Fluorine-containing pyrimidine compound, harmful fungus control agent, and method for producing fluorine-containing pyrimidine compound

Abstract

Provided are novel fluorine-containing pyrimidine compounds and a method for producing the same.　Compounds represented by general formula (1), (2), or (3). (In the formula, W and X each independently represent a hydrogen atom, a halogen atom, a C1-10 hydrocarbon group, -CmF2m+1, a nitro group, -OA1, -SOlA1, -SA1, -NA1A2, -B(OA1)(OA2), -COA1, -COOA1, or -CONA1A2, Y represents a halogen atom or -OA3, Z represents a halogen atom, a C1-10 hydrocarbon group, -CmF2m+1, a nitro group, -OA1, -SOlA1, -SA1, or -NA1A2, A1 and A2 each independently represent a hydrogen atom or a C1-10 hydrocarbon group, A3 represents a C1-12 hydrocarbon group, m represents an integer of 1-10, l represents an integer of 1-3, and n represents an integer of 0-3.)

Description

[Technical field]

[0001] The present invention relates to a fluorine-containing pyrimidine compound, a harmful fungi control agent, and a method for producing a fluorine-containing pyrimidine compound. [Background technology]

[0002] Fluorine-containing pyrimidine compounds have been reported to have various biological activities. Among them, compounds with a pyridine ring at the 2-position and a trifluoromethyl group at the 5-position of the pyrimidine ring are considered to be promising for use in the pharmaceutical and agricultural chemical fields.

[0003] More specifically, Patent Documents 1 and 6 report that 2-(4-pyridyl)-5-trifluoromethylpyrimidine derivatives have human melanin-concentrating hormone inhibitory activity and acetyl-CoA carboxylase 2 inhibitory activity. Patent Documents 2, 4, 5, and 7 report that 2-(3-pyridyl)-5-trifluoromethylpyrimidine derivatives have fungicidal activity, insecticidal activity, orexin receptor inhibitory activity, focal adhesion kinase inhibitory activity, and acetyl-CoA carboxylase 2 inhibitory activity. Patent Documents 2 and 3 report that 2-(2-pyridyl)-5-trifluoromethylpyrimidine derivatives have fungicidal activity, insecticidal activity, and herbicidal activity.

[0004] In addition, pyridylpyrimidine derivatives have been reported to have fungicidal activity. For example, Patent Document 8 reports that pyridylpyrimidine derivatives having various substituents exhibit preventive or curative control effects against many plant diseases such as rice blast, wheat eyespot, and apple scab. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2009 / 089482 [Patent Document 2] International Publication No. 2015 / 016372 [Patent Document 3] International Publication No. 1999 / 028301 [Patent Document 4] International Publication No. 2010 / 063663 [Patent Document 5] International Publication No. 2013 / 004332 [Patent Document 6] International Publication No. 2015 / 056782 [Patent Document 7] International Publication No. 2016 / 030229 [Patent Document 8] Japanese Patent Application Publication No. 7-118235 Summary of the Invention [Problem to be solved by the invention]

[0006] From the standpoint of reactivity and selectivity, it is difficult to produce a fluorine-containing pyrimidine compound having a fluorine-containing substituent at the 5-position of the pyrimidine ring, a heterocyclic substituent at the 2-position, and further having substituents at the 4- and 6-positions, and such a fluorine-containing pyrimidine compound has not been reported so far. The fluorine-containing pyrimidine compound may have useful biological activity.

[0007] The present invention provides a novel fluorine-containing pyrimidine compound and a process for producing the same. [Means for solving the problem]

[0008] The gist and configuration of the present invention are as follows. [1] A fluorine-containing pyrimidine compound represented by the following general formula (1), (2) or (3):

[0009] [ka]

[0010] (In the above general formulas (1) to (3), W and X each independently represent a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -Cm F 2m+1 (m is an integer from 1 to 10), a nitro group, -OA 1 , -SO l A 1 (l is an integer from 1 to 3), -SA 1 , -NA 1 A 2 , -B(OA 1 )(OA 2 ), -COA 1 , -COOA 1 or -CONA 1 A 2 represents Y is a halogen atom or -OA 3 represents Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C m F 2m+1 (m is an integer from 1 to 10), a nitro group, -OA 1 , -SO l A 1 (l is an integer from 1 to 3), -SA 1 or -NA 1 A 2 represents A 1 and A 2 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, A 3 represents a hydrocarbon group having 1 to 12 carbon atoms, n represents an integer of 0 to 3; In W, X and Z, each A 1 , A 2 , m and l may be the same or different; When there are multiple Z's, each of the multiple Z's may be the same or different. [2] A harmful fungus control agent comprising the fluorine-containing pyrimidine compound or a salt thereof according to [1] above as an active ingredