,5-dimethyl-3H-pyrazol-3-one (0.70 g, 6.3 mmol) in N,Λ/-dimethylformamide (15 mL).
3,4,5-Trifluorobenzonitrile (0.94 g, 6.0 mmol) was added, and the reaction mixture was heated at 75 0C under a nitrogen atmosphere for 16 h, then allowed to cool. The reaction mixture was partitioned between water (60 mL) and ethyl acetate (30 mL). The organic phase was washed with water (2 x 30 mL) and brine (30 mL), dried over MgSOφ and concentrated to give the title compound as a yellow oil (1.38 g).
1H NMR δ 7.36 (m, 2H), 5.24 (s, IH), 3.78 (s, 3H), 2.16 (s, 3H).
Step B: Preparation of 3,5-Difluoro-4-[(4-iodo-l,3-dimethyl-lH-pyrazol-
5 -yl)oxy]benzonitrile A solution of 4-[(l,3-dimethyl-lH-pyrazol-5-yl)oxy]-3,5-difluorobenzonitrile (i.e. the product of Step A) (1.38 g, 5.5 mmol) in acetonitrile (20 mL) was stirred at ambient temperature, and TV-iodosuccinimide (1.35 g, 6.0 mmol) was added in one portion. The reaction mixture was heated at reflux for 2 h, cooled, and then poured into water (40 mL).
The resulting mixture was extracted with ethyl acetate (40 mL). The organic phase was washed with water (20 mL) and saturated aqueous NaΗCC>3 solution (20 mL), dried over
MgSOφ and concentrated under reduced pressure to give the title compound as a tan solid
(2.I g).
1H NMR (acetone-d6) δ 7.80 (m, 2H), 3.82 (s, 3H), 2.09 (s, 3H). MS: 376 amu (AP+). Step C: Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol- 5 -y 1] oxy ] -3 , 5 -difluorobenzonitrile
To a solution of 3,5-difluoro-4-[(4-iodo-l,3-dimethyl-lH-pyrazol-5-yl)oxy]- benzonitrile (i.e. the product of Step B) (1.0 g, 2.67 mmol) in 1,4-dioxane (6 mL) was added 2-chloro-4-fluorobenzeneboronic acid (alternatively named i?-(2-chloro-4-fiuorophenyl)- boronic acid) (0.93 g, 5.33 mmol), dichloro (bis)triphenylphosphine palladium(II) (alternatively named bis(triphenylphosphine)palladium(II) dichloride) (93 mg, 0.13 mmol), potassium carbonate (0.74 g, 5.33 mmol), and water (4 mL). The resulting mixture was heated at reflux for 5 h, allowed to cool, and partitioned between water (20 mL) and ethyl acetate (20 mL). The organic layer was dried over MgSθ4 and concentrated. The residue was purified by chromatography on silica gel with a gradient of hexanes / ethyl acetate to obtain the title compound, a compound of the present invention, as an off-white solid (l lO mg). 1H NMR δ 7.00-7.09 (m, 3H), 6.97 (m, IH), 6.86 (m, IH), 3.85 (s, 3H), 2.02 (s, 3H).
SYNTHESIS EXAMPLE 5 Preparation of 4-(2,4-Dichlorophenyl)-N-(2,4-difluorophenyl)-l, 3-dimethyl- lH-pyrazol-
5 -amine (Compound 69)
Step A: Preparation of α-Acetyl-2,4-dichloro-iV-(2,4-difiuorophenyl)benzene- ethanethioamide
2,4-Difluorophenyl isothiocyanate (0.27 mL, 2.0 mmol) was added to a stirred suspension of sodium hydride (60% in mineral oil) (112 mg, 2.8 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice-water bath under a nitrogen atmosphere. A solution of (2,4-dichlorophenyl)-2-propanone (570 mg, 2.8 mmol) in tetrahydrofuran (4 mL) was added dropwise over 5 min. The resultant yellow solution was stirred at 5-10 0C for 1 h. Water (10 mL) was carefully added, and the reaction mixture was extracted with ethyl acetate (10 mL). The aqueous phase was acidified to pΗ 3 with 1 N aqueous HCl, then extracted with ethyl acetate (20 mL). The organic extract was washed with water (10 mL) and brine (10 mL), dried over MgSOφ and concentrated to leave a solid. The solid was triturated with hexanes / ethyl acetate (2:1), collected on a glass frit, and air-dried to give the title compound as a white solid (240 mg). MS: 373 amu (AP+). Step B: Preparation of 4-(2,4-Dichlorophenyl)-Λ/-(2,4-difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine
Acetic acid (50 μL) and methylhydrazine (41 μL) were added to a stirred suspension of α-acetyl-2,4-dichloro-Λ/-(2,4-difluorophenyl)benzeneethanethioamide (238 mg,
0.64 mmol) in ethanol (4 mL). The reaction mixture was heated at reflux for 2 h and allowed to cool. Then the reaction mixture was diluted with ethyl acetate (10 mL) and washed with 1 N aqueous NaOH (10 mL), water (10 mL) and brine (10 mL), dried over
MgSOφ and concentrated to leave a solid residue. The residue was purified by column chromatography on 5 g of silica gel with a gradient of hexanes/ethyl acetate (2:1 to 1 :1) to give the title compound as a solid (170 mg).
1H NMR δ 7.43 (s, IH), 7.19 (m, IH), 7.07 (m, IH), 6.78 (m, IH), 6.62 (m, IH), 6.37 (m, IH), 5.22 (br s, IH), 3.70 (s, 3H), 2.18 (s, 3H). MS: 368 amu (AP+). SYNTHESIS EXAMPLE 6 Preparation of 4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazole-5-methanol (Compound 351)
5-Bromo-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole (i.e. the product of Synthesis Example 2, Step A) (0.25 g, 0.82 mmol) was dissolved in anhydrous tetrahydrofuran (12 mL), and the mixture was cooled in a dry ice/acetone bath under a nitrogen atmosphere. A cyclohexane solution of n-butyllithium (2.0 M, 0.49 mL,
0.98 mmol) was added dropwise over 5 minutes. After 15 minutes, a solution of
2,4-difluorobenzaldehyde (0.09 mL, 0.82 mmol) in anhydrous tetrahydrofuran (3 mL) was added slowly dropwise, causing the dark red-colored solution to lighten to a yellow color.
After 45 minutes, the reaction mixture was quenched by the addition of saturated aqueous
NH4Cl solution (~20 mL) and allowed to warm to ambient temperature. This mixture was extracted with ethyl acetate, and the organic phase was washed with saturated aqueous
NH4Cl solution (25 mL) and with brine, dried over Na2SO4, and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (7% to 10%) to give the title product, a compound of the present invention, as a white semi-solid (109 mg).
1H NMR δ 7.5 (m, IH), 7.1 (m, 2H), 7.0 (m, IH), 6.85 (m, 2H), 6.0 (br s, IH), 5.9 (s, IH), 3.8 (s, 3H), 2.1 (s, 3H). MS: 367 amu (AP+). SYNTHESIS EXAMPLE 7
Preparation of [4-(2-Chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl](2,4- difluorophenyl)methanone (Compound 370)
4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazole-
5-methanol (i.e. the product of Synthesis Example 6) (90 mg, 0.25 mmol) was dissolved in dichloromethane (8 mL), and pyridinium dichromate (113 mg, 0.3 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 16 h, and then the reaction mixture was partitioned between water (5 mL) and dichloromethane (5 mL). The organic phase was washed with additional water (5 mL) and with brine (5 mL), dried over
Na2SO4 and concentrated under reduced pressure to give a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (25% to 30%) to give the title product, a compound of the present invention, as a pale yellow viscous oil (29 mg).
1H NMR δ 7.94 (m, IH), 7.32 (s, IH), 7.27 (m, IH), 7.03 (m, IH), 6.95 (m, IH), 6.78 (m, IH), 3.82 (s, 3H), 2.13 (s, 3H). MS: 365 amu (AP+). SYNTHESIS EXAMPLE 8
Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-l,3-dimethyl-4-(2,4,6-trifluorophenyl)- IH- pyrazole (Compound 54) Step A: Preparation of Methyl 2,4,6-trifluorobenzeneacetate
A solution of 2,4,6-trifluorobenzeneacetic acid (5.00 g, 26.3 mmol) in methanol (25 rnL) was stirred at ambient temperature, and thionyl chloride (6 mL, ~ 3 eq.) was added dropwise, causing the temperature of the reaction mixture to reach 60 0C. The reaction mixture was allowed to cool to ambient temperature and was stirred for 3 h. Water (25 mL) was added with ice cooling. The mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic phases were washed with water (2x), with saturated aqueous sodium bicarbonate solution and with brine, and dried over MgSOφ Concentration provided the title product as a clear oil (5.38 g). 1H NMR δ 6.68 (m, 2H), 3.72 (s, 3H), 3.66 (s, 2H).
Step B: Preparation of Methyl α-acetyl-2,4,6-trifluorobenzeneacetate
To a commercially obtained tetrahydrofuran solution of lithium bis(trimethyl- silyl)amide (1.0 M, 21.0 mL), stirred under a nitrogen atmosphere and cooled to an internal temperature of -65 0C, was added dropwise over 30 minutes a solution of methyl 2,4,6-trifluorobenzeneacetate (i.e. the product of Step A) (2.04 g, 10.0 mmol) dissolved in dry tetrahydrofuran (10 mL). The reaction mixture was stirred for an additional 30 minutes, and then while maintaining the -65 0C temperature, a solution of freshly distilled acetyl chloride (0.80 mL, 11 mmol) in dry tetrahydrofuran (3 mL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature, and then water (30 mL) was added. The resultant mixture was extracted with ethyl acetate (60 mL). The aqueous phase was acidified with 1 N hydrochloric acid and extracted with ethyl acetate (60 mL). Only the first extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product. The initial organic phase was further washed with 1 N hydrochloric acid, water and brine, dried over MgSO^ and concentrated to provide the title product as a clear oil (1.86 g). 1H NMR δ 6.69 (m, 2H), 3.7 (m, IH and s, 3H), 1.87 (s, 3 H); minor resonances at 13.2 ppm and 4.9 ppm indicated presence of enolic tautomer. Step C: Preparation of l,3-Dimethyl-4-(2,4,6-trifluorophenyl)-lH-pyrazol-5-ol
To a solution of methyl α-acetyl-2,4,6-trifluorobenzeneacetate (i.e. the product of Step B) (2.46 g, 10.0 mmol) in methanol (15 mL) was added methylhydrazine (0.665 mL, 12.5 mmol), and the mixture was stirred at ambient temperature over 3 days. Aqueous citric acid solution (1 M, 10 mL) was added, and then water (50 mL) was added. The mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic extracts were washed with water and with brine, dried over MgSOφ and concentrated to leave a yellow solid. This solid was suspended in a small volume of ethyl acetate (about 5 mL), an equal volume of hexanes was gradually added, and the suspension was stirred for 30 minutes. The solid component was collected on a glass frit, washed with small portions of ethyl acetate/ hexanes (1 :1 and 1 :2 v:v), and allowed to dry in air to provide a white solid (1.02 g). Evaporation of the mother liquor and treatment of the resultant residue with small volumes of ethyl acetate and hexanes as already described provided an additional 0.13 g of solid containing the title product (1.15 g total). Analysis of the combined solids by LC/MS showed a primary component of mass 242 (AP+) and a minor component, eluting later by reverse-phase LC, also having a mass of 242 (AP+). The apparent ratio of components was 94:6. 1H NMR (acetone-^) δ 6.95 (m, 2H), 3.52 (s, 3H), 1.98 (s, 3H); 5-hydroxy resonance was not observed in this solvent. Step D: Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-l,3-dimethyl-4-(2,4,6- trifluorophenyl)-lH-pyrazole l,3-Dimethyl-4-(2,4,6-trifluorophenyl)-lH-pyrazol-5-ol (i.e. the product of Step C) (0.310 g, 1.28 mmol), was combined with 3,4,5-trifluoronitrobenzene (157 μL, 1.35 mmol) and potassium carbonate powder (0.27 g, 2 mmol) in dry Λf,Λ/-dimethylformamide (4 mL). This mixture was stirred and heated at 80 0C for 45 minutes and then allowed to cool. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The organic phase was washed with water and with brine, dried over MgSOφ and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate (30% to 100%) in hexane to give the title product, a compound of the present invention, as an off- white solid (209 mg).
1H NMR δ 7.71 (m, 2H), 6.54 (m, 2H), 3.86 (s, 3H), 2.07 (s, 3H); 400 amu (AP+).
SYNTHESIS EXAMPLE 9
Preparation of 4-[[l,3-Dimethyl-4-(2,4,6-trifluorophenyl)-lH-pyrazol-5-yl]oxy]-3,5- difluorobenzenamine (Compound 371) 5-(2,6-Difluoro-4-nitrophenoxy)-l,3-dimethyl-4-(2,4,6-trifluorophenyl)-lH-pyrazole
(i.e. the product of Synthesis Example 8) (0.780 g, 1.95 mmol) was combined with iron powder (325 mesh, 0.58 g, 10 mmol) and ammonium chloride (64 mg, 1.2 mmol) in ethanol (27 mL) to which water (3 mL) had been added. The mixture was heated at reflux for 1.25 h and then allowed to cool. The reaction mixture was diluted with an equal volume of ethyl acetate and filtered through Celite filter aid. The filtrate was dried with MgSC>4 and concentrated. Analysis by LC/MS showed the major component (93%) to have mass 370 amu (AP+). The residue was dissolved in anhydrous dimethyl sulfoxide (8 mL), and a commercial solution of sodium methoxide in methanol (0.45 mL of 25% solution) was added. This solution was stirred under nitrogen and heated at reflux for 1 h. Additional sodium methoxide/methanol solution (0.20 mL) was added, and heating was continued for an additional 30 minutes. The reaction mixture was allowed to cool, and it was then treated with aqueous citric acid solution (1 M, 5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2 x 25 mL). The organic phase was washed with water (3x) and with brine, dried over MgSO4, and concentrated to leave the title product, a compound of the present invention, as a viscous oil (0.52 g).
1H NMR δ 6.29 (m, 2H), 5.95 (m, 2H), 3.80 (s, 3H), 3.75 (s, 3H), 3.55-3.75 (br s, NH2), 2.01 (s, 3H); 382 amu (AP+). SYNTHESIS EXAMPLE 10
Preparation of 5-(4-Chloro-2,6-difluorophenoxy)-4-(2,6-difluoro-4-methoxyphenyl)-
1,3-dimethyl-lH-pyrazole (Compound 58)
Copper(I) chloride (56 mg, 0.42 mmol) was added to a solution of 4-[[4-(2,6-difluoro- 4-methoxyphenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (prepared analogous to Synthesis Example 9) (132 mg, 0.346 mmol) in acetonitrile (5 mL). The stirred mixture was cooled using an ice-water bath, and tert-butyi nitrite (90% technical grade, 72 μL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature and stirred at room temperature overnight, and then it was heated at reflux for 1 h. Hydrochloric acid (1 N, 5 mL) was added, and the mixture was extracted with ethyl acetate (~20 mL). The organic phase was washed with brine, dried over MgSO4, and concentrated. The residue was purified by column chromatography through silica gel eluted with 20% ethyl acetate in hexane to give the title product, a compound of the present invention, as a viscous oil (45 mg).
1H NMR δ 6.74 (m, 2H), 6.30 (m, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 2.03 (s, 3H); 401 amu (AP+).
By the procedures described herein together with methods known in the art, the compounds disclosed in the Tables that follow can be prepared. The following abbreviations are used in the Table which follows: Me means methyl, Et means ethyl, n-Pr means n-propyl, c-Pr means cyclopropyl, Ph means phenyl, OMe (or MeO) means methoxy, OEt (or EtO) means ethoxy, -CN means cyano, and -NO2 means nitro.
TABLE 1
Figure imgf000066_0001
Q1 is 2,6-di-F-Ph, and R2 is Me.
Figure imgf000066_0002
Figure imgf000066_0003
2-C1-4-F 2-F-4-C1 2,4-di-Cl 2,6-di-Cl 2,4,6-tri-Cl
2-Br-4-F 2-I-4-F 2-Me-4-F 2-F-4-MeO 2-Cl-4-MeO
2-Br-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-C1-4-CN 2-Br-4-CN
2,6-di-F-4-CN 2-Cl-4,5-di-F 2-Cl-4,6-di-F 2-Br-4,5-di-F 2-Br-4,6-di-F
4-Cl-2,5-di-F 4-Cl-2,6-di-F 4-Br-2,5-di-F 4-Br-2,6-di-F 2,4-di-Cl-6-F
2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF3-4-F 4-Me 2,4-di-Me
2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F
The present disclosure also includes Tables 2 through 84, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. "Q1 is 2,6-di-F-Ph, and R2 is Me.") is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is "Q1 is 2,6-di-F-Ph, and R2 is CL", and (R3)p is as defined in Table 1 above. Thus, the first entry in Table 2 specifically discloses 2-chloro-4-(2,6- difluorophenyl)-Λ/-(2-fluorophenyl)-l -methyl- lH-pyrazol-5-amine. Tables 3 through 84 are constructed similarly.
Table Row Heading Table Row Heading
2 Q1 is 2,6-di-F -Ph, and R2 is Cl. 47 Q1 is 2-Br-Ph, and R2 is Cl.
J Q1 is 2,6-di-F -Ph, and R2 is Br. 48 Q1 is 2-Br-Ph, and R2 is Br.
4 Q1 is 2,4-di-F ■Ph, and R2 is Me. 49 Q1 is 2-F-4-Cl-Ph, and R2 is Me. 5 Q1 is 2,4-di-F -Ph, and R2 is Cl. 50 Q1 is 2-F-4-Cl-Ph, and R2 is Cl. 6 Q1 is 2,4-di-F Ph, and R2 is Br. 51 Q1 is 2-F-4-Cl-Ph, and R2 is Br.
7 Q1 is 2,4,6-tri -F-Ph, and R2 is Me. 52 Q1 is 2,4-di-Cl-Ph, and R2 is Me. Q1 is 2,4,6-tri -F-Ph, and R2 is Cl. 53 Q1 is 2,4-di-Cl-Ph, and R2 is Cl. Q1 is 2,4,6-tri -F-Ph, and R2 is Br. 54 Q1 is 2,4-di-Cl-Ph, and R2 is Br.
10 Q1 is 2,6-di-F -4-OMe-Ph, and R2 is Me. 55 Q1 is 2,6-di-Cl-Ph, and R2 is Me.
11 Q1 is 2,6-di-F 4-OMe-Ph, and R2 is Cl. 56 Q1 is 2,6-di-Cl-Ph, and R2 is Cl.
12 Q1 is 2,6-di-F -4-OMe-Ph, and R2 is Br. 57 Q1 is 2,6-di-Cl-Ph, and R2 is Br. 12A Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Me. 58 Q1 is 2-F-4-MeO-Ph, and R2 is Me. 12B Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Cl. 59 Q1 is 2-F-4-MeO-Ph, and R2 is Cl. 12C Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Br. 60 Q1 is 2-F-4-MeO-Ph, and R2 is Br.
13 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Me. 6OA Q1 is 2-F-4-EtO-Ph, and R2 is Me.
14 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Cl. 6OB Q1 is 2-F-4-EtO-Ph, and R2 is Cl.
15 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Br. 6OC Q1 is 2-F-4-EtO-Ph, and R2 is Br.
16 Q1 is 2-Cl-4-F-Ph, and R2 is Me. 61 Q1 is 2-Cl-4-MeO-Ph, and R2 is Me.
17 Q1 is 2-Cl-4-F-Ph, and R2 is Cl. 62 Q1 is 2-Cl-4-MeO-Ph, and R2 is Cl.
18 Q1 is 2-Cl-4-F-Ph, and R2 is Br. 63 Q1 is 2-Cl-4-MeO-Ph, and R2 is Br.
19 Q1 is 2-Cl-6-F-Ph, and R2 is Me. 63A Q1 is 2-Cl-4-EtO-Ph, and R2 is Me.
20 Q1 is 2-Cl-6-F-Ph, and R2 is Cl. 63B Q1 is 2-Cl-4-EtO-Ph, and R2 is Cl.
21 Q1 is 2-Cl-6-F-Ph, and R2 is Br. 63C Q1 is 2-Cl-4-EtO-Ph, and R2 is Br. Table Row Heading Table Row Heading
22 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Me. 64 Q1 is 2-Br-4-MeO-Ph, and R2 is Me. 23 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Cl. 65 Q1 is 2-Br-4-MeO-Ph, and R2 is Cl. 24 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Br. 66 Q1 is 2-Br-4-MeO-Ph, and R2 is Br. 25 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Me. 66A Q1 is 2-Br-4-EtO-Ph, and R2 is Me. 26 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Cl. 66B Q1 is 2-Br-4-EtO-Ph, and R2 is Cl. 27 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Br. 66C Q1 is 2-Br-4-EtO-Ph, and R2 is Br. 28 Q1 is 2-Br-4-F-Ph, and R2 is Me. 67 Q1 is 2-F-4-CN-Ph, and R2 is Me. 29 Q1 is 2-Br-4-F-Ph, and R2 is Cl. 68 Q1 is 2-F-4-CN-Ph, and R2 is Cl. 30 Q1 is 2-Br-4-F-Ph, and R2 is Br. 69 Q1 is 2-F-4-CN-Ph, and R2 is Br. 31 Q1 is 2-Br-6-F-Ph, and R2 is Me. 70 Q1 is 2-Cl-4-CN-Ph, and R2 is Me. 32 Q1 is 2-Br-6-F-Ph, and R2 is Cl. 71 Q1 is 2-Cl -4-CN-Ph, and R2 is Cl. 33 Q1 is 2-Br-6-F-Ph, and R2 is Br. 72 Q1 is 2-Cl -4-CN-Ph, and R2 is Br. 34 Q1 is 2-Me-4-F-Ph, and R2 is Me. 73 Q1 is 2-Br-4-CN-Ph, and R2 is Me. 35 Q1 is 2-Me-4-F-Ph, and R2 is Cl. 74 Q1 is 2-Br -4-CN-Ph, and R2 is Cl. 36 Q1 is 2-Me-4-F-Ph, and R2 is Br. 75 Q1 is 2-Br-4-CN-Ph, and R2 is Br. 37 Q1 is 2-1-4-F-Ph, and R2 is Me. 76 Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Me. 38 Q1 is 2-1-4-F-Ph, and R2 is Cl. 77 Q1 is 2,5-di-Cl-3-pyridinyl, and Rz is Cl. 39 Q1 is 2-1-4-F-Ph, and R2 is Br. 78 Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Br. 40 Q1 is 2-F-Ph, and R2 is Me. 79 Q1 is 2-Cl-3-thienyl, and R2 is Me. 41 Q1 is 2-F-Ph, and R2 is Cl. 80 Q1 is 2-Cl-3-thienyl, and R2 is Cl. 42 Q1 is 2-F-Ph, and R2 is Br. 81 Q1 is 2-Cl-3-thienyl, and R2 is Br. 43 Q1 is 2-Cl-Ph, and R2 is Me. 82 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Me. 44 Q1 is 2-Cl-Ph, and R2 is Cl. 83 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Cl. 45 Q1 is 2-Cl-Ph, and R2 is Br. 84 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Br. 46 Q1 is 2-Br-Ph, and R2 is Me.
TABLE 85
Figure imgf000068_0001
Q1 is 2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
Figure imgf000068_0002
Figure imgf000068_0003
2-F-4-Br 2-Br-6-F 2-Cl-4-Br 2-Br-4-Cl 2-I-4-F
2-F-4-I 2-Cl-4,6-di-F 4-Cl-2,6-di-F 2-Br-4,6-di-F 4-Br-2,6-di-F
2-F-4-MeO 2-Cl-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-C1-4-CN
2-Br-4-CN 2,6-di-F-4-CN 2-F-4-NO2 2-Cl-4-NO2 2-Br-4-NO2
2,5-di-F-4-CN 4-Cl-2,5-di-F 2-Br-4,5-di-F 4-Br-2,5-di-F 2-Cl-4,5-di-F
The present disclosure also includes Tables 86 through 280, each of which is constructed the same as Table 85 above, except that the row heading in Table 85 (i.e. "pi is 2,6-di-F-Ph, X is O, RI and R^ a are both H, and R^ is Me.") is replaced with the respective row heading shown below. For Example, in Table 86 the row heading is "Q1 is 2,6-di-F-Ph, X is O, R1 and Rla are both H, and R2 is Cl." and (R3)p is as defined in Table 85 above. Thus, the first entry in Table 86 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-5-(4- fluorophenoxy)-! -methyl- lH-pyrazole. Tables 87 through 280 are constructed similarly.
Table Row Heading
Q1 is 2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
87 Q1 is 2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
88 Q1 is 2,4-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
89 Q1 is 2,4-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
90 Q1 is 2,4-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
91 Q1 is 2,4,6-tri-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
92 Q1 is 2,4,6-tri-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
93 Q1 is 2,4,6-tri-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
94 Q1 is 2,6-di-F-4-OMe-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
95 Q1 is 2,6-di-F-4-OMe-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
96 Q1 is 2,6-di-F-4-OMe-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
96A Q1 is 2,6-di-F-4-OEt-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
96B Q1 is 2,6-di-F-4-OEt-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
96C Q1 is 2,6-di-F-4-OEt-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
97 Q1 is 2,6-di-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
Q1 is 2,6-di-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
99 Q1 is 2,6-di-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
100 Q1 is 2-Cl-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 101 Q1 is 2-Cl-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 102 Q1 is 2-Cl-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 103 Q1 is 2-Cl-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 104 Q1 is 2-Cl-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 105 Q1 is 2-Cl-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 106 Q1 is 2-Cl-4,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 107 Q1 is 2-Cl-4,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. Table Row Heading
108 Q1 is 2-Cl-4,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 109 Q1 is 4-Cl-2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 110 Q1 is 4-Cl-2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 111 Q1 is 4-Cl-2,6-di-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 112 Q1 is 2-Br-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 113 Q1 is 2-Br-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 114 Q1 is 2-Br-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 115 Q1 is 2-Br-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 116 Q1 is 2-Br-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 117 Q1 is 2-Br-6-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 118 Q1 is 2-Me-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 119 Q1 is 2-Me-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 120 Q1 is 2-Me-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 121 Q1 is 2-1-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 122 QI is 2-1-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 123 Q1 is 2-1-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 124 Q1 is 2-F-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 125 Q1 is 2-F-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 126 Q1 is 2-F-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 127 Q1 is 2-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 128 Q1 is 2-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 129 Q1 is 2-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 130 Q1 is 2-Br-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 131 Q1 is 2-Br-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 132 Q1 is 2-Br-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 133 Q1 is 2-F-4-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 134 Q1 is 2-F-4-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 135 Q1 is 2-F-4-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 136 Q1 is 2,4-di-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 137 Q1 is 2,4-di-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 138 Q1 is 2,4-di-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Br. 139 Q1 is 2,6-di-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 140 Q1 is 2,6-di-Cl-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 141 Q1 is 2,6-di-Cl-Ph, X is O, R1 and Rla are both H, and R2 is Br. 142 Q1 is 2-F-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Me. 143 Q1 is 2-F-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl. 144 Q1 is 2-F-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Br. Table Row Heading
144 A Q1 is 2-F-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
144B Q1 is 2-F-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
144C Q1 is 2-F-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
145 Q1 is 2-Cl-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
146 Q1 is 2-Cl-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
147 Q1 is 2-Cl-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
147 A Q1 is 2-Cl-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
147B Q1 is 2-Cl-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
147C Q1 is 2-Cl-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
148 Q1 is 2-Br-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
149 Q1 is 2-Br-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
150 Q1 is 2-Br-4-MeO-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
150A Q1 is 2-Br-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
150B Q1 is 2-Br-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
150C Q1 is 2-Br-4-EtO-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
151 Q1 is 2-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
152 Q1 is 2-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
153 Q1 is 2-F-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
154 Q1 is 2-Cl-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
155 Q1 is 2-Cl-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
156 Q1 is 2-Cl-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
157 Q1 is 2-Br-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Me.
158 Q1 is 2-Br-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Cl.
159 Q1 is 2-Br-4-CN-Ph, X is O, R1 and Rl a are both H, and R2 is Br.
160 Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and Rl a are both H, and R2 is Me.
161 Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and Rl a are both H, and R2 is Cl.
162 Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and Rl a are both H, and R2 is Br.
163 Q1 is 2-Cl-3-thienyl, X is O, R1 and Rl a are both H, and R2 is Me.
164 Q1 is 2-Cl-3-thienyl, X is O, R1 and Rl a are both H, and R2 is Cl.
165 Q1 is 2-Cl-3-thienyl, X is O, R1 and Rl a are both H, and R2 is Br.
166 Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and Rla are both H, and R2 is Me.
167 Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and Rla are both H, and R2 is Cl.
168 Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and Rla are both H, and R2 is Br.
169 Q1 is 2,6-di-F-Ph, X is S, R1 and Rla are both H, and R2 is Me.
170 Q1 is 2,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
171 Q1 is 2,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
172 Q1 is 2,4-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. Table Row Heading
173 Q1 is 2,4-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 174 Q1 is 2,4-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 175 Q1 is 2,4,6-tri-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 176 Q1 is 2,4,6-tri-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 177 Q1 is 2,4,6-tri-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 178 Q1 is 2,6-di-F-4-OMe-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 179 Q1 is 2,6-di-F-4-OMe-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 180 Q1 is 2,6-di-F-4-OMe-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 180A Q1 is 2,6-di-F-4-OEt-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 180B Q1 is 2,6-di-F-4-OEt-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 180C Q1 is 2,6-di-F-4-OEt-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 181 Q1 is 2,6-di-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 182 Q1 is 2,6-di-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 183 Q1 is 2,6-di-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 184 Q1 is 2-Cl-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 185 Q1 is 2-Cl-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 186 Q1 is 2-Cl-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 187 Q1 is 2-Cl-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 188 Q1 is 2-Cl-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 189 Q1 is 2-Cl-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 190 Q1 is 2-Cl-4,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 191 Q1 is 2-Cl-4,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 192 Q1 is 2-Cl-4,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 193 Q1 is 4-Cl-2,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 194 Q1 is 4-Cl-2,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 195 Q1 is 4-Cl-2,6-di-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 196 Q1 is 2-Br-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 197 Q1 is 2-Br-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 198 Q1 is 2-Br-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 199 Q1 is 2-Br-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 200 Q1 is 2-Br-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 201 Q1 is 2-Br-6-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 202 Q1 is 2-Me-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 203 Q1 is 2-Me-4-F-Ph, X is S, R1 and Rla are both H, and R2 is Cl. 204 Q1 is 2-Me-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 205 Q1 is 2-1-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 206 QI is 2-1-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. Table Row Heading
207 Q1 is 2-1-4-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
208 Q1 is 2-F-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
209 Q1 is 2-F-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
210 Q1 is 2-F-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
211 Q1 is 2-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
212 Q1 is 2-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
213 Q1 is 2-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
214 Q1 is 2-Br-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
215 Q1 is 2-Br-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
216 Q1 is 2-Br-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
217 Q1 is 2-F-4-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
218 Q1 is 2-F-4-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
219 Q1 is 2-F-4-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
220 Q1 is 2,4-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
221 Q1 is 2,4-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
222 Q1 is 2,4-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
223 Q1 is 2,6-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
224 Q1 is 2,6-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
225 Q1 is 2,6-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
226 Q1 is 2-F-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
227 Q1 is 2-F-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
228 Q1 is 2-F-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
228A Q1 is 2-F-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
228B Q1 is 2-F-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
228C Q1 is 2-F-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
229 Q1 is 2-Cl-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
230 Q1 is 2-Cl-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
231 Q1 is 2-Cl-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
231A Q1 is 2-Cl-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
231B Q1 is 2-Cl-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
231C Q1 is 2-Cl-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
232 Q1 is 2-Br-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
233 Q1 is 2-Br-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
234 Q1 is 2-Br-4-MeO-Ph, X is S, R1 and Rl a are both H, and R2 is Br.
234A Q1 is 2-Br-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Me.
234B Q1 is 2-Br-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Cl.
234C Q1 is 2-Br-4-EtO-Ph, X is S, R1 and Rl a are both H, and R2 is Br. Table Row Heading
235 Q1 is 2-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 236 Q1 is 2-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 237 Q1 is 2-F-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 238 Q1 is 2-Cl-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 239 Q1 is 2-Cl-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 240 Q1 is 2-Cl-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 241 Q1 is 2-Br-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Me. 242 Q1 is 2-Br-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Cl. 243 Q1 is 2-Br-4-CN-Ph, X is S, R1 and Rl a are both H, and R2 is Br. 244 Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and Rl a are both H, and R2 is Me. 245 Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and Rl a are both H, and R2 is Cl. 246 Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and Rl a are both H, and R2 is Br. 247 Q1 is 2-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Me. 248 Q1 is 2-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Cl. 249 Q1 is 2-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Br. 250 Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Me. 251 Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Cl. 252 Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Br. 253 Q1 is 2,6-di-F-Ph, X is NH, R1 and Rl a form c-Pr, and R2 is Me. 254 Q1 is 2,4-di-F-Ph, X is O, R1 is Et, Rl a is H, and R2 is Cl. 255 Q1 is 2,4,6-tri-F-Ph, X is S, R1 and Rl a are both H, and R2 is Et. 256 Q1 is 2,6-di-F-4-OMe-Ph, X is CHOH, R1 and Rl a are both H, and R2 is CF3. 257 Q1 is 2,6-di-F-4-CN-Ph, X is NH, R1 is CH=CH2, Rl a is H, and R2 is Cl. 258 Q1 is 2-Cl-4-F-Ph, X is CHOH, X is O, R1 is c-Pr, Rl a is H, and R2 is Br. 259 Q1 is 2-Cl-6-F-Ph, X is S, R1 and Rl a form c-Pr, and R2 is Me. 260 Q1 is 2-Cl-4,6-di-F-Ph, X is CHOH, R1 is c-Pr, Rl a is H, and R2 is Cl. 261 Q1 is 4-Cl-2,6-di-F-Ph, X is NH, X is NH, R1 is Et, Rl a is H, and R2 is Br. 262 Q1 is 2-Br-4-F-Ph, X is O, R1 and Rl a are both H, and R2 is Et. 263 Q1 is 2-Br-6-F-Ph, X is S, R1 is CH2CH=CH2, Rl a is H, and R2 is Cl. 264 Q1 is 2-Me-4-F-Ph, X is CHOH, R1 and Rl a are both H, and R2 is c-Pr. 265 Q1 is 2-1-4-F-Ph, X is NH, R1 is CH2CF3, Rl a is H, and R2 is Me. 266 Q1 is 2-F-Ph, X is O, R1 is CH2F, Rl a is H, and R2 is Cl. 267 Q1 is 2-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is CH2Cl. 268 Q1 is 2-Br-Ph, X is CHCH3, R1 and Rl a are both H, and R2 is Me. 269 Q1 is 2-F-4-Cl-Ph, X is C(CH3)OH, R1 and Rl a are both H, and R2 is Me. 270 Q1 is 2,4-di-Cl-Ph, X is O, R1 is Et, Rl a is H, and R2 is Br. 271 Q1 is 2,6-di-Cl-Ph, X is S, R1 and Rl a are both H, and R2 is OMe. Table Row Heading
272 Q1 is 2-F-4-MeO-Ph, X is CHOCH3, R1 and Rl a are both H, and R2 is Cl. 273 Q1 is 2-Cl-4-MeO-Ph, X is NH, R1 and Rl a form c-Pr, and R2 is Br. 274 Q1 is 2-Br-4-MeO-Ph, X is O, R1 is «-Pr, Rl a is H, and R2 is Me. 275 Q1 is 2-F-4-CN-Ph, X is NH, R1 is CH2C≡CH, Rl a is H, and R2 is Cl. 276 Q1 is 2-Cl-4-CN-Ph, X is C(OCH3)2, R1 and Rl a are both H, and R2 is Br. 277 Q1 is 2-Br-4-CN-Ph, X is NH, R1 and Rl a form c-Pr, and R2 is Me. 278 Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 is c-Pr, Rl a is H, and R2 is Cl. 279 Q1 is 2-Cl-3-thienyl, X is S, R1 and Rl a are both H, and R2 is Et. 280 Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, R1 is Et, Rl a is H, and R2 is Me.
TABLE 281
Figure imgf000075_0001
Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Me.
Figure imgf000075_0002
Figure imgf000075_0003
The present disclosure also includes Tables 282 through 448, each of which is constructed the same as Table 281 above, except that the row heading in Table 281 (i.e. "Q1 is 2,6-di-F-Ph, X is CHOH, and R^ is Me.") is replaced with the respective row heading shown below. For Example, in Table 282 the row heading is "Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Cl." and (R3)p is as defined in Table 281 above. Thus, the first entry in Table 282 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-α-(4-fluorophenyl)- 1 -methyl- lH-pyrazole-5-methanol. Tables 283 through 448 are constructed similarly.
Table Row Heading
282 Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Cl. 283 Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Br. 284 Q1 is 2,4-di-F-Ph, X is CHOH, and R2 is Me. Table Row Heading
285 Q1 is 2,4-di-F-Ph, X is CHOH, and R2 is Cl.
286 Q1 is 2,4-di-F-Ph, X is CHOH, and R2 is Br.
287 Q1 is 2,4,6-tri-F-Ph, X is CHOH, and R2 is Me.
288 Q1 is 2,4,6-tri-F-Ph, X is CHOH, and R2 is Cl.
289 Q1 is 2,4,6-tri-F-Ph, X is CHOH, and R2 is Br.
290 Q1 is 2,6-di-F-4-OMe-Ph, X is CHOH, and R2 is Me.
291 Q1 is 2,6-di-F-4-OMe-Ph, X is CHOH, and R2 is Cl.
292 Q1 is 2,6-di-F-4-OMe-Ph, X is CHOH, and R2 is Br.
292A Q1 is 2,6-di-F-4-OEt-Ph, X is CHOH, and R2 is Me.
292B Q1 is 2,6-di-F-4-OEt-Ph, X is CHOH, and R2 is Cl.
292C Q1 is 2,6-di-F-4-OEt-Ph, X is CHOH, and R2 is Br.
293 Q1 is 2,6-di-F-4-CN-Ph, X is CHOH, and R2 is Me.
294 Q1 is 2,6-di-F-4-CN-Ph, X is CHOH, and R2 is Cl.
295 Q1 is 2,6-di-F-4-CN-Ph, X is CHOH, and R2 is Br.
296 Q1 is 2-Cl-4-F-Ph, X is CHOH, and R2 is Me.
297 Q1 is 2-Cl-4-F-Ph, X is CHOH, and R2 is Cl.
298 Q1 is 2-Cl-4-F-Ph, X is CHOH, and R2 is Br.
299 Q1 is 2-Cl-6-F-Ph, X is CHOH, and R2 is Me.
300 Q1 is 2-Cl-6-F-Ph, X is CHOH, and R2 is Cl.
301 Q1 is 2-Cl-6-F-Ph, X is CHOH, and R2 is Br.
302 Q1 is 2-Cl-4,6-di-F-Ph, X is CHOH, and R2 is Me.
303 Q1 is 2-Cl-4,6-di-F-Ph, X is CHOH, and R2 is Cl.
304 Q1 is 2-Cl-4,6-di-F-Ph, X is CHOH, and R2 is Br.
305 Q1 is 4-Cl-2,6-di-F-Ph, X is CHOH, and R2 is Me.
306 Q1 is 4-Cl-2,6-di-F-Ph, X is CHOH, and R2 is Cl.
307 Q1 is 4-Cl-2,6-di-F-Ph, X is CHOH, and R2 is Br.
308 Q1 is 2-Br-4-F-Ph, X is CHOH, and R2 is Me.
309 Q1 is 2-Br-4-F-Ph, X is CHOH, and R2 is Cl.
310 Q1 is 2-Br-4-F-Ph, X is CHOH, and R2 is Br.
311 Q1 is 2-Br-6-F-Ph, X is CHOH, and R2 is Me.
312 Q1 is 2-Br-6-F-Ph, X is CHOH, and R2 is Cl.
313 Q1 is 2-Br-6-F-Ph, X is CHOH, and R2 is Br.
314 Q1 is 2-Me-4-F-Ph, X is CHOH, and R2 is Me.
315 Q1 is 2-Me-4-F-Ph, X is CHOH, and R2 is Cl.
316 Q1 is 2-Me-4-F-Ph, X is CHOH, and R2 is Br.
317 Q1 is 2-1-4-F-Ph, X is CHOH, and R2 is Me.
318 Q1 is 2-1-4-F-Ph, X is CHOH, and R2 is Cl. Table Row Heading
319 Q1 is 2-1-4-F-Ph, X is CHOH, and R2 is Br.
320 Q1 is 2-F-Ph, X is CHOH, and R2 is Me.
321 Q1 is 2-F-Ph, X is CHOH, and R2 is Cl.
322 Q1 is 2-F-Ph, X is CHOH, and R2 is Br.
323 Q1 is 2-Cl-Ph, X is CHOH, and R2 is Me.
324 Q1 is 2-Cl-Ph, X is CHOH, and R2 is Cl.
325 Q1 is 2-Cl-Ph, X is CHOH, and R2 is Br.
326 Q1 is 2-Br-Ph, X is CHOH, and R2 is Me.
327 Q1 is 2-Br-Ph, X is CHOH, and R2 is Cl.
328 Q1 is 2-Br-Ph, X is CHOH, and R2 is Br.
329 Q1 is 2-F-4-Cl-Ph, X is CHOH, and R2 is Me.
330 Q1 is 2-F-4-Cl-Ph, X is CHOH, and R2 is Cl.
331 Q1 is 2-F-4-Cl-Ph, X is CHOH, and R2 is Br.
332 Q1 is 2,4-di-Cl-Ph, X is CHOH, and R2 is Me.
333 Q1 is 2,4-di-Cl-Ph, X is CHOH, and R2 is Cl.
334 Q1 is 2,4-di-Cl-Ph, X is CHOH, and R2 is Br.
335 Q1 is 2,6-di-Cl-Ph, X is CHOH, and R2 is Me.
336 Q1 is 2,6-di-Cl-Ph, X is CHOH, and R2 is Cl.
337 Q1 is 2,6-di-Cl-Ph, X is CHOH, and R2 is Br.
338 Q1 is 2-F-4-MeO-Ph, X is CHOH, and R2 is Me.
339 Q1 is 2-F-4-MeO-Ph, X is CHOH, and R2 is Cl.
340 Q1 is 2-F-4-MeO-Ph, X is CHOH, and R2 is Br.
340A Q1 is 2-F-4-EtO-Ph, X is CHOH, and R2 is Me.
340B Q1 is 2-F-4-EtO-Ph, X is CHOH, and R2 is Cl.
340C Q1 is 2-F-4-EtO-Ph, X is CHOH, and R2 is Br.
341 Q1 is 2-Cl-4-MeO-Ph, X is CHOH, and R2 is Me.
342 Q1 is 2-Cl-4-MeO-Ph, X is CHOH, and R2 is Cl.
343 Q1 is 2-Cl-4-MeO-Ph, X is CHOH, and R2 is Br.
343A Q1 is 2-Cl-4-EtO-Ph, X is CHOH, and R2 is Me.
343B Q1 is 2-Cl-4-EtO-Ph, X is CHOH, and R2 is Cl.
343C Q1 is 2-Cl-4-EtO-Ph, X is CHOH, and R2 is Br.
344 Q1 is 2-Br-4-MeO-Ph, X is CHOH, and R2 is Me.
345 Q1 is 2-Br-4-MeO-Ph, X is CHOH, and R2 is Cl.
346 Q1 is 2-Br-4-MeO-Ph, X is CHOH, and R2 is Br.
346A Q1 is 2-Br-4-EtO-Ph, X is CHOH, and R2 is Me.
346B Q1 is 2-Br-4-EtO-Ph, X is CHOH, and R2 is Cl.
346C Q1 is 2-Br-4-EtO-Ph, X is CHOH, and R2 is Br. Table Row Heading
347 Q1 is 2-F-4-CN-Ph, X is CHOH, and R2 is Me.
348 Q1 is 2-F-4-CN-Ph, X is CHOH, and R2 is Cl.
349 Q1 is 2-F-4-CN-Ph, X is CHOH, and R2 is Br.
350 Q1 is 2-Cl-4-CN-Ph, X is CHOH, and R2 is Me.
351 Q1 is 2-Cl-4-CN-Ph, X is CHOH, and R2 is Cl.
352 Q1 is 2-Cl-4-CN-Ph, X is CHOH, and R2 is Br.
353 Q1 is 2-Br-4-CN-Ph, X is CHOH, and R2 is Me.
354 Q1 is 2-Br-4-CN-Ph, X is CHOH, and R2 is Cl.
355 Q1 is 2-Br-4-CN-Ph, X is CHOH, and R2 is Br.
356 Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Me.
357 Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Cl.
358 Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Br.
359 Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Me.
360 Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Cl.
361 Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Br.
362 Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Me.
363 Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Cl.
364 Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Br.
365 Q1 is 2,6-di-F-Ph, X is C(O), and R2 is Cl.
366 Q1 is 2,6-di-F-Ph, X is C(O), and R2 is Cl.
367 Q1 is 2,6-di-F-Ph, X is C(O), and R2 is Br.
368 Q1 is 2,4-di-F-Ph, X is C(O), and R2 is Me.
369 Q1 is 2,4-di-F-Ph, X is C(O), and R2 is Cl.
370 Q1 is 2,4-di-F-Ph, X is C(O), and R2 is Br.
371 Q1 is 2,4,6-tri-F-Ph, X is C(O), and R2 is Me.
372 Q1 is 2,4,6-tri-F-Ph, X is C(O), and R2 is Cl.
373 Q1 is 2,4,6-tri-F-Ph, X is C(O), and R2 is Br.
374 Q1 is 2,6-di-F-4-OMe-Ph, X is C(O), and R2 is Me.
375 Q1 is 2,6-di-F-4-OMe-Ph, X is C(O), and R2 is Cl.
376 Q1 is 2,6-di-F-4-OMe-Ph, X is C(O), and R2 is Br.
376 A Q1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R2 is Me.
376B Q1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R2 is Cl.
376C Q1 is 2,6-di-F-4-OEt-Ph, X is C(O), and R2 is Br.
377 Q1 is 2,6-di-F-4-CN-Ph, X is C(O), and R2 is Me.
378 Q1 is 2,6-di-F-4-CN-Ph, X is C(O), and R2 is Cl.
379 Q1 is 2,6-di-F-4-CN-Ph, X is C(O), and R2 is Br.
380 Q1 is 2-Cl-4-F-Ph, X is C(O), and R2 is Me. Table Row Heading
381 Q1 is 2-Cl-4-F-Ph, X is C(O), and R2 is Cl.
382 Q1 is 2-Cl-4-F-Ph, X is C(O), and R2 is Br.
383 Q1 is 2-Cl-6-F-Ph, X is C(O), and R2 is Me.
384 Q1 is 2-Cl-6-F-Ph, X is C(O), and R2 is Cl.
385 Q1 is 2-Cl-6-F-Ph, X is C(O), and R2 is Br.
386 Q1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R2 is Me.
387 Q1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R2 is Cl.
388 Q1 is 2-Cl-4,6-di-F-Ph, X is C(O), and R2 is Br.
389 Q1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R2 is Me.
390 Q1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R2 is Cl.
391 Q1 is 4-Cl-2,6-di-F-Ph, X is C(O), and R2 is Br.
392 Q1 is 2-Br-4-F-Ph, X is C(O), and R2 is Me.
393 Q1 is 2-Br-4-F-Ph, X is C(O), and R2 is Cl.
394 Q1 is 2-Br-4-F-Ph, X is C(O), and R2 is Br.
395 Q1 is 2-Br-6-F-Ph, X is C(O), and R2 is Me.
396 Q1 is 2-Br-6-F-Ph, X is C(O), and R2 is Cl.
397 Q1 is 2-Br-6-F-Ph, X is C(O), and R2 is Br.
398 Q1 is 2-Me-4-F-Ph, X is C(O), and R2 is Me.
399 Q1 is 2-Me-4-F-Ph, X is C(O), and R2 is Cl.
400 Q1 is 2-Me-4-F-Ph, X is C(O), and R2 is Br.
401 Q1 is 2-1-4-F-Ph, X is C(O), and R2 is Me.
402 Q1 is 2-1-4-F-Ph, X is C(O), and R2 is Cl.
403 Q1 is 2-1-4-F-Ph, X is C(O), and R2 is Br.
404 Q1 is 2-F-Ph, X is C(O), and R2 is Me.
405 Q1 is 2-F-Ph, X is C(O), and R2 is Cl.
406 Q1 is 2-F-Ph, X is C(O), and R2 is Br.
407 Q1 is 2-Cl-Ph, X is C(O), and R2 is Me.
408 Q1 is 2-Cl-Ph, X is C(O), and R2 is Cl.
409 Q1 is 2-Cl-Ph, X is C(O), and R2 is Br.
410 Q1 is 2-Br-Ph, X is C(O), and R2 is Me.
411 Q1 is 2-Br-Ph, X is C(O), and R2 is Cl.
412 Q1 is 2-Br-Ph, X is C(O), and R2 is Br.
413 Q1 is 2-F-4-Cl-Ph, X is C(O), and R2 is Me.
414 Q1 is 2-F-4-Cl-Ph, X is C(O), and R2 is Cl.
415 Q1 is 2-F-4-Cl-Ph, X is C(O), and R2 is Br.
416 Q1 is 2,4-di-Cl-Ph, X is C(O), and R2 is Me.
417 Q1 is 2,4-di-Cl-Ph, X is C(O), and R2 is Cl. Table Row Heading
418 Q1 is 2,4-di-Cl-Ph, X is C(O), and R2 is Br.
419 Q1 is 2,6-di-Cl-Ph, X is C(O), and R2 is Me.
420 Q1 is 2,6-di-Cl-Ph, X is C(O), and R2 is Cl.
421 Q1 is 2,6-di-Cl-Ph, X is C(O), and R2 is Br.
422 Q1 is 2-F-4-MeO-Ph, X is C(O), and R2 is Me.
423 Q1 is 2-F-4-MeO-Ph, X is C(O), and R2 is Cl.
424 Q1 is 2-F-4-MeO-Ph, X is C(O), and R2 is Br.
424A Q1 is 2-F-4-EtO-Ph, X is C(O), and R2 is Me.
424B Q1 is 2-F-4-EtO-Ph, X is C(O), and R2 is Cl.
424C Q1 is 2-F-4-EtO-Ph, X is C(O), and R2 is Br.
425 Q1 is 2-Cl-4-MeO-Ph, X is C(O), and R2 is Me.
426 Q1 is 2-Cl-4-MeO-Ph, X is C(O), and R2 is Cl.
427 Q1 is 2-Cl-4-MeO-Ph, X is C(O), and R2 is Br.
427A Q1 is 2-Cl-4-EtO-Ph, X is C(O), and R2 is Me.
427B Q1 is 2-Cl-4-EtO-Ph, X is C(O), and R2 is Cl.
427C Q1 is 2-Cl-4-EtO-Ph, X is C(O), and R2 is Br.
428 Q1 is 2-Br-4-MeO-Ph, X is C(O), and R2 is Me.
429 Q1 is 2-Br-4-MeO-Ph, X is C(O), and R2 is Cl.
430 Q1 is 2-Br-4-MeO-Ph, X is C(O), and R2 is Br.
430A Q1 is 2-Br-4-EtO-Ph, X is C(O), and R2 is Me.
430B Q1 is 2-Br-4-EtO-Ph, X is C(O), and R2 is Cl.
430C Q1 is 2-Br-4-EtO-Ph, X is C(O), and R2 is Br.
431 Q1 is 2-F-4-CN-Ph, X is C(O), and R2 is Me.
432 Q1 is 2-F-4-CN-Ph, X is C(O), and R2 is Cl.
433 Q1 is 2-F-4-CN-Ph, X is C(O), and R2 is Br.
434 Q1 is 2-Cl-4-CN-Ph, X is C(O), and R2 is Me.
435 Q1 is 2-Cl-4-CN-Ph, X is C(O), and R2 is Cl.
436 Q1 is 2-Cl-4-CN-Ph, X is C(O), and R2 is Br.
437 Q1 is 2-Br-4-CN-Ph, X is C(O), and R2 is Me.
438 Q1 is 2-Br-4-CN-Ph, X is C(O), and R2 is Cl.
439 Q1 is 2-Br-4-CN-Ph, X is C(O), and R2 is Br.
440 Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Me.
441 Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Cl.
442 Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Br.
443 Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Me.
444 Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Cl.
445 Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Br. Table Row Heading
446 Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Me. 447 Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Cl. 448 Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Br.
TABLE 449
Figure imgf000081_0001
Q1 is 2,6-di-F-Ph, and X is NH.
Figure imgf000081_0002
The present disclosure also includes Tables 450 through 587, each of which is constructed the same as Table 449 above, except that the row heading in Table 449 (i.e. "Q is 2,6-di-F-Ph, and X is NH.") is replaced with the respective row heading shown below. For Example, in Table 450 the row heading is "Q1 is 2,4-di-F-Ph, and X is NH." and Q2 is as defined in Table 449 above. Thus, the first entry in Table 450 specifically discloses 2-chloro-Λ/-[4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]-3-pyridinamine. Tables 451 through 587 are constructed similarly.
Table Row Heading Table Row Heading
450 Q1 is 2,4-di-F-Ph, and X is NH. 519 Q1 is 2-Cl-Ph, and X is S.
451 Q1 is 2,4,6-tri-F-Ph, and X is NH. 520 Q1 is 2-Br-Ph, and X is S.
452 Q1 is 2,6-di-F-4-OMe-Ph, and X is NH. 521 Q1 is 2-F-4-Cl-Ph, and X is S.
453 Q1 is 2,6-di-F-4-CN-Ph, and X is NH. 522 Q1 is 2,4-di-Cl-Ph, and X is S.
454 Q1 is 2-Cl-4-F-Ph, and X is NH. 523 Q1 is 2,6-di-Cl-Ph, and X is S.
455 Q1 is 2-Cl-6-F-Ph, and X is NH. 524 Q1 is 2-F-4-MeO-Ph, and X is S.
456 Q1 is 2-Cl-4,6-di-F-Ph, and X is NH. 525 Q1 is 2-Cl-4-MeO-Ph, and X is S.
457 Q1 is 4-Cl-2,6-di-F-Ph, and X is NH. 526 Q1 is 2-Br-4-MeO-Ph, and X is S.
458 Q1 is 2-Br-4-F-Ph, and X is NH. 527 Q1 is 2-F-4-CN-Ph, and X is S.
459 Q1 is 2-Br-6-F-Ph, and X is NH. 528 Q1 is 2-Cl-4-CN-Ph, and X is S.
460 Q1 is 2-Me-4-F-Ph, and X is NH. 529 Q1 is 2-Br-4-CN-Ph, and X is S.
461 Q1 is 2-1-4-F-Ph, and X is NH. 530 Q1 is 2,5-di-Cl-3-pyridinyl, and X is S. Table Row Heading Table Row Heading
462 Q1 is 2-F-Ph, and X is NH. 531 Q1 is 2-Cl-3-thienyl, and X is S.
463 Q1 is 2-Cl-Ph, and X is NH. 532 Q1 is 2,5-di-Cl-3-thienyl, and X is S.
464 Q1 is 2-Br-Ph, and X is NH. 533 Q1 is 2,6-di-F-Ph, and X is CHOH.
465 Q1 is 2-F-4-Cl-Ph, and X is NH. 534 Q1 is 2,4-di-F-Ph, and X is CHOH.
466 Q1 is 2,4-di-Cl-Ph, and X is NH. 535 Q1 is 2,4,6-tri-F-Ph, and X is CHOH.
467 Q1 is 2,6-di-Cl-Ph, and X is NH. 536 Q1 is 2,6-di-F-4-OMe-Ph, and X is CHOH.
468 Q1 is 2-F-4-MeO-Ph, and X is NH. 537 Q1 is 2,6-di-F-4-CN-Ph, and X is CHOH.
469 Q1 is 2-Cl-4-MeO-Ph, and X is NH. 538 Q1 is 2-Cl-4-F-Ph, and X is CHOH.
470 Q1 is 2-Br-4-MeO-Ph, and X is NH. 539 Q1 is 2-Cl-6-F-Ph, and X is CHOH.
471 Q1 is 2-F-4-CN-Ph, and X is NH. 540 Q1 is 2-Cl-4,6-di-F-Ph, and X is CHOH.
472 Q1 is 2-Cl-4-CN-Ph, and X is NH. 541 Q1 is 4-Cl-2,6-di-F-Ph, and X is CHOH.
473 Q1 is 2-Br-4-CN-Ph, and X is NH. 542 Q1 is 2-Br-4-F-Ph, and X is CHOH.
474 Q1 is 2,5-di-Cl-3-pyridinyl, and X is NH. 543 Q1 is 2-Br-6-F-Ph, and X is CHOH.
475 Q1 is 2-Cl-3-thienyl, and X is NH. 544 Q1 is 2-Me-4-F-Ph, and X is CHOH.
476 Q1 is 2,5-di-Cl-3-thienyl, and X is NH. 545 Q1 is 2-1-4-F-Ph, and X is CHOH.
477 Q1 is 2,6-di-F-Ph, and X is O. 546 Q1 is 2-F-Ph, and X is CHOH.
478 Q1 is 2,4-di-F-Ph, and X is O. 547 Q1 is 2-Cl-Ph, and X is CHOH.
479 Q1 is 2,4,6-tri-F-Ph, and X is O. 548 Q1 is 2-Br-Ph, and X is CHOH.
480 Q1 is 2,6-di-F-4-OMe-Ph, and X is O. 549 Q1 is 2-F-4-Cl-Ph, and X is CHOH.
481 Q1 is 2,6-di-F-4-CN-Ph, and X is O. 550 Q1 is 2,4-di-Cl-Ph, and X is CHOH.
482 Q1 is 2-Cl-4-F-Ph, and X is O. 551 Q1 is 2,6-di-Cl-Ph, and X is CHOH.
483 Q1 is 2-Cl-6-F-Ph, and X is O. 552 Q1 is 2-F-4-MeO-Ph, and X is CHOH.
484 Q1 is 2-Cl-4,6-di-F-Ph, and X is O. 553 Q1 is 2-Cl-4-MeO-Ph, and X is CHOH.
485 Q1 is 4-Cl-2,6-di-F-Ph, and X is O. 554 Q1 is 2-Br-4-MeO-Ph, and X is CHOH.
486 Q1 is 2-Br-4-F-Ph, and X is O. 555 Q1 is 2-F-4-CN-Ph, and X is CHOH.
487 Q1 is 2-Br-6-F-Ph, and X is O. 556 Q1 is 2-Cl-4-CN-Ph, and X is CHOH.
488 Q1 is 2-Me-4-F-Ph, and X is O. 557 Q1 is 2-Br-4-CN-Ph, and X is CHOH.
489 Q1 is 2-1-4-F-Ph, and X is O. 558 Q1 is 2,5-di-Cl-pyridin-3-yl, and X is CHOH.
490 Q1 is 2-F-Ph, and X is O. 559 Q1 is 2,5-di-Cl-thien-3-yl, and X is CHOH.
491 Q1 is 2-Cl-Ph, and X is O. 560 Q1 is 2,6-di-F-Ph, and X is C(O).
492 Q1 is 2-Br-Ph, and X is O. 561 Q1 is 2,4-di-F-Ph, and X is C(O).
493 Q1 is 2-F-4-Cl-Ph, and X is O. 562 Q1 is 2,4,6-tri-F-Ph, and X is C(O).
494 Q1 is 2,4-di-Cl-Ph, and X is O. 563 Q1 is 2,6-di-F-4-OM-Ph e, and X is C(O).
495 Q1 is 2,6-di-Cl-Ph, and X is O. 564 Q1 is 2,6-di-F-4-CN-Ph, and X is C(O).
496 Q1 is 2-F-4-MeO-Ph, and X is O. 565 Q1 is 2-Cl-4-F-Ph, and X is C(O).
497 Q1 is 2-Cl-4-MeO-Ph, and X is O. 566 Q1 is 2-Cl-6-F-Ph, and X is C(O).
498 Q1 is 2-Br-4-MeO-Ph, and X is O. 567 Q1 is 2-Cl-4,6-di-F-Ph, and X is C(O). Table Row Heading Table Row Heading 499 Q1 is 2-F-4-CN-Ph, and X is O. 568 Q1 is 4-Cl-2,6-di-F-Ph, and X is C(O). 500 Q1 is 2-Cl-4-CN-Ph, and X is O. 569 Q1 is 2-Br-4-F-Ph, and X is C(O). 501 Q1 is 2-Br-4-CN-Ph, and X is O. 570 Q1 is 2-Br-6-F-Ph, and X is C(O). 502 Q1 is 2,5-di-Cl-pyridin-3-yl, and X is O. 571 Q1 is 2-Me-4-F-Ph, and X is C(O). 503 Q1 is 2-Cl-thien-3-yl, and X is O. 572 Q1 is 2-1-4-F-Ph, and X is C(O). 504 Q1 is 2,5-di-Cl-thien-3-yl, and X is O. 573 Q1 is 2-F-Ph, and X is C(O). 505 Q1 is 2,6-di-F-Ph, and X is S. 574 Q1 is 2-Cl-Ph, and X is C(O). 506 Q1 is 2,4-di-F-Ph, and X is S. 575 Q1 is 2-Br-Ph, and X is C(O). 507 Q1 is 2,4,6-tri-F-Ph, and X is S. 576 Q1 is 2-F-4-Cl-Ph, and X is C(O). 508 Q1 is 2,6-di-F-4-OMe-Ph, and X is S. 577 Q1 is 2,4-di-Cl-Ph, and X is C(O). 509 Q1 is 2,6-di-F-4-CN-Ph, and X is S. 578 Q1 is 2,6-di-Cl-Ph, and X is C(O). 510 Q1 is 2-Cl-4-F-Ph, and X is S. 579 Q1 is 2-F-4-MeO-Ph, and X is C(O). 511 Q1 is 2-Cl-6-F-Ph, and X is S. 580 Q1 is 2-Cl-4-MeO-Ph, and X is C(O). 512 Q1 is 2-Cl-4,6-di-F-Ph, and X is S. 581 Q1 is 2-Br-4-MeO-Ph, and X is C(O). 513 Q1 is 4-Cl-2,6-di-F-Ph, and X is S. 582 Q1 is 2-F-4-CN-Ph, and X is C(O). 514 Q1 is 2-Br-4-F-Ph, and X is S. 583 Q1 is 2-Cl-4-CN-Ph, and X is C(O). 515 Q1 is 2-Br-6-F-Ph, and X is S. 584 Q1 is 2-Br-4-CN-Ph, and X is C(O). 516 Q1 is 2-Me-4-F-Ph, and X is S. 585 Q1 is 2,5-di-Cl-3-pyridinyl, and X is C(O). 517 Q1 is 2-1-4-F-Ph, and X is S. 586 Q1 is 2-Cl-3-thienyl, and X is C(O). 518 Q1 is 2-F-Ph, and X is S. 587 Q1 is 2,5-di-Cl-3-thienyl, and X is C(O).
Figure imgf000083_0001
Q1 is 2,6-di-F-Ph, and R2 is Me.
Figure imgf000083_0002
Figure imgf000083_0003
Figure imgf000083_0004
2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF3-4-F 4-Me 2,4-di-Me 2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F
The present disclosure also includes Tables 589 through 671, each of which is constructed the same as Table 588 above, except that the row heading in Table 588 (i.e. "Q1 is 2,6-di-F-Ph, and R2 is Me.") is replaced with the respective row heading shown below. For Example, in Table 589 the row heading is "Q1 is 2,6-di-F-Ph, and R2 is CL", and (R3)p is as defined in Table 588 above. Thus, the first entry in Table 589 specifically discloses 5-chloro-4-(2,6-difluorophenyl)-Λ/-(2-fluorophenyl)-lH-pyrazol-3-amine. Tables 589 through 671 are constructed similarly.
Table Row Heading Table Row Heading
589 Q1 is 2,6-di-F-Ph, and R2 is Cl. 634 Q1 is 2-Br-Ph, and R2 is Cl.
590 Q1 is 2,6-di-F-Ph, and R2 is Br. 635 Q1 is 2-Br-Ph, and R2 is Br.
591 Q1 is 2,4-di-F-Ph, and R2 is Me. 636 Q1 is 2-F-4-Cl-Ph, and R2 is Me.
592 Q1 is 2,4-di-F-Ph, and R2 is Cl. 637 Q1 is 2-F-4-Cl-Ph, and R2 is Cl.
593 Q1 is 2,4-di-F-Ph, and R2 is Br. 638 Q1 is 2-F-4-Cl-Ph, and R2 is Br.
594 Q1 is 2,4,6-tri-F-Ph, and R2 is Me. 639 Q1 is 2,4-di-Cl-Ph, and R2 is Me.
595 Q1 is 2,4,6-tri-F-Ph, and R2 is Cl. 640 Q1 is 2,4-di-Cl-Ph, and R2 is Cl.
596 Q1 is 2,4,6-tri-F-Ph, and R2 is Br. 641 Q1 is 2,4-di-Cl-Ph, and R2 is Br.
597 Q1 is 2,6-di-F-4-OMe-Ph, and R2 is Me. 642 Q1 is 2,6-di-Cl-Ph, and R2 is Me.
598 Q1 is 2,6-di-F-4-OMe-Ph, and R2 is Cl. 643 Q1 is 2,6-di-Cl-Ph, and R2 is Cl.
599 Q1 is 2,6-di-F-4-OMe-Ph, and R2 is Br. 644 Q1 is 2,6-di-Cl-Ph, and R2 is Br.
599A Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Me. 645 Q1 is 2-F-4-MeO-Ph, and R2 is Me.
599B Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Cl. 646 Q1 is 2-F-4-MeO-Ph, and R2 is Cl.
599C Q1 is 2,6-di-F-4-OEt-Ph, and R2 is Br. 647 Q1 is 2-F-4-MeO-Ph, and R2 is Br.
600 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Me. 647A Q1 is 2-F-4-EtO-Ph, and R2 is Me.
601 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Cl. 647B Q1 is 2-F-4-EtO-Ph, and R2 is Cl.
602 Q1 is 2,6-di-F-4-CN-Ph, and R2 is Br. 647C Q1 is 2-F-4-EtO-Ph, and R2 is Br.
603 Q1 is 2-Cl-4-F-Ph, and R2 is Me. 648 Q1 is 2-Cl-4-MeO-Ph, and R2 is Me.
604 Q1 is 2-Cl-4-F-Ph, and R2 is Cl. 649 Q1 is 2-Cl-4-MeO-Ph, and R2 is Cl.
605 Q1 is 2-Cl-4-F-Ph, and R2 is Br. 650 Q1 is 2-Cl-4-MeO-Ph, and R2 is Br.
606 Q1 is 2-Cl-6-F-Ph, and R2 is Me. 650A Q1 is 2-Cl-4-EtO-Ph, and R2 is Me.
607 Q1 is 2-Cl-6-F-Ph, and R2 is Cl. 650B Q1 is 2-Cl-4-EtO-Ph, and R2 is Cl.
608 Q1 is 2-Cl-6-F-Ph, and R2 is Br. 650C Q1 is 2-Cl-4-EtO-Ph, and R2 is Br.
609 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Me. 651 Q1 is 2-Br-4-MeO-Ph, and R2 is Me.
610 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Cl. 652 Q1 is 2-Br-4-MeO-Ph, and R2 is Cl.
611 Q1 is 2-Cl-4,6-di-F-Ph, and R2 is Br. 653 Q1 is 2-Br-4-MeO-Ph, and R2 is Br.
612 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Me. 653A Q1 is 2-Br-4-EtO-Ph, and R2 is Me.
613 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Cl. 653B Q1 is 2-Br-4-EtO-Ph, and R2 is Cl. Table Row Heading Table Row Heading
614 Q1 is 4-Cl-2,6-di-F-Ph, and R2 is Br. 653C Q1 is 2-Br-4-EtO-Ph, and R2 is Br.
615 Q1 is 2-Br-4-F-Ph, and R2 is Me. 654 Q1 is 2-F-4-CN-Ph, and R2 is Me.
616 Q1 is 2-Br-4-F-Ph, and R2 is Cl. 655 Q1 is 2-F-4-CN-Ph, and R2 is Cl.
617 Q1 is 2-Br-4-F-Ph, and R2 is Br. 656 Q1 is 2-F-4-CN-Ph, and R2 is Br.
618 Q1 is 2-Br-6-F-Ph, and R2 is Me. 657 Q1 is 2-Cl-4-CN-Ph, and R2 is Me.
619 Q1 is 2-Br-6-F-Ph, and R2 is Cl. 658 Q1 is 2-Cl -4-CN-Ph, and R2 is Cl.
620 Q1 is 2-Br-6-F-Ph, and R2 is Br. 659 Q1 is 2-Cl -4-CN-Ph, and R2 is Br.
621 Q1 is 2-Me-4-F-Ph, and R2 is Me. 660 Q1 is 2-Br-4-CN-Ph, and R2 is Me.
622 Q1 is 2-Me-4-F-Ph, and R2 is Cl. 661 Q1 is 2-Br -4-CN-Ph, and R2 is Cl.
623 Q1 is 2-Me-4-F-Ph, and R2 is Br. 662 Q1 is 2-Br-4-CN-Ph, and R2 is Br.
624 Q1 is 2-1-4-F-Ph, and R2 is Me. 663 Q1 is 2,5-di-Cl-3-pyridinyl, and Rz is Me.
625 Q1 is 2-1-4-F-Ph, and R2 is Cl. 664 Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Cl.
626 Q1 is 2-1-4-F-Ph, and R2 is Br. 665 Q1 is 2,5-di-Cl-3-pyridinyl, and Rz is Br.
627 Q1 is 2-F-Ph, and R2 is Me. 666 Q1 is 2-Cl-3-thienyl, and R2 is Me.
628 Q1 is 2-F-Ph, and R2 is Cl. 667 Q1 is 2-Cl-3-thienyl, and R2 is Cl.
629 Q1 is 2-F-Ph, and R2 is Br. 668 Q1 is 2-Cl-3-thienyl, and R2 is Br.
630 Q1 is 2-Cl-Ph, and R2 is Me. 669 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Me.
631 Q1 is 2-Cl-Ph, and R2 is Cl. 670 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Cl.
632 Q1 is 2-Cl-Ph, and R2 is Br. 671 Q1 is 2,5-di-Cl-3-thienyl, and R2 is Br.
633 Q1 is 2-Br-Ph, and R2 is Me.
The compounds of Tables 588 through 671 illustrate compounds of Formula 2 wherein X is NH, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 2.
TABLE 672
Figure imgf000085_0001
G1 is -OH.
Figure imgf000085_0002
2-Cl-4-F-Ph 2-1-4-F-Ph 2-F-4-MeO-Ph 2-Cl-3-thienyl 2-Cl-6-F-Ph 2-F-Ph 2-Cl-4-MeO-Ph 2,5-di-Cl-3-thienyl 2,6-di-F-4-EtO-Ph 2-F-4-EtO-Ph 2-Cl-4-EtO-Ph 2-Br-4-EtO-Ph
The present disclosure also includes Tables 673 through 676, each of which is constructed the same as Table 672 above, except that the row heading in Table 672 (i.e. "G1 is -OH.") is replaced with the respective row heading shown below. For Example, in Table 673 the row heading is "G1 is -SH.", and Q1 is as defined in Table 672 above. Thus, the first entry in Table 673 specifically discloses 4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5- thiol. Tables 674 through 676 are constructed similarly.
Table Row Heading Table Row Heading
673 G1 is -SH. 675A G1 is I.
674 G1 Is Cl. 676 G1 Is -NH2.
675 G1 is Br.
The compounds of Tables 672 and 673 illustrate compounds of Formula 4 wherein X is O or S, R1 and Rla are each H, and R2 is CH3, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 3. The compounds of Table 672 further illustrate compounds of Formula 4b wherein R1 and Rla are each H, and R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 6a using the method of Scheme 6 and to prepare intermediate compounds of Formula 6b using the method of Scheme 7. Tables 674 and 675 illustrate compounds of Formula 6 wherein G is Cl or Br, and Rla are each H, and R2 is CH3 which are useful intermediates to prepare compounds of Formula Ic using the method of Scheme 4. Table 676 illustrates compounds of Formula 4a wherein R1 and Rla are each H, and R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 6 using the method of Scheme 5.
Figure imgf000086_0001
Q1 is 2,6-di-F-Ph and R^2 is Me.
Figure imgf000086_0002
2-F 3 -F
4-Cl 2-Br
2,6-di-F 2,4,6-tri-F
2-C1-4-F 2-F-4-C1
Figure imgf000086_0003
2-Br-4-F 2-I-4-F 2-Me-4-F 2-F-4-MeO 2-Cl-4-MeO 2-Br-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-C1-4-CN 2-Br-4-CN
2,6-di-F-4-CN 2-Cl-4,5-di-F 2-Cl-4,6-di-F 2-Br-4,5-di-F 2-Br-4,6-di-F
4-Cl-2,5-di-F 4-Cl-2,6-di-F 4-Br-2,5-di-F 4-Br-2,6-di-F 2,4-di-Cl-6-F
2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF3-4-F 4-Me 2,4-di-Me
2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F
The present disclosure also includes Tables 678 through 704, each of which is constructed the same as Table 677 above, except that the row heading in Table 677 (i.e. "Q1 is 2,6-di-F-Ph.") is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is "Q1 is 2,4-di-F-Ph.", and (R3)p is as defined in Table 677 above. Thus, the first entry in Table 678 specifically discloses 3-(2,6-difluorophenyl)-4-[(2,4- difluorophenyl)amino]-4-(methylthio)-3-buten-2-one. Tables 679 through 704 are constructed similarly.
Table Row Heading Table Row Heading
678 Q1 is 2,4-di-F-Ph, and R32 is Me. 721 Q1 is 2-F-4-Cl-Ph, and R32 is Et. 679 Q1 is 2,4,6-tri-F-Ph, and R32 is Me. 722 Q1 is 2,4-di-Cl-Ph, and R32 is Et. 680 Q1 is 2,6-di-F-4-OMe-Ph, and R32 is Me. 723 Q1 is 2,6-di-Cl-Ph, and R32 is Et.
680A Q1 is 2,6-di-F-4-OEt-Ph, and R32 is Me. 724 Q1 is 2-F-4-MeO-Ph, and R32 is Et. 681 Q1 is 2,6-di-F-4-CN-Ph, and R32 is Me. 724A Q1 is 2-F-4-EtO-Ph, and R32 is Et. 682 Q1 is 2-Cl-4-F-Ph, and R32 is Me. 725 Q1 is 2-Cl-4-MeO-Ph, and R32 is Et. 683 Q1 is 2-Cl-6-F-Ph, and R32 is Me. 725A Q1 is 2-Cl-4-EtO-Ph, and R32 is Et. 684 Q1 is 2-Cl-4,6-di-F-Ph, and R32 is Me. 726 Q1 is 2-Br-4-MeO-Ph, and R32 is Et. 685 Q1 is 4-Cl-2,6-di-F-Ph, and R32 is Me. 726A Q1 is 2-Br-4-EtO-Ph, and R32 is Et. 686 Q1 is 2-Br-4-F-Ph, and R32 is Me. 727 Q1 is 2-F-4-CN-Ph, and R32 is Et. 687 Q1 is 2-Br-6-F-Ph, and R32 is Me. 728 Q1 is 2-Cl-4-CN-Ph, and R32 is Et. 688 Q1 is 2-Me-4-F-Ph, and R32 is Me. 729 Q1 is 2-Br-4-CN-Ph, and R32 is Et. 689 Q1 is 2-1-4-F-Ph, and R32 is Me. 730 Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is Et. 690 Q1 is 2-F-Ph, and R32 is Me. 731 Q1 is 2-Cl-3-thienyl, and R32 is Et. 691 Q1 is 2-Cl-Ph, and R32 is Me. 732 Q1 is 2,5-di-Cl-3-thienyl, and R32 is Et. 692 Q1 is 2-Br-Ph, and R32 is Me. 733 Q1 is 2,6-di-F-Ph, and R32 is «-Pr. 693 Q1 is 2-F-4-Cl-Ph, and R32 is Me. 734 Q1 is 2,4-di-F-Ph, and R32 is «-Pr. 694 Q1 is 2,4-di-Cl-Ph, and R32 is Me. 735 Q1 is 2,4,6-tri-F-Ph, and R32 is «-Pr. 695 Q1 is 2,6-di-Cl-Ph, and R32 is Me. 736 Q1 is 2,6-di-F-4-OMe-Ph, and R32 is «-Pr. 696 Q1 is 2-F-4-MeO-Ph, and R32 is Me. 736A Q1 is 2,6-di-F-4-OEt-Ph, and R32 is «-Pr.
696A Q1 is 2-F-4-EtO-Ph, and R32 is Me. 737 Q1 is 2,6-di-F-4-CN-Ph, and R32 is «-Pr. 697 Q1 is 2-Cl-4-MeO-Ph, and R32 is Me. 738 Q1 is 2-Cl-4-F-Ph, and R32 is «-Pr.
697A Q1 is 2-Cl-4-EtO-Ph, and R32 is Me. 739 Q1 is 2-Cl-6-F-Ph, and R32 is «-Pr. 698 Q1 is 2-Br-4-MeO-Ph, and R32 is Me. 740 Q1 is 2-Cl-4,6-di-F-Ph, and R32 is «-Pr. Table Row Heading Table Row Heading 698A Q1 is 2-Br-4-EtO-Ph, and R32 is Me. 741 Q1 is 4-Cl-2,6-di-F-Ph, and R32 is «-Pr.
699 Q1 is 2-F-4-CN-Ph, and R32 is Me. 742 Q1 is 2-Br-4-F-Ph, and R32 is «-Pr.
700 Q1 is 2-Cl-4-CN-Ph, and R32 is Me. 743 Q1 is 2-Br-6-F-Ph, and R32 is «-Pr.
701 Q1 is 2-Br-4-CN-Ph, and R32 is Me. 744 Q1 is 2-Me-4-F-Ph, and R32 is «-Pr.
702 Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is Me. 745 Q1 is 2-1-4-F-Ph, and R32 is «-Pr.
703 Q1 is 2-Cl-3-thienyl, and R32 is Me. 746 Q1 is 2-F-Ph, and R32 is «-Pr.
704 Q1 is 2,5-di-Cl-3-thienyl, and R32 is Me. 747 Q1 is 2-Cl-Ph, and R32 is «-Pr.
705 Q1 is 2,6-di-F-Ph, and R32 is Et. 748 Q1 is 2-Br-Ph, and R32 is «-Pr.
706 Q1 is 2,4-di-F-Ph, and R32 is Et. 749 Q1 is 2-F-4-Cl-Ph, and R32 is «-Pr.
707 Q1 is 2,4,6-tri-F-Ph, and R32 is Et. 750 Q1 is 2,4-di-Cl-Ph, and R32 is «-Pr.
708 Q1 is 2,6-di-F-4-OMe-Ph, and R32 is Et. 751 Q1 is 2,6-di-Cl-Ph, and R32 is «-Pr. 708A Q1 is 2,6-di-F-4-OEt-Ph, and R32 is Et. 752 Q1 is 2-F-4-MeO-Ph, and R32 is «-Pr.
709 Q1 is 2,6-di-F-4-CN-Ph, and R32 is Et. 752A Q1 is 2-F-4-EtO-Ph, and R32 is «-Pr.
710 Q1 is 2-Cl-4-F-Ph, and R32 is Et. 753 Q1 is 2-Cl-4-MeO-Ph, and R32 is «-Pr.
711 Q1 is 2-Cl-6-F-Ph, and R32 is Et. 753A Q1 is 2-Cl-4-EtO-Ph, and R32 is «-Pr.
712 Q1 is 2-Cl-4,6-di-F-Ph, and R32 is Et. 754 Q1 is 2-Br-4-MeO-Ph, and R32 is «-Pr.
713 Q1 is 4-Cl-2,6-di-F-Ph, and R32 is Et. 754A Q1 is 2-Br-4-EtO-Ph, and R32 is «-Pr.
714 Q1 is 2-Br-4-F-Ph, and R32 is Et. 755 Q1 is 2-F-4-CN-Ph, and R32 is «-Pr.
715 Q1 is 2-Br-6-F-Ph, and R32 is Et. 756 Q1 is 2-Cl-4-CN-Ph, and R32 is «-Pr.
716 Q1 is 2-Me-4-F-Ph, and R32 is Et. 757 Q1 is 2-Br-4-CN-Ph, and R32 is «-Pr.
717 Q1 is 2-1-4-F-Ph, and R32 is Et. 758 Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is «-Pr.
718 Q1 is 2-F-Ph, and R32 is Et. 759 Q1 is 2-Cl-3-thienyl, and R32 is «-Pr.
719 Q1 is 2-Cl-Ph, and R32 is Et. 760 Q1 is 2,5-di-Cl-3-thienyl, and R32 is «-Pr.
720 Q1 is 2-Br-Ph, and R32 is Et.
The compounds of Tables 677 through 760 illustrate compounds of Formula 17 wherein R2 is CH3, which are useful intermediates to prepare compounds of Formula Ic using the method of Scheme 16.
TABLE 761
Figure imgf000088_0001
Figure imgf000088_0002
2,4,6-tri-F-Ph 2-Br-4-F-Ph 2-F-4-Cl-Ph 2-Cl-4-CN-Ph
2,6-di-F-4-OMe-Ph 2-Br-6-F-Ph 2,4-di-Cl-Ph 2-Br-4-CN-Ph
2,6-di-F-4-CN-Ph 2-Me-4-F-Ph 2,6-di-Cl-Ph 2,5-di-Cl-3-pyridinyl
2-Cl-4-F-Ph 2-1-4-F-Ph 2-F-4-MeO-Ph 2-Cl-3-thienyl
2-Cl-6-F-Ph 2-F-Ph 2-Cl-4-MeO-Ph 2,5-di-Cl-3-thienyl
2,6-di-F-4-EtO-Ph 2-F-4-EtO-Ph 2-Cl-4-EtO-Ph 2-Br-4-EtO-Ph
The present disclosure also includes Tables 762 through 764, each of which is constructed the same as Table 761 above, except that the row heading in Table 761 (i.e. "Each R33 is Me.") is replaced with the respective row heading shown below. For Example, in Table 762 the row heading is "Each R33 is Et.", and Q1 is as defined in Table 761 above. Thus, the first entry in Table 762 specifically discloses 3-(2,6-difluorophenyl)-4,4- bis(ethylthio)-3-buten-2-one. Tables 763 and 764 are constructed similarly.
Table Row Heading Table Row Heading
762 Each R33 is Et. 764 The two R33 are taken together as -CH2-.
763 Each R33 is «-Pr.
The compounds of Tables 761 through 763 illustrate compounds of Formula 18 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 17 using the method of Scheme 17. The compounds of Table 764 illustrate compounds of Formula 18 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 4c using the method described below Scheme 17.
TABLE 765
Figure imgf000089_0001
B1 Is Me.
Figure imgf000089_0002
The present disclosure also includes Tables 766 through 769, each of which is constructed the same as Table 765 above, except that the row heading in Table 765 (i.e. "B1 is Me.") is replaced with the respective row heading shown below. For Example, in Table
766 the row heading is "B1 is Et.", and Q1 is as defined in Table 765 above. Thus, the first entry in Table 766 specifically discloses ethyl α-acetyl-2,6-difluorobenzeneacetate. Tables
767 through 769 are constructed similarly.
Table Row Heading Table Row Heading
766 B1 Is Et. 768 B1 Is Ph.
767 B1 is is «-Pr. 769 B1 Is CH2Ph. The compounds of Tables 765 through 769 illustrate compounds of Formula 16 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 4b using the method of Scheme 14. Formulation/Utility
A compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High- strength compositions are primarily used as intermediates for further formulation.
Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and Powders
Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.001-95 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
Liquid diluents include, for example, water, Λ/,iV-dimethylalkanamides (e.g., Λ/,Λ/-dimethylformamide), limonene, dimethyl sulfoxide, JV-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, Methylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifϊers or defoaming agents. Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as 7V,iV-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts. Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon' s Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000. In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.
Example A High Strength Concentrate
Compound 18 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%
Example B
Wettable Powder
Compound 22 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0% Example C
Granule
Compound 23 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
U.S.S. No. 25-50 sieves)
Example D
Extruded Pellet
Compound 24 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
Example E
Emulsifiable Concentrate
Compound 36 10.0% polyoxyethylene sorbitol hexoleate 20.0%
C6-C10 fatty acid methyl ester 70.0% Example F Microemulsion
Compound 41 5.0% polyvinylpyrrolidone -vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%
Example G
Seed Treatment
Compound 45 20.00% polyvinylpyrrolidone -vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
Formulations such as those in the Formulation Table are typically diluted with water to form aqueous compositions before application. Aqueous compositions for direct applications to the plant or portion thereof (e.g., spray tank compositions) typically at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rutstroemia floccosum (also known as Sclerontina homoeocarpa); Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species. Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants.
Accordingly, this aspect of the present invention can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of a compound of Formula 1, an JV-oxide, or salt thereof to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 1O g per kilogram of seed.
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a compound of Formula 1 and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession. As mentioned in the Summary of the Invention, one aspect of the present invention is a fungicidal composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an JV-oxide, or a salt thereof (i.e. component a), and at least one other fungicide (i.e. component b).
Of note is a composition which, in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (bl) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides; (b3) demethylation inhibitor (DMI) fungicides; (b4) phenylamide fungicides; (b5) amine/morpholine fungicides; (b6) phospholipid biosynthesis inhibitor fungicides; (b7) carboxamide fungicides; (b8) hydroxy(2-amino-)pyrimidine fungicides; (b9) anilinopyrimidine fungicides; (blO) //-phenyl carbamate fungicides; (bl 1) quinone outside inhibitor (QoI) fungicides; (bl2) phenylpyrrole fungicides; (bl3) quinoline fungicides; (bl4) lipid peroxidation inhibitor fungicides; (bl5) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (bl6) melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides; (bl7) hydroxyanilide fungicides; (bl8) squalene-epoxidase inhibitor fungicides; (bl9) polyoxin fungicides; (b20) phenylurea fungicides; (b21) quinone inside inhibitor (QiI) fungicides; (b22) benzamide fungicides; (b23) enopyranuronic acid antibiotic fungicides; (b24) hexopyranosyl antibiotic fungicides; (b25) glucopyranosyl antibiotic: protein synthesis fungicides; (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; (b27) cyanoacetamideoxime fungicides; (b28) carbamate fungicides; (b29) oxidative phosphorylation uncoupling fungicides; (b30) organo tin fungicides; (b31) carboxylic acid fungicides; (b32) heteroaromatic fungicides; (b33) phosphonate fungicides; (b34) phthalamic acid fungicides; (b35) benzotriazine fungicides; (b36) benzene-sulfonamide fungicides; (b37) pyridazinone fungicides; (b38) thiophene-carboxamide fungicides; (b39) pyrimidinamide fungicides; (b40) carboxylic acid amide (CAA) fungicides; (b41) tetracycline antibiotic fungicides; (b42) thiocarbamate fungicides; (b43) benzamide fungicides; (b44) host plant defense induction fungicides; (b45) multi-site contact activity fungicides; (b46) fungicides other than classes (bl) through (b45); and salts of compounds of classes (bl) through (b46).
Further descriptions of these classes of fungicidal compounds are provided below, (bl) "Methyl benzimidazole carbamate (MBC) fungicides" (FRAC (Fungicide Resistance Action Committee) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methy 1.
(b2) "Dicarboximide fungicides" (FRAC code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
(b3) "Demethylation inhibitor (DMI) fungicides" (FRAC code 3) inhibit C14-demethylase which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258. (b4) "Phenylamide fungicides" (FRAC code 4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M (also known as mefenoxam). The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
(b5) "Amine/morpholine fungicides" (FRAC code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ8 → Δ7 isomerase and Δ14 reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpho lines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.
(b6) "Phospholipid biosynthesis inhibitor fungicides" (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
(b7) "Carboxamide fungicides" (FRAC code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole carboxamide and pyridine carboxamide. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include bixafen, furametpyr, isopyrazam, fluxapyroxad, sedaxane (N- [2- ( 1 S,2R)- [1,1 '-bicyclopropyl] -2-ylphenyl] -3 -(difluoromethyl)- 1 -methyl- 1 H-pyrazole-4- carboxamide) and penflufen (7V-[2-(l,3-dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH- pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)). The pyridine carboxamides include boscalid. (b8) "Hydroxy(2-amino-)pyrimidine fungicides" (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
(b9) "Anilinopyrimidine fungicides" (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydro lytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
(blO) 'W-Phenyl carbamate fungicides" (FRAC code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
(bl l) "Quinone outside inhibitor (QoI) fungicides" (FRAC code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q0) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides (also known as strobilurin fungicides) include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione, dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin and pyrametostrobin. The oximinoacetates include kresoxim-methyl, pyraoxystrobin and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, α-[methoxyimino]-iV-methyl-2-[[[ 1 -[3-(trifluoromethyl)phenyl]ethoxy]imino]- methyljbenzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)-l-methyl-2-propen-l-ylidene]- amino]oxy]methyl]-α-(methoxyimino)-Λ/-methylbenzeneacetamide. The oxazolidinediones include famoxadone. The dihydrodioxazines include fluoxastrobin. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.
(bl2) "Phenylpyrrole fungicides" (FRAC code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.
(bl3) "Quinoline fungicides" (FRAC code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
(bl4) "Lipid peroxidation inhibitor fungicides" (FRAC code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4- thiadiazole fungicides. The aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazole fungicides include etridiazole.
(bl5) "Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides" (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole. (bl6) "Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides" (FRAC code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.
(bl7) "Hydroxyanilide fungicides (FRAC code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid.
(bl8) "Squalene-epoxidase inhibitor fungicides" (FRAC code 18) inhibit squalene- epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifine and terbinafme.
(bl9) "Polyoxin fungicides" (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.
(b20) "Phenylurea fungicides" (FRAC code 20) are proposed to affect cell division. Examples include pencycuron. (b21) "Quinone inside inhibitor (QiI) fungicides" (FRAC code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the "quinone inside" (Qj) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom.
(b22) "Benzamide fungicides" (FRAC code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide. (b23) "Enopyranuronic acid antibiotic fungicides" (FRAC code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
(b24) "Hexopyranosyl antibiotic fungicides" (FRAC code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.
(b25) "Glucopyranosyl antibiotic: protein synthesis fungicides" (FRAC code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
(b26) "Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides" (FRAC code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin. (b27) "Cyanoacetamideoxime fungicides (FRAC code 27) include cymoxanil.
(b28) "Carbamate fungicides" (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb- hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.
(b29) "Oxidative phosphorylation uncoupling fungicides" (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
(b30) "Organo tin fungicides" (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.
(b31) "Carboxylic acid fungicides" (FRAC code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
(b32) "Heteroaromatic fungicides" (FRAC code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.
(b33) "Phosphonate fungicides" (FRAC code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.
(b34) "Phthalamic acid fungicides" (FRAC code 34) include teclofthalam.
(b35) "Benzotriazine fungicides" (FRAC code 35) include triazoxide. (b36) "Benzene-sulfonamide fungicides" (FRAC code 36) include flusulfamide.
(b37) "Pyridazinone fungicides" (Fungicide Resistance Action Committee (FRAC) code 37) include diclomezine.
(b38) "Thiophene-carboxamide fungicides" (FRAC code 38) are proposed to affect ATP production. Examples include silthiofam. (b39) "Pyrimidinamide fungicides" (FRAC code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
(b40) "Carboxylic acid amide (CAA) fungicides" (FRAC code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (valiphenal). The mandelic acid amides include mandipropamid, JV-[2-[4-[[3-(4- chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)- amino Jbutanamide and Λ/-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]- ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide.
(b41) "Tetracycline antibiotic fungicides" (FRAC code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.
(b42) "Thiocarbamate fungicides (b42)" (FRAC code 42) include methasulfocarb. (b43) "Benzamide fungicides" (FRAC code 43) inhibit growth of fungi by derealization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.
(b44) "Host plant defense induction fungicides" (FRAC code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole- carboxamides include tiadinil and isotianil.
(b45) "Multi-site contact fungicides" inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: (b45.1) "copper fungicides" (FRAC code Ml)", (b45.2) "sulfur fungicides" (FRAC code M2), (b45.3) "dithiocarbamate fungicides" (FRAC code M3), (b45.4) "phthalimide fungicides" (FRAC code M4), (b45.5) "chloronitrile fungicides" (FRAC code M5), (b45.6) "sulfamide fungicides" (FRAC code M6), (b45.7) "guanidine fungicides" (FRAC code M7), (b45.8) "triazine fungicides" (FRAC code M8) and (b45.9) "quinone fungicides" (FRAC code M9). "Copper fungicides" are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). "Sulfur fungicides" are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. "Dithiocarbamate fungicides" contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. "Phthalimide fungicides" contain a phthalimide molecular moiety; examples include folpet, captan and captafol. "Chloronitrile fungicides" contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. "Sulfamide fungicides" include dichlofluanid and tolyfluanid. "Guanidine fungicides" include dodine, guazatine and imoctadine, including iminoctadine albesilate and iminoctadine triacetate. "Triazine fungicides" include anilazine. "Quinone fungicides" include dithianon. (b46) "Fungicides other than fungicides of classes (bl) through (b45)" include certain fungicides whose mode of action may be unknown. These include: (b46.1) "thiazole carboxamide fungicides" (FRAC code U5), (b46.2) "phenyl-acetamide fungicides" (FRAC code U6), (b46.3) "quinazolinone fungicides" (FRAC code U7) and (b46.4) "benzophenone fungicides" (FRAC code U8). The thiazole carboxamides include ethaboxam. The phenyl- acetamides include cyflufenamid and Λ/-[[(cyclopropylmethoxy)amino][6- (difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one. The benzophenones include metrafenone and pyriofenone. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, Λ/-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxy- phenyl] ethyl]-3 -methyl-2- [(methylsulfonyl)amino]butanamide, N-[2- [4- [ [3 -(4-chloro- phenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]- butanamide, 2- [ [2-fluoro-5 -(trifluoromethyl)phenyl]thio] -2- [3 -(2-methoxyphenyl)-2-thiazo- lidinylidene]acetonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine,
4-fluorophenyl N-[ 1 -[[[ 1 -(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-chloro- 6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo[ 1 ,5-α]pyrimidine, N-(4- chloro-2-nitrophenyl)-Λ/-ethyl-4-methylbenzenesulfonamide, iV-[[(cyclopropylmethoxy)- amino] [6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, Λ/"-[4-[4- chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-Λ/-ethyl-N-methylmethanimid- amide and l-[(2-propenylthio)carbonyl]-2-(l-methylethyl)-4-(2-methylphenyl)-5-amino-lH- pyrazol-3-one.
Therefore of note is a mixture (i.e. composition) comprising as component (a) a compound of Formula 1 (or an JV-oxide or salt thereof) and as component (b) at least one fungicidal compound selected from the group consisting of the aforedescribed classes (bl) through (b46). Also of note are embodiments wherein component (b) comprises at least one fungicide from each of two different groups selected from (bl) through (b46). Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (bl) through (b46). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.
Examples of other biologically active compounds or agents with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet (S-1955), amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole (DPX-E2Y45), chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole (3 -bromo- 1 -(3 -chloro-2-pyridinyl)-JV- [4-cy ano-2-methyl-6- [(methylamino)- carbonyl]phenyl]-lH-pyrazole-5-carboxamide), cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fϊpronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron (XDE-007), noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, prothiocarb, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyenopyrafen, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as ΗzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
General references for agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.
For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 (or an iV-oxide or salt thereof) is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example ratios between about 1 :30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins. Of note is a combination of a compound of Formula 1 (or an JV-oxide or salt thereof) with at least one other fungicidal active ingredient. Of particular note is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
Of particular note are compositions which in addition to a compound of Formula 1 include at least one compound selected from the group consisting of (1) alkylenebis(dithiocarbamate) fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4) pyrimidinone fungicides; (5) chlorothalonil; (6) carboxamides acting at complex II of the fungal mitochondrial respiratory electron transfer site; (7) quinoxyfen; (8) metrafenone or pyriofenone; (9) cyflufenamid; (10) cyprodinil; (11) copper compounds; (12) phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb; (18) propamocarb; (19) validomycin; (20) dichlorophenyl dicarboximide fungicides; (21) zoxamide; (22) fluopicolide; (23) mandipropamid; (24) carboxylic acid amides acting on phospholipid biosynthesis and cell wall deposition; (25) dimethomorph; (26) non-DMI sterol biosynthesis inhibitors; (27) inhibitors of demethylase in sterol biosynthesis; (28) bcγ complex fungicides; and salts of compounds of (1) through (28).
Further descriptions of classes of fungicidal compounds are provided below. Pyrimidinone fungicides (group (4)) include compounds of Formula Al
Figure imgf000108_0001
Al wherein M forms a fused phenyl, thiophene or pyridine ring; Ral4 is C^-Cg alkyl; Ral5 is C^-Cg alkyl or C^-Cg alkoxy; Ral6 is halogen; and Ral7 is hydrogen or halogen. Pyrimidinone fungicides are described in PCT Patent Application Publication
WO 94/26722 and U.S. Patents 6,066,638, 6,245,770, 6,262,058 and 6,277,858. Of note are pyrimidinone fungicides selected from the group: 6-bromo-3-propyl-2-propyloxy- 4(3H)-quinazolinone, 6,8-diiodo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6-iodo- 3-propyl-2-propyloxy-4(3H)-quinazolinone (proquinazid), 6-chloro-2-propoxy-3-propyl- thieno[2,3-<i]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylthieno[2,3-<i]pyrimidin- 4(3H)-one, 7-bromo-2-propoxy-3-propylthieno[3,2-J]pyrimidin-4(3H)-one, 6-bromo- 2-propoxy-3-propylpyrido[2,3-d]pyrimidin-4(3H)-one, 6,7-dibromo-2-propoxy-3-propyl- thieno[3,2-J]pyrimidin-4(3H)-one, and 3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido- [2 , 3 -<i]pyrimidin-4(3H)-one . Sterol biosynthesis inhibitors (group (27)) control fungi by inhibiting enzymes in the sterol biosynthesis pathway. Demethylase-inhibiting fungicides have a common site of action within the fungal sterol biosynthesis pathway, involving inhibition of demethylation at position 14 of lanosterol or 24-methylene dihydrolanosterol, which are precursors to sterols in fungi. Compounds acting at this site are often referred to as demethylase inhibitors, DMI fungicides, or DMIs. The demethylase enzyme is sometimes referred to by other names in the biochemical literature, including cytochrome P-450 (14DM). The demethylase enzyme is described in, for example, J. Biol. Chem. 1992, 267, 13175-79 and references cited therein. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258. bcγ Complex Fungicides (group 28) have a fungicidal mode of action which inhibits the be i complex in the mitochondrial respiration chain. The bcγ complex is sometimes referred to by other names in the biochemical literature, including complex III of the electron transfer chain, and ubihydroquinone: cytochrome c oxidoreductase. This complex is uniquely identified by Enzyme Commission number EC 1.10.2.2. The bcγ complex is described in, for example, J. Biol. Chem. 1989, 264, 14543-48; Methods Enzymol. 1986, 126, 253-71; and references cited therein. Strobilurin fungicides such as azoxystrobin, dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin are known to have this mode of action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38, 1328-1349). Other fungicidal compounds that inhibit the bcγ complex in the mitochondrial respiration chain include famoxadone and fenamidone.
Alkylenebis(dithiocarbamate)s (group (I)) include compounds such as mancozeb, maneb, propineb and zineb. Phenylamides (group (3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and oxadixyl. Carboxamides (group (6)) include compounds such as boscalid, carboxin, fenfuram, flutolanil, fluxapyroxad, furametpyr, mepronil, oxycarboxin, thifluzamide, penthiopyrad and penflufen (Λ/-[2-(l,3-dimethylbutyl)phenyl]-5- fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)), and are known to inhibit mitochondrial function by disrupting complex II (succinate dehydrogenase) in the respiratory electron transport chain. Copper compounds (group (H)) include compounds such as copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). Phthalimides (group (12)) include compounds such as folpet and captan. Benzimidazole fungicides (group (14)) include benomyl and carbendazim. Dichlorophenyl dicarboximide fungicides (group (20)) include chlozolinate, dichlozoline, iprodione, isovaledione, myclozolin, procymidone and vinclozolin. Non-DMI sterol biosynthesis inhibitors (group (26)) include morpholine and piperidine fungicides. The morpholines and piperidines are sterol biosynthesis inhibitors that have been shown to inhibit steps in the sterol biosynthesis pathway at a point later than the inhibitions achieved by the DMI sterol biosynthesis (group (27)). The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin.
Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper salts such as Bordeaux mixture (tribasic copper sulfate), copper hydroxide and copper oxychloride, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluopicolide (also known as picobenzamid), fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil (2-[[2-fluoro-5- (trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile), flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazol, guazatine, imazalil, imibenconazole, iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metrafenone, myclobutanil, naftifϊne, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, pefurazoate, phosphorous acid and salts, phthalide, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyrrolnitrin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecloftalam, tecnazene, terbinafme, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole, trifloxystrobin, triforine, trimorphamide, triticonazole, uniconazole, validamycin, valifenalate (valiphenal), vinclozolin, zineb, ziram, zoxamide, Λ/'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5- dimethylphenyl]-Λ/-ethyl-Λ/-methylmethanimidamide, 5-chloro-6-(2,4,6-trifluorophenyl)-7- (4-methylpiperidin-l-yl)[l,2,4]triazolo[l,5-α]pyrimidine (BAS600), penflufen (iV-[2-(l,3- dimethylbutyl)phenyl] -5 -fluoro- 1 ,3 -dimethyl- lH-pyrazole-4-carboxamide), N- [2- [4-[ [3 -(4- chlorophenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2- [(methylsulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3- methoxyphenyl] ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide, 2-butoxy-6-iodo-3 - propyl-4H- 1 -benzopyran-4-one, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]- pyridine, 4-fluorophenyl N-[ 1 -[[[ 1 -(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, Λ/-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluoro- phenyl]methylene]benzeneacetamide, α-(methoxyimino)-iV-methyl-2-[ [ [ 1 - [3 -(trifluoro- methyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, ^-[4-[4-ChIOrO-S-(MfIuOrO- methyl)phenoxy]-2,5-dimethylphenyl]-Λ/-ethyl-Λ/-methylmethanimidamide, JV-(4-chloro-2- nitrophenyl)-Λ/-ethyl-4-methylbenzenesulfonamide, 2-[[[[3-(2,6-dichlorophenyl)-l-methyl- 2-propen- 1 -ylidene]amino]oxy]methyl]-α-(methoxyimino)-Λ/-methylbenzeneacetamide, 1 - [(2-propenylthio)carbonyl] -2-( 1 -methylethyl)-4-(2-methylphenyl)-5 -amino- lH-pyrazol-3 - one, ethyl-6-octyl-[l,2,4]triazolo[l,5-a]pyrimidin-7-ylamine, pentyl JV-[4-[[[[(l-methyl-lH- tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamate and pentyl N-[6- [[ [ [( 1 -methyl- lH-tetrazol-5 -yl)phenylmethylene] amino]oxy]methyl] -2-pyridinyl] carbamate
Of note are combinations of compounds of Formula 1 (or an JV-oxide or salt thereof) (i.e. Component (a) in compositions) with azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, fluxapyroxad, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen) (i.e. as Component (b) in compositions).
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group: azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone and penthiopyrad. Tables Al through A54 list specific combinations of a Component (b) compound with
Component (a) (compound numbers refer to compounds in Index Table A) illustrative of the mixtures, compositions and methods of the present invention. In Table Al, each line below the column headings "Component (a)" and "Component (b)" specifically discloses a combination (i.e. mixture) of Component (a), which is Compound 22, with a Component (b) fungicide. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of Component (b) to Component (a) for the disclosed mixture. For example, the first line of Table Al discloses a mixture of Compound 22 with acibenzolar-S-methyl and lists weight ratios of acibenzolar-S-methyl to Compound 22 of 1 : 1 , 1 :4 or 1 : 17. Table Al
Component (a) Component (b) Illustrative Ratios(*)
Compound 22 acibenzolar-jS-methyl 1:1 1:4 1:18
Compound 22 aldimorph 7:1 3:1 1:1
Compound 22 ametoctradin 3:1 1:1 1:3
Compound 22 amisulbrom 1:1 1:2 1:6
Compound 22 anilazine 22:1 8:1 4:1
Compound 22 azaconazole 2:1 1:2 1:4
Compound 22 azoxystrobin 3:1 1:1 1:3
Compound 22 benalaxyl 1:1 1:2 1:6
Compound 22 benalaxyl-M 1:1 1:3 1:8
Compound 22 benodanil 4:1 2:1 1:2
Compound 22 benomyl 11:1 4:1 1:1
Compound 22 benthiavalicarb 1:1 1:4 1:12
Compound 22 benthiavalicarb-isopropyl 1:1 1:4 1:12
Compound 22 bethoxazin 15:1 5:1 2:1
Compound 22 binapacryl 15:1 5:1 2:1
Compound 22 biphenyl 15:1 5:1 2:1
Compound 22 bitertanol 3:1 1:1 1:2
Compound 22 bixafen 2:1 1:1 1:3
Compound 22 blasticidin-S 1:4 1:12 1:30
Compound 22 Bordeaux mixture (tribasic copper sulfate) 45:1 15:1 5:1
Compound 22 boscalid 4:1 2:1 1:2
Compound 22 bromuconazole 3:1 1:1 1:3
Compound 22 bupirimate 1:3 1:10 1:30
Compound 22 captafol 15:1 5:1 2:1
Compound 22 captan 15:1 5:1 2:1
Compound 22 carbendazim 11:1 4:1 2:1
Compound 22 carboxin 4:1 2:1 1:2
Compound 22 carpropamid 3:1 1:1 1:3
Compound 22 chloroneb 100:1 35:1 14:1
Compound 22 chlorothalonil 15:1 5:1 2:1
Compound 22 chlozolinate 11:1 4:1 2:1
Compound 22 clotrimazole 3:1 1:1 1:3
Compound 22 copper hydroxide 45:1 15:1 5:1
Compound 22 copper oxychloride 45:1 15:1 5:1
Compound 22 cyazofamid 1:1 1:2 1:6
Compound 22 cyflufenamid 1:2 1:6 1:24 Component (a) Component (b) Illustrative Ratios(*)
Compound 22 cymoxanil 1:1 1:2 1:5
Compound 22 cyproconazole 1:1 1:2 1:6
Compound 22 cyprodinil 4:1 2:1 1:2
Compound 22 dichlofluanid 15:1 5:1 2:1
Compound 22 diclocymet 15:1 5:1 2:1
Compound 22 diclomezine 3:1 1:1 1:3
Compound 22 dicloran 15:1 5:1 2:1
Compound 22 diethofencarb 7:1 2:1 1:2
Compound 22 difenoconazole 1:1 1:3 1:12
Compound 22 diflumetorim 15:1 5:1 2:1
Compound 22 dimethirimol 1:3 1:8 1:30
Compound 22 dimethomorph 3:1 1:1 1:2
Compound 22 dimoxystrobin 2:1 1:1 1:4
Compound 22 diniconazole 1:1 1:3 1:8
Compound 22 diniconazole-M 1:1 1:3 1:12
Compound 22 dinocap 2:1 1:1 1:3
Compound 22 dithianon 5:1 2:1 1:2
Compound 22 dodemorph 7:1 3:1 1:1
Compound 22 dodine 10:1 4:1 2:1
Compound 22 edifenphos 3:1 1:1 1:3
Compound 22 enestroburin 2:1 1:1 1:4
Compound 22 epoxiconazole 1:1 1:3 1:7
Compound 22 ethaboxam 2:1 1:1 1:3
Compound 22 ethirimol 7:1 3:1 1:1
Compound 22 etridiazole 7:1 2:1 1:2
Compound 22 famoxadone 2:1 1:1 1:4
Compound 22 fenamidone 2:1 1:1 1:4
Compound 22 fenarimol 1:2 1:7 1:24
Compound 22 fenbuconazole 1:1 1:3 1:10
Compound 22 fenfuram 4:1 1:1 1:2
Compound 22 fenhexamid 10:1 4:1 2:1
Compound 22 fenoxanil 15:1 4:1 1:1
Compound 22 fenpiclonil 15:1 5:1 2:1
Compound 22 fenpropidin 7:1 2:1 1:1
Compound 22 fenpropimorph 7:1 2:1 1:1
Compound 22 fenpyrazamine 3:1 1:1 1:3
Compound 22 fentin salt such as fentin acetate, fentin chloride or fentin 3:1 1:1 1:3 Component (a) Component (b) Illustrative Ratios(*) hydroxide
Compound 22 ferbam 30:1 10:1 4:1 Compound 22 ferimzone 7:1 2:1 1:2 Compound 22 fluazinam 3:1 1:1 1:2 Compound 22 fludioxonil 2:1 1:1 1:4 Compound 22 flumetover 3:1 1:1 1:2 Compound 22 flumoφh 3:1 1:1 1:3 Compound 22 fluopicolide 1:1 1:2 1:6 Compound 22 fluopyram 3:1 1:1 1:3 Compound 22 fluoroimide 37:1 14:1 5:1 Compound 22 fluoxastrobin 1:1 1:2 1:6 Compound 22 fluquinconazole 1:1 1:2 1:4 Compound 22 flusilazole 3:1 1:1 1:3 Compound 22 flusulfamide 15:1 5:1 2:1 Compound 22 flutianil 1:1 1:2 1:6 Compound 22 flutolanil 4:1 1:1 1:2 Compound 22 flutriafol 1:1 1:2 1:4 Compound 22 fluxapyroxad 2:1 1:1 1:3 Compound 22 folpet 15:1 5:1 2:1 Compound 22 fosetyl-aluminum 30:1 12:1 5:1 Compound 22 fuberidazole 11:1 4:1 2:1 Compound 22 furalaxyl 1:1 1:2 1:6 Compound 22 furametpyr 15:1 5:1 2:1 Compound 22 guazatine 15:1 5:1 2:1 Compound 22 hexaconazole 1:1 1:2 1:5 Compound 22 hymexazol 75:1 25:1 9:1 Compound 22 imazalil 1:1 1:2 1:5 Compound 22 imibenconazole 1:1 1:2 1:5 Compound 22 iminoctadine 15:1 4:1 1:1 Compound 22 iodocarb 15:1 5:1 2:1 Compound 22 ipconazole 1:1 1:2 1:5 Compound 22 iprobenfos 15:1 5:1 2:1 Compound 22 iprodione 15:1 5:1 2:1 Compound 22 iprovalicarb 2:1 1:1 1:3 Compound 22 isoprothiolane 45:1 15:1 5:1 Compound 22 isopyrazam 2:1 1:1 1:3 Compound 22 isotianil 2:1 1:1 1:3 Component (a) Component (b) Illustrative Ratios(*)
Compound 22 kasugamycin 1:2 1:7 1:24 Compound 22 kre soxim-methyl 2:1 1:1 1:4 Compound 22 mancozeb 22:1 7:1 3:1 Compound 22 mandipropamid 2:1 1:1 1:4 Compound 22 maneb 22:1 7:1 3:1 Compound 22 mepanipyrim 6:1 2:1 1:1 Compound 22 mepronil 1:1 1:2 1:6 Compound 22 meptyldinocap 2:1 1:1 1:3 Compound 22 metalaxyl 1:1 1:2 1:6 Compound 22 metalaxyl-M 1:1 1:4 1:12 Compound 22 metconazole 1:1 1:2 1:6 Compound 22 methasulfocarb 15:1 5:1 2:1 Compound 22 metiram 15:1 5:1 2:1 Compound 22 metominostrobin 3:1 1:1 1:3 Compound 22 metrafenone 2:1 1:1 1:4 Compound 22 myclobutanil 1:1 1:3 1:8 Compound 22 naftifine 15:1 5:1 2:1 Compound 22 neo-asozin (ferric methane arsonate) 15:1 5:1 2:1 Compound 22 nuarimol 3:1 1:1 1:3 Compound 22 octhilinone 15:1 4:1 1:1 Compound 22 ofurace 1:1 1:2 1:6 Compound 22 orysastrobin 3:1 1:1 1:3 Compound 22 oxadixyl 1:1 1:2 1:6 Compound 22 oxolinic acid 7:1 2:1 1:2 Compound 22 oxpoconazole 1:1 1:2 1:5 Compound 22 oxycarboxin 4:1 1:1 1:2 Compound 22 oxytetracycline 3:1 1:1 1:3 Compound 22 pefurazoate 15:1 5:1 2:1 Compound 22 penconazole 1:2 1:6 1:15 Compound 22 pencycuron 11:1 4:1 2:1 Compound 22 penthiopyrad 2:1 1:1 1:3 Compound 22 phosphorous acid or a salt thereof 15:1 6:1 2:1 Compound 22 phthalide 15:1 6:1 2:1 Compound 22 picoxystrobin 1:1 1:2 1:5 Compound 22 piperalin 3:1 1:1 1:3 Compound 22 polyoxin 3:1 1:1 1:3 Compound 22 probenazole 3:1 1:1 1:3 Component (a) Component (b) Illustrative Ratios(*)
Compound 22 prochloraz 7:1 2:1 1:2
Compound 22 procymidone 11:1 4:1 2:1
Compound 22 propamocarb or propamocarb-hydrochloride 10:1 4:1 2:1
Compound 22 propiconazole 1:1 1:2 1:5
Compound 22 propineb 11:1 4:1 2:1
Compound 22 proquinazid 1:1 1:3 1:12
Compound 22 prothiocarb 3:1 1:1 1:3
Compound 22 prothioconazole 1:1 1:2 1:5
Compound 22 pyraclostrobin 2:1 1:1 1:4
Compound 22 pyrametostrobin 2:1 1:1 1:4
Compound 22 pyraoxystrobin 2:1 1:1 1:4
Compound 22 pyrazophos 15:1 4:1 1:1
Compound 22 pyribencarb 4:1 1:1 1:2
Compound 22 pyributicarb 15:1 4:1 1:1
Compound 22 pyrifenox 3:1 1:1 1:3
Compound 22 pyrimethanil 3:1 1:1 1:2
Compound 22 pyriofenone 2:1 1:1 1:4
Compound 22 pyroquilon 3:1 1:1 1:3
Compound 22 pyrrolnitrin 15:1 5:1 2:1
Compound 22 quinomethionate 15:1 5:1 2:1
Compound 22 quinoxyfen 1:1 1:2 1:6
Compound 22 quintozene 15:1 5:1 2:1
Compound 22 silthiofam 2:1 1:1 1:4
Compound 22 simeconazole 1:1 1:2 1:5
Compound 22 spiroxamine 5:1 2:1 1:2
Compound 22 streptomycin 3:1 1:1 1:3
Compound 22 sulfur 75:1 25:1 9:1
Compound 22 tebuconazole 1:1 1:2 1:5
Compound 22 tebufloquin 3:1 1:1 1:3
Compound 22 tecloftalam 15:1 5:1 2:1
Compound 22 tecnazene 15:1 5:1 2:1
Compound 22 terbinafine 15:1 5:1 2:1
Compound 22 tetraconazole 1:1 1:2 1:5
Compound 22 thiabendazole 11:1 4:1 2:1
Compound 22 thifluzamide 3:1 1:1 1:3
Compound 22 thiophanate 11:1 4:1 2:1
Compound 22 thiophanate -methyl 11:1 4:1 2:1 Component (a) Component (b) Illustrative Ratios(*)
Compound 22 thiram 37:1 14: 1 5:1 Compound 22 tiadinil 2:1 1:1 1:3 Compound 22 tolclofos-methyl 37:1 14: 1 5:1 Compound 22 tolylfluanid 15:1 5: 1 2: 1 Compound 22 triadimefon 1:1 1:2 1:5 Compound 22 triadimenol 1:1 1:2 1:5 Compound 22 triazoxide 15:1 5: 1 2: 1 Compound 22 tricyclazole 3: 1 1: 1 1:3 Compound 22 tridemorph 7:1 2:1 1:1 Compound 22 trifloxystrobin 2:1 1:1 1:4 Compound 22 triflumizole 3: 1 1: 1 1:3 Compound 22 triforine 3: 1 1:1 1:3 Compound 22 trimorphamide 7: 1 2: 1 1:2 Compound 22 triticonazole 1: 1 1:2 1:5 Compound 22 uniconazole 1: 1 1:2 1:5 Compound 22 validamycin 3: 1 1: 1 1:3 Compound 22 valifenalate (valiphenal) 2: 1 1: 1 1:4 Compound 22 vinclozolin 15:1 6: 1 2: 1 Compound 22 zineb 37:1 14:1 5:1 Compound 22 ziram 37:1 14:1 5: 1 Compound 22 zoxamide 2: 1 1: 1 1:4
5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin- 1 -
Compound 22 1: 1 1:2 1:6 yl)[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidine
Penflufen (N-[2-( 1 ,3 -dimethylbutyl)phenyl] -5-fluoro- 1,3- Compound 22 2: 1 1: 1 1:3 dimethyl-l//-pyrazole-4-carboxamide)
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-
Compound 22 methoxyphenyl]ethyl] -3 -methyl-2- 2: 1 1: 1 1:4
[(methylsulfonyl)amino]butanamide
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-
Compound 22 methoxyphenyljethyl] -3 -methyl-2- 2: 1 1: 1 1:4
[(ethylsulfonyl)amino]butanamide
Compound 22 2-butoxy-6-iodo-3 -propyl-4//- 1 -benzopyran-4-one 1: 1 1:3 1:12
3-[5-(4-chlorophenyl)-2,3-dimethyl-3- Compound 22 3: 1 1: 1 1:3 isoxazolidinyl]pyridine
4-fluorophenyl N-[l-[[[l-(4-
Compound 22 2: 1 1: 1 1:4 cyanophenyl)ethyl] sulfonyl]methyl]propyl] carbamate λf-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3- Compound 22 1:2 1:7 1:24 difluorophenyl]methylene]benzeneacetamide Component (a) Component (b) Illustrative Ratios(*) α-[methoxyimino]-N-methyl-2-[[[ 1 -[3-
Compound 22 (trifluoromethyl)phenyl] ethoxy] imino]methyl] - 3: 1 1: 1 1:3 benzeneacetamide
A"-[4-[4-chloro-3-(trifluorometliyl)plienoxy]-2,5-
Compound 22 3: 1 1: 1 1:3 dimethylphenyl]-Λf-ethyl-Λf-methylmethanimidamide
N-(4-chloro-2-nitrophenyl)-N-ethyl-4- Compound 22 3: 1 1: 1 1:3 methylbenzene sulfonamide
2-[[[3-(2,6-dichlorophenyl)- 1 -methyl-2-propen- 1 -
Compound 22 ylidene]amino]oxy]methyl]-α-(methoxyimino)-λf- 3: 1 1: 1 1:3 methylbenzeneacetamide pentyl N- [4- [ [ [ [( 1 -methyl- l//-tetrazol-5 -yl)phenyl-
Compound 22 3: 1 1: 1 1:3 methylene] amino]oxy]methyl] -2-thiazolyl] carbamate pentyl N- [6- [[[[( 1 -methyl- l//-tetrazol-5 -yl)phenyl- Compound 22 3: 1 1: 1 1:3 methylene] amino]oxy]methyl] -2-pyridinyl] carbamate
(*) Ratios of Component (b) relative to Component (a) by weight.
Tables A2 through A54 are each constructed the same as Table Al above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table A2 the entries below the "Component (a)" column heading all recite "Compound 18", and the first line below the column headings in Table A2 specifically discloses a mixture of Compound 18 with acibenzolar-S-methyl. Tables A3 through A54 are constructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
A2 Compound 18 A29 Compound 351 A3 Compound 23 A30 Compound 352 A4 Compound 24 A31 Compound 357 A5 Compound 36 A32 Compound 358 A6 Compound 41 A33 Compound 360 A7 Compound 45 A34 Compound 361 A8 Compound 87 A35 Compound 364 A9 Compound 91 A36 Compound 365 AlO Compound 118 A37 Compound 367 Al l Compound 139 A38 Compound 368 A12 Compound 148 A39 Compound 369 A13 Compound 172 A40 Compound 372 A14 Compound 175 A41 Compound 373 A15 Compound 193
Figure imgf000118_0001
A42 Compound 374 Table Number Component (a) Column Entries Table Number Component (a) Column Entries
A16 Compound 232 A43 Compound 375
A17 Compound 265 A44 Compound 376
A18 Compound 266 A45 Compound 377
A19 Compound 284 A46 Compound 378
A20 Compound 286 A47 Compound 379
A21 Compound 287 A48 Compound 380
A22 Compound 292 A49 Compound 381
A23 Compound 297 A50 Compound 382
A24 Compound 332 A51 Compound 383
A25 Compound 336 A52 Compound 384
A26 Compound 343 A53 Compound 385
A27 Compound 346 A54 Compound 386
A28 Compound 349
Figure imgf000119_0001
Table B 1 lists specific combinations of a Component (b) compound with Component (a) illustrative of the mixtures, compositions and methods of the present invention. The first column of Table Bl lists the specific Component (b) compound (e.g., "acibenzolar-51- methyl" in the first line). The second, third and fourth columns of Table Bl lists ranges of weight ratios for rates at which the Component (b) compound is typically applied to a field- grown crop relative to Component (a) (e.g., "2:1 to 1 :180" of acibenzolar-S-methyl relative to Component (a) by weight). Thus, for example, the first line of Table Bl specifically discloses the combination of acibenzolar-S-methyl with Component (a) is typically applied in a weight ratio between 2:1 to 1 :180. The remaining lines of Table Bl are to be construed similarly. Table Bl thus supplements the specific ratios disclosed in Tables Al through A54 with ranges of ratios for these combinations.
Table Bl
Figure imgf000119_0002
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
As already noted, the present invention includes embodiments wherein in the composition comprising components (a) and (b), component (b) comprises at least one fungicide from each of two groups selected from (bl) through (b46). Tables Cl through C54 list specific mixtures (compound numbers refer to compounds in Index Table A) to illustrate embodiments wherein component (b) includes at least one fungicide from each of two groups selected from (bl) through (b46). In Table Cl, each line below the column headings "Component (a)" and "Component (b)" specifically discloses a mixture of Component (a), which is Compound 22, with at least two Component (b) fungicides. The entries under the heading "Illustrative Ratios" disclose three specific weight ratios of Component (a) to each Component (b) fungicide in sequence for the disclosed mixture. For example, the first line discloses a mixture of Compound 22 with cyproconazole and azoxystrobin and lists weight ratios of Compound 22 to cyproconazole to azoxystrobin of 1:1:1 ,2:1:1 or 3:1:1.
Table Cl
Figure imgf000127_0001
Component (a) Component (b) Illustrative Ratios(*)
Compound 22 difenconazole trifloxystrobin proquinazid 1:1:1:1 2:1: 1: 1 3:1 :1:1
Compound 22 epoxiconazole azoxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole kresoxim-methyl 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole picoxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole pyraclostrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole trifloxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole bixafen 1:1:2 2:1 :2 3: 1:2
Compound 22 epoxiconazole boscalid 1:1:2 2:1 •2 3: 1:2
Compound 22 epoxiconazole cyflufenamid 1:2:1 2-2 :1 3: 2:1
Compound 22 epoxiconazole fluopyram 1:1:2 2:1 •2 3: 1:2
Compound 22 epoxiconazole isopyrazam 1:1:2 2:1 :2 3: 1:2
Compound 22 epoxiconazole metrafenone 1:1:2 2:1 •2 3: 1:2
Compound 22 epoxiconazole penthiopyrad 1:1:2 2:1 :2 3: 1:2
Compound 22 epoxiconazole proquinazid 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole quinoxyfen 1:1:1 2:1 :1 3: 1:1
Compound 22 epoxiconazole sedaxane 1:1:2 2:1 •2 3: 1:2
Compound 22 epoxiconazole picoxystrobin proquinazid 1:1:1:1 2:1: 1: 1 3:1 :1:1
Compound 22 epoxiconazole trifloxystrobin proquinazid 1:1:1:1 2:1: 1: 1 3:1 :1:1
Compound 22 metconazole azoxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole kresoxim-methyl 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole picoxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole pyraclostrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole trifloxystrobin 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole bixafen 1:1:2 2:1 :2 3: 1:2
Compound 22 metconazole boscalid 1:1:2 2:1 •2 3: 1:2
Compound 22 metconazole cyflufenamid 1:2:1 2-2 :1 3: 2:1
Compound 22 metconazole fluopyram 1:1:2 2:1 •2 3: 1:2
Compound 22 metconazole isopyrazam 1:1:2 2:1 :2 3: 1:2
Compound 22 metconazole metrafenone 1:1:2 2:1 •2 3: 1:2
Compound 22 metconazole penthiopyrad 1:1:2 2:1 :2 3: 1:2
Compound 22 metconazole proquinazid 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole quinoxyfen 1:1:1 2:1 :1 3: 1:1
Compound 22 metconazole sedaxane 1:1:2 2:1 :2 3: 1:2
Compound 22 metconazole picoxystrobin proquinazid 1:1:1:1 2:1: 1: 1 3:1 :1:1
Compound 22 metconazole trifloxystrobin proquinazid 1:1:1:1 2:1: 1: 1 3:1 :1:1
Compound 22 myclobutanil azoxystrobin 1:1:1 2:1 :1 3: 1:1
Figure imgf000129_0001
Component (a) Component (b) Illustrative Ratios( *)
Compound 22 tebuconazole pyraclostrobin 1: 1:1 2:1: 1 3:1: 1
Compound 22 tebuconazole trifloxystrobin 1: 1:1 2: 1:1 3:1: 1
Compound 22 tebuconazole bixafen 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole boscalid 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole cyflufenamid 1:2:1 2-2- 1 3:2: 1
Compound 22 tebuconazole fluopyram 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole isopyrazam 1:1:2 2:1:2 3:1:2
Compound 22 tebuconazole metrafenone 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole penthiopyrad 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole proquinazid 1: 1:1 2:1: 1 3:1: 1
Compound 22 tebuconazole quinoxyfen 1:1: 1 2: 1:1 3:1: 1
Compound 22 tebuconazole sedaxane 1: 1:2 2:1:2 3:1:2
Compound 22 tebuconazole picoxystrobin proquinazid 1: 1:1: 1 2:1: 1:1 3:1: 1:1
Compound 22 tebuconazole trifloxystrobin proquinazid 1: 1:1: 1 2:1: 1:1 3:1: 1:1
(*) Ratios of Component (a) relative to Component (b) in sequence, by weight.
Tables C2 through C54 are each constructed the same as Table Cl above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table C2 the entries below the "Component (a)" column heading all recite "Compound 18", and the first line in below the column headings in Table C2 specifically discloses a mixture of Compound 18 with cyproconazole and azoxystrobin, and the illustrative weight ratios of 1 :1 :1, 2:1 :1 and 3:1 :1 of Compound 18:cyproconazole:azoxystrobin. Tables C3 through C54 are constructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
C2 Compound 18 C29 Compound 351 C3 Compound 23 C30 Compound 352 C4 Compound 24 C31 Compound 357 C5 Compound 36 C32 Compound 358 C6 Compound 41 C33 Compound 360 C7 Compound 45 C34 Compound 361 C8 Compound 87 C35 Compound 364 C9 Compound 91 C36 Compound 365 ClO Compound 118 C37 Compound 367 CI l Compound 139 C38 Compound 368 C12 Compound 148
Figure imgf000130_0001
C39 Compound 369 C13 Compound 172 C40 Compound 372
C14 Compound 175 C41 Compound 373
C15 Compound 193 C42 Compound 374
C16 Compound 232 C43 Compound 375
C17 Compound 265 C44 Compound 376
C18 Compound 266 C45 Compound 377
C19 Compound 284 C46 Compound 378
C20 Compound 286 C47 Compound 379
C21 Compound 287 C48 Compound 380
C22 Compound 292 C49 Compound 381
C23 Compound 297 C50 Compound 382
C24 Compound 332 C51 Compound 383
C25 Compound 336 C52 Compound 384
C26 Compound 343 C53 Compound 385
C27 Compound 346 C54 Compound 386
C28 Compound 349
Figure imgf000131_0001
As mentioned in the Summary of the Invention, one aspect of the present invention is a composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent (e.g., insecticide, acaricide). Of note is a composition comprising component (a) and at least one (i.e. one or more) invertebrate pest control compound or agent, which then can be subsequently combined with component (b) to provide a composition comprising components (a) and (b) and the one or more invertebrate pest control compounds or agents. Alternatively without first mixing with component (b), a biologically effective amount of the composition comprising component (a) with at least one invertebrate pest control agent can be applied to a plant or plant seed (directly or through the environment of the plant or plant seed) to protect the plant or plant seed from diseases caused by fungal pathogens and injury caused by invertebrate pests.
For embodiments where one or more of invertebrate pest control compounds are used, the weight ratio of these compounds (in total) to the component (a) compounds is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example ratios between about 1 :30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity.
Of note is a composition of the present invention which comprises in addition to a component (a) compound, alone or in combination with fungicidal component (b), at least one invertebrate pest control compound or agent selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda- cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fϊpronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses, encapsulated delta-endotoxins of Bacillus thuringiensis, baculoviruses, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
In certain instances, combinations of a compound of Formula 1 or an JV-oxide or salt thereof (i.e. component (a)), alone or in mixture with fungicidal component (b), with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load. Table Dl lists specific combinations of invertebrate pest control agents with
Compound 22 (identified in Index Table A) as a component (a) compound illustrative of mixtures and compositions comprising these active ingredients and methods using them according to the present invention. The second column of Table Dl lists the specific invertebrate pest control agents (e.g., "Abamectin" in the first line). The third column of Table Dl lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The fourth column of Table Dl lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent is typically applied relative to Compound 22 alone or in combination with fungicidal component (b) (e.g., "50:1 to 1 :50" of abamectin relative to a Compound 22 by weight). Thus, for example, the first line of Table Dl specifically discloses the combination of Compound 22 with abamectin is typically applied in a weight ratio between 50:1 to 1 :50. The remaining lines of Table Dl are to be construed similarly.
Table Dl
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0002
Tables D2 through D54 are each constructed the same as Table Dl above except that entries below the "Component (a)" column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table D2 the entries below the "Component (a)" column heading all recite "Compound 18", and the first line in below the column headings in Table D2 specifically discloses a mixture of Compound 18 with abamectin. Tables D3 through D54 are constructed similarly.
Table Number Component (a) Column Entries Table Number Component (a) Column Entries
D2 Compound 18 D29 Compound 351 D3 Compound 23 D30 Compound 352 D4 Compound 24 D31 Compound 357 D5 Compound 36 D32 Compound 358 D6 Compound 41 D33 Compound 360 D7 Compound 45 D34 Compound 361 D8 Compound 87 D35 Compound 364 D9 Compound 91 D35 Compound 365 DlO Compound 118 D37 Compound 367 DI l Compound 139 D38 Compound 368 D12 Compound 148
Figure imgf000135_0001
D39 Compound 369 D13 Compound 172 D40 Compound 372
D14 Compound 175 D41 Compound 373
D15 Compound 193 D42 Compound 374
D16 Compound 232 D43 Compound 375
D17 Compound 265 D44 Compound 376
D18 Compound 266 D45 Compound 377
D19 Compound 284 D46 Compound 378
D20 Compound 286 D47 Compound 379
D21 Compound 287 D48 Compound 380
D22 Compound 292 D49 Compound 381
D23 Compound 297 D50 Compound 382
D24 Compound 332 D51 Compound 383
D25 Compound 336 D52 Compound 384
D26 Compound 343 D53 Compound 385
D27 Compound 346 D54 Compound 386
D28 Compound 349
Figure imgf000136_0001
One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with compounds of Formula 1 (and iV-oxides and salts thereof) include sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-regulated chloride channel blockers such as endosulfan, ethiprole and fϊpronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin; cyflumetofen; fenothiocarb; flonicamid; metaflumizone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; spirotetramat; and thiosultap-sodium. One embodiment of biological agents for mixing with compounds of component (a) include nucleopolyhedro virus such as HzNPV and AfNPV; Bacillus thuringiensis and encapsulated delta-endotoxins of Bacillus thuringiensis such as Cellcap, MPV and MPVII; as well as naturally occurring and genetically modified viral insecticides including members of the family Baculoviridae as well as entomophagous fungi. Of note is a composition comprising component (a) and at least one additional biologically active compound or agent selected from the Invertebrate Pest Control Agents listed in Table Dl above.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions. The following abbreviations are used in the Index Tables which follow: Me is methyl, Ph is phenyl, OMe is methoxy, -CN is cyano, -NO2 is nitro. Also, "pyridin-2-yl" is synonymous with "2-pyridinyl", "pyridin-3-yl" is synonymous with "3-pyridinyl", and "pyrimidin-5-yl" is synonymous with 5-pyrimidinyl". The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared. "Cmpd No. " means compound number. Mass spectra (M.S.) are reported as the molecular weight of the highest isotopic abundance parent ion (M+ 1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP+).
INDEX TABLE A
Figure imgf000137_0001
Cmpd
No. Rl R2 Q1 Q2 X M.S
1 (Ex. 1) H Me 2,4-di-F-Ph 3 -Cl-Ph NH **
2 H Me 2,4-di-F-Ph 3,5-di-OMe-Ph NH 360
3 H Me 2,4-di-F-Ph 3 -Cl-Ph NMe *
4 H Me 4-Cl-Ph 2,4-di-F-Ph NH 334
5 H Me 4-Cl-Ph 3,5-di-F-Ph NH 334
6 H Me 4-Cl-Ph 3,5-di-F-Ph NMe 348
7 H Me 2-Cl-4-F-Ph 3-Cl-4-F-Ph NH 369
8 H Me 2-Cl-4-F-Ph 3-F-Ph NH 334
9 H Me 2-Cl-4-F-Ph 3,5-di-F-Ph NH 352
10 H Me 4-Cl-Ph 2,3,5-tri-F-Ph NH 352 Cmpd
No. Rl R2 Q1 Q2 X M.S
11 H Me 2-Cl-4-F-Ph 4-F-Ph NH 334
12 H Me 2-Cl-4-F-Ph 2-F-Ph NH 334
13 H Me 2-Cl-4-F-Ph 2,4-di-F-Ph NH 352
14 H Me 2,4,6-tri-F-Ph 3-F-4-Cl-Ph NH 370
15 H Me 2-F-4-OMe-Ph 4-Cl-Ph O 347
16 H Me 3,5-di-OMe-Ph 4-Cl-Ph O 359 (Ex. 2) H Me 2-Cl-4-F-Ph 2,6-di-F-4-OMe-Ph NH **
18 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NH 370
19 H Me 2-Cl-4-F-Ph 4-Cl-Ph NH 350
20 H Me 2-Cl-4-F-Ph 2-F-4-NO2-Ph O 380
21 H Me 2-Cl-4-F-Ph 2-F-4-OMe-Ph O 365
22 H Me 2,6-di-F-4-OMe-Ph 4-Cl-Ph NH 364
23 H Me 2,6-di-F-4-OMe-Ph 2,4-di-F-Ph NH 366 (Ex. 3) H Me 2,6-di-F-4-OMe-Ph 2,4,6-tri-F-Ph NH **
25 H Me 3 -Cl-Ph 2,6-di-F-4-OMe-Ph NH 364
26 H Me 2,4,6-tri-F-Ph 4-NO2-Ph O 364
27 H Me 2,4,6-tri-F-Ph 4-Cl-Ph O 353
28 H Me 4-Cl-Ph 2,4,6-tri-F-Ph NH 352
29 H Me 4-Cl-Ph 2,6-di-F-4-OMe-Ph NH 364
30 H Me 2,4,6-tri-F-Ph 2,6-di-Cl-4-CF3-Ph O 455
31 H Me 2,4,6-tri-F-Ph 2,6-di-F-4-CN-Ph O 380
32 H Me 2,4,6-tri-F-Ph 2-Cl-4-NO2-Ph O 398
33 H Me 4-Cl-Ph 2,6-di-F-Ph NH 334
34 H Me 2,6-di-F-4-OMe-Ph 6-Cl-pyridin-3-yl NH 365
35 H Me 3,4-di-F-Ph 2,4,6-tri-F-Ph NH 354
36 H Me 3,4-di-F-Ph 2,6-di-F-4-OMe-Ph NH 366
37 H Me 2,6-di-F-Ph 3,5-di-OMe-Ph NH 360
38 H Me 2,4,6-tri-F-Ph 2,4-di-Cl-Ph O 387
39 H Me 2,4,6-tri-F-Ph 5-Cl-pyridin-2-yl O 354
40 H Me 2,6-di-F-4-OMe-Ph 2,4-di-Cl-Ph O 399
41 H Me 2,4-di-F-Ph 2,4,6-tri-F-Ph NH 354
42 H Me 2,4-di-F-Ph 2,6-di-F-4-OMe-Ph NH 366 Cmpd
No. Rl R2 Q1 Q2 X M.S
43 H Me 3-F-Ph 2,6-di-F-4-CN-Ph O 344
44 H Me 4-Cl-Ph 2,6-di-F-4-CN-Ph O 360 (Ex. 4) H Me 2-Cl-4-F-Ph 2,6-di-F-4-CN-Ph O **
46 H Me 2-F-4-OMe-Ph 2,6-di-F-4-CN-Ph O 374
47 H Me 2,6-di-F-4-OMe-Ph 5-Cl-pyridin-2-yl O 366
48 H Me 2,6-di-F-4-OMe-Ph 3,4-di-F-Ph NH 366
49 H Me 2,6-di-F-4-OMe-Ph 3-F-4-Cl-Ph NH 382
50 H Me 2,6-di-F-4-OMe-Ph 4-Me-Ph NH 344
51 H Me 2,6-di-F-4-OMe-Ph 2,4-di-OMe-Ph NH 390
52 H Me 4-Me-Ph 2-Cl-4-NO2-Ph O 358
53 Ph Me 2,4,6-tri-F-Ph 2,6-di-F-4-NO2-Ph O 476 (Ex. 8) H Me 2,4,6-tri-F-Ph 2,6-di-F-4-NO2-Ph O **
55 H Me 4-Me-Ph 2-C1- 4-OMe-Ph O 343
56 H Me 4-Cl-Ph 4-OMe-Ph NH 328
57 H Me 2,4-di-Cl-Ph 2,4-di-OMe-Ph NH 392 (Ex. 10) H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-4-Cl-Ph O **
59 H Me 2,6-di-F-4-OMe-Ph 2,4-di-OMe-6-Cl-Ph NH 424
60 H Me 4-Cl-Ph 2-Cl-4-OMe-Ph NH 362
61 Me Me 4-Cl-Ph 2,6-di-F-Ph NH 348
62 H Me 2,4-di-Cl-Ph 2,6-di-F-4-OMe-Ph NH 398
63 Me Me 2,6-di-F-Ph 3,5-di-OMe-Ph NH 374
64 H Me 2,4,6-tri-F-Ph 3,5-di-Cl-pyridin-2-yl O 388
65 -CO2Et Me 2,4,6-tri-F-Ph 2,6-di-F, 4-NO2-Ph O 472
66 H Me 2,6-di-F-4-OMe-Ph 5-Me-pyridin-2-yl NH 345
67 H Me 2-Cl-4-F-Ph 5-CN-pyridin-2-yl NH 342
68 -CO2H Me 2,4,6-tri-F-Ph 2,6-di-F-4-NO2-Ph O 444 (Ex. 5) H Me 2,4-di-Cl-Ph 2,4-di-F-Ph NH **
70 Me Me 2,4-di-Cl-Ph 2,4-di-F-Ph NH 382
71 H Me 2-Cl-4-F-Ph 2-F-4-(NHC(O)Me)-Ph O 392
72 H Me 2,4-di-F-Ph 3,4-di-OMe-Ph NH 360
73 H Me 2-Cl-4-F-Ph 3,5-di-Cl-pyridin-2-yl NH 387 Cmpd
No. Rl R2 Q1 Q2 X M.S
74 H Me 2,4-di-Cl-Ph 3,4-di-OMe-Ph NH 392
75 H Me 2,4-di-Cl-Ph 2,4,6-tri-F-Ph NH 386
76 H Me 2,4-di-F-Ph 6-Cl-pyridin-3-yl NH 331
77 H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-4-NH2-Ph O 382
78 H Me 2,4,6-tri-F-Ph 2,6-di-F-4-OMe-Ph NH 384
79 H Me 4-Me-Ph 2,4,6-tri-F-Ph NH 332
80 H Me 4-Me-Ph 2,6-di-F-4-OMe-Ph NH 344
81 H Me 2,6-di-F-4-OMe-Ph 5-Cl-2,4-di-OMe-Ph NH 424
82 H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-4-CN-Ph NH 391
83 H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-4-OMe-Ph NH 396
84 H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-Ph O 367
85 H Me 3,5-di-OMe-Ph 2,6-di-F-4-CN-Ph O 386
86 H Me 6-Cl-pyridin-3 -yl 2,6-di-F-4-CN-Ph O 361
87 H Me 2,6-di-F-4-OMe-Ph 2-Cl-4-F-Ph NH 382
88 H Me 2,6-di-F-4-OMe-Ph 4-F-2-Me-Ph NH 362
89 H Me 4-F-2-OMe-Ph 2,6-di-F-4-CN-Ph O 374
90 H Me 2,6-di-F-4-OMe-Ph 4-Br-2,6-di-F-Ph O 447
91 H Me 2-Cl-4-F-Ph 2,6-di-F-4-CN-Ph NH 377
92 H Me 2,4,6-tri-F-Ph 2,6-di-F-4-CN-Ph NH 379
93 H Me 2,4,6-tri-F-Ph 3,4-di-OMe-Ph NH 378
94 H Me 2,4,6-tri-F-Ph 6 -OMe -pyridin- 3 -yl NH 349
95 H Me 2,6-di-F-4-OMe-Ph 6 -OMe -pyridin- 3 -yl NH 361
96 H Me 2,4,6-tri-F-Ph 2-F-4-CN-Ph O 362
97 H Me 4-F-2-Me-Ph 2,6-di-F-4-CN-Ph O 358
98 H Me 2,4,6-tri-F-Ph 2-Cl-4-CN-Ph O 378
99 H Me 2,4,6-tri-F-Ph 2,5-di-F-4-CN-Ph O 380
100 H Me 2,4,6-tri-F-Ph 5-Cl-2,4-di-OMe-Ph NH 412
101 H Me 2,4,6-tri-F-Ph 3,5-di-Cl-pyridin-2-yl NH 386
102 H Me 2,6-di-F-4-OMe-Ph 3,5-di-Cl-pyridin-2-yl NH 398
103 H Me 2,6-di-F-4-OH-Ph 2,4-di-F-Ph NH 352
104 H Me 2-Cl-4-OMe-Ph 2,4,6-tri-F-Ph NH 382 Cmpd
Figure imgf000141_0001
105 H Me 2,6-di-F-4-OS(O)2CF3 2,4-di-F-Ph NH 484
106 H Me 2,6-di-F-4-CN-Ph 2,4-di-F-Ph NH 361
107 H Me 2-Cl-4-F-Ph 2,6-di-Cl-pyridin-3-yl NH 386
108 H c-Pr 2-Cl-4-F-Ph 2,4-di-F-Ph NH 378
109 H Me 2,4,6-tri-F-Ph 3,5-di-F-pyridin-2-yl NH 355
110 H Me 2,6-di-F-4-CN-Ph 4-Cl-Ph NH ***
111 H Me 2,6-di-F-4-CN-Ph 4-F-Ph NH ***
112 H Me 2,6-di-F-4-CN-Ph 2-Cl-4-F-Ph NH ***
113 H Me 2,6-di-F-4-CN-Ph 3-F-4-OMe-Ph NH ***
114 H Me 2,6-di-F-4-CN-Ph 3,4-di-F-Ph NH ***
115 H Me 2,6-di-F-4-CN-Ph 3 -Cl-Ph NH ***
116 H Me 2-Cl-4-F-Ph 3-F-5-CN-Ph O 360
117 H Me 2,6-di-F-4-OMe-Ph 2-Cl-4-CN-Ph NH 389
118 H Me 2-Cl-4-F-Ph 2-F-4-CN-Ph O 360
119 H Me 2-Cl-4-F-Ph 2-Cl-4-NO2-Ph O 396
120 H Me 2,4,6-tri-F-Ph 2-F-4-CN-Ph NH 361
121 H Me 2-Cl-4-F-Ph 2,6-di-F-4-NO2-Ph O 398
122 H Me 2-Cl-4-F-Ph 4-F-2-NO2-Ph O 380
123 H Me 2,6-di-F-4-CN-Ph 3,4-di-Cl-Ph NH ***
124 H Me 2,6-di-F-4-CN-Ph 4-Me-Ph NH ***
125 H Me 2,6-di-F-4-CN-Ph 4-Cl-3-F-Ph NH ***
126 H Me 2,6-di-F-4-CN-Ph 4-OMe-Ph NH ***
127 H Me 2,6-di-F-4-CN-Ph 4-F-3 -OMe-Ph NH 373
128 H Me 2,6-di-F-4-OMe-Ph 3,5-di-F-pyridin-2-yl NH 367
129 H Me 2,4,6-tri-F-Ph 4.Cl-3-F-Ph O ***
130 H Me 2,4,6-tri-F-Ph 4-Br-3-F-Ph O ***
131 H Me 2,4,6-tri-F-Ph 3-F-4-NO2-Ph O ***
132 H Me 2-Cl-4-F-Ph 3,4,5-tri-F-Ph NH 370
133 H Me 2,6-di-F-4-CN-Ph 2,4,6-tri-F-Ph NH ***
134 H Me 2,6-di-F-4-CN-Ph 2,6-di-F-4-OMe-Ph NH ***
135 H Me 2,4,6-tri-F-Ph 3-Me-4-NO9-Ph O *** Cmpd
No. Rl R2 Q1 Q2 X M.S
136 H Me 2,6-di-F-4-CN-Ph 3-F-Ph NH ***
137 H Me 2,6-di-F-4-CN-Ph 2,5-di-F-Ph NH ***
138 H Me 2,6-di-F-4-CN-Ph 2,4,5-tri-F-Ph NH ***
139 H Me 2-Cl-4-F-Ph 2-Cl-4-CN-Ph O 376
140 H Me 2,6-di-F-4-OMe-Ph 2,6-di-F-4-CN-Ph O 392
141 H Me 2,6-di-F-4-OEt-Ph 2,4-di-F-Ph NH 380
142 H Me 2,6-di-F-4-CN-Ph 5-Cl-2-F-Ph NH ***
143 H Me 2,6-di-F-4-CN-Ph 4-Cl-2-F-Ph NH ***
144 H Me 2,6-di-F-4-CN-Ph 3-Cl-4-F-Ph NH ***
145 H Me 2,6-di-F-4-CN-Ph 2,3-di-F-Ph NH ***
146 H Me 2,6-di-F-4-CN-Ph 2,5-di-Cl-Ph NH ***
147 H Me 2,6-di-F-4-CN-Ph 2,3-di-Cl-Ph NH ***
148 H Me 2-Cl-4-F-Ph 2,5-di-F-4-CN-Ph O 378
149 H Me 2-Cl-4-F-Ph 4-F-2-CN-Ph O 360
150 H Me 2-Cl-4-F-Ph 2-Cl-4,5-di-CN-Ph O 401
151 H Me 2,4,6-tri-F-Ph 3-OMe-4-NO2-Ph O ***
152 H Me 2,6-di-F-4-OMe-Ph 4-Cl-3-F-Ph O 383
153 H Me 2,6-di-F-4-OMe-Ph 4-Br-3-F-Ph O 429
154 H Me 2-Cl-4-F-Ph 3,5-di-F-pyridin-2-yl NH 353
155 H Me 2-Cl-4-OMe-Ph 2,6-di-F-4-CN-Ph O 390
156 H Me 2,4,6-tri-F-Ph 3-CN-4-NO2-Ph O ***
157 H Me 2,4,6-tri-F-Ph 4-C1-3 -Me-Ph O ***
158 H Me 2-Cl-4-F-Ph 2,6-di-F-4-OMe-Ph NEt 410
159 H Me 2-Cl-4-F-Ph 2,6-di-F-4-OMe-Ph NCH2CH=CH2 422
160 H Me 2-Cl-4-OMe-Ph 2,4-di-F-Ph NH 364
161 H Me 2-Cl-4-OMe-Ph 2,6-di-F-Ph NH 364
162 H Me 2-Cl-4-F-Ph 2-Cl-4-CN-Ph NH 375
163 H Me 2,4,6-tri-F-Ph 2-Cl-4,5-di-CN-Ph O 403
164 H Me 2,4,6-tri-F-Ph 4-C1-3 -OMe-Ph O ***
165 H Me 2,4,6-tri-F-Ph 4-Br-3 -Me-Ph O ***
166 H Me 2,4,6-tri-F-Ph 4-Br-3 -OMe-Ph O 429 Cmpd
No. Rl R2 Q1 Q2 X M.S
167 H Me 2,4,6-tri-F-Ph 2,3,5-tri-F-Ph O 373
168 H Me 2-Cl-4-F-Ph 3,4-di-CN-Ph O 367
169 H Me 2,4,6-tri-F-Ph 3,4-di-CN-Ph O 369
