[go: up one dir, main page]

WO2010134628A1 - Amide compound and use thereof for control of plant diseases - Google Patents

Amide compound and use thereof for control of plant diseases Download PDF

Info

Publication number
WO2010134628A1
WO2010134628A1 PCT/JP2010/058856 JP2010058856W WO2010134628A1 WO 2010134628 A1 WO2010134628 A1 WO 2010134628A1 JP 2010058856 W JP2010058856 W JP 2010058856W WO 2010134628 A1 WO2010134628 A1 WO 2010134628A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
halogen
carboxylic acid
optionally substituted
amino
Prior art date
Application number
PCT/JP2010/058856
Other languages
French (fr)
Japanese (ja)
Inventor
有本翔
大平大輔
久保田真由美
倉橋真
Original Assignee
住友化学株式会社
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
Application filed by 住友化学株式会社 filed Critical 住友化学株式会社
Publication of WO2010134628A1 publication Critical patent/WO2010134628A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole 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
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles

Definitions

  • the present invention relates to an amide compound and its use for controlling plant diseases.
  • An object of the present invention is to provide a compound having an excellent plant disease control effect.
  • the present inventors have found that the amide compound represented by the following formula (1) has an excellent plant disease control effect and completed the present invention. did. That is, the present invention is as follows.
  • R 1 is hydrogen, halogen, cyano group, nitro group, —O—R 4 group, —S—R 4 group, —S ( ⁇ O) —R 4 group, —S ( ⁇ O) 2 —R 4 group, A methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a C3-C5 cycloalkyl group, fluoromethyl Represents a group or a difluoromethyl group, p represents any integer from 0 to 5;
  • R 2 is a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D , Phenyl group, halogen, cyano group, nitro group, —O—R 5 group, —S—R 5 group, —C ( ⁇
  • R 5 and R 6 are independently hydrogen, a C1-C10 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and one or more groups selected from group D.
  • R 2 may be the same as or different from each other.
  • Group A represents a group consisting of chlorine, bromine, iodine, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group
  • Group B represents a group consisting of halogen, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group
  • Group C is a C3-C10 cycloalkyl group optionally substituted with one or more groups selected from Group D, a halogen, a cyano group, a C1-C4 alkoxy group optionally substituted with halogen, or a halogen-substituted group
  • an salt thereof (hereinafter referred to as the present compound).
  • R 1 is hydrogen and R 2 is fluorine or bromine.
  • a plant disease control agent comprising the amide compound or salt thereof according to any one of [1] to [10] and an inert carrier.
  • a method for controlling plant diseases comprising a step of applying an effective amount of the amide compound or salt thereof according to any one of [1] to [10] to a plant or soil where the plant grows.
  • Halogen means fluorine, chlorine, bromine and iodine.
  • methyl group substituted with one or more groups selected from group A include, for example, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, cyanomethyl group, dicyanomethyl group, Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group Butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfiny
  • Examples of the “C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B” include, for example, an ethyl group, a 2-fluoroethyl group, a 2,2,2-trifluoroethyl group, Perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group, Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodo Propyl group, Isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoroisopropyl group, Butyl group, 4-fluorobutyl
  • Examples of the “C3 to C5 cycloalkyl group” include a cyclopropyl group, a cyclobutyl group, and a cyclopentyl group.
  • Examples of the “C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group, Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group, Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chlor
  • C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D examples include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl.
  • cyclodecyl group methylcyclopropyl group, 1,1-dimethylcyclopropyl group, ethylcyclopropyl group, propylcyclopropyl group, butylcyclopropyl group, pentylcyclopropyl group, 2-methylcyclohexyl group, 2-ethylcyclohexyl group 2-propylcyclohexyl group, 2-butylcyclohexyl group, 2-pentylcyclohexyl group, 3-methylcyclohexyl group, 3-ethylcyclohexyl group, 3-propylcyclohexyl group, 3-butylcyclohexyl group, 3-pentylcyclo Hexyl group, 4-methylcyclohexyl group, 4-ethylcyclohexyl group, 4-propylcyclohexyl group, 4-butylcyclohexyl group, 4-pentylcyclohexyl group, 4-methyl
  • phenyl group optionally substituted with one or more groups selected from group E examples include, for example, phenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-iodophenyl group, 3-iodophenyl group, 4-iodophenyl group, 2-cyanophenyl Group, 3-cyanophenyl group, 4-cyanophenyl group, 2-nitrophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2-propylphenyl group, 3-propylphenyl group
  • Examples of the “C2-C5 polymethylene group optionally substituted with one or more groups selected from group E” include, for example, an ethylene group, a 1,3-propylene group, a 1,4-butylene group, and a 1,5-pentylene group.
  • Fluoroethylene group chloroethylene group, bromoethylene group, cyanoethylene group, nitroethylene group, 1,2-propylene group, 3,3,3-trifluoro-1,2-propylene group, cyclopropylethylene group, methoxy Ethylene group, trifluoromethoxyethylene group, methylthioethylene group, trifluoromethylthioethylene group, methanesulfinylethylene group, trifluoromethanesulfinylethylene group, methanesulfonylethylene group, trifluoromethanesulfonylethylene group, acetylethylene group, trifluoroacetylethylene group , Methoxycal Examples thereof include bonylethylene group, trifluoromethoxycarbonylethylene group, acetoxyethylene group and trifluoroacetoxyethylene group.
  • propene-1,3-diyl group optionally substituted with one or more groups selected from group E examples include propene-1,3-diyl group, 2-fluoropropene-1,3-diyl group 3-fluoropropene-1,3-diyl group, 3,3-difluoropropene-1,3-diyl group, 2-chloropropene-1,3-diyl group, 2-bromopropene-1,3-diyl group 2-cyanopropene-1,3-diyl group, 2-nitropropene-1,3-diyl group, 2-methylpropene-1,3-diyl group, 3-methylpropene-1,3-diyl group, 3 , 3-Dimethylpropene-1,3-diyl group, 2-trifluoromethylpropene-1,3-diyl group, 2-cyclopropylpropene-1,3-diyl group, 2-methoxyprop
  • Examples of the “1,3-butadiene-1,4-diyl group optionally substituted with one or more groups selected from group E” include 1,3-butadiene-1,4-diyl group, 1-fluoro -1,3-butadiene-1,4-diyl group, 2-fluoro-1,3-butadiene-1,4-diyl group, 1-chloro-1,3-butadiene-1,4-diyl group, 2- Chloro-1,3-butadiene-1,4-diyl group, 1-bromo-1,3-butadiene-1,4-diyl group, 2-bromo-1,3-butadiene-1,4-diyl group, 1 -Cyano-1,3-butadiene-1,4-diyl group, 1-nitro-1,3-butadiene-1,4-diyl group, 1-methyl-1,3-butadiene-1,4-diyl group, 2-methyl-1,
  • C1-C4 chain hydrocarbon group examples include methyl group, ethyl group, ethynyl group, propyl group, isopropyl group, allyl group, propargyl group, butyl group, isobutyl group and t-butyl group.
  • Examples of the “C1-C10 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group, Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group, Propyl group, 3-fluoropropyl group, 3,3,3-triflu
  • Examples of the “C1-C4 alkoxy group” include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, and a t-butoxy group.
  • Examples of the “C1-C4 alkylthio group” include a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, and a t-butylthio group.
  • C1-C4 alkylsulfinyl group examples include a methanesulfinyl group, an ethanesulfinyl group, a propanesulfinyl group, an isopropanesulfinyl group, a butanesulfinyl group, an isobutanesulfinyl group, and a t-butanesulfinyl group.
  • C1-C4 alkylsulfonyl group examples include a methanesulfonyl group, an ethanesulfonyl group, a propanesulfonyl group, an isopropanesulfonyl group, a butanesulfonyl group, an isobutanesulfonyl group, and a t-butanesulfonyl group.
  • Examples of the “C1-C4 alkoxy group optionally substituted with halogen” include a methoxy group, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a chloromethoxy group, a dichloromethoxy group, a trichloromethoxy group, and a bromomethoxy group.
  • Examples of the “C1-C4 alkylthio group optionally substituted with halogen” include a methylthio group, a fluoromethylthio group, a difluoromethylthio group, a trifluoromethylthio group, a chloromethylthio group, a dichloromethylthio group, a trichloromethylthio group, and a bromomethylthio group.
  • C1-C4 alkylsulfinyl group optionally substituted with halogen examples include methanesulfinyl group, fluoromethanesulfinyl group, difluoromethanesulfinyl group, trifluoromethanesulfinyl group, chloromethanesulfinyl group, dichloromethanesulfinyl group, trichloromethane.
  • Sulfinyl group bromomethanesulfinyl group, dibromomethanesulfinyl group, iodomethanesulfinyl group, chlorodifluoromethanesulfinyl group, Ethanesulfinyl group, 2-fluoroethanesulfinyl group, 2,2,2-trifluoroethanesulfinyl group, perfluoroethanesulfinyl group, 2-chloroethanesulfinyl group, 2,2,2-trichloroethanesulfinyl group, 2-bromoethanesulfinyl group Group, 2-iodoethanesulfinyl group, Propanesulfinyl group, 3-fluoropropanesulfinyl group, 3,3,3-trifluoropropanesulfinyl group, perfluoropropanesulfinyl group, isopropanesulfin
  • Examples of the “optionally substituted C1-C4 alkylsulfonyl group” include a methanesulfonyl group, a fluoromethanesulfonyl group, a difluoromethanesulfonyl group, a trifluoromethanesulfonyl group, a chloromethanesulfonyl group, a dichloromethanesulfonyl group, and trichloromethane.
  • Sulfonyl group bromomethanesulfonyl group, dibromomethanesulfonyl group, iodomethanesulfonyl group, chlorodifluoromethanesulfonyl group, Ethanesulfonyl group, 2-fluoroethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group, perfluoroethanesulfonyl group, 2-chloroethanesulfonyl group, 2,2,2-trichloroethanesulfonyl group, 2-bromoethanesulfonyl Group, 2-iodoethanesulfonyl group, Propanesulfonyl group, 3-fluoropropanesulfonyl group, 3,3,3-trifluoropropanesulfonyl group, perfluoropropanesulfonyl group, isopropanesulfony
  • Examples of the “(C1-C4 alkyl) carbonyl group optionally substituted with halogen” include acetyl group, fluoroacetyl group, difluoroacetyl group, trifluoroacetyl group, chloroacetyl group, dichloroacetyl group, trichloroacetyl group, Bromoacetyl group, dibromoacetyl group, iodoacetyl group, chlorodifluoroacetyl group, Propanoyl group, 3-fluoropropanoyl group, 3,3,3-trifluoropropanoyl group, perfluoropropanoyl group, 3-chloropropanoyl group, 3,3,3-trichloropropanoyl group, 3-bromopropanoyl group Noyl group, 3-iodopropanoyl group, Butanoyl group, 4-fluorobutanoyl group, 4,4,4-
  • Examples of the “optionally substituted (C1-C4 alkoxy) carbonyl group with halogen” include a methoxycarbonyl group, a fluoromethoxycarbonyl group, a difluoromethoxycarbonyl group, a trifluoromethoxycarbonyl group, a chloromethoxycarbonyl group, and a dichloromethoxycarbonyl group.
  • Examples of the “(C1-C4 alkyl) carbonyloxy group optionally substituted with halogen” include, for example, an acetoxy group, a fluoroacetoxy group, a difluoroacetoxy group, a trifluoroacetoxy group, a chloroacetoxy group, a dichloroacetoxy group, and a trichloroacetoxy group , Bromoacetoxy group, dibromoacetoxy group, iodoacetoxy group, chlorodifluoroacetoxy group, Propanoyloxy group, 3-fluoropropanoyloxy group, 3,3,3-trifluoropropanoyloxy group, perfluoropropanoyloxy group, 3-chloropropanoyloxy group, 3,3,3-trichloropropanoyl An oxy group, a 3-bromopropanoyloxy group, a 3-iodopropanoyloxy group, Butano
  • C1-C5 alkyl group examples include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a t-butyl group, and a pentyl group.
  • Examples of the “C1-C10 chain hydrocarbon group optionally substituted with halogen” include a methyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, Bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group, Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group, Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexa
  • R 1 Is hydrogen, halogen, cyano group, methyl group substituted with one or more groups selected from group A, C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, fluoro An amide compound which is a methyl group or a difluoromethyl group;
  • R 1 Is hydrogen, halogen, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a fluoromethyl group, or An amide compound which is a difluoromethyl group;
  • formula (1) R 1 Is hydrogen, halogen, cyano group, methyl group substituted with one or more groups selected from group A,
  • the compound of the present invention or a salt thereof can be produced by reacting compound (3) or a salt thereof with compound (2) in the presence of a dehydration condensing agent.
  • a dehydration condensing agent [In the formula, R 1 , R 2 And p represent the same meaning as described above. ] The reaction is usually performed in the presence of a solvent.
  • ethers such as tetrahydrofuran (hereinafter sometimes referred to as THF), ethylene glycol dimethyl ether, tert-butyl methyl ether (hereinafter sometimes referred to as MTBE), hexane, Aliphatic hydrocarbons such as heptane and octane, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N -Acid amides such as dimethylformamide (hereinafter sometimes referred to as DMF), sulfoxides such as dimethylsulfoxide (hereinafter sometimes referred to as DMSO), and mixtures thereof.
  • THF tetrahydrofuran
  • MTBE tert-butyl methyl ether
  • hexane Aliphatic hydrocarbons such as
  • Examples of the dehydrating condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC), benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexa Examples thereof include fluorophosphate (hereinafter referred to as BOP reagent) and 1,3-dicyclohexylcarbodiimide.
  • WSC 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride
  • benzotriazol-1-yloxy) tris dimethylamino) phosphonium hexa
  • BOP reagent fluorophosphate
  • 1,3-dicyclohexylcarbodiimide 1,3-dicyclohexylcarbodiimide.
  • the reaction temperature of the reaction is usually in the range of 0 to 200 ° C.
  • the reaction time is usually in the range of 1 to 24 hours.
  • a BOP reagent when used, the reaction is performed in the presence of a base as necessary.
  • bases include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
  • the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (2).
  • the compound of the present invention can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer.
  • the isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
  • the compound of the present invention can be produced by reacting compound (3) or a salt thereof with compound (4) or a salt thereof in the presence of a base. [In the formula, R 1 , R 2 And p represent the same meaning as described above. ] The reaction is usually performed in the presence of a solvent.
  • solvent used in the reaction examples include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and halogens such as chlorobenzene.
  • Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
  • the compound (3) is usually used in a proportion of 1 to 3 mol
  • the base is usually used in a proportion of 1 to 10 mol.
  • the reaction temperature is usually in the range of ⁇ 20 to 140 ° C.
  • the reaction time is usually in the range of 0.1 to 24 hours.
  • the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer.
  • the isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
  • Step (I-1) Compound (6) can be produced by reacting compound (5) with compound (3) or a salt thereof in the presence of a dehydration condensing agent. The reaction is usually performed in the presence of a solvent.
  • solvent used in the reaction examples include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and halogens such as chlorobenzene.
  • Examples of the dehydrating condensing agent used in the reaction include WSC, BOP reagent, and 1,3-dicyclohexylcarbodiimide.
  • the compound (3) is usually used in a proportion of 1 to 3 mol
  • the dehydrating condensing agent is usually used in a proportion of 1 to 5 mol.
  • the reaction temperature of the reaction is usually in the range of 0 to 200 ° C.
  • the reaction time is usually in the range of 1 to 24 hours.
  • the reaction when a BOP reagent is used, the reaction is performed in the presence of a base as necessary.
  • the base examples include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
  • the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (5).
  • the compound (6) can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. The isolated compound (6) can be further purified by chromatography, recrystallization and the like.
  • Step (I-2) The compound of the present invention can be produced by reacting compound (6) with an acid. The reaction is usually performed in the presence of a solvent.
  • Examples of the solvent used in the reaction include aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene, sulfoxides such as DMSO, methanol, ethanol, 2-methylethanol and the like. Alcohols, acetones, ketones such as methyl ethyl ketone and methyl isobutyl ketone, water, and mixtures thereof.
  • Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as trifluoroacetic acid, p-toluenesulfonic acid, and methanesulfonic acid.
  • the acid is usually used in an amount of 1 mol to excess with respect to 1 mol of the compound (6).
  • the reaction temperature of the reaction is usually in the range of 0 to 150 ° C.
  • the reaction time is usually in the range of 0.1 to 24 hours.
  • the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer.
  • the isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
  • the compound of the present invention is capable of forming an agriculturally acceptable salt.
  • Such a salt of the compound of the present invention is usually a salt of the compound of the present invention and an acid.
  • Examples of the salt with an acid include inorganic acid salts such as hydrochloride, hydrobromide, and sulfate, and organic acid salts such as methanesulfonate, formate, acetate, and trifluoroacetate.
  • the salt of this invention compound and an acid can be manufactured by making this invention compound react with an acid. [In the formula, R 1 , R 2 And p represent the same meaning as described above, and HX represents an acid. ] The reaction is performed in the presence of a solvent or in the absence of a solvent.
  • Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, water, and these.
  • Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, and sulfuric acid, and organic acids such as acetic acid, trifluoroacetic acid, formic acid, p-toluenesulfonic acid, and methanesulfonic acid. Can be mentioned.
  • an acid is usually used at a ratio of 1 to 100 mol per 1 mol of the compound of the present invention.
  • the reaction temperature of the reaction is usually in the range of 0 to 200 ° C.
  • the reaction time is usually in the range of 1 to 24 hours.
  • the salt of the compound of the present invention and the acid can be isolated by removing the unreacted acid.
  • the plant disease control agent of the present invention contains the compound of the present invention or a salt thereof and an inert carrier (solid carrier, liquid carrier or gas carrier).
  • the plant disease control agent of the present invention is further mixed with a surfactant and other formulation adjuvants, wettable powder, granular wettable powder, flowable powder, granules, dry flowable powder, emulsion, aqueous liquid, oil, Formulated into smoking agents, aerosols, microcapsules and the like.
  • a surfactant and other formulation adjuvants usually contain the compound of the present invention or a salt thereof in a weight ratio of 0.1 to 99%, preferably 0.2 to 90%.
  • the solid support include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, wax clay, bentonite, acid clay, talc), and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon).
  • liquid carrier examples include water, alcohols (eg, methanol, ethanol), ketones (eg, acetone, methyl ethyl ketone), aromatic hydrocarbons (eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene), fat Group hydrocarbons (eg, hexane, cyclohexanone, kerosene), esters (eg, ethyl acetate, butyl acetate), nitriles (eg, acetonitrile, isobutyronitrile), ethers (eg, dioxane, diisopropyl ether), Acid amides (for example, dimethylformamide, dimethylacetamide), halogenated hydrocarbons (for example, dichloroethane, trichloroethylene, carbon tetrachloride) and the like can be mentioned
  • gaseous carrier examples include dimethyl ether and carbon dioxide.
  • surfactant examples include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylene compounds thereof, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.
  • formulation adjuvants include, for example, fixing agents, dispersants, thickeners, wetting agents, extenders and antioxidants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, Alginic acid), lignin derivatives, bentonite sugars, synthetic water-soluble polymers (eg, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-) Methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, fatty acid or ester thereof, and the like.
  • fixing agents eg starch, arabic gum, cellulose derivatives, Alginic acid
  • lignin derivatives lignin derivatives
  • bentonite sugars synthetic water-soluble polymers (eg
  • the compound of the present invention or a salt thereof is used for controlling plant diseases by applying to a plant or soil where the plant grows.
  • Examples of the method of applying the compound of the present invention or a salt thereof to the plant or the soil where the plant grows include, for example, a method of spraying foliage on the plant, a method of applying to the soil where the plant is cultivated, and a method of applying to the plant seed. It is done.
  • the plant disease control method of the present invention the plant disease control agent of the present invention is usually used.
  • the application amount of the plant disease control agent of the present invention is 1,000 m.
  • the amount of the compound of the present invention or a salt thereof is usually 1 to 500 g, preferably 2 to 200 g.
  • the concentration of the compound of the present invention or a salt thereof is usually 0.0005 to 2% by weight, preferably It is diluted with water so as to be 0.005 to 1% by weight.
  • the plant disease control agent of the present invention is formulated into a powder, granule or the like, the formulation is applied as it is without dilution.
  • the application amount of the plant disease control agent of the present invention is usually 0.001 to 1 kg of the present compound or a salt thereof per 1 kg seed.
  • the ratio is 100 g, preferably 0.01 to 50 g.
  • the plant disease control agent of the present invention can be mixed and / or used in combination with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers or soil conditioners. Examples of the active ingredient of such a bactericide include the following.
  • Azole bactericidal active compound Propiconazole, Prothioconazole, Triadimenol, Prochloraz, Penconazole, Dibuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole bromconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumizole, triflumizole aconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, tertanol, tertanol Hall, flutriafol, simeconazole, ipconazole and the like;
  • Amine fungicidal active compounds Fenpropimorph, tridemorph,
  • a compound represented by Examples of the active ingredient of such an acaricide include acequinocyl, amitraz, benzoximate, bifenate, phenobromolate, quinomethionate, and chinomethionate.
  • chlorobenzilate CPCBS (chlorfenson), clofentezine, cyflumetofen, quercene, dioxol, etoxazole, fenbutatin phenothiophene Fenpyroximate, fluacrylpyrim, fluproxyfen, penthiridinepirpene, fenpyridine , Tetradiphon, spirodiclofen, spiromesifen, spirotetramat, amidoflumet, cenopyrofene ), And the like.
  • Examples of the active ingredient of the nematicide include DCIP, fostiazate, levamisole hydrochloride, methylisothiocyanate, morantartrate tartrate, and imiciafos.
  • Examples of the active ingredient of such a plant growth regulator include etephon, chlormequat-chloride, mepiquat-chloride, and the like.
  • the plant disease control agent of the present invention can be used, for example, in agricultural lands such as fields, paddy fields, lawns, orchards. Examples of the “crop” in which the plant disease control agent of the present invention can be used include the following.
  • Agricultural crops corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplants, tomatoes, peppers, peppers, potatoes) Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, Jatropha, etc., Bridegroom, Foliage plant,
  • Trees other than fruit trees Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.
  • “Crop” also includes genetically modified crops. Examples of plant diseases in which the compound of the present invention or a salt thereof is effective include plant diseases caused by filamentous fungi, and specific examples include the following plant diseases.
  • Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuri); Wheat diseases: powdery mildew (Erysiphe graminis), red mold disease (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivare), rust (Puccinia striformi.
  • Ustilago nuda cloud disease (Rhynchosporium secalis), reticular disease (Pyrenophora teres), spot disease (Cochliobolus sativus), leafy leaf disease (Pyrenophora graminea) Citrus black spot (Diaporthe citri), scab (Elsinoe fawceti), fruit rot (Penicillium digitatum, P.
  • Sojae rust ps Green Bean Anthracnose (Colletotrichum lindemthianum) Peanut black astringency (Cercospora personata), brown spot (Cercospora arachidicola), white silkworm (Sclerotium rolfsii); Pea powdery mildew (Erysiphe pisi); Potato summer plague (Alternaria solani), plague (Phytophthora infestans), Scarlet rot (Phytophthora erythroseptica), half body wilt (Verticillium albo-arum, re.
  • Strawberry powdery mildew (Sphaerotheca humuli); Tea net blast (Exobasidium reticulatum); white scab (Elsinoe leucospila), ring spot disease (Pestarotropis sp.), Anthracnose (Colletotrichum theae-sinensis) Tobacco red leaf disease (Alternaria longipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), plague (Phytophathorophora) Sugar beet brown spot (Cercospora beticola), leaf rot (Thanatephorus cucumeris), root rot (Thanatephorus cucumeris), black root (Aphanomyces cochlioides); Rose scab (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa); Chrysant
  • Black soot disease (Alternaria brassicicola); Shiva dollar spot disease (Sclerotinia homeocarpa), brown patch disease and large patch disease (Rhizotonia solani); Banana sigatoka disease (Mycosphaerella fijiensis, Mycosphaerella musicola, Pseudocercospora musae); and Viral diseases of various plants mediated by Polymixa spp. Or Olpidium spp.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate.
  • the extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • the obtained solid was washed with t-butyl methyl ether, and 2-amino-N- (4-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (2)) was reduced to 0. 21 g was obtained.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate.
  • the extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • the obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (3)) to 0. 10 g was obtained.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate.
  • the extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • the obtained solid was washed with t-butyl methyl ether, and 2-amino-N- (2-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (4)) was reduced to 0. 15 g was obtained.
  • the reaction mixture was poured into aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and t-butyl methyl ether and hexane were added to the residue. The crystals were collected by filtration to obtain 0.39 g of 2-amino-N- (2-bromobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (10)).
  • the reaction mixture was poured into water and extracted with ethyl acetate.
  • the extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2,3-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (13)) was 0. .36 g was obtained.
  • the reaction mixture was poured into water and extracted with ethyl acetate.
  • the extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2-chloro-4-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (14)). 0.42 g was obtained.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate.
  • the extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • the obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-methoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (25)) to 0. 19 g was obtained.
  • Production Example 97 A mixture of 0.54 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 3 mL of DMF, 0.20 g of triethylamine, 0.89 g of BOP reagent, and 0.31 g of 3,4-difluoro-2-methylbenzylamine, The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • Production Example 99 Mix 0.54 g 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.14 g triethylamine, 0.62 g BOP reagent, and 0.22 g 4,5-difluoro-2-methylbenzylamine, The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • Production Example 102 Mix 0.78 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.41 g of triethylamine, 0.89 g of BOP reagent, and 0.52 g of 2-bromo-3,5-difluorobenzylamine hydrochloride And the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate.
  • the extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate.
  • the mixture was concentrated under reduced pressure, and hexane, t-butyl methyl ether, and ethyl acetate were added to the residue.
  • the crystals were collected by filtration, and 2-amino-N- (2,6-dichlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (107)) was 0. .32 g was obtained.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2-chloro-6-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (108)). 0.23 g was obtained.
  • the reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and t-butyl methyl ether and ethyl acetate were added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2,3-dimethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (109)) was 0. .29 g was obtained.
  • the present compound (109) 2-amino-N- (2,3-dimethylbenzyl) -thiazole-5-carboxylic acid amide
  • the mixture was heated and stirred at 80 ° C. for 4 hours.
  • the reaction mixture was allowed to cool to room temperature, hexane was added to the reaction mixture to precipitate a precipitate, the solid was filtered off, and the filtrate was concentrated.
  • To the obtained residue were added 30 ml of EtOH and 2.3 g of thiourea, and the mixture was stirred at 80 ° C. for 2 hours. After allowing to cool to room temperature, 47 ml of 5% NaOH aqueous solution was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours.
  • the mixture was stirred at room temperature for 3 hours, and 46.4 mL of 4N aqueous sodium hydroxide solution was added.
  • the mixture was stirred at room temperature for 1 hour, and 87.5 mL of 1N hydrochloric acid was added.
  • the reaction mixture was allowed to stand and the THF layer was separated.
  • the aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer.
  • the extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Under ice-cooling, 1.5 mL of concentrated hydrochloric acid was added, and toluene was added to azeotrope water.
  • reaction mixture was left overnight at room temperature, and 30 mL of aqueous ammonia (28%) was added. The mixture was stirred at room temperature for 3 hours, 94 mL of 4N aqueous sodium hydroxide solution was added, and the mixture was stirred at room temperature for 1 hour. 177 mL of 1N hydrochloric acid was added here.
  • the reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 10 mL of THF was added to the residue.
  • reaction mixture was left at room temperature overnight, and then the reaction mixture was poured into 80 mL of water. The mixture was extracted with t-butyl methyl ether. The organic layer was washed with water and saturated brine in this order. Dried over magnesium sulfate and concentrated under reduced pressure. To the residue was added 100 mL of THF, 7.27 g of triphenylphosphine was added under ice cooling, and the mixture was stirred at room temperature for 1.5 hours. After leaving at room temperature for 3 days, 28 mL of aqueous ammonia (28%) was added and stirred for 3 hours. To the mixture, 94 mL of 4N aqueous sodium hydroxide solution was added and stirred for 1 hour.
  • the reaction mixture was left at room temperature overnight and then concentrated under reduced pressure. Water and ethyl acetate were added to the residue, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the previous ethyl acetate layer. The extract was washed with saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography to obtain 6.603 g of 2-bromo-3,4,5-trifluorobenzyl alcohol.
  • Each wettable powder is obtained by thoroughly pulverizing and mixing 50 parts of any one of the compounds (1) to (111) of the present invention, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate, and 45 parts of synthetic silicon hydroxide. Get.
  • Formulation Example 2 20 parts of any one of the compounds (1) to (111) of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol. After pulverization, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and stirred to obtain each flowable preparation.
  • Formulation Example 3 Each powder agent is obtained by thoroughly crushing and mixing 2 parts of any one of the compounds (1) to (111) of the present invention, 88 parts of kaolin clay and 10 parts of talc.
  • Formulation Example 4 Each emulsion is obtained by thoroughly mixing 5 parts of any one of the compounds (1) to (111) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene. Get. Formulation Example 5 After thoroughly mixing 2 parts of any one of the compounds (1) to (111) of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay, water is added. Kneaded well and granulated and dried to obtain each granule.
  • Formulation Example 6 10 parts of any one of the compounds (1) to (111) of the present invention; 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water are mixed and pulverized by a wet pulverization method. Thus, each flowable preparation is obtained.
  • Formulation Example 8 50 parts of any one of the compounds (1) to (111) of the present invention, 38.5 parts of NN kaolin clay (manufactured by Takehara Chemical Industry), 10 parts of Morwet D425, 1.5 parts of Morwer EFW (Akzo Nobel) And the mixture is pulverized with a jet mill to obtain each powder.
  • test examples show that the compounds of the present invention are useful for controlling plant diseases. The control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.
  • Test example 1 A plastic pot was filled with soil, seeded with wheat (variety: Shirogane), grown in a greenhouse for 9 days, and then sprinkled with spores of wheat red rust fungus (Puccinia redondota f. Sp. Tritici). After inoculation, it was placed in a dark and humid place at 23 ° C. for 1 day, and then air-dried to obtain a wheat rust-infected seedling.
  • Each of the compounds (15), (18), (52), (57), (58), (85), (90) and (97) of the present invention was made into a flowable formulation according to Formulation Example 6, was diluted to a predetermined concentration (500 ppm) and sprayed on the foliage so as to adhere well to the leaf surface of the wheat. After spraying, the plants were air-dried and placed under illumination for 6 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compounds (15), (18), (52), (57), (58), (85), (90) and (97) of the present invention was untreated. It was 30% or less of the lesion area in the plant.
  • Test example 2 A plastic pot was filled with soil, seeded with wheat (variety: Apogee), and grown in a greenhouse for 10 days. Each of the compounds (2), (9), (18), (40), (43), (52), and (89) of the present invention was made into a flowable formulation according to Formulation Example 6, and then diluted with water. A predetermined concentration (500 ppm) was applied, and the foliage was sprayed so as to sufficiently adhere to the leaf surface of the wheat. After spraying, the plants were air-dried and sprayed and inoculated with an aqueous suspension of Septoria tritici spores after 3 or 4 days. After the inoculation, the area was first placed under a high humidity of 18 ° C.
  • the lesion area in the plant treated with the compounds (2), (9), (18), (40), (43), (52), and (89) of the present invention is the disease in the untreated plant. It was 30% or less of the spot area.
  • Test example 3 The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days.
  • Each of the compounds (17), (18) and (19) of the present invention is made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm) so that it adheres well to the cucumber leaf surface. The foliage was sprayed.
  • test example 4 A plastic pot was stuffed with soil, seeded with green beans (variety; Nagahama peas) and grown in a greenhouse for 8 days.
  • Each of the compounds (16), (17), (18), (89), (95), (96) and (101) of the present invention was made into a flowable formulation according to Formulation Example 6, then diluted with water to give The concentration was set to 500 ppm, and the foliage was sprayed so as to adhere well to the kidney leaf surface. After spraying, the plants were air-dried, and a mycelia-containing PDA medium of Sclerotinia sclerotiorum was placed on the kidney leaf surface. After inoculation, the lesion area was investigated after 23 days at 23 ° C. and high humidity.
  • the lesion area in the plant treated with the compounds (16), (17), (18), (89), (95), (96) and (101) of the present invention is the lesion spot in the untreated plant. It was 30% or less of the area.
  • Test Example 5 Cucumber downy mildew treatment effect test (Pseudoperonospora cubensis) The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. The pot was spray-inoculated with an aqueous suspension of cucumber downy mildew zoosporangium, placed at 23 ° C.
  • the plants were air-dried and placed in a greenhouse at 23 ° C. for 5 days, and then the lesion area was examined.
  • the present compounds (10), (12), (13), (14), (16), (27), (33), (36), (37), (40), (41), (43), (49), (52), (56), (57), (58), (59), (61), (62), (63), (64), (65), (66 ), (69), (72), (75), (76), (77), (78), (81), (82), (84), (86), (89), (90),
  • the lesion area in the plant which processed (91), (92), (99), (100), (101), (102) and (110) is 30% or less of the lesion area in an untreated plant.
  • Test Example 6 The plastic pot was filled with soil, tomato (variety: patio) was sown and grown in a greenhouse for 20 days.
  • Compounds of the present invention (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12) , (13), (14), (15), (16), (17), (26), (27), (28), (30), (31), (33), (35), ( 36), (37), (38), (39), (40), (41), (43), (45), (49), (50), (52), (56), (57) , (58), (59), (61), (62), (63), (64), (65), (69), (71), (72), (73), (75), ( 76), (77), (78), (80), (81), (82), (84), (85), (86), (88), (89), (90), (91) , (92), (93), (94), (95), (96), ( 7), (98), (99), (100), (101), (
  • an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
  • Test Example 7 The plastic pot was filled with soil, tomato (variety: patio) was sown and grown in a greenhouse for 20 days.
  • Each of the compounds (18), (20), (21), (22) and (23) of the present invention was made into a flowable formulation according to Formulation Example 6, then diluted with water to a predetermined concentration (200 ppm), and the tomato The foliage was sprayed so as to adhere well to the leaf surface of the seedling. After air-drying the diluted solution on the leaf surface to dryness, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C.
  • Test Example 8 Tomato (variety: patio) was sown on a plastic sponge piece and hydroponically cultivated in a plastic cup for about 20 days.
  • Compound (1), (2), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13) , (14), (15), (16), (17), (26), (33), (36), (40), (41), (43), (49), (52), ( 53), (62), (63), (65), (72), (75), (76), (77), (78), (81), (82), (84), (85) , (86), (87), (88), (89), (90), (91), (93), (94), (95), (96), (97), (98), ( 99), (100), (101), (102), (106) and (110) are each made into a flowable formulation according to Formulation Example 6, and then 1 mg of the above tomato hydroponics per plant in terms of weight In a seedling cup Off to.
  • an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
  • Test Example 9 Tomato (variety: patio) was sown on a plastic sponge piece and hydroponically cultivated in a plastic cup for about 20 days.
  • Each of the compounds (18), (20), (21), (22) and (23) of the present invention was made into a flowable formulation according to Formulation Example 6, and then 0.4 mg per plant in terms of weight was added to the tomato water. It put into the cup of the cultivation seedling. Further, after hydroponics for 7 days, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days. The lesion area in the plant which processed this invention compound (18), (20), (21), (22) and (23) was 30% or less of the lesion area in an untreated plant.
  • the compound of the present invention or a salt thereof is useful for plant disease control because it has an excellent plant disease control effect.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

An amide compound represented by formula (1) [wherein R1 represents a hydrogen atom, a halogen atom, a cyano group, a nitro group, or the like; p represents an integer of 0 to 5; and R2 represents a halogen atom, a cyano group, a nitro group, or the like] or a salt thereof, which has an excellent plant disease control effect.

Description

アミド化合物とその植物病害防除用途Amide compounds and their plant disease control applications
　本発明は、アミド化合物及びその植物病害防除用途に関する。 The present invention relates to an amide compound and its use for controlling plant diseases.
　従来より、植物病害の防除のために多くの化合物が開発され、使用されてきた。 Conventionally, many compounds have been developed and used for controlling plant diseases.
　本発明は、優れた植物病害防除効力を有する化合物を提供することを課題とする。
　本発明者等は、優れた植物病害防除効力を有する化合物を見出すべく鋭意検討した結果、下記式（１）で示されるアミド化合物が優れた植物病害防除効力を有することを見出し、本発明を完成した。すなわち、本発明は以下のものである。
［１］　式（１）
Figure JPOXMLDOC01-appb-I000002
〔式中、
Ｒ１は水素、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ４基、−Ｓ−Ｒ４基、−Ｓ（＝Ｏ）−Ｒ４基、−Ｓ（＝Ｏ）２−Ｒ４基、群Ａより選ばれる１以上の基で置換されたメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ５シクロアルキル基、フルオロメチル基又はジフルオロメチル基を表し、
ｐは０から５の整数のいずれかを表し、
Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基、−Ｓ−Ｒ５基、−Ｃ（＝Ｏ）−Ｒ５基、−Ｃ（＝Ｏ）−ＯＲ５基、−ＯＣ（＝Ｏ）−Ｒ５基、−ＮＲ５Ｒ６基、−Ｃ（＝Ｏ）−ＮＲ５Ｒ６基又は−ＮＲ５−Ｃ（＝Ｏ）−Ｒ６基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、群Ｅより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５ポリメチレン基、群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基、群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基を表し、
Ｒ４はＣ１~Ｃ４鎖式炭化水素基を表し、
Ｒ５及びＲ６は独立して、水素、群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基又は群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基を表す。
　但し、ｐが２から５の整数のいずれかである場合、Ｒ２は相互に同一でも相異なっていてもよい。
　なお、群Ａは塩素、臭素、沃素、シアノ基、Ｃ１−Ｃ４アルコキシ基、Ｃ１−Ｃ４アルキルチオ基、Ｃ１−Ｃ４アルキルスルフィニル基及びＣ１−Ｃ４アルキルスルホニル基からなる群を表し、
群Ｂはハロゲン、シアノ基、Ｃ１~Ｃ４アルコキシ基、Ｃ１~Ｃ４アルキルチオ基、Ｃ１~Ｃ４アルキルスルフィニル基及びＣ１~Ｃ４アルキルスルホニル基からなる群を表し、
群Ｃは群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、ハロゲン、シアノ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルコキシ）カルボニル基、及びハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニルオキシ基からなる群を表し、
群ＤはＣ１~Ｃ５アルキル基及びハロゲンからなる群を表し、
群Ｅはハロゲン、シアノ基、ニトロ基、ハロゲンで置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルコキシ）カルボニル基及びハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニルオキシ基からなる群を表す。〕
で示されるアミド化合物（以下、本発明化合物と記す）又はその塩。
［２］　Ｒ１が水素又はハロゲンであり、Ｒ２がハロゲンである［１］記載のアミド化合物又はその塩。
［３］　Ｒ１が水素であり、Ｒ２がハロゲンである［１］記載のアミド化合物又はその塩。
［４］　Ｒ１が水素であり、Ｒ２がフッ素又は塩素である［１］記載のアミド化合物又はその塩。
［５］　Ｒ１が水素であり、Ｒ２がフッ素又は臭素である［１］記載のアミド化合物又はその塩。
［６］　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、ハロゲンである［１］記載のアミド化合物又はその塩。
［７］　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、フッ素又は塩素である［１］記載のアミド化合物又はその塩。
［８］　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、フッ素又は臭素である［１］記載のアミド化合物又はその塩。
［９］　２−アミノ−Ｎ−（２−クロロ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド。
［１０］　２−アミノ−Ｎ−（２−ブロモ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド。
［１１］　［１］~［１０］いずれか１項記載のアミド化合物又はその塩と、不活性担体と、を含有する植物病害防除剤。
［１２］　［１］~［１０］いずれか１項記載のアミド化合物又はその塩の有効量を植物又は植物が生育する土壌に施用する工程を有する植物病害の防除方法。
［１３］　植物病害を防除するための［１］~［１０］いずれか１項記載のアミド化合物又はその塩の使用。 An object of the present invention is to provide a compound having an excellent plant disease control effect.
As a result of intensive studies to find a compound having an excellent plant disease control effect, the present inventors have found that the amide compound represented by the following formula (1) has an excellent plant disease control effect and completed the present invention. did. That is, the present invention is as follows.
[1] Formula (1)
Figure JPOXMLDOC01-appb-I000002
[Where,
R 1 is hydrogen, halogen, cyano group, nitro group, —O—R 4 group, —S—R 4 group, —S (═O) —R 4 group, —S (═O) 2 —R 4 group, A methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a C3-C5 cycloalkyl group, fluoromethyl Represents a group or a difluoromethyl group,
p represents any integer from 0 to 5;
R 2 is a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D , Phenyl group, halogen, cyano group, nitro group, —O—R 5 group, —S—R 5 group, —C (═O) —R optionally substituted with one or more groups selected from group E 5 groups, —C (═O) —OR 5 groups, —OC (═O) —R 5 groups, —NR 5 R 6 groups, —C (═O) —NR 5 R 6 groups or —NR 5 —C (= O) —R 6 group is represented,
Alternatively, when p is 2 or more and two R 2 are bonded to adjacent carbons of the benzene ring, the two R 2 are bonded and substituted with one or more groups selected from group E. An optionally substituted C2-C5 polymethylene group, a propene-1,3-diyl group optionally substituted with one or more groups selected from group E, and one or more groups selected from group E. Represents a 1,3-butadiene-1,4-diyl group or a methylenedioxy group,
R 4 represents a C1-C4 chain hydrocarbon group,
R 5 and R 6 are independently hydrogen, a C1-C10 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and one or more groups selected from group D. Represents a C3 to C10 cycloalkyl group which may be substituted or a phenyl group which may be substituted with one or more groups selected from group E.
However, when p is any integer of 2 to 5, R 2 may be the same as or different from each other.
Group A represents a group consisting of chlorine, bromine, iodine, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group,
Group B represents a group consisting of halogen, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group,
Group C is a C3-C10 cycloalkyl group optionally substituted with one or more groups selected from Group D, a halogen, a cyano group, a C1-C4 alkoxy group optionally substituted with halogen, or a halogen-substituted group An optionally substituted C1-C4 alkylthio group, a C1-C4 alkylsulfinyl group optionally substituted with halogen, a C1-C4 alkylsulfonyl group optionally substituted with halogen, and optionally substituted with halogen (C1- C4 alkyl) represents a group consisting of a carbonyl group, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a (C1-C4 alkyl) carbonyloxy group optionally substituted with halogen;
Group D represents a group consisting of a C1-C5 alkyl group and halogen,
Group E is halogen, cyano group, nitro group, C1-C10 chain hydrocarbon group optionally substituted with halogen, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D C1-C4 alkoxy group optionally substituted with halogen, C1-C4 alkylthio group optionally substituted with halogen, C1-C4 alkylsulfinyl group optionally substituted with halogen, halogen-substituted May be a C1-C4 alkylsulfonyl group, a (C1-C4 alkyl) carbonyl group optionally substituted with halogen, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a halogen-substituted Represents a group of good (C1-C4 alkyl) carbonyloxy groups. ]
Or an salt thereof (hereinafter referred to as the present compound).
[2] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen or halogen, and R 2 is halogen.
[3] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen and R 2 is halogen.
[4] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen and R 2 is fluorine or chlorine.
[5] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen and R 2 is fluorine or bromine.
[6] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen, p is 3, R 2 is the same or different from each other, and is halogen.
[7] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen, p is 3, R 2 is the same or different from each other, and is fluorine or chlorine.
[8] The amide compound or a salt thereof according to [1], wherein R 1 is hydrogen, p is 3, R 2 is the same or different from each other, and is fluorine or bromine.
[9] 2-Amino-N- (2-chloro-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide.
[10] 2-Amino-N- (2-bromo-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide.
[11] A plant disease control agent comprising the amide compound or salt thereof according to any one of [1] to [10] and an inert carrier.
[12] A method for controlling plant diseases comprising a step of applying an effective amount of the amide compound or salt thereof according to any one of [1] to [10] to a plant or soil where the plant grows.
[13] Use of the amide compound or a salt thereof according to any one of [1] to [10] for controlling plant diseases.
　本明細書の記載において用いられる種々の置換基について、例を挙げて以下に説明する。
　「ハロゲン」とは、フッ素、塩素、臭素および沃素を意味する。
　「群Ａより選ばれる１以上の基で置換されたメチル基」としては、例えばクロロメチル基、ジクロロメチル基、トリクロロメチル基、ブロモメチル基、ジブロモメチル基、ヨードメチル基、シアノメチル基、ジシアノメチル基、メトキシメチル基、エトキシメチル基、プロポキシメチル基、イソプロポキシメチル基、ブトキシメチル基、イソブトキシメチル基、ｔ−ブトキシメチル基、メチルチオメチル基、エチルチオメチル基、プロピルチオメチル基、イソプロピルチオメチル基、ブチルチオメチル基、イソブチルチオメチル基、ｔ−ブチルチオメチル基、メタンスルフィニルメチル基、エタンスルフィニルメチル基、プロパンスルフィニルメチル基、イソプロパンスルフィニルメチル基、ブタンスルフィニルメチル基、イソブタンスルフィニルメチル基、ｔ−ブタンスルフィニルメチル基、メタンスルホニルメチル基、エタンスルホニルメチル基、プロパンスルホニルメチル基、イソプロパンスルホニルメチル基、ブタンスルホニルメチル基、イソブタンスルホニルメチル基及びｔ−ブタンスルホニルメチル基が挙げられる。
　「群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基」としては、例えばエチル基、２−フルオロエチル基、２，２，２−トリフルオロエチル基、パーフルオロエチル基、２−クロロエチル基、２，２，２−トリクロロエチル基、２−ブロモエチル基、２−ヨードエチル基、
プロピル基、３−フルオロプロピル基、３，３，３−トリフルオロプロピル基、パーフルオロプロピル基、３−クロロプロピル基、３，３，３−トリクロロプロピル基、３−ブロモプロピル基、３−ヨードプロピル基、
イソプロピル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロピル基、パーフルオロイソプロピル基、
ブチル基、４−フルオロブチル基、４，４，４−トリフルオロブチル基、パーフルオロブチル基、４−クロロブチル基、４，４，４−トリクロロブチル基、４−ブロモブチル基、４−ヨードブチル基、ｓ−ブチル基、ｔ−ブチル基、
ペンチル基、５−フルオロペンチル基、５，５，５−トリフルオロペンチル基、パーフルオロペンチル基、５−クロロペンチル基、５，５，５−トリクロロペンチル基、５−ブロモペンチル基、５−ヨードペンチル基、
２−シアノエチル基、２，２−ジシアノエチル基、３−シアノプロピル基、３，３−ジシアノプロピル基、４−シアノブチル基、４，４−ジシアノブチル基、５−フルオロペンチル基、５，５−ジシアノペンチル基、
２−メトキシエチル基、３−メトキシプロピル基、４−メトキシブチル基、５−メトキシペンチル基、２−エトキシエチル基、３−エトキシプロピル基、４−エトキシブチル基、５−エトキシペンチル基、２−プロポキシエチル基、３−プロポキシプロピル基、４−プロポキシブチル基、５−プロポキシペンチル基、２−ブトキシエチル基、３−ブトキシプロピル基、４−ブトキシブチル基、５−ブトキシペンチル基、
２−メチルチオエチル基、３−メチルチオプロピル基、４−メチルチオブチル基、５−メチルチオペンチル基、２−エチルチオエチル基、３−エチルチオプロピル基、４−エチルチオブチル基、５−エチルチオペンチル基、２−プロピルチオエチル基、３−プロピルチオプロピル基、４−プロピルチオブチル基、５−プロピルチオペンチル基、２−ブチルチオエチル基、３−ブチルチオプロピル基、４−ブチルチオブチル基、５−ブチルチオペンチル基、
２−メタンスルフィニルエチル基、３−メタンスルフィニルプロピル基、４−メタンスルフィニルブチル基、５−メタンスルフィニルペンチル基、２−エタンスルフィニルエチル基、３−エタンスルフィニルプロピル基、４−エタンスルフィニルブチル基、５−エタンスルフィニルペンチル基、２−プロパンスルフィニルエチル基、３−プロパンスルフィニルプロピル基、４−プロパンスルフィニルブチル基、５−プロパンスルフィニルペンチル基、２−ブタンスルフィニルエチル基、３−ブタンスルフィニルプロピル基、４−ブタンスルフィニルブチル基、５−ブタンスルフィニルペンチル基、
２−メタンスルホニルエチル基、３−メタンスルホニルプロピル基、４−メタンスルホニルブチル基、５−メタンスルホニルペンチル基、２−エタンスルホニルエチル基、３−エタンスルホニルプロピル基、４−エタンスルホニルブチル基、５−エタンスルホニルペンチル基、２−プロパンスルホニルエチル基、３−プロパンスルホニルプロピル基、４−プロパンスルホニルブチル基、５−プロパンスルホニルペンチル基、２−ブタンスルホニルエチル基、３−ブタンスルホニルプロピル基、４−ブタンスルホニルブチル基及び５−ブタンスルホニルペンチル基が挙げられる。
　「Ｃ３~Ｃ５シクロアルキル基」としては、シクロプロピル基、シクロブチル基及びシクロペンチル基が挙げられる。
　「群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基」としては、例えばシクロプロピルメチル基、２−シクロプロピルエチル基、３−シクロプロピルプロピル基、４−シクロプロピルブチル基、５−シクロプロピルペンチル基、
メチル基、フルオロメチル基、ジフルオロメチル基、トリフルオロメチル基、クロロメチル基、ジクロロメチル基、トリクロロメチル基、ブロモメチル基、ジブロモメチル基、ヨードメチル基、クロロジフルオロメチル基、
エチル基、２−フルオロエチル基、２，２，２−トリフルオロエチル基、パーフルオロエチル基、２−クロロエチル基、２，２，２−トリクロロエチル基、２−ブロモエチル基、２−ヨードエチル基、
プロピル基、３−フルオロプロピル基、３，３，３−トリフルオロプロピル基、パーフルオロプロピル基、イソプロピル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロピル基、パーフルオロイソプロピル基、３−クロロプロピル基、３，３，３−トリクロロプロピル基、３−ブロモプロピル基、３−ヨードプロピル基、
ブチル基、４−フルオロブチル基、４，４，４−トリフルオロブチル基、パーフルオロブチル基、４−クロロブチル基、４，４，４−トリクロロブチル基、４−ブロモブチル基、４−ヨードブチル基、ｓ−ブチル基、ｔ−ブチル基、
ペンチル基、５−フルオロペンチル基、５，５，５−トリフルオロペンチル基、パーフルオロペンチル基、５−クロロペンチル基、５，５，５−トリクロロペンチル基、５−ブロモペンチル基、５−ヨードペンチル基、
シアノメチル基、ジシアノメチル基、２−シアノエチル基、２，２−ジシアノエチル基、３−シアノプロピル基、３，３−ジシアノプロピル基、４−シアノブチル基、４，４−ジシアノブチル基、５−シアノペンチル基、５，５−ジシアノペンチル基、
メトキシメチル基、エトキシメチル基、プロポキシメチル基、イソプロポキシメチル基、ブトキシメチル基、イソブトキシメチル基、ｔ−ブトキシメチル基、２−メトキシエチル基、３−メトキシプロピル基、４−メトキシブチル基、５−メトキシペンチル基、２−エトキシエチル基、３−エトキシプロピル基、４−エトキシブチル基、５−エトキシペンチル基、２−プロポキシエチル基、３−プロポキシプロピル基、４−プロポキシブチル基、５−プロポキシペンチル基、２−ブトキシエチル基、３−ブトキシプロピル基、４−ブトキシブチル基、５−ブトキシペンチル基、
メチルチオメチル基、エチルチオメチル基、プロピルチオメチル基、イソプロピルチオメチル基、ブチルチオメチル基、イソブチルチオメチル基、ｔ−ブチルチオメチル基、２−メチルチオエチル基、３−メチルチオプロピル基、４−メチルチオブチル基、５−メチルチオペンチル基、２−エチルチオエチル基、３−エチルチオプロピル基、４−エチルチオブチル基、５−エチルチオペンチル基、２−プロピルチオエチル基、３−プロピルチオプロピル基、４−プロピルチオブチル基、５−プロピルチオペンチル基、２−ブチルチオエチル基、３−ブチルチオプロピル基、４−ブチルチオブチル基、５−ブチルチオペンチル基、
メタンスルフィニルメチル基、エタンスルフィニルメチル基、プロパンスルフィニルメチル基、イソプロパンスルフィニルメチル基、ブタンスルフィニルメチル基、イソブタンスルフィニルメチル基、ｔ−ブタンスルフィニルメチル基、２−メタンスルフィニルエチル基、３−メタンスルフィニルプロピル基、４−メタンスルフィニルブチル基、５−メタンスルフィニルペンチル基、２−エタンスルフィニルエチル基、３−エタンスルフィニルプロピル基、４−エタンスルフィニルブチル基、５−エタンスルフィニルペンチル基、２−プロパンスルフィニルエチル基、３−プロパンスルフィニルプロピル基、４−プロパンスルフィニルブチル基、５−プロパンスルフィニルペンチル基、２−ブタンスルフィニルエチル基、３−ブタンスルフィニルプロピル基、４−ブタンスルフィニルブチル基、５−ブタンスルフィニルペンチル基、
メタンスルホニルメチル基、エタンスルホニルメチル基、プロパンスルホニルメチル基、イソプロパンスルホニルメチル基、ブタンスルホニルメチル基、イソブタンスルホニルメチル基、ｔ−ブタンスルホニルメチル基、２−メタンスルホニルエチル基、３−メタンスルホニルプロピル基、４−メタンスルホニルブチル基、５−メタンスルホニルペンチル基、２−エタンスルホニルエチル基、３−エタンスルホニルプロピル基、４−エタンスルホニルブチル基、５−エタンスルホニルペンチル基、２−プロパンスルホニルエチル基、３−プロパンスルホニルプロピル基、４−プロパンスルホニルブチル基、５−プロパンスルホニルペンチル基、２−ブタンスルホニルエチル基、３−ブタンスルホニルプロピル基、４−ブタンスルホニルブチル基及び５−ブタンスルホニルペンチル基が挙げられる。
　「群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基」としては、例えばシクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、シクロヘプチル基、シクロオクチル基、シクロノニル基、シクロデシル基、メチルシクロプロピル基、１，１−ジメチルシクロプロピル基、エチルシクロプロピル基、プロピルシクロプロピル基、ブチルシクロプロピル基、ペンチルシクロプロピル基、２−メチルシクロヘキシル基、２−エチルシクロヘキシル基、２−プロピルシクロヘキシル基、２−ブチルシクロヘキシル基、２−ペンチルシクロヘキシル基、３−メチルシクロヘキシル基、３−エチルシクロヘキシル基、３−プロピルシクロヘキシル基、３−ブチルシクロヘキシル基、３−ペンチルシクロヘキシル基、４−メチルシクロヘキシル基、４−エチルシクロヘキシル基、４−プロピルシクロヘキシル基、４−ブチルシクロヘキシル基、４−ペンチルシクロヘキシル基、フルオロシクロプロピル基、クロロシクロプロピル基、１，１−ジフルオロシクロプロピル基、１，１−ジクロロシクロプロピル基、２−フルオロシクロヘキシル基、３−フルオロシクロヘキシル基、４−フルオロシクロヘキシル基、２−クロロシクロヘキシル基、３−クロロシクロヘキシル基及び４−クロロシクロヘキシル基が挙げられる。
　「群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基」としては、例えばフェニル基、２−フルオロフェニル基、３−フルオロフェニル基、４−フルオロフェニル基、２−クロロフェニル基、３−クロロフェニル基、４−クロロフェニル基、２−ブロモフェニル基、３−ブロモフェニル基、４−ブロモフェニル基、２−ヨードフェニル基、３−ヨードフェニル基、４−ヨードフェニル基、２−シアノフェニル基、３−シアノフェニル基、４−シアノフェニル基、２−ニトロフェニル基、３−ニトロフェニル基、４−ニトロフェニル基、２−メチルフェニル基、３−メチルフェニル基、４−メチルフェニル基、２−エチルフェニル基、３−エチルフェニル基、４−エチルフェニル基、２−プロピルフェニル基、３−プロピルフェニル基、４−プロピルフェニル基、２−イソプロピルフェニル基、３−イソプロピルフェニル基、４−イソプロピルフェニル基、２−ブチルフェニル基、３−ブチルフェニル基、４−ブチルフェニル基、２−イソブチルフェニル基、３−イソブチルフェニル基、４−イソブチルフェニル基、２−ｔ−ブチルフェニル基、３−ｔ−ブチルフェニル基、４−ｔ−ブチルフェニル基、２−ペンチルフェニル基、３−ヘキシルフェニル基、４−ヘプチルフェニル基、２−オクチルフェニル基、３−ノニルフェニル基、４−デシルフェニル基、２−トリフルオロメチルフェニル基、３−トリフルオロメチルフェニル基、４−トリフルオロメチルフェニル基、２−（２，２，２−トリフルオロエチル）フェニル基、３−（３，３，３−トリフルオロプロピル）フェニル基、４−（４，４，４−トリフルオロブチル）フェニル基、２−（５，５，５−トリフルオロペンチル）フェニル基、３−（６，６，６−トリフルオロヘキシル）フェニル基、４−（７，７，７−トリフルオロヘプチル）フェニル基、２−（８，８，８−トリフルオロオクチル）フェニル基、３−（９，９，９−トリフルオロノニル）フェニル基、４−（１０，１０，１０−トリフルオロデシル）フェニル基、
２−シクロプロピルフェニル基、３−シクロプロピルフェニル基、４−シクロプロピルフェニル基、２−シクロブチルフェニル基、３−シクロペンチルフェニル基、４−シクロヘキシルフェニル基、２−シクロヘプチルフェニル基、３−シクロオクチルフェニル基、４−シクロノニルフェニル基、２−シクロデシルフェニル基、３−（メチルシクロプロピル）フェニル基、４−（１，１−ジメチルシクロプロピル）フェニル基、３−（フルオロシクロプロピル）フェニル基、４−（クロロシクロプロピル）フェニル基、２−（１，１−ジフルオロシクロプロピル）フェニル基、３−（１，１−ジクロロシクロプロピル）フェニル基、４−（２−フルオロシクロヘキシル）フェニル基、４−（２−クロロシクロヘキシル）フェニル基、
２−メトキシフェニル基、３−メトキシフェニル基、４−メトキシフェニル基、２−トリフルオロメトキシフェニル基、３−トリフルオロメトキシフェニル基、４−トリフルオロメトキシフェニル基、２−エトキシフェニル基、３−プロポキシフェニル基、４−ブトキシフェニル基、
２−メチルチオフェニル基、３−メチルチオフェニル基、４−メチルチオフェニル基、２−トリフルオロメチルチオフェニル基、３−トリフルオロメチルチオフェニル基、４−トリフルオロメチルチオフェニル基、２−エチルチオフェニル基、３−プロピルチオフェニル基、４−ブチルチオフェニル基、
２−メタンスルフィニルフェニル基、３−メタンスルフィニルフェニル基、４−メタンスルフィニルフェニル基、２−メタンスルフィニルフェニル基、３−メタンスルフィニルフェニル基、４−メタンスルフィニルフェニル基、２−エチルスルフィニルフェニル基、３−プロピルスルフィニルフェニル基、４−ブチルスルフィニルフェニル基、
２−メタンスルホニルフェニル基、３−メタンスルホニルフェニル基、４−メタンスルホニルフェニル基、２−メタンスルホニルフェニル基、３−メタンスルホニルフェニル基、４−メタンスルホニルフェニル基、２−エチルスルホニルフェニル基、３−プロピルスルホニルフェニル基、４−ブチルスルホニルフェニル基、２−アセチルフェニル基、３−アセチルフェニル基、４−アセチルフェニル基、２−ジフルオロアセチルフェニル基、３−トリフルオロアセチルフェニル基、４−ジクロロアセチルフェニル基、２−トリクロロアセチルフェニル基、３−プロパノイルフェニル基、４−ブタノイルフェニル基、２−イソブタノイルフェニル基、３−ペンタノイルフェニル基、４−ピバロイルフェニル基、
２−（メトキシカルボニル）フェニル基、３−（メトキシカルボニル）フェニル基、４−（メトキシカルボニル）フェニル基、２−（トリフルオロメトキシカルボニル）フェニル基、３−（トリクロロメトキシカルボニル）フェニル基、４−（エトキシカルボニル）フェニル基、２−（プロポキシカルボニル）フェニル基、３−（イソプロポキシカルボニル）フェニル基、４−（ブトキシカルボニル）フェニル基、
２−アセトキシフェニル基、３−アセトキシフェニル基、４−アセトキシフェニル基、２−ジフルオロアセトキシフェニル基、３−トリフルオロアセトキシフェニル基、４−トリクロロアセトキシフェニル基、２−プロパノイルオキシフェニル基、３−ブタノイルオキシフェニル基、４−イソブタノイルオキシフェニル基、２−ペンタノイルオキシフェニル基及び３−ピバロイルオキシフェニル基が挙げられる。
　「群Ｅより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５ポリメチレン基」としては、例えばエチレン基、１，３−プロピレン基、１，４−ブチレン基、１，５−ペンチレン基、フルオロエチレン基、クロロエチレン基、ブロモエチレン基、シアノエチレン基、ニトロエチレン基、１，２−プロピレン基、３，３，３−トリフルオロ−１，２−プロピレン基、シクロプロピルエチレン基、メトキシエチレン基、トリフルオロメトキシエチレン基、メチルチオエチレン基、トリフルオロメチルチオエチレン基、メタンスルフィニルエチレン基、トリフルオロメタンスルフィニルエチレン基、メタンスルホニルエチレン基、トリフルオロメタンスルホニルエチレン基、アセチルエチレン基、トリフルオロアセチルエチレン基、メトキシカルボニルエチレン基、トリフルオロメトキシカルボニルエチレン基、アセトキシエチレン基及びトリフルオロアセトキシエチレン基が挙げられる。
　「群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基」としては、例えばプロペン−１，３−ジイル基、２−フルオロプロペン−１，３−ジイル基、３−フルオロプロペン−１，３−ジイル基、３，３−ジフルオロプロペン−１，３−ジイル基、２−クロロプロペン−１，３−ジイル基、２−ブロモプロペン−１，３−ジイル基、２−シアノプロペン−１，３−ジイル基、２−ニトロプロペン−１，３−ジイル基、２−メチルプロペン−１，３−ジイル基、３−メチルプロペン−１，３−ジイル基、３，３−ジメチルプロペン−１，３−ジイル基、２−トリフルオロメチルプロペン−１，３−ジイル基、２−シクロプロピルプロペン−１，３−ジイル基、２−メトキシプロペン−１，３−ジイル基、２−トリフルオロメトキシプロペン−１，３−ジイル基、２−メチルチオプロペン−１，３−ジイル基、２−トリフルオロメチルチオプロペン−１，３−ジイル基、２−メタンスルフィニルプロペン−１，３−ジイル基、２−トリフルオロメタンスルフィニルプロペン−１，３−ジイル基、２−アセチルプロペン−１，３−ジイル基、２−トリフルオロアセチルプロペン−１，３−ジイル基、２−メトキシカルボニルプロペン−１，３−ジイル基、２−トリフルオロメトキシカルボニルプロペン−１，３−ジイル基、２−アセトキシプロペン−１，３−ジイル基及び２−トリフルオロアセトキシプロペン−１，３−ジイル基が挙げられる。
　「群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基」としては、例えば１，３−ブタジエン−１，４−ジイル基、１−フルオロ−１，３−ブタジエン−１，４−ジイル基、２−フルオロ−１，３−ブタジエン−１，４−ジイル基、１−クロロ−１，３−ブタジエン−１，４−ジイル基、２−クロロ−１，３−ブタジエン−１，４−ジイル基、１−ブロモ−１，３−ブタジエン−１，４−ジイル基、２−ブロモ−１，３−ブタジエン−１，４−ジイル基、１−シアノ−１，３−ブタジエン−１，４−ジイル基、１−ニトロ−１，３−ブタジエン−１，４−ジイル基、１−メチル−１，３−ブタジエン−１，４−ジイル基、２−メチル−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロメチル−１，３−ブタジエン−１，４−ジイル基、１−シクロプロピル−１，３−ブタジエン−１，４−ジイル基、１−メトキシ−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロメトキシプ−１，３−ブタジエン−１，４−ジイル基、１−メチルチオ−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロメチルチオ−１，３−ブタジエン−１，４−ジイル基、１−メタンスルフィニル−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロメタンスルフィニル−１，３−ブタジエン−１，４−ジイル基、１−アセチル−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロアセチル−１，３−ブタジエン−１，４−ジイル基、１−メトキシカルボニル−１，３−ブタジエン−１，４−ジイル基、１−トリフルオロメトキシカルボニル−１，３−ブタジエン−１，４−ジイル基、１−アセトキシ−１，３−ブタジエン−１，４−ジイル基及び１−トリフルオロアセトキシ−１，３−ブタジエン−１，４−ジイル基が挙げられる。
　「Ｃ１~Ｃ４鎖式炭化水素基」としては、例えばメチル基、エチル基、エチニル基、プロピル基、イソプロピル基、アリル基、プロパルギル基、ブチル基、イソブチル基及びｔ−ブチル基が挙げられる。
　「群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基」としては、例えばシクロプロピルメチル基、２−シクロプロピルエチル基、３−シクロプロピルプロピル基、４−シクロプロピルブチル基、５−シクロプロピルペンチル基、
メチル基、フルオロメチル基、ジフルオロメチル基、トリフルオロメチル基、クロロメチル基、ジクロロメチル基、トリクロロメチル基、ブロモメチル基、ジブロモメチル基、ヨードメチル基、
エチル基、２−フルオロエチル基、２，２，２−トリフルオロエチル基、パーフルオロエチル基、２−クロロエチル基、２，２，２−トリクロロエチル基、２−ブロモエチル基、２−ヨードエチル基、
プロピル基、３−フルオロプロピル基、３，３，３−トリフルオロプロピル基、パーフルオロプロピル基、イソプロピル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロピル基、パーフルオロイソプロピル基、３−クロロプロピル基、３，３，３−トリクロロプロピル基、３−ブロモプロピル基、３−ヨードプロピル基、
ブチル基、４−フルオロブチル基、４，４，４−トリフルオロブチル基、パーフルオロブチル基、４−クロロブチル基、４，４，４−トリクロロブチル基、４−ブロモブチル基、４−ヨードブチル基、ｓ−ブチル基、ｔ−ブチル基、
ペンチル基、５−フルオロペンチル基、５，５，５−トリフルオロペンチル基、パーフルオロペンチル基、５−クロロペンチル基、５，５，５−トリクロロペンチル基、５−ブロモペンチル基、５−ヨードペンチル基、
ヘキシル基、６，６，６−トリフルオロヘキシル基、６−クロロヘキシル基、
ヘプチル基、７，７，７−トリフルオロヘプチル基、７−クロロヘプチル基、
オクチル基、８，８，８、−トリフルオロオクチル基、８−クロロオクチル基、ノニル基、９，９，９−トリフルオロノニル基、９−クロロノニル基、
デシル基、１０，１０，１０−トリフルオロデシル基、１０−クロロデシル基、シアノメチル基、ジシアノメチル基、２−シアノエチル基、２，２−ジシアノエチル基、３−シアノプロピル基、３，３−ジシアノプロピル基、４−シアノブチル基、４，４−ジシアノブチル基、５−シアノペンチル基、５，５−ジシアノペンチル基、
メトキシメチル基、エトキシメチル基、プロポキシメチル基、イソプロポキシメチル基、ブトキシメチル基、イソブトキシメチル基、ｔ−ブトキシメチル基、２−メトキシエチル基、３−メトキシプロピル基、４−メトキシブチル基、５−メトキシペンチル基、２−エトキシエチル基、３−エトキシプロピル基、４−エトキシブチル基、５−エトキシペンチル基、２−プロポキシエチル基、３−プロポキシプロピル基、４−プロポキシブチル基、５−プロポキシペンチル基、２−ブトキシエチル基、３−ブトキシプロピル基、４−ブトキシブチル基、５−ブトキシペンチル基、
メチルチオメチル基、エチルチオメチル基、プロピルチオメチル基、イソプロピルチオメチル基、ブチルチオメチル基、イソブチルチオメチル基、ｔ−ブチルチオメチル基、２−メチルチオエチル基、３−メチルチオプロピル基、４−メチルチオブチル基、５−メチルチオペンチル基、２−エチルチオエチル基、３−エチルチオプロピル基、４−エチルチオブチル基、５−エチルチオペンチル基、２−プロピルチオエチル基、３−プロピルチオプロピル基、４−プロピルチオブチル基、５−プロピルチオペンチル基、２−ブチルチオエチル基、３−ブチルチオプロピル基、４−ブチルチオブチル基、５−ブチルチオペンチル基、
メタンスルフィニルメチル基、エタンスルフィニルメチル基、プロパンスルフィニルメチル基、イソプロパンスルフィニルメチル基、ブタンスルフィニルメチル基、イソブタンスルフィニルメチル基、ｔ−ブタンスルフィニルメチル基、２−メタンスルフィニルエチル基、３−メタンスルフィニルプロピル基、４−メタンスルフィニルブチル基、５−メタンスルフィニルペンチル基、２−エタンスルフィニルエチル基、３−エタンスルフィニルプロピル基、４−エタンスルフィニルブチル基、５−エタンスルフィニルペンチル基、２−プロパンスルフィニルエチル基、３−プロパンスルフィニルプロピル基、４−プロパンスルフィニルブチル基、５−プロパンスルフィニルペンチル基、２−ブタンスルフィニルエチル基、３−ブタンスルフィニルプロピル基、４−ブタンスルフィニルブチル基、５−ブタンスルフィニルペンチル基、
メタンスルホニルメチル基、エタンスルホニルメチル基、プロパンスルホニルメチル基、イソプロパンスルホニルメチル基、ブタンスルホニルメチル基、イソブタンスルホニルメチル基、ｔ−ブタンスルホニルメチル基、２−メタンスルホニルエチル基、３−メタンスルホニルプロピル基、４−メタンスルホニルブチル基、５−メタンスルホニルペンチル基、２−エタンスルホニルエチル基、３−エタンスルホニルプロピル基、４−エタンスルホニルブチル基、５−エタンスルホニルペンチル基、２−プロパンスルホニルエチル基、３−プロパンスルホニルプロピル基、４−プロパンスルホニルブチル基、５−プロパンスルホニルペンチル基、２−ブタンスルホニルエチル基、３−ブタンスルホニルプロピル基、４−ブタンスルホニルブチル基及び５−ブタンスルホニルペンチル基が挙げられる。
　「Ｃ１−Ｃ４アルコキシ基」としては、メトキシ基、エトキシ基、プロポキシ基、イソプロポキシ基、ブトキシ基、イソブトキシ基及びｔ−ブトキシ基が挙げられる。
　「Ｃ１−Ｃ４アルキルチオ基」としては、メチルチオ基、エチルチオ基、プロピルチオ基、イソプロピルチオ基、ブチルチオ基、イソブチルチオ基及びｔ−ブチルチオ基が挙げられる。
　「Ｃ１−Ｃ４アルキルスルフィニル基」としては、メタンスルフィニル基、エタンスルフィニル基、プロパンスルフィニル基、イソプロパンスルフィニル基、ブタンスルフィニル基、イソブタンスルフィニル基及びｔ−ブタンスルフィニル基が挙げられる。
　「Ｃ１−Ｃ４アルキルスルホニル基」としては、メタンスルホニル基、エタンスルホニル基、プロパンスルホニル基、イソプロパンスルホニル基、ブタンスルホニル基、イソブタンスルホニル基及びｔ−ブタンスルホニル基が挙げられる。
　「ハロゲンで置換されていてもよいＣ１~Ｃ４アルコキシ基」としては、例えばメトキシ基、フルオロメトキシ基、ジフルオロメトキシ基、トリフルオロメトキシ基、クロロメトキシ基、ジクロロメトキシ基、トリクロロメトキシ基、ブロモメトキシ基、ジブロモメトキシ基、ヨードメトキシ基、クロロジフルオロメトキシ基、
エトキシ基、２−フルオロエトキシ基、２，２，２−トリフルオロエトキシ基、パーフルオロエトキシ基、２−クロロエトキシ基、２，２，２−トリクロロエトキシ基、２−ブロモエトキシ基、２−ヨードエトキシ基、
プロポキシ基、３−フルオロプロポキシ基、３，３，３−トリフルオロプロポキシ基、パーフルオロプロポキシ基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロポキシ基、パーフルオロイソプロポキシ基、３−クロロプロポキシ基、３，３，３−トリクロロプロポキシ基、３−ブロモプロポキシ基、３−ヨードプロポキシ基、
ブトキシ基、４−フルオロブトキシ基、４，４，４−トリフルオロブトキシ基、パーフルオロブトキシ基、４−クロロブトキシ基、４，４，４−トリクロロブトキシ基、４−ブロモブトキシ基及び４−ヨードブトキシ基が挙げられる。
　「ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルチオ基」としては、例えばメチルチオ基、フルオロメチルチオ基、ジフルオロメチルチオ基、トリフルオロメチルチオ基、クロロメチルチオ基、ジクロロメチルチオ基、トリクロロメチルチオ基、ブロモメチルチオ基、ジブロモメチルチオ基、ヨードメチルチオ基、クロロジフルオロメチルチオ基、
エチルチオ基、２−フルオロエチルチオ基、２，２，２−トリフルオロエチルチオ基、パーフルオロエチルチオ基、２−クロロエチルチオ基、２，２，２−トリクロロエチルチオ基、２−ブロモエチルチオ基、２−ヨードエチルチオ基、
プロピルチオ基、３−フルオロプロピルチオ基、３，３，３−トリフルオロプロピルチオ基、パーフルオロプロピルチオ基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロピルチオ基、パーフルオロイソプロピルチオ基、３−クロロプロピルチオ基、３，３，３−トリクロロプロピルチオ基、３−ブロモプロピルチオ基、３−ヨードプロピルチオ基、
ブチルチオ基、４−フルオロブチルチオ基、４，４，４−トリフルオロブチルチオ基、パーフルオロブチルチオ基、４−クロロブチルチオ基、４，４，４−トリクロロブチルチオ基、４−ブロモブチルチオ基及び４−ヨードブチルチオ基が挙げられる。
　「ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルフィニル基」としては、例えばメタンスルフィニル基、フルオロメタンスルフィニル基、ジフルオロメタンスルフィニル基、トリフルオロメタンスルフィニル基、クロロメタンスルフィニル基、ジクロロメタンスルフィニル基、トリクロロメタンスルフィニル基、ブロモメタンスルフィニル基、ジブロモメタンスルフィニル基、ヨードメタンスルフィニル基、クロロジフルオロメタンスルフィニル基、
エタンスルフィニル基、２−フルオロエタンスルフィニル基、２，２，２−トリフルオロエタンスルフィニル基、パーフルオロエタンスルフィニル基、２−クロロエタンスルフィニル基、２，２，２−トリクロロエタンスルフィニル基、２−ブロモエタンスルフィニル基、２−ヨードエタンスルフィニル基、
プロパンスルフィニル基、３−フルオロプロパンスルフィニル基、３，３，３−トリフルオロプロパンスルフィニル基、パーフルオロプロパンスルフィニル基、イソプロパンスルフィニル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロパンスルフィニル基、パーフルオロイソプロパンスルフィニル基、３−クロロプロパンスルフィニル基、３，３，３−トリクロロプロパンスルフィニル基、３−ブロモプロパンスルフィニル基、３−ヨードプロパンスルフィニル基、ブタンスルフィニル基、４−フルオロブタンスルフィニル基、４，４，４−トリフルオロブタンスルフィニル基、パーフルオロブタンスルフィニル基、４−クロロブタンスルフィニル基、４，４，４−トリクロロブタンスルフィニル基、４−ブロモブタンスルフィニル基及び４−ヨードブタンスルフィニル基が挙げられる。
　「ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルホニル基」としては、例えばメタンスルホニル基、フルオロメタンスルホニル基、ジフルオロメタンスルホニル基、トリフルオロメタンスルホニル基、クロロメタンスルホニル基、ジクロロメタンスルホニル基、トリクロロメタンスルホニル基、ブロモメタンスルホニル基、ジブロモメタンスルホニル基、ヨードメタンスルホニル基、クロロジフルオロメタンスルホニル基、
エタンスルホニル基、２−フルオロエタンスルホニル基、２，２，２−トリフルオロエタンスルホニル基、パーフルオロエタンスルホニル基、２−クロロエタンスルホニル基、２，２，２−トリクロロエタンスルホニル基、２−ブロモエタンスルホニル基、２−ヨードエタンスルホニル基、
プロパンスルホニル基、３−フルオロプロパンスルホニル基、３，３，３−トリフルオロプロパンスルホニル基、パーフルオロプロパンスルホニル基、イソプロパンスルホニル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロパンスルホニル基、パーフルオロイソプロパンスルホニル基、３−クロロプロパンスルホニル基、３，３，３−トリクロロプロパンスルホニル基、３−ブロモプロパンスルホニル基、３−ヨードプロパンスルホニル基、
ブタンスルホニル基、４−フルオロブタンスルホニル基、４，４，４−トリフルオロブタンスルホニル基、パーフルオロブタンスルホニル基、４−クロロブタンスルホニル基、４，４，４−トリクロロブタンスルホニル基、４−ブロモブタンスルホニル基及び４−ヨードブタンスルホニル基が挙げられる。
　「ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニル基」としては、例えばアセチル基、フルオロアセチル基、ジフルオロアセチル基、トリフルオロアセチル基、クロロアセチル基、ジクロロアセチル基、トリクロロアセチル基、ブロモアセチル基、ジブロモアセチル基、ヨードアセチル基、クロロジフルオロアセチル基、
プロパノイル基、３−フルオロプロパノイル基、３，３，３−トリフルオロプロパノイル基、パーフルオロプロパノイル基、３−クロロプロパノイル基、３，３，３−トリクロロプロパノイル基、３−ブロモプロパノイル基、３−ヨードプロパノイル基、
ブタノイル基、４−フルオロブタノイル基、４，４，４−トリフルオロブタノイル基、パーフルオロブタノイル基、３，３，３，３’，３’，３’−ヘキサフルオロイソブタノイル基、パーフルオロイソブタノイル基、４−クロロブタノイル基、４，４，４−トリクロロブタノイル基、４−ブロモブタノイル基、４−ヨードブタノイル基、イソブタノイル基、２，２，２，２’，２’，２’−ヘキサフルオロイソブタノイル基、パーフルオロイソブタノイル基、
ペンタノイル基、５−フルオロペンタノイル基、５，５，５−トリフルオロペンタノイル基、パーフルオロペンタノイル基、５−クロロペンタノイル基、５，５，５−トリクロロペンタノイル基、５−ブロモペンタノイル基、５−ヨードペンタノイル基及びピバロイル基が挙げられる。
　「ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルコキシ）カルボニル基」としては、例えばメトキシカルボニル基、フルオロメトキシカルボニル基、ジフルオロメトキシカルボニル基、トリフルオロメトキシカルボニル基、クロロメトキシカルボニル基、ジクロロメトキシカルボニル基、トリクロロメトキシカルボニル基、ブロモメトキシカルボニル基、ジブロモメトキシカルボニル基、ヨードメトキシカルボニル基、クロロジフルオロメトキシカルボニル基、
エトキシカルボニル基、２−フルオロエトキシカルボニル基、２，２，２−トリフルオロエトキシカルボニル基、パーフルオロエトキシカルボニル基、２−クロロエトキシカルボニル基、２，２，２−トリクロロエトキシカルボニル基、２−ブロモエトキシカルボニル基、２−ヨードエトキシカルボニル基、
プロポキシカルボニル基、３−フルオロプロポキシカルボニル基、３，３，３−トリフルオロプロポキシカルボニル基、パーフルオロプロポキシカルボニル基、イソプロポキシカルボニル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロポキシカルボニル基、パーフルオロイソプロポキシカルボニル基、３−クロロプロポキシカルボニル基、３，３，３−トリクロロプロポキシカルボニル基、３−ブロモプロポキシカルボニル基、３−ヨードプロポキシカルボニル基、
ブトキシカルボニル基、４−フルオロブトキシカルボニル基、４，４，４−トリフルオロブトキシカルボニル基、パーフルオロブトキシカルボニル基、４−クロロブトキシカルボニル基、４，４，４−トリクロロブトキシカルボニル基、４−ブロモブトキシカルボニル基、４−ヨードブトキシカルボニル基及びｔ−ブトキシカルボニル基が挙げられる。
　「ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニルオキシ基」としては、例えばアセトキシ基、フルオロアセトキシ基、ジフルオロアセトキシ基、トリフルオロアセトキシ基、クロロアセトキシ基、ジクロロアセトキシ基、トリクロロアセトキシ基、ブロモアセトキシ基、ジブロモアセトキシ基、ヨードアセトキシ基、クロロジフルオロアセトキシ基、
プロパノイルオキシ基、３−フルオロプロパノイルオキシ基、３，３，３−トリフルオロプロパノイルオキシ基、パーフルオロプロパノイルオキシ基、３−クロロプロパノイルオキシ基、３，３，３−トリクロロプロパノイルオキシ基、３−ブロモプロパノイルオキシ基、３−ヨードプロパノイルオキシ基、
ブタノイルオキシ基、４−フルオロブタノイルオキシ基、４，４，４−トリフルオロブタノイルオキシ基、パーフルオロブタノイルオキシ基、イソブタノイルオキシ基、３，３，３，３’，３’，３’−ヘキサフルオロイソブタノイルオキシ基、パーフルオロイソブタノイルオキシ基、４−クロロブタノイルオキシ基、４，４，４−トリクロロブタノイルオキシ基、４−ブロモブタノイルオキシ基、４−ヨードブタノイルオキシ基、ペンタノイルオキシ基、５−フルオロペンタノイルオキシ基、５，５，５−トリフルオロペンタノイルオキシ基、パーフルオロペンタノイルオキシ基、５−クロロペンタノイルオキシ基、５，５，５−トリクロロペンタノイルオキシ基、５−ブロモペンタノイルオキシ基、５−ヨードペンタノイルオキシ基及びピバロイルオキシ基等が挙げられる。
　「Ｃ１~Ｃ５アルキル基」としては、例えばメチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｔ−ブチル基及びペンチル基が挙げられる。
　「ハロゲンで置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基」としては、例えばメチル基、フルオロメチル基、ジフルオロメチル基、トリフルオロメチル基、クロロメチル基、ジクロロメチル基、トリクロロメチル基、ブロモメチル基、ジブロモメチル基、ヨードメチル基、クロロジフルオロメチル基、
エチル基、２−フルオロエチル基、２，２，２−トリフルオロエチル基、パーフルオロエチル基、２−クロロエチル基、２，２，２−トリクロロエチル基、２−ブロモエチル基、２−ヨードエチル基、
プロピル基、３−フルオロプロピル基、３，３，３−トリフルオロプロピル基、パーフルオロプロピル基、イソプロピル基、２，２，２，２’，２’，２’−ヘキサフルオロイソプロピル基、パーフルオロイソプロピル基、３−クロロプロピル基、３，３，３−トリクロロプロピル基、３−ブロモプロピル基、３−ヨードプロピル基、
ブチル基、４−フルオロブチル基、４，４，４−トリフルオロブチル基、パーフルオロブチル基、４−クロロブチル基、４，４，４−トリクロロブチル基、４−ブロモブチル基、４−ヨードブチル基、ｓ−ブチル基、ｔ−ブチル基、
ペンチル基、５−フルオロペンチル基、５，５，５−トリフルオロペンチル基、パーフルオロペンチル基、５−クロロペンチル基、５，５，５−トリクロロペンチル基、５−ブロモペンチル基及び５−ヨードペンチル基が挙げられる。
　本発明化合物の態様としては、例えば以下のアミド化合物が挙げられる。
式（１）において、Ｒ１が水素、ハロゲン、シアノ基、群Ａより選ばれる１以上の基で置換されたメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されたメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されたメチル基、フルオロメチル基又はジフルオロメチル基であるアミド化合物；
式（１）において、Ｒ１が水素又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素又は塩素であるアミド化合物；
式（１）において、Ｒ１が水素であるアミド化合物；
式（１）において、Ｒ１がハロゲンであるアミド化合物；
式（１）において、Ｒ１が塩素であるアミド化合物；
式（１）において、Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基又は−Ｓ−Ｒ５基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、群Ｅより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５ポリメチレン基、群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基、群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基であるアミド化合物；
式（１）において、Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基、−Ｓ−Ｒ５基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、Ｃ２~Ｃ５ポリメチレン基、プロペン−１，３−ジイル基、１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基であるアミド化合物；
式（１）において、Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基、フェニル基、ハロゲンを表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、Ｃ２~Ｃ５ポリメチレン基、プロペン−１，３−ジイル基又は１，３−ブタジエン−１，４−ジイル基であるアミド化合物；
式（１）において、Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基又はハロゲンであるアミド化合物；
式（１）において、Ｒ２はハロゲンで置換されていてもよいメチル基又はハロゲンであるアミド化合物；
式（１）において、ｐが０であるアミド化合物；
式（１）において、Ｒ２がメチル基であるアミド化合物；
式（１）において、Ｒ２がトリフルオロメチル基であるアミド化合物；
式（１）において、Ｒ２がフッ素原であるアミド化合物；
式（１）において、Ｒ２が塩素であるアミド化合物；
式（１）において、Ｒ２が臭素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がトリフルオロメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がフッ素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２が塩素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２が臭素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の２位に位置するメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の３位に位置するメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の４位に位置するメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の２位に位置するトリフルオロメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の４位に位置するトリフルオロメチル基であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の２位に位置するフッ素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の３位に位置するフッ素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の４位に位置するフッ素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の２位に位置する塩素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の４位に位置する塩素であるアミド化合物；
式（１）において、ｐが１であり、Ｒ２がベンゼン環上の２位に位置する臭素であるアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がともにフッ素であるアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がフッ素及び塩素であるアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がともにフッ素であり、２つのＲ２がベンゼン環上の２位及び３位に位置するアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がともにフッ素であり、２つのＲ２がベンゼン環上の２位及び４位に位置するアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がともにフッ素であり、２つのＲ２がベンゼン環上の２位及び６位に位置するアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がフッ素及び塩素であるアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がベンゼン環上の２位に位置するフッ素及び４位に位置する塩素であるアミド化合物；
式（１）において、ｐが２であり、２つのＲ２がベンゼン環上の４位に位置するフッ素及び２位に位置する塩素であるアミド化合物；
式（１）において、ｐが３であり、３つのＲ２がともにフッ素であるアミド化合物；
式（１）において、ｐが３であり、３つのＲ２がともにフッ素であり、３つのＲ２がベンゼン環上の２位、３位及び４位に位置するアミド化合物；
式（１）において、ｐが３であり、３つのＲ２がともにフッ素であり、３つのＲ２がベンゼン環上の３位、４位及び５位に位置するアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、シアノ基、群Ａより選ばれる１以上の基で置換されているメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であり、Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基又は−Ｓ−Ｒ５基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、群Ｅより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５ポリメチレン基、群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基、群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基であるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、シアノ基、群Ａより選ばれる１以上の基で置換されているメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であり、Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基又は−Ｓ−Ｒ５基を表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、Ｃ２~Ｃ５ポリメチレン基、プロペン−１，３−ジイル基、１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基であるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、シアノ基、群Ａより選ばれる１以上の基で置換されているメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基、フェニル基又はハロゲンを表すか、
或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、Ｃ２~Ｃ５ポリメチレン基、プロペン−１，３−ジイル基又は１，３−ブタジエン−１，４−ジイル基であるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、シアノ基、群Ａより選ばれる１以上の基で置換されているメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されているメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されているメチル基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ１０シクロアルキル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されているメチル基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２はハロゲンで置換されていてもよいＣ１~Ｃ５鎖式炭化水素基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素、ハロゲン、群Ａより選ばれる１以上の基で置換されているメチル基、フルオロメチル基又はジフルオロメチル基であり、
Ｒ２はハロゲンで置換されていてもよいメチル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素又はハロゲンであり、
Ｒ２はハロゲンで置換されていてもよいメチル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素又は塩素であり、
Ｒ２はハロゲンで置換されていてもよいメチル基又はハロゲンであるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが１であり、Ｒ２がメチル基であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが１であり、Ｒ２がトリフルオロメチル基であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが１であり、Ｒ２がフッ素であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが１であり、Ｒ２が塩素であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが１であり、Ｒ２が臭素であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが２であり、２つのＲ２がともにフッ素であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが２であり、２つのＲ２がフッ素及び塩素であるアミド化合物；
式（１）において、Ｒ１が水素であり、ｐが３であり、３つのＲ２がともにフッ素であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが１であり、Ｒ２がメチル基であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが１であり、Ｒ２がトリフルオロメチル基であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが１であり、Ｒ２がフッ素であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが１であり、Ｒ２が塩素であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが１であり、Ｒ２が臭素であるアミド化合物；
式（１）において、Ｒ１が塩素であり、ｐが２であり、２つのＲ２がともにフッ素であるアミド化合物；
及び、
式（１）において、Ｒ１が塩素であり、ｐが２であり、２つのＲ２がフッ素及び塩素であるアミド化合物。
（製造法１）
　本発明化合物又はその塩は、化合物（３）又はその塩と化合物（２）とを、脱水縮合剤の存在下に反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-I000003
〔式中、Ｒ１、Ｒ２及びｐは前記と同じ意味を表す。〕
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばテトラヒドロフラン（以下、ＴＨＦと記す場合がある。）、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル（以下、ＭＴＢＥと記す場合がある。）等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド（以下、ＤＭＦと記す場合がある。）等の酸アミド類、ジメチルスルホキシド（以下、ＤＭＳＯと記す場合がある。）等のスルホキシド類及びこれらの混合物が挙げられる。
　該反応に用いられる脱水縮合剤としては、１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（以下、ＷＳＣと記す。）、ベンゾトリアゾール−１−イルオキシ）トリス（ジメチルアミノ）ホスホニウムヘキサフルオロホスフェート（以下、ＢＯＰ試薬と記す。）及び１，３−ジシクロヘキシルカルボジイミド等が挙げられる。
　該反応には化合物（２）１モルに対して、化合物（３）が通常１~３モルの割合、脱水縮合剤が通常１~５モルの割合で用いられる。
　該反応の反応温度は、通常０~２００℃の範囲である。該反応の反応時間は通常１~２４時間の範囲である。
　該反応において、ＢＯＰ試薬を使用する場合は、必要に応じて塩基の存在下で反応を行う。かかる塩基としては、例えばトリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
　該反応には化合物（２）１モルに対して、塩基が通常１~１０モルの割合で用いられる。
　反応終了後は、反応混合物に水を加えた後、有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。
（製造法２）
　本発明化合物は、化合物（３）又はその塩と化合物（４）又はその塩とを、塩基の存在下、反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-I000004
〔式中、Ｒ１、Ｒ２及びｐは前記と同じ意味を表す。〕
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類及びこれらの混合物が挙げられる。
　該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
　該反応には化合物（４）１モルに対して、化合物（３）が通常１~３モルの割合、塩基が通常１~１０モルの割合で用いられる。
　該反応の反応温度は通常−２０~１４０℃の範囲である。該反応の反応時間は通常０．１~２４時間の範囲である。
　反応終了後は、反応混合物を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。
（製造法３）
　本発明化合物は、例えば化合物（５）から下記のスキームに従って製造することができる。
Figure JPOXMLDOC01-appb-I000005
〔式中、Ｒ１、Ｒ２及びｐは前記と同じ意味を表す。〕
工程（Ｉ−１）
　化合物（６）は、化合物（５）と化合物（３）又はその塩とを、脱水縮合剤の存在下に反応させることにより製造することができる。
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類及びこれらの混合物が挙げられる。
　該反応に用いられる脱水縮合剤としては、ＷＳＣ、ＢＯＰ試薬及び１，３−ジシクロヘキシルカルボジイミド等が挙げられる。
　該反応には化合物（５）１モルに対して、化合物（３）が通常１~３モルの割合、脱水縮合剤が通常１~５モルの割合で用いられる。
　該反応の反応温度は、通常０~２００℃の範囲である。該反応の反応時間は通常１~２４時間の範囲である。
　該反応において、ＢＯＰ試薬を使用する場合は、必要に応じて塩基の存在下で反応を行う。かかる塩基としては、例えばトリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
　該反応には化合物（５）１モルに対して、塩基が通常１~１０モルの割合で用いられる。
　反応終了後は、反応混合物に水を加えた後、有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、化合物（６）を単離することができる。単離された化合物（６）は、クロマトグラフィー、再結晶等によりさらに精製することもできる。
工程（Ｉ−２）
　本発明化合物は、化合物（６）と酸とを反応させることにより製造することができる。
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばトルエン、キシレン等の芳香族炭化水素類、塩化メチレン、クロロホルム、クロロベンゼン等のハロゲン化炭化水素類、ＤＭＳＯ等のスルホキシド類、メタノール、エタノール、２−メチルエタノール等のアルコール類、アセトン、メチルエチルケトン、メチルイソブチルケトン等のケトン類、水及びこれらの混合物が挙げられる。
　該反応に用いられる酸としては、例えば塩酸、硫酸等の無機酸、トリフルオロ酢酸、ｐ−トルエンスルホン酸、メタンスルホン酸等の有機酸が挙げられる。
　該反応には化合物（６）１モルに対して、酸は通常１モル~過剰量の割合で用いられる。
　該反応の反応温度は、通常０~１５０℃の範囲である。該反応の反応時間は通常０．１~２４時間の範囲である。
　反応終了後は、反応混合物を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。
　本発明化合物は、農学上許容される塩（ａｇｒｉｃｕｌｔｕｒａｌｌｙ　ａｃｃｅｐｔａｂｌｅ　ｓａｌｔ）を形成できる。かかる本発明化合物の塩は、通常本発明化合物と酸との塩である。酸との塩としては例えば、塩酸塩、臭化水素塩、硫酸塩等の無機酸塩、メタンスルホン酸塩、ギ酸塩、酢酸塩、トリフルオロ酢酸塩等の有機酸塩が挙げられる。
　本発明化合物と酸との塩は、本発明化合物を酸と反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-I000006
〔式中、Ｒ１、Ｒ２及びｐは前記と同じ意味を表し、ＨＸは酸を表す。〕
　該反応は、溶媒の存在下又は溶媒の非存在下で行われる。
　該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、水及びこれらの混合物が挙げられる。
　該反応に用いられる酸としては、例えば塩酸、臭化水素酸、ヨウ化水素酸、硫酸等の無機酸、酢酸、トリフルオロ酢酸、ギ酸、ｐ−トルエンスルホン酸、メタンスルホン酸等の有機酸が挙げられる。
　該反応には本発明化合物１モルに対して、酸が通常１~１００モルの割合で用いられる。
　該反応の反応温度は、通常０~２００℃の範囲である。該反応の反応時間は通常１~２４時間の範囲である。
　反応終了後は、未反応の酸を除去して本発明化合物と酸との塩を単離することができる。
　本発明の植物病害防除剤は、本発明化合物又はその塩と不活性担体（固体担体、液体担体又はガス担体）を含有する。本発明の植物病害防除剤は、さらに界面活性剤、その他の製剤用補助剤が混合され、水和剤、顆粒水和剤、フロアブル剤、粒剤、ドライフロアブル剤、乳剤、水性液剤、油剤、くん煙剤、エアゾール剤、マイクロカプセル剤等に製剤化されている。これらの製剤には本発明化合物又はその塩が重量比で通常０．１~９９％、好ましくは０．２~９０％含有される。
　固体担体としては、例えば、粘土類（例えば、カオリン、珪藻土、合成含水酸化珪素、ろう石クレー、ベントナイト、酸性白土、タルク）、その他の無機鉱物（例えば、セリサイト、石英粉末、硫黄粉末、活性炭、炭酸カルシウム、水和シリカ）等の微粉末あるいは粒状物が挙げられる。液体担体としては、例えば、水、アルコール類（例えば、メタノール、エタノール）、ケトン類（例えば、アセトン、メチルエチルケトン）、芳香族炭化水素類（例えば、ベンゼン、トルエン、キシレン、エチルベンゼン、メチルナフタレン）、脂肪族炭化水素類（例えば、ヘキサン、シクロヘキサノン、灯油）、エステル類（例えば、酢酸エチル、酢酸ブチル）、ニトリル類（例えば、アセトニトリル、イソブチロニトリル）、エーテル類（例えば、ジオキサン、ジイソプロピルエーテル）、酸アミド類（例えば、ジメチルホルムアミド、ジメチルアセトアミド）、ハロゲン化炭化水素類（例えば、ジクロロエタン、トリクロロエチレン、四塩化炭素）等が挙げられる。ガス状担体としては、例えばジメチルエーテル及び二酸化炭素が挙げられる。
　界面活性剤としては、例えばアルキル硫酸エステル類、アルキルスルホン酸塩、アルキルアリールスルホン酸塩、アルキルアリールエーテル類及びそのポリオキシエチレン化物、ポリオキシエチレングリコールエーテル類、多価アルコールエステル類、糖アルコール誘導体等が挙げられる。
　その他の製剤用補助剤としては、例えば固着剤、分散剤、増粘剤、濡れ剤、増量剤や酸化防止剤、具体的にはカゼイン、ゼラチン、多糖類（例えば、デンプン、アラビヤガム、セルロース誘導体、アルギン酸）、リグニン誘導体、ベントナイト糖類、合成水溶性高分子（例えば、ポリビニルアルコール、ポリビニルピロリドン、ポリアクリル酸類）、ＰＡＰ（酸性りん酸イソプロピル）、ＢＨＴ（２，６−ジ−ｔｅｒｔ−ブチル−４−メチルフェノール）、ＢＨＡ（２−ｔｅｒｔ−ブチル−４−メトキシフェノールと３−ｔｅｒｔ−ブチル−４−メトキシフェノールとの混合物）、植物油、鉱物油、脂肪酸又はそのエステル等が挙げられる。
　本発明化合物又はその塩は、植物又は植物が生育する土壌に施用することによる植物病害の防除用途に用いられる。本発明化合物又はその塩を植物又は植物が生育する土壌に施用する方法としては、例えば植物に茎葉散布する方法、植物を栽培している土壌に施用する方法、及び植物種子に施用する方法が挙げられる。
　本発明の植物病害防除方法には、通常本発明の植物病害防除剤が用いられる。
　本発明の植物病害防除剤を植物に茎葉散布する方法又は植物を栽培している土壌に施用する方法に用いられる場合において、本発明の植物病害防除剤の施用量は、施用場所１，０００ｍ２あたり、本発明化合物又はその塩の量で通常１~５００ｇの割合、好ましくは２~２００ｇの割合である。本発明の植物病害防除剤が乳剤、水和剤、懸濁剤等に製剤化されている場合は、その製剤は本発明化合物又はその塩の濃度が通常０．０００５~２重量％、好ましくは０．００５~１重量％となるように水で希釈して施用される。本発明の植物病害防除剤が粉剤、粒剤等に製剤化されている場合は、その製剤は希釈することなくそのまま施用される。
　本発明の植物病害防除剤を植物種子に施用する方法に用いられる場合において、本発明の植物病害防除剤の施用量は、種子１Ｋｇあたり、本発明化合物又はその塩の量で通常０．００１~１００ｇの割合、好ましくは０．０１~５０ｇの割合である。
　本発明の植物病害防除剤は、他の殺菌剤、殺虫剤、殺ダニ剤、殺線虫剤、除草剤、植物生長調節剤、肥料または土壌改良剤と混合及び／又は併用できる。
　かかる殺菌剤の有効成分としては、例えば以下のものが挙げられる。
（１）　アゾール殺菌活性化合物
プロピコナゾール（ｐｒｏｐｉｃｏｎａｚｏｌｅ）、プロチオコナゾール（ｐｒｏｔｈｉｏｃｏｎａｚｏｌｅ）、トリアジメノール（ｔｒｉａｄｉｍｅｎｏｌ）、プロクロラズ（ｐｒｏｃｈｌｏｒａｚ）、ペンコナゾール（ｐｅｎｃｏｎａｚｏｌｅ）、テブコナゾール（ｔｅｂｕｃｏｎａｚｏｌｅ）、フルシラゾール（ｆｌｕｓｉｌａｚｏｌｅ）、ジニコナゾール（ｄｉｎｉｃｏｎａｚｏｌｅ）、ブロムコナゾール（ｂｒｏｍｕｃｏｎａｚｏｌｅ）、エポキシコナゾール（ｅｐｏｘｉｃｏｎａｚｏｌｅ）、ジフェノコナゾール（ｄｉｆｅｎｏｃｏｎａｚｏｌｅ）、シプロコナゾール（ｃｙｐｒｏｃｏｎａｚｏｌｅ）、メトコナゾール（ｍｅｔｃｏｎａｚｏｌｅ）、トリフルミゾール（ｔｒｉｆｌｕｍｉｚｏｌｅ）、テトラコナゾール（ｔｅｔｒａｃｏｎａｚｏｌｅ）、マイクロブタニル（ｍｉｃｒｏｂｕｔａｎｉｌ）、フェンブコナゾール（ｆｅｎｂｕｃｏｎａｚｏｌｅ）、ヘキサコナゾール（ｈｅｘａｃｏｎａｚｏｌｅ）、フルキンコナゾール（ｆｌｕｑｕｉｎｃｏｎａｚｏｌｅ）、トリティコナゾール（ｔｒｉｔｉｃｏｎａｚｏｌｅ）、ビテルタノール（ｂｉｔｅｒｔａｎｏｌ）、イマザリル（ｉｍａｚａｌｉｌ）、フルトリアホール（ｆｌｕｔｒｉａｆｏｌ）、シメコナゾール（ｓｉｍｅｃｏｎａｚｏｌｅ）、イプコナゾール（ｉｐｃｏｎａｚｏｌｅ）等；
（２）　アミン殺菌活性化合物
フェンプロピモルフ（ｆｅｎｐｒｏｐｉｍｏｒｐｈ）、トリデモルフ（ｔｒｉｄｅｍｏｒｐｈ）、フェンプロピジン（ｆｅｎｐｒｏｐｉｄｉｎ）、スピロキサミン（ｓｐｉｒｏｘａｍｉｎｅ）等；
（３）　ベンズイミダゾール殺菌活性化合物
カルベンダジム（ｃａｒｂｅｎｄａｚｉｍ）、ベノミル（ｂｅｎｏｍｙｌ）、チアベンダゾール（ｔｈｉａｂｅｎｄａｚｏｌｅ）、チオファネートメチル（ｔｈｉｏｐｈａｎａｔｅ—Ｍｅｔｈｙｌ）等；
（４）　ジカルボキシイミド殺菌活性化合物
プロシミドン（ｐｒｏｃｙｍｉｄｏｎｅ）、イプロジオン（ｉｐｒｏｄｉｏｎｅ）、ビンクロゾリン（ｖｉｎｃｌｏｚｏｌｉｎ）等；
（５）　アニリノピリミジン殺菌活性化合物
シプロディニル（ｃｙｐｒｏｄｉｎｉｌ）、ピリメタニル（ｐｙｒｉｍｅｔｈａｎｉｌ）、メパニピリム（ｍｅｐａｎｉｐｙｒｉｍ）等；
（６）　フェニルピロール殺菌活性化合物
　フェンピクロニル（ｆｅｎｐｉｃｌｏｎｉｌ）、フルジオキソニル（ｆｌｕｄｉｏｘｏｎｉｌ）等；
（７）　ストロビルリン殺菌活性化合物
クレソキシムメチル（ｋｒｅｓｏｘｉｍ−ｍｅｔｈｙｌ）、アゾキシストロビン（ａｚｏｘｙｓｔｒｏｂｉｎ）、トリフロキシストロビン（ｔｒｉｆｌｏｘｙｓｔｒｏｂｉｎ）、フルオキサストロビン（ｆｌｕｏｘａｓｔｒｏｂｉｎ）、ピコキシストロビン（ｐｉｃｏｘｙｓｔｒｏｂｉｎ）、ピラクロストロビン（ｐｙｒａｃｌｏｓｔｒｏｂｉｎ）、ジモキシストロビン（ｄｉｍｏｘｙｓｔｒｏｂｉｎ）、ピリベンカルブ（ｐｙｒｉｂｅｎｃａｒｂ）、メトミノストロビン（ｍｅｔｏｍｉｎｏｓｔｒｏｂｉｎ）、オリザストロビン（ｏｒｙｚａｓｔｒｏｂｉｎ）、エネストロビン（ｅｎｅｓｔｒｏｂｉｎ）等；
（８）　フェニルアマイド殺菌活性化合物
メタラキシル（ｍｅｔａｌａｘｙｌ）、メタラキシルＭまたはメフェノキサム（ｍｅｔａｌａｘｙｌ−Ｍ　ｏｒ　ｍｅｆｅｎｏｘａｍ）、ベナラキシル（ｂｅｎａｌａｘｙｌ）、ベナラキシルＭまたはキララキシル（ｂｅｎａｌａｘｙｌ−Ｍ　ｏｒ　ｋｉｒａｌａｘｙｌ）等；
（９）　カルボン酸アミド殺菌活性化合物
ジメトモルフ（ｄｉｍｅｔｈｏｍｏｒｐｈ）、イプロバリカルブ（ｉｐｒｏｖａｌｉｃａｒｂ）、ベンチアバリカルブイソプロピル（ｂｅｎｔｈｉａｖａｌｉｃａｒｂ−ｉｓｏｐｒｏｐｙｌ）、マンジプロパミド（ｍａｎｄｉｐｒｏｐａｍｉｄ）、バリフェナル（ｖａｌｉｐｈｅｎａｌ）
（１０）　カルボン酸アミド殺菌活性化合物
カルボキシン（ｃａｒｂｏｘｉｎ）、メプロニル（ｍｅｐｒｏｎｉｌ）、フルトラニル（ｆｌｕｔｏｌａｎｉｌ）、チフルザミド（ｔｈｉｆｌｕｚａｍｉｄｅ）、フラメトピル（ｆｕｒａｍｅｔｐｙｒ）、ボスカリド（ｂｏｓｃａｌｉｄ）、ペンチオピラド（ｐｅｎｔｈｉｏｐｙｒａｄ）、フルオピラン（ｆｌｕｏｐｙｒａｍ）、ビキサフェン（ｂｉｘａｆｅｎ）、
（１１）　その他の殺菌活性化合物
ジエトフェンカルブ；チウラム；フルアジナム；マンコゼブ；クロロタロニル；キャプタン；ジクロフルアニド；フォルペット；キノキシフェン；フェンヘキサミド；ファモキサドン；フェナミドン；ゾキサミド；エタボキサム；アミスルブロム；シアゾファミド；メトラフェノン；シフルフェナミド；プロキナジド；フルスルファミド；フルオピコリド；フォセチル；シモキサニル；ペンシクロン；トルクロホスメチル；カルプロパミド；ジクロシメット；フェノキサニル；トリシクラゾール；ピロキロン；プロベナゾール；イソチアニル；チアジニル；テブフロキン；ジクロメジン；カスガマイシン；フェリムゾン；フサライド；バリダマイシン；ヒドロキシイソキサゾール；イミノクタジン酢酸塩；イソプロチオラン；オキソリニック酸；オキシテトラサイクリン；ストレプトマイシン；塩基性塩化銅；水酸化第二銅；塩基性硫酸銅；有機銅；硫黄；
式（８）
Figure JPOXMLDOC01-appb-I000007
〔式中、Ｘ１は水素、またはハロゲンを表し、Ｘ２はメチル基、ジフルオロメチル基、又はトリフルオロメチル基を表し、Ｑは下記のいずれかの基
　Ｑ：
Figure JPOXMLDOC01-appb-I000008
を表す。〕
で示されるピラゾールカルボン酸アミド化合物；
式（９）
Figure JPOXMLDOC01-appb-I000009
〔式中、Ｘ３はメチル基、ジフルオロメチル基、またはエチル基を表し、Ｘ４はメトキシ基、またはメチルアミノ基を表し、Ｘ５はフェニル基、２−メチルフェニル基、または２，５−ジメチルフェニル基を表す。〕
で示されるα−アルコキシフェニル酢酸化合物；
　式（１０）
Figure JPOXMLDOC01-appb-I000010
〔式中、Ｘ６はメトキシ基、エトキシ基、プロポキシ基、２−プロペニルオキシ基、２−プロピニルオキシ基、３−ブテニルオキシ基、３−ブチニルオキシ基、メチルチオ基、エチルチオ基、または２−プロペニルチオ基を表し、Ｘ７は１−メチルエチル基、または１−メチルプロピル基を表し、Ｘ８は２−メチルフェニル基、または２，６−ジクロロフェニル基を表す。〕
で示されるピラゾリノン化合物。
　かかる殺虫剤の有効成分としては、例えば以下のものが挙げられる。
（１）　有機リン殺虫活性化合物
　アセフェート（ａｃｅｐｈａｔｅ）、りん化アルミニウム（Ａｌｕｍｉｎｉｕｍ　ｐｈｏｓｐｈｉｄｅ）、ブタチオホス（ｂｕｔａｔｈｉｏｆｏｓ）、キャドサホス（ｃａｄｕｓａｆｏｓ）、クロルエトキシホス（ｃｈｌｏｒｅｔｈｏｘｙｆｏｓ）、クロルフェンビンホス（ｃｈｌｏｒｆｅｎｖｉｎｐｈｏｓ）、クロルピリホス（ｃｈｌｏｒｐｙｒｉｆｏｓ）、クロルピリホスメチル（ｃｈｌｏｒｐｙｒｉｆｏｓ−ｍｅｔｈｙｌ）、シアノホス（ｃｙａｎｏｐｈｏｓ：ＣＹＡＰ）、ダイアジノン（ｄｉａｚｉｎｏｎ）、ＤＣＩＰ（ｄｉｃｈｌｏｒｏｄｉｉｓｏｐｒｏｐｙｌ　ｅｔｈｅｒ）、ジクロフェンチオン（ｄｉｃｈｌｏｆｅｎｔｈｉｏｎ：ＥＣＰ）、ジクロルボス（ｄｉｃｈｌｏｒｖｏｓ：ＤＤＶＰ）、ジメトエート（ｄｉｍｅｔｈｏａｔｅ）、ジメチルビンホス（ｄｉｍｅｔｈｙｌｖｉｎｐｈｏｓ）、ジスルホトン（ｄｉｓｕｌｆｏｔｏｎ）、ＥＰＮ、エチオン（ｅｔｈｉｏｎ）、エトプロホス（ｅｔｈｏｐｒｏｐｈｏｓ）、エトリムホス（ｅｔｒｉｍｆｏｓ）、フェンチオン（ｆｅｎｔｈｉｏｎ：ＭＰＰ）、フエニトロチオン（ｆｅｎｉｔｒｏｔｈｉｏｎ：ＭＥＰ）、ホスチアゼート（ｆｏｓｔｈｉａｚａｔｅ）、ホルモチオン（ｆｏｒｍｏｔｈｉｏｎ）、りん化水素（Ｈｙｄｒｏｇｅｎ　ｐｈｏｓｐｈｉｄｅ）、イソフェンホス（ｉｓｏｆｅｎｐｈｏｓ）、イソキサチオン（ｉｓｏｘａｔｈｉｏｎ）、マラチオン（ｍａｌａｔｈｉｏｎ）、メスルフェンホス（ｍｅｓｕｌｆｅｎｆｏｓ）、メチダチオン（ｍｅｔｈｉｄａｔｈｉｏｎ：ＤＭＴＰ）、モノクロトホス（ｍｏｎｏｃｒｏｔｏｐｈｏｓ）、ナレッド（ｎａｌｅｄ：ＢＲＰ）、オキシデプロホス（ｏｘｙｄｅｐｒｏｆｏｓ：ＥＳＰ）、パラチオン（ｐａｒａｔｈｉｏｎ）、ホサロン（ｐｈｏｓａｌｏｎｅ）、ホスメット（ｐｈｏｓｍｅｔ：ＰＭＰ）、ピリミホスメチル（ｐｉｒｉｍｉｐｈｏｓ−ｍｅｔｈｙｌ）、ピリダフェンチオン（ｐｙｒｉｄａｆｅｎｔｈｉｏｎ）、キナルホス（ｑｕｉｎａｌｐｈｏｓ）、フェントエート（ｐｈｅｎｔｈｏａｔｅ：ＰＡＰ）、プロフェノホス（ｐｒｏｆｅｎｏｆｏｓ）、プロパホス（ｐｒｏｐａｐｈｏｓ）、プロチオホス（ｐｒｏｔｈｉｏｆｏｓ）、ピラクロホス（ｐｙｒａｃｌｏｒｆｏｓ）、サリチオン（ｓａｌｉｔｈｉｏｎ）、スルプロホス（ｓｕｌｐｒｏｆｏｓ）、テブピリムホス（ｔｅｂｕｐｉｒｉｍｆｏｓ）、テメホス（ｔｅｍｅｐｈｏｓ）、テトラクロルビンホス（ｔｅｔｒａｃｈｌｏｒｖｉｎｐｈｏｓ）、テルブホス（ｔｅｒｂｕｆｏｓ）、チオメトン（ｔｈｉｏｍｅｔｏｎ）、トリクロルホン（ｔｒｉｃｈｌｏｒｐｈｏｎ：ＤＥＰ）、バミドチオン（ｖａｍｉｄｏｔｈｉｏｎ）、フォレート（ｐｈｏｒａｔｅ）、カズサホス（ｃａｄｕｓａｆｏｓ）等；
（２）　カーバメート殺虫活性化合物
　アラニカルブ（ａｌａｎｙｃａｒｂ）、ベンダイオカルブ（ｂｅｎｄｉｏｃａｒｂ）、ベンフラカルブ（ｂｅｎｆｕｒａｃａｒｂ）、ＢＰＭＣ、カルバリル（ｃａｒｂａｒｙｌ）、カルボフラン（ｃａｒｂｏｆｕｒａｎ）、カルボスルファン（ｃａｒｂｏｓｕｌｆａｎ）、クロエトカルブ（ｃｌｏｅｔｈｏｃａｒｂ）、エチオフェンカルブ（ｅｔｈｉｏｆｅｎｃａｒｂ）、フェノブカルブ（ｆｅｎｏｂｕｃａｒｂ）、フェノチオカルブ（ｆｅｎｏｔｈｉｏｃａｒｂ）、フェノキシカルブ（ｆｅｎｏｘｙｃａｒｂ）、フラチオカルブ（ｆｕｒａｔｈｉｏｃａｒｂ）、イソプロカルブ（ｉｓｏｐｒｏｃａｒｂ：ＭＩＰＣ）、メトルカルブ（ｍｅｔｏｌｃａｒｂ）、メソミル（ｍｅｔｈｏｍｙｌ）、メチオカルブ（ｍｅｔｈｉｏｃａｒｂ）、ＮＡＣ、オキサミル（ｏｘａｍｙｌ）、ピリミカーブ（ｐｉｒｉｍｉｃａｒｂ）、プロポキスル（ｐｒｏｐｏｘｕｒ：ＰＨＣ）、ＸＭＣ、チオジカルブ（ｔｈｉｏｄｉｃａｒｂ）、キシリルカルブ（ｘｙｌｙｌｃａｒｂ）、アルジカルブ（ａｌｄｉｃａｒｂ）等；
（３）　合成ピレスロイド殺虫活性化合物
　アクリナトリン（ａｃｒｉｎａｔｈｒｉｎ）、アレスリン（ａｌｌｅｔｈｒｉｎ）、ベンフルスリン（ｂｅｎｆｌｕｔｈｒｉｎ）、ベーターシフルトリン（ｂｅｔａ−ｃｙｆｌｕｔｈｒｉｎ）、ビフェントリン（ｂｉｆｅｎｔｈｒｉｎ）、シクロプロトリン（ｃｙｃｌｏｐｒｏｔｈｒｉｎ）、シフルトリン（ｃｙｆｌｕｔｈｒｉｎ）、シハロトリン（ｃｙｈａｌｏｔｈｒｉｎ）、シペルメトリン（ｃｙｐｅｒｍｅｔｈｒｉｎ）、デルタメトリン（ｄｅｌｔａｍｅｔｈｒｉｎ）、エスフェンバレレート（ｅｓｆｅｎｖａｌｅｒａｔｅ）、エトフェンプロックス（ｅｔｈｏｆｅｎｐｒｏｘ）、フェンプロパトリン（ｆｅｎｐｒｏｐａｔｈｒｉｎ）、フェンバレレート（ｆｅｎｖａｌｅｒａｔｅ）、フルシトリネート（ｆｌｕｃｙｔｈｒｉｎａｔｅ）、フルフェンプロックス（ｆｌｕｆｅｎｏｐｒｏｘ）、フルメスリン（ｆｌｕｍｅｔｈｒｉｎ）、フルバリネート（ｆｌｕｖａｌｉｎａｔｅ）、ハルフェンプロックス（ｈａｌｆｅｎｐｒｏｘ）、イミプロトリン（ｉｍｉｐｒｏｔｈｒｉｎ）、ペルメトリン（ｐｅｒｍｅｔｈｒｉｎ）、プラレトリン（ｐｒａｌｌｅｔｈｒｉｎ）、ピレトリン（ｐｙｒｅｔｈｒｉｎｓ）、レスメトリン（ｒｅｓｍｅｔｈｒｉｎ）、シグマ−サイパーメスリン（ｓｉｇｍａ−ｃｙｐｅｒｍｅｔｈｒｉｎ）、シラフルオフェン（ｓｉｌａｆｌｕｏｆｅｎ）、テフルトリン（ｔｅｆｌｕｔｈｒｉｎ）、トラロメトリン（ｔｒａｌｏｍｅｔｈｒｉｎ）、トランスフルトリン（ｔｒａｎｓｆｌｕｔｈｒｉｎ）、テトラメトリン（ｔｅｔｒａｍｅｔｈｒｉｎ）、フェノトリン（ｐｈｅｎｏｔｈｒｉｎ）、シフェノトリン（ｃｙｐｈｅｎｏｔｈｒｉｎ）、アルファシペルメトリン（ａｌｐｈａ−ｃｙｐｅｒｍｅｔｈｒｉｎ）、ゼータシペルメトリン（ｚｅｔａ−ｃｙｐｅｒｍｅｔｈｒｉｎ）、ラムダシハロトリン（ｌａｍｂｄａ−ｃｙｈａｌｏｔｈｒｉｎ）、フラメトリン（ｆｕｒａｍｅｔｈｒｉｎ）、タウフルバリネート（ｔａｕ−ｆｌｕｖａｌｉｎａｔｅ）、２，３，５，６−テトラフルオロ−４−（メトキシメチル）ベンジル（ＥＺ）−（１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）−２，２−ジメチル−３−プロプ−１−エニルシクロプロパンカルボキシレート、２，３，５，６−テトラフルオロ−４−メチルベンジル（ＥＺ）−（１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）−２，２−ジメチル−３−プロプ−１−エニルシクロプロパンカルボキシレート、２，３，５，６−テトラフルオロ−４−（メトキシメチル）ベンジル（１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）−２，２−ジメチル−３−（２−メチル−１−プロペニル）シクロプロパンカルボキシレート等；
（４）　ネライストキシン殺虫活性化合物
　カルタップ（ｃａｒｔａｐ）、ベンスルタップ（ｂｅｎｓｕ１ｔａｐ）、チオシクラム（ｔｈｉｏｃｙｃｌａｍ）、モノスルタップ（ｍｏｎｏｓｕｌｔａｐ）、ビスルタップ（ｂｉｓｕｌｔａｐ）等；
（５）　ネオニコチノイド殺虫活性化合物
　イミダクロプリド（ｉｍｉｄａｃｌｏｐｒｉｄ）、ニテンピラム（ｎｉｔｅｎｐｙｒａｍ）、アセタミプリド（ａｃｅｔａｍｉｐｒｉｄ）、チアメトキサム（ｔｈｉａｍｅｔｈｏｘａｍ）、チアクロプリド（ｔｈｉａｃｌｏｐｒｉｄ）、ジノテフラン（ｄｉｎｏｔｅｆｕｒａｎ）、クロチアニジン（ｃｌｏｔｈｉａｎｉｄｉｎ）等；
（６）　ベンゾイル尿素殺虫活性化合物
　クロルフルアズロン（ｃｈｌｏｒｆｌｕａｚｕｒｏｎ）、ビストリフルロン（ｂｉｓｔｒｉｆｌｕｒｏｎ）、ジアフェンチウロン（ｄｉａｆｅｎｔｈｉｕｒｏｎ）、ジフルベンズロン（ｄｉｆｌｕｂｅｎｚｕｒｏｎ）、フルアズロン（ｆｌｕａｚｕｒｏｎ）、フルシクロクスロン（ｆｌｕｃｙｃｌｏｘｕｒｏｎ）、フルフェノクスロン（ｆｌｕｆｅｎｏｘｕｒｏｎ）、ヘキサフルムロン（ｈｅｘａｆｌｕｍｕｒｏｎ）、ルフェヌロン（ｌｕｆｅｎｕｒｏｎ）、ノバルロン（ｎｏｖａｌｕｒｏｎ）、ノビフルムロン（ｎｏｖｉｆｌｕｍｕｒｏｎ）、テフルベンズロン（ｔｅｆｌｕｂｅｎｚｕｒｏｎ）、トリフルムロン（ｔｒｉｆｌｕｍｕｒｏｎ）、トリアズロン等；
（７）　フェニルピラゾール殺虫活性化合物
　アセトプロール（ａｃｅｔｏｐｒｏｌｅ）、エチプロール（ｅｔｈｉｐｒｏｌｅ）、フィプロニル（ｆｉｐｒｏｎｉｌ）、バニリプロール（ｖａｎｉｌｉｐｒｏｌｅ）、ピリプロール（ｐｙｒｉｐｒｏｌｅ）、ピラフルプロール（ｐｙｒａｆｌｕｐｒｏｌｅ）等；
（８）　Ｂｔトキシン
　バチルス・チューリンゲンシス菌由来の生芽胞および産生結晶毒素、並びにそれらの混合物；
（９）　ヒドラジン殺虫活性化合物
　クロマフェノジド（ｃｈｒｏｍａｆｅｎｏｚｉｄｅ）、ハロフェノジド（ｈａｌｏｆｅｎｏｚｉｄｅ）、メトキシフェノジド（ｍｅｔｈｏｘｙｆｅｎｏｚｉｄｅ）、テブフェノジド（ｔｅｂｕｆｅｎｏｚｉｄｅ）等；
（１０）　有機塩素系化合物
　アルドリン（ａｌｄｒｉｎ）、ディルドリン（ｄｉｅｌｄｒｉｎ）、ジエノクロル（ｄｉｅｎｏｃｈｌｏｒ）、エンドスルファン（ｅｎｄｏｓｕｌｆａｎ）、メトキシクロル（ｍｅｔｈｏｘｙｃｈｌｏｒ）等；
（１１）　その他の殺虫有効成分
　マシン油（ｍａｃｈｉｎｅ　ｏｉｌ）、硫酸ニコチン（ｎｉｃｏｔｉｎｅ−ｓｕｌｆａｔｅ）；
　アベルメクチン（ａｖｅｒｍｅｃｔｉｎ−Ｂ）、ブロモプロピレート（ｂｒｏｍｏｐｒｏｐｙｌａｔｅ）、ブプロフェジン（ｂｕｐｒｏｆｅｚｉｎ）、クロルフェナピル（ｃｈｌｏｒｐｈｅｎａｐｙｒ）、シロマジン（ｃｙｒｏｍａｚｉｎｅ）、Ｄ−Ｄ（１，３−Ｄｉｃｈｌｏｒｏｐｒｏｐｅｎｅ）、エマメクチンベンゾエート（ｅｍａｍｅｃｔｉｎ−ｂｅｎｚｏａｔｅ）、フェナザキン（ｆｅｎａｚａｑｕｉｎ）、フルピラゾホス（ｆｌｕｐｙｒａｚｏｆｏｓ）、ハイドロプレン（ｈｙｄｒｏｐｒｅｎｅ）、メトプレン（ｍｅｔｈｏｐｒｅｎｅ）、インドキサカルブ（ｉｎｄｏｘａｃａｒｂ）、メトキサジアゾン（ｍｅｔｏｘａｄｉａｚｏｎｅ）、ミルベマイシンＡ（ｍｉｌｂｅｍｙｃｉｎ−Ａ）、ピメトロジン（ｐｙｍｅｔｒｏｚｉｎｅ）、ピリダリル（ｐｙｒｉｄａｌｙｌ）、ピリプロキシフェン（ｐｙｒｉｐｒｏｘｙｆｅｎ）、スピノサッド（ｓｐｉｎｏｓａｄ）、スルフラミド（ｓｕｌｆｌｕｒａｍｉｄ）、トルフェンピラド（ｔｏｌｆｅｎｐｙｒａｄ）、トリアゼメイト（ｔｒｉａｚａｍａｔｅ）、フルベンジアミド（ｆｌｕｂｅｎｄｉａｍｉｄｅ）、レピメクチン（ｌｅｐｉｍｅｃｔｉｎ）、亜ひ酸（Ａｒｓｅｎｉｃ　ａｃｉｄ）、ベンクロチアズ（ｂｅｎｃｌｏｔｈｉａｚ）、石灰窒素（Ｃａｌｃｉｕｍ　ｃｙａｎａｍｉｄｅ）、石灰硫黄合剤（Ｃａｌｃｉｕｍ　ｐｏｌｙｓｕｌｆｉｄｅ）、クロルデン（ｃｈｌｏｒｄａｎｅ）、ＤＤＴ、ＤＳＰ、フルフェネリウム（ｆｌｕｆｅｎｅｒｉｍ）、フロニカミド（ｆｌｏｎｉｃａｍｉｄ）、フルリムフェン（ｆｌｕｒｉｍｆｅｎ）、ホルメタネート（ｆｏｒｍｅｔａｎａｔｅ）、メタム・アンモニウム（ｍｅｔａｍ−ａｍｍｏｎｉｕｍ）、メタム・ナトリウム（ｍｅｔａｍ−ｓｏｄｉｕｍ）、臭化メチル（Ｍｅｔｈｙｌ　ｂｒｏｍｉｄｅ）、ニディノテフラン（ｎｉｄｉｎｏｔｅｆｕｒａｎ）、オレイン酸カリウム（Ｐｏｔａｓｓｉｕｍ　ｏｌｅａｔｅ）、プロトリフェンビュート（ｐｒｏｔｒｉｆｅｎｂｕｔｅ）、スピロメシフェン（ｓｐｉｒｏｍｅｓｉｆｅｎ）、硫黄（Ｓｕｌｆｕｒ）、メタフルミゾン（ｍｅｔａｆｌｕｍｉｚｏｎｅ）、スピロテトラマット（ｓｐｉｒｏｔｅｔｒａｍａｔ）、ピリフルキナゾン（ｐｙｒｉｆｌｕｑｕｉｎａｚｏｎｅ）、スピネトラム（ｓｐｉｎｅｔｏｒａｍ）、クロラントラニリプロール（ｃｈｌｏｒａｎｔｒａｎｉｌｉｐｒｏｌｅ）、
式（１１）
Figure JPOXMLDOC01-appb-I000011
［式中、
　Ｒ１０は、Ｍｅ、Ｃｌ、ＢｒまたはＦ、
　Ｒ２０は、Ｆ、Ｃｌ、Ｂｒ、Ｃ１−Ｃ４ハロアルキル、またはＣ１−Ｃ４ハロアルコキシ、
　Ｒ３０は、Ｆ、ＣｌまたはＢｒ、
　Ｒ４０は、Ｈ、１以上のハロゲン；ＣＮ；ＳＭｅ；Ｓ（Ｏ）Ｍｅ；Ｓ（Ｏ）２ＭｅおよびＯＭｅで置換されていてもよいＣ１−Ｃ４アルキル、Ｃ３−Ｃ４アルケニル、Ｃ３−Ｃ４アルキニル、または、Ｃ３−Ｃ５シクロアルキルアルキル、
　Ｒ５０は、ＨまたはＭｅ、
　Ｒ６０は、Ｈ、ＦまたはＣｌ、
　Ｒ７０は、Ｈ、ＦまたはＣｌを表す。］で示される化合物、
式（１２）
Figure JPOXMLDOC01-appb-I000012
［式中、Ｘは、Ｃｌ、ＢｒまたはＩを表す。］
で示される化合物。
　かかる殺ダニ剤の有効成分としては、例えばアセキノシル（ａｃｅｑｕｉｎｏｃｙｌ）、アミトラズ（ａｍｉｔｒａｚ）、ベンゾキシメート（ｂｅｎｚｏｘｉｍａｔｅ）、ビフェナゼート（ｂｉｆｅｎａａｔｅ）、フェニソブロモレート（ｂｒｏｍｏｐｒｏｐｙｌａｔｅ）、キノメチオネート（ｃｈｉｎｏｍｅｔｈｉｏｎａｔ）、クロルベンジレート（ｃｈｌｏｒｏｂｅｎｚｉｌａｔｅ）、ＣＰＣＢＳ（ｃｈｌｏｒｆｅｎｓｏｎ）、クロフェンテジン（ｃｌｏｆｅｎｔｅｚｉｎｅ）、シフルメトフェン（ｃｙｆｌｕｍｅｔｏｆｅｎ）、ケルセン（ジコホル：ｄｉｃｏｆｏｌ）、エトキサゾール（ｅｔｏｘａｚｏｌｅ）、酸化フェンブタスズ（ｆｅｎｂｕｔａｔｉｎ　ｏｘｉｄｅ）、フェノチオカルブ（ｆｅｎｏｔｈｉｏｃａｒｂ）、フェンピロキシメート（ｆｅｎｐｙｒｏｘｉｍａｔｅ）、フルアクリピリム（ｆｌｕａｃｒｙｐｙｒｉｍ）、フルプロキシフェン（ｆｌｕｐｒｏｘｙｆｅｎ）、ヘキシチアゾクス（ｈｅｘｙｔｈｉａｚｏｘ）、プロパルギット（ｐｒｏｐａｒｇｉｔｅ：ＢＰＰＳ）、ポリナクチン複合体（ｐｏｌｙｎａｃｔｉｎｓ）、ピリダベン（ｐｙｒｉｄａｂｅｎ）、ピリミジフェン（Ｐｙｒｉｍｉｄｉｆｅｎ）、テブフェンピラド（ｔｅｂｕｆｅｎｐｙｒａｄ）、テトラジホン（ｔｅｔｒａｄｉｆｏｎ）、スピロディクロフェン（ｓｐｉｒｏｄｉｃｌｏｆｅｎ）、スピロメシフェン（ｓｐｉｒｏｍｅｓｉｆｅｎ）、スピロテトラマット（ｓｐｉｒｏｔｅｔｒａｍａｔ）、アミドフルメット（ａｍｉｄｏｆｌｕｍｅｔ）、シエノピラフェン（ｃｙｅｎｏｐｙｒａｆｅｎ）等が挙げられる。
　かかる殺線虫剤の有効成分としては、例えば、ＤＣＩＰ、フォスチアゼート（ｆｏｓｔｈｉａｚａｔｅ）、塩酸レバミゾール（ｌｅｖａｍｉｓｏｌ）、メチルイソチオシアネート（ｍｅｔｈｙｉｓｏｔｈｉｏｃｙａｎａｔｅ）、酒石酸モランテル（ｍｏｒａｎｔｅｌ　ｔａｒｔａｒａｔｅ）、イミシアホス（ｉｍｉｃｙａｆｏｓ）等が挙げられる。
　かかる植物生長調節剤の有効成分としては、例えば、エテホン（ｅｔｈｅｐｈｏｎ）、クロルメコート（ｃｈｌｏｒｍｅｑｕａｔ−ｃｈｌｏｒｉｄｅ）、メピコート（ｍｅｐｉｑｕａｔ−ｃｈｌｏｒｉｄｅ）、等が挙げられる。
　本発明の植物病害防除剤は、例えば畑、水田、芝生、果樹園等の農耕地で使用することができる。本発明の植物病害防除剤を使用できる「作物」としては、例えば以下のものが挙げられる。
　農作物；トウモロコシ、イネ、コムギ、オオムギ、ライムギ、エンバク、ソルガム、ワタ、ダイズ、ピーナッツ、ソバ、テンサイ、ナタネ、ヒマワリ、サトウキビ、タバコ等、野菜；ナス科野菜（ナス、トマト、ピーマン、トウガラシ、ジャガイモ等）、ウリ科野菜（キュウリ、カボチャ、ズッキーニ、スイカ、メロン等）、アブラナ科野菜（ダイコン、カブ、セイヨウワサビ、コールラビ、ハクサイ、キャベツ、カラシナ、ブロッコリー、カリフラワー等）、キク科野菜（ゴボウ、シュンギク、アーティチョーク、レタス等）、ユリ科野菜（ネギ、タマネギ、ニンニク、アスパラガス）、セリ科野菜（ニンジン、パセリ、セロリ、アメリカボウフウ等）、アカザ科野菜（ホウレンソウ、フダンソウ等）、シソ科野菜（シソ、ミント、バジル等）、イチゴ、サツマイモ、ヤマノイモ、サトイモ、ヤトロファ等、
　花卉、
　観葉植物、
　果樹；仁果類（リンゴ、セイヨウナシ、ニホンナシ、カリン、マルメロ等）、核果類（モモ、スモモ、ネクタリン、ウメ、オウトウ、アンズ、プルーン等）、カンキツ類（ウンシュウミカン、オレンジ、レモン、ライム、グレープフルーツ等）、堅果類（クリ、クルミ、ハシバミ、アーモンド、ピスタチオ、カシューナッツ、マカダミアナッツ等）、液果類（ブルーベリー、クランベリー、ブラックベリー、ラズベリー等）、ブドウ、カキ、オリーブ、ビワ、バナナ、コーヒー、ナツメヤシ、ココヤシ等、
　果樹以外の樹；チャ、クワ、花木、街路樹（トネリコ、カバノキ、ハナミズキ、ユーカリ、イチョウ、ライラック、カエデ、カシ、ポプラ、ハナズオウ、フウ、プラタナス、ケヤキ、クロベ、モミノキ、ツガ、ネズ、マツ、トウヒ、イチイ）等。
　「作物」には、遺伝子組換作物も含まれる。
　本発明化合物又はその塩が効力を有する植物病害としては、例えば糸状菌による植物病害が挙げられ、具体的には以下の植物病害が挙げられる。
　イネのいもち病（Ｍａｇｎａｐｏｒｔｈｅ　ｇｒｉｓｅａ）、ごま葉枯病（Ｃｏｃｈｌｉｏｂｏｌｕｓ　ｍｉｙａｂｅａｎｕｓ）、紋枯病（Ｒｈｉｚｏｃｔｏｎｉａ　ｓｏｌａｎｉ）、馬鹿苗病（Ｇｉｂｂｅｒｅｌｌａ　ｆｕｊｉｋｕｒｏｉ）；
コムギの病害：うどんこ病（Ｅｒｙｓｉｐｈｅ　ｇｒａｍｉｎｉｓ）、赤かび病（Ｆｕｓａｒｉｕｍ　ｇｒａｍｉｎｅａｒｕｍ、Ｆ．ａｖｅｎａｃｅｒｕｍ、Ｆ．ｃｕｌｍｏｒｕｍ、Ｍｉｃｒｏｄｏｃｈｉｕｍ　ｎｉｖａｌｅ）、さび病（Ｐｕｃｃｉｎｉａ　ｓｔｒｉｉｆｏｒｍｉｓ、Ｐ．ｇｒａｍｉｎｉｓ、Ｐ．ｒｅｃｏｎｄｉｔａ）、紅色雪腐病（Ｍｉｃｒｏｎｅｃｔｒｉｅｌｌａ　ｎｉｖａｌｅ）、雪腐小粒菌核病（Ｔｙｐｈｕｌａ　ｓｐ．）、裸黒穂病（Ｕｓｔｉｌａｇｏ　ｔｒｉｔｉｃｉ）、なまぐさ黒穂病（Ｔｉｌｌｅｔｉａ　ｃａｒｉｅｓ）、眼紋病（Ｐｓｅｕｄｏｃｅｒｃｏｓｐｏｒｅｌｌａ　ｈｅｒｐｏｔｒｉｃｈｏｉｄｅｓ）、葉枯病（Ｍｙｃｏｓｐｈａｅｒｅｌｌａ　ｇｒａｍｉｎｉｃｏｌａ）、ふ枯病（Ｓｔａｇｏｎｏｓｐｏｒａ　ｎｏｄｏｒｕｍ）、黄斑病（Ｐｙｒｅｎｏｐｈｏｒａ　ｔｒｉｔｉｃｉ−ｒｅｐｅｎｔｉｓ）；
オオムギの病害：うどんこ病（Ｅｒｙｓｉｐｈｅ　ｇｒａｍｉｎｉｓ）、赤かび病（Ｆｕｓａｒｉｕｍ　ｇｒａｍｉｎｅａｒｕｍ、Ｆ．ａｖｅｎａｃｅｒｕｍ、Ｆ．ｃｕｌｍｏｒｕｍ、Ｍｉｃｒｏｄｏｃｈｉｕｍ　ｎｉｖａｌｅ）、さび病（Ｐｕｃｃｉｎｉａ　ｓｔｒｉｉｆｏｒｍｉｓ、Ｐ．ｇｒａｍｉｎｉｓ、Ｐ．ｈｏｒｄｅｉ）、裸黒穂病（Ｕｓｔｉｌａｇｏ　ｎｕｄａ）、雲形病（Ｒｈｙｎｃｈｏｓｐｏｒｉｕｍ　ｓｅｃａｌｉｓ）、網斑病（Ｐｙｒｅｎｏｐｈｏｒａ　ｔｅｒｅｓ）、斑点病（Ｃｏｃｈｌｉｏｂｏｌｕｓ　ｓａｔｉｖｕｓ）、斑葉病（Ｐｙｒｅｎｏｐｈｏｒａ　ｇｒａｍｉｎｅａ）、リゾクトニア属菌による苗立枯れ病（Ｒｈｉｚｏｃｔｏｎｉａ　ｓｏｌａｎｉ）；
カンキツ類の黒点病（Ｄｉａｐｏｒｔｈｅ　ｃｉｔｒｉ）、そうか病（Ｅｌｓｉｎｏｅ　ｆａｗｃｅｔｔｉ）、果実腐敗病（Ｐｅｎｉｃｉｌｌｉｕｍ　ｄｉｇｉｔａｔｕｍ，Ｐ．ｉｔａｌｉｃｕｍ）、フィトフトラ病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｐａｒａｓｉｔｉｃａ，Ｐｈｙｔｏｐｈｔｈｏｒａ　ｃｉｔｒｏｐｈｔｈｏｒａ）；
リンゴのモニリア病（Ｍｏｎｉｌｉｎｉａ　ｍａｌｉ）、腐らん病（Ｖａｌｓａ　ｃｅｒａｔｏｓｐｅｒｍａ）、うどんこ病（Ｐｏｄｏｓｐｈａｅｒａ　ｌｅｕｃｏｔｒｉｃｈａ）、斑点落葉病（Ａｌｔｅｒｎａｒｉａ　ａｌｔｅｒｎａｔａ　ａｐｐｌｅ　ｐａｔｈｏｔｙｐｅ）、黒星病（Ｖｅｎｔｕｒｉａ　ｉｎａｅｑｕａｌｉｓ）、炭そ病（Ｇｌｏｍｅｒｅｌｌａ　ｃｉｎｇｕｌａｔａ）、疫病（Ｐｈｙｔｏｐｈｔｏｒａ　ｃａｃｔｏｒｕｍ）；
ナシの黒星病（Ｖｅｎｔｕｒｉａ　ｎａｓｈｉｃｏｌａ，Ｖ．ｐｉｒｉｎａ）、黒斑病（Ａｌｔｅｒｎａｒｉａ　ａｌｔｅｒｎａｔａ　Ｊａｐａｎｅｓｅ　ｐｅａｒ　ｐａｔｈｏｔｙｐｅ）、赤星病（Ｇｙｍｎｏｓｐｏｒａｎｇｉｕｍ　ｈａｒａｅａｎｕｍ）；
モモの灰星病（Ｍｏｎｉｌｉｎｉａ　ｆｒｕｃｔｉｃｏｌａ）、黒星病（Ｃｌａｄｏｓｐｏｒｉｕｍ　ｃａｒｐｏｐｈｉｌｕｍ）、フォモプシス腐敗病（Ｐｈｏｍｏｐｓｉｓ　ｓｐ．）；
ブドウの黒とう病（Ｅｌｓｉｎｏｅ　ａｍｐｅｌｉｎａ）、晩腐病（Ｇｌｏｍｅｒｅｌｌａ　ｃｉｎｇｕｌａｔａ）、うどんこ病（Ｕｎｃｉｎｕｌａ　ｎｅｃａｔｏｒ）、さび病（Ｐｈａｋｏｐｓｏｒａ　ａｍｐｅｌｏｐｓｉｄｉｓ）、ブラックロット病（Ｇｕｉｇｎａｒｄｉａ　ｂｉｄｗｅｌｌｉｉ）、べと病（Ｐｌａｓｍｏｐａｒａ　ｖｉｔｉｃｏｌａ）；
カキの炭そ病（Ｇｌｏｅｏｓｐｏｒｉｕｍ　ｋａｋｉ）、落葉病（Ｃｅｒｃｏｓｐｏｒａ　ｋａｋｉ，Ｍｙｃｏｓｐｈａｅｒｅｌｌａ　ｎａｗａｅ）；
ウリ類の炭そ病（Ｃｏｌｌｅｔｏｔｒｉｃｈｕｍ　ｌａｇｅｎａｒｉｕｍ）、うどんこ病（Ｓｐｈａｅｒｏｔｈｅｃａ　ｆｕｌｉｇｉｎｅａ）、つる枯病（Ｍｙｃｏｓｐｈａｅｒｅｌｌａ　ｍｅｌｏｎｉｓ）、つる割病（Ｆｕｓａｒｉｕｍ　ｏｘｙｓｐｏｒｕｍ）、べと病（Ｐｓｅｕｄｏｐｅｒｏｎｏｓｐｏｒａ　ｃｕｂｅｎｓｉｓ）、疫病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｓｐ．）、苗立枯病（Ｐｙｔｈｉｕｍ　ｓｐ．）；
トマトの輪紋病（Ａｌｔｅｒｎａｒｉａ　ｓｏｌａｎｉ）、葉かび病（Ｃｌａｄｏｓｐｏｒｉｕｍ　ｆｕｌｖｕｍ）、疫病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）；
ナスの褐紋病（Ｐｈｏｍｏｐｓｉｓ　ｖｅｘａｎｓ）、うどんこ病（Ｅｒｙｓｉｐｈｅ　ｃｉｃｈｏｒａｃｅａｒｕｍ）；
アブラナ科野菜の黒斑病（Ａｌｔｅｒｎａｒｉａ　ｊａｐｏｎｉｃａ）、白斑病（Ｃｅｒｃｏｓｐｏｒｅｌｌａ　ｂｒａｓｓｉｃａｅ）；
ネギのさび病（Ｐｕｃｃｉｎｉａ　ａｌｌｉｉ）、ダイズの紫斑病（Ｃｅｒｃｏｓｐｏｒａ　ｋｉｋｕｃｈｉｉ）、黒とう病（Ｅｌｓｉｎｏｅ　ｇｌｙｃｉｎｅｓ）、黒点病（Ｄｉａｐｏｒｔｈｅ　ｐｈａｓｅｏｌｏｒｕｍ　ｖａｒ．ｓｏｊａｅ）、さび病（Ｐｈａｋｏｐｓｏｒａ　ｐａｃｈｙｒｈｉｚｉ）、茎疫病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｓｏｊａｅ）；
インゲンの炭そ病（Ｃｏｌｌｅｔｏｔｒｉｃｈｕｍ　ｌｉｎｄｅｍｔｈｉａｎｕｍ）
ラッカセイの黒渋病（Ｃｅｒｃｏｓｐｏｒａ　ｐｅｒｓｏｎａｔａ）、褐斑病（Ｃｅｒｃｏｓｐｏｒａ　ａｒａｃｈｉｄｉｃｏｌａ）、白絹病（Ｓｃｌｅｒｏｔｉｕｍ　ｒｏｌｆｓｉｉ）；
エンドウのうどんこ病（Ｅｒｙｓｉｐｈｅ　ｐｉｓｉ）；
ジャガイモの夏疫病（Ａｌｔｅｒｎａｒｉａ　ｓｏｌａｎｉ）、疫病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）、緋色腐敗病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｅｒｙｔｈｒｏｓｅｐｔｉｃａ）、半身萎凋病（Ｖｅｒｔｉｃｉｌｌｉｕｍ　ａｌｂｏ−ａｔｒｕｍ，Ｖ．ｄａｈｌｉａｅ，Ｖ．ｎｉｇｒｅｓｃｅｎｓ）；
イチゴのうどんこ病（Ｓｐｈａｅｒｏｔｈｅｃａ　ｈｕｍｕｌｉ）；
チャの網もち病（Ｅｘｏｂａｓｉｄｉｕｍ　ｒｅｔｉｃｕｌａｔｕｍ）；白星病（Ｅｌｓｉｎｏｅ　ｌｅｕｃｏｓｐｉｌａ）、輪斑病（Ｐｅｓｔａｌｏｔｉｏｐｓｉｓ　ｓｐ．）、炭そ病（Ｃｏｌｌｅｔｏｔｒｉｃｈｕｍ　ｔｈｅａｅ−ｓｉｎｅｎｓｉｓ）
タバコの赤星病（Ａｌｔｅｒｎａｒｉａ　ｌｏｎｇｉｐｅｓ）、うどんこ病（Ｅｒｙｓｉｐｈｅ　ｃｉｃｈｏｒａｃｅａｒｕｍ）、炭そ病（Ｃｏｌｌｅｔｏｔｒｉｃｈｕｍ　ｔａｂａｃｕｍ）、べと病（Ｐｅｒｏｎｏｓｐｏｒａ　ｔａｂａｃｉｎａ）、疫病（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｎｉｃｏｔｉａｎａｅ）；
テンサイの褐斑病（Ｃｅｒｃｏｓｐｏｒａ　ｂｅｔｉｃｏｌａ）、葉腐病（Ｔｈａｎａｔｅｐｈｏｒｕｓ　ｃｕｃｕｍｅｒｉｓ）、根腐病（Ｔｈａｎａｔｅｐｈｏｒｕｓ　ｃｕｃｕｍｅｒｉｓ）、黒根病（Ａｐｈａｎｏｍｙｃｅｓ　ｃｏｃｈｌｉｏｉｄｅｓ）；
バラの黒星病（Ｄｉｐｌｏｃａｒｐｏｎ　ｒｏｓａｅ）、うどんこ病（Ｓｐｈａｅｒｏｔｈｅｃａ　ｐａｎｎｏｓａ）；
キクの褐斑病（Ｓｅｐｔｏｒｉａ　ｃｈｒｙｓａｎｔｈｅｍｉ−ｉｎｄｉｃｉ）、白さび病（Ｐｕｃｃｉｎｉａ　ｈｏｒｉａｎａ）；
ヒマワリのべと病（Ｐｌａｓｍｏｐａｒａ　ｈａｌｓｔｅｄｉｉ）；
タマネギの白斑葉枯病（Ｂｏｔｒｙｔｉｓ　ｃｉｎｅｒｅａ，Ｂ．ｂｙｓｓｏｉｄｅａ，Ｂ．ｓｑｕａｍｏｓａ）、灰色腐敗病（Ｂｏｔｒｙｔｉｓ　ａｌｌｉ）、小菌核性腐敗病（Ｂｏｔｒｙｔｉｓ　ｓｑｕａｍｏｓａ）；
種々の作物の灰色かび病（Ｂｏｔｒｙｔｉｓ　ｃｉｎｅｒｅａ）、菌核病（Ｓｃｌｅｒｏｔｉｎｉａ　ｓｃｌｅｒｏｔｉｏｒｕｍ）、ピシウム属菌による苗立枯病（Ｐｙｔｈｉｕｍ　ａｐｈａｎｉｄｅｒｍａｔｕｍ、Ｐ．ｄｅｂａｒｉａｎｕｍ，Ｐ．ｇｒａｍｉｎｉｃｏｌａ，Ｐ．ｉｒｒｅｇｕｌａｒｅ，Ｐ．ｕｌｔｉｍｕｍ）；ダイコンの黒すす病（Ａｌｔｅｒｎａｒｉａ　ｂｒａｓｓｉｃｉｃｏｌａ）；
シバのダラースポット病（Ｓｃｌｅｒｏｔｉｎｉａ　ｈｏｍｅｏｃａｒｐａ）、シバのブラウンパッチ病およびラージパッチ病（Ｒｈｉｚｏｃｔｏｎｉａ　ｓｏｌａｎｉ）；
バナナのシガトカ病（Ｍｙｃｏｓｐｈａｅｒｅｌｌａ　ｆｉｊｉｅｎｓｉｓ、Ｍｙｃｏｓｐｈａｅｒｅｌｌａ　ｍｕｓｉｃｏｌａ、Ｐｓｅｕｄｏｃｅｒｃｏｓｐｏｒａ　ｍｕｓａｅ）；並びに
ポリミクサ属（Ｐｏｌｙｍｉｘａ　ｓｐｐ．）またはオルピディウム属（Ｏｌｐｉｄｉｕｍ　ｓｐｐ．）等によって媒介される各種植物のウイルス病。 Various substituents used in the description of the present specification will be described below with examples.
“Halogen” means fluorine, chlorine, bromine and iodine.
Examples of the “methyl group substituted with one or more groups selected from group A” include, for example, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, cyanomethyl group, dicyanomethyl group, Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group Butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfinylmethyl group, isopropanesulfinylmethyl group, butanesulfinylmethyl group, isobutanesulfur Examples include nylmethyl group, t-butanesulfinylmethyl group, methanesulfonylmethyl group, ethanesulfonylmethyl group, propanesulfonylmethyl group, isopropanesulfonylmethyl group, butanesulfonylmethyl group, isobutanesulfonylmethyl group, and t-butanesulfonylmethyl group. .
Examples of the “C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B” include, for example, an ethyl group, a 2-fluoroethyl group, a 2,2,2-trifluoroethyl group, Perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodo Propyl group,
Isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoroisopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group, 5-iodo Pentyl group,
2-cyanoethyl group, 2,2-dicyanoethyl group, 3-cyanopropyl group, 3,3-dicyanopropyl group, 4-cyanobutyl group, 4,4-dicyanobutyl group, 5-fluoropentyl group, 5,5- Dicyanopentyl group,
2-methoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, 5-methoxypentyl group, 2-ethoxyethyl group, 3-ethoxypropyl group, 4-ethoxybutyl group, 5-ethoxypentyl group, 2- Propoxyethyl group, 3-propoxypropyl group, 4-propoxybutyl group, 5-propoxypentyl group, 2-butoxyethyl group, 3-butoxypropyl group, 4-butoxybutyl group, 5-butoxypentyl group,
2-methylthioethyl group, 3-methylthiopropyl group, 4-methylthiobutyl group, 5-methylthiopentyl group, 2-ethylthioethyl group, 3-ethylthiopropyl group, 4-ethylthiobutyl group, 5-ethylthiopentyl Group, 2-propylthioethyl group, 3-propylthiopropyl group, 4-propylthiobutyl group, 5-propylthiopentyl group, 2-butylthioethyl group, 3-butylthiopropyl group, 4-butylthiobutyl group , 5-butylthiopentyl group,
2-methanesulfinylethyl group, 3-methanesulfinylpropyl group, 4-methanesulfinylbutyl group, 5-methanesulfinylpentyl group, 2-ethanesulfinylethyl group, 3-ethanesulfinylpropyl group, 4-ethanesulfinylbutyl group, 5 -Ethanesulfinylpentyl group, 2-propanesulfinylethyl group, 3-propanesulfinylpropyl group, 4-propanesulfinylbutyl group, 5-propanesulfinylpentyl group, 2-butanesulfinylethyl group, 3-butanesulfinylpropyl group, 4- Butanesulfinylbutyl group, 5-butanesulfinylpentyl group,
2-methanesulfonylethyl group, 3-methanesulfonylpropyl group, 4-methanesulfonylbutyl group, 5-methanesulfonylpentyl group, 2-ethanesulfonylethyl group, 3-ethanesulfonylpropyl group, 4-ethanesulfonylbutyl group, 5 -Ethanesulfonylpentyl group, 2-propanesulfonylethyl group, 3-propanesulfonylpropyl group, 4-propanesulfonylbutyl group, 5-propanesulfonylpentyl group, 2-butanesulfonylethyl group, 3-butanesulfonylpropyl group, 4- Examples include butanesulfonylbutyl group and 5-butanesulfonylpentyl group.
Examples of the “C3 to C5 cycloalkyl group” include a cyclopropyl group, a cyclobutyl group, and a cyclopentyl group.
Examples of the “C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group,
Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group, 5-iodo Pentyl group,
Cyanomethyl group, dicyanomethyl group, 2-cyanoethyl group, 2,2-dicyanoethyl group, 3-cyanopropyl group, 3,3-dicyanopropyl group, 4-cyanobutyl group, 4,4-dicyanobutyl group, 5-cyano Pentyl group, 5,5-dicyanopentyl group,
Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, 2-methoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, 5-methoxypentyl group, 2-ethoxyethyl group, 3-ethoxypropyl group, 4-ethoxybutyl group, 5-ethoxypentyl group, 2-propoxyethyl group, 3-propoxypropyl group, 4-propoxybutyl group, 5- Propoxypentyl group, 2-butoxyethyl group, 3-butoxypropyl group, 4-butoxybutyl group, 5-butoxypentyl group,
Methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group, butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, 2-methylthioethyl group, 3-methylthiopropyl group, 4- Methylthiobutyl group, 5-methylthiopentyl group, 2-ethylthioethyl group, 3-ethylthiopropyl group, 4-ethylthiobutyl group, 5-ethylthiopentyl group, 2-propylthioethyl group, 3-propylthiopropyl group Group, 4-propylthiobutyl group, 5-propylthiopentyl group, 2-butylthioethyl group, 3-butylthiopropyl group, 4-butylthiobutyl group, 5-butylthiopentyl group,
Methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfinylmethyl group, isopropanesulfinylmethyl group, butanesulfinylmethyl group, isobutanesulfinylmethyl group, t-butanesulfinylmethyl group, 2-methanesulfinylethyl group, 3-methanesulfinylpropyl group Group, 4-methanesulfinylbutyl group, 5-methanesulfinylpentyl group, 2-ethanesulfinylethyl group, 3-ethanesulfinylpropyl group, 4-ethanesulfinylbutyl group, 5-ethanesulfinylpentyl group, 2-propanesulfinylethyl group 3-propanesulfinylpropyl group, 4-propanesulfinylbutyl group, 5-propanesulfinylpentyl group, 2-butanesulfinylethyl group, 3-butanesulfy group Rupuropiru group, 4-Bed ethanesulfinyl butyl group, 5- butane sulfinyl point pen butyl group,
Methanesulfonylmethyl group, ethanesulfonylmethyl group, propanesulfonylmethyl group, isopropanesulfonylmethyl group, butanesulfonylmethyl group, isobutanesulfonylmethyl group, t-butanesulfonylmethyl group, 2-methanesulfonylethyl group, 3-methanesulfonylpropyl group Group, 4-methanesulfonylbutyl group, 5-methanesulfonylpentyl group, 2-ethanesulfonylethyl group, 3-ethanesulfonylpropyl group, 4-ethanesulfonylbutyl group, 5-ethanesulfonylpentyl group, 2-propanesulfonylethyl group 3-propanesulfonylpropyl group, 4-propanesulfonylbutyl group, 5-propanesulfonylpentyl group, 2-butanesulfonylethyl group, 3-butanesulfonylpropyl group, 4-butanesulfonylbutyl group And it includes 5-butane sulfonyl pentyl group.
Examples of the “C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D” include cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl. Group, cyclodecyl group, methylcyclopropyl group, 1,1-dimethylcyclopropyl group, ethylcyclopropyl group, propylcyclopropyl group, butylcyclopropyl group, pentylcyclopropyl group, 2-methylcyclohexyl group, 2-ethylcyclohexyl group 2-propylcyclohexyl group, 2-butylcyclohexyl group, 2-pentylcyclohexyl group, 3-methylcyclohexyl group, 3-ethylcyclohexyl group, 3-propylcyclohexyl group, 3-butylcyclohexyl group, 3-pentylcyclo Hexyl group, 4-methylcyclohexyl group, 4-ethylcyclohexyl group, 4-propylcyclohexyl group, 4-butylcyclohexyl group, 4-pentylcyclohexyl group, fluorocyclopropyl group, chlorocyclopropyl group, 1,1-difluorocyclopropyl Group, 1,1-dichlorocyclopropyl group, 2-fluorocyclohexyl group, 3-fluorocyclohexyl group, 4-fluorocyclohexyl group, 2-chlorocyclohexyl group, 3-chlorocyclohexyl group and 4-chlorocyclohexyl group.
Examples of the “phenyl group optionally substituted with one or more groups selected from group E” include, for example, phenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-iodophenyl group, 3-iodophenyl group, 4-iodophenyl group, 2-cyanophenyl Group, 3-cyanophenyl group, 4-cyanophenyl group, 2-nitrophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2-propylphenyl group, 3-propylpheny Group, 4-propylphenyl group, 2-isopropylphenyl group, 3-isopropylphenyl group, 4-isopropylphenyl group, 2-butylphenyl group, 3-butylphenyl group, 4-butylphenyl group, 2-isobutylphenyl group, 3-isobutylphenyl group, 4-isobutylphenyl group, 2-t-butylphenyl group, 3-t-butylphenyl group, 4-t-butylphenyl group, 2-pentylphenyl group, 3-hexylphenyl group, 4- Heptylphenyl group, 2-octylphenyl group, 3-nonylphenyl group, 4-decylphenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 2- (2 , 2,2-trifluoroethyl) phenyl group, 3- (3,3,3-trifluoropropyl) Phenyl group, 4- (4,4,4-trifluorobutyl) phenyl group, 2- (5,5,5-trifluoropentyl) phenyl group, 3- (6,6,6-trifluorohexyl) phenyl group 4- (7,7,7-trifluoroheptyl) phenyl group, 2- (8,8,8-trifluorooctyl) phenyl group, 3- (9,9,9-trifluorononyl) phenyl group, 4 -(10,10,10-trifluorodecyl) phenyl group,
2-cyclopropylphenyl group, 3-cyclopropylphenyl group, 4-cyclopropylphenyl group, 2-cyclobutylphenyl group, 3-cyclopentylphenyl group, 4-cyclohexylphenyl group, 2-cycloheptylphenyl group, 3-cyclo Octylphenyl group, 4-cyclononylphenyl group, 2-cyclodecylphenyl group, 3- (methylcyclopropyl) phenyl group, 4- (1,1-dimethylcyclopropyl) phenyl group, 3- (fluorocyclopropyl) phenyl Group, 4- (chlorocyclopropyl) phenyl group, 2- (1,1-difluorocyclopropyl) phenyl group, 3- (1,1-dichlorocyclopropyl) phenyl group, 4- (2-fluorocyclohexyl) phenyl group 4- (2-chlorocyclohexyl) phenyl group,
2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-trifluoromethoxyphenyl group, 3-trifluoromethoxyphenyl group, 4-trifluoromethoxyphenyl group, 2-ethoxyphenyl group, 3- Propoxyphenyl group, 4-butoxyphenyl group,
2-methylthiophenyl group, 3-methylthiophenyl group, 4-methylthiophenyl group, 2-trifluoromethylthiophenyl group, 3-trifluoromethylthiophenyl group, 4-trifluoromethylthiophenyl group, 2-ethylthiophenyl group, 3 -Propylthiophenyl group, 4-butylthiophenyl group,
2-methanesulfinylphenyl group, 3-methanesulfinylphenyl group, 4-methanesulfinylphenyl group, 2-methanesulfinylphenyl group, 3-methanesulfinylphenyl group, 4-methanesulfinylphenyl group, 2-ethylsulfinylphenyl group, 3 -Propylsulfinylphenyl group, 4-butylsulfinylphenyl group,
2-methanesulfonylphenyl group, 3-methanesulfonylphenyl group, 4-methanesulfonylphenyl group, 2-methanesulfonylphenyl group, 3-methanesulfonylphenyl group, 4-methanesulfonylphenyl group, 2-ethylsulfonylphenyl group, 3 -Propylsulfonylphenyl group, 4-butylsulfonylphenyl group, 2-acetylphenyl group, 3-acetylphenyl group, 4-acetylphenyl group, 2-difluoroacetylphenyl group, 3-trifluoroacetylphenyl group, 4-dichloroacetyl Phenyl group, 2-trichloroacetylphenyl group, 3-propanoylphenyl group, 4-butanoylphenyl group, 2-isobutanoylphenyl group, 3-pentanoylphenyl group, 4-pivaloylphenyl group,
2- (methoxycarbonyl) phenyl group, 3- (methoxycarbonyl) phenyl group, 4- (methoxycarbonyl) phenyl group, 2- (trifluoromethoxycarbonyl) phenyl group, 3- (trichloromethoxycarbonyl) phenyl group, 4- (Ethoxycarbonyl) phenyl group, 2- (propoxycarbonyl) phenyl group, 3- (isopropoxycarbonyl) phenyl group, 4- (butoxycarbonyl) phenyl group,
2-acetoxyphenyl group, 3-acetoxyphenyl group, 4-acetoxyphenyl group, 2-difluoroacetoxyphenyl group, 3-trifluoroacetoxyphenyl group, 4-trichloroacetoxyphenyl group, 2-propanoyloxyphenyl group, 3- Examples include butanoyloxyphenyl group, 4-isobutanoyloxyphenyl group, 2-pentanoyloxyphenyl group and 3-pivaloyloxyphenyl group.
Examples of the “C2-C5 polymethylene group optionally substituted with one or more groups selected from group E” include, for example, an ethylene group, a 1,3-propylene group, a 1,4-butylene group, and a 1,5-pentylene group. , Fluoroethylene group, chloroethylene group, bromoethylene group, cyanoethylene group, nitroethylene group, 1,2-propylene group, 3,3,3-trifluoro-1,2-propylene group, cyclopropylethylene group, methoxy Ethylene group, trifluoromethoxyethylene group, methylthioethylene group, trifluoromethylthioethylene group, methanesulfinylethylene group, trifluoromethanesulfinylethylene group, methanesulfonylethylene group, trifluoromethanesulfonylethylene group, acetylethylene group, trifluoroacetylethylene group , Methoxycal Examples thereof include bonylethylene group, trifluoromethoxycarbonylethylene group, acetoxyethylene group and trifluoroacetoxyethylene group.
Examples of the “propene-1,3-diyl group optionally substituted with one or more groups selected from group E” include propene-1,3-diyl group, 2-fluoropropene-1,3-diyl group 3-fluoropropene-1,3-diyl group, 3,3-difluoropropene-1,3-diyl group, 2-chloropropene-1,3-diyl group, 2-bromopropene-1,3-diyl group 2-cyanopropene-1,3-diyl group, 2-nitropropene-1,3-diyl group, 2-methylpropene-1,3-diyl group, 3-methylpropene-1,3-diyl group, 3 , 3-Dimethylpropene-1,3-diyl group, 2-trifluoromethylpropene-1,3-diyl group, 2-cyclopropylpropene-1,3-diyl group, 2-methoxypropene-1,3-diyl Group, 2-trif Olomethoxypropene-1,3-diyl group, 2-methylthiopropene-1,3-diyl group, 2-trifluoromethylthiopropene-1,3-diyl group, 2-methanesulfinylpropene-1,3-diyl group, 2-trifluoromethanesulfinylpropene-1,3-diyl group, 2-acetylpropene-1,3-diyl group, 2-trifluoroacetylpropene-1,3-diyl group, 2-methoxycarbonylpropene-1,3- Examples include a diyl group, a 2-trifluoromethoxycarbonylpropene-1,3-diyl group, a 2-acetoxypropene-1,3-diyl group, and a 2-trifluoroacetoxypropene-1,3-diyl group.
Examples of the “1,3-butadiene-1,4-diyl group optionally substituted with one or more groups selected from group E” include 1,3-butadiene-1,4-diyl group, 1-fluoro -1,3-butadiene-1,4-diyl group, 2-fluoro-1,3-butadiene-1,4-diyl group, 1-chloro-1,3-butadiene-1,4-diyl group, 2- Chloro-1,3-butadiene-1,4-diyl group, 1-bromo-1,3-butadiene-1,4-diyl group, 2-bromo-1,3-butadiene-1,4-diyl group, 1 -Cyano-1,3-butadiene-1,4-diyl group, 1-nitro-1,3-butadiene-1,4-diyl group, 1-methyl-1,3-butadiene-1,4-diyl group, 2-methyl-1,3-butadiene-1,4-diyl group, 1-trifluoromethyl -1,3-butadiene-1,4-diyl group, 1-cyclopropyl-1,3-butadiene-1,4-diyl group, 1-methoxy-1,3-butadiene-1,4-diyl group, 1 -Trifluoromethoxy-1,3-butadiene-1,4-diyl group, 1-methylthio-1,3-butadiene-1,4-diyl group, 1-trifluoromethylthio-1,3-butadiene-1, 4-diyl group, 1-methanesulfinyl-1,3-butadiene-1,4-diyl group, 1-trifluoromethanesulfinyl-1,3-butadiene-1,4-diyl group, 1-acetyl-1,3- Butadiene-1,4-diyl group, 1-trifluoroacetyl-1,3-butadiene-1,4-diyl group, 1-methoxycarbonyl-1,3-butadiene-1,4-diyl group, 1-trifluoro Methoxycarbonyl-1,3-butadiene-1,4-diyl group, 1-acetoxy-1,3-butadiene-1,4-diyl group and 1-trifluoroacetoxy-1,3-butadiene-1,4-diyl Groups.
Examples of the “C1-C4 chain hydrocarbon group” include methyl group, ethyl group, ethynyl group, propyl group, isopropyl group, allyl group, propargyl group, butyl group, isobutyl group and t-butyl group.
Examples of the “C1-C10 chain hydrocarbon group optionally substituted with one or more groups selected from group C” include cyclopropylmethyl group, 2-cyclopropylethyl group, 3-cyclopropylpropyl group, 4 -Cyclopropylbutyl group, 5-cyclopropylpentyl group,
Methyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, dibromomethyl group, iodomethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group, 5-iodo Pentyl group,
Hexyl group, 6,6,6-trifluorohexyl group, 6-chlorohexyl group,
Heptyl group, 7,7,7-trifluoroheptyl group, 7-chloroheptyl group,
Octyl group, 8,8,8, -trifluorooctyl group, 8-chlorooctyl group, nonyl group, 9,9,9-trifluorononyl group, 9-chlorononyl group,
Decyl group, 10,10,10-trifluorodecyl group, 10-chlorodecyl group, cyanomethyl group, dicyanomethyl group, 2-cyanoethyl group, 2,2-dicyanoethyl group, 3-cyanopropyl group, 3,3-dicyano Propyl group, 4-cyanobutyl group, 4,4-dicyanobutyl group, 5-cyanopentyl group, 5,5-dicyanopentyl group,
Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, t-butoxymethyl group, 2-methoxyethyl group, 3-methoxypropyl group, 4-methoxybutyl group, 5-methoxypentyl group, 2-ethoxyethyl group, 3-ethoxypropyl group, 4-ethoxybutyl group, 5-ethoxypentyl group, 2-propoxyethyl group, 3-propoxypropyl group, 4-propoxybutyl group, 5- Propoxypentyl group, 2-butoxyethyl group, 3-butoxypropyl group, 4-butoxybutyl group, 5-butoxypentyl group,
Methylthiomethyl group, ethylthiomethyl group, propylthiomethyl group, isopropylthiomethyl group, butylthiomethyl group, isobutylthiomethyl group, t-butylthiomethyl group, 2-methylthioethyl group, 3-methylthiopropyl group, 4- Methylthiobutyl group, 5-methylthiopentyl group, 2-ethylthioethyl group, 3-ethylthiopropyl group, 4-ethylthiobutyl group, 5-ethylthiopentyl group, 2-propylthioethyl group, 3-propylthiopropyl group Group, 4-propylthiobutyl group, 5-propylthiopentyl group, 2-butylthioethyl group, 3-butylthiopropyl group, 4-butylthiobutyl group, 5-butylthiopentyl group,
Methanesulfinylmethyl group, ethanesulfinylmethyl group, propanesulfinylmethyl group, isopropanesulfinylmethyl group, butanesulfinylmethyl group, isobutanesulfinylmethyl group, t-butanesulfinylmethyl group, 2-methanesulfinylethyl group, 3-methanesulfinylpropyl group Group, 4-methanesulfinylbutyl group, 5-methanesulfinylpentyl group, 2-ethanesulfinylethyl group, 3-ethanesulfinylpropyl group, 4-ethanesulfinylbutyl group, 5-ethanesulfinylpentyl group, 2-propanesulfinylethyl group 3-propanesulfinylpropyl group, 4-propanesulfinylbutyl group, 5-propanesulfinylpentyl group, 2-butanesulfinylethyl group, 3-butanesulfy group Rupuropiru group, 4-Bed ethanesulfinyl butyl group, 5- butane sulfinyl point pen butyl group,
Methanesulfonylmethyl group, ethanesulfonylmethyl group, propanesulfonylmethyl group, isopropanesulfonylmethyl group, butanesulfonylmethyl group, isobutanesulfonylmethyl group, t-butanesulfonylmethyl group, 2-methanesulfonylethyl group, 3-methanesulfonylpropyl group Group, 4-methanesulfonylbutyl group, 5-methanesulfonylpentyl group, 2-ethanesulfonylethyl group, 3-ethanesulfonylpropyl group, 4-ethanesulfonylbutyl group, 5-ethanesulfonylpentyl group, 2-propanesulfonylethyl group 3-propanesulfonylpropyl group, 4-propanesulfonylbutyl group, 5-propanesulfonylpentyl group, 2-butanesulfonylethyl group, 3-butanesulfonylpropyl group, 4-butanesulfonylbutyl group And it includes 5-butane sulfonyl pentyl group.
Examples of the “C1-C4 alkoxy group” include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, and a t-butoxy group.
Examples of the “C1-C4 alkylthio group” include a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, and a t-butylthio group.
Examples of the “C1-C4 alkylsulfinyl group” include a methanesulfinyl group, an ethanesulfinyl group, a propanesulfinyl group, an isopropanesulfinyl group, a butanesulfinyl group, an isobutanesulfinyl group, and a t-butanesulfinyl group.
Examples of the “C1-C4 alkylsulfonyl group” include a methanesulfonyl group, an ethanesulfonyl group, a propanesulfonyl group, an isopropanesulfonyl group, a butanesulfonyl group, an isobutanesulfonyl group, and a t-butanesulfonyl group.
Examples of the “C1-C4 alkoxy group optionally substituted with halogen” include a methoxy group, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a chloromethoxy group, a dichloromethoxy group, a trichloromethoxy group, and a bromomethoxy group. , Dibromomethoxy group, iodomethoxy group, chlorodifluoromethoxy group,
Ethoxy group, 2-fluoroethoxy group, 2,2,2-trifluoroethoxy group, perfluoroethoxy group, 2-chloroethoxy group, 2,2,2-trichloroethoxy group, 2-bromoethoxy group, 2-iodo An ethoxy group,
Propoxy group, 3-fluoropropoxy group, 3,3,3-trifluoropropoxy group, perfluoropropoxy group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropoxy group, perfluoroisopropoxy group Group, 3-chloropropoxy group, 3,3,3-trichloropropoxy group, 3-bromopropoxy group, 3-iodopropoxy group,
Butoxy group, 4-fluorobutoxy group, 4,4,4-trifluorobutoxy group, perfluorobutoxy group, 4-chlorobutoxy group, 4,4,4-trichlorobutoxy group, 4-bromobutoxy group and 4-iodo A butoxy group is mentioned.
Examples of the “C1-C4 alkylthio group optionally substituted with halogen” include a methylthio group, a fluoromethylthio group, a difluoromethylthio group, a trifluoromethylthio group, a chloromethylthio group, a dichloromethylthio group, a trichloromethylthio group, and a bromomethylthio group. , Dibromomethylthio group, iodomethylthio group, chlorodifluoromethylthio group,
Ethylthio group, 2-fluoroethylthio group, 2,2,2-trifluoroethylthio group, perfluoroethylthio group, 2-chloroethylthio group, 2,2,2-trichloroethylthio group, 2-bromoethyl A thio group, a 2-iodoethylthio group,
Propylthio group, 3-fluoropropylthio group, 3,3,3-trifluoropropylthio group, perfluoropropylthio group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropylthio group, Fluoroisopropylthio group, 3-chloropropylthio group, 3,3,3-trichloropropylthio group, 3-bromopropylthio group, 3-iodopropylthio group,
Butylthio group, 4-fluorobutylthio group, 4,4,4-trifluorobutylthio group, perfluorobutylthio group, 4-chlorobutylthio group, 4,4,4-trichlorobutylthio group, 4-bromobutyl A thio group and a 4-iodobutylthio group are mentioned.
Examples of the “C1-C4 alkylsulfinyl group optionally substituted with halogen” include methanesulfinyl group, fluoromethanesulfinyl group, difluoromethanesulfinyl group, trifluoromethanesulfinyl group, chloromethanesulfinyl group, dichloromethanesulfinyl group, trichloromethane. Sulfinyl group, bromomethanesulfinyl group, dibromomethanesulfinyl group, iodomethanesulfinyl group, chlorodifluoromethanesulfinyl group,
Ethanesulfinyl group, 2-fluoroethanesulfinyl group, 2,2,2-trifluoroethanesulfinyl group, perfluoroethanesulfinyl group, 2-chloroethanesulfinyl group, 2,2,2-trichloroethanesulfinyl group, 2-bromoethanesulfinyl group Group, 2-iodoethanesulfinyl group,
Propanesulfinyl group, 3-fluoropropanesulfinyl group, 3,3,3-trifluoropropanesulfinyl group, perfluoropropanesulfinyl group, isopropanesulfinyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropanesulfinyl group, perfluoroisopropanesulfinyl group, 3-chloropropanesulfinyl group, 3,3,3-trichloropropanesulfinyl group, 3-bromopropanesulfinyl group, 3-iodopropanesulfinyl group, butanesulfinyl group, 4- Fluorobutanesulfinyl group, 4,4,4-trifluorobutanesulfinyl group, perfluorobutanesulfinyl group, 4-chlorobutanesulfinyl group, 4,4,4-trichlorobutanesulfinyl group, 4-bromobutanesulfinyl group It includes groups and 4-iodo Bed ethanesulfinyl group.
Examples of the “optionally substituted C1-C4 alkylsulfonyl group” include a methanesulfonyl group, a fluoromethanesulfonyl group, a difluoromethanesulfonyl group, a trifluoromethanesulfonyl group, a chloromethanesulfonyl group, a dichloromethanesulfonyl group, and trichloromethane. Sulfonyl group, bromomethanesulfonyl group, dibromomethanesulfonyl group, iodomethanesulfonyl group, chlorodifluoromethanesulfonyl group,
Ethanesulfonyl group, 2-fluoroethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group, perfluoroethanesulfonyl group, 2-chloroethanesulfonyl group, 2,2,2-trichloroethanesulfonyl group, 2-bromoethanesulfonyl Group, 2-iodoethanesulfonyl group,
Propanesulfonyl group, 3-fluoropropanesulfonyl group, 3,3,3-trifluoropropanesulfonyl group, perfluoropropanesulfonyl group, isopropanesulfonyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropanesulfonyl group, perfluoroisopropanesulfonyl group, 3-chloropropanesulfonyl group, 3,3,3-trichloropropanesulfonyl group, 3-bromopropanesulfonyl group, 3-iodopropanesulfonyl group,
Butanesulfonyl group, 4-fluorobutanesulfonyl group, 4,4,4-trifluorobutanesulfonyl group, perfluorobutanesulfonyl group, 4-chlorobutanesulfonyl group, 4,4,4-trichlorobutanesulfonyl group, 4-bromo A butanesulfonyl group and a 4-iodobutanesulfonyl group are mentioned.
Examples of the “(C1-C4 alkyl) carbonyl group optionally substituted with halogen” include acetyl group, fluoroacetyl group, difluoroacetyl group, trifluoroacetyl group, chloroacetyl group, dichloroacetyl group, trichloroacetyl group, Bromoacetyl group, dibromoacetyl group, iodoacetyl group, chlorodifluoroacetyl group,
Propanoyl group, 3-fluoropropanoyl group, 3,3,3-trifluoropropanoyl group, perfluoropropanoyl group, 3-chloropropanoyl group, 3,3,3-trichloropropanoyl group, 3-bromopropanoyl group Noyl group, 3-iodopropanoyl group,
Butanoyl group, 4-fluorobutanoyl group, 4,4,4-trifluorobutanoyl group, perfluorobutanoyl group, 3,3,3,3 ′, 3 ′, 3′-hexafluoroisobutanoyl group, Perfluoroisobutanoyl group, 4-chlorobutanoyl group, 4,4,4-trichlorobutanoyl group, 4-bromobutanoyl group, 4-iodobutanoyl group, isobutanoyl group, 2,2,2,2 ′ , 2 ′, 2′-hexafluoroisobutanoyl group, perfluoroisobutanoyl group,
Pentanoyl group, 5-fluoropentanoyl group, 5,5,5-trifluoropentanoyl group, perfluoropentanoyl group, 5-chloropentanoyl group, 5,5,5-trichloropentanoyl group, 5-bromopenta Examples include a noyl group, a 5-iodopentanoyl group, and a pivaloyl group.
Examples of the “optionally substituted (C1-C4 alkoxy) carbonyl group with halogen” include a methoxycarbonyl group, a fluoromethoxycarbonyl group, a difluoromethoxycarbonyl group, a trifluoromethoxycarbonyl group, a chloromethoxycarbonyl group, and a dichloromethoxycarbonyl group. Group, trichloromethoxycarbonyl group, bromomethoxycarbonyl group, dibromomethoxycarbonyl group, iodomethoxycarbonyl group, chlorodifluoromethoxycarbonyl group,
Ethoxycarbonyl group, 2-fluoroethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, perfluoroethoxycarbonyl group, 2-chloroethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, 2-bromo Ethoxycarbonyl group, 2-iodoethoxycarbonyl group,
Propoxycarbonyl group, 3-fluoropropoxycarbonyl group, 3,3,3-trifluoropropoxycarbonyl group, perfluoropropoxycarbonyl group, isopropoxycarbonyl group, 2,2,2,2 ′, 2 ′, 2′-hexa Fluoroisopropoxycarbonyl group, perfluoroisopropoxycarbonyl group, 3-chloropropoxycarbonyl group, 3,3,3-trichloropropoxycarbonyl group, 3-bromopropoxycarbonyl group, 3-iodopropoxycarbonyl group,
Butoxycarbonyl group, 4-fluorobutoxycarbonyl group, 4,4,4-trifluorobutoxycarbonyl group, perfluorobutoxycarbonyl group, 4-chlorobutoxycarbonyl group, 4,4,4-trichlorobutoxycarbonyl group, 4-bromo A butoxycarbonyl group, a 4-iodobutoxycarbonyl group, and a t-butoxycarbonyl group are mentioned.
Examples of the “(C1-C4 alkyl) carbonyloxy group optionally substituted with halogen” include, for example, an acetoxy group, a fluoroacetoxy group, a difluoroacetoxy group, a trifluoroacetoxy group, a chloroacetoxy group, a dichloroacetoxy group, and a trichloroacetoxy group , Bromoacetoxy group, dibromoacetoxy group, iodoacetoxy group, chlorodifluoroacetoxy group,
Propanoyloxy group, 3-fluoropropanoyloxy group, 3,3,3-trifluoropropanoyloxy group, perfluoropropanoyloxy group, 3-chloropropanoyloxy group, 3,3,3-trichloropropanoyl An oxy group, a 3-bromopropanoyloxy group, a 3-iodopropanoyloxy group,
Butanoyloxy group, 4-fluorobutanoyloxy group, 4,4,4-trifluorobutanoyloxy group, perfluorobutanoyloxy group, isobutanoyloxy group, 3,3,3,3 ′, 3 ′ , 3′-hexafluoroisobutanoyloxy group, perfluoroisobutanoyloxy group, 4-chlorobutanoyloxy group, 4,4,4-trichlorobutanoyloxy group, 4-bromobutanoyloxy group, 4- Iodobutanoyloxy group, pentanoyloxy group, 5-fluoropentanoyloxy group, 5,5,5-trifluoropentanoyloxy group, perfluoropentanoyloxy group, 5-chloropentanoyloxy group, 5,5 , 5-trichloropentanoyloxy group, 5-bromopentanoyloxy group, 5-iodopentanoyloxy group and piva Yloxy group, and the like.
Examples of the “C1-C5 alkyl group” include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a t-butyl group, and a pentyl group.
Examples of the “C1-C10 chain hydrocarbon group optionally substituted with halogen” include a methyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, Bromomethyl group, dibromomethyl group, iodomethyl group, chlorodifluoromethyl group,
Ethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, 2-chloroethyl group, 2,2,2-trichloroethyl group, 2-bromoethyl group, 2-iodoethyl group,
Propyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, perfluoropropyl group, isopropyl group, 2,2,2,2 ′, 2 ′, 2′-hexafluoroisopropyl group, perfluoro Isopropyl group, 3-chloropropyl group, 3,3,3-trichloropropyl group, 3-bromopropyl group, 3-iodopropyl group,
Butyl group, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, perfluorobutyl group, 4-chlorobutyl group, 4,4,4-trichlorobutyl group, 4-bromobutyl group, 4-iodobutyl group, s-butyl group, t-butyl group,
Pentyl group, 5-fluoropentyl group, 5,5,5-trifluoropentyl group, perfluoropentyl group, 5-chloropentyl group, 5,5,5-trichloropentyl group, 5-bromopentyl group and 5-iodo A pentyl group is mentioned.
As an aspect of this invention compound, the following amide compounds are mentioned, for example.
In formula (1), R 1 Is hydrogen, halogen, cyano group, methyl group substituted with one or more groups selected from group A, C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, fluoro An amide compound which is a methyl group or a difluoromethyl group;
In formula (1), R 1 Is hydrogen, halogen, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a fluoromethyl group, or An amide compound which is a difluoromethyl group;
In formula (1), R 1 An amide compound wherein is a methyl group, a fluoromethyl group or a difluoromethyl group substituted with one or more groups selected from hydrogen, halogen, and group A;
In formula (1), R 1 An amide compound in which is hydrogen or halogen;
In formula (1), R 1 An amide compound in which is hydrogen or chlorine;
In formula (1), R 1 An amide compound in which is hydrogen;
In formula (1), R 1 An amide compound in which is a halogen;
In formula (1), R 1 An amide compound wherein is chlorine;
In formula (1), R 2 Is a C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D, group Phenyl group, halogen, cyano group, nitro group, —O—R optionally substituted with one or more groups selected from E 5 Group or -SR 5 Represents a group,
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 And C2-C5 polymethylene group which may be substituted with one or more groups selected from group E, or propene-1,3-diyl which may be substituted with one or more groups selected from group E An amide compound which is a 1,3-butadiene-1,4-diyl group or a methylenedioxy group optionally substituted by one or more groups selected from the group, group E;
In formula (1), R 2 Is a C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group C, phenyl optionally substituted with one or more groups selected from group E Group, halogen, cyano group, nitro group, -O-R 5 Group, -S-R 5 Represents a group,
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 An amide compound in which is bonded and is a C2-C5 polymethylene group, a propene-1,3-diyl group, a 1,3-butadiene-1,4-diyl group or a methylenedioxy group;
In formula (1), R 2 Represents a C1-C5 chain hydrocarbon group, a C3-C10 cycloalkyl group, a phenyl group, a halogen which may be substituted with one or more groups selected from the group C;
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 An amide compound in which is bonded and is a C2-C5 polymethylene group, a propene-1,3-diyl group, or a 1,3-butadiene-1,4-diyl group;
In formula (1), R 2 Is an optionally substituted C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group or halogen amide compound optionally substituted with halogen;
In formula (1), R 2 Is an amide compound which is a C1-C5 chain hydrocarbon group optionally substituted with halogen or halogen;
In formula (1), R 2 Is an amide compound which is a methyl group or halogen optionally substituted with halogen;
An amide compound in which p is 0 in formula (1);
In formula (1), R 2 An amide compound in which is a methyl group;
In formula (1), R 2 An amide compound in which is a trifluoromethyl group;
In formula (1), R 2 An amide compound in which is a fluorine atom;
In formula (1), R 2 An amide compound wherein is chlorine;
In formula (1), R 2 An amide compound wherein is bromine;
In formula (1), p is 1 and R 2 An amide compound in which is a methyl group;
In formula (1), p is 1 and R 2 An amide compound in which is a trifluoromethyl group;
In formula (1), p is 1 and R 2 An amide compound in which is fluorine;
In formula (1), p is 1 and R 2 An amide compound wherein is chlorine;
In formula (1), p is 1 and R 2 An amide compound wherein is bromine;
In formula (1), p is 1 and R 2 An amide compound in which is a methyl group located at the 2-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is a methyl group located at the 3-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is a methyl group located at the 4-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is a trifluoromethyl group located at the 2-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is a trifluoromethyl group located at the 4-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is fluorine at the 2-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is fluorine at the 3-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is fluorine at the 4-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is chlorine at the 2-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is chlorine at the 4-position on the benzene ring;
In formula (1), p is 1 and R 2 An amide compound in which is bromine located at the 2-position on the benzene ring;
In formula (1), p is 2, and two R 2 An amide compound in which both are fluorine;
In formula (1), p is 2, and two R 2 An amide compound in which is fluorine and chlorine;
In formula (1), p is 2, and two R 2 Are both fluorine and two R 2 An amide compound in which is located at the 2-position and 3-position on the benzene ring;
In formula (1), p is 2, and two R 2 Are both fluorine and two R 2 An amide compound in which is located at the 2- and 4-positions on the benzene ring;
In formula (1), p is 2, and two R 2 Are both fluorine and two R 2 An amide compound in which is located at the 2- and 6-positions on the benzene ring;
In formula (1), p is 2, and two R 2 An amide compound in which is fluorine and chlorine;
In formula (1), p is 2, and two R 2 An amide compound in which is fluorine located at the 2-position and chlorine located at the 4-position on the benzene ring;
In formula (1), p is 2, and two R 2 An amide compound in which is fluorine at the 4-position and chlorine at the 2-position on the benzene ring;
In formula (1), p is 3, and three R 2 An amide compound in which both are fluorine;
In formula (1), p is 3, and three R 2 Are both fluorine, and three R 2 An amide compound in which is located at the 2-position, 3-position and 4-position on the benzene ring;
In formula (1), p is 3, and three R 2 Are both fluorine, and three R 2 An amide compound in which is located at the 3-position, 4-position and 5-position on the benzene ring;
In formula (1), R 1 Is a hydrogen, halogen, cyano group, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, A fluoromethyl group or a difluoromethyl group, R 2 Is a C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D, group Phenyl group, halogen, cyano group, nitro group, —O—R optionally substituted with one or more groups selected from E 5 Group or -SR 5 Represents a group,
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 And C2-C5 polymethylene group which may be substituted with one or more groups selected from group E, or propene-1,3-diyl which may be substituted with one or more groups selected from group E An amide compound which is a 1,3-butadiene-1,4-diyl group or a methylenedioxy group optionally substituted by one or more groups selected from the group, group E;
In formula (1), R 1 Is a hydrogen, halogen, cyano group, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, A fluoromethyl group or a difluoromethyl group, R 2 Is a C1-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group C, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D, group Phenyl group, halogen, cyano group, nitro group, —O—R optionally substituted with one or more groups selected from E 5 Group or -SR 5 Represents a group,
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 An amide compound in which is bonded and is a C2-C5 polymethylene group, a propene-1,3-diyl group, a 1,3-butadiene-1,4-diyl group or a methylenedioxy group;
In formula (1), R 1 Is a hydrogen, halogen, cyano group, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, A fluoromethyl group or a difluoromethyl group,
R 2 Represents a C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group, phenyl group or halogen optionally substituted with one or more groups selected from group C;
Or, p is 2 or more and two R 2 Is bonded to the adjacent carbon of the benzene ring, the two R 2 An amide compound in which is bonded and is a C2-C5 polymethylene group, a propene-1,3-diyl group, or a 1,3-butadiene-1,4-diyl group;
In formula (1), R 1 Is a hydrogen, halogen, cyano group, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, A fluoromethyl group or a difluoromethyl group,
R 2 Is an optionally substituted C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group or halogen amide compound optionally substituted with halogen;
In formula (1), R 1 Is hydrogen, halogen, a methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a fluoromethyl group Or a difluoromethyl group,
R 2 Is an optionally substituted C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group or halogen amide compound optionally substituted with halogen;
In formula (1), R 1 Is a methyl group, a fluoromethyl group or a difluoromethyl group substituted with one or more groups selected from hydrogen, halogen and group A;
R 2 Is an optionally substituted C1-C5 chain hydrocarbon group, C3-C10 cycloalkyl group or halogen amide compound optionally substituted with halogen;
In formula (1), R 1 Is a methyl group, a fluoromethyl group or a difluoromethyl group substituted with one or more groups selected from hydrogen, halogen and group A;
R 2 Is an amide compound which is a C1-C5 chain hydrocarbon group optionally substituted with halogen or halogen;
In formula (1), R 1 Is a methyl group, a fluoromethyl group or a difluoromethyl group substituted with one or more groups selected from hydrogen, halogen and group A;
R 2 Is an amide compound which is a methyl group or halogen optionally substituted with halogen;
In formula (1), R 1 Is hydrogen or halogen;
R 2 Is an amide compound which is a methyl group or halogen optionally substituted with halogen;
In formula (1), R 1 Is hydrogen or chlorine,
R 2 Is an amide compound which is a methyl group or halogen optionally substituted with halogen;
In formula (1), R 1 Is hydrogen, p is 1, and R 2 An amide compound in which is a methyl group;
In formula (1), R 1 Is hydrogen, p is 1, and R 2 An amide compound in which is a trifluoromethyl group;
In formula (1), R 1 Is hydrogen, p is 1, and R 2 An amide compound in which is fluorine;
In formula (1), R 1 Is hydrogen, p is 1, and R 2 An amide compound wherein is chlorine;
In formula (1), R 1 Is hydrogen, p is 1, and R 2 An amide compound wherein is bromine;
In formula (1), R 1 Is hydrogen, p is 2, and two R 2 An amide compound in which both are fluorine;
In formula (1), R 1 Is hydrogen, p is 2, and two R 2 An amide compound in which is fluorine and chlorine;
In formula (1), R 1 Is hydrogen, p is 3, and three R 2 An amide compound in which both are fluorine;
In formula (1), R 1 Is chlorine, p is 1, and R 2 An amide compound in which is a methyl group;
In formula (1), R 1 Is chlorine, p is 1, and R 2 An amide compound in which is a trifluoromethyl group;
In formula (1), R 1 Is chlorine, p is 1, and R 2 An amide compound in which is fluorine;
In formula (1), R 1 Is chlorine, p is 1, and R 2 An amide compound wherein is chlorine;
In formula (1), R 1 Is chlorine, p is 1, and R 2 An amide compound wherein is bromine;
In formula (1), R 1 Is chlorine, p is 2, and two R 2 An amide compound in which both are fluorine;
as well as,
In formula (1), R 1 Is chlorine, p is 2, and two R 2 Amide compound in which is fluorine and chlorine.
(Production method 1)
The compound of the present invention or a salt thereof can be produced by reacting compound (3) or a salt thereof with compound (2) in the presence of a dehydration condensing agent.
Figure JPOXMLDOC01-appb-I000003
[In the formula, R 1 , R 2 And p represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as tetrahydrofuran (hereinafter sometimes referred to as THF), ethylene glycol dimethyl ether, tert-butyl methyl ether (hereinafter sometimes referred to as MTBE), hexane, Aliphatic hydrocarbons such as heptane and octane, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N -Acid amides such as dimethylformamide (hereinafter sometimes referred to as DMF), sulfoxides such as dimethylsulfoxide (hereinafter sometimes referred to as DMSO), and mixtures thereof.
Examples of the dehydrating condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC), benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexa Examples thereof include fluorophosphate (hereinafter referred to as BOP reagent) and 1,3-dicyclohexylcarbodiimide.
In the reaction, with respect to 1 mol of the compound (2), the compound (3) is usually used in a proportion of 1 to 3 mol, and the dehydrating condensing agent is usually used in a proportion of 1 to 5 mol.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
In the reaction, when a BOP reagent is used, the reaction is performed in the presence of a base as necessary. Examples of such bases include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
In the reaction, the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (2).
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
(Production method 2)
The compound of the present invention can be produced by reacting compound (3) or a salt thereof with compound (4) or a salt thereof in the presence of a base.
Figure JPOXMLDOC01-appb-I000004
[In the formula, R 1 , R 2 And p represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and halogens such as chlorobenzene. Hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
In the reaction, with respect to 1 mol of the compound (4), the compound (3) is usually used in a proportion of 1 to 3 mol, and the base is usually used in a proportion of 1 to 10 mol.
The reaction temperature is usually in the range of −20 to 140 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
(Production method 3)
The compound of the present invention can be produced, for example, from compound (5) according to the following scheme.
Figure JPOXMLDOC01-appb-I000005
[In the formula, R 1 , R 2 And p represent the same meaning as described above. ]
Step (I-1)
Compound (6) can be produced by reacting compound (5) with compound (3) or a salt thereof in the presence of a dehydration condensing agent.
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and halogens such as chlorobenzene. Hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
Examples of the dehydrating condensing agent used in the reaction include WSC, BOP reagent, and 1,3-dicyclohexylcarbodiimide.
In the reaction, with respect to 1 mol of the compound (5), the compound (3) is usually used in a proportion of 1 to 3 mol, and the dehydrating condensing agent is usually used in a proportion of 1 to 5 mol.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
In the reaction, when a BOP reagent is used, the reaction is performed in the presence of a base as necessary. Examples of such bases include tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
In the reaction, the base is usually used at a ratio of 1 to 10 mol per 1 mol of the compound (5).
After completion of the reaction, the compound (6) can be isolated by performing post-treatment operations such as adding water to the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. The isolated compound (6) can be further purified by chromatography, recrystallization and the like.
Step (I-2)
The compound of the present invention can be produced by reacting compound (6) with an acid.
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene, sulfoxides such as DMSO, methanol, ethanol, 2-methylethanol and the like. Alcohols, acetones, ketones such as methyl ethyl ketone and methyl isobutyl ketone, water, and mixtures thereof.
Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as trifluoroacetic acid, p-toluenesulfonic acid, and methanesulfonic acid.
In the reaction, the acid is usually used in an amount of 1 mol to excess with respect to 1 mol of the compound (6).
The reaction temperature of the reaction is usually in the range of 0 to 150 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
The compound of the present invention is capable of forming an agriculturally acceptable salt. Such a salt of the compound of the present invention is usually a salt of the compound of the present invention and an acid. Examples of the salt with an acid include inorganic acid salts such as hydrochloride, hydrobromide, and sulfate, and organic acid salts such as methanesulfonate, formate, acetate, and trifluoroacetate.
The salt of this invention compound and an acid can be manufactured by making this invention compound react with an acid.
Figure JPOXMLDOC01-appb-I000006
[In the formula, R 1 , R 2 And p represent the same meaning as described above, and HX represents an acid. ]
The reaction is performed in the presence of a solvent or in the absence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, water, and these. A mixture is mentioned.
Examples of the acid used in the reaction include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, and sulfuric acid, and organic acids such as acetic acid, trifluoroacetic acid, formic acid, p-toluenesulfonic acid, and methanesulfonic acid. Can be mentioned.
In the reaction, an acid is usually used at a ratio of 1 to 100 mol per 1 mol of the compound of the present invention.
The reaction temperature of the reaction is usually in the range of 0 to 200 ° C. The reaction time is usually in the range of 1 to 24 hours.
After completion of the reaction, the salt of the compound of the present invention and the acid can be isolated by removing the unreacted acid.
The plant disease control agent of the present invention contains the compound of the present invention or a salt thereof and an inert carrier (solid carrier, liquid carrier or gas carrier). The plant disease control agent of the present invention is further mixed with a surfactant and other formulation adjuvants, wettable powder, granular wettable powder, flowable powder, granules, dry flowable powder, emulsion, aqueous liquid, oil, Formulated into smoking agents, aerosols, microcapsules and the like. These preparations usually contain the compound of the present invention or a salt thereof in a weight ratio of 0.1 to 99%, preferably 0.2 to 90%.
Examples of the solid support include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, wax clay, bentonite, acid clay, talc), and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon). , Calcium carbonate, hydrated silica) and the like. Examples of the liquid carrier include water, alcohols (eg, methanol, ethanol), ketones (eg, acetone, methyl ethyl ketone), aromatic hydrocarbons (eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene), fat Group hydrocarbons (eg, hexane, cyclohexanone, kerosene), esters (eg, ethyl acetate, butyl acetate), nitriles (eg, acetonitrile, isobutyronitrile), ethers (eg, dioxane, diisopropyl ether), Acid amides (for example, dimethylformamide, dimethylacetamide), halogenated hydrocarbons (for example, dichloroethane, trichloroethylene, carbon tetrachloride) and the like can be mentioned. Examples of the gaseous carrier include dimethyl ether and carbon dioxide.
Examples of the surfactant include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylene compounds thereof, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.
Other formulation adjuvants include, for example, fixing agents, dispersants, thickeners, wetting agents, extenders and antioxidants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, Alginic acid), lignin derivatives, bentonite sugars, synthetic water-soluble polymers (eg, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-) Methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, fatty acid or ester thereof, and the like.
The compound of the present invention or a salt thereof is used for controlling plant diseases by applying to a plant or soil where the plant grows. Examples of the method of applying the compound of the present invention or a salt thereof to the plant or the soil where the plant grows include, for example, a method of spraying foliage on the plant, a method of applying to the soil where the plant is cultivated, and a method of applying to the plant seed. It is done.
In the plant disease control method of the present invention, the plant disease control agent of the present invention is usually used.
In the case where the plant disease control agent of the present invention is used in a method of spraying foliage on a plant or a method of applying to a soil where a plant is cultivated, the application amount of the plant disease control agent of the present invention is 1,000 m. 2 The amount of the compound of the present invention or a salt thereof is usually 1 to 500 g, preferably 2 to 200 g. When the plant disease control agent of the present invention is formulated into an emulsion, wettable powder, suspension, etc., the concentration of the compound of the present invention or a salt thereof is usually 0.0005 to 2% by weight, preferably It is diluted with water so as to be 0.005 to 1% by weight. When the plant disease control agent of the present invention is formulated into a powder, granule or the like, the formulation is applied as it is without dilution.
When used in the method of applying the plant disease control agent of the present invention to plant seeds, the application amount of the plant disease control agent of the present invention is usually 0.001 to 1 kg of the present compound or a salt thereof per 1 kg seed. The ratio is 100 g, preferably 0.01 to 50 g.
The plant disease control agent of the present invention can be mixed and / or used in combination with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers or soil conditioners.
Examples of the active ingredient of such a bactericide include the following.
(1) Azole bactericidal active compound
Propiconazole, Prothioconazole, Triadimenol, Prochloraz, Penconazole, Dibuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole, Tebuconazole bromconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumizole, triflumizole aconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, tertanol, tertanol Hall, flutriafol, simeconazole, ipconazole and the like;
(2) Amine fungicidal active compounds
Fenpropimorph, tridemorph, fenpropidin, spiroxamine and the like;
(3) Benzimidazole bactericidal active compound
Carbendazim, benomyl, thiabendazole, thiophanate-methyl and the like;
(4) Dicarboximide bactericidal active compound
Procymidone, iprodione, vinclozolin and the like;
(5) Anilinopyrimidine bactericidal active compound
Cyprodinil, pyrimethanil, mepanipyrim and the like;
(6) Phenylpyrrole bactericidal active compound
Fenpiclonil, fludioxonil, etc .;
(7) Strobilurin bactericidal active compound
Cresoxime-methyl, azoxystrobin, trifloxystrobin, floxastrobin, picoxystrobin, pyracrostrobin, spirobistrobin (Dimoxystrobin), pyribencarb, methinostrobin, oryzatrobin, enestrobin, etc .;
(8) Phenylamide bactericidal active compound
Metalaxyl, metalaxyl-M or mefenoxam, metalaxyl-M or mexillax, benalaxyl-M, benalaxyl-M or kiralaxyl, etc .;
(9) Carboxylic acid amide fungicidal compound
Dimethomorph, iprovalivalb, benchavaricarb-isopropyl, mandipropamide, varifenal
(10) Carboxylic acid amide bactericidal active compound
Carboxin, mepronil, flutolanil, thifluzamide, furamethpyr, boscalid, penthiopyrad, fluopyrad, fluopyrad
(11) Other bactericidal active compounds
Dietofencarb; thiuram; fluazinam; mancozeb; chlorothalonil; captan; diclofluanide; folpetto; quinoxifen; Pencyclon; tolcrofosmethyl; carpropamide; diclocimet; phenoxanil; tricyclazole; pyroxilone; probenazole; isotianil; thiazinyl; tebufloquine; ; Oxytetracycline; streptomycin; basic copper chloride; cupric hydroxide; basic copper sulfate; organic copper; sulfur;
Formula (8)
Figure JPOXMLDOC01-appb-I000007
[Where X 1 Represents hydrogen or halogen, X 2 Represents a methyl group, a difluoromethyl group, or a trifluoromethyl group, and Q is any of the following groups:
Q:
Figure JPOXMLDOC01-appb-I000008
Represents. ]
A pyrazolecarboxylic acid amide compound represented by:
Formula (9)
Figure JPOXMLDOC01-appb-I000009
[Where X 3 Represents a methyl group, a difluoromethyl group, or an ethyl group, and X 4 Represents a methoxy group or a methylamino group, and X 5 Represents a phenyl group, a 2-methylphenyl group, or a 2,5-dimethylphenyl group. ]
An α-alkoxyphenylacetic acid compound represented by:
Formula (10)
Figure JPOXMLDOC01-appb-I000010
[Where X 6 Represents a methoxy group, an ethoxy group, a propoxy group, a 2-propenyloxy group, a 2-propynyloxy group, a 3-butenyloxy group, a 3-butynyloxy group, a methylthio group, an ethylthio group, or a 2-propenylthio group; 7 Represents 1-methylethyl group or 1-methylpropyl group, X 8 Represents a 2-methylphenyl group or a 2,6-dichlorophenyl group. ]
A pyrazolinone compound represented by:
Examples of the active ingredient of such an insecticide include the following.
(1) Organophosphorus insecticidal compound
Acetate, Aluminum phosphide, Butathiofos, Cadusafos, Chlorethoxyphos, Chlorfenvinphos, Chlorpyriphos , Cyanophos (CYAP), diazinon, DCIP (dichloropropionic ether), diclofenthion (ECP), dichlorvos (DDVP), dimethoate (dimethoa) e), dimethylvinphos, disulfoton, EPN, ethion, ethophos, etrimfos, fenthion: MPP, phenothiothion, EP , Formothion, hydrogen phosphide, isofenphos, isoxathion, malathion, mesulfenfos, methidathione monochromate, TP rotophos, naled (BRP), oxydeprofos (ESP), parathion, fosarone, phosmet (PMP), pirimiphos-methyl, pyridenethiop quinalphos), phentoate (PAP), profenofos, propopafos, prothiofos, pyrachlorfos, salithion, sulprofos, sulprofos Temefos, tetrachlorvinphos, terbufos, thiomethon, trichlorphon (DEP), bamidithione, folate, etc .;
(2) Carbamate insecticidal active compound
Aranicarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbofuran, carbosulfane, cloethocarb, cloethocarb , Phenothiocarb, phenoxycarb, furathiocarb, isoprocarb (MIPC), metocarb, methomyl, meNiocarb, methiocarb, Oxamyl (oxamyl), pirimicarb (pirimicarb), propoxur (propoxur: PHC), XMC, thiodicarb (thiodicarb), xylylcarb (xylylcarb), aldicarb (aldicarb) or the like;
(3) Synthetic pyrethroid insecticidal compound
Acrinathrin, allethrin, benfluthrin, beta-cyfluthrin, bifenthrin, cycloprothrin, cyfluthrin (cy), fluthrin (cy) ), Deltamethrin, esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, flucitrinate , Flufenprox, flumethrin, fluvalinate, halfenprox, imiprothrin, permethrin, praretrin, piletrethrin, palletrin. , Sigma-cypermethrin, silafluofen, tefluthrin, tralomethrin, transfluthrin, tetramethrin, tetramethrin. Phenothrin, cyphenothrin, alpha-cypermethrin, zeta-permethrin, lambda-cyhalothrin, urmethaurine, framethrin, urmeturin fluvalinate), 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3-prop-1-enylcyclopropane Carboxylate, 2,3,5,6-tetrafluoro-4-methylbenzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3-prop-1-enyl Cyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3- (2-methyl-1-propenyl) Cyclopropanecarboxylate and the like;
(4) Nereistoxin insecticidal compound
Cartap, bensultap, thiocyclam, monosultap, bisultap, etc .;
(5) Neonicotinoid insecticidal active compound
Imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloprid, dinotefuran, lothianidin, lothianidine, etc.
(6) Benzoylurea insecticidal active compound
Chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron, flucycloxuron Mufluron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron, triazuron, etc .;
(7) Phenylpyrazole insecticidal compound
Acetoprole, etiprole, fipronil, vaniliprole, pyriprole, pyrafluprole, etc .;
(8) Bt toxin
Live spores and produced crystal toxins from Bacillus thuringiensis, and mixtures thereof;
(9) Hydrazine insecticidal compound
Chromafenozide, halofenozide, methoxyphenozide, tebufenozide and the like;
(10) Organochlorine compounds
Aldrin, dieldrin, dienochlor, endosulfan, methoxychlor and the like;
(11) Other insecticidal active ingredients
Machine oil, nicotine-sulfate;
Avermectin (vermectin-B), bromopropyrate, buprofezin, chlorphenapyr, cyromazine, D-D (1,3-Dichloropropene, D-D (1,3-Dichloropropene) fenazaquin, flupyrazofos, hydroprene, metoprene, indoxacarb, methoxadiazone, milbemycine, milbemycine , Pyridalyl, pyriproxyfen, spinosad, sulfuramide, tolfenpyrad, triazemid, flubendiamide, flubendiamide ), Benclothiaz, Calcium cyanoamide, Calcium polysulfide, Chlorden, DDT, DSP, flufenerim, flunicam flu en), formatenate, metham-ammonium, metham-sodium, methyl bromide, ninototefuran, potassium oleate (potassium proleole) Butto (protrifenbute), spiromesifen (spiromesifen), sulfur (Sulfur), metaflumizone (spiratetrazone), pyrifluinazone (pirifluquinone), spinetoram (spiretranol) le),
Formula (11)
Figure JPOXMLDOC01-appb-I000011
[Where:
R 10 Is Me, Cl, Br or F,
R 20 Is F, Cl, Br, C1-C4 haloalkyl, or C1-C4 haloalkoxy,
R 30 Is F, Cl or Br,
R 40 Is H, one or more halogens; CN; SMe; S (O) Me; S (O) 2 C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, or C3-C5 cycloalkylalkyl optionally substituted with Me and OMe,
R 50 Is H or Me,
R 60 H, F or Cl,
R 70 Represents H, F or Cl. A compound represented by
Formula (12)
Figure JPOXMLDOC01-appb-I000012
[Wherein X represents Cl, Br, or I. ]
A compound represented by
Examples of the active ingredient of such an acaricide include acequinocyl, amitraz, benzoximate, bifenate, phenobromolate, quinomethionate, and chinomethionate. chlorobenzilate, CPCBS (chlorfenson), clofentezine, cyflumetofen, quercene, dioxol, etoxazole, fenbutatin phenothiophene Fenpyroximate, fluacrylpyrim, fluproxyfen, penthiridinepirpene, fenpyridine , Tetradiphon, spirodiclofen, spiromesifen, spirotetramat, amidoflumet, cenopyrofene ), And the like.
Examples of the active ingredient of the nematicide include DCIP, fostiazate, levamisole hydrochloride, methylisothiocyanate, morantartrate tartrate, and imiciafos.
Examples of the active ingredient of such a plant growth regulator include etephon, chlormequat-chloride, mepiquat-chloride, and the like.
The plant disease control agent of the present invention can be used, for example, in agricultural lands such as fields, paddy fields, lawns, orchards. Examples of the “crop” in which the plant disease control agent of the present invention can be used include the following.
Agricultural crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplants, tomatoes, peppers, peppers, potatoes) Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, Jatropha, etc.,
Bridegroom,
Foliage plant,
Fruit trees; pears (apples, pears, Japanese pears, quince, quince, etc.), nuclear fruits (peaches, plums, nectarines, ume, sweet cherry, apricots, prunes, etc.), citrus (satsuma mandarin, orange, lemon, lime, grapefruit) ), Nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, oyster, olive, loquat, banana, coffee, Date palm, coconut palm, etc.
Trees other than fruit trees: Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.
“Crop” also includes genetically modified crops.
Examples of plant diseases in which the compound of the present invention or a salt thereof is effective include plant diseases caused by filamentous fungi, and specific examples include the following plant diseases.
Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuri);
Wheat diseases: powdery mildew (Erysiphe graminis), red mold disease (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivare), rust (Puccinia striformi. (Microlectriella nivale), Snow rot microspora nuclear disease (Typhula sp.), Bare scab (Ustilago tritici), Tuna scab (Pseudocercosporella herposis), Blight (Stagonospora nodorum), macular disease (Pyrenophora tritici-repentis);
Diseases of barley: powdery mildew (Erysiphe graminis), red mold disease (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivare), rust (Puccinia striformi. Ustilago nuda), cloud disease (Rhynchosporium secalis), reticular disease (Pyrenophora teres), spot disease (Cochliobolus sativus), leafy leaf disease (Pyrenophora graminea)
Citrus black spot (Diaporthe citri), scab (Elsinoe fawceti), fruit rot (Penicillium digitatum, P. italicum), Phytophthora parasitica, Phytophthora
Apple monilia disease (Valsa ceratosperma), powdery mildew (Podosphaera leucotrica), spotted leaf disease (Alternaria alternata apple disease), black spot disease (Alternaria alternata apple disease) (Phytophotocatarum);
Pear black spot (Venturia nashicola, V. pilina), black spot (Alternaria alternata Japan pair pathotype), red scab (Gymnosporangium haraaeum);
Peach ash scab (Monilinia fracticola), black scab (Cladosporium carpophilum), Phomopsis spoilage (Phomopsis sp.);
Grapes black rot (Elsinoe ampelina), late rot (Glomerella gingulata), powdery mildew (Uncinula apelopidis), black rot (Guignardia olividid)
Oyster anthracnose (Gloeosporium kaki), deciduous leaf disease (Cercospora kaki, Mycosphaerella nawae);
Colletotrichum lagenarium, powdery mildew (Sphaerotheca fuligenea), vine blight (Mycosphaerella meloniis), tsuba disease (Fusium oxysporum), psoriasis (Puso) Seedling blight (Pythium sp.);
Tomato ring rot (Alternaria solani), leaf mold (Cladosporium fulvum), plague (Phytophthora infestans);
Eggplant brown spot (Phomopsis vexans), powdery mildew (Erysiphe cichoacearum);
Brassicaceae vegetable black spot (Alternaria japonica), white spot (Cercosporella brassicae);
Leek rust (Puccinia alli), soybean purpura (Cercospora kikuchii), black scab (Elsinoe glycycines), black spot (Diaporthe pharorum var. Sojae), rust ps
Green Bean Anthracnose (Colletotrichum lindemthianum)
Peanut black astringency (Cercospora personata), brown spot (Cercospora arachidicola), white silkworm (Sclerotium rolfsii);
Pea powdery mildew (Erysiphe pisi);
Potato summer plague (Alternaria solani), plague (Phytophthora infestans), Scarlet rot (Phytophthora erythroseptica), half body wilt (Verticillium albo-arum, re.
Strawberry powdery mildew (Sphaerotheca humuli);
Tea net blast (Exobasidium reticulatum); white scab (Elsinoe leucospila), ring spot disease (Pestarotropis sp.), Anthracnose (Colletotrichum theae-sinensis)
Tobacco red leaf disease (Alternaria longipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), plague (Phytophathorophora)
Sugar beet brown spot (Cercospora beticola), leaf rot (Thanatephorus cucumeris), root rot (Thanatephorus cucumeris), black root (Aphanomyces cochlioides);
Rose scab (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa);
Chrysanthemum brown spot (Septoria chrysanthemi-indici), white rust (Puccinia horiana);
Sunflower downy mildew (Plasmopara halstedii);
Onion white spot blight (Botrytis cinerea, B. byssidea, B. squamosa), gray rot (Botrytis alli), sclerotia rot (Botrytis squamosa);
Various crops of gray mold disease (Botrytis cinerea), sclerotia sclerotia, seedling blight caused by Pythium spp. (Pythium aphanidermatum, P. debarianum, P. Black soot disease (Alternaria brassicicola);
Shiva dollar spot disease (Sclerotinia homeocarpa), brown patch disease and large patch disease (Rhizotonia solani);
Banana sigatoka disease (Mycosphaerella fijiensis, Mycosphaerella musicola, Pseudocercospora musae); and
Viral diseases of various plants mediated by Polymixa spp. Or Olpidium spp.
　以下、本発明を製造例、製剤例及び試験例等によりさらに詳しく説明するが、本発明はこれらの例のみに限定されるものではない。
　まず、本発明化合物の製造例を示す。
製造例１
Figure JPOXMLDOC01-appb-I000013
　２−アミノ−チアゾール−５−カルボン酸塩酸塩０．７５ｇ、ベンジルアミン０．３０ｇ、ピリジン５ｍＬ、１−ヒドロキシベンゾトリアゾール０．３７ｇ、ＷＳＣ０．５３ｇを混合した。その混合物を１０分間加熱還流した後、室温で１日攪拌した。反応混合物を水に注加し、クロロホルムで抽出した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−ベンジル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１）と記す。）を０．１１ｇ得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ［ｐｐｍ］：４．５８（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），５．４３（２Ｈ，ｂｒｓ），６．２５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ），７．２８−７．３８（５Ｈ，ｍ），７．５１（１Ｈ，ｓ）
製造例２
Figure JPOXMLDOC01-appb-I000014
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、４−メチルベンジルアミン０．１７ｇを加え、室温で２時間１０分攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた固体をｔ−ブチルメチルエーテルで洗浄し、２−アミノ−Ｎ−（４−メチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２）と記す。）を０．２１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］〕：２．２７（３Ｈ，ｓ），４．３２（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．１１−７．１８（４Ｈ，ｍ），７．４４（２Ｈ，ｂｒｓ），７．６４（１Ｈ，ｓ），８．５８（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例３
Figure JPOXMLDOC01-appb-I000015
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、３−メチルベンジルアミン０．１７ｇを加え、室温で３時間１０分攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−メチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３）と記す。）を０．１０ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：２．２８（３Ｈ，ｓ），４．３３（２Ｈ，ｄ，Ｊ＝６．１Ｈｚ），７．０３−７．０９（３Ｈ，ｍ），７．１８−７．２２（１Ｈ，ｍ），７．４５（２Ｈ，ｂｒｓ），７．６５（１Ｈ，ｓ），８．５９（１Ｈ，ｔ，Ｊ＝６．１Ｈｚ）．
製造例４
Figure JPOXMLDOC01-appb-I000016
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、２−メチルベンジルアミン０．１７ｇを加え、室温で２時間１０分攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた固体をｔ−ブチルメチルエーテルで洗浄し、２−アミノ−Ｎ−（２−メチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４）と記す。）を０．１５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：２．２９（３Ｈ，ｓ），４．３５（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１４−７．２２（４Ｈ，ｍ），７．４５（２Ｈ，ｂｒｓ），７．６８（１Ｈ，ｓ），８．４９（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例５
Figure JPOXMLDOC01-appb-I000017
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、４−クロロベンジルアミン０．２０ｇを加え、室温で５時間１５分攪拌した。反応混合物を室温にて終夜放置し、反応混合物を氷水に注加したところ、結晶が生じた。その混合物に超音波をあてた後、結晶を濾過により集めた。減圧下で乾燥し、２−アミノ−Ｎ−（４−クロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５）と記す。）を０．１９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３５（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．２９−７．４０（４Ｈ，ｍ），７．４７（２Ｈ，ｂｒｓ），７．６４（１Ｈ，ｓ），８．６５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例６
Figure JPOXMLDOC01-appb-I000018
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、２−クロロベンジルアミン０．２０ｇを加え、室温で３時間３０分攪拌した。反応混合物を氷水に注加したところ、結晶が生じた。超音波をあてた後、結晶を濾過により集めた。減圧下で乾燥し、２−アミノ−Ｎ−（２−クロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６）と記す。）を０．２２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４４（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．２７−７．３５（４Ｈ，ｍ），７．５０（２Ｈ，ｓ），７．７０（１Ｈ，ｂｒｓ），８．６５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例７
Figure JPOXMLDOC01-appb-I000019
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、４−フルオロベンジルアミン０．８７ｇの混合物に、ＢＯＰ試薬０．７４ｇを加え、室温で終夜攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７）と記す。）を０．１８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３５（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．１２−７．１８（２Ｈ，ｍ），７．３１（２Ｈ，ｄｄ，Ｊ＝８．５，５．８Ｈｚ），７．４６（２Ｈ，ｂｒｓ），７．６４（１Ｈ，ｓ），８．６３（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例８
Figure JPOXMLDOC01-appb-I000020
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、３−フルオロベンジルアミン０．８７ｇの混合物に、ＢＯＰ試薬０．７４ｇを加え、室温で４時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（８）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３９（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．０５−７．１３（３Ｈ，ｍ），７．３４−７．４０（１Ｈ，ｍ），７．４８（２Ｈ，ｂｒｓ），７．６６（１Ｈ，ｓ），８．６６（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例９
Figure JPOXMLDOC01-appb-I000021
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、２−フルオロベンジルアミン０．８７ｇの混合物に、ＢＯＰ試薬０．７４ｇを加え、室温で５時間２０分攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、２−アミノ−Ｎ−（２−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（９）と記す。）を０．１８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４１（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１４−７．２０（２Ｈ，ｍ），７．２８−７．３６（２Ｈ，ｍ），７．４７（２Ｈ，ｂｒｓ），７．６７（１Ｈ，ｓ），８．６１（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例１０
Figure JPOXMLDOC01-appb-I000022
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン１．２６ｇ、２−ブロモベンジルアミン塩酸塩０．９３ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２時間攪拌した。反応混合物を重曹水に注加し、酢酸エチルで抽出した。水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にｔ−ブチルメチルエーテルとヘキサンを加えた。結晶を濾過により集め、２−アミノ−Ｎ−（２−ブロモベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０）と記す。）を０．３９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４０（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１９−７．４０（３Ｈ，ｍ），７．５１（２Ｈ，ｂｒｓ），７．６１（１Ｈ，ｄ，Ｊ＝８．０Ｈｚ），７．７１（１Ｈ，ｓ），８．６６（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）
製造例１１
Figure JPOXMLDOC01-appb-I000023
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４２ｇ、２，６−ジフルオロベンジルアミン０．３６ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２時間攪拌した。反応混合物を水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，６−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１１）と記す。）を０．０８９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４１（２Ｈ，ｄ，Ｊ＝４．９Ｈｚ），７．０５−７．１１（２Ｈ，ｍ），７．３５−７．４３（１Ｈ，ｍ），７．４５（２Ｈ，ｂｒｓ），７．６２（１Ｈ，ｓ），８．４７（１Ｈ，ｔ，Ｊ＝４．９Ｈｚ）
製造例１２
Figure JPOXMLDOC01-appb-I000024
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２，４−ジフルオロベンジルアミン０．６０ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２時間攪拌した。反応混合物を氷水に注加したところ結晶が生じた。この結晶を濾過により集めた。結晶を飽和重曹水、水、ヘキサン、ｔ−ブチルメチルエーテルで洗浄し、２−アミノ−Ｎ−（２，４−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１２）と記す。）を０．３８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３７（２Ｈ，ｄ，Ｊ＝５．４Ｈｚ），７．０４−７．０９（１Ｈ，ｍ），７．１９−７．２４（１Ｈ，ｍ），７．３５−７．４１（１Ｈ，ｍ），７．４９（２Ｈ，ｂｒｓ），７．６６（１Ｈ，ｓ），８．６１（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）
製造例１３
Figure JPOXMLDOC01-appb-I000025
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２，３−ジフルオロベンジルアミン０．６０ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２時間攪拌した。反応混合物を水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にクロロホルムを加えた。超音波をあてた後、結晶を濾過により集め、２−アミノ−Ｎ−（２，３−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１３）と記す。）を０．３６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１４−７．２１（２Ｈ，ｍ），７．２９−７．３６（１Ｈ，ｍ），７．５０（２Ｈ，ｂｒｓ），７．６７（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）
製造例１４
Figure JPOXMLDOC01-appb-I000026
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２−クロロ−４−フルオロベンジルアミン０．６６ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で１時間攪拌した。反応混合物を水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にクロロホルムを加えた。超音波をあてた後、結晶を濾過により集め、２−アミノ−Ｎ−（２−クロロ−４−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１４）と記す。）を０．４２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４１（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．２０−７．２５（１Ｈ，ｍ），７．３６−７．３９（１Ｈ，ｍ），７．４３−７．４６（１Ｈ，ｍ），７．５１（２Ｈ，ｂｒｓ），７．７０（１Ｈ，ｓ），８．６４（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）
製造例１５
Figure JPOXMLDOC01-appb-I000027
　２−アミノチアゾール−５−カルボン酸０．１４ｇ、ＤＭＦ２ｍｌ、トリエチルアミン０．４２ｇ及び２、３、４−トリフルオロベンジルアミン０．３２ｇの混合物にＢＯＰ試薬０．５３ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−Ｎ−（２、３、４−トリフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１５）と記す。）０．２１ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３９（２Ｈ，ｄ，Ｊ＝４．９Ｈｚ），７．１４−７．３１（２Ｈ，ｍ），７．４９（２Ｈ，ｂｒｓ），７．６４（１Ｈ，ｓ），８．６６（１Ｈ，ｔ，Ｊ＝４．９Ｈｚ）
製造例１６
Figure JPOXMLDOC01-appb-I000028
　２−アミノチアゾール−５−カルボン酸０．１４ｇ、ＤＭＦ２ｍｌ、トリエチルアミン０．４２ｇ及び３、４、５−トリフルオロベンジルアミン０．３２ｇの混合物にＢＯＰ試薬０．５３ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−Ｎ−（３、４、５−トリフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１６）と記す。）０．１５ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．３４（２Ｈ，ｄ，Ｊ＝５．４Ｈｚ），７．１７−７．３３（２Ｈ，ｍ），７．５０（２Ｈ，ｂｒｓ），７．６５（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）
製造例１７
Figure JPOXMLDOC01-appb-I000029
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．１８ｇ、ＤＭＦ２ｍｌ、トリエチルアミン０．４２ｇ及び２−クロロ−４−フルオロベンジルアミン０．３２ｇの混合物にＢＯＰ試薬０．５３ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−４−クロロ−Ｎ−（２−クロロ−４−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１７）と記す。）０．２３ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４２（２Ｈ，ｄ，Ｊ＝５．３Ｈｚ），７．１９−７．２４（１Ｈ，ｍ），７．３３−７．３８（１Ｈ，ｍ），７．４１−７．４４（１Ｈ，ｍ），７．９１（２Ｈ，ｂｒｓ），８．１５（１Ｈ，ｔ，Ｊ＝５．３Ｈｚ）
製造例１８
Figure JPOXMLDOC01-appb-I000030
　２−アミノ−４−クロロチアゾール−５−カルボン酸１．７９ｇ、ＤＭＦ３０ｍｌ、トリエチルアミン１．０１ｇ及び２、４−ジフルオロベンジルアミン１．４３ｇの混合物にＢＯＰ試薬４．４３ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−４−クロロ−Ｎ−（２、４−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド１．２０ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４１（２Ｈ，ｄ，Ｊ＝５．８０Ｈｚ）．，７．０８−７．０６（１Ｈ，ｍ），７．２３−７．１９（１Ｈ，ｍ），７．３８（１Ｈ，ｑ，Ｊ＝８．１３Ｈｚ），７．９１（２Ｈ，ｓ），８．１４（１Ｈ，ｔ，Ｊ＝５．９２Ｈｚ）
製造例１９
Figure JPOXMLDOC01-appb-I000031
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ５ｍｌ、トリエチルアミン０．２２ｇ及び４−トリフルオロメチルベンジルアミン０．３９ｇの混合物にＢＯＰ試薬０．９７ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−Ｎ−（４−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１９）と記す。）０．３８ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．６４（２Ｈ，ｄ，Ｊ＝６．３Ｈｚ），５．２４（２Ｈ，ｂｒｓ），６．１０（１Ｈ，ｂｒｓ），７．４５（２Ｈ，ｄ，Ｊ＝７．７Ｈｚ），７．５１（１Ｈ，ｓ），７．６１（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）．
製造例２０
Figure JPOXMLDOC01-appb-I000032
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．３６ｇ、ベンジルアミン０．２４ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇの混合物に、氷冷下にてＢＯＰ試薬０．９３ｇを加えた。その混合物を氷冷下にて５分間攪拌後、室温で１３時間攪拌した。反応混合物を室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、飽和食塩水で洗浄した。硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付し、得られた結晶をクロロホルムで洗浄し、２−アミノ−Ｎ−ベンジル−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（２０）と記す。）を０．３９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４１（２Ｈ，ｄ，Ｊ＝６．１Ｈｚ），７．２０−７．３３（５Ｈ，ｍ），７．７５（２Ｈ，ｂｒｓ），８．０１（１Ｈ，ｔ，Ｊ＝６．１Ｈｚ）
製造例２１
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．３６ｇ、２−クロロベンジルアミン０．２４ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇの混合物に、氷冷下にてＢＯＰ試薬０．９３ｇを加えた。その混合物を氷冷下にて５分間攪拌後、室温で１３時間攪拌した。反応混合物を室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、飽和食塩水で洗浄した。硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付し、得られた結晶をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−クロロベンジル）−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（２１）と記す。）を０．４１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４９（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．２６−７．４４（４Ｈ，ｍ），７．７９（２Ｈ，ｂｒｓ），８．０２（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）
製造例２２
Figure JPOXMLDOC01-appb-I000034
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．３６ｇ、２−メチルベンジルアミン０．２７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇの混合物に、氷冷下にてＢＯＰ試薬０．９３ｇを加えた。その混合物を氷冷下にて５分間攪拌後、室温で１２時間攪拌した。反応混合物を室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、飽和食塩水で洗浄した。硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付し、得られた結晶をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−メチルベンジル）−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（２２）と記す。）を０．４２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：２．３０（３Ｈ，ｓ），４．３９（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１４−７．２５（４Ｈ，ｍ），７．７４（２Ｈ，ｂｒｓ），７．８７（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）
製造例２３
Figure JPOXMLDOC01-appb-I000035
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．３６ｇ、２−フルオロベンジルアミン０．２８ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇの混合物に、氷冷下にてＢＯＰ試薬０．９３ｇを加えた。その混合物を氷冷下にて５分間攪拌後、室温で１２時間攪拌した。反応混合物を室温にて終夜放置し、反応混合物を飽和重曹水に注加した。その混合物を酢酸エチルで抽出し、飽和食塩水で洗浄した。硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付し、得られた結晶をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−フルオロベンジル）−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（２３）と記す。）を０．４５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．４６（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１２−７．１８（２Ｈ，ｍ），７．２７−７．３６（２Ｈ，ｍ），７．７７（２Ｈ，ｂｒｓ），８．００（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）
製造例２４
Figure JPOXMLDOC01-appb-I000036
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−メトキシベンジルアミン０．２７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−メトキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２４）と記す。）を０．２５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．７１（３Ｈ，ｓ），４．２８（２Ｈ，ｄ，Ｊ＝５．３１Ｈｚ），６．８７（２Ｈ，ｄ，Ｊ＝８．６９Ｈｚ），７．１９（２Ｈ，ｄ，Ｊ＝７．２４Ｈｚ），７．４２（２Ｈ，ｓ），７．６１−７．６１（１Ｈ，ｓ），８．５５（１Ｈ，ｔ，Ｊ＝５．６７Ｈｚ）．
製造例２５
Figure JPOXMLDOC01-appb-I000037
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−メトキシベンジルアミン０．２７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−メトキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２５）と記す。）を０．１９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．７２（３Ｈ，ｓ），４．３３（２Ｈ，ｄ，Ｊ＝５．１Ｈｚ），６．７８−６．８４（３Ｈ，ｍ），７．２２（１Ｈ，ｔ，Ｊ＝７．７３Ｈｚ），７．４５（２Ｈ，ｓ），７．６４（１Ｈ，ｓ），８．６０（１Ｈ，ｔ，Ｊ＝５．１Ｈｚ）．
製造例２６
Figure JPOXMLDOC01-appb-I000038
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−トリフルオロメチルベンジルアミン０．３５ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２６）と記す。）を０．３２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．５５（２Ｈ，ｄ，Ｊ＝５．３Ｈｚ），７．４４−７．５２（４Ｈ，ｍ），７．６３−７．７１（３Ｈ，ｍ），８．７２（１Ｈ，ｔ，Ｊ＝５．３Ｈｚ）．
製造例２７
Figure JPOXMLDOC01-appb-I000039
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−トリフルオロメチルベンジルアミン０．３５ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２７）と記す。）を０．０５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４４（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．４９（２Ｈ，ｓ），７．５５−７．６１（４Ｈ，ｍ），７．６４（１Ｈ，ｓ），８．７２（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例２８
Figure JPOXMLDOC01-appb-I000040
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−シアノベンジルアミン０．３４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−シアノベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２８）と記す。）を０．３５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４３（２Ｈ，ｄ，Ｊ＝６．３Ｈｚ），７．４５（２Ｈ，ｄ，Ｊ＝８．０Ｈｚ），７．４９（２Ｈ，ｓ），７．６５（１Ｈ，ｓ），７．７８（２Ｈ，ｄ，Ｊ＝７．７Ｈｚ），８．７４（１Ｈ，ｔ，Ｊ＝６．３Ｈｚ）．
製造例２９
Figure JPOXMLDOC01-appb-I000041
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−ｔ−ブチルベンジルアミン０．３３ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−ｔ−ブチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（２９）と記す。）を０．１４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：１．２４（９Ｈ，ｓ），４．３１（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１９（２Ｈ，ｄ，Ｊ＝８．０Ｈｚ），７．３２（２Ｈ，ｄ，Ｊ＝７．７Ｈｚ），７．４４（２Ｈ，ｓ），７．６２（１Ｈ，ｓ），８．５８（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例３０
Figure JPOXMLDOC01-appb-I000042
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−ブロモベンジルアミン０．４５ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−ブロモベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３０）と記す。）を０．２０ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３５（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２８−７．３０（２Ｈ，ｍ），７．４３−７．４７（４Ｈ，ｍ），７．６４（１Ｈ，ｄ，Ｊ＝３．６Ｈｚ），８．６７（１Ｈ，ｓ）．
製造例３１
Figure JPOXMLDOC01-appb-I000043
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−ヨードベンジルアミン０．５４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−ヨードベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３１）と記す。）を０．３４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３１（２Ｈ，ｄ，Ｊ＝４．６Ｈｚ），７．１２（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），７．２８（１Ｈ，ｄ，Ｊ＝６．５Ｈｚ），７．４８（２Ｈ，ｓ），７．５８−７．６４（２Ｈ，ｍ），８．６５（１Ｈ，ｓ）．
製造例３２
Figure JPOXMLDOC01-appb-I000044
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−フェニルベンジルアミン０．３７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−フェニルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３２）と記す。）を０．２１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．３３−７．３６（３Ｈ，ｍ），７．４３−７．４５（４Ｈ，ｍ），７．６１−７．６５（５Ｈ，ｍ），８．６８（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例３３
Figure JPOXMLDOC01-appb-I000045
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３−ニトロベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−ニトロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３３）と記す。）を０．２７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４８（２Ｈ，ｄ，Ｊ＝６．１Ｈｚ），７．５４（２Ｈ，ｓ），７．６０−７．６８（２Ｈ，ｍ），７．７２−７．７５（１Ｈ，ｍ），８．０９−８．１２（２Ｈ，ｍ），８．７９（１Ｈ，ｔ，Ｊ＝６．１Ｈｚ）．
製造例３４
Figure JPOXMLDOC01-appb-I000046
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジブロモメチル−チアゾール−５−カルボン酸アミド０．４４ｇをトリフルオロ酢酸１ｍＬに溶解させた。その混合物を室温で４時間攪拌した。反応混合物に１Ｎ水酸化ナトリウム水溶液を加えアルカリ性になったのを確認し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。残渣をｔ−ブチルメチルエーテルで洗浄して、２−アミノ−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジブロモメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３４）と記す。）０．２５ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１７−７．４１（３Ｈ，ｍ），７．７８（１Ｈ，ｓ），７．８３（２Ｈ，ｂｒｓ），８．４４（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例３５
Figure JPOXMLDOC01-appb-I000047
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジクロロメチル−チアゾール−５−カルボン酸アミド０．５１ｇをトリフルオロ酢酸１ｍＬに溶解させた。その混合物を室温で３時間攪拌した。反応混合物に酢酸エチル３０ｍＬを加え、１Ｎ水酸化ナトリウム水溶液、飽和食塩水の順で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。残渣をｔ−ブチルメチルエーテルで洗浄して、２−アミノ−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジクロロメチル−チアゾール−５−カルボン酸アミド０．３８ｇ（以下、本発明化合物（３５）と記す。）を得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４１（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１７−７．４１（３Ｈ，ｍ），７．８３（２Ｈ，ｂｒｓ），７．８６（１Ｈ，ｓ），８．４８（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例３６
Figure JPOXMLDOC01-appb-I000048
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルチオメチル−チアゾール−５−カルボン酸アミド０．２５ｇをトリフルオロ酢酸１．５ｍＬに溶解させた。その混合物を室温で３時間攪拌した。反応混合物に酢酸エチル３０ｍＬを加え、１Ｎ水酸化ナトリウム水溶液、飽和食塩水の順で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。残渣をｔ−ブチルメチルエーテルとヘキサンの混合液で洗浄して、２−アミノ−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルチオメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３６）と記す。）０．１１ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．０３（３Ｈ，ｓ），３．８９（２Ｈ，ｓ），４．３８（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１６−７．３９（３Ｈ，ｍ），７．３９（２Ｈ，ｂｒｓ），８．０３（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例３７
Figure JPOXMLDOC01-appb-I000049
　２−アミノ−４−エチル−チアゾール−５−カルボン酸０．３４ｇのＤＭＦ溶液（１ｍＬ）、２−クロロ−４−フルオロ−ベンジルアミン０．３５ｇのＤＭＦ溶液（１ｍＬ）、トリエチルアミン０．２１ｇの混合物に、氷冷下にてＢＯＰ試薬０．９３ｇを加えた。その混合物を氷冷下にて５分間攪拌した後、室温で３時間攪拌した。反応混合物を一晩室温で放置し、反応混合物を飽和重曹水１０ｍＬに注加した。その混合物を酢酸エチルで抽出し、飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥して、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付した。得られた２−アミノ−４−エチル−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−チアゾール−５−カルボン酸アミドをクロロホルムで洗浄し、２−アミノ−４−エチル−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−チアゾール−５−カルボン酸アミドを０．２２ｇ（以下、本発明化合物（３７）と記す。）得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：１．１０（３Ｈ，ｔ，Ｊ＝７．５Ｈｚ），２．８０（２Ｈ，ｑ，Ｊ＝７．５Ｈｚ），４．３８（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１９（１Ｈ，ｄｄｄ，Ｊ１＝８．９Ｈｚ，Ｊ２＝８．８Ｈｚ，Ｊ３＝２．７Ｈｚ），７．２８（２Ｈ，ｂｒｓ），７．３４（１Ｈ，ｄｄ，Ｊ１＝８．９Ｈｚ，Ｊ２＝６．７Ｈｚ），７．３７（１Ｈ，ｄｄ，Ｊ１＝８．８Ｈｚ，Ｊ２＝２．７Ｈｚ），７．８８（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例３８
Figure JPOXMLDOC01-appb-I000050
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３，４—ジメチルベンジルアミン０．２７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３，４−ジメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３８）と記す。）を０．１６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．１８（３Ｈ，ｓ），２．１９（３Ｈ，ｓ），４．２９（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．９８（１Ｈ，ｄ，Ｊ＝７．５Ｈｚ），７．０４−７．０８（２Ｈ，ｍ），７．４４（２Ｈ，ｓ），７．６４（１Ｈ，ｓ），８．５４（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）．
製造例３９
Figure JPOXMLDOC01-appb-I000051
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４—ブロモ−２−フルオロベンジルアミン０．４１ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−ブロモ−２−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（３９）と記す。）を０．２９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３６（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２９（１Ｈ，ｔ，Ｊ＝８．２Ｈｚ），７．４１（１Ｈ，ｄ，Ｊ＝８．２Ｈｚ），７．４８−７．５５（３Ｈ，ｍ），７．６６（１Ｈ，ｓ），８．６４（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例４０
Figure JPOXMLDOC01-appb-I000052
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３，４−ジフルオロベンジルアミン０．２９ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３，４−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４０）と記す。）を０．２８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３５（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１２−７．１４（１Ｈ，ｍ），７．２７−７．４４（２Ｈ，ｍ），７．５２（２Ｈ，ｓ），７．６６（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例４１
Figure JPOXMLDOC01-appb-I000053
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２，５−ジフルオロベンジルアミン０．２９ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，５−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４１）と記す。）を０．３３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１０−７．１８（２Ｈ，ｍ），７．２４（１Ｈ，ｔｄ，Ｊ＝９．１，４．６Ｈｚ），７．５２（２Ｈ，ｓ），７．６８（１Ｈ，ｓ），８．６５（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例４３
Figure JPOXMLDOC01-appb-I000054
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、３、５−ジフルオロベンジルアミン０．２１ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３、５−ジフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４３）と記す。）を０．３４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３９（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．９６−７．０１（２Ｈ，ｍ），７．０８−７．１２（１Ｈ，ｍ），７．５１（２Ｈ，ｓ），７．６７（１Ｈ，ｓ），８．７０（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例４４
Figure JPOXMLDOC01-appb-I000055
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２、５−ジクロロベンジルアミン０．３５ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２、５−ジクロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４４）と記す。）を０．２２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４２（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．３３（１Ｈ，ｍ），７．３６−７．４０（１Ｈ，ｍ），７．４８−７．５１（１Ｈ，ｍ），７．５３（２Ｈ，ｓ），７．７１（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例４５
Figure JPOXMLDOC01-appb-I000056
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−ニトロベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ニトロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４５）と記す。）を０．１１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．６６（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．５２−７．５６（４Ｈ，ｍ），７．７０（１Ｈ，ｓ），７．７４（１Ｈ，ｔ，Ｊ＝７．６Ｈｚ），８．０３（１Ｈ，ｄ，Ｊ＝８．５Ｈｚ），８．７１（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例４６
Figure JPOXMLDOC01-appb-I000057
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−フェノキシベンジルアミン０．４７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−フェノキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４６）と記す。）を０．４３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３７（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），６．８６（１Ｈ，ｄ，Ｊ＝８．０Ｈｚ），６．９５（２Ｈ，ｄ，Ｊ＝８．２Ｈｚ），７．０８−７．１６（２Ｈ，ｍ），７．２４−７．２８（１Ｈ，ｍ），７．３２−７．３８（３Ｈ，ｍ），７．４６（２Ｈ，ｓ），７．６４（１Ｈ，ｓ），８．５４（１Ｈ，ｔ，Ｊ＝５．７Ｈｚ）．
製造例４７
Figure JPOXMLDOC01-appb-I000058
２−アミノ−４−メトキシメチル−チアゾール−５−カルボン酸０．３８ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、ベンジルアミン０．２１ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−４−メトキシメチル−Ｎ−ベンジル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４７）と記す。）を０．２４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．１８（２Ｈ，ｓ），４．３６（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），４．４４（３Ｈ，ｓ），７．２１−７．３８（５Ｈ，ｍ），７．４３（２Ｈ，ｓ），８．２２（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例４８
Figure JPOXMLDOC01-appb-I000059
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２，３−ジメトキシベンジルアミン０．３４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，３−ジメトキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４８）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．７３（３Ｈ，ｓ），３．７８（３Ｈ，ｓ），４．３６（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．８１（１Ｈ，ｄ，Ｊ＝７．８Ｈｚ），６．９３（１Ｈ，ｄ，Ｊ＝７．８Ｈｚ），７．００（１Ｈ，ｔ，Ｊ＝７．８Ｈｚ），７．４４（２Ｈ，ｓ），７．６５（１Ｈ，ｓ），８．４９（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例４９
Figure JPOXMLDOC01-appb-I000060
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−フルオロ−２−メチルベンジルアミン０．２８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−フルオロ−２−メチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（４９）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２８（３Ｈ，ｓ），４．３０（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．９３−７．０２（２Ｈ，ｍ），７．２１（１Ｈ，ｄｄ，Ｊ＝８．２，６．３Ｈｚ），７．４５（２Ｈ，ｓ），７．６５（１Ｈ，ｓ），８．４９（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例５０
Figure JPOXMLDOC01-appb-I000061
２−アミノ−４−シクロプロピル−チアゾール−５−カルボン酸ｇ０．３７、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、ベンジルアミン０．２２ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−ベンジル−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５０）と記す。）を０．１２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．８０−０．８２（４Ｈ，ｍ），２．８４−２．８８（１Ｈ，ｍ），４．３３（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．１９−７．３２（５Ｈ，ｍ），７．３７（２Ｈ，ｓ），８．００（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例５２
Figure JPOXMLDOC01-appb-I000062
２−アミノ−チアゾール−５−カルボン酸ｇ０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−トリフルオロメトキシベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−トリフルオロメトキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５２）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３７（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．３０（２Ｈ，ｄ，Ｊ＝８．２Ｈｚ），７．３８（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），７．４７（２Ｈ，ｓ），７．６３（１Ｈ，ｓ），８．６９（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例５３
Figure JPOXMLDOC01-appb-I000063
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルフィニルメチル−チアゾール−５−カルボン酸アミド０．２３ｇをトリフルオロ酢酸１ｍＬに溶解させ、その混合物を室温で２．５時間攪拌した。反応混合物に酢酸エチル４０ｍＬを加え、１Ｎ水酸化ナトリウム水溶液を加えてアルカリ性にし、酢酸エチル層を分取した。水層は酢酸エチルで抽出し、先の酢酸エチル層に合わせた。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。残渣をクロロホルムで洗浄して、２−アミノ−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルフィニルメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５３）と記す。）０．１９ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．５７（３Ｈ，ｓ），４．２６（２Ｈ，ｄ，Ｊ＝１．７Ｈｚ），４．３９（２Ｈ，ｄ，Ｊ＝５．４Ｈｚ），７．１８（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．５Ｈｚ，Ｊ３＝２．７Ｈｚ），７．３８−７．４３（２Ｈ，ｍ），７．４７（２Ｈ，ｂｒｓ），８．６４（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）．
製造例５４
Figure JPOXMLDOC01-appb-I000064
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルホニルメチル−チアゾール−５−カルボン酸アミド０．３０ｇをトリフルオロ酢酸１ｍＬに溶解させた。その混合物を室温で２時間攪拌した。反応混合物に酢酸エチル３０ｍＬを加え、１Ｎ水酸化ナトリウム水溶液を加えてアルカリ性にし、酢酸エチル層を分取した。水層は酢酸エチルで抽出し、先の酢酸エチル層に合わせた。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。残渣をクロロホルムで洗浄して、２−アミノ−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルホニルメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５４）と記す。）０．２０ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．０１（３Ｈ，ｓ），４．４０（２Ｈ，ｄ，Ｊ＝５．４Ｈｚ），４．７８（２Ｈ，ｓ），７．１８（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．５Ｈｚ，Ｊ３＝２．４Ｈｚ），７．３５−７．４０（２Ｈ，ｍ），７．５９（２Ｈ，ｂｒｓ），８．２６（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）．
製造例５５
Figure JPOXMLDOC01-appb-I000065
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−ニトロベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−ニトロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５５）と記す。）を０．１５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４６（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．４９−７．５２（４Ｈ，ｍ），７．６４（１Ｈ，ｓ），８．１７（２Ｈ，ｄ，Ｊ＝７．７Ｈｚ），８．８４（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例５６
Figure JPOXMLDOC01-appb-I000066
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、ベンジルアミン０．２４ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−ベンジル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５６）と記す。）を０．１３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３７（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１７−７．６１（６Ｈ，ｍ），７．８２（２Ｈ，ｂｒｓ），８．６３（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例５７
Figure JPOXMLDOC01-appb-I000067
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−メチルベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−（２−メチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５７）と記す。）を０．２１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２９（３Ｈ，ｓ），４．３５（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．９６−７．６４（５Ｈ，ｍ），７．８１（２Ｈ，ｂｒｓ），８．５３（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例５８
Figure JPOXMLDOC01-appb-I000068
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−フルオロベンジルアミン０．２８ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−（２−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５８）と記す。）を０．１６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４１（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１６−７．４９（５Ｈ，ｍ），７．８４（２Ｈ，ｂｒｓ），８．６３（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例５９
Figure JPOXMLDOC01-appb-I000069
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−クロロ−４−フルオロベンジルアミン０．３５ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−Ｎ−（２−クロロ−４−フルオロベンジル）−４−ジフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（５９）と記す。）を０．１９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１８−７．４９（４Ｈ，ｍ），７．８６（２Ｈ，ｂｒｓ），８．６４（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例６０
Figure JPOXMLDOC01-appb-I000070
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−エチルベンジルアミン０．３０ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−（２−エチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６０）と記す。）を０．１６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：１．１６（３Ｈ，ｔ，Ｊ＝７．５Ｈｚ），２．６５（２Ｈ，ｑ，Ｊ＝７．５Ｈｚ），４．３９（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１１−７．２７（４Ｈ，ｍ），７．８２（２Ｈ，ｂｒｓ），８．５６（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例６１
Figure JPOXMLDOC01-appb-I000071
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−エチルベンジルアミン０．２７ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−エチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６１）と記す。）を０．０７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：１．１６（３Ｈ，ｔ，Ｊ＝７．５Ｈｚ），２．６５（２Ｈ，ｑ，Ｊ＝７．５Ｈｚ），４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１２−７．２６（４Ｈ，ｍ），７．４５（２Ｈ，ｓ），７．６７（１Ｈ，ｓ），８．５１（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例６２
Figure JPOXMLDOC01-appb-I000072
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−メチル−４−フルオロベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−（４−フルオロ−２−メチルベンジル）−チアゾール−５−カルボン酸アミドを０．２０ｇ（以下、本発明化合物（６２）と記す。）得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．３０（３Ｈ，ｓ），４．３１（２Ｈ，ｄ，Ｊ＝５．５Ｈｚ），６．８８−７．０９（２Ｈ，ｍ），７．１２−７．２２（１Ｈ，ｍ），７．３６（１Ｈ，ｔ，Ｊ＝５０．０Ｈｚ），７．８２（２Ｈ，ｂｒｓ），８．５４（１Ｈ，ｔ，Ｊ＝５．５Ｈｚ）．
製造例６３
Figure JPOXMLDOC01-appb-I000073
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−クロロベンジルアミン０．３１ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をＨｅｘａｎｅ，クロロホルムで洗浄し、２−アミノ−Ｎ−（２−クロロベンジル）−４−ジフルオロメチル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６３）と記す。）を０．２１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１６−７．５５（５Ｈ，ｍ），７．８７（２Ｈ，ｂｒｓ），８．６５（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例６４
Figure JPOXMLDOC01-appb-I000074
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−フルオロベンジルアミン０．２８ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−フルオロベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６４）と記す。）を０．３７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７４−０．９６（４Ｈ，ｍ），２．８１−２．９９（１Ｈ，ｍ），４．４０（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．０９−７．２４（２Ｈ，ｍ），７．２４−７．３９（２Ｈ，ｍ），７．４２（２Ｈ，ｂｒｓ），７．９９（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例６５
Figure JPOXMLDOC01-appb-I000075
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−メチルベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−メチルベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６５）と記す。）を０．３１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７６−０．９０（４Ｈ，ｍ），２．２９（３Ｈ，ｓ），２．８２−２．９７（１Ｈ，ｍ），４．３３（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．０６−７．２８（４Ｈ，ｍ），７．３９（２Ｈ，ｂｒｓ），７．９０（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例６６
Figure JPOXMLDOC01-appb-I000076
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−トリフルオロメトキシベンジルアミン０．３８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−トリフルオロメトキシベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６６）と記す。）を０．２６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４４（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．３３−７．４５（４Ｈ，ｍ），７．５０（２Ｈ，ｓ），７．６８（１Ｈ，ｓ），８．６５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例６７
Figure JPOXMLDOC01-appb-I000077
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−ヨードベンジルアミン０．５４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−ヨードベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６７）と記す。）を０．２５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３２（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．１０（２Ｈ，ｄ，Ｊ＝８．３Ｈｚ），７．４８（２Ｈ，ｓ），７．６４（１Ｈ，ｓ），７．６８（２Ｈ，ｄ，Ｊ＝８．３Ｈｚ），８．６５（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例６８
Figure JPOXMLDOC01-appb-I000078
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−エチルベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−エチルベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６８）と記す。）を０．２９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７６−０．８７（４Ｈ，ｍ），１．１７（３Ｈ，ｔ，Ｊ＝７．５Ｈｚ），２．６６（２Ｈ，ｑ，Ｊ＝７．５Ｈｚ），２．８３−２．９６（１Ｈ，ｍ），４．３８（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１０−７．２６（４Ｈ，ｍ），７．３８（２Ｈ，ｂｒｓ），７．９１（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例６９
Figure JPOXMLDOC01-appb-I000079
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、２−クロロ−４−フルオロベンジルアミン０．３５ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（２−クロロ−４−フルオロベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（６９）と記す。）を０．１３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７６−０．８６（４Ｈ，ｍ），２．８２−２．９２（１Ｈ，ｍ），４．３６（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１６−７．２５（１Ｈ，ｍ），７．２９−７．３６（１Ｈ，ｍ），７．３７−７．４７（３Ｈ，ｍ），８．００（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例７０
Figure JPOXMLDOC01-appb-I000080
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、３−メチルベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（３−メチルベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７０）と記す。）を０．３７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７５−０．９４（４Ｈ，ｍ），２．２８（３Ｈ，ｓ），２．７４−３．０３（１Ｈ，ｍ），４．３１（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），６．９７−７．１３（３Ｈ，ｍ），７．１３−７．２８（１Ｈ，ｍ），７．３８（２Ｈ，ｂｒｓ），７．９７（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例７１
Figure JPOXMLDOC01-appb-I000081
２−アミノ−４−シクロプロピルチアゾール−５−カルボン酸０．３７ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−メチルベンジルアミン０．２７ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−Ｎ−（４−メチルベンジル）−４−シクロプロピル−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７１）と記す。）を０．３３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：０．７７−０．８６（４Ｈ，ｍ），２．２７（３Ｈ，ｓ），２．８２−２．９６（１Ｈ，ｍ），４．３０（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），７．１１（２Ｈ，ｄ，Ｊ＝８．０Ｈｚ），７．１７（２Ｈ，ｄ，Ｊ＝８．０Ｈｚ），７．３７（２Ｈ，ｂｒｓ），７．９５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例７２
Figure JPOXMLDOC01-appb-I000082
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−ブロモ−４−フルオロベンジルアミン０．４１ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−４−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７２）と記す。）を０．４２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３８（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２７（１Ｈ，ｔｄ，Ｊ＝８．６，２．４Ｈｚ），７．３５（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），７．５２（２Ｈ，ｓ），７．５８（１Ｈ，ｄｄ，Ｊ＝８．５，２．４Ｈｚ），７．７０（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝５．４Ｈｚ）．
製造例７３
Figure JPOXMLDOC01-appb-I000083
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．４０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−ヨードベンジルアミン塩酸塩０．５４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ヨードベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７３）と記す。）を０．３９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３２（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０３（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），７．２５（１Ｈ，ｄ，Ｊ＝７．４Ｈｚ），７．３９（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），７．５２（２Ｈ，ｓ），７．７２（１Ｈ，ｓ），７．８６（１Ｈ，ｄ，Ｊ＝７．４Ｈｚ），８．６８（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例７４
Figure JPOXMLDOC01-appb-I000084
２−アミノ−チアゾール−５−カルボン酸０．３５ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇの混合物に、２，４，５−トリフルオロベンジルアミン０．３９ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，４，５−トリフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７４）と記す。）を０．１５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３４（２Ｈ，ｄ，Ｊ＝６．３Ｈｚ），７．３６（１Ｈ，ｄｄｄ，Ｊ＝１３．４，６．５，４．１Ｈｚ），７．４７−７．５５（３Ｈ，ｍ），７．６４（１Ｈ，ｓ），８．６４（１Ｈ，ｔ，Ｊ＝６．３Ｈｚ）．
製造例７５
Figure JPOXMLDOC01-appb-I000085
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、５−フルオロ−２−トリフルオロメチルベンジルアミン０．３９ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（５−フルオロ−２−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７５）と記す。）を０．４４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．５３（２Ｈ，ｄ，Ｊ＝５．１Ｈｚ），７．２３（１Ｈ，ｄ，Ｊ＝９．２Ｈｚ），７．２９（１Ｈ，ｔ，Ｊ＝８．３Ｈｚ），７．５４（２Ｈ，ｓ），７．７０（１Ｈ，ｓ），７．７９（１Ｈ，ｔ，Ｊ＝７．０Ｈｚ），８．７６（１Ｈ，ｄ，Ｊ＝５．１Ｈｚ）．
製造例７６
Figure JPOXMLDOC01-appb-I000086
２−アミノ−チアゾール−５−カルボン酸ｇ０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−フルオロ−２−ヨードベンジルアミン塩酸塩０．５８ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−フルオロ−２−ヨードベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７６）と記す。）を０．４５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．２８（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２３−７．２５（２Ｈ，ｍ），７．４９（２Ｈ，ｓ），７．６８（１Ｈ，ｓ），７．７２（１Ｈ，ｄ，Ｊ＝８．５Ｈｚ），８．６６（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例７７
Figure JPOXMLDOC01-appb-I000087
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、４−フルオロ−２−トリフルオロメチルベンジルアミン０．３９ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４−フルオロ−２−トリフルオロメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７７）と記す。）を０．４４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．５０（２Ｈ，ｄ，Ｊ＝５．３Ｈｚ），７．５０−７．５３（４Ｈ，ｍ），７．５９（１Ｈ，ｄ，Ｊ＝９．２Ｈｚ），７．６８（１Ｈ，ｓ），８．７２（１Ｈ，ｔ，Ｊ＝５．３Ｈｚ）．
製造例７８
Figure JPOXMLDOC01-appb-I000088
２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．３９ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．２１ｇ、ＢＯＰ試薬０．９３ｇの混合物に、４−フルオロ−２−ヨードベンジルアミン塩酸塩０．６３ｇを加え、室温で６時間攪拌した。反応混合物を飽和炭酸水素ナトリウム水溶液に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーで精製した。得られた固体をクロロホルムで洗浄し、２−アミノ−４−ジフルオロメチル−Ｎ−（４−フルオロ−２−ヨードベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７８）と記す。）を０．２４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．２９（２Ｈ，ｄ，Ｊ＝５．３Ｈｚ），７．１６−７．５６（３Ｈ，ｍ），７．６６−７．８１（１Ｈ，ｍ），７．８６（２Ｈ，ｂｒｓ），８．６４（１Ｈ，ｔ，Ｊ＝５．３Ｈｚ）．
製造例７９
Figure JPOXMLDOC01-appb-I000089
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２，３，４，５−テトラフルオロベンジルアミン０．４３ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，３，４，５−テトラフルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（７９）と記す。）を０．２１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３８（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１９−７．２５（１Ｈ，ｍ），７．５１（２Ｈ，ｓ），７．６２（１Ｈ，ｓ），８．７２（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８０
２−アミノ−チアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ１０ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８８ｇの混合物に、２−メチル−３−ニトロベンジルアミン０．３４ｇを加え、室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−メチル−３−ニトロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（８０）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．４９（３Ｈ，ｓ），４．４２（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．３８（１Ｈ，ｔ，Ｊ＝７．８Ｈｚ），７．４９−７．５３（３Ｈ，ｍ），７．６５（１Ｈ，ｓ），７．６９（１Ｈ，ｄ，Ｊ＝８．０Ｈｚ），８．６７（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８１
Figure JPOXMLDOC01-appb-I000091
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３−フルオロ−２−メチルベンジルアミン０．２９ｇを混合し、室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−フルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８１）と記す。）を０．３４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２０（３Ｈ，ｓ），４．３８（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０２−７．０９（２Ｈ，ｍ），７．１６−７．２２（１Ｈ，ｍ），７．４８（２Ｈ，ｓ），７．６８（１Ｈ，ｓ），８．５５（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８２
Figure JPOXMLDOC01-appb-I000092
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および５−フルオロ−２−メチルベンジルアミン０．２８ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（５−フルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８２）と記す。）を０．３９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２６（３Ｈ，ｓ），４．３３（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），６．９５−７．０１（２Ｈ，ｍ），７．１７−７．２１（１Ｈ，ｍ），７．５０（２Ｈ，ｓ），７．６９（１Ｈ，ｓ），８．５７（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例８３
Figure JPOXMLDOC01-appb-I000093
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−５−ニトロベンジルアミン塩酸塩０．４５ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−クロロ−５−ニトロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８３）と記す。）を０．０６ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．５２（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．５７（２Ｈ，ｓ），７．７３（１Ｈ，ｓ），７．７８（１Ｈ，ｄ，Ｊ＝９．８Ｈｚ），８．１４−８．１８（２Ｈ，ｍ），８．８３（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８４
Figure JPOXMLDOC01-appb-I000094
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−５−フルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−クロロ−５−フルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８４）と記す。）を０．３８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４２（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１２（１Ｈ，ｄｄ，Ｊ＝９．５，２．９Ｈｚ），７．１５−７．２０（１Ｈ，ｍ），７．４８−７．５５（３Ｈ，ｍ），７．７１（１Ｈ，ｓ），８．６８（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例８５
Figure JPOXMLDOC01-appb-I000095
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−３−フルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−クロロ−３−フルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８５）と記す。）を０．１３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４７（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１８（１Ｈ，ｄ，Ｊ＝７．６Ｈｚ），７．３０−７．４１（２Ｈ，ｍ），７．５２（２Ｈ，ｓ），７．７０（１Ｈ，ｓ），８．７０（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例８６
Figure JPOXMLDOC01-appb-I000096
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−５−フルオロベンジルアミン塩酸塩０．４９ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−５−フルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８６）と記す。）を０．４９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３８（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．０８−７．１４（２Ｈ，ｍ），７．５４（２Ｈ，ｓ），７．６６（１Ｈ，ｄｄ，Ｊ＝８．４，５．２Ｈｚ），７．７２（１Ｈ，ｓ），８．６９（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例８７
Figure JPOXMLDOC01-appb-I000097
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および２，３，５−トリフルオロベンジルアミン０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２，３，５−トリフルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８７）と記す。）を０．３９ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），６．９８−７．０３（１Ｈ，ｍ），７．４０−７．４８（１Ｈ，ｍ），７．５４（２Ｈ，ｓ），７．６７（１Ｈ，ｓ），８．７０（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８８
Figure JPOXMLDOC01-appb-I000098
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−クロロ−４，５−ジフルオロベンジルアミン塩酸塩０．４３ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−クロロ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８８）と記す。）を０．４３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３９（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．３４−７．３９（１Ｈ，ｍ），７．５３（２Ｈ，ｓ），７．６９−７．７６（２Ｈ，ｍ），８．６７（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例８９
Figure JPOXMLDOC01-appb-I000099
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．７１ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−４，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（８９）と記す。）を０．４０ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３５（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．３４（１Ｈ，ｄｄ，Ｊ＝１１．６，８．４Ｈｚ），７．５４（２Ｈ，ｓ），７．７１（１Ｈ，ｓ），７．８７（１Ｈ，ｄｄ，Ｊ＝１０．２，７．６Ｈｚ），８．６８（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９０
Figure JPOXMLDOC01-appb-I000100
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３，４−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３，４−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９０）と記す。）を０．２２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２５（３Ｈ，ｄ，Ｊ＝２．２Ｈｚ），４．３４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０５−７．０９（１Ｈ，ｍ），７．２１（１Ｈ，ｄｄ，Ｊ＝１８．７，８．４Ｈｚ），７．４８（２Ｈ，ｓ），７．６６（１Ｈ，ｓ），８．５４（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９１
Figure JPOXMLDOC01-appb-I000101
　２−アミノチアゾール−５−カルボン酸０．２４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４０ｇ、ＢＯＰ試薬０．８８ｇ、および４，５−ジフルオロ−２−メチルベンジルアミン塩酸塩０．３２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（４，５−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９１）と記す。）を０．３０ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２７（３Ｈ，ｓ），４．３０（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１８（１Ｈ，ｄｄ，Ｊ＝１１．８，８．４Ｈｚ），７．２６（１Ｈ，ｄｄ，Ｊ＝１１．８，８．２Ｈｚ），７．５０（２Ｈ，ｓ），７．６７（１Ｈ，ｓ），８．５８（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例９２
Figure JPOXMLDOC01-appb-I000102
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−３，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９２）と記す。）を０．５１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４３（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０１（１Ｈ，ｄ，Ｊ＝９．３Ｈｚ），７．３８−７．４４（１Ｈ，ｍ），７．５５（２Ｈ，ｓ），７．７２（１Ｈ，ｓ），８．７１（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９３
Figure JPOXMLDOC01-appb-I000103
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３，４，５−トリフルオロ−２−メチルベンジルアミン０．３５ｇを混合し、その混合物を室温で１時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３，４，５−トリフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９３）と記す。）を０．２７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２２（３Ｈ，ｄ，Ｊ＝１．５Ｈｚ），４．３４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０８−７．１４（１Ｈ，ｍ），７．５１（２Ｈ，ｓ），７．６７（１Ｈ，ｓ），８．５７（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９４
Figure JPOXMLDOC01-appb-I000104
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４９ｇ、ＢＯＰ試薬１．０６ｇ、および２−ブロモ−３，４，５−トリフルオロベンジルアミン塩酸塩０．５５ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−３，４，５−トリフルオロベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９４）と記す。）を０．６１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２４−７．３０（１Ｈ，ｍ），７．５５（２Ｈ，ｓ），７．７１（１Ｈ，ｓ），８．７０（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９５
Figure JPOXMLDOC01-appb-I000105
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．５４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８９ｇ、および４，５−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−４−クロロ−Ｎ−（４，５−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９５）と記す。）を０．３５ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２６（３Ｈ，ｓ），４．３０（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．１７（１Ｈ，ｄｄ，Ｊ＝１２．０，８．５Ｈｚ），７．２４（１Ｈ，ｄｄ，Ｊ＝１１．７，８．３Ｈｚ），７．８９（２Ｈ，ｓ），８．１１（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例９６
Figure JPOXMLDOC01-appb-I000106
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．５４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４１ｇ、ＢＯＰ試薬０．８９ｇ、および２−ブロモ−４，５−ジフルオロベンジルアミン０．３９ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−４，５−ジフルオロベンジル）−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（９６）と記す。）を０．４８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３６（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．３０（１Ｈ，ｄｄ，Ｊ＝１１．５，８．５Ｈｚ），７．８５（１Ｈ，ｄｄ，Ｊ＝１０．０，７．６Ｈｚ），７．９３（２Ｈ，ｓ），８．２０（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例９７
Figure JPOXMLDOC01-appb-I000107
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．５４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８９ｇ、および３，４−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−４−クロロ−Ｎ−（３，４−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９７）と記す。）を０．３４ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２５（３Ｈ，ｄ，Ｊ＝２．０Ｈｚ），４．３６（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０５−７．０９（１Ｈ，ｍ），７．２２（１Ｈ，ｄｄ，Ｊ＝１８．７，８．７Ｈｚ），７．９０（２Ｈ，ｓ），８．１０（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例９８
Figure JPOXMLDOC01-appb-I000108
　２−アミノ−４−クロロチアゾール−５−カルボン酸０．５４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４１ｇ、ＢＯＰ試薬０．８９ｇ、および２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で２時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−３，５−ジフルオロベンジル）−４−クロロチアゾール−５−カルボン酸アミド（以下、本発明化合物（９８）と記す。）を０．５０ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４５（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．００（１Ｈ，ｄ，Ｊ＝８．５Ｈｚ），７．３８−７．４３（１Ｈ，ｍ），７．９６（２Ｈ，ｓ），８．２６（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ）．
製造例９９
Figure JPOXMLDOC01-appb-I000109
　２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．５４ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．１４ｇ、ＢＯＰ試薬０．６２ｇ、および４，５−ジフルオロ−２−メチルベンジルアミン０．２２ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−４−ジフルオロメチル−Ｎ−（４，５−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（９９）と記す。）を０．２２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２７（３Ｈ，ｓ），４．２９（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．１７（１Ｈ，ｄｄ，Ｊ＝１２．２，８．８Ｈｚ），７．２６（１Ｈ，ｄｄ，Ｊ＝１１．５，８．３Ｈｚ），７．３３（１Ｈ，ｔ，Ｊ＝５４．６Ｈｚ），７．８４（２Ｈ，ｓ），８．５６（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例１００
Figure JPOXMLDOC01-appb-I000110
　２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．７８ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４１ｇ、ＢＯＰ試薬０．８９ｇ、および２−ブロモ−３，４，５−トリフルオロベンジルアミン塩酸塩０．５５ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−３，４，５−トリフルオロベンジル）−４−ジフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（１００）と記す。）を０．４７ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３９（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．２５−７．３１（１Ｈ，ｍ），７．３２（１Ｈ，ｔ，Ｊ＝５４．４Ｈｚ），７．８９（２Ｈ，ｓ），８．６６（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例１０１
Figure JPOXMLDOC01-appb-I000111
　２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．７８ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２０ｇ、ＢＯＰ試薬０．８９ｇ、および３，４−ジフルオロ−２−メチルベンジルアミン０．３１ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−４−ジフルオロメチル−Ｎ−（３，４−ジフルオロ−２−メチルベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０１）と記す。）を０．３１ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：２．２５（３Ｈ，ｄ，Ｊ＝２．２Ｈｚ），４．３３（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．０３−７．０７（１Ｈ，ｍ），７．２２（１Ｈ，ｄｄ，Ｊ＝１９．１，７．９Ｈｚ），７．３４（１Ｈ，ｔ，Ｊ＝５４．３Ｈｚ），７．８３（２Ｈ，ｓ），８．５６（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例１０２
Figure JPOXMLDOC01-appb-I000112
　２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸０．７８ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．４１ｇ、ＢＯＰ試薬０．８９ｇ、および２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩０．５２ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−ブロモ−３，５−ジフルオロベンジル）−４−ジフルオロメチルチアゾール−５−カルボン酸アミド（以下、本発明化合物（１０２）と記す。）を０．３８ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４２（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），７．００（１Ｈ，ｄ，Ｊ＝８．３Ｈｚ），７．３２（１Ｈ，ｔ，Ｊ＝５４．４Ｈｚ），７．３９−７．４４（１Ｈ，ｍ），７．８９（２Ｈ，ｓ），８．６９（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ）．
製造例１０３
Figure JPOXMLDOC01-appb-I000113
　２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ３ｍＬ、トリエチルアミン０．２４ｇ、ＢＯＰ試薬１．０６ｇ、および３−トリフルオロメトキシベンジルアミン０．３８ｇを混合し、その混合物を室温で３時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（３−トリフルオロメトキシベンジル）チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０３）と記す。）を０．４３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．４２（２Ｈ，ｄ，Ｊ＝６．１Ｈｚ），７．２３−７．２６（２Ｈ，ｍ），７．３２（１Ｈ，ｄ，Ｊ＝７．６Ｈｚ），７．４５−７．４９（１Ｈ，ｍ），７．５２（２Ｈ，ｓ），７．６６（１Ｈ，ｓ），８．７２（１Ｈ，ｔ，Ｊ＝６．１Ｈｚ）．
製造例１０４
Figure JPOXMLDOC01-appb-I000114
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、ＢＯＰ試薬０．７４ｇの混合物に、３−クロロベンジルアミン０．２０ｇを加え、室温で５時間１５分攪拌した。反応混合物を室温にて終夜放置し、反応混合物を氷水に注加し、析晶を生じさせた。超音波をあてた後、結晶を濾過により集めた。この結晶を減圧下で乾燥し、２−アミノ−Ｎ−（３−クロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０４）と記す。）を０．２２ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．３７（２Ｈ，ｄ，Ｊ＝６．０Ｈｚ），７．２４−７．３８（４Ｈ，ｍ），７．４９（２Ｈ，ｂｒｓ），７．６５（１Ｈ，ｓ），８．６７（１Ｈ，ｔ，Ｊ＝６．０Ｈｚ）．
製造例１０５
Figure JPOXMLDOC01-appb-I000115
　２−アミノ−チアゾール−５−カルボン酸０．２０ｇ、ＤＭＦ５ｍＬ、トリエチルアミン０．２８ｇ、２−メトキシベンジルアミン０．８７ｇの混合物に、ＢＯＰ試薬０．７４ｇを加え、室温で４時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−アミノ−Ｎ−（２−メトキシベン
ジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０５）と記す。）を０．２３ｇ得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：３．８１（３Ｈ，ｓ），４．３４（２Ｈ，ｄ，Ｊ＝５．８Ｈｚ），６．８８−６．９４（１Ｈ，ｍ），６．９８（１Ｈ，ｄ，Ｊ＝８．２Ｈｚ），７．１６（１Ｈ，ｄ，Ｊ＝７．７Ｈｚ），７．２１−７．２６（１Ｈ，ｍ），７．４６（２Ｈ，ｂｒｓ），７．６９（１Ｈ，ｓ），８．４５（１Ｈ，ｔ，Ｊ＝５．８Ｈｚ）．
製造例１０６
Figure JPOXMLDOC01-appb-I000116
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２，３−ジクロロベンジルアミン０．７３ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２時間攪拌した。反応混合物を重曹水に注加し、酢酸エチルで抽出した。水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にｔ−ブチルメチルエーテルとヘキサンを加えた。結晶を濾過により集め、２−アミノ−Ｎ−（２，３−ジクロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０６）と記す。）を０．４４ｇ得た。
１ＨＮＭＲ（ＤＭＳＯ−ｄ６）δｐｐｍ：４．４７（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ，Ｂｎ），７．３０~７．３８（２Ｈ，ｍ，Ａｒ），７．５２（２Ｈ，ｂｒｓ，ＮＨ２），７．５６（１Ｈ，ｄ，Ｊ＝６．８Ｈｚ，Ａｒ），７．７１（１Ｈ，ｓ，Ａｒ），８．７１（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ，ＮＨ）
製造例１０７
Figure JPOXMLDOC01-appb-I000117
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２，６−ジクロロベンジルアミン０．７３ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で５時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にヘキサン、ｔ−ブチルメチルエーテル、酢酸エチルを加えた。超音波をあてた後、結晶を濾過により集め、２−アミノ−Ｎ−（２，６−ジクロロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０７）と記す。）を０．３２ｇ得た。
１ＨＮＭＲ（ＤＭＳＯ−ｄ６）δｐｐｍ：４．５９（２Ｈ，ｄ，Ｊ＝４．６Ｈｚ，Ｂｎ），７．３１~７．４１（１Ｈ，ｍ，Ａｒ），７．４４（２Ｈ，ｂｒｓ，ＮＨ２），７．４８~７．５２（２Ｈ，ｍ，Ａｒ），７．６４（１Ｈ，ｓ，Ａｒ），８．２５（１Ｈ，ｔ，Ｊ＝４．６Ｈｚ，ＮＨ）
製造例１０８
Figure JPOXMLDOC01-appb-I000118
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２−クロロ−６−フルオロベンジルアミン０．６６ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で５時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にクロロホルムを加えた。超音波をあてた後、結晶を濾過により集め、２−アミノ−Ｎ−（２−クロロ−６−フルオロベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０８）と記す。）を０．２３ｇ得た。
１ＨＮＭＲ（ＤＭＳＯ−ｄ６）δｐｐｍ：４．４８（２Ｈ，ｄ，Ｊ１＝４．８Ｈｚ，Ｊ２＝１．２Ｈｚ，Ｂｎ），７．２１~７．２５（１Ｈ，ｍ，Ａｒ），７．３２~７．４２（２Ｈ，ｍ，Ａｒ），７．４４（２Ｈ，ｂｒｓ，ＮＨ２），７．６２（１Ｈ，ｓ，Ａｒ），８．３６（１Ｈ，ｔ，Ｊ＝４．８Ｈｚ，ＮＨ）
製造例１０９
Figure JPOXMLDOC01-appb-I000119
　２−アミノ−チアゾール−５−カルボン酸０．３０ｇ、ＤＭＦ２ｍＬ、トリエチルアミン０．４２ｇ、２，３−ジメチルベンジルアミン０．５６ｇの混合物に、ＢＯＰ試薬１．１０ｇを加え、室温で２．５時間攪拌した。反応混合物を氷水に注加し、酢酸エチルで抽出した。飽和重曹水、飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣にｔ−ブチルメチルエーテル、酢酸エチルを加えた。超音波をあてた後、結晶を濾過により集め、２−アミノ−Ｎ−（２，３−ジメチルベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１０９）と記す。）を０．２９ｇ得た。
１ＨＮＭＲ（ＤＭＳＯ−ｄ６）δｐｐｍ：２．１７（３Ｈ，ｓ，Ｍｅ），２．２４（３Ｈ，ｓ，Ｍｅ），４．３６（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ，Ｂｎ），７．０１~７．０８（３Ｈ，ｍ，Ａｒ），７．４４（２Ｈ，ｂｒｓ，ＮＨ２），７．６７（１Ｈ，ｓ），８．４４（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ，ＮＨ）
製造例１１０
Figure JPOXMLDOC01-appb-I000120
２−アミノチアゾール−５−カルボン酸０．１４ｇ、ＤＭＦ２ｍｌ、トリエチルアミン０．４２ｇ及び２，４，６−トリフルオロベンジルアミン０．３２ｇの混合物にＢＯＰ試薬０．５３ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付してＮ−（２，４，６−トリフルオロベンジル）−２−アミノチアゾール−５−カルボン酸アミド（以下、本発明化合物（１１０）と記す。）０．１５ｇを得た。
１ＨＮＭＲ（ＤＭＳＯ−ｄ６）δｐｐｍ：４．３５（２Ｈ，ｄ，Ｊ＝４．６Ｈｚ），７．０９~７．１９（２Ｈ，ｍ），７．４４（２Ｈ，ｂｒｓ，ＮＨ２），７．６０（１Ｈ，ｓ），８．４５（１Ｈ，ｔ，Ｊ＝４．９Ｈｚ，ＮＨ）
製造例１１１
Figure JPOXMLDOC01-appb-I000121
２−アミノチアゾール−５−カルボン酸０．２９ｇ、ＤＭＦ５ｍｌ、トリエチルアミン０．２２ｇ及び４−ブロモベンジルアミン０．５０ｇの混合物にＢＯＰ試薬０．９７ｇを加え、室温で終夜撹拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２−アミノ−Ｎ−（４−ブロモベンジル）−チアゾール−５−カルボン酸アミド（以下、本発明化合物（１１１）と記す。）０．１０ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．５２（２Ｈ，ｄ，Ｊ＝６．４Ｈｚ），５．３７（２Ｈ，ｓ），６．２７（１Ｈ，ｓ），７．２２（２Ｈ，ｄ，Ｊ＝８．１Ｈｚ），７．４７（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），７．５２（１Ｈ，ｓ）．
参考製造例１
　ｎ−ヘプタン１００ｍｌで共沸脱水したスルホラン４００ｍｌにフッ化カリウム５２．３ｇ、ｎ−ヘプタン１００ｍｌを加え、１時間共沸脱水した。反応混合物を室温まで冷却した。ここに２，４−ジクロロチアゾール９２．４ｇを加え、１８０℃で５時間攪拌した。反応混合物を室温まで冷却し、減圧蒸留して４−クロロ−２−フルオロチアゾール６２．５ｇを得た。
　４−クロロ−２−フルオロチアゾール
Figure JPOXMLDOC01-appb-I000122
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ［ｐｐｍ］：６．７２（１Ｈ，ｓ）
参考製造例２
　ジイソプロピルアミン１０．７ｇをテトラヒドロフラン２００ｍｌに溶解し、−７０℃に冷却した。ここにｎ−ブチルリチウム（１．６５ｍｏｌ／Ｌ）６４ｍｌを滴下し、０℃まで昇温した。再び−７０℃まで冷却し、４−クロロ−２−フルオロチアゾール１３．２ｇのテトラヒドロフラン溶液３０ｍｌを滴下した。−７０℃で３時間保温した後、細かく砕いたドライアイスを加えた後、室温で終夜攪拌した。反応混合物を減圧下で濃縮して、得られた固体に酢酸エチル、１０％硫酸を加え分液した。有機層を水及び飽和食塩水で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮して４−クロロ−２−フルオロチアゾール−５−カルボン酸１３．５ｇを得た。
　４−クロロ−２−フルオロチアゾール−５−カルボン酸
Figure JPOXMLDOC01-appb-I000123
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：４．１４（１Ｈ，ｓ）
参考製造例３
　２８％アンモニア水溶液３０ｍｌを０℃に冷却し、４−クロロ−２−フルオロチアゾール−５−カルボン酸３．６３ｇを数回に分割して加えた。その混合物を室温で終夜攪拌した後、１０％硫酸を固体が生じるまで滴下した。生じた固体をろ過、乾燥して２−アミノ−４−クロロチアゾール−５−カルボン酸３．１０ｇを得た。
　２−アミノ−４−クロロチアゾール−５−カルボン酸
Figure JPOXMLDOC01-appb-I000124
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ［ｐｐｍ］：７．２０（１Ｈ，ｂｒ　ｓ），８．０４（２Ｈ，ｓ）
参考製造例４
Figure JPOXMLDOC01-appb-I000125
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチル−チアゾール−５−カルボン酸アミド２．４０ｇをクロロホルム１８０ｍＬに溶解させ、５０℃に昇温してＮ−ブロモスクシンイミド１．０７ｇとアゾビスイソブチロニトリル９９ｍｇを加えた。１時間加熱還流した後、再度アゾビスイソブチロニトリル９９ｍｇを加えた。さらに１時間加熱還流した後、もう一度アゾビスイソブチロニトリル９９ｍｇを加えた。２時間加熱還流を行い、反応混合物を室温まで冷却した。反応混合物を飽和重曹水、飽和食塩水の順で洗浄し、硫酸マグネシウムで乾燥した後、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジブロモメチル−チアゾール−５−カルボン酸アミド０．４４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５４（９Ｈ，ｓ），４．６１（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），６，１４（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ），６．９９（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．４Ｈｚ，Ｊ３＝２．６Ｈｚ），７．１５（１Ｈ，ｄｄ，Ｊ１＝８．４Ｈｚ，Ｊ２＝２．６Ｈｚ），７．４３（１Ｈ，ｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝６．１Ｈｚ），７．７４（１Ｈ，ｓ），７．８３（１Ｈ，ｂｒｓ）
参考製造例５
Figure JPOXMLDOC01-appb-I000126
２−（ｔ−ブトキシカルボニルアミノ）−４−メチル−チアゾール−５−カルボン酸５．１７ｇのＤＭＦ溶液に２−クロロ−４−フルオロ−ベンジルアミン３．５１ｇのＤＭＦ溶液（１０ｍＬ）とトリエチルアミン２．９２ｍＬを加え、さらに氷冷下でＢＯＰ試薬９．２９ｇを加えた。その混合物を氷冷下で５分間攪拌した後、室温で１２時間攪拌した。その混合物を室温で一晩放置した後、反応混合物を飽和重曹水１００ｍＬに注加したところ結晶が生じた。結晶を濾過により集め、水、トルエンの順に洗浄した後、乾燥させて２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチル−チアゾール−５−カルボン酸アミド８．９３ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５４（９Ｈ，ｓ），２．６３（３Ｈ，ｓ），４．６１（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），６．０７（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ），６．９７（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．３Ｈｚ，Ｊ３＝２．７Ｈｚ），７．１４（１Ｈ，ｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝２．７Ｈｚ），７．４４（１Ｈ，ｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝６．１Ｈｚ），１０．１７（１Ｈ，ｂｒｓ）
参考製造例６
Figure JPOXMLDOC01-appb-I000127
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチル−チアゾール−５−カルボン酸アミド０．８０ｇをクロロホルム２０ｍＬに溶解させ、Ｎ−クロロスクシンイミド０．５６ｇとアゾビスイソブチロニトリル３３ｍｇを加えた。１時間加熱還流した後、再度アゾビスイソブチロニトリル３３ｍｇを加えた。さらに１時間加熱還流した後、もう一度アゾビスイソブチロニトリル３３ｍｇを加えた。１時間加熱還流を行い、反応混合物を室温まで冷却した。反応混合物を飽和重曹水、飽和食塩水の順で洗浄し、硫酸マグネシウムで乾燥した後、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−ジクロロメチル−チアゾール−５−カルボン酸アミド０．４４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５４（９Ｈ，ｓ），４．６１（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），６，１６（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ），６．９９（１Ｈ，ｄｄｄ，Ｊ１＝８．４Ｈｚ，Ｊ２＝８．３Ｈｚ，Ｊ３＝２．４Ｈｚ），７．１５（１Ｈ，ｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝２．４Ｈｚ），７．４３（１Ｈ，ｄｄ，Ｊ１＝８．４Ｈｚ，Ｊ２＝６．２Ｈｚ），７．７９（１Ｈ，ｓ），８．２５（１Ｈ，ｂｒｓ）
参考製造例７
Figure JPOXMLDOC01-appb-I000128
４−ブロモメチル−２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−チアゾール−５−カルボン酸アミド０．３１ｇにエタノール２ｍＬ、テトラヒドロフラン１ｍＬ、メチルメルカプタンナトリウム５５ｍｇを加えた。その混合物を室温で３時間攪拌した。ここにメチルメルカプタンナトリウム１１ｍｇを追加し、さらに２時間攪拌した。反応混合物に酢酸エチル４０ｍＬを加え、１Ｎ水酸化ナトリウム水溶液、飽和食塩水の順で洗浄した後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。残渣にｔ−ブチルメチルエーテルとヘキサンを加え、もう一度濃縮し、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルチオメチル−チアゾール−５−カルボン酸アミド０．２５ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５５（９Ｈ，ｓ），２．０４（３Ｈ，ｓ），４．０５（２Ｈ，ｓ），４．６１（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），６．７８（１Ｈ，ｂｒｓ），６．９７（１Ｈ，ｄｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝８．２Ｈｚ，Ｊ３＝２．２Ｈｚ），７．１４（１Ｈ，ｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝２．２Ｈｚ），７．４５（１Ｈ，ｄｄ，Ｊ１＝８．２Ｈｚ，Ｊ２＝６．２Ｈｚ）
参考製造例８
Figure JPOXMLDOC01-appb-I000129
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチル−チアゾール−５−カルボン酸アミド０．８０ｇのクロロホルム溶液（２０ｍＬ）にＮ−ブロモスクシンイミド０．３６ｇとアゾビスイソブチロニトリル３３ｍｇを加えた。１．５時間加熱還流した後、再度アゾビスイソブチロニトリル３３ｍｇを加えた。さらに２時間加熱還流した後、もう一度アゾビスイソブチロニトリル３３ｍｇを加えた。２時間加熱還流を行い、反応混合物を室温まで冷却した。反応混合物を飽和重曹水、飽和食塩水の順で洗浄し、硫酸マグネシウムで乾燥した後、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、４−ブロモメチル−２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−チアゾール−５−カルボン酸アミド０．４４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５７（９Ｈ，ｓ），４．６４（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），４．９５（２Ｈ，ｓ），６．５０（１Ｈ，ｔ，Ｊ＝５．６Ｈｚ），６．９７（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．４Ｈｚ，Ｊ３＝２．６Ｈｚ），７．１４（１Ｈ，ｄｄ，Ｊ１＝８．４Ｈｚ，Ｊ２＝２．６Ｈｚ），７．４４（１Ｈ，ｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝５．９Ｈｚ），１０．５９（１Ｈ，ｂｒｓ）
参考製造例１０
Figure JPOXMLDOC01-appb-I000130
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチル−チアゾール−５−カルボン酸アミド１０．２１ｇのクロロホルム溶液（２５５ｍＬ）にＮ−クロロスクシンイミド３．４１ｇとアゾビスイソブチロニトリル０．４２ｇを加えた。１時間加熱還流した後、再度アゾビスイソブチロニトリル０．４２ｇを加えた。さらに１時間加熱還流した後、もう一度アゾビスイソブチロニトリル０．４２ｇを加えた。２時間加熱還流を行い、反応混合物を室温まで冷却した。反応混合物を飽和重曹水、飽和食塩水の順で洗浄し、硫酸マグネシウムで乾燥した後、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−クロロメチル−チアゾール−５−カルボン酸アミド１０．６４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５６（９Ｈ，ｓ），４．６３（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），５．００（２Ｈ，ｓ），６．３９（１Ｈ，ｂｒｓ），６．９８（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．４Ｈｚ，Ｊ３＝２．４Ｈｚ），７．１４（１Ｈ，ｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝２．４Ｈｚ），７．４４（１Ｈ，ｄｄ，Ｊ１＝８．４Ｈｚ，Ｊ２＝６．２Ｈｚ），１０．０５（１Ｈ，ｂｒｓ）
参考製造例１１
Figure JPOXMLDOC01-appb-I000131
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルチオメチル−チアゾール−５−カルボン酸アミド０．７５ｇのクロロホルム溶液（５ｍＬ）に、氷冷下にてｍ−クロロ過安息香酸０．４５ｇを加えた。その混合物を徐々に室温まで昇温しながら４．５時間攪拌した。反応混合物にクロロホルム３０ｍＬを加え、飽和重曹水、飽和食塩水の順で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルフィニルメチル−チアゾール−５−カルボン酸アミド０．２３ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５６（９Ｈ，ｓ），２．６１（３Ｈ，ｓ），４．２６（１Ｈ，ｄ，Ｊ＝１２．４Ｈｚ），４．４９−４．６４（３Ｈ，ｍ），６．９６（１Ｈ，ｄｄ，Ｊ１＝７．３Ｈｚ，Ｊ２＝７．２Ｈｚ），７．１３（１Ｈ，ｄ，Ｊ＝７．６Ｈｚ），７．４６（１Ｈ，ｄｄ，Ｊ１＝７．３Ｈｚ，Ｊ２＝６．２Ｈｚ），８．７８（０．６Ｈ，ｂｒｓ），９．５９（１Ｈ，ｂｒｓ），１１．０６（０．４Ｈ，ｂｒｓ）
参考製造例１２
Figure JPOXMLDOC01-appb-I000132
２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルチオメチル−チアゾール−５−カルボン酸アミド０．７５ｇのクロロホルム溶液（５ｍＬ）に、氷冷下にてｍ−クロロ過安息香酸０．４５ｇを加えた。その混合物を徐々に室温まで昇温しながら４．５時間攪拌した。反応混合物にクロロホルム３０ｍＬを加え、飽和重曹水、飽和食塩水の順で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して、２−（ｔ−ブトキシカルボニルアミノ）−Ｎ−（２−クロロ−４−フルオロ−ベンジル）−４−メチルスルホニルメチル−チアゾール−５−カルボン酸アミド０．３０ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：１．５６（９Ｈ，ｓ），２．９７（３Ｈ，ｓ），４．６０（２Ｈ，ｄ，Ｊ＝５．６Ｈｚ），４．８３（２Ｈ，ｓ），６．９７（１Ｈ，ｄｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝８．３Ｈｚ，Ｊ３＝２．４Ｈｚ），７．１４（１Ｈ，ｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝２．４Ｈｚ），７．３１（１Ｈ，ｂｒｓ），９．５８（１Ｈ，ｂｒｓ），７．４４（１Ｈ，ｄｄ，Ｊ１＝８．５Ｈｚ，Ｊ２＝６．１Ｈｚ）
参考製造例１３
Figure JPOXMLDOC01-appb-I000133
　４，４−ジフルオロアセト酢酸エチル５．０ｇとクロロベンゼン３０ｍｌの混合物にＮ−クロロスクシンイミド４．０ｇを加えた。その混合物を８０℃で４時間加熱攪拌した。反応混合物を室温まで放冷した後、反応混合物にヘキサンを加えて沈殿を析出させ、固体を濾別し、濾液を濃縮した。得られた残渣にＥｔＯＨ３０ｍｌ、チオ尿素２．３ｇを加え、８０℃で２時間攪拌した。室温まで放冷した後、反応混合物に５％ＮａＯＨ水溶液４７ｍｌを加えて、室温で２時間攪拌した。反応混合物に１２Ｎ塩酸を加えて中和した後、溶媒を留去し、２−アミノ−４−ジフルオロメチルチアゾール−５−カルボン酸１０ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：７．２５（２Ｈ，ｂｒｓ），７．６４（１Ｈ，ｔ，Ｊ＝５５．１Ｈｚ）．
参考製造例１４
Figure JPOXMLDOC01-appb-I000134
２−ブロモ−４，５−ジフルオロベンジルアジド３．３５ｇのＴＨＦ溶液（４０ｍＬ）に、氷冷下にてトリフェニルホスフィン３．９１ｇを加えた。その混合物を室温で６時間攪拌した。反応混合物を終夜室温で放置し、アンモニア水（２８％）を１５ｍＬ加えた。その混合物を室温で３時間攪拌した後、４Ｎ水酸化ナトリウム水溶液４６．４ｍＬを加えた。その混合物を室温で１時間攪拌した後、１Ｎ塩酸を８７．５ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸１．５ｍＬを加え、トルエンを加えて水を共沸させた。残渣をＴＨＦで洗浄し、得られた結晶を乾燥して、２−ブロモ−４，５−ジフルオロベンジルアミン塩酸塩１．９４ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．１０（２Ｈ，ｓ），７．８２（１Ｈ，ｄｄ，Ｊ１＝１１．７Ｈｚ，Ｊ２＝８．３Ｈｚ），７．９３（１Ｈ，ｄｄ，Ｊ１＝１０．１Ｈｚ，Ｊ２＝７．７Ｈｚ），８．５５（３Ｈ，ｂｒｓ）
参考製造例１５
Figure JPOXMLDOC01-appb-I000135
２−ブロモ−４，５−ジフルオロベンジルクロリド３．２８ｇのＤＭＳＯ溶液（３０ｍＬ）にアジ化ナトリウム１．０８ｇを加えた。その混合物を室温で１．５時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水５０ｍＬに注加した。その混合物をｔ−ブチルメチルエーテルで抽出した。有機層を、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−ブロモ−４，５−ジフルオロベンジルアジド３．３５ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．４５（２Ｈ，ｓ），７．２８（１Ｈ，ｄｄ，Ｊ１＝１０．０Ｈｚ，Ｊ２＝７．６Ｈｚ），７．４４（１Ｈ，ｄｄ，Ｊ１＝９．５Ｈｚ，Ｊ２＝７．３Ｈｚ）
参考製造例１６
Figure JPOXMLDOC01-appb-I000136
２−ブロモ−４，５−ジフルオロベンジルアルコール４．０２ｇのトルエン溶液（１５ｍＬ）に塩化チオニル１．４５ｍＬとＤＭＦ２滴を加えた。その混合物を８０℃にて１時間攪拌した。反応混合物を減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−４，５−ジフルオロベンジルクロリド３．２８ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．６２（２Ｈ，ｓ），７．３６（１Ｈ，ｄｄ，Ｊ１＝１０．５Ｈｚ，Ｊ２＝８．１Ｈｚ），７．４３（１Ｈ，ｄｄ，Ｊ１＝９．５Ｈｚ，Ｊ２＝７．４Ｈｚ）
参考製造例１７
Figure JPOXMLDOC01-appb-I000137
２−ブロモ−３，５−ジフルオロベンジルアジド６．９０ｇのＴＨＦ溶液（１００ｍＬ）に、氷冷下にてトリフェニルホスフィン７．９１ｇを加えた。その混合物を室温で９時間攪拌した。反応混合物を終夜室温で放置し、アンモニア水（２８％）を３０ｍＬ加えた。その混合物を室温で３時間攪拌した後、４Ｎ水酸化ナトリウム水溶液９４ｍＬを加え、室温で１時間攪拌した。ここに１Ｎ塩酸を１７７ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ１０ｍＬを加えた。氷冷下にて濃塩酸３ｍＬを加え、生じた結晶を濾過により集めた。得られた結晶をＴＨＦで洗浄した後、乾燥して、２−ブロモ−３，５−ジフルオロベンジルアミン塩酸塩２．８９ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．１７（２Ｈ，ｓ），７．４８−７．５３（２Ｈ，ｍ），８．７１（３Ｈ，ｂｒｓ）
参考製造例１８
Figure JPOXMLDOC01-appb-I000138
２−ブロモ−３，５−ジフルオロベンジルクロリド７．００ｇのＤＭＳＯ溶液（５５ｍＬ）にアジ化ナトリウム２．１８ｇを加えた。その混合物を室温で２．５時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水２００ｍＬに注加した。その混合物をｔ−ブチルメチルエーテルで抽出した。有機層を、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−ブロモ−３，５−ジフルオロベンジルアジド６．９０ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．５２（２Ｈ，ｓ），６．８７−６．９２（１Ｈ，ｍ），７．０２−７．０５（１Ｈ，ｍ）
参考製造例１９
Figure JPOXMLDOC01-appb-I000139
２−ブロモ−３，５−ジフルオロベンジルアルコール６．１２ｇのトルエン溶液（２００ｍＬ）に塩化チオニル２．４０ｍＬとＤＭＦ４滴を加えた。その混合物を８０℃にて１時間攪拌した。反応混合物を減圧下で濃縮し２−ブロモ−３，５−ジフルオロベンジルクロリド７．００ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．６８（２Ｈ，ｓ），６．８７−７．１８（２Ｈ，ｍ）
参考製造例２０
Figure JPOXMLDOC01-appb-I000140
２−ブロモ−３，５−ジフルオロ安息香酸１９．５１ｇのＴＨＦ溶液（３００ｍＬ）に１，１’−カルボニルジイミダゾール２０．０１ｇを加え、３時間４０分加熱還流した。反応混合物を室温まで放冷し、水素化ホウ素ナトリウム５．０７ｇの水溶液（１６０ｍＬ）に４時間かけて滴下した。水素化ホウ素ナトリウム２．５ｇを追加し、３時間攪拌した後、室温で一晩放置した。反応混合物を濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，５−ジフルオロベンジルアルコール７．４１４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：２．０１（１Ｈ，ｂｒｓ），４．７６（２Ｈ，ｓ），６．８４（１Ｈ，ｄｄｄ，Ｊ１＝８．３Ｈｚ，Ｊ２＝８．３Ｈｚ，Ｊ３＝２．９Ｈｚ），７．１３−７．１６（１Ｈ，ｍ）
参考製造例２１
Figure JPOXMLDOC01-appb-I000141
２−ブロモ−３，４，５−トリフルオロベンジルクロリド６．５４ｇのＤＭＳＯ溶液（５５ｍＬ）にアジ化ナトリウム２．１８ｇを加えた。その混合物を室温で３０分間攪拌した。反応混合物を室温で一晩放置した後、反応混合物を水８０ｍＬに注加した。その混合物をｔ−ブチルメチルエーテルで抽出した。有機層を、水、飽和食塩水の順で洗浄した。硫酸マグネシウムで乾燥し、減圧下で濃縮した。残渣にＴＨＦ１００ｍＬを加え、氷冷下にてトリフェニルホスフィン７．２７ｇを加え、室温で１．５時間攪拌した。室温で３日間放置した後、アンモニア水（２８％）２８ｍＬを加え、３時間攪拌した。その混合物に４Ｎ水酸化ナトリウム水溶液９４ｍＬを加え、１時間攪拌した。１Ｎ塩酸を１５０ｍＬ加えた後、反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。飽和食塩水で洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸５ｍＬを加え、トルエンを加えて水を共沸させた。残渣をクロロホルムで洗浄し、得られた結晶を乾燥して、２−ブロモ−３，４，５−トリフルオロベンジルアミン塩酸塩３．３６ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．１５（２Ｈ，ｓ），７．７５−７．８０（１Ｈ，ｍ），８．６９（３Ｈ，ｂｒｓ）
参考製造例２２
Figure JPOXMLDOC01-appb-I000142
２−ブロモ−３，４，５−トリフルオロベンジルアルコール１６．６５ｇのトルエン溶液（２００ｍＬ）に塩化チオニル７．５６ｍＬとＤＭＦ４滴を加えた。その混合物を１１０℃にて３時間攪拌した。反応混合物を減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，４，５−トリフルオロベンジルクロリド６．５３７ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．６４（２Ｈ，ｓ），７．２１−７．２６（１Ｈ，ｍ）
参考製造例２３
Figure JPOXMLDOC01-appb-I000143
２−ブロモ−３，４，５−トリフルオロ安息香酸１６．９１ｇのトルエン溶液（２００ｍＬ）に塩化チオニル７．２６ｍＬとＤＭＦ４滴を加えた。その混合物を１１０℃で６時間攪拌した。反応混合物を減圧下で濃縮し、残渣をＴＨＦ１５０ｍＬに溶解させた。このＴＨＦ溶液を氷冷した水素化ホウ素ナトリウム４．０９ｇのエタノール溶液（３００ｍＬ）に１．５時間かけて滴下し、その後室温で１時間攪拌した。反応混合物を室温で一晩放置した後、減圧下で濃縮した。残渣に水と酢酸エチルを加え、酢酸エチル層を分取した。水層は酢酸エチルで抽出し、先の酢酸エチル層と合わせた。飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。減圧下で濃縮し、残渣をシリカゲルカラムクロマトに付して、２−ブロモ−３，４，５−トリフルオロベンジルアルコール６．６０３ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：２．０８（１Ｈ，ｔ，Ｊ＝５．９Ｈｚ），４．７２（２Ｈ，ｄ，Ｊ＝５．９Ｈｚ），７．２４−７．２９（１Ｈ，ｍ）
参考製造例２４
Figure JPOXMLDOC01-appb-I000144
２−クロロ−４，５−ジフルオロ−ベンジルアジド２．６３ｇのＴＨＦ溶液（５０ｍＬ）に、氷冷下にてトリフェニルホスフィン３．７２ｇを加えた。その混合物を室温で７．５時間攪拌した。反応混合物を１日間室温で放置し、アンモニア水（２８％）を１４ｍＬ加えた。室温で３．５時間攪拌した後、４Ｎ水酸化ナトリウム水溶液４５ｍＬを加えた。室温で２時間攪拌した後、１Ｎ塩酸を８５ｍＬ加えた。反応混合物を静置し、ＴＨＦ層を分取した。水層はｔ−ブチルエチルエーテルで抽出し、ＴＨＦ層とあわせた。水、飽和食塩水の順に洗浄し、硫酸ナトリウムで乾燥した。減圧下で濃縮して、残渣にＴＨＦ５ｍＬを加えた。氷冷下にて濃塩酸１．５ｍＬを加え、生じた結晶を濾過により集めた。得られた結晶をＴＨＦで洗浄した後、乾燥して、２−クロロ−４，５−ジフルオロ−ベンジルアミン塩酸塩１．４１ｇを得た。
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６）δ：４．１０（２Ｈ，ｓ），７．７９（１Ｈ，ｄｄ，Ｊ１＝１０．４Ｈｚ，Ｊ１＝７．４Ｈｚ），７．８８（１Ｈ，ｄｄ，Ｊ１＝１１．５Ｈｚ，Ｊ１＝８．５Ｈｚ），８．７２（３Ｈ，ｂｒｓ）
参考製造例２５
Figure JPOXMLDOC01-appb-I000145
２−クロロ−４，５−ジフルオロ−ベンジルブロミド３．１５ｇのＤＭＳＯ溶液（２５ｍＬ）にアジ化ナトリウム１．０３ｇを加えた。その混合物を室温で１時間攪拌した。反応混合物を終夜室温で放置し、反応混合物を水１００ｍＬに注加した。その混合物をｔ−ブチルメチルエーテルで抽出した。有機層を、水、飽和食塩水の順に洗浄した後、硫酸マグネシウムで乾燥した。減圧下で濃縮して、２−クロロ−４，５−ジフルオロ−ベンジルアジド２．６３ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ３）δ：４．４６（２Ｈ，ｓ），７．２５−７．２９（２Ｈ，ｍ）
　次に製剤例を示す。なお、部とは重量部を示す。
製剤例１
　本発明化合物（１）~（１１１）のいずれか１種５０部、リグニンスルホン酸カルシウム３部、ラウリル硫酸マグネシウム２部及び合成含水酸化珪素４５部をよく粉砕混合することにより、各々の水和剤を得る。
製剤例２
　本発明化合物（１）~（１１１）のいずれか１種２０部とソルビタントリオレエ−ト１．５部とを、ポリビニルアルコール２部を含む水溶液２８．５部と混合し、湿式粉砕法で微粉砕した後、この中に、キサンタンガム０．０５部及びアルミニウムマグネシウムシリケート０．１部を含む水溶液４０部を加え、さらにプロピレングリコール１０部を加えて攪拌混合し、各々のフロアブル製剤を得る。
製剤例３
　本発明化合物（１）~（１１１）のいずれか１種２部、カオリンクレー８８部及びタルク１０部をよく粉砕混合することにより、各々の粉剤を得る。
製剤例４
　本発明化合物（１）~（１１１）のいずれか１種５部、ポリオキシエチレンスチリルフェニルエ−テル１４部、ドデシルベンゼンスルホン酸カルシウム６部及びキシレン７５部をよく混合することにより、各々の乳剤を得る。
製剤例５
　本発明化合物（１）~（１１１）のいずれか１種２部、合成含水酸化珪素１部、リグニンスルホン酸カルシウム２部、ベントナイト３０部及びカオリンクレー６５部をよく粉砕混合した後、水を加えてよく練り合せ、造粒乾燥することにより、各々の粒剤を得る。
製剤例６
　本発明化合物（１）~（１１１）のいずれか１種１０部；ポリオキシエチレンアルキルエーテルサルフェートアンモニウム塩５０部を含むホワイトカーボン３５部；及び水５５部を混合し、湿式粉砕法で微粉砕することにより、各々のフロアブル製剤を得る。
　製剤例７
　本発明化合物（１）~（１１１）のいずれか１種４０部、プロピレングリコールを５部（ナカライテスク製）、Ｓｏｐｒｏｐｈｏｒ　ＦＬＫを５部（ローディア日華製）、アンチフォームＣエマルションを０．２部（ダウコーニング社製）、プロキセルＧＸＬを０．３部（アーチケミカル製）、及びイオン交換水を４９．５部の割合で混合し、原体スラリーを調製する。該スラリー１００部に１５０部のガラスビーズ（Φ＝１ｍｍ）を投入し、冷却水で冷却しながら、２時間粉砕する。粉砕後、ガラスビーズをろ過により除き、各々のフロアブル製剤を得る。
　製剤例８
　本発明化合物（１）~（１１１）のいずれか１種５０部、ＮＮカオリンクレーを３８．５部（竹原化学工業製）、Ｍｏｒｗｅｔ　Ｄ４２５を１０部、Ｍｏｒｗｅｒ　ＥＦＷを１．５部（アクゾノーベル社製）の割合で混合し、該混合物をジェットミルで粉砕し、各々の粉剤を得る。
　次に、本発明化合物が植物病害の防除に有用であることを試験例で示す。
　なお防除効果は、調査時の供試植物上の病斑の面積を目視観察し、本発明化合物を処理した植物の病斑の面積と、無処理の植物の病斑の面積を比較することにより評価した。
試験例１
　プラスチックポットに土壌を詰め、コムギ（品種；シロガネ）を播種し、温室内で９日間生育させた後、コムギ赤さび病菌（Ｐｕｃｃｉｎｉａ　ｒｅｄｏｎｄｉｔａ　ｆ．ｓｐ．ｔｒｉｔｉｃｉ）の胞子をふりかけ接種した。接種後２３℃、暗黒多湿下に１日置いた後、風乾させコムギ赤さび病感染苗とした。本発明化合物（１５）、（１８）、（５２）、（５７）、（５８）、（８５）、（９０）及び（９７）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記コムギの葉面に充分付着するように茎葉散布した。散布後植物を風乾し、さらに照明下に６日間置いた後、病斑面積を調査した。その結果、本発明化合物（１５）、（１８）、（５２）、（５７）、（５８）、（８５）、（９０）及び（９７）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例２
　プラスチックポットに土壌を詰め、コムギ（品種；アポジー）を播種し、温室内で１０日間生育させた。本発明化合物（２）、（９）、（１８）、（４０）、（４３）、（５２）、及び（８９）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記コムギの葉面に充分付着するように茎葉散布した。散布後植物を風乾し、３日後または４日後にコムギ葉枯病菌（Ｓｅｐｔｏｒｉａ　ｔｒｉｔｉｃｉ）胞子の水懸濁液を噴霧接種した。接種後はじめは１８℃多湿下に３日置き、さらに照明下に１４日から１８日間置いた後、病斑面積を調査した。その結果、本発明化合物（２）、（９）、（１８）、（４０）、（４３）、（５２）、及び（８９）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例３
　プラスチックポットに土壌を詰め、キュウリ（品種；相模半白）を播種し、温室内で１２日間生育させた。本発明化合物（１７）、（１８）及び（１９）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記キュウリ葉面に充分付着するように茎葉散布した。散布後植物を風乾し、キュウリ灰色かび病菌（Ｂｏｔｒｙｔｉｓ　ｃｉｎｅｒｅａ）の胞子含有ＰＤＡ培地をキュウリ葉面上に置いた。接種後１２℃、多湿下に４日置いた後、病斑面積を調査した。その結果、本発明化合物（１７）、（１８）及び（１９）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例４
　プラスチックポットに土壌を詰め、インゲン（品種；長鶉菜豆）を播種し、温室内で８日間生育させた。本発明化合物（１６）、（１７）、（１８）、（８９）、（９５）、（９６）及び（１０１）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記インゲン葉面に充分付着するように茎葉散布した。散布後植物を風乾し、菌核病菌（Ｓｃｌｅｒｏｔｉｎｉａ　ｓｃｌｅｒｏｔｉｏｒｕｍ）の菌糸含有ＰＤＡ培地をインゲン葉面上に置いた。接種後２３℃、多湿下に５日置いた後、病斑面積を調査した。その結果、本発明化合物（１６）、（１７）、（１８）、（８９）、（９５）、（９６）及び（１０１）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例５　キュウリべと病治療効果試験（Ｐｓｅｕｄｏｐｅｒｏｎｏｓｐｏｌａ　ｃｕｂｅｎｓｉｓ）
　プラスチックポットに土壌を詰め、キュウリ（品種；相模半白）を播種し、温室内で１２日間生育させた。上記ポットにキュウリべと病菌遊走子嚢の水懸濁液を噴霧接種し、２３℃、多湿下に１日置いた後、風乾し、キュウリべと病感染苗とした。本発明化合物（１０）、（１２）、（１３）、（１４）、（１６）、（２７）、（３３）、（３６）、（３７）、（４０）、（４１）、（４３）、（４９）、（５２）、（５６）、（５７）、（５８）、（５９）、（６１）、（６２）、（６３）、（６４）、（６５）、（６６）、（６９）、（７２）、（７５）、（７６）、（７７）、（７８）、（８１）、（８２）、（８４）、（８６）、（８９）、（９０）、（９１）、（９２）、（９９）、（１００）、（１０１）、（１０２）及び（１１０）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記キュウリ葉面に充分付着するように茎葉散布した。散布後植物を風乾し、２３℃の温室内で５日置いた後、病斑面積を調査した。その結果、本発明化合物（１０）、（１２）、（１３）、（１４）、（１６）、（２７）、（３３）、（３６）、（３７）、（４０）、（４１）、（４３）、（４９）、（５２）、（５６）、（５７）、（５８）、（５９）、（６１）、（６２）、（６３）、（６４）、（６５）、（６６）、（６９）、（７２）、（７５）、（７６）、（７７）、（７８）、（８１）、（８２）、（８４）、（８６）、（８９）、（９０）、（９１）、（９２）、（９９）、（１００）、（１０１）、（１０２）及び（１１０）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例６
　プラスチックポットに土壌を詰め、トマト（品種：パティオ）を播種し、温室内で２０日間生育させた。本発明化合物（１）、（２）、（３）、（４）、（５）、（６）、（７）、（８）、（９）、（１０）、（１１）、（１２）、（１３）、（１４）、（１５）、（１６）、（１７）、（２６）、（２７）、（２８）、（３０）、（３１）、（３３）、（３５）、（３６）、（３７）、（３８）、（３９）、（４０）、（４１）、（４３）、（４５）、（４９）、（５０）、（５２）、（５６）、（５７）、（５８）、（５９）、（６１）、（６２）、（６３）、（６４）、（６５）、（６９）、（７１）、（７２）、（７３）、（７５）、（７６）、（７７）、（７８）、（８０）、（８１）、（８２）、（８４）、（８５）、（８６）、（８８）、（８９）、（９０）、（９１）、（９２）、（９３）、（９４）、（９５）、（９６）、（９７）、（９８）、（９９）、（１００）、（１０１）、（１０２）、（１０４）、（１０６）及び（１１０）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記トマト苗の葉面に充分付着するように茎葉散布した。葉面上の該希釈液が乾く程度に風乾した後、トマト疫病菌（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）胞子の水懸濁液を噴霧接種した。接種後はじめは２３℃、多湿下に１日置き、続いて２０℃の人工気象室内で４日間栽培した後、病斑面積を調査した。
　本発明化合物（１）、（２）、（３）、（４）、（５）、（６）、（７）、（８）、（９）、（１０）、（１１）、（１２）、（１３）、（１４）、（１５）、（１６）、（１７）、（２６）、（２７）、（２８）、（３０）、（３１）、（３３）、（３５）、（３６）、（３７）、（３８）、（３９）、（４０）、（４１）、（４３）、（４５）、（４９）、（５０）、（５２）、（５６）、（５７）、（５８）、（５９）、（６１）、（６２）、（６３）、（６４）、（６５）、（６９）、（７１）、（７２）、（７３）、（７５）、（７６）、（７７）、（７８）、（８０）、（８１）、（８２）、（８４）、（８５）、（８６）、（８８）、（８９）、（９０）、（９１）、（９２）、（９３）、（９４）、（９５）、（９６）、（９７）、（９８）、（９９）、（１００）、（１０１）、（１０２）、（１０４）、（１０６）及び（１１０）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例７
　プラスチックポットに土壌を詰め、トマト（品種：パティオ）を播種し、温室内で２０日間生育させた。本発明化合物（１８）、（２０）、（２１）、（２２）及び（２３）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（２００ｐｐｍ）にし、上記トマト苗の葉面に充分付着するように茎葉散布した。葉面上の該希釈液が乾く程度に風乾した後、トマト疫病菌（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）胞子の水懸濁液を噴霧接種した。接種後はじめは２３℃、多湿下に１日置き、続いて２０℃の人工気象室内で４日間栽培した後、病斑面積を調査した。
　本発明化合物（１８）、（２０）、（２１）、（２２）及び（２３）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例８
　プラスチック製スポンジ片にトマト（品種：パティオ）を播種し、プラスチックカップ中で約２０日間水耕栽培した。本発明化合物（１）、（２）、（４）、（５）、（６）、（７）、（８）、（９）、（１０）、（１１）、（１２）、（１３）、（１４）、（１５）、（１６）、（１７）、（２６）、（３３）、（３６）、（４０）、（４１）、（４３）、（４９）、（５２）、（５３）、（６２）、（６３）、（６５）、（７２）、（７５）、（７６）、（７７）、（７８）、（８１）、（８２）、（８４）、（８５）、（８６）、（８７）、（８８）、（８９）、（９０）、（９１）、（９３）、（９４）、（９５）、（９６）、（９７）、（９８）、（９９）、（１００）、（１０１）、（１０２）、（１０６）及び（１１０）の各々を製剤例６に準じてフロアブル製剤とした後、重量換算で１植物あたり１ｍｇを上記トマト水耕栽培苗のカップ中に投入した。さらに７日間水耕栽培後、トマト疫病菌（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）胞子の水懸濁液を噴霧接種した。接種後はじめは２３℃、多湿下に１日置き、続いて２０℃の人工気象室内で４日間栽培した後、病斑面積を調査した。
　本発明化合物（１）、（２）、（４）、（５）、（６）、（７）、（８）、（９）、（１０）、（１１）、（１２）、（１３）、（１４）、（１５）、（１６）、（１７）、（２６）、（３３）、（３６）、（４０）、（４１）、（４３）、（４９）、（５２）、（５３）、（６２）、（６３）、（６５）、（７２）、（７５）、（７６）、（７７）、（７８）、（８１）、（８２）、（８４）、（８５）、（８６）、（８７）、（８８）、（８９）、（９０）、（９１）、（９３）、（９４）、（９５）、（９６）、（９７）、（９８）、（９９）、（１００）、（１０１）、（１０２）、（１０６）及び（１１０）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。
試験例９
　プラスチック製スポンジ片にトマト（品種：パティオ）を播種し、プラスチックカップ中で約２０日間水耕栽培した。本発明化合物（１８）、（２０）、（２１）、（２２）及び（２３）の各々を製剤例６に準じてフロアブル製剤とした後、重量換算で１植物あたり０．４ｍｇを上記トマト水耕栽培苗のカップ中に投入した。さらに７日間水耕栽培後、トマト疫病菌（Ｐｈｙｔｏｐｈｔｈｏｒａ　ｉｎｆｅｓｔａｎｓ）胞子の水懸濁液を噴霧接種した。接種後はじめは２３℃、多湿下に１日置き、続いて２０℃の人工気象室内で４日間栽培した後、病斑面積を調査した。
　本発明化合物（１８）、（２０）、（２１）、（２２）及び（２３）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Hereinafter, although this invention is demonstrated in more detail by a manufacture example, a formulation example, a test example, etc., this invention is not limited only to these examples.
First, the manufacture example of this invention compound is shown.
Production Example 1
Figure JPOXMLDOC01-appb-I000013
0.75 g of 2-amino-thiazole-5-carboxylic acid hydrochloride, 0.30 g of benzylamine, 5 mL of pyridine, 0.37 g of 1-hydroxybenzotriazole, and 0.53 g of WSC were mixed. The mixture was heated to reflux for 10 minutes and then stirred at room temperature for 1 day. The reaction mixture was poured into water and extracted with chloroform. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 0.11 g of 2-amino-N-benzyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (1)).
1 H-NMR (CDCl 3 ) [Ppm]: 4.58 (2H, d, J = 5.8 Hz), 5.43 (2H, brs), 6.25 (1H, t, J = 5.8 Hz), 7.28-7 .38 (5H, m), 7.51 (1H, s)
Production Example 2
Figure JPOXMLDOC01-appb-I000014
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine, and 0.74 g of BOP reagent, 0.17 g of 4-methylbenzylamine was added and stirred at room temperature for 2 hours and 10 minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was washed with t-butyl methyl ether, and 2-amino-N- (4-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (2)) was reduced to 0. 21 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]]: 2.27 (3H, s), 4.32 (2H, d, J = 6.0 Hz), 7.11-7.18 (4H, m), 7.44 (2H, brs), 7.64 (1H, s), 8.58 (1H, t, J = 6.0 Hz).
Production Example 3
Figure JPOXMLDOC01-appb-I000015
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine, and 0.74 g of BOP reagent, 0.17 g of 3-methylbenzylamine was added and stirred at room temperature for 3 hours and 10 minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (3)) to 0. 10 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 2.28 (3H, s), 4.33 (2H, d, J = 6.1 Hz), 7.03-7.09 (3H, m), 7.18-7.22 (1H, m), 7.45 (2H, brs), 7.65 (1H, s), 8.59 (1H, t, J = 6.1 Hz).
Production Example 4
Figure JPOXMLDOC01-appb-I000016
To a mixture of 2-amino-thiazole-5-carboxylic acid 0.20 g, DMF 5 mL, triethylamine 0.28 g, and BOP reagent 0.74 g was added 2-methylbenzylamine 0.17 g, and the mixture was stirred at room temperature for 2 hours and 10 minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was washed with t-butyl methyl ether, and 2-amino-N- (2-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (4)) was reduced to 0. 15 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 2.29 (3H, s), 4.35 (2H, d, J = 5.6 Hz), 7.14-7.22 (4H, m), 7.45 (2H, brs) ), 7.68 (1H, s), 8.49 (1H, t, J = 5.6 Hz).
Production Example 5
Figure JPOXMLDOC01-appb-I000017
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine, and 0.74 g of BOP reagent, 0.20 g of 4-chlorobenzylamine was added and stirred at room temperature for 5 hours and 15 minutes. The reaction mixture was allowed to stand at room temperature overnight, and the reaction mixture was poured into ice water to produce crystals. The mixture was sonicated and the crystals were collected by filtration. The extract was dried under reduced pressure to obtain 0.19 g of 2-amino-N- (4-chlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (5)).
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.35 (2H, d, J = 5.8 Hz), 7.29-7.40 (4H, m), 7.47 (2H, brs), 7.64 (1H, s) ), 8.65 (1H, t, J = 5.8 Hz).
Production Example 6
Figure JPOXMLDOC01-appb-I000018
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine, and 0.74 g of BOP reagent, 0.20 g of 2-chlorobenzylamine was added and stirred at room temperature for 3 hours and 30 minutes. When the reaction mixture was poured into ice water, crystals were formed. After sonication, the crystals were collected by filtration. The extract was dried under reduced pressure to obtain 0.22 g of 2-amino-N- (2-chlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (6)).
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.44 (2H, d, J = 5.8 Hz), 7.27-7.35 (4H, m), 7.50 (2H, s), 7.70 (1H, brs) ), 8.65 (1H, t, J = 5.8 Hz).
Production Example 7
Figure JPOXMLDOC01-appb-I000019
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine and 0.87 g of 4-fluorobenzylamine, 0.74 g of BOP reagent was added and stirred at room temperature overnight. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (7)) to 0. 18g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.35 (2H, d, J = 6.0 Hz), 7.12-7.18 (2H, m), 7.31 (2H, dd, J = 8.5, 5. 8 Hz), 7.46 (2H, brs), 7.64 (1 H, s), 8.63 (1 H, t, J = 6.0 Hz).
Production Example 8
Figure JPOXMLDOC01-appb-I000020
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine and 0.87 g of 3-fluorobenzylamine, 0.74 g of BOP reagent was added and stirred at room temperature for 4 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (8)) to 0. 23 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.39 (2H, d, J = 6.0 Hz), 7.05-7.13 (3H, m), 7.34-7.40 (1H, m), 7.48 (2H, brs), 7.66 (1H, s), 8.66 (1H, t, J = 6.0 Hz).
Production Example 9
Figure JPOXMLDOC01-appb-I000021
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine and 0.87 g of 2-fluorobenzylamine, 0.74 g of BOP reagent was added and stirred at room temperature for 5 hours and 20 minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate. Concentration under reduced pressure afforded 0.18 g of 2-amino-N- (2-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (9)).
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.41 (2H, d, J = 5.8 Hz), 7.14-7.20 (2H, m), 7.28-7.36 (2H, m), 7.47 (2H, brs), 7.67 (1H, s), 8.61 (1H, t, J = 5.8 Hz).
Production Example 10
Figure JPOXMLDOC01-appb-I000022
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 1.26 g of triethylamine and 0.93 g of 2-bromobenzylamine hydrochloride, 1.10 g of BOP reagent was added and stirred at room temperature for 2 hours. The reaction mixture was poured into aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and t-butyl methyl ether and hexane were added to the residue. The crystals were collected by filtration to obtain 0.39 g of 2-amino-N- (2-bromobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (10)).
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.40 (2H, d, J = 5.9 Hz), 7.19-7.40 (3H, m), 7.51 (2H, brs), 7.61 (1H, d) , J = 8.0 Hz), 7.71 (1H, s), 8.66 (1H, t, J = 5.9 Hz)
Production Example 11
Figure JPOXMLDOC01-appb-I000023
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 3 mL of DMF, 0.42 g of triethylamine, and 0.36 g of 2,6-difluorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,6-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (11)). 0.089 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.41 (2H, d, J = 4.9 Hz), 7.05-7.11 (2H, m), 7.35-7.43 (1H, m), 7.45 (2H, brs), 7.62 (1H, s), 8.47 (1H, t, J = 4.9 Hz)
Production Example 12
Figure JPOXMLDOC01-appb-I000024
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine, and 0.60 g of 2,4-difluorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 2 hours. When the reaction mixture was poured into ice water, crystals were formed. The crystals were collected by filtration. The crystals were washed with saturated aqueous sodium hydrogen carbonate, water, hexane and t-butyl methyl ether to give 2-amino-N- (2,4-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (12)). 0.38 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.37 (2H, d, J = 5.4 Hz), 7.04-7.09 (1H, m), 7.19-7.24 (1H, m), 7.35 −7.41 (1H, m), 7.49 (2H, brs), 7.66 (1H, s), 8.61 (1H, t, J = 5.4 Hz)
Production Example 13
Figure JPOXMLDOC01-appb-I000025
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine, and 0.60 g of 2,3-difluorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2,3-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (13)) was 0. .36 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.44 (2H, d, J = 5.6 Hz), 7.14-7.21 (2H, m), 7.29-7.36 (1H, m), 7.50 (2H, brs), 7.67 (1H, s), 8.67 (1H, t, J = 5.6 Hz)
Production Example 14
Figure JPOXMLDOC01-appb-I000026
1.10 g of BOP reagent is added to a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine, and 0.66 g of 2-chloro-4-fluorobenzylamine, and stirred at room temperature for 1 hour. did. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2-chloro-4-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (14)). 0.42 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.41 (2H, d, J = 5.8 Hz), 7.20-7.25 (1H, m), 7.36-7.39 (1H, m), 7.43 -7.46 (1H, m), 7.51 (2H, brs), 7.70 (1H, s), 8.64 (1H, t, J = 5.8 Hz)
Production Example 15
Figure JPOXMLDOC01-appb-I000027
0.53 g of BOP reagent was added to a mixture of 0.14 g of 2-aminothiazole-5-carboxylic acid, 2 ml of DMF, 0.42 g of triethylamine and 0.32, g of 2,3,4-trifluorobenzylamine, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue is subjected to silica gel column chromatography and described as 2-amino-N- (2,3,4-trifluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (15)). ) 0.21 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.39 (2H, d, J = 4.9 Hz), 7.14-7.31 (2H, m), 7.49 (2H, brs), 7.64 (1H, s) ), 8.66 (1H, t, J = 4.9 Hz)
Production Example 16
Figure JPOXMLDOC01-appb-I000028
0.53 g of BOP reagent was added to a mixture of 0.14 g of 2-aminothiazole-5-carboxylic acid, 2 ml of DMF, 0.42 g of triethylamine and 0.32, g of 3,4,5-trifluorobenzylamine, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (3,4,5-trifluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (16)). ) 0.15 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.34 (2H, d, J = 5.4 Hz), 7.17-7.33 (2H, m), 7.50 (2H, brs), 7.65 (1H, s) ), 8.67 (1H, t, J = 5.4 Hz)
Production Example 17
Figure JPOXMLDOC01-appb-I000029
To a mixture of 0.18 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 2 ml of DMF, 0.42 g of triethylamine and 0.32 g of 2-chloro-4-fluorobenzylamine, 0.53 g of BOP reagent was added, and at room temperature overnight. Stir. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-chloro-N- (2-chloro-4-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (17)). 0.23 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.42 (2H, d, J = 5.3 Hz), 7.19-7.24 (1H, m), 7.33-7.38 (1H, m), 7.41 −7.44 (1H, m), 7.91 (2H, brs), 8.15 (1H, t, J = 5.3 Hz)
Production Example 18
Figure JPOXMLDOC01-appb-I000030
To a mixture of 1.79 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 30 ml of DMF, 1.01 g of triethylamine and 1.43 g of 2,4-difluorobenzylamine, 4.43 g of BOP reagent was added and stirred at room temperature overnight. . A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 1.20 g of 2-amino-4-chloro-N- (2,4-difluorobenzyl) -thiazole-5-carboxylic acid amide.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.41 (2H, d, J = 5.80 Hz). 7.08-7.06 (1H, m), 7.23-7.19 (1H, m), 7.38 (1H, q, J = 8.13 Hz), 7.91 (2H, s) , 8.14 (1H, t, J = 5.92 Hz)
Production Example 19
Figure JPOXMLDOC01-appb-I000031
To a mixture of 0.29 g of 2-aminothiazole-5-carboxylic acid, 5 ml of DMF, 0.22 g of triethylamine and 0.39 g of 4-trifluoromethylbenzylamine, 0.97 g of BOP reagent was added and stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (19)). 38 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.64 (2H, d, J = 6.3 Hz), 5.24 (2H, brs), 6.10 (1H, brs), 7.45 (2H, d, J = 7) .7 Hz), 7.51 (1 H, s), 7.61 (2 H, d, J = 8.5 Hz).
Production Example 20
Figure JPOXMLDOC01-appb-I000032
To a mixture of 0.36 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 0.24 g of benzylamine, 2 mL of DMF, and 0.21 g of triethylamine, 0.93 g of BOP reagent was added under ice cooling. The mixture was stirred under ice-cooling for 5 minutes and then at room temperature for 13 hours. The reaction mixture was left at room temperature overnight, and the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and washed with saturated brine. Dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and the obtained crystal was washed with chloroform to give 2-amino-N-benzyl-4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (20)). 0.39 g was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.41 (2H, d, J = 6.1 Hz), 7.20-7.33 (5H, m), 7.75 (2H, brs), 8.01 (1H, t) , J = 6.1 Hz)
Production Example 21
To a mixture of 0.36 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 0.24 g of 2-chlorobenzylamine, 2 mL of DMF, and 0.21 g of triethylamine, 0.93 g of BOP reagent was added under ice cooling. The mixture was stirred under ice-cooling for 5 minutes and then at room temperature for 13 hours. The reaction mixture was left at room temperature overnight, and the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and washed with saturated brine. Dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and the obtained crystal was washed with chloroform to give 2-amino-N- (2-chlorobenzyl) -4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present product). 0.41 g of Inventive Compound (21) was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.49 (2H, d, J = 5.9 Hz), 7.26-7.44 (4H, m), 7.79 (2H, brs), 8.02 (1H, t) , J = 5.9 Hz)
Production Example 22
Figure JPOXMLDOC01-appb-I000034
To a mixture of 0.36 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 0.27 g of 2-methylbenzylamine, 2 mL of DMF, and 0.21 g of triethylamine, 0.93 g of BOP reagent was added under ice cooling. The mixture was stirred for 5 minutes under ice-cooling and then stirred at room temperature for 12 hours. The reaction mixture was left at room temperature overnight, and the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and washed with saturated brine. Dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and the obtained crystal was washed with chloroform to give 2-amino-N- (2-methylbenzyl) -4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present product). 0.42 g of Inventive Compound (22)) was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 2.30 (3H, s), 4.39 (2H, d, J = 5.9 Hz), 7.14-7.25 (4H, m), 7.74 (2H, brs) ), 7.87 (1H, t, J = 5.9 Hz)
Production Example 23
Figure JPOXMLDOC01-appb-I000035
To a mixture of 0.36 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 0.28 g of 2-fluorobenzylamine, 2 mL of DMF, and 0.21 g of triethylamine, 0.93 g of BOP reagent was added under ice cooling. The mixture was stirred for 5 minutes under ice-cooling and then stirred at room temperature for 12 hours. The reaction mixture was left at room temperature overnight, and the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and washed with saturated brine. Dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and the obtained crystal was washed with chloroform to give 2-amino-N- (2-fluorobenzyl) -4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present product). 0.45 g of Inventive Compound (23) was obtained.
1 H-NMR (DMSO-d 6 ) [Ppm]: 4.46 (2H, d, J = 5.9 Hz), 7.12-7.18 (2H, m), 7.27-7.36 (2H, m), 7.77 (2H, brs), 8.00 (1H, t, J = 5.9 Hz)
Production Example 24
Figure JPOXMLDOC01-appb-I000036
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.27 g of 4-methoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-methoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (24)) to 0. 25 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 3.71 (3H, s), 4.28 (2H, d, J = 5.31 Hz), 6.87 (2H, d, J = 8.69 Hz), 7.19 (2H, d, J = 7.24 Hz), 7.42 (2H, s), 7.61-7.61 (1 H, s), 8.55 (1 H, t, J = 5.67 Hz).
Production Example 25
Figure JPOXMLDOC01-appb-I000037
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.27 g of 3-methoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-methoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (25)) to 0. 19 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 3.72 (3H, s), 4.33 (2H, d, J = 5.1 Hz), 6.78-6.84 (3H, m), 7.22 (1H, t, J = 7.73 Hz), 7.45 (2H, s), 7.64 (1 H, s), 8.60 (1 H, t, J = 5.1 Hz).
Production Example 26
Figure JPOXMLDOC01-appb-I000038
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.35 g of 2-trifluoromethylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (26)). 0.32 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.55 (2H, d, J = 5.3 Hz), 7.44-7.52 (4H, m), 7.63-7.71 (3H, m), 8.72 (1H, t, J = 5.3 Hz).
Production Example 27
Figure JPOXMLDOC01-appb-I000039
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.35 g of 3-trifluoromethylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (27)). 0.05 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.44 (2H, d, J = 6.0 Hz), 7.49 (2H, s), 7.55-7.61 (4H, m), 7.64 (1H, s), 8 .72 (1H, t, J = 6.0 Hz).
Production Example 28
Figure JPOXMLDOC01-appb-I000040
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.34 g of 4-cyanobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-cyanobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (28)) to 0. 35 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.43 (2H, d, J = 6.3 Hz), 7.45 (2H, d, J = 8.0 Hz), 7.49 (2H, s), 7.65 (1H, s) , 7.78 (2H, d, J = 7.7 Hz), 8.74 (1H, t, J = 6.3 Hz).
Production Example 29
Figure JPOXMLDOC01-appb-I000041
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.33 g of 4-t-butylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-t-butylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (29)). 0.14 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 1.24 (9H, s), 4.31 (2H, d, J = 5.8 Hz), 7.19 (2H, d, J = 8.0 Hz), 7.32 (2H, d, J = 7.7 Hz), 7.44 (2H, s), 7.62 (1H, s), 8.58 (1H, t, J = 5.8 Hz).
Production Example 30
Figure JPOXMLDOC01-appb-I000042
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.45 g of 3-bromobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-bromobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (30)) to 0. 20 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.35 (2H, d, J = 5.6 Hz), 7.28-7.30 (2H, m), 7.43-7.47 (4H, m), 7.64 (1H, d, J = 3.6 Hz), 8.67 (1H, s).
Production Example 31
Figure JPOXMLDOC01-appb-I000043
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.54 g of 3-iodobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-iodobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (31)) to 0. 34 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.31 (2H, d, J = 4.6 Hz), 7.12 (1H, t, J = 7.4 Hz), 7.28 (1H, d, J = 6.5 Hz), 7. 48 (2H, s), 7.58-7.64 (2H, m), 8.65 (1H, s).
Production Example 32
Figure JPOXMLDOC01-appb-I000044
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.37 g of 4-phenylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-phenylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (32)) to 0. 21 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.40 (2H, d, J = 5.6 Hz), 7.33-7.36 (3H, m), 7.43-7.45 (4H, m), 7.61-7. 65 (5H, m), 8.68 (1H, t, J = 5.6 Hz).
Production Example 33
Figure JPOXMLDOC01-appb-I000045
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.38 g of 3-nitrobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-nitrobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (33)) to 0. 27 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.48 (2H, d, J = 6.1 Hz), 7.54 (2H, s), 7.60-7.68 (2H, m), 7.72-7.75 (1H, m), 8.09-8.12 (2H, m), 8.79 (1H, t, J = 6.1 Hz).
Production Example 34
Figure JPOXMLDOC01-appb-I000046
0.44 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-dibromomethyl-thiazole-5-carboxylic acid amide was dissolved in 1 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 4 hours. A 1N aqueous sodium hydroxide solution was added to the reaction mixture to make it alkaline, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with t-butyl methyl ether to give 2-amino-N- (2-chloro-4-fluoro-benzyl) -4-dibromomethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (34). ) 0.25 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.40 (2H, d, J = 5.6 Hz), 7.17-7.41 (3H, m), 7.78 (1H, s), 7.83 (2H, brs), 8 .44 (1H, t, J = 5.6 Hz).
Production Example 35
Figure JPOXMLDOC01-appb-I000047
0.51 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-dichloromethyl-thiazole-5-carboxylic acid amide was dissolved in 1 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 3 hours. 30 mL of ethyl acetate was added to the reaction mixture, and the mixture was washed with 1N aqueous sodium hydroxide solution and saturated brine in that order, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with t-butyl methyl ether to give 0.38 g of 2-amino-N- (2-chloro-4-fluoro-benzyl) -4-dichloromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). Compound (35)) was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.41 (2H, d, J = 5.8 Hz), 7.17-7.41 (3H, m), 7.83 (2H, brs), 7.86 (1H, s), 8 .48 (1H, t, J = 5.8 Hz).
Production Example 36
Figure JPOXMLDOC01-appb-I000048
0.25 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylthiomethyl-thiazole-5-carboxylic acid amide was dissolved in 1.5 mL of trifluoroacetic acid. . The mixture was stirred at room temperature for 3 hours. 30 mL of ethyl acetate was added to the reaction mixture, and the mixture was washed with 1N aqueous sodium hydroxide solution and saturated brine in that order, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with a mixture of t-butyl methyl ether and hexane to give 2-amino-N- (2-chloro-4-fluoro-benzyl) -4-methylthiomethyl-thiazole-5-carboxylic acid amide (hereinafter, This is referred to as the present compound (36).) 0.11 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.03 (3H, s), 3.89 (2H, s), 4.38 (2H, d, J = 5.9 Hz), 7.16-7.39 (3H, m), 7 .39 (2H, brs), 8.03 (1H, t, J = 5.9 Hz).
Production Example 37
Figure JPOXMLDOC01-appb-I000049
A mixture of 0.34 g of 2-amino-4-ethyl-thiazole-5-carboxylic acid in DMF (1 mL), 0.35 g of 2-chloro-4-fluoro-benzylamine in DMF (1 mL) and 0.21 g of triethylamine Was added with 0.93 g of BOP reagent under ice-cooling. The mixture was stirred for 5 minutes under ice cooling, and then stirred at room temperature for 3 hours. The reaction mixture was left overnight at room temperature, and the reaction mixture was poured into 10 mL of saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography. The resulting 2-amino-4-ethyl-N- (2-chloro-4-fluoro-benzyl) -thiazole-5-carboxylic acid amide was washed with chloroform to give 2-amino-4-ethyl-N- (2 0.22 g (hereinafter referred to as the present compound (37)) of -chloro-4-fluoro-benzyl) -thiazole-5-carboxylic acid amide was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 1.10 (3H, t, J = 7.5 Hz), 2.80 (2H, q, J = 7.5 Hz), 4.38 (2H, d, J = 5.9 Hz), 7. 19 (1H, ddd, J 1 = 8.9Hz, J 2 = 8.8Hz, J 3 = 2.7 Hz), 7.28 (2H, brs), 7.34 (1H, dd, J 1 = 8.9Hz, J 2 = 6.7 Hz), 7.37 (1H, dd, J 1 = 8.8Hz, J 2 = 2.7 Hz), 7.88 (1 H, t, J = 5.9 Hz).
Production Example 38
Figure JPOXMLDOC01-appb-I000050
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.27 g of 3,4-dimethylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4-dimethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (38)). 0.16 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.18 (3H, s), 2.19 (3H, s), 4.29 (2H, d, J = 5.8 Hz), 6.98 (1H, d, J = 7.5 Hz) 7.04-7.08 (2H, m), 7.44 (2H, s), 7.64 (1H, s), 8.54 (1H, t, J = 5.4 Hz).
Production Example 39
Figure JPOXMLDOC01-appb-I000051
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.41 g of 4-bromo-2-fluorobenzylamine was added and stirred at room temperature for 3 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (4-bromo-2-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (39)). ) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.36 (2H, d, J = 5.6 Hz), 7.29 (1H, t, J = 8.2 Hz), 7.41 (1H, d, J = 8.2 Hz), 7. 48-7.55 (3H, m), 7.66 (1H, s), 8.64 (1H, t, J = 5.6 Hz).
Production Example 40
Figure JPOXMLDOC01-appb-I000052
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.29 g of 3,4-difluorobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (40)). 0.28 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.35 (2H, d, J = 5.8 Hz), 7.12-7.14 (1H, m), 7.27-7.44 (2H, m), 7.52 (2H, s), 7.66 (1H, s), 8.67 (1H, t, J = 5.8 Hz).
Production Example 41
Figure JPOXMLDOC01-appb-I000053
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.29 g of 2,5-difluorobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,5-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (41)). 0.33 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.40 (2H, d, J = 5.6 Hz), 7.10-7.18 (2H, m), 7.24 (1H, td, J = 9.1, 4.6 Hz), 7.52 (2H, s), 7.68 (1H, s), 8.65 (1H, t, J = 5.6 Hz).
Production Example 43
Figure JPOXMLDOC01-appb-I000054
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.21 g of 3,5-difluorobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,5-difluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (43)). 0.34 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.39 (2H, d, J = 5.8 Hz), 6.96-7.01 (2H, m), 7.08-7.12 (1H, m), 7.51 (2H, s), 7.67 (1H, s), 8.70 (1H, t, J = 5.9 Hz).
Production Example 44
Figure JPOXMLDOC01-appb-I000055
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.35 g of 2,5-dichlorobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,5-dichlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (44)). 0.22 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.42 (2H, d, J = 5.8 Hz), 7.33 (1H, m), 7.36-7.40 (1H, m), 7.48-7.51 (1H, m), 7.53 (2H, s), 7.71 (1H, s), 8.67 (1H, t, J = 5.6 Hz).
Production Example 45
Figure JPOXMLDOC01-appb-I000056
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.38 g of 2-nitrobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-nitrobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (45)) to 0. 11 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.66 (2H, d, J = 5.8 Hz), 7.52-7.56 (4H, m), 7.70 (1H, s), 7.74 (1H, t, J = 7.6 Hz), 8.03 (1H, d, J = 8.5 Hz), 8.71 (1H, t, J = 5.8 Hz).
Production Example 46
Figure JPOXMLDOC01-appb-I000057
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.47 g of 2-phenoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and 2-amino-N- (2-phenoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (46)) was reduced to 0.00. 43 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.37 (2H, d, J = 5.6 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.95 (2H, d, J = 8.2 Hz), 7. 08-7.16 (2H, m), 7.24-7.28 (1H, m), 7.32-7.38 (3H, m), 7.46 (2H, s), 7.64 ( 1H, s), 8.54 (1H, t, J = 5.7 Hz).
Production Example 47
Figure JPOXMLDOC01-appb-I000058
To a mixture of 0.38 g of 2-amino-4-methoxymethyl-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.21 g of benzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-methoxymethyl-N-benzyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (47)) to 0. 24 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 3.18 (2H, s), 4.36 (2H, d, J = 5.6 Hz), 4.44 (3H, s), 7.21-7.38 (5H, m), 7 .43 (2H, s), 8.22 (1H, t, J = 5.6 Hz).
Production Example 48
Figure JPOXMLDOC01-appb-I000059
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.34 g of 2,3-dimethoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,3-dimethoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (48)). 0.23 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 3.73 (3H, s), 3.78 (3H, s), 4.36 (2H, d, J = 5.8 Hz), 6.81 (1H, d, J = 7.8 Hz) 6.93 (1H, d, J = 7.8 Hz), 7.00 (1H, t, J = 7.8 Hz), 7.44 (2H, s), 7.65 (1H, s), 8 .49 (1H, t, J = 5.8 Hz).
Production Example 49
Figure JPOXMLDOC01-appb-I000060
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.28 g of 4-fluoro-2-methylbenzylamine was added and stirred at room temperature for 3 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (4-fluoro-2-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (49)). ) Was obtained.
1 H-NMR (DMSO-d 6 ): 2.28 (3H, s), 4.30 (2H, d, J = 5.8 Hz), 6.93-7.02 (2H, m), 7.21 (1H, dd, J = 8.2, 6.3 Hz), 7.45 (2H, s), 7.65 (1 H, s), 8.49 (1 H, t, J = 5.6 Hz).
Production Example 50
Figure JPOXMLDOC01-appb-I000061
To a mixture of 2-amino-4-cyclopropyl-thiazole-5-carboxylic acid g 0.37, DMF 10 mL, triethylamine 0.20 g, and BOP reagent 0.88 g, 0.22 g of benzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N-benzyl-4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (50)) to 0. 12 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 0.80-0.82 (4H, m), 2.84-2.88 (1H, m), 4.33 (2H, d, J = 6.0 Hz), 7.19-7. 32 (5H, m), 7.37 (2H, s), 8.00 (1H, t, J = 6.0 Hz).
Production Example 52
Figure JPOXMLDOC01-appb-I000062
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.38 g of 4-trifluoromethoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-trifluoromethoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (52)). 0.23 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.37 (2H, d, J = 6.0 Hz), 7.30 (2H, d, J = 8.2 Hz), 7.38 (2H, d, J = 8.5 Hz), 7. 47 (2H, s), 7.63 (1H, s), 8.69 (1H, t, J = 6.0 Hz).
Production Example 53
Figure JPOXMLDOC01-appb-I000063
0.23 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylsulfinylmethyl-thiazole-5-carboxylic acid amide was dissolved in 1 mL of trifluoroacetic acid, The mixture was stirred at room temperature for 2.5 hours. 40 mL of ethyl acetate was added to the reaction mixture, and 1N sodium hydroxide aqueous solution was added to make the mixture alkaline, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the previous ethyl acetate layer. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with chloroform, and 2-amino-N- (2-chloro-4-fluoro-benzyl) -4-methylsulfinylmethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (53)). .) 0.19 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.57 (3H, s), 4.26 (2H, d, J = 1.7 Hz), 4.39 (2H, d, J = 5.4 Hz), 7.18 (1H, ddd, J 1 = 8.5Hz, J 2 = 8.5Hz, J 3 = 2.7 Hz), 7.38-7.43 (2H, m), 7.47 (2H, brs), 8.64 (1 H, t, J = 5.4 Hz).
Production Example 54
Figure JPOXMLDOC01-appb-I000064
0.30 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylsulfonylmethyl-thiazole-5-carboxylic acid amide was dissolved in 1 mL of trifluoroacetic acid. The mixture was stirred at room temperature for 2 hours. 30 mL of ethyl acetate was added to the reaction mixture, and 1N sodium hydroxide aqueous solution was added to make it alkaline, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the previous ethyl acetate layer. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with chloroform, and 2-amino-N- (2-chloro-4-fluoro-benzyl) -4-methylsulfonylmethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (54)). .) 0.20 g was obtained.
1 H-NMR (DMSO-d 6 ): 3.01 (3H, s), 4.40 (2H, d, J = 5.4 Hz), 4.78 (2H, s), 7.18 (1H, ddd, J) 1 = 8.5Hz, J 2 = 8.5Hz, J 3 = 2.4 Hz), 7.35-7.40 (2H, m), 7.59 (2H, brs), 8.26 (1H, t, J = 5.4 Hz).
Production Example 55
Figure JPOXMLDOC01-appb-I000065
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.38 g of 4-nitrobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-nitrobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (55)) to 0. 15 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.46 (2H, d, J = 6.0 Hz), 7.49-7.52 (4H, m), 7.64 (1H, s), 8.17 (2H, d, J = 7.7 Hz), 8.84 (1H, t, J = 6.0 Hz).
Production Example 56
Figure JPOXMLDOC01-appb-I000066
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.24 g of benzylamine was added and stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform to obtain 0.13 g of 2-amino-4-difluoromethyl-N-benzyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (56)). It was.
1 H-NMR (DMSO-d 6 ) Δ: 4.37 (2H, d, J = 5.8 Hz), 7.17-7.61 (6H, m), 7.82 (2H, brs), 8.63 (1H, t, J = 5.8 Hz).
Production Example 57
Figure JPOXMLDOC01-appb-I000067
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 2-methylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform, and 2-amino-4-difluoromethyl-N- (2-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (57)). 0.21 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.29 (3H, s), 4.35 (2H, d, J = 5.8 Hz), 6.96-7.64 (5H, m), 7.81 (2H, brs), 8 .53 (1H, t, J = 5.8 Hz).
Production Example 58
Figure JPOXMLDOC01-appb-I000068
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.28 g of 2-fluorobenzylamine is added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform, and 2-amino-4-difluoromethyl-N- (2-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (58)). 0.16 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.41 (2H, d, J = 5.6 Hz), 7.16-7.49 (5H, m), 7.84 (2H, brs), 8.63 (1H, t, J = 5.6 Hz).
Production Example 59
Figure JPOXMLDOC01-appb-I000069
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.35 g of 2-chloro-4-fluorobenzylamine was added at room temperature. For 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform to give 2-amino-N- (2-chloro-4-fluorobenzyl) -4-difluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (59)). 0.19 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.40 (2H, d, J = 5.6 Hz), 7.18-7.49 (4H, m), 7.86 (2H, brs), 8.64 (1H, t, J = 5.6 Hz).
Production Example 60
Figure JPOXMLDOC01-appb-I000070
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.30 g of 2-ethylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform, and 2-amino-4-difluoromethyl-N- (2-ethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (60)). 0.16 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 1.16 (3H, t, J = 7.5 Hz), 2.65 (2H, q, J = 7.5 Hz), 4.39 (2H, d, J = 5.6 Hz), 7. 11-7.27 (4H, m), 7.82 (2H, brs), 8.56 (1H, t, J = 5.6 Hz).
Production Example 61
Figure JPOXMLDOC01-appb-I000071
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.27 g of 2-ethylbenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-ethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (61)) to 0. 07 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 1.16 (3H, t, J = 7.5 Hz), 2.65 (2H, q, J = 7.5 Hz), 4.40 (2H, d, J = 5.6 Hz), 7. 12-7.26 (4H, m), 7.45 (2H, s), 7.67 (1H, s), 8.51 (1H, t, J = 5.6 Hz).
Production Example 62
Figure JPOXMLDOC01-appb-I000072
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.31 g of 2-methyl-4-fluorobenzylamine was added at room temperature. For 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform, and 0.20 g of 2-amino-4-difluoromethyl-N- (4-fluoro-2-methylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present invention). Compound (62).) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.30 (3H, s), 4.31 (2H, d, J = 5.5 Hz), 6.88-7.09 (2H, m), 7.12-7.22 (1H, m), 7.36 (1H, t, J = 50.0 Hz), 7.82 (2H, brs), 8.54 (1H, t, J = 5.5 Hz).
Production Example 63
Figure JPOXMLDOC01-appb-I000073
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.31 g of 2-chlorobenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with Hexane and chloroform, and 2-amino-N- (2-chlorobenzyl) -4-difluoromethyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (63)). 0.21 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.44 (2H, d, J = 5.6 Hz), 7.16-7.55 (5H, m), 7.87 (2H, brs), 8.65 (1H, t, J = 5.6 Hz).
Production Example 64
Figure JPOXMLDOC01-appb-I000074
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine, and 0.93 g of BOP reagent, 0.28 g of 2-fluorobenzylamine is added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (2-fluorobenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (64)) was 0. .37 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 0.74-0.96 (4H, m), 2.81-2.99 (1H, m), 4.40 (2H, d, J = 5.8 Hz), 7.09-7. 24 (2H, m), 7.24-7.39 (2H, m), 7.42 (2H, brs), 7.99 (1H, t, J = 5.8 Hz).
Production Example 65
Figure JPOXMLDOC01-appb-I000075
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 2-methylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-methylbenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (65)). .31 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 0.76-0.90 (4H, m), 2.29 (3H, s), 2.82-2.97 (1H, m), 4.33 (2H, d, J = 5. 8 Hz), 7.06-7.28 (4 H, m), 7.39 (2 H, brs), 7.90 (1 H, t, J = 5.8 Hz).
Production Example 66
Figure JPOXMLDOC01-appb-I000076
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.38 g of 2-trifluoromethoxybenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-trifluoromethoxybenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (66)). 0.26 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.44 (2H, d, J = 5.8 Hz), 7.33-7.45 (4H, m), 7.50 (2H, s), 7.68 (1H, s), 8 .65 (1H, t, J = 5.8 Hz).
Production Example 67
Figure JPOXMLDOC01-appb-I000077
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.54 g of 4-iodobenzylamine was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and 2-amino-N- (4-iodobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (67)) was reduced to 0. 25 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.32 (2H, d, J = 6.0 Hz), 7.10 (2H, d, J = 8.3 Hz), 7.48 (2H, s), 7.64 (1H, s) 7.68 (2H, d, J = 8.3 Hz), 8.65 (1H, t, J = 6.0 Hz).
Production Example 68
Figure JPOXMLDOC01-appb-I000078
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 2-ethylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform to give 2-amino-N- (2-ethylbenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (68)). .29 g was obtained.
1 H-NMR (DMSO-d 6 ): 0.76-0.87 (4H, m), 1.17 (3H, t, J = 7.5 Hz), 2.66 (2H, q, J = 7.5 Hz), 2.83- 2.96 (1H, m), 4.38 (2H, d, J = 5.8 Hz), 7.10-7.26 (4H, m), 7.38 (2H, brs), 7.91 ( 1H, t, J = 5.8 Hz).
Production Example 69
Figure JPOXMLDOC01-appb-I000079
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.35 g of 2-chloro-4-fluorobenzylamine was added at room temperature. For 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (2-chloro-4-fluorobenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (69)). 0.13 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 0.76-0.86 (4H, m), 2.82-2.92 (1H, m), 4.36 (2H, d, J = 5.6 Hz), 7.16-7. 25 (1H, m), 7.29-7.36 (1 H, m), 7.37-7.47 (3H, m), 8.00 (1 H, t, J = 5.6 Hz).
Production Example 70
Figure JPOXMLDOC01-appb-I000080
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 3-methylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (3-methylbenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (70)) was 0. .37 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 0.75-0.94 (4H, m), 2.28 (3H, s), 2.74-3.03 (1H, m), 4.31 (2H, d, J = 6. 0 Hz), 6.97-7.13 (3H, m), 7.13-7.28 (1 H, m), 7.38 (2H, brs), 7.97 (1 H, t, J = 6. 0 Hz).
Production Example 71
Figure JPOXMLDOC01-appb-I000081
To a mixture of 0.37 g of 2-amino-4-cyclopropylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.27 g of 4-methylbenzylamine was added and stirred at room temperature for 6 hours. did. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-N- (4-methylbenzyl) -4-cyclopropyl-thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (71)) was 0. Obtained .33 g.
1 H-NMR (DMSO-d 6 ) Δ: 0.77-0.86 (4H, m), 2.27 (3H, s), 2.82-2.96 (1H, m), 4.30 (2H, d, J = 5. 8 Hz), 7.11 (2H, d, J = 8.0 Hz), 7.17 (2H, d, J = 8.0 Hz), 7.37 (2H, brs), 7.95 (1H, t, J = 5.8 Hz).
Production Example 72
Figure JPOXMLDOC01-appb-I000082
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.41 g of 2-bromo-4-fluorobenzylamine was added and stirred at room temperature for 3 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (2-bromo-4-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (72)). ) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.38 (2H, d, J = 5.6 Hz), 7.27 (1H, td, J = 8.6, 2.4 Hz), 7.35 (1H, t, J = 7.4 Hz) ), 7.52 (2H, s), 7.58 (1H, dd, J = 8.5, 2.4 Hz), 7.70 (1H, s), 8.67 (1H, t, J = 5) .4 Hz).
Production Example 73
Figure JPOXMLDOC01-appb-I000083
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.40 g of triethylamine, and 0.88 g of BOP reagent, 0.54 g of 2-iodobenzylamine hydrochloride was added and stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-iodobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (73)) to 0. 39 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.32 (2H, d, J = 5.6 Hz), 7.03 (1H, t, J = 7.4 Hz), 7.25 (1H, d, J = 7.4 Hz), 7. 39 (1H, t, J = 7.4 Hz), 7.52 (2H, s), 7.72 (1H, s), 7.86 (1H, d, J = 7.4 Hz), 8.68 ( 1H, t, J = 5.6 Hz).
Production Example 74
Figure JPOXMLDOC01-appb-I000084
To a mixture of 0.35 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.24 g of triethylamine and 1.06 g of BOP reagent, 0.39 g of 2,4,5-trifluorobenzylamine was added, and the mixture was stirred at room temperature for 3 hours. Stir. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,4,5-trifluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (74)). 0.15 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.34 (2H, d, J = 6.3 Hz), 7.36 (1H, ddd, J = 13.4, 6.5, 4.1 Hz), 7.47-7.55 (3H) M), 7.64 (1H, s), 8.64 (1H, t, J = 6.3 Hz).
Production Example 75
Figure JPOXMLDOC01-appb-I000085
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.39 g of 5-fluoro-2-trifluoromethylbenzylamine was added. Stir for hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (5-fluoro-2-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (75)). 0.44 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.53 (2H, d, J = 5.1 Hz), 7.23 (1H, d, J = 9.2 Hz), 7.29 (1H, t, J = 8.3 Hz), 7. 54 (2H, s), 7.70 (1H, s), 7.79 (1H, t, J = 7.0 Hz), 8.76 (1H, d, J = 5.1 Hz).
Production Example 76
Figure JPOXMLDOC01-appb-I000086
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.58 g of 4-fluoro-2-iodobenzylamine hydrochloride was added and mixed at room temperature. Stir for hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (4-fluoro-2-iodobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (76)). ) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.28 (2H, d, J = 5.6 Hz), 7.23-7.25 (2H, m), 7.49 (2H, s), 7.68 (1H, s), 7 .72 (1H, d, J = 8.5 Hz), 8.66 (1H, t, J = 5.6 Hz).
Production Example 77
Figure JPOXMLDOC01-appb-I000087
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.39 g of 4-fluoro-2-trifluoromethylbenzylamine was added. Stir for hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4-fluoro-2-trifluoromethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (77)). 0.44 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.50 (2H, d, J = 5.3 Hz), 7.50-7.53 (4H, m), 7.59 (1H, d, J = 9.2 Hz), 7.68 ( 1H, s), 8.72 (1H, t, J = 5.3 Hz).
Production Example 78
Figure JPOXMLDOC01-appb-I000088
To a mixture of 0.39 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 2 mL of DMF, 0.21 g of triethylamine and 0.93 g of BOP reagent, 0.63 g of 4-fluoro-2-iodobenzylamine hydrochloride was added. And stirred at room temperature for 6 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained solid was washed with chloroform, and 2-amino-4-difluoromethyl-N- (4-fluoro-2-iodobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (78)). 0.24 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.29 (2H, d, J = 5.3 Hz), 7.16-7.56 (3H, m), 7.66-7.81 (1H, m), 7.86 (2H, br)), 8.64 (1H, t, J = 5.3 Hz).
Production Example 79
Figure JPOXMLDOC01-appb-I000089
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine and 0.88 g of BOP reagent, 0.43 g of 2,3,4,5-tetrafluorobenzylamine was added at room temperature. Stir for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2,3,4,5-tetrafluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (79)). 0.21 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.38 (2H, d, J = 5.6 Hz), 7.19-7.25 (1H, m), 7.51 (2H, s), 7.62 (1H, s), 8 .72 (1H, t, J = 5.6 Hz).
Production Example 80
To a mixture of 0.29 g of 2-amino-thiazole-5-carboxylic acid, 10 mL of DMF, 0.20 g of triethylamine, and 0.88 g of BOP reagent, 0.34 g of 2-methyl-3-nitrobenzylamine was added and stirred at room temperature for 3 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (2-methyl-3-nitrobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (80)). ) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.49 (3H, s), 4.42 (2H, d, J = 5.6 Hz), 7.38 (1H, t, J = 7.8 Hz), 7.49-7.53 ( 3H, m), 7.65 (1H, s), 7.69 (1H, d, J = 8.0 Hz), 8.67 (1H, t, J = 5.6 Hz).
Production Example 81
Figure JPOXMLDOC01-appb-I000091
2-Aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 3-fluoro-2-methylbenzylamine 0.29 g were mixed and stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-fluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (81)). 0.34 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.20 (3H, s), 4.38 (2H, d, J = 5.6 Hz), 7.02-7.09 (2H, m), 7.16-7.22 (1H, m), 7.48 (2H, s), 7.68 (1H, s), 8.55 (1H, t, J = 5.6 Hz).
Production Example 82
Figure JPOXMLDOC01-appb-I000092
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 5-fluoro-2-methylbenzylamine 0.28 g were mixed and the mixture was allowed to reach room temperature for 1 hour. Stir. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (5-fluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (82)). 0.39 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.26 (3H, s), 4.33 (2H, d, J = 5.9 Hz), 6.95-7.01 (2H, m), 7.17-7.21 (1H, m), 7.50 (2H, s), 7.69 (1H, s), 8.57 (1H, t, J = 5.9 Hz).
Production Example 83
Figure JPOXMLDOC01-appb-I000093
A mixture of 0.29 g 2-aminothiazole-5-carboxylic acid, 3 mL DMF, 0.49 g triethylamine, 1.06 g BOP reagent, and 0.45 g 2-chloro-5-nitrobenzylamine hydrochloride and the mixture at room temperature Stir for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-5-nitrobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (83)). Of 0.06 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.52 (2H, d, J = 5.6 Hz), 7.57 (2H, s), 7.73 (1H, s), 7.78 (1 H, d, J = 9.8 Hz) 8.14-8.18 (2H, m), 8.83 (1H, t, J = 5.6 Hz).
Production Example 84
Figure JPOXMLDOC01-appb-I000094
0.29 g of 2-aminothiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.32 g of 2-chloro-5-fluorobenzylamine were mixed, and the mixture was stirred at room temperature for 1 hour. Stir. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-5-fluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (84)). 0.38 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.42 (2H, d, J = 5.9 Hz), 7.12 (1H, dd, J = 9.5, 2.9 Hz), 7.15-7.20 (1H, m), 7.48-7.55 (3H, m), 7.71 (1H, s), 8.68 (1H, t, J = 5.9 Hz).
Production Example 85
Figure JPOXMLDOC01-appb-I000095
0.29 g of 2-aminothiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.32 g of 2-chloro-3-fluorobenzylamine were mixed, and the mixture was stirred at room temperature for 1 hour. Stir. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-3-fluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (85)). 0.13 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.47 (2H, d, J = 5.9 Hz), 7.18 (1H, d, J = 7.6 Hz), 7.30-7.41 (2H, m), 7.52 ( 2H, s), 7.70 (1H, s), 8.70 (1H, t, J = 5.9 Hz).
Production Example 86
Figure JPOXMLDOC01-appb-I000096
0.29 g of 2-aminothiazole-5-carboxylic acid, 3 mL of DMF, 0.49 g of triethylamine, 1.06 g of BOP reagent, and 0.49 g of 2-bromo-5-fluorobenzylamine hydrochloride were mixed, and the mixture was mixed at room temperature. Stir for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-5-fluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (86)). 0.49 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.38 (2H, d, J = 5.9 Hz), 7.08-7.14 (2H, m), 7.54 (2H, s), 7.66 (1H, dd, J = 8.4, 5.2 Hz), 7.72 (1 H, s), 8.69 (1 H, t, J = 5.9 Hz).
Production Example 87
Figure JPOXMLDOC01-appb-I000097
0.29 g of 2-aminothiazole-5-carboxylic acid, 3 mL of DMF, 0.24 g of triethylamine, 1.06 g of BOP reagent, and 0.32 g of 2,3,5-trifluorobenzylamine were mixed, and the mixture was mixed with 1 at room temperature. Stir for hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (2,3,5-trifluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (87)). ) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.44 (2H, d, J = 5.6 Hz), 6.98-7.03 (1H, m), 7.40-7.48 (1H, m), 7.54 (2H, s), 7.67 (1H, s), 8.70 (1H, t, J = 5.6 Hz).
Production Example 88
Figure JPOXMLDOC01-appb-I000098
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-chloro-4,5-difluorobenzylamine hydrochloride 0.43 g were mixed and the mixture was Stir at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-chloro-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (88)). 0.43 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.39 (2H, d, J = 5.6 Hz), 7.34-7.39 (1H, m), 7.53 (2H, s), 7.69-7.76 (2H, m), 8.67 (1H, t, J = 5.6 Hz).
Production Example 89
Figure JPOXMLDOC01-appb-I000099
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.71 g, BOP reagent 1.06 g, and 2-bromo-4,5-difluorobenzylamine hydrochloride 0.52 g were mixed, and the mixture was Stir at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (89)). 0.40 g) was obtained.
1 H-NMR (DMSO-d 6 ): 4.35 (2H, d, J = 5.6 Hz), 7.34 (1H, dd, J = 11.6, 8.4 Hz), 7.54 (2H, s), 7.71 ( 1H, s), 7.87 (1H, dd, J = 10.2, 7.6 Hz), 8.68 (1H, t, J = 5.6 Hz).
Production Example 90
Figure JPOXMLDOC01-appb-I000100
0.29 g 2-aminothiazole-5-carboxylic acid, 3 mL DMF, 0.24 g triethylamine, 1.06 g BOP reagent, and 0.31 g 3,4-difluoro-2-methylbenzylamine were mixed and the mixture was Stir for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (90)). 0.22 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.25 (3H, d, J = 2.2 Hz), 4.34 (2H, d, J = 5.6 Hz), 7.05-7.09 (1H, m), 7.21 ( 1H, dd, J = 18.7, 8.4 Hz), 7.48 (2H, s), 7.66 (1H, s), 8.54 (1H, t, J = 5.6 Hz).
Production Example 91
Figure JPOXMLDOC01-appb-I000101
2-aminothiazole-5-carboxylic acid 0.24 g, DMF 3 mL, triethylamine 0.40 g, BOP reagent 0.88 g, and 4,5-difluoro-2-methylbenzylamine hydrochloride 0.32 g were mixed, and the mixture was Stir at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (4,5-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (91)). 0.30 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.27 (3H, s), 4.30 (2H, d, J = 5.9 Hz), 7.18 (1H, dd, J = 11.8, 8.4 Hz), 7.26 ( 1H, dd, J = 11.8, 8.2 Hz), 7.50 (2H, s), 7.67 (1H, s), 8.58 (1H, t, J = 5.9 Hz).
Production Example 92
Figure JPOXMLDOC01-appb-I000102
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-bromo-3,5-difluorobenzylamine hydrochloride 0.52 g were mixed and the mixture was mixed. Stir at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as 2-amino-N- (2-bromo-3,5-difluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (92)). 0.51 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.43 (2H, d, J = 5.6 Hz), 7.01 (1H, d, J = 9.3 Hz), 7.38-7.44 (1H, m), 7.55 ( 2H, s), 7.72 (1H, s), 8.71 (1H, t, J = 5.6 Hz).
Production Example 93
Figure JPOXMLDOC01-appb-I000103
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 3,4,5-trifluoro-2-methylbenzylamine 0.35 g were mixed and the mixture Was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3,4,5-trifluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (93). 0.27 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.22 (3H, d, J = 1.5 Hz), 4.34 (2H, d, J = 5.6 Hz), 7.08-7.14 (1H, m), 7.51 ( 2H, s), 7.67 (1H, s), 8.57 (1H, t, J = 5.6 Hz).
Production Example 94
Figure JPOXMLDOC01-appb-I000104
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.49 g, BOP reagent 1.06 g, and 2-bromo-3,4,5-trifluorobenzylamine hydrochloride 0.55 g were mixed, The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,4,5-trifluorobenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (94). ) Was obtained.
1 H-NMR (DMSO-d 6 ): 4.40 (2H, d, J = 5.6 Hz), 7.24-7.30 (1H, m), 7.55 (2H, s), 7.71 (1H, s), 8 .70 (1H, t, J = 5.6 Hz).
Production Example 95
Figure JPOXMLDOC01-appb-I000105
2-amino-4-chlorothiazole-5-carboxylic acid 0.54 g, DMF 3 mL, triethylamine 0.20 g, BOP reagent 0.89 g, and 4,5-difluoro-2-methylbenzylamine 0.31 g were mixed, The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-chloro-N- (4,5-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 95).) Was obtained in an amount of 0.35 g.
1 H-NMR (DMSO-d 6 ) Δ: 2.26 (3H, s), 4.30 (2H, d, J = 5.9 Hz), 7.17 (1H, dd, J = 12.0, 8.5 Hz), 7.24 ( 1H, dd, J = 11.7, 8.3 Hz), 7.89 (2H, s), 8.11 (1H, t, J = 5.9 Hz).
Production Example 96
Figure JPOXMLDOC01-appb-I000106
2-amino-4-chlorothiazole-5-carboxylic acid 0.54 g, DMF 3 mL, triethylamine 0.41 g, BOP reagent 0.89 g, and 2-bromo-4,5-difluorobenzylamine 0.39 g were mixed, The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-4,5-difluorobenzyl) -4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 96).) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.36 (2H, d, J = 5.9 Hz), 7.30 (1H, dd, J = 11.5, 8.5 Hz), 7.85 (1H, dd, J = 10.0) , 7.6 Hz), 7.93 (2H, s), 8.20 (1 H, t, J = 5.9 Hz).
Production Example 97
Figure JPOXMLDOC01-appb-I000107
A mixture of 0.54 g of 2-amino-4-chlorothiazole-5-carboxylic acid, 3 mL of DMF, 0.20 g of triethylamine, 0.89 g of BOP reagent, and 0.31 g of 3,4-difluoro-2-methylbenzylamine, The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-chloro-N- (3,4-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 97).) Was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.25 (3H, d, J = 2.0 Hz), 4.36 (2H, d, J = 5.6 Hz), 7.05-7.09 (1H, m), 7.22 ( 1H, dd, J = 18.7, 8.7 Hz), 7.90 (2H, s), 8.10 (1H, t, J = 5.6 Hz).
Production Example 98
Figure JPOXMLDOC01-appb-I000108
2-amino-4-chlorothiazole-5-carboxylic acid 0.54 g, DMF 3 mL, triethylamine 0.41 g, BOP reagent 0.89 g, and 2-bromo-3,5-difluorobenzylamine hydrochloride 0.52 g were mixed. The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,5-difluorobenzyl) -4-chlorothiazole-5-carboxylic acid amide (hereinafter referred to as the present compound ( 98)) was obtained in an amount of 0.50 g.
1 H-NMR (DMSO-d 6 ): 4.45 (2H, d, J = 5.9 Hz), 7.00 (1H, d, J = 8.5 Hz), 7.38-7.43 (1H, m), 7.96 ( 2H, s), 8.26 (1H, t, J = 5.9 Hz).
Production Example 99
Figure JPOXMLDOC01-appb-I000109
Mix 0.54 g 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.14 g triethylamine, 0.62 g BOP reagent, and 0.22 g 4,5-difluoro-2-methylbenzylamine, The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-difluoromethyl-N- (4,5-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.22 g of (99).
1 H-NMR (DMSO-d 6 ) Δ: 2.27 (3H, s), 4.29 (2H, d, J = 5.6 Hz), 7.17 (1H, dd, J = 12.2, 8.8 Hz), 7.26 ( 1H, dd, J = 11.5, 8.3 Hz), 7.33 (1H, t, J = 54.6 Hz), 7.84 (2H, s), 8.56 (1H, t, J = 5) .6 Hz).
Production Example 100
Figure JPOXMLDOC01-appb-I000110
0.78 g 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 3 mL DMF, 0.41 g triethylamine, 0.89 g BOP reagent, and 2-bromo-3,4,5-trifluorobenzylamine hydrochloride. 55 g were mixed and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,4,5-trifluorobenzyl) -4-difluoromethylthiazole-5-carboxylic acid amide (hereinafter, 0.47 g of the present compound (100) was obtained.
1 H-NMR (DMSO-d 6 ): 4.39 (2H, d, J = 5.6 Hz), 7.25-7.31 (1H, m), 7.32 (1H, t, J = 54.4 Hz), 7.89 ( 2H, s), 8.66 (1H, t, J = 5.6 Hz).
Production Example 101
Figure JPOXMLDOC01-appb-I000111
2-amino-4-difluoromethylthiazole-5-carboxylic acid 0.78 g, DMF 3 mL, triethylamine 0.20 g, BOP reagent 0.89 g, and 3,4-difluoro-2-methylbenzylamine 0.31 g were mixed, The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-4-difluoromethyl-N- (3,4-difluoro-2-methylbenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.31 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 2.25 (3H, d, J = 2.2 Hz), 4.33 (2H, d, J = 5.6 Hz), 7.03-7.07 (1H, m), 7.22 ( 1H, dd, J = 19.1, 7.9 Hz), 7.34 (1H, t, J = 54.3 Hz), 7.83 (2H, s), 8.56 (1H, t, J = 5) .6 Hz).
Production Example 102
Figure JPOXMLDOC01-appb-I000112
Mix 0.78 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid, 3 mL of DMF, 0.41 g of triethylamine, 0.89 g of BOP reagent, and 0.52 g of 2-bromo-3,5-difluorobenzylamine hydrochloride And the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-bromo-3,5-difluorobenzyl) -4-difluoromethylthiazole-5-carboxylic acid amide (hereinafter referred to as the present compound). 0.38 g was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 4.42 (2H, d, J = 5.6 Hz), 7.00 (1H, d, J = 8.3 Hz), 7.32 (1H, t, J = 54.4 Hz), 7. 39-7.44 (1H, m), 7.89 (2H, s), 8.69 (1H, t, J = 5.6 Hz).
Production Example 103
Figure JPOXMLDOC01-appb-I000113
2-aminothiazole-5-carboxylic acid 0.29 g, DMF 3 mL, triethylamine 0.24 g, BOP reagent 1.06 g, and 3-trifluoromethoxybenzylamine 0.38 g were mixed, and the mixture was stirred at room temperature for 3 hours. . The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (3-trifluoromethoxybenzyl) thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (103)) to 0. .43 g was obtained.
1 H-NMR (DMSO-d 6 ): 4.42 (2H, d, J = 6.1 Hz), 7.23-7.26 (2H, m), 7.32 (1H, d, J = 7.6 Hz), 7.45- 7.49 (1H, m), 7.52 (2H, s), 7.66 (1H, s), 8.72 (1 H, t, J = 6.1 Hz).
Production Example 104
Figure JPOXMLDOC01-appb-I000114
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine, and 0.74 g of BOP reagent, 0.20 g of 3-chlorobenzylamine was added and stirred at room temperature for 5 hours and 15 minutes. The reaction mixture was allowed to stand at room temperature overnight, and the reaction mixture was poured into ice water to form crystallized crystals. After sonication, the crystals were collected by filtration. The crystals were dried under reduced pressure to obtain 0.22 g of 2-amino-N- (3-chlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (104)).
1 H-NMR (DMSO-d 6 ) Δ: 4.37 (2H, d, J = 6.0 Hz), 7.24-7.38 (4H, m), 7.49 (2H, brs), 7.65 (1H, s), 8 .67 (1H, t, J = 6.0 Hz).
Production Example 105
Figure JPOXMLDOC01-appb-I000115
To a mixture of 0.20 g of 2-amino-thiazole-5-carboxylic acid, 5 mL of DMF, 0.28 g of triethylamine and 0.87 g of 2-methoxybenzylamine, 0.74 g of BOP reagent was added and stirred at room temperature for 4 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2-amino-N- (2-methoxyben
0.23 g of (zyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (105)) was obtained.
1 H-NMR (DMSO-d 6 ) Δ: 3.81 (3H, s), 4.34 (2H, d, J = 5.8 Hz), 6.88-6.94 (1H, m), 6.98 (1H, d, J = 8.2 Hz), 7.16 (1 H, d, J = 7.7 Hz), 7.21-7.26 (1 H, m), 7.46 (2 H, brs), 7.69 (1 H, s) , 8.45 (1H, t, J = 5.8 Hz).
Production Example 106
Figure JPOXMLDOC01-appb-I000116
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine and 0.73 g of 2,3-dichlorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 2 hours. The reaction mixture was poured into aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and t-butyl methyl ether and hexane were added to the residue. The crystals were collected by filtration to obtain 0.44 g of 2-amino-N- (2,3-dichlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (106)).
1 HNMR (DMSO-d 6 ) Δ ppm: 4.47 (2H, d, J = 5.9 Hz, Bn), 7.30-7.38 (2H, m, Ar), 7.52 (2H, brs, NH) 2 ), 7.56 (1H, d, J = 6.8 Hz, Ar), 7.71 (1H, s, Ar), 8.71 (1H, t, J = 5.9 Hz, NH)
Production Example 107
Figure JPOXMLDOC01-appb-I000117
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine, 0.73 g of 2,6-dichlorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 5 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and hexane, t-butyl methyl ether, and ethyl acetate were added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2,6-dichlorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (107)) was 0. .32 g was obtained.
1 HNMR (DMSO-d 6 ) Δ ppm: 4.59 (2H, d, J = 4.6 Hz, Bn), 7.31 to 7.41 (1H, m, Ar), 7.44 (2H, brs, NH) 2 ), 7.48 to 7.52 (2H, m, Ar), 7.64 (1H, s, Ar), 8.25 (1H, t, J = 4.6 Hz, NH)
Production Example 108
Figure JPOXMLDOC01-appb-I000118
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine, and 0.66 g of 2-chloro-6-fluorobenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 5 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. Concentrated under reduced pressure, and chloroform was added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2-chloro-6-fluorobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (108)). 0.23 g was obtained.
1 HNMR (DMSO-d 6 ) Δ ppm: 4.48 (2H, d, J 1 = 4.8Hz, J 2 = 1.2 Hz, Bn), 7.21 to 7.25 (1H, m, Ar), 7.32 to 7.42 (2H, m, Ar), 7.44 (2H, brs, NH) 2 ), 7.62 (1H, s, Ar), 8.36 (1H, t, J = 4.8 Hz, NH)
Production Example 109
Figure JPOXMLDOC01-appb-I000119
To a mixture of 0.30 g of 2-amino-thiazole-5-carboxylic acid, 2 mL of DMF, 0.42 g of triethylamine and 0.56 g of 2,3-dimethylbenzylamine, 1.10 g of BOP reagent was added and stirred at room temperature for 2.5 hours. did. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. The mixture was concentrated under reduced pressure, and t-butyl methyl ether and ethyl acetate were added to the residue. After applying ultrasonic waves, the crystals were collected by filtration, and 2-amino-N- (2,3-dimethylbenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (109)) was 0. .29 g was obtained.
1 HNMR (DMSO-d 6 ) Δ ppm: 2.17 (3H, s, Me), 2.24 (3H, s, Me), 4.36 (2H, d, J = 5.6 Hz, Bn), 7.01 to 7.08 ( 3H, m, Ar), 7.44 (2H, brs, NH) 2 ), 7.67 (1H, s), 8.44 (1H, t, J = 5.6 Hz, NH)
Production Example 110
Figure JPOXMLDOC01-appb-I000120
To a mixture of 0.14 g of 2-aminothiazole-5-carboxylic acid, 2 ml of DMF, 0.42 g of triethylamine and 0.32 g of 2,4,6-trifluorobenzylamine, 0.53 g of BOP reagent was added and stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give N- (2,4,6-trifluorobenzyl) -2-aminothiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (110)). 0.15 g was obtained.
1 HNMR (DMSO-d 6 ) Δ ppm: 4.35 (2H, d, J = 4.6 Hz), 7.09 to 7.19 (2H, m), 7.44 (2H, brs, NH) 2 ), 7.60 (1H, s), 8.45 (1H, t, J = 4.9 Hz, NH)
Production Example 111
Figure JPOXMLDOC01-appb-I000121
To a mixture of 0.29 g of 2-aminothiazole-5-carboxylic acid, 5 ml of DMF, 0.22 g of triethylamine and 0.50 g of 4-bromobenzylamine, 0.97 g of BOP reagent was added and stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 0.10 g of 2-amino-N- (4-bromobenzyl) -thiazole-5-carboxylic acid amide (hereinafter referred to as the present compound (111)). Obtained.
1 H-NMR (CDCl3) δ: 4.52 (2H, d, J = 6.4 Hz), 5.37 (2H, s), 6.27 (1H, s), 7.22 (2H, d, J = 8.1 Hz), 7.47 (2H, d, J = 8.7 Hz), 7.52 (1H, s).
Reference production example 1
To 400 ml of sulfolane dehydrated azeotropically with 100 ml of n-heptane, 52.3 g of potassium fluoride and 100 ml of n-heptane were added and azeotropically dehydrated for 1 hour. The reaction mixture was cooled to room temperature. To this, 92.4 g of 2,4-dichlorothiazole was added and stirred at 180 ° C. for 5 hours. The reaction mixture was cooled to room temperature and distilled under reduced pressure to obtain 62.5 g of 4-chloro-2-fluorothiazole.
4-chloro-2-fluorothiazole
Figure JPOXMLDOC01-appb-I000122
1 H-NMR (CDCl 3 ) Δ [ppm]: 6.72 (1H, s)
Reference production example 2
10.7 g of diisopropylamine was dissolved in 200 ml of tetrahydrofuran and cooled to -70 ° C. Here, 64 ml of n-butyllithium (1.65 mol / L) was dropped, and the temperature was raised to 0 ° C. The mixture was again cooled to -70 ° C, and 30 ml of a tetrahydrofuran solution containing 13.2 g of 4-chloro-2-fluorothiazole was added dropwise. After incubating at -70 ° C for 3 hours, finely crushed dry ice was added, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and 10% sulfuric acid were added to the resulting solid for liquid separation. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 13.5 g of 4-chloro-2-fluorothiazole-5-carboxylic acid.
4-chloro-2-fluorothiazole-5-carboxylic acid
Figure JPOXMLDOC01-appb-I000123
1 H-NMR (DMSO-d 6 ) Δ [ppm]: 4.14 (1H, s)
Reference production example 3
30 ml of 28% aqueous ammonia solution was cooled to 0 ° C., and 3.63 g of 4-chloro-2-fluorothiazole-5-carboxylic acid was added in several portions. The mixture was stirred overnight at room temperature and 10% sulfuric acid was added dropwise until a solid formed. The resulting solid was filtered and dried to obtain 3.10 g of 2-amino-4-chlorothiazole-5-carboxylic acid.
2-Amino-4-chlorothiazole-5-carboxylic acid
Figure JPOXMLDOC01-appb-I000124
1 H-NMR (DMSO-d 6 ) Δ [ppm]: 7.20 (1H, br s), 8.04 (2H, s)
Reference production example 4
Figure JPOXMLDOC01-appb-I000125
2- (t-Butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methyl-thiazole-5-carboxylic acid amide (2.40 g) is dissolved in chloroform (180 mL) and the temperature is raised to 50 ° C. Then, 1.07 g of N-bromosuccinimide and 99 mg of azobisisobutyronitrile were added. After heating under reflux for 1 hour, 99 mg of azobisisobutyronitrile was added again. After further refluxing for 1 hour, 99 mg of azobisisobutyronitrile was added again. The mixture was heated under reflux for 2 hours, and the reaction mixture was cooled to room temperature. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-dibromomethyl-thiazole-5-carboxylic acid amide. 0.44 g was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.54 (9H, s), 4.61 (2H, d, J = 5.9 Hz), 6, 14 (1H, t, J = 5.9 Hz), 6.99 (1H, ddd, J 1 = 8.5Hz, J 2 = 8.4Hz, J 3 = 2.6 Hz), 7.15 (1H, dd, J 1 = 8.4Hz, J 2 = 2.6 Hz), 7.43 (1H, dd, J 1 = 8.5Hz, J 2 = 6.1 Hz), 7.74 (1H, s), 7.83 (1H, brs)
Reference production example 5
Figure JPOXMLDOC01-appb-I000126
2- (t-butoxycarbonylamino) -4-methyl-thiazole-5-carboxylic acid 5.17 g of DMF solution and 2-chloro-4-fluoro-benzylamine 3.51 g of DMF solution (10 mL) and triethylamine 92 mL was added, and 9.29 g of BOP reagent was further added under ice cooling. The mixture was stirred for 5 minutes under ice-cooling and then stirred at room temperature for 12 hours. The mixture was allowed to stand at room temperature overnight, and then the reaction mixture was poured into 100 mL of saturated aqueous sodium bicarbonate to form crystals. The crystals were collected by filtration, washed with water and toluene, and then dried to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methyl-thiazole-5- 8.93 g of carboxylic acid amide was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.54 (9H, s), 2.63 (3H, s), 4.61 (2H, d, J = 5.9 Hz), 6.07 (1H, t, J = 5.9 Hz) , 6.97 (1H, ddd, J 1 = 8.5Hz, J 2 = 8.3Hz, J 3 = 2.7 Hz), 7.14 (1H, dd, J 1 = 8.3Hz, J 2 = 2.7 Hz), 7.44 (1H, dd, J 1 = 8.5Hz, J 2 = 6.1 Hz), 10.17 (1H, brs)
Reference production example 6
Figure JPOXMLDOC01-appb-I000127
0.80 g of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methyl-thiazole-5-carboxylic acid amide was dissolved in 20 mL of chloroform, and N-chlorosuccinimide 0 .56 g and azobisisobutyronitrile 33 mg were added. After heating under reflux for 1 hour, 33 mg of azobisisobutyronitrile was added again. After further refluxing for 1 hour, 33 mg of azobisisobutyronitrile was added once more. The mixture was heated to reflux for 1 hour, and the reaction mixture was cooled to room temperature. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-dichloromethyl-thiazole-5-carboxylic acid amide. 0.44 g was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.54 (9H, s), 4.61 (2H, d, J = 5.9 Hz), 6, 16 (1H, t, J = 5.9 Hz), 6.99 (1H, ddd, J 1 = 8.4Hz, J 2 = 8.3Hz, J 3 = 2.4 Hz), 7.15 (1H, dd, J 1 = 8.3Hz, J 2 = 2.4 Hz), 7.43 (1H, dd, J 1 = 8.4Hz, J 2 = 6.2 Hz), 7.79 (1H, s), 8.25 (1H, brs)
Reference production example 7
Figure JPOXMLDOC01-appb-I000128
4-bromomethyl-2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -thiazole-5-carboxylic acid amide (0.31 g) was added with ethanol (2 mL), tetrahydrofuran (1 mL) and methyl mercaptan sodium (55 mg). added. The mixture was stirred at room temperature for 3 hours. To this was added 11 mg of methyl mercaptan sodium, and the mixture was further stirred for 2 hours. 40 mL of ethyl acetate was added to the reaction mixture, and the mixture was washed with 1N aqueous sodium hydroxide solution and saturated brine in that order, dried over magnesium sulfate, and concentrated under reduced pressure. To the residue was added t-butyl methyl ether and hexane, concentrated once more, and 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylthiomethyl-thiazole-5-carbon. 0.25 g of acid amide was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.55 (9H, s), 2.04 (3H, s), 4.05 (2H, s), 4.61 (2H, d, J = 5.6 Hz), 6.78 (1H) , Brs), 6.97 (1H, ddd, J 1 = 8.3Hz, J 2 = 8.2 Hz, J 3 = 2.2 Hz), 7.14 (1H, dd, J 1 = 8.3Hz, J 2 = 2.2 Hz), 7.45 (1H, dd, J 1 = 8.2 Hz, J 2 = 6.2Hz)
Reference production example 8
Figure JPOXMLDOC01-appb-I000129
2- (t-Butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methyl-thiazole-5-carboxylic acid amide 0.80 g in chloroform solution (20 mL) was added N-bromosuccinimide 0. .36 g and azobisisobutyronitrile 33 mg were added. After heating at reflux for 1.5 hours, 33 mg of azobisisobutyronitrile was added again. After further heating under reflux for 2 hours, 33 mg of azobisisobutyronitrile was added once more. The mixture was heated under reflux for 2 hours, and the reaction mixture was cooled to room temperature. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 4-bromomethyl-2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -thiazole-5-carboxylic acid amide 0. .44 g was obtained.
1 H-NMR (CDCl 3 ): 1.57 (9H, s), 4.64 (2H, d, J = 5.6 Hz), 4.95 (2H, s), 6.50 (1H, t, J = 5.6 Hz) , 6.97 (1H, ddd, J 1 = 8.5Hz, J 2 = 8.4Hz, J 3 = 2.6 Hz), 7.14 (1H, dd, J 1 = 8.4Hz, J 2 = 2.6 Hz), 7.44 (1H, dd, J 1 = 8.5Hz, J 2 = 5.9 Hz), 10.59 (1 H, brs)
Reference production example 10
Figure JPOXMLDOC01-appb-I000130
2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methyl-thiazole-5-carboxylic acid amide was added to 10.21 g of chloroform solution (255 mL) in N-chlorosuccinimide 3 .41 g and azobisisobutyronitrile 0.42 g were added. After heating under reflux for 1 hour, 0.42 g of azobisisobutyronitrile was added again. After further refluxing for 1 hour, 0.42 g of azobisisobutyronitrile was added once more. The mixture was heated under reflux for 2 hours, and the reaction mixture was cooled to room temperature. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-chloromethyl-thiazole-5-carboxylic acid amide. 10.64 g was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.56 (9H, s), 4.63 (2H, d, J = 5.6 Hz), 5.00 (2H, s), 6.39 (1H, brs), 6.98 (1H) , Ddd, J 1 = 8.5Hz, J 2 = 8.4Hz, J 3 = 2.4 Hz), 7.14 (1H, dd, J 1 = 8.5Hz, J 2 = 2.4 Hz), 7.44 (1H, dd, J 1 = 8.4Hz, J 2 = 6.2 Hz), 10.05 (1H, brs)
Reference production example 11
Figure JPOXMLDOC01-appb-I000131
To a chloroform solution (5 mL) of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylthiomethyl-thiazole-5-carboxylic acid amide in chloroform (5 mL) was cooled with ice. At 0.45 g m-chloroperbenzoic acid was added. The mixture was stirred for 4.5 hours while gradually warming to room temperature. Chloroform 30mL was added to the reaction mixture, and it wash | cleaned in order of saturated sodium hydrogen carbonate solution and a saturated salt solution. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylsulfinylmethyl-thiazole-5-carboxylic acid. 0.23 g of amide was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.56 (9H, s), 2.61 (3H, s), 4.26 (1H, d, J = 12.4 Hz), 4.49-4.64 (3H, m), 6 .96 (1H, dd, J 1 = 7.3Hz, J 2 = 7.2 Hz), 7.13 (1H, d, J = 7.6 Hz), 7.46 (1H, dd, J 1 = 7.3Hz, J 2 = 6.2 Hz), 8.78 (0.6 H, brs), 9.59 (1 H, brs), 11.06 (0.4 H, brs)
Reference production example 12
Figure JPOXMLDOC01-appb-I000132
To a chloroform solution (5 mL) of 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylthiomethyl-thiazole-5-carboxylic acid amide in chloroform (5 mL) was cooled with ice. At 0.45 g m-chloroperbenzoic acid was added. The mixture was stirred for 4.5 hours while gradually warming to room temperature. Chloroform 30mL was added to the reaction mixture, and it wash | cleaned in order of saturated sodium hydrogen carbonate solution and a saturated salt solution. Dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 2- (t-butoxycarbonylamino) -N- (2-chloro-4-fluoro-benzyl) -4-methylsulfonylmethyl-thiazole-5-carboxylic acid. 0.30 g of amide was obtained.
1 H-NMR (CDCl 3 ) Δ: 1.56 (9H, s), 2.97 (3H, s), 4.60 (2H, d, J = 5.6 Hz), 4.83 (2H, s), 6.97 (1H) , Ddd, J 1 = 8.5Hz, J 2 = 8.3Hz, J 3 = 2.4 Hz), 7.14 (1H, dd, J 1 = 8.3Hz, J 2 = 2.4 Hz), 7.31 (1H, brs), 9.58 (1H, brs), 7.44 (1H, dd, J 1 = 8.5Hz, J 2 = 6.1Hz)
Reference production example 13
Figure JPOXMLDOC01-appb-I000133
4.0 g of N-chlorosuccinimide was added to a mixture of 5.0 g of ethyl 4,4-difluoroacetoacetate and 30 ml of chlorobenzene. The mixture was heated and stirred at 80 ° C. for 4 hours. The reaction mixture was allowed to cool to room temperature, hexane was added to the reaction mixture to precipitate a precipitate, the solid was filtered off, and the filtrate was concentrated. To the obtained residue were added 30 ml of EtOH and 2.3 g of thiourea, and the mixture was stirred at 80 ° C. for 2 hours. After allowing to cool to room temperature, 47 ml of 5% NaOH aqueous solution was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was neutralized with 12N hydrochloric acid, and then the solvent was distilled off to obtain 10 g of 2-amino-4-difluoromethylthiazole-5-carboxylic acid.
1 H-NMR (DMSO-d 6 ) Δ: 7.25 (2H, brs), 7.64 (1H, t, J = 55.1 Hz).
Reference production example 14
Figure JPOXMLDOC01-appb-I000134
To a THF solution (40 mL) of 2.35 g of 2-bromo-4,5-difluorobenzyl azide, 3.91 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 6 hours. The reaction mixture was left overnight at room temperature, and 15 mL of aqueous ammonia (28%) was added. The mixture was stirred at room temperature for 3 hours, and 46.4 mL of 4N aqueous sodium hydroxide solution was added. The mixture was stirred at room temperature for 1 hour, and 87.5 mL of 1N hydrochloric acid was added. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Under ice-cooling, 1.5 mL of concentrated hydrochloric acid was added, and toluene was added to azeotrope water. The residue was washed with THF, and the obtained crystal was dried to obtain 1.94 g of 2-bromo-4,5-difluorobenzylamine hydrochloride.
1 H-NMR (DMSO-d 6 ) Δ: 4.10 (2H, s), 7.82 (1H, dd, J 1 = 11.7Hz, J 2 = 8.3 Hz), 7.93 (1H, dd, J 1 = 10.1Hz, J 2 = 7.7 Hz), 8.55 (3H, brs)
Reference production example 15
Figure JPOXMLDOC01-appb-I000135
To a solution of 2.28 g of 2-bromo-4,5-difluorobenzyl chloride in DMSO (30 mL) was added 1.08 g of sodium azide. The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was left overnight at room temperature and the reaction mixture was poured into 50 mL of water. The mixture was extracted with t-butyl methyl ether. The organic layer was washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure yielded 3.35 g of 2-bromo-4,5-difluorobenzyl azide.
1 H-NMR (CDCl 3 ) Δ: 4.45 (2H, s), 7.28 (1H, dd, J 1 = 10.0 Hz, J 2 = 7.6 Hz), 7.44 (1H, dd, J 1 = 9.5Hz, J 2 = 7.3Hz)
Reference Production Example 16
Figure JPOXMLDOC01-appb-I000136
To a toluene solution (15 mL) of 2-bromo-4,5-difluorobenzyl alcohol 4.02 g, 1.45 mL of thionyl chloride and 2 drops of DMF were added. The mixture was stirred at 80 ° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 3.28 g of 2-bromo-4,5-difluorobenzyl chloride.
1 H-NMR (CDCl 3 ) Δ: 4.62 (2H, s), 7.36 (1H, dd, J 1 = 10.5Hz, J 2 = 8.1 Hz), 7.43 (1H, dd, J 1 = 9.5Hz, J 2 = 7.4Hz)
Reference Production Example 17
Figure JPOXMLDOC01-appb-I000137
To a THF solution (100 mL) of 6.90 g of 2-bromo-3,5-difluorobenzyl azide, 7.91 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 9 hours. The reaction mixture was left overnight at room temperature, and 30 mL of aqueous ammonia (28%) was added. The mixture was stirred at room temperature for 3 hours, 94 mL of 4N aqueous sodium hydroxide solution was added, and the mixture was stirred at room temperature for 1 hour. 177 mL of 1N hydrochloric acid was added here. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 10 mL of THF was added to the residue. Under ice-cooling, 3 mL of concentrated hydrochloric acid was added, and the resulting crystals were collected by filtration. The obtained crystals were washed with THF and dried to obtain 2.89 g of 2-bromo-3,5-difluorobenzylamine hydrochloride.
1 H-NMR (DMSO-d 6 ) Δ: 4.17 (2H, s), 7.48-7.53 (2H, m), 8.71 (3H, brs)
Reference Production Example 18
Figure JPOXMLDOC01-appb-I000138
2.18 g of sodium azide was added to a DMSO solution (55 mL) of 7.00 g of 2-bromo-3,5-difluorobenzyl chloride. The mixture was stirred at room temperature for 2.5 hours. The reaction mixture was left overnight at room temperature and the reaction mixture was poured into 200 mL of water. The mixture was extracted with t-butyl methyl ether. The organic layer was washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure gave 6.90 g of 2-bromo-3,5-difluorobenzyl azide.
1 H-NMR (CDCl 3 ) Δ: 4.52 (2H, s), 6.87-6.92 (1H, m), 7.02-7.05 (1H, m)
Reference Production Example 19
Figure JPOXMLDOC01-appb-I000139
To a toluene solution (200 mL) of 6.12 g of 2-bromo-3,5-difluorobenzyl alcohol, 2.40 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 80 ° C. for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain 7.00 g of 2-bromo-3,5-difluorobenzyl chloride.
1 H-NMR (CDCl 3 ) Δ: 4.68 (2H, s), 6.87-7.18 (2H, m)
Reference Production Example 20
Figure JPOXMLDOC01-appb-I000140
20.01 g of 1,1′-carbonyldiimidazole was added to a THF solution (300 mL) of 19.51 g of 2-bromo-3,5-difluorobenzoic acid, and the mixture was heated to reflux for 3 hours and 40 minutes. The reaction mixture was allowed to cool to room temperature and added dropwise to an aqueous solution (160 mL) of sodium borohydride 5.07 g over 4 hours. After adding 2.5 g of sodium borohydride and stirring for 3 hours, the mixture was allowed to stand overnight at room temperature. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography to obtain 7.414 g of 2-bromo-3,5-difluorobenzyl alcohol.
1 H-NMR (CDCl 3 ) Δ: 2.01 (1H, brs), 4.76 (2H, s), 6.84 (1H, ddd, J) 1 = 8.3Hz, J 2 = 8.3Hz, J 3 = 2.9 Hz), 7.13-7.16 (1H, m)
Reference Production Example 21
Figure JPOXMLDOC01-appb-I000141
2.18 g of sodium azide was added to a DMSO solution (55 mL) of 6.54 g of 2-bromo-3,4,5-trifluorobenzyl chloride. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was left at room temperature overnight, and then the reaction mixture was poured into 80 mL of water. The mixture was extracted with t-butyl methyl ether. The organic layer was washed with water and saturated brine in this order. Dried over magnesium sulfate and concentrated under reduced pressure. To the residue was added 100 mL of THF, 7.27 g of triphenylphosphine was added under ice cooling, and the mixture was stirred at room temperature for 1.5 hours. After leaving at room temperature for 3 days, 28 mL of aqueous ammonia (28%) was added and stirred for 3 hours. To the mixture, 94 mL of 4N aqueous sodium hydroxide solution was added and stirred for 1 hour. After adding 150 mL of 1N hydrochloric acid, the reaction mixture was allowed to stand, and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with saturated brine and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Under ice-cooling, 5 mL of concentrated hydrochloric acid was added, and toluene was added to azeotrope water. The residue was washed with chloroform, and the obtained crystals were dried to obtain 3.36 g of 2-bromo-3,4,5-trifluorobenzylamine hydrochloride.
1 H-NMR (DMSO-d 6 ) Δ: 4.15 (2H, s), 7.75-7.80 (1H, m), 8.69 (3H, brs)
Reference Production Example 22
Figure JPOXMLDOC01-appb-I000142
To a toluene solution (200 mL) of 16.65 g of 2-bromo-3,4,5-trifluorobenzyl alcohol, 7.56 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 110 ° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 6.537 g of 2-bromo-3,4,5-trifluorobenzyl chloride.
1 H-NMR (CDCl 3 ) Δ: 4.64 (2H, s), 7.21-7.26 (1H, m)
Reference Production Example 23
Figure JPOXMLDOC01-appb-I000143
To a toluene solution (200 mL) of 16.91 g of 2-bromo-3,4,5-trifluorobenzoic acid, 7.26 mL of thionyl chloride and 4 drops of DMF were added. The mixture was stirred at 110 ° C. for 6 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 150 mL of THF. The THF solution was added dropwise to ice-cooled sodium borohydride 4.09 g ethanol solution (300 mL) over 1.5 hours, and then stirred at room temperature for 1 hour. The reaction mixture was left at room temperature overnight and then concentrated under reduced pressure. Water and ethyl acetate were added to the residue, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate and combined with the previous ethyl acetate layer. The extract was washed with saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography to obtain 6.603 g of 2-bromo-3,4,5-trifluorobenzyl alcohol.
1 H-NMR (CDCl 3 ) Δ: 2.08 (1H, t, J = 5.9 Hz), 4.72 (2H, d, J = 5.9 Hz), 7.24-7.29 (1H, m)
Reference Production Example 24
Figure JPOXMLDOC01-appb-I000144
To a THF solution (50 mL) of 2.63 g of 2-chloro-4,5-difluoro-benzyl azide, 3.72 g of triphenylphosphine was added under ice cooling. The mixture was stirred at room temperature for 7.5 hours. The reaction mixture was allowed to stand at room temperature for 1 day, and 14 mL of aqueous ammonia (28%) was added. After stirring at room temperature for 3.5 hours, 45 mL of 4N aqueous sodium hydroxide solution was added. After stirring at room temperature for 2 hours, 85 mL of 1N hydrochloric acid was added. The reaction mixture was allowed to stand and the THF layer was separated. The aqueous layer was extracted with t-butyl ethyl ether and combined with the THF layer. The extract was washed with water and saturated brine in that order and dried over sodium sulfate. Concentrated under reduced pressure and 5 mL of THF was added to the residue. Concentrated hydrochloric acid (1.5 mL) was added under ice cooling, and the resulting crystals were collected by filtration. The obtained crystals were washed with THF and dried to obtain 1.41 g of 2-chloro-4,5-difluoro-benzylamine hydrochloride.
1 H-NMR (DMSO-d 6 ) Δ: 4.10 (2H, s), 7.79 (1H, dd, J 1 = 10.4Hz, J 1 = 7.4 Hz), 7.88 (1H, dd, J 1 = 11.5Hz, J 1 = 8.5 Hz), 8.72 (3H, brs)
Reference Production Example 25
Figure JPOXMLDOC01-appb-I000145
To a solution of 2-chloro-4,5-difluoro-benzyl bromide 3.15 g in DMSO (25 mL) was added 1.03 g of sodium azide. The mixture was stirred at room temperature for 1 hour. The reaction mixture was left at room temperature overnight and the reaction mixture was poured into 100 mL of water. The mixture was extracted with t-butyl methyl ether. The organic layer was washed with water and saturated brine in that order, and then dried over magnesium sulfate. Concentration under reduced pressure gave 2.63 g of 2-chloro-4,5-difluoro-benzyl azide.
1 H-NMR (CDCl 3 ) Δ: 4.46 (2H, s), 7.25-7.29 (2H, m)
Next, formulation examples are shown. In addition, a part shows a weight part.
Formulation Example 1
Each wettable powder is obtained by thoroughly pulverizing and mixing 50 parts of any one of the compounds (1) to (111) of the present invention, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate, and 45 parts of synthetic silicon hydroxide. Get.
Formulation Example 2
20 parts of any one of the compounds (1) to (111) of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol. After pulverization, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and stirred to obtain each flowable preparation.
Formulation Example 3
Each powder agent is obtained by thoroughly crushing and mixing 2 parts of any one of the compounds (1) to (111) of the present invention, 88 parts of kaolin clay and 10 parts of talc.
Formulation Example 4
Each emulsion is obtained by thoroughly mixing 5 parts of any one of the compounds (1) to (111) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene. Get.
Formulation Example 5
After thoroughly mixing 2 parts of any one of the compounds (1) to (111) of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay, water is added. Kneaded well and granulated and dried to obtain each granule.
Formulation Example 6
10 parts of any one of the compounds (1) to (111) of the present invention; 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water are mixed and pulverized by a wet pulverization method. Thus, each flowable preparation is obtained.
Formulation Example 7
40 parts of any one of the compounds (1) to (111) of the present invention, 5 parts of propylene glycol (manufactured by Nacalai Tesque), 5 parts of Soprophor FLK (manufactured by Rhodia Nikka), 0.2 part of anti-form C emulsion (Dow Corning), 0.3 part of Proxel GXL (manufactured by Arch Chemical), and 49.5 parts of ion-exchanged water are mixed to prepare a base slurry. 150 parts of glass beads (Φ = 1 mm) are added to 100 parts of the slurry, and pulverized for 2 hours while cooling with cooling water. After grinding, the glass beads are removed by filtration to obtain each flowable formulation.
Formulation Example 8
50 parts of any one of the compounds (1) to (111) of the present invention, 38.5 parts of NN kaolin clay (manufactured by Takehara Chemical Industry), 10 parts of Morwet D425, 1.5 parts of Morwer EFW (Akzo Nobel) And the mixture is pulverized with a jet mill to obtain each powder.
Next, test examples show that the compounds of the present invention are useful for controlling plant diseases.
The control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.
Test example 1
A plastic pot was filled with soil, seeded with wheat (variety: Shirogane), grown in a greenhouse for 9 days, and then sprinkled with spores of wheat red rust fungus (Puccinia redondota f. Sp. Tritici). After inoculation, it was placed in a dark and humid place at 23 ° C. for 1 day, and then air-dried to obtain a wheat rust-infected seedling. Each of the compounds (15), (18), (52), (57), (58), (85), (90) and (97) of the present invention was made into a flowable formulation according to Formulation Example 6, Was diluted to a predetermined concentration (500 ppm) and sprayed on the foliage so as to adhere well to the leaf surface of the wheat. After spraying, the plants were air-dried and placed under illumination for 6 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compounds (15), (18), (52), (57), (58), (85), (90) and (97) of the present invention was untreated. It was 30% or less of the lesion area in the plant.
Test example 2
A plastic pot was filled with soil, seeded with wheat (variety: Apogee), and grown in a greenhouse for 10 days. Each of the compounds (2), (9), (18), (40), (43), (52), and (89) of the present invention was made into a flowable formulation according to Formulation Example 6, and then diluted with water. A predetermined concentration (500 ppm) was applied, and the foliage was sprayed so as to sufficiently adhere to the leaf surface of the wheat. After spraying, the plants were air-dried and sprayed and inoculated with an aqueous suspension of Septoria tritici spores after 3 or 4 days. After the inoculation, the area was first placed under a high humidity of 18 ° C. for 3 days and further under illumination for 14 to 18 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compounds (2), (9), (18), (40), (43), (52), and (89) of the present invention is the disease in the untreated plant. It was 30% or less of the spot area.
Test example 3
The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds (17), (18) and (19) of the present invention is made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm) so that it adheres well to the cucumber leaf surface. The foliage was sprayed. After spraying, the plants were air-dried, and a spore-containing PDA medium of Botrytis cinerea was placed on the cucumber leaf surface. After the inoculation, the lesion area was examined after 4 days in a humid environment at 12 ° C. As a result, the lesion area in the plant treated with the compounds (17), (18) and (19) of the present invention was 30% or less of the lesion area in the untreated plant.
Test example 4
A plastic pot was stuffed with soil, seeded with green beans (variety; Nagahama peas) and grown in a greenhouse for 8 days. Each of the compounds (16), (17), (18), (89), (95), (96) and (101) of the present invention was made into a flowable formulation according to Formulation Example 6, then diluted with water to give The concentration was set to 500 ppm, and the foliage was sprayed so as to adhere well to the kidney leaf surface. After spraying, the plants were air-dried, and a mycelia-containing PDA medium of Sclerotinia sclerotiorum was placed on the kidney leaf surface. After inoculation, the lesion area was investigated after 23 days at 23 ° C. and high humidity. As a result, the lesion area in the plant treated with the compounds (16), (17), (18), (89), (95), (96) and (101) of the present invention is the lesion spot in the untreated plant. It was 30% or less of the area.
Test Example 5 Cucumber downy mildew treatment effect test (Pseudoperonospora cubensis)
The plastic pot was filled with soil, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. The pot was spray-inoculated with an aqueous suspension of cucumber downy mildew zoosporangium, placed at 23 ° C. under high humidity for 1 day, and then air-dried to obtain a cucumber downy mildew-infected seedling. Compound (10), (12), (13), (14), (16), (27), (33), (36), (37), (40), (41), (43) , (49), (52), (56), (57), (58), (59), (61), (62), (63), (64), (65), (66), ( 69), (72), (75), (76), (77), (78), (81), (82), (84), (86), (89), (90), (91) , (92), (99), (100), (101), (102) and (110) are each made into a flowable formulation according to Formulation Example 6, then diluted with water to a predetermined concentration (500 ppm), The foliage was sprayed so as to adhere well to the cucumber leaf surface. After spraying, the plants were air-dried and placed in a greenhouse at 23 ° C. for 5 days, and then the lesion area was examined. As a result, the present compounds (10), (12), (13), (14), (16), (27), (33), (36), (37), (40), (41), (43), (49), (52), (56), (57), (58), (59), (61), (62), (63), (64), (65), (66 ), (69), (72), (75), (76), (77), (78), (81), (82), (84), (86), (89), (90), The lesion area in the plant which processed (91), (92), (99), (100), (101), (102) and (110) is 30% or less of the lesion area in an untreated plant. there were.
Test Example 6
The plastic pot was filled with soil, tomato (variety: patio) was sown and grown in a greenhouse for 20 days. Compounds of the present invention (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12) , (13), (14), (15), (16), (17), (26), (27), (28), (30), (31), (33), (35), ( 36), (37), (38), (39), (40), (41), (43), (45), (49), (50), (52), (56), (57) , (58), (59), (61), (62), (63), (64), (65), (69), (71), (72), (73), (75), ( 76), (77), (78), (80), (81), (82), (84), (85), (86), (88), (89), (90), (91) , (92), (93), (94), (95), (96), ( 7), (98), (99), (100), (101), (102), (104), (106) and (110) were each made into a flowable formulation according to Formulation Example 6, and then water Was diluted to a predetermined concentration (500 ppm) and sprayed on the foliage so as to adhere well to the leaf surface of the tomato seedling. After air-drying the diluted solution on the leaf surface to dryness, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
Compounds of the present invention (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12) , (13), (14), (15), (16), (17), (26), (27), (28), (30), (31), (33), (35), ( 36), (37), (38), (39), (40), (41), (43), (45), (49), (50), (52), (56), (57) , (58), (59), (61), (62), (63), (64), (65), (69), (71), (72), (73), (75), ( 76), (77), (78), (80), (81), (82), (84), (85), (86), (88), (89), (90), (91) , (92), (93), (94), (95), (96), ( 7), (98), (99), (100), (101), (102), (104), (106) and the lesion area in the (110) plant is the lesion area in the untreated plant It was 30% or less of the spot area.
Test Example 7
The plastic pot was filled with soil, tomato (variety: patio) was sown and grown in a greenhouse for 20 days. Each of the compounds (18), (20), (21), (22) and (23) of the present invention was made into a flowable formulation according to Formulation Example 6, then diluted with water to a predetermined concentration (200 ppm), and the tomato The foliage was sprayed so as to adhere well to the leaf surface of the seedling. After air-drying the diluted solution on the leaf surface to dryness, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
The lesion area in the plant which processed this invention compound (18), (20), (21), (22) and (23) was 30% or less of the lesion area in an untreated plant.
Test Example 8
Tomato (variety: patio) was sown on a plastic sponge piece and hydroponically cultivated in a plastic cup for about 20 days. Compound (1), (2), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13) , (14), (15), (16), (17), (26), (33), (36), (40), (41), (43), (49), (52), ( 53), (62), (63), (65), (72), (75), (76), (77), (78), (81), (82), (84), (85) , (86), (87), (88), (89), (90), (91), (93), (94), (95), (96), (97), (98), ( 99), (100), (101), (102), (106) and (110) are each made into a flowable formulation according to Formulation Example 6, and then 1 mg of the above tomato hydroponics per plant in terms of weight In a seedling cup Off to. Further, after hydroponics for 7 days, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
Compound (1), (2), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13) , (14), (15), (16), (17), (26), (33), (36), (40), (41), (43), (49), (52), ( 53), (62), (63), (65), (72), (75), (76), (77), (78), (81), (82), (84), (85) , (86), (87), (88), (89), (90), (91), (93), (94), (95), (96), (97), (98), ( 99), (100), (101), (102), (106), and the lesion area in the plant which processed (110) was 30% or less of the lesion area in an untreated plant.
Test Example 9
Tomato (variety: patio) was sown on a plastic sponge piece and hydroponically cultivated in a plastic cup for about 20 days. Each of the compounds (18), (20), (21), (22) and (23) of the present invention was made into a flowable formulation according to Formulation Example 6, and then 0.4 mg per plant in terms of weight was added to the tomato water. It put into the cup of the cultivation seedling. Further, after hydroponics for 7 days, an aqueous suspension of Phytophthora infestans spores was spray-inoculated. After inoculation, the plant was first placed at 23 ° C. under high humidity for 1 day, and then cultivated in an artificial climate room at 20 ° C. for 4 days.
The lesion area in the plant which processed this invention compound (18), (20), (21), (22) and (23) was 30% or less of the lesion area in an untreated plant.
　本発明化合物又はその塩は優れた植物病害防除効力を有することから、植物病害防除用途に有用である。 The compound of the present invention or a salt thereof is useful for plant disease control because it has an excellent plant disease control effect.

Claims (13)

  1. 　式（１）
    Figure JPOXMLDOC01-appb-I000001
    〔式中、
    Ｒ１は水素、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ４基、−Ｓ−Ｒ４基、−Ｓ（＝Ｏ）−Ｒ４基、−Ｓ（＝Ｏ）２−Ｒ４基、群Ａより選ばれる１以上の基で置換されたメチル基、群Ｂより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５鎖式炭化水素基、Ｃ３~Ｃ５シクロアルキル基、フルオロメチル基又はジフルオロメチル基を表し、
    ｐは０から５の整数のいずれかを表し、
    Ｒ２は群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ５鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基、ハロゲン、シアノ基、ニトロ基、−Ｏ−Ｒ５基、−Ｓ−Ｒ５基、−Ｃ（＝Ｏ）−Ｒ５基、−Ｃ（＝Ｏ）−ＯＲ５基、−ＯＣ（＝Ｏ）−Ｒ５基、−ＮＲ５Ｒ６基、−Ｃ（＝Ｏ）−ＮＲ５Ｒ６基又は−ＮＲ５−Ｃ（＝Ｏ）−Ｒ６基を表すか、
    或いは、ｐが２以上あり、かつ２つのＲ２がベンゼン環の隣接する炭素に結合する場合には、該２つのＲ２が結合して、群Ｅより選ばれる１以上の基で置換されていてもよいＣ２~Ｃ５ポリメチレン基、群Ｅより選ばれる１以上の基で置換されていてもよいプロペン−１，３−ジイル基、群Ｅより選ばれる１以上の基で置換されていてもよい１，３−ブタジエン−１，４−ジイル基又はメチレンジオキシ基を表し、
    Ｒ４はＣ１~Ｃ４鎖式炭化水素基を表し、
    Ｒ５及びＲ６は独立して、水素、群Ｃより選ばれる１以上の基で置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基又は群Ｅより選ばれる１以上の基で置換されていてもよいフェニル基を表す。
    　但し、ｐが２から５の整数のいずれかである場合、Ｒ２は相互に同一でも相異なっていてもよい。
    　なお、群Ａは塩素、臭素、沃素、シアノ基、Ｃ１−Ｃ４アルコキシ基、Ｃ１−Ｃ４アルキルチオ基、Ｃ１−Ｃ４アルキルスルフィニル基及びＣ１−Ｃ４アルキルスルホニル基からなる群を表し、
    群Ｂはハロゲン、シアノ基、Ｃ１~Ｃ４アルコキシ基、Ｃ１~Ｃ４アルキルチオ基、Ｃ１~Ｃ４アルキルスルフィニル基及びＣ１~Ｃ４アルキルスルホニル基からなる群を表し、
    群Ｃは群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、ハロゲン、シアノ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルコキシ）カルボニル基、及びハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニルオキシ基からなる群を表し、
    群ＤはＣ１~Ｃ５アルキル基及びハロゲンからなる群を表し、
    群Ｅはハロゲン、シアノ基、ニトロ基、ハロゲンで置換されていてもよいＣ１~Ｃ１０鎖式炭化水素基、群Ｄより選ばれる１以上の基で置換されていてもよいＣ３~Ｃ１０シクロアルキル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルコキシ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルチオ基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルフィニル基、ハロゲンで置換されていてもよいＣ１~Ｃ４アルキルスルホニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニル基、ハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルコキシ）カルボニル基及びハロゲンで置換されていてもよい（Ｃ１~Ｃ４アルキル）カルボニルオキシ基からなる群を表す。〕
    で示されるアミド化合物又はその塩。     Formula (1)
    Figure JPOXMLDOC01-appb-I000001
    [Where,
    R 1 is hydrogen, halogen, cyano group, nitro group, —O—R 4 group, —S—R 4 group, —S (═O) —R 4 group, —S (═O) 2 —R 4 group, A methyl group substituted with one or more groups selected from group A, a C2-C5 chain hydrocarbon group optionally substituted with one or more groups selected from group B, a C3-C5 cycloalkyl group, fluoromethyl Represents a group or a difluoromethyl group,
    p represents any integer from 0 to 5;
    R 2 is a C1-C5 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and a C3-C10 cycloalkyl group which may be substituted with one or more groups selected from group D , Phenyl group, halogen, cyano group, nitro group, —O—R 5 group, —S—R 5 group, —C (═O) —R optionally substituted with one or more groups selected from group E 5 groups, —C (═O) —OR 5 groups, —OC (═O) —R 5 groups, —NR 5 R 6 groups, —C (═O) —NR 5 R 6 groups or —NR 5 —C (= O) —R 6 group is represented,
    Alternatively, when p is 2 or more and two R 2 are bonded to adjacent carbons of the benzene ring, the two R 2 are bonded and substituted with one or more groups selected from group E. An optionally substituted C2-C5 polymethylene group, a propene-1,3-diyl group optionally substituted with one or more groups selected from group E, and one or more groups selected from group E. Represents a 1,3-butadiene-1,4-diyl group or a methylenedioxy group,
    R 4 represents a C1-C4 chain hydrocarbon group,
    R 5 and R 6 are independently hydrogen, a C1-C10 chain hydrocarbon group which may be substituted with one or more groups selected from group C, and one or more groups selected from group D. Represents a C3 to C10 cycloalkyl group which may be substituted or a phenyl group which may be substituted with one or more groups selected from group E.
    However, when p is any integer of 2 to 5, R 2 may be the same as or different from each other.
    Group A represents a group consisting of chlorine, bromine, iodine, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group,
    Group B represents a group consisting of halogen, cyano group, C1-C4 alkoxy group, C1-C4 alkylthio group, C1-C4 alkylsulfinyl group and C1-C4 alkylsulfonyl group,
    Group C is a C3-C10 cycloalkyl group optionally substituted with one or more groups selected from Group D, a halogen, a cyano group, a C1-C4 alkoxy group optionally substituted with halogen, or a halogen-substituted group An optionally substituted C1-C4 alkylthio group, a C1-C4 alkylsulfinyl group optionally substituted with halogen, a C1-C4 alkylsulfonyl group optionally substituted with halogen, and optionally substituted with halogen (C1- C4 alkyl) represents a group consisting of a carbonyl group, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a (C1-C4 alkyl) carbonyloxy group optionally substituted with halogen;
    Group D represents a group consisting of a C1-C5 alkyl group and halogen,
    Group E is halogen, cyano group, nitro group, C1-C10 chain hydrocarbon group optionally substituted with halogen, C3-C10 cycloalkyl group optionally substituted with one or more groups selected from group D C1-C4 alkoxy group optionally substituted with halogen, C1-C4 alkylthio group optionally substituted with halogen, C1-C4 alkylsulfinyl group optionally substituted with halogen, halogen-substituted May be a C1-C4 alkylsulfonyl group, a (C1-C4 alkyl) carbonyl group optionally substituted with halogen, a (C1-C4 alkoxy) carbonyl group optionally substituted with halogen, and a halogen-substituted Represents a group of good (C1-C4 alkyl) carbonyloxy groups. ]
    Or an salt thereof.
  2. 　Ｒ１が水素又はハロゲンであり、Ｒ２がハロゲンである請求項１記載のアミド化合物又はその塩。 R 1 is hydrogen or halogen, amide compound or its salt according to claim 1, wherein R 2 is halogen.
  3. 　Ｒ１が水素であり、Ｒ２がハロゲンである請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1, wherein R 1 is hydrogen and R 2 is halogen.
  4. 　Ｒ１が水素であり、Ｒ２がフッ素又は塩素である請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1, wherein R 1 is hydrogen and R 2 is fluorine or chlorine.
  5. 　Ｒ１が水素であり、Ｒ２がフッ素又は臭素である請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1, wherein R 1 is hydrogen and R 2 is fluorine or bromine.
  6. 　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、ハロゲンである請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1 , wherein R 1 is hydrogen, p is 3, and R 2 is the same or different from each other and is halogen.
  7. 　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、フッ素又は塩素である請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1 , wherein R 1 is hydrogen, p is 3, and R 2 is the same or different from each other and is fluorine or chlorine.
  8. 　Ｒ１が水素であり、ｐが３であり、Ｒ２は相互に同一又は相異なり、フッ素又は臭素である請求項１記載のアミド化合物又はその塩。 The amide compound or a salt thereof according to claim 1 , wherein R 1 is hydrogen, p is 3, and R 2 is the same or different from each other and is fluorine or bromine.
  9. 　２−アミノ−Ｎ−（２−クロロ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド。 2-amino-N- (2-chloro-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide.
  10. 　２−アミノ−Ｎ−（２−ブロモ−４，５−ジフルオロベンジル）チアゾール−５−カルボン酸アミド。 2-amino-N- (2-bromo-4,5-difluorobenzyl) thiazole-5-carboxylic acid amide.
  11. 　請求項１記載のアミド化合物又はその塩と、不活性担体と、を含有する植物病害防除剤。 A plant disease control agent comprising the amide compound or a salt thereof according to claim 1 and an inert carrier.
  12. 　請求項１記載のアミド化合物又はその塩の有効量を植物又は植物が生育する土壌に施用する工程を有する植物病害の防除方法。 A method for controlling plant diseases comprising a step of applying an effective amount of the amide compound or a salt thereof according to claim 1 to a plant or a soil in which the plant grows.
  13. 　植物病害を防除するための請求項１記載のアミド化合物又はその塩の使用。 Use of the amide compound or a salt thereof according to claim 1 for controlling plant diseases.
PCT/JP2010/058856 2009-05-20 2010-05-19 Amide compound and use thereof for control of plant diseases WO2010134628A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2009121870 2009-05-20
JP2009-121870 2009-05-20

Publications (1)

Publication Number Publication Date
WO2010134628A1 true WO2010134628A1 (en) 2010-11-25

Family

ID=43126298

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2010/058856 WO2010134628A1 (en) 2009-05-20 2010-05-19 Amide compound and use thereof for control of plant diseases

Country Status (2)

Country Link
JP (1) JP2011001353A (en)
WO (1) WO2010134628A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023176458A1 (en) * 2022-03-18 2023-09-21 石原産業株式会社 Disinfecting composition containing thiazole carboxylic acid hydrazide compound

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1211889A (en) * 1966-12-07 1970-11-11 Uniroyal Inc The use of carboxamidothiazoles as agricultural chemicals
JPH04128275A (en) * 1990-09-19 1992-04-28 Mitsubishi Kasei Corp N-benzylamides and insecticidal miticide containing the compound as active component
JPH0789946A (en) * 1993-08-16 1995-04-04 Lucky Co Ltd New 2-aminothiazolecarboxamide derivative, its preparation and antibacterial agent for plant pathogenic fungi
JP2001342183A (en) * 2000-06-01 2001-12-11 Ube Ind Ltd 4- (1-fluoroethyl) thiazole-5-carboxylic acid amide derivative and pesticide for agricultural and horticultural use
WO2007087906A1 (en) * 2006-02-01 2007-08-09 Bayer Cropscience Sa Fungicide n-cycloalkyl-benzyl-amide derivatives
WO2010012794A1 (en) * 2008-08-01 2010-02-04 Bayer Cropscience Sa Fungicide n-cycloalkyl-n-biphenylmethyl-carboxamide derivatives

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1211889A (en) * 1966-12-07 1970-11-11 Uniroyal Inc The use of carboxamidothiazoles as agricultural chemicals
JPH04128275A (en) * 1990-09-19 1992-04-28 Mitsubishi Kasei Corp N-benzylamides and insecticidal miticide containing the compound as active component
JPH0789946A (en) * 1993-08-16 1995-04-04 Lucky Co Ltd New 2-aminothiazolecarboxamide derivative, its preparation and antibacterial agent for plant pathogenic fungi
JP2001342183A (en) * 2000-06-01 2001-12-11 Ube Ind Ltd 4- (1-fluoroethyl) thiazole-5-carboxylic acid amide derivative and pesticide for agricultural and horticultural use
WO2007087906A1 (en) * 2006-02-01 2007-08-09 Bayer Cropscience Sa Fungicide n-cycloalkyl-benzyl-amide derivatives
WO2010012794A1 (en) * 2008-08-01 2010-02-04 Bayer Cropscience Sa Fungicide n-cycloalkyl-n-biphenylmethyl-carboxamide derivatives

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023176458A1 (en) * 2022-03-18 2023-09-21 石原産業株式会社 Disinfecting composition containing thiazole carboxylic acid hydrazide compound

Also Published As

Publication number Publication date
JP2011001353A (en) 2011-01-06

Similar Documents

Publication Publication Date Title
CN104884442B (en) Tetrazolinone compounds and uses thereof
CN105263921B (en) Terazololine-one compound and its application
JP5133985B2 (en) Tetrazoyl oxime derivatives and plant disease control agents
US9781933B2 (en) Tetrazolinone compound and use thereof
EP2990404A1 (en) Tetrazolinone compound and use of same
JP2011157294A (en) Pest-controlling composition
WO2014104268A1 (en) Tetrazolinone compound and applications thereof
JP5550913B2 (en) Tetrazoyloxime derivative and salt thereof, and plant disease control agent
WO2010134628A1 (en) Amide compound and use thereof for control of plant diseases
WO2010134631A1 (en) Amide compound and use thereof for control of plant diseases
WO2010134634A1 (en) Amide compound and use thereof for control of plant diseases
WO2010134635A1 (en) Amide compound and use thereof for control of plant diseases
WO2010134636A1 (en) Amide compound and use thereof for control of plant diseases
JP2011001292A (en) Amide compound and application thereof
ES2365680T3 (en) N-CICLOALQUILMETIL-2-AMINOTIAZOL-5-CARBOXAMIDS FOR USE IN THE CONTROL OF DISEASES IN PLANTS.
WO2010134629A1 (en) Amide compound and use thereof for control of plant diseases
JP2016030727A (en) Amide compound and its use for control of harmful arthropod
JP2010285352A (en) Amide compounds and uses thereof
WO2010134632A1 (en) Amide compound and use thereof for control of plant diseases
JP2010270038A (en) Amide compound and plant disease control agent containing the same
WO2010134637A1 (en) Amide compound and use thereof for control of plant diseases
JP2007161621A (en) Nitrogen-containing heterocyclic compound and agricultural/horticultural fungicide
WO2010134633A1 (en) Amide compound and use thereof for control of plant diseases
JP2010138142A (en) Pyridazine-n-oxide compound and controller for plant disease damage containing the same as active ingredient
JP2006327973A (en) Derivative of aryl heterocyclic compound and bactericide for agriculture and horticulture

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10777855

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10777855

Country of ref document: EP

Kind code of ref document: A1