170 H Me 2,4-di-F-Ph 2,6-di-F-4-CN-Ph O 362
171 H Me 2-Cl-4-F-Ph 2,3,6-tri-F-Ph NH 370
172 H Me 2-Cl-4-F-Ph 2,6-di-F-Ph NH 352
173 H Me 2-Cl-4-F-Ph 2,5-di-F-Ph NH 352
174 H Me 2-Cl-4-OMe-Ph 2,3,6-tri-F-Ph NH 382
175 H Me 2-Cl-4-F-Ph 2-Cl-4-F-Ph NH 368
176 H Me 2-Cl-4-OMe-Ph 2,5-di-F-Ph NH 364
177 H Me 2-Cl-6-F-Ph 2,4-di-F-Ph NH 352
178 H Me 2,6-di-F-Ph 2,4-di-F-Ph NH ***
179 H Me 2,6-di-F-Ph 2,4-di-Cl-Ph NH ***
180 H Me 2,6-di-F-Ph 2-F-4-OMe-Ph NH ***
181 H Me 2-F-Ph 2,4-di-F-Ph NH 318
182 H Me 2-F-Ph 2,4,6-tri-F-Ph NH 336
183 H Me 2-F-Ph 2,6-di-F-4-OMe-Ph NH 348
184 H Me 2-F-Ph 4-F-Ph NH 300
185 H Me 2,6-di-F-4-OMe-Ph 4-C1-3 -Me-Ph O 379
186 H Me 2,6-di-F-4-OMe-Ph 4-Br-3 -Me-Ph O ***
187 H Me 2,4,6-tri-F-Ph 3-F-4-Me-Ph O ***
188 H Me 2,6-di-F-4-OMe-Ph 3-F-4-Me_Ph O 363
189 H Me 2-Cl-4-F-Ph 3,5-di-F-pyridin-2-yl O 354
190 H Me 2-Cl-6-F-Ph 2,6-di-F-4-OMe-Ph NH 382
191 H Me 2-Cl-6-F-Ph 2,4,6-tri-F-Ph NH 369
192 H Me 2-Cl-6-F-Ph 2,6-di-F-4-CN-Ph NH 377
193 H Me 2-Cl-6-F-Ph 2-Cl-4-F-Ph NH 368
194 H Me 2,4-di-F-Ph 4-F-Ph NH ***
195 H Me 2,4-di-F-Ph 4-Cl-Ph NH ***
196 H Me 2,6-di-F-Ph 2-F-4-CN-Ph NH 343
197 H Me 2,6-di-F-Ph 2,5-di-F-Ph NH *** Cmpd
No. Rl R2 Q1 Q2 X M.S
198 H Me 2,6-di-F-Ph 2,3-di-F-Ph NH ***
199 H Me 2,6-di-F-Ph 4-F-2-OMe-Ph NH ***
200 H Me 2,6-di-F-Ph 3-OMe-Ph NH ***
201 H Me 2,6-di-F-Ph 2-Cl-4-OMe-Ph NH ***
202 H Me 2,3-di-F-Ph 2,4-di-F-Ph NH 336
203 H Me 2,3-di-F-Ph 2,4,6-tri-F-Ph NH 354
204 H Me 2,3-di-F-Ph 2,6-di-F-4-OMe-Ph NH 366
205 H Me 2,3-di-F-Ph 4-F-Ph NH 318
206 H Me 2,6-di-F-4-OMe-Ph 4-Cl-Ph O 365
207 H Me 2,4-di-F-Ph 2-Cl-4-F-Ph NH ***
208 H Me 2,6-di-F-4-OMe-Ph 2,4-di-F-Ph CHOH 381
209 H Me 2,4,6-tri-F-Ph 3,4-di-Me-Ph O ***
210 H Me 2,6-di-F-4-OMe-Ph 3,4-di-Me-Ph O ***
211 H Me 2,6-di-F-4-OMe-Ph 4-C1-3 -OMe-Ph O ***
212 H Me 2,6-di-F-4-OMe-Ph 4-Br-3 -OMe-Ph O ***
213 H Me 2,4,6-tri-F-Ph 3-OMe-Ph O 349
214 H Me 2,4-di-F-Ph 2,3-di-F-Ph NH ***
215 H Me 2,6-di-F-Ph 2-Cl-5-OMe-Ph NH ***
216 H Me 2,6-di-F-Ph 2-F-5-OMe-Ph NH ***
217 H Me 2,4,6-tri-F-Ph 3-OMe-4-Me-Ph O ***
218 H Me 2,6-di-F-4-OMe-Ph 4-C1-3 -CN-Ph O ***
219 H Me 2,4,6-tri-F-Ph 3-Me-Ph O 333
220 H Me 2,6-di-F-4-OMe-Ph 3-Me-Ph O 345
221 H Me 2,6-di-F-4-OMe-Ph 3-OMe-Ph O 361
222 H Me 2,4,6-tri-F-Ph 3 -CN-Ph O 344
223 H Me 2,6-di-F-4-OMe-Ph 3 -CN-Ph O 356
224 H Me 2,4,6-tri-F-Ph 4-C1-3 -CN-Ph O ***
225 H Me 2,4,6-tri-F-Ph 4-Br-3 -CN-Ph O ***
226 H Me 2,4-di-F-Ph 2,5-di-F-Ph NH ***
227 H Me 2,4-di-F-Ph 2-Cl-5-OMe-Ph NH ***
228 H Me 2,4-di-F-Ph 2-F-4-OMe-Ph NH *** Cmpd
No. Rl R2 Q1 Q2 X M.S
229 H Me 2,4-di-F-Ph 2,4,5-tri-F-Ph NH ***
230 H Me 2,4-di-F-Ph 2,4-di-F-Ph NH 336
231 H Me 2,4-di-F-Ph 2,3-di-Cl-Ph NH ***
232 H Me 2-Br-4-F-Ph 2,6-di-F-4-CN-Ph O 423
233 H Me 2-Br-4-F-Ph 2,5-di-F-4-CN-Ph O 423
234 H Me 2-Cl-4-F-Ph 4-F-3 -CN-Ph NH 359
235 H Me 2-Cl-4-F-Ph 2-Cl-5-CN-Ph NH 375
236 H Me 2-CF3-Ph 2-Cl-4-F-Ph NH 384
237 H Me 2-CF3-Ph 4-F-Ph NH 350
238 H Me 2-CF3-Ph 2,4-di-F-Ph NH 368
239 H Me 2-CF3-Ph 2,4,6-tri-F-Ph NH 386
240 H Me 2-CF3-Ph 2,6-di-F-4-OMe-Ph NH 398
241 H Me 2,4,6-tri-F-Ph 3 -Cl-pyridin-2-yl NH 353
242 H Me 2,4-di-F-Ph 2-Cl-4-OMe-Ph NH ***
243 H Me 2,4-di-F-Ph 2,4-di-Cl-Ph NH ***
244 H Me 2,4-di-F-Ph 2-F-5-OMe-Ph NH ***
245 H Me 2,4-di-F-Ph 2,5-di-Cl-Ph NH ***
246 H Me 2,4-di-F-Ph 2-F-4-CN-Ph NH ***
247 H Me 2,6-di-F-Ph 2,6-di-F-Ph NH ***
248 H Me 2-Br-Ph 2,4,6-tri-F-Ph NH 398
249 H Me 2,6-di-F-4-OMe-Ph 3-OMe-4-Me-Ph O ***
250 H Me 2,4,6-tri-F-Ph 3-CN-4-Me-Ph O ***
251 H Me 2-CF3-Ph 3,5-di-Cl-pyridin-2-yl NH 401
252 H Me 2-Cl-6-F-Ph 3,5-di-Cl-pyridin-2-yl NH 387
253 H Me 2-F-6-CF3-Ph 2-Cl-4-F-Ph NH 402
254 H Me 2-F-6-CF3-Ph 4-F-Ph NH 368
255 H Me 2-F-6-CF3-Ph 2,4-di-F-Ph NH 368
256 H Me 2,4-di-F-Ph 2,6-di-F-Ph NH ***
257 H Me 2,6-di-F-Ph 2,6-di-F-4-OMe-Ph NH ***
258 H Me 2,6-di-F-4-OMe-Ph 4-Br-3 -CN-Ph O ***
259 H Me 2,6-di-F-4-OMe-Ph 3-CN-4-Me-Ph O *** Cmpd
No. Rl R2 Q1 Q2 X M.S
260 H Me 2-Br-4-F-Ph 3-F-5-CF3-pyridin-2-yl O 449
261 H Me 2-Br-4-F-Ph 3-Cl-5-CF3-pyridin-2-yl O 465
262 H Me 2-F-O-CF3-Ph 2,4,6-tri-F-Ph NH 404
263 H Me 2-F-O-CF3-Ph 2,6-di-F-4-OMe-Ph NH 416
264 H Me 2-F-6-CF3-Ph 3,5-di-F-pyridin-2-yl NH 387
265 H Me 2-Cl-4-F-Ph 2-Br-4-F-Ph NH 413
266 H Me 2-Br-4-F-Ph 2,4,6-tri-F-Ph NH 415
267 H Me 2-Cl-4-OMe-Ph 3,5-di-Cl-pyridin-2-yl NH 399
268 H Me 2-Cl-4-F-Ph 2-Cl-pyrimidin-5-yl NH ***
269 H Me 2-Cl-4-F-Ph 2-Me-pyrimidin-5-yl NH ***
270 H Me 2-Cl-4-F-Ph pyrimidin-5-yl NH ***
271 H Me 2-Cl-Ph 2,6-di-F-4-CN-Ph O ***
272 H Me 2-Br-Ph 2,6-di-F-4-CN-Ph O ***
273 H Me 2,3-di-Cl-Ph 2,6-di-F-4-CN-Ph O ***
274 H Me 2,3-di-F-Ph 2,6-di-F-4-CN-Ph O ***
275 H Me 2,5-di-Cl-Ph 2,6-di-F-4-CN-Ph O ***
276 H Me 2-Cl-5-F-Ph 2,6-di-F-4-CN-Ph O ***
277 H Me 2-Cl-5-OMe-Ph 2,6-di-F-4-CN-Ph O ***
278 H Me 2-F-5-OMe-Ph 2,6-di-F-4-CN-Ph O ***
279 H Me 2-Cl-6-F-Ph 3,5-di-F-pyridin-2-yl NH 353
280 H Me 2-CF3-Ph 3,5-di-F-pyridin-2-yl NH 369
281 H Me 2,4-di-F-Ph 2-C1-3 -OMe-Ph NH ***
282 H Me 2-Cl-4-OMe-Ph 2,4-di-Cl-Ph NH 397
283 H Me 2-Cl-6-F-Ph 2,4-di-Cl-Ph NH 386
284 H Me 2-Br-4-F-Ph 2-F-4-CN-Ph O 406
285 H Me 2-Br-4-F-Ph 2-Cl-4-CN-Ph O 422
286 H Me 2-Cl-4-F-Ph 4-Cl-2,6-di-F-Ph NH 386
287 H Me 2-Cl-4-F-Ph 2-Cl-4,6-di-F-Ph NH 386
288 H Me 2-Cl-4-F-Ph 4-OMe-Ph NH 346
289 H Me 2,6-di-F-Ph 2-C1-3 -OMe-Ph NH ***
290 H Me 2,4-di-F-Ph 2,6-di-F-4-CN-Ph NH *** Cmpd
No. Rl R2 Q1 Q2 X M.S
291 H Me 2,4-di-F-Ph 2-Cl-5-CN-Ph NH ***
292 H Me 2-Br-4-F-Ph 2-Cl-4,6-di-F-Ph NH 431
293 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NMe ***
294 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NEt ***
295 H Me 2-Br-4-F-Ph 3,5-di-Cl-pyridin-2-yl NH 430
296 H Me 2-Cl-4-F-Ph 2,6-di-Cl-4-OMe-Ph NH 413
297 H Me 2,6-di-F-Ph 2-Cl-4,6-di-F-Ph NH 370
298 H Me 2-Cl-6-F-Ph 2-Cl-4,6-di-F-Ph NH 386
299 H Me 2-Cl-4-F-Ph 2,4-di-Cl-Ph NH 383
300 H Me 2,6-di-F-Ph 2,4,6-tri-F-Ph NH ***
301 H Me 2,6-di-F-Ph 2,6-di-F-4-CN-Ph NH ***
302 H Me 2,3-di-Cl-Ph 2,4-di-F-Ph NH 368
303 H Me 2,3-di-Cl-Ph 3,5-di-Cl-pyridin-2-yl NH 400
304 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NS(O)2Me ***
305 H Me 2-F-Ph 2,6-di-F-4-CN-Ph O ***
306 H Me 2-CF3-Ph 2,6-di-F-4-CN-Ph O ***
307 H Me 2-Cl-5-CF3-Ph 2,6-di-F-4-CN-Ph O ***
308 H Me 2-Cl-pyridin-3-yl 2,6-di-F-4-CN-Ph O ***
309 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NCH2OMe ***
310 H Me 2-Cl-4-OMe-Ph 2-F-4-CN-Ph O 372
311 H Me 2-Cl-4-OMe-Ph 2-Cl-4-CN-Ph O 388
312 H Me 2-Br-4-F-Ph 2,4-di-F-Ph NH 398
313 H Me 2-Br-4-F-Ph 2-Br-4-F-Ph NH 458
314 H Me 2-Br-4-F-Ph 2-Cl-4-F-Ph NH 414
315 H Me 2-Cl-Ph 2,4-di-F-Ph NH 334
316 H Me 2-Br-4-F-Ph 2,6-di-Cl-4-F-Ph NH 448
317 H Me 2-Br-4-F-Ph 4-OMe-Ph NH 392
318 H Me 2-Br-4-OMe-Ph 2-Cl-4-CN-Ph O 433
319 H Me 2-Br-4-OMe-Ph 2-F-4-CN-Ph O 418
320 H Me 2-Cl-Ph 3,5-di-Cl-pyridin-2-yl NH 368
321 H Me 2,6-di-F-Ph 3,5-di-Cl-pyridin-2-yl NH 369 Cmpd
No. Rl R2 Q1 Q2 X M.S
322 H Me 2-Cl-4-F-Ph 2-Cl-4-OMe-Ph NH 380
323 H Me 2-Br-4-F-Ph 2,6-di-Cl-4-OMe-Ph NH 459
324 H Me 2-Br-4-F-Ph 2-Cl-4-OMe-Ph NH 425
325 H Me 2-Cl-4-F-Ph 2-Cl-4-OEt-Ph NH 394
326 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph NCH2CN 409
327 H Me 2,6-di-Cl-Ph 2,4-di-Cl-Ph NH ***
328 H Me 2,4-di-F-Ph 3,5-di-Cl-pyridin-2-yl NH 369
329 H Me 2,5-di-F-Ph 2,6-di-F-4-CN-Ph O ***
330 H Me 2-Cl-4,6-di-F-Ph 2,6-di-F-4-CN-Ph NH 395
331 H Me 2-Cl-4-CN-Ph 2,4-di-F-Ph NH 359
332 H Me 2-Cl-4-CN-Ph 2-Cl-4,6-di-F-Ph NH 393
333 H Me 2,6-di-Cl-Ph 4-OMe-Ph NH ***
334 H Me 2,6-di-Cl-Ph 2-Cl-4-F-Ph NH ***
335 H Me 2-Cl-4-CN-Ph 2,6-di-F-Ph NH 359
336 H Me 2-Cl-4-CN-Ph 4-Cl-2,6-di-F-Ph NH 393
337 H Me 2,6-di-Cl-Ph 4-F-Ph NH ***
338 H Me 2-Cl-4-CN-Ph 2-Cl-4-F-Ph NH 375
339 H Me 2,6-di-Cl-Ph 2,4-di-F-Ph NH ***
340 H Me 2,6-di-Cl-Ph 2-Br-4-F-Ph NH ***
341 H Me 2,6-di-Cl-Ph 2,6-di-Cl-4-F-Ph NH ***
342 H Me 2-Cl-6-F-Ph 2-F-4-CN-Ph O 360
343 H Me 2,4-di-F-Ph 2-Cl-4,6-di-F-Ph NH 369
344 H Me 2-Cl-4-F-Ph 2-F-4-NO2-Ph NH 380
345 H Me 2-Cl-4-F-Ph 2-F-5-NO2-Ph NH 380
346 H Me 2,4-di-F-Ph 2-Br-4-F-Ph NH 398
347 H Me 4-Cl-2-F-Ph 2-F-4-CN-Ph O 360
348 H Me 2,4-di-F-Ph 2-Br-6-Cl-4-F-Ph NH 432
349 H Me 2,6-di-F-Ph 4-Cl-2,6-di-F-Ph NH 370
350 H Me 2-Cl-4-F-Ph 4-F-Ph CHOH 349
351 (Ex. 6) H Me 2-Cl-4-F-Ph 2,4-di-F-Ph CHOH **
352 H Me 2-Cl-4-F-Ph 2-Cl-4-F-Ph CHOH 383 Cmpd
Figure imgf000149_0001
353 H Me 2,4-di-Cl-Ph 2,6-di-F-Ph NH ***
354 H Me 2,4-di-Cl-Ph 2-Cl-4-F-Ph NH ***
355 H Me 2,4-di-Cl-Ph 4-OMe-Ph NH ***
356 H Me 2-Cl-4-F-Ph 2,3,6-tri-F-Ph CHOH 385
357 H Me 2,4-di-F-Ph 4-Cl-2,6-di-F-Ph NH 370
358 H Me 2,6-di-F-Ph 2-Cl-4-CN-Ph O 360
359 H Me 2,4-di-F-Ph 2-F-4-CN-Ph O 376
360 H Me 2-Br-4-F-Ph 4-Cl-2,6-di-F-Ph NH 432
361 H Me 2,6-di-F-Ph 2-F-4-CN-Ph O 344
362 H Me 2,4-di-Cl-Ph 2-Cl-4-CN-Ph O 394
363 H Me 2,4-di-Cl-Ph 2,6-di-Cl-4-F-Ph NH ***
364 H Me 2,4-di-F-Ph 4-Br-2,6-di-F-Ph NH 416
365 H Me 2-Cl-4-F-Ph 4-Br-2,6-di-F-Ph NH 432
366 H Me 2-Cl-4-F-Ph 4-Br-2-F-Ph NH 414
367 H Me 2-Cl-4-F-Ph 2,4-di-Cl-6-F-Ph NH 402
368 H Me 2,4-di-F-Ph 2,6-di-Cl-4-F-Ph NH
369 H Me 2-Cl-4-F-Ph 2,6-di-Cl-4-F-Ph NH
370 (Ex. 7) H Me 2-Cl-4-F-Ph 2,4-di-F-Ph C(=O) **
371 (Ex. 9) H Me 2,4,6-tri-F-Ph 2,6-di-F-4-NH2-Ph O **
372 H Me 2,4-di-F-Ph 2-Br-4-CN-Ph O
373 H Me 2,4-di-F-Ph 2-Cl-4-CN-Ph O
374 H Me 2,4-di-F-Ph 2,4-di-Cl-6-F-Ph NH 386
375 H Me 2,6-di-F-Ph 2,6-di-Cl-4-F-Ph NH
376 H Me 2,4-di-F-Ph 2-Br-4,6-di-F-Ph NH 416
377 H Me 2-Cl-4-F-Ph 2-Br-4,6-di-F-Ph NH 432
378 H Me 2,6-di-F-Ph 4-Br-2,6-di-F-Ph NH
379 H Me 2,6-di-F-Ph 2-Br-4,6-di-F-Ph NH
380 H Me 2-Cl-6-F-Ph 2-Br-4,6-di-F-Ph NH
381 H Me 2-Cl-4-F-Ph 2,6-di-F-4-Cl-Ph CHOH 402
382 H Me 2-F-4-CN-Ph 2-Cl-4,6-di-F-Ph NH
383 H Me 2-F-4-CN-Ph 2,6-di-F-4-Cl-Ph NH Cmpd
Figure imgf000150_0001
384 H Me 2-Cl-4-F-Ph 2-Cl-4,6-di-F-Ph CHOH
385 H Me 2,4-di-F-Ph 2-Br-4-F-Ph CHOH
386 H Me 2-Cl-4-F-Ph 2-Br-4-F-Ph CHOH
387 H Me 2-Cl-4-OH-Ph 2,4-di-F-Ph NH 350
388 H Me 2-Cl-4-OCH2CN-Ph 2,4-di-F-Ph NH 389
389 H Me 2,4-di-F-Ph 4-Br-4-F-Ph NH 396
390 H Me 2,4-di-F-Ph 4-Br-2,6-di-Cl-Ph NH 448
391 H Me 2,4-di-Cl-Ph 2-Cl-4,6-di-F-Ph NH ***
392 H Me 2,4-di-Cl-Ph 4-Cl-2,6-di-F-Ph NH ***
393 H Me 2-Cl-4-F-Ph 4-OEt NH 360
394 H Me 2-Cl-4-F-Ph 4-C1-2-F O 369
395 H Me 2,4-di-F-Ph 2-F-4-CN-Ph O 344
396 H Me 2,4-di-F-Ph 4.Cl-2-F-Ph NH 352
397 H Me 2,4-di-F-Ph 2,4-di-Cl-6-F-Ph NH 386
398 H Me 2,6-di-F-Ph 4.Cl-2-F-Ph NH 352
399 H Me 2,6-di-F-4- 2-F-4-CN-Ph O 445
(OCH2CH2CH2NMe2)-
Ph
400 H Me 4-Cl-Ph 2,6-di-F-Ph NH 334
401 H Me 2-Cl-4-F-Ph 4-Cl-2,5-di-F-Ph NH 386
402 H Me 2-Br-4-F-Ph 4-Br-2,6-di-F-Ph NH 474
403 H Me 2-Cl-4-F-Ph 4-Br-2,6-di-Cl-Ph NH 464
404 H Me 2-Cl-4-F-Ph 2-Cl-4,5-di-F-Ph NH 386
405 H Me 2,4-di-F-Ph 2,4,6-tri-Cl-Ph NH 404
406 H Me 2,4-di-F-Ph 2-Br-4,6-di-F-Ph NH 416
407 H Me 2,4-di-F-Ph 4-Br-2-Cl-Ph NH 414
408 H Me 2-Br-4-F-Ph 4-Br-2,6-di-Cl-Ph NH 508
409 H Me 2-Br-4-F-Ph 4-Br-2-F-Ph NH 458
410 H Me 2-Cl-4-F-Ph 2,4,6-tri-Cl-Ph NH 420
411 H Me 2-Cl-4-F-Ph 2-Br-4,6-di-F-Ph NH 432
412 H Me 2-Cl-4-F-Ph 4-Br-2-Cl-Ph NH 430
413 H Me 2-Br-4-F-Ph 4-Br-2-Cl-Ph NH 474 Cmpd
No. Rl R2 Q1 Q2 X M.S
414 H Me 2-Br-4-F-Ph 2,4,6-tri-Cl-Ph NH 464
415 H Me 2,4-di-F-Ph 4-F-2-I-Ph NH 444
416 H Me 2,4-di-F-Ph 2,4,6-tri-Me-Ph NH 342
417 H Me 2-Cl-4-F-Ph 4-Cl-2,5-di-F-Ph NH 386
418 H Me 2-Cl-4-F-Ph 2-Cl-4,5-di-F-Ph NH 386
419 H Me 2-Cl-4-F-Ph 2,4-di-F-Ph CHOAc 409
420 H Me 2-Cl-4-F-Ph pyridin-2-yl CHOH 332
421 H Me 2-Cl-4-F-Ph 4-Cl-2-F-Ph CHOH 384
422 H Me 2-Cl-4-F-Ph 2,4,6-tri-F-Ph CHOH 385
423 H Me 2-Cl-4-F-Ph 2-F-4-CN-Ph CHOH 374
424 H Me 2,4-di-F-Ph 4-01-2-F-O-I-Ph NH 478
425 H Me 2-C1-4- 2,4-di-F-Ph NH 421
(OCH2CH2CH2NHMe)-
Ph
426 H Me 2-C1-4- 2,4-di-F-Ph NH 422
(OCH2CH2CH2OMe)-Pl 1
427 H Et 2-Cl-4-F-Ph 2,4-di-F-Ph NH 366
428 H Et 2-Cl-4-F-Ph 2,4-di-F-Ph CHOH 382
* 1H NMR 1 iata found in Index Table B
** AP+ data or ^H NMR data found in the Synthesis Examples
*** MP data found in Index ' Table C
INDEX TABLE B
Cmpd No. 1H ] NMR Data (CDCI3 solution unless indicated otherwise)a δ 7.11 (m, IH), 6.99 (m, IH), 6.75-6.85 (m, 3H), 6.58 (m, IH), 6.40 (m, IH), 3.58 (s, 3H), 3.07 (s, 3H), 2.21 (s, 3H). a ^H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet and (m) -multiple!
INDEX TABLE C
Cmpd No. Melting Point b Cmpd No. Melting Point Cmpd No. Melting Point
110 85-87 197 115-117 271 132-135 111 165-167 198 106-108 272 132-134 Cmpd No. Melting Point
273 152-153
274 141-143
275 168-171
276 115-117
277 131-134
278 112-114
281 49-52
289 148-150
290 181-183
291 146-149
293 116-118
294 113-115
300 178-180
301 168-170
304 186-191
305 101-105
306 134-138
307 161-166
308 142-145
309 118-123
327 118-120
329 98-100
333 177-179
334 117-119
337 186-188
339 135-136
340 137-139
341 151-153
353 169-171
354 111-113
355 90-92
363 229-231
391 181-183
392 155-157
Figure imgf000152_0001
b Melting point data are 0C. BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Tests A-J: the test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-J. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of 500 g/ha. Unless otherwise indicated, the rating values indicate a 200 ppm test suspension was used. (An asterisk "*" next to the rating value indicates a 40 ppm test suspension was used.) TEST A
Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 0C for 24 h. After a short drying period, the test suspension was sprayed to the point of run-off on the grape seedlings and then moved to a growth chamber at 20 0C for 4 days, after which time the test units were placed back into a saturated atmosphere at 20 0C for 24 h. Upon removal, visual disease ratings were made.
TEST B
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in saturated atmosphere at 20 0C for 48 h, and then moved to a growth chamber at 24 0C for 3 additional days, after which time visual disease ratings were made.
TEST C
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Alternaria solani
(the causal agent of tomato early blight) and incubated in a saturated atmosphere at 27 0C for
48 h, and then moved to a growth chamber at 20 0C for 5 days, after which time visual disease ratings were made.
TEST D The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 5 days, after which time visual disease ratings were made. TEST E
The test suspension was sprayed to the point of run-off on creeping bent grass
(Agrostis sp.) seedlings. The following day the seedlings were inoculated with a bran and mycelial slurry of Rhizoctonia solani (the causal agent of turf brown patch) and incubated in a saturated atmosphere at 27 0C for 48 h, and then moved to a growth chamber at 27 0C for
3 days, after which time disease ratings were made.
TEST F
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of Septoria glume blotch) and incubated in a saturated atmosphere at 24 0C for 48 h, and then moved to a growth chamber at 20 0C for 6 days, after which time visual disease ratings were made.
TEST G
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24 0C for 48 h. and then the seedlings were moved to a growth chamber at 20 0C for 19 additional days, after which time visual disease ratings were made.
TEST H Wheat seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 2 days. At the end of this time the test suspension was sprayed to the point of run-off, and then the seedlings were moved to a growth chamber at 20 0C for 6 days after which time visual disease ratings were made. TEST I
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 7 days, after which time visual disease ratings were made
TEST J
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f. sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 0C for 8 days, after which time visual disease ratings were made. Results for Tests A-J are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results.
TABLE A
Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
1 0 99 0 0 47 0 99 - 0 98
2 8 1 0 0 0 0 0 - 0 0
3 6 0 25 9 0 0 13 - 0 99
4 29 87 46 0 0 0 98 - 53 97
5 36 0 25 0 0 0 0 - 0 0
6 65 10 23 0 0 0 0 - 0 93
7 29 99 0 0 63 0 100 - 74 92
8 55 99 54 0 99 0 100 - 97 99
9 - 99 0 0 55 0 100 - 98 97
10 - 47 0 0 0 0 0 - 0 0
11 - 99 99 0 99 0 100 - 99 100
12 - 99 93 0 99 0 100 - 99 100
13 - 99 100 0 98 64 100 - 100 99
14 - 98 0 - 0 99 - 99 98
15 - 99 67 - - 73 99 - 98 99
16 - 60 0 - - 0 47 48 28 0
17 - 100 100 - - 93 97 96 100 100
18 - 99 100 - 99 95 99 100 100
19 - 100 85 - - 0 96 0 92 98
20 - 100 99 - - 100 100 79 100 99
21 - 98 100 - - 97 - - 100 99
22 - 90 85 - 90 94 9 94 100
23 - 98 100 - - 99 93 92 100 100
24 - 98 100 - - 0 94 9 97 100
25 - 100 0 - - 0 100 0 94 79
26 - 99 83 - 0 100 0 99 100
27 - 99 88 - - 0 95 0 25 87
28 - 99 0 - - 0 96 7 91 0
29 - 94 0 - - 0 98 0 46 0
30 - 7 0 - 0 41 0 79 0
31 - 99* 98* - - 0* 47* 15* 79* 60*
32 - 99 0 - - 0 96 0 99 97
33 0 0 0 95 0 18 0 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
34 - 100* 97* - - O* 96* O* 76* O*
35 - 100 O - - O 95 O 97 100
36 - 100 O - - O 96 O 96 98
37 O O O O O O 3 - O 0
38 - 99 9 - O 97 O 99 99
39 - 100 99 - - O 99 99 99 99
40 - 99 O - - O 94 92 99 99
41 - 100 99 - - 90 94 O 100 99
42 - 100 O - O 93 O 94 82
43 - 76 O - - O 97 66 82 99
44 - 82 O - - O 96 7 9 0
45 - 100 100 - - 100 100 7 100 100
46 - 99 100 - 99 100 37 100 99
47 - 100* 87* - - O* 99* 37* 96* 99*
48 - 100 78 - - O 99 O 98 98
49 - 100 17 - - 35 99 O 89 79
50 - 99 57 - O 100 O 98 99
51 - 100 O - - O 100 O 89 78
52 - 54 O - - O 97 O 92 64
53 - O O - - O O O O 0
54 - 96 O - O 41 O 95 95
55 - 6 O - - O 98 O 41 73
56 - 43 O - - O 99 O 28 64
57 - 98 O - - O 94 85 85 0
58 - 98 100 - 89 98 82 100 100
59 - 94 O - - O 88 O 68 0
60 - 75 O - - O 97 59 79 0
61 - 97 O - - O 99 O 38 73
62 - 99 98 - 84 98 98 99 99
63 - O O - - O O O O 0
64 - 97 80 - - O 100 O 95 98
65 - O O - - O 1 O 58 0
66 - 100 99 - O 100 6 100 99
67 - 95 O - - O 99 24 95 86
68 - O O - - O O 6 O 0
69 - 100 73 - - 60 99 91 99 100
70 99 O O 99 41 85 98 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
71 93 O O 96 0 91 67
72 O O O 0 59 0 0
73 100 99 64 100 88 100 99
74 O O O 25 4 0 0
75 100 98 98 99 95 99 97
76 100 O O 98 6 0 0
77 99 O O 95 6 97 0
78 99 82 O 98 0 89 91
79 99 O O 99 0 55 0
80 100 O O 99 18 86 89
81 97 O O 0 0 27 0
82 100 100 40 99 0 68 13
83 100 100 89 99 99 96 94
84 100 100 78 100 98 100 99
85 O O O 17 0 19 0
86 O O O 48 0 0 0
87 100 100 95 98 85 99 100
88 100 100 99 98 95 99 100
89 99 O O 99 0 0 97
90 99 95 84 100 0 98 100
91 100 99 95 99 0 100 100
92 100 100 99 100 41 99 100
93 41 O O 77 0 9 0
94 99 70 29 98 0 9 0
95 99 16 O 97 0 0 0
96 99 99 99 100 9 99 100
97 100 99 95 100 0 99 99
98 100 17 69 100 26 99 99
99 100 99 100 99 40 100 100
100 38 O 0 48 0 41 0
101 100 99 100 100 99 99 100
102 100 100 98 99 0 100 98
103 100 64 0 95 0 91 0
104 100 99 97 99 99 99 100
105 23 O 0 73 9 0 72
106 100 99 90 100 82 99 100
107 99* O* 0* 99* 8* 24* 0* Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
108 97 O O 98 0 16 97
109 100 99 97 100 99 100 100
110 99 66 98 99 0 97 94
111 99 75 90 99 0 97 99
112 100 98 99 99 53 100 100
113 99 47 O 100 8 95 48
114 99 24 69 99 8 99 84
115 99 O O 100 0 91 0
116 100 94 73 100 16 97 99
117 99 97 82 100 11 98 97
118 100 100 98 100 99 100 99
119 100 O O 100 16 99 96
120 100 99 94 100 0 99 99
121 100 86 82 99 83 100 97
122 O O O O 11 0 0
123 99 O 40 99 - 80 0
124 100 78 60 99 - 96 94
125 100 67 60 99 - 92 0
126 99 96 60 100 0 94 0
127 70 O O 99 0 68 0
128 100 100 97 99 66 100 100
129 99 O O 96 0 0 0
130 97 O O 99 0 19 0
131 99 O O 98 0 86 94
132 99 O O 100 0 94 92
133 100 100 60 99 0 100 94
134 99 O O 99 0 41 0
135 O O O 97 16 74 95
136 99 71 86 99 0 99 100
137 96 97 78 99 8 100 100
138 99 96 84 99 38 100 98
139 100 86 100 100 69 99 100
140 99 94 87 99 0 96 97
141 99 99 98 100 0 99 100
142 33 13 20 99 0 95 90
143 99 99 100 100 63 100 100
144 99 9 40 99 0 98 91 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
145 96 98 100 100 88 100 100
146 99 O O 99 0 97 56
147 99 88 100 100 0 98 92
148 99 99 100 100 61 100 99
149 100 98 100 100 99 100 100
150 19 O 60 7 0 74 50
151 99 9 O 96 0 54 64
152 100 82 87 99 9 97 99
153 100 O 73 100 0 96 98
154 99 99 97 100 41 100 100
155 100 99 100 100 92 100 99
156 94 O O 73 0 41 47
157 O O O 0 0 54 73
158 100 O O 99 18 99 98
159 99 O O 100 74 99 100
160 98 99 O 99 8 100 100
161 98 100 O 100 95 100 98
162 99 O O 99 8 98 94
163 O 9 O 83 0 88 0
164 49 57 O 99 15 9 97
165 O O O 52 8 0 99
166 O O O 97 0 68 96
167 75 O O 0 0 0 0
168 14 O O 33 0 0 0
169 24 O O 85 0 0 0
170 100 99 99 98 0 100 99
171 100 97 O 97 68 99 100
172 100 100 87 100 0 99 100
173 100 86 O 98 0 83 100
174 100 99 O 96 0 97 99
175 100 99 82 96 93 99 100
176 100 71 O 96 0 68 100
177 100 100 73 98 0 83 100
178 100 100 80 98 0 83 100
179 100 99 73 95 0 93 100
180 100 99 O 98 0 68 100
181 94 44 O 100 0 60 98 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
182 97 99 87 100 0 95 99
183 97 100 67 99 27 94 99
184 97 O O 99 0 82 98
185 O O O 100 0 74 98
186 O O O 99 0 54 93
187 33 O O 20 0 9 13
188 87 O O 100 0 97 97
189 99 100 80 100 99 99 98
190 99 99 80 100 94 100 99
191 98 100 O 100 0 97 99
192 97 100 73 100 0 99 99
193 99 100 O 100 32 99 100
194 97 86 O 99 0 91 99
195 100 97 60 100 0 98 97
196 99 94 73 100 9 98 98
197 97 O 95 99 0 79 96
198 97 68 O 100 0 94 97
199 99 86 O 99 0 68 98
200 82 O O 97 0 0 94
201 99 97 20 100 18 97 99
202 99 O O 99 0 28 99
203 99 O O 98 0 96 100
204 100* 77* O* 99* 0* 86* 99*
205 100 17 O 99 0 91 100
206 99 99 84 99 41 99 100
207 100 93 64 100 0 99 100
208 100 100 99 100 0 99 99
209 O O O 0 0 0 97
210 O O O 100 99 94 99
211 77 O O 99 0 17 96
212 O 17 - 98 0 - -
213 97 30 O 85 94 96 100
214 98 51 O 100 9 99 100
215 89 O O 98 0 94 99
216 96 O O 76 0 26 99
217 75 O O 83 40 79 99
218 94 O O 99 17 92 87 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
219 70 O O O 17 O 0
220 98 97 40 98 40 99 100
221 98 94 82 100 17 99 100
222 99 99 O 100 88 99 100
223 96 9 99 100 O 100 100
224 99 51 O 100 17 91 100
225 65 O O 99 O 79 98
226 99 O O 96 28 91 100
227 87 O O 99 O 74 98
228 99 99 O 99 O 80 99
229 99 17 O 99 O 91 98
230 99 99 O 100 O 97 100
231 98 34 O 100 O 86 100
232 100 99 99 100 O 100 100
233 100 99 99 100 O 100 100
234 99 O O 99 O 92 84
235 84 O O 17 O O 79
236 97 O O 96 O 68 97
237 99 O O 97 O 68 97
238 99 O O O 53 9 43
239 99 95 O 67 O 68 100
240 100 99 O 99 O 99 100
241 99 99 O 100 97 100 100
242 99 37 O 100 O 91 100
243 100 64 O 100 O 97 100
244 82 O O 91 O 0 96
245 90 O O 97 O 68 93
246 99 51 O 100 O 80 100
247 100 99 60 100 O 99 100
248 99 26 73 100 O 99 100
249 40 O O 99 O 96 100
250 98 O O 77 O 86 100
251 99 O O 98 O 86 100
252 100 97 O 100 O 100 100
253 99 O O O O 0 76
254 100 O O 84 O 0 64
255 100 O O O O 0 39 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
256 - 99 99 - - 96 100 O 99 100
257 - 100 99 - - O 100 O 97 98
258 - 41 9 - - O 89 O 68 90
259 - 98 9 - - O 100 O 86 97
260 - O O - - O O O 0 0
261 - O O - - O O O 0 47
262 - 99 51 - - O O O 68 99
263 - 100 98 - - O 100 O 98 100
264 - 100 98 - - O 92 O 99 98
265 - 100 99 - - 78 100 90 100 100
266 - 100 100 - - 98 100 0 100 100
267 - 100 79 - - 60 100 0 96 93
268 - 95 93 - - O 99 0 74 0
269 - 80 O - - O 67 8 0 0
270 - 92 86 - - O 91 8 0 81
271 - 100 99 - - 99 100 0 99 98
272 - 100 97 - - 99 99 0 99 99
273 - O O - - O 72 0 27 43
274 - 8 O - - O 96 8 0 69
275 - 97 46 - - O 99 8 97 99
276 - 100 99 - - 98 100 31 100 100
277 - 100 O - - O 100 0 96 98
278 - 99 O - - O 99 0 82 100
279 - 100 99 - - O 100 8 98 100
280 - 99 O - - O 96 8 18 87
281 - 98 44 - - O - 0 94 98
282 - 99 98 - - O - 0 99 100
283 - 99 65 - - O - 9 99 100
284 - 99 99 - - 100 - 28 100 100
285 - 98 O - - 60 - 9 99 99
286 - 98* 85* - - 60* - 100* 100* 100*
288 9 99 52 O 92 O - - 74 92
289 - 100 O - - O 99 0 96 97
290 - 100 99 - - 87 100 0 100 100
291 - 99 O - - O 98 0 85 43
292 - 100 99 - - 96 100 92 100 100
293 O 97 47 O 99 O 94 99 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
294 O 98 O O 80 O - - 0 84
296 - 99 O - - O 100 0 99 -
297 - 100 99 - - 90 100 0 100 100
298 - 100 93 - - 87 100 0 100 100
299 - 100 95 - - 51 41 100 100
300 - 100 99 - - 82 100 9 99 100
301 - 99 87 - - 87 100 0 98 99
302 - 99* O* - - O* 99* 0* 18* 97*
303 - 99 O - - O 98 0 92 71
304 - O O - O O 16 - 0 0
305 - 99 99 - - 94 100 0 99 99
306 - 7 O - - O 93 0 28 64
307 - O O - - O 0 0 0 0
308 - 81 O - - O 98 9 100 0
309 - 97 61 - 92 60 100 - 0 99
310 - 100 99 - - 99 100 0 99 96
311 - 100 O - - 60 100 0 99 91
313 - 100 97 - - 51 100 91 100 100
314 - 100 95 - - O 100 94 100 100
315 - 99 99 - - O 100 0 96 100
316 - 99 O - - O - 9 99 96
318 - 99 O - - O 100 0 97 89
319 - 92 88 - - 100 100 0 99 95
320 - 99 67 - - O 100 0 99 98
321 - 100 99 - - 78 100 9 99 100
322 - 100 93 - - O 100 99 100 100
323 - 98 O - - O 98 0 94 -
324 - 99 83 - - O 100 63 99 99
325 - 100 O - - O 100 0 97 99
326 8 99 99 O 99 73 100 - 99 94
327 - 99 O - - O 100 0 96 99
328 - 100 86 - - O 100 0 98 100
329 - 100 99 - - 69 100 0 100 100
331 - 100 80 - - 73 100 8 100 97
333 - 100 O - - O 100 9 74 0
334 - 100 O - - O 100 0 97 100
336 100 97 95 100 94 100 99 Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
337 99 O O 99 9 41 98
338 100 37 40 100 8 100 99
339 100 O O 100 0 98 100
340 99 O O 100 0 91 100
341 99 O O 99 0 99 93
342 100 33 99 100 0 100 100
343 100 100 97 100 91 100 100
344 100 40 87 100 62 100 100
345 O O O 67 0 9 0
348 100 80 94 100 19 100 100
350 99 9 O - 9 96 0
351 100 99 92 - 96 100 99
353 97 17 O 99 3 99 99
354 99 O O 100 82 98 100
355 99 O O 100 3 91 0
356 100 O O - 100 100 0
357 100 86 87 100 0 99 100
358 99 O O 100 0 97 97
359 100 99 97 100 0 100 99
360 100 97 95 100 79 100 100
361 100 90 O 100 0 100 100
362 100 O O 100 0 96 96
363 65 O O 99 0 96 43
364 99 97 88 100 0 99 100
365 100 99 64 100 74 100 100
366 100 58 O 100 9 99 100
367 100 100 100 - 100 100 100
369 100 66 O - 17 100 99
389 100 9 O - 68 98 99
391 100 99 73 - 31 99 99
403 99 O O 99 100 99
"Cmpd No. " means compound number and refers to the same compound number as in Index Table A.

Claims

CLAIMSWhat is claimed is:
1. A compound selected from Formula 1, JV-oxides and salts thereof,
Figure imgf000165_0001
wherein
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6- membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from
C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C3-C12 cycloalkyl or C3-C12 cycloalkenyl, each optionally substituted with up to 5 substituents independently selected from R3; X is O, S(O)m, NR4, CR15R16, C(O) or C(=S);
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3- C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or
C2-C5 alkoxyalkyl; or R1 is phenyl optionally substituted with up to 3 R8; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R915 on nitrogen atom ring members;
Rla is H; or Rla and R1 are taken together with the carbon atom to which they are attached to form a cyclopropyl ring optionally substituted with up to 2 substituents independently selected from halogen and methyl; R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, halomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C2-C3 alkylcarbonylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfmyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C1-C2 alkylsulfonyloxy, C1-C2 haloalkylsulfonyloxy, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, hydroxy, formyl, C2-C3 alkylcarbonyl, C2-C3 alkylcarbonyloxy,
-SF5, -SCN, C(=S)NR19R20 or -U-V-T; R4 is H, formyl, C2-C5 alkenyl, C3-C5 alkynyl, C3-C7 cycloalkyl, -SO3-M+, -
S(=O)tR10, -(C=W)R11, NH2 or OR21; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
R6 and R7 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C4-Cg cycloalkylalkyl and C4-Cg alkylcycloalkyl; or R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O)n and NR13; each R8, R9a and R9b is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano, nitro, SCH3, S(O)CH3 and S(O)2CH3;
R10 is C1-C6 alkyl or C1-C6 haloalkyl; each R11 is independently C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxyalkyl, C2-C7 alkylaminoalkyl, C2-Cg dialkylaminoalkyl, C1-C6 alkylthio or C2-C7 alkylthioalkyl; each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl or cyano; R13 is H, C1-C3 alkyl or C2-C3 haloalkyl; each R14 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl;
R15 is H, C1-C4 alkyl or OR18;
R16 is C1-C4 alkyl or OR18; or
R15 and R16 are taken together as -OCH2CH2O-; each R18 is independently H, formyl, C3-C7 cycloalkyl, -SO3-M+ or -(C=W)R11; or
C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12; each R19 and R20 is independently H or CH3;
R21 is H, formyl, C3-C7 cycloalkyl, -SO3-M+ or -(C=W)R11; or C1-C6 alkyl or C1-
C6 haloalkyl, each optionally substituted with up to 2 R12; each U is independently O, S(=O)W, NR22 or a direct bond; each V is independently C1-C6 alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy; each T is independently cyano, NR23aR23b, OR24 or S(=O)yR25 each R22 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2- C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R23a and R23b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or a pair of R23a and R23b attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R26; each R24 and R25 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-Cg cycloalkylcarbonyl, C4-Cg cycloalkoxycarbonyl, C4-Cg (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R26 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; each W is independently O or S; each M+ is independently a cation; m is 0, 1 or 2; n is 0, 1 or 2; t is 0, 1 or 2; each u and v are independently 0, 1 or 2 in each instance of S(=O)U(=NR14)V, provided that the sum of u and v is 0, 1 or 2; each w is independently 0, 1 or 2; and each y is independently 0, 1 or 2; provided that: when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from -U-V-T wherein U is a direct bond, V is C(=O) and T is NR23aR23b or OR24, then X is other than NR4. 2. A compound of Claim 1 wherein:
Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3; provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano; Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1 ,
2 or 3 substituents independently selected from R3, provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano; X is O, NR4, C(=O) or CR15R16; R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; Rla is H;
R2 is CH3, CH2CH3, Cl or Br; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfϊnyl, C1-C3 haloalkylsulfϊnyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(=S)NH2 and -U-V-T; R4 is H, foπnyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
R5 is C1-C6 alkyl;
R6 is H or C1-C6 alkyl; R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl; or
R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13; each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy or cyano;
R13 is H or CH3;
R15 is H or CH3; and
R16 is OR18.
3. A compound of Claim 2 wherein Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
Q2 is phenyl or pyridinyl, each substituted with 1 , 2 or 3 substituents independently selected from R3;
R1 is H, halogen or C1-C6 alkyl; R2 is CH3, Cl or Br; each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and -U-V-T;
R4 is H, foπnyl, C3-C7 cycloalkyl or -SR10; or C1-C6 alkyl substituted with one R12; each R12 is independently cyclopropyl, -OCH3 or cyano; R15 is H; each U is independently O or NH; each V is C2~C4 alkylene; each T is independently NR23aR23b or OR24; each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and each R24 is independently H, C1-C6 alkyl or C1-C6 haloalkyl.
4. A compound of Claim 3 wherein at least one of Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3; R1 is H or CH3; R2 is CH3;
R4 is H; each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl,
C1-C3 alkoxy and C1-C3 haloalkoxy; and R18 is H.
5. A compound of Claim 4 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3; X is O, NR4 or CR15R16; R1 is H; each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; and R4 is H.
6. A compound of Claim 5 wherein each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
7. A compound of Claim 6 wherein X is O or NH; and each R3 is independently selected from F, Cl, Br, cyano and methoxy.
8. A compound of Claim 1 which is selected from the group: 4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-
5-amine, Λ/-(4-chlorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-l,3-dimethyl-lH-pyrazol-
5-amine,
4-(2,6-difluoro-4-methoxyphenyl)-Λ/-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol- 5-amine,
4-(2,6-difluoro-4-methoxyphenyl)- 1 ,3-dimethyl-Λ/-(2,4,6-trifluorophenyl)- lH-pyrazol-
5-amine, Λ/-(2,6-difluoro-4-methoxyphenyl)-4-(3,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-
5-amine, 4-(2,4-difluorophenyl)-l,3-dimethyl-Λ/-(2,4,6-trifluorophenyl)-lH-pyrazol-5-amine,
4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]- 3,5-difluorobenzonitrile, 4-[[4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-5-yl]oxy]-3-fluorobenzonitrile,
4-(2-chloro-4-fluorophenyl)-Λ/-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine,
4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-
3 -fluorobenzonitrile, 3-chloro-4-[[4-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile,
4-(2-chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazole-
5 -methanol,
N,4-bis(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine, Λ/-(2-chloro-4-fluorophenyl)-4-(2-chloro-6-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol- 5-amine,
Λ/-(2-chloro-4,6-difluorophenyl)-4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(2-chloro-4,6-difluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(4-chloro-2,6-difluorophenyl)-4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(4-chloro-2,6-difluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine,
3-chloro-4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol- 5-yl]oxy]benzonitrile,
4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]amino]-3,5-difluoro- benzonitrile, 4-[[4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-2,5-difluoro- benzonitrile, Λ/-(2-chloro-4-fluorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)- 1 ,3-dimethyl- lH-pyrazol-5-amine, α,4-bis(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole-5-methanol, Λ/-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazole-5-amine, Λ/-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine, Λ/-(2,6-dichloro-4-fluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine,
3-chloro-4-[5-[(2-chloro-4,6-difluorophenyl)amino]-l,3-dimethyl-lH-pyrazol-4-yl]- benzonitrile,
3-chloro-4-[5-[(4-chloro-2,6-difluorophenyl)amino]-l,3-dimethyl-lH-pyrazol-4-yl]- benzonitrile, Λ/-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-
5-amine, 4-(2-chloro-4-fluorophenyl)-Λ/-(2,4-dichloro-6-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine, 4-(2-chloro-4-fluorophenyl)-Λ/-(2,6-dichloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine, 4-[[4-(2-bromo-4-fluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-5-yl]oxy]-
3 -fluorobenzonitrile,
Λ/-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol- 5-amine,
4-(2-bromo-4-fluorophenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-
5-amine, Λ/-(4-bromo-2,6-difluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, 4-[[4-(2-bromo-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]-3,5-difluoro- benzonitrile, 4-(2-bromo-4-fluorophenyl)-Λ/-(2-chloro-4,6-difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine,
4-(2-bromo-4-fluorophenyl)-Λ/-(4-chloro-2,6-difluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine,
Λ/-(4-bromo-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine,
3-bromo-4-[[4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile, 3-chloro-4-[[4-(2,4-difluorophenyl)-l,3-dimethyl-lH-pyrazol-5-yl]oxy]benzonitrile, Λ/-(2,4-dichloro-6-fluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(2,6-dichloro-4-fluorophenyl)-4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine,
Λ/-(2-bromo-4,6-difluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol- 5-amine,
Λ/-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine, Λ/-(4-bromo-2,6-difluorophenyl)-4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(2-bromo-4,6-difluorophenyl)-4-(2,6-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazol-
5-amine, Λ/-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-6-fluorophenyl)-l,3-dimethyl- lH-pyrazol-5-amine, α-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazole-5-methanol, 4-[5-[(2-chloro-4,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]-
3 -fluorobenzonitrile, 4-[5-[(4-chloro-2,6-difluorophenyl)amino]- 1 ,3-dimethyl- lH-pyrazol-4-yl]-
3 -fluorobenzonitrile, α-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl- lH-pyrazole-5-methanol, α-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)- 1 ,3-dimethyl- lH-pyrazole- 5 -methanol, and α-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazole-
5-methanol.
9. The compound of Claim 1 which is 4-(2,6-difluoro-4-methoxyphenyl)- 1 ,3-dimethyl-JV-(2,4,6-trifluorophenyl)- lH-pyrazol-5-amine.
10. A fungicidal composition comprising (a) a compound of Claim 1; and (b) at least one other fungicide.
11. A fungicidal composition comprising: (a) a compound of Claim 1; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
12. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Claim 1.
13. A composition comprising a compound of Claim 1, and at least one invertebrate pest control compound or agent.
14. A compound of Formula 2 or a salt thereof
Figure imgf000173_0001
wherein
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6- membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)U(=NR14)V, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C3-C12 cycloalkyl or C3-C12 cycloalkenyl, each optionally substituted with up to 5 substituents independently selected from R3;
X is NH;
R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, halomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl; each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C2-C3 alkylcarbonylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfϊnyl, C1-C3 haloalkylsulfmyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C1-C2 alkylsulfonyloxy, C1-C2 haloalkylsulfonyloxy, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, hydroxy, formyl, C2-C3 alkylcarbonyl, C2-C3 alkylcarbonyloxy, -SF5, -SCN, C(=S)NR19R20 or -U-V-T; each R14 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl; each R19 and R20 is independently H or CH3; each U is independently O, S(=O)W, NR22 or a direct bond; each V is independently C1-Cg alkylene, C2-C6 alkenylene, C3-Cg alkynylene, C3-Cg cycloalkylene or C3-Cg cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-Cg haloalkyl, C1-Cg alkoxy and C1-Cg haloalkoxy; each T is independently cyano, NR23aR23b, OR24 or S(=O)yR25 each R22 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2-
C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R23a and R23b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl,
C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or a pair of R23a and R23b attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R26; each R24 and R25 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8
(cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R26 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; each u and v are independently 0, 1 or 2 in each instance of S(=O)U(=NR14)V, provided that the sum of u and v is 0, 1 or 2; each w is independently 0, 1 or 2; and each y is independently 0, 1 or 2; provided that:
(a) when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from -U-V-T wherein U is a direct bond and T is NR23aR23b or OR24, then V is other than C(=O); and
(b) when Q1 is phenyl and Q2 is 4-(trifluoromethyl)phenyl, then R2 is other than methyl.
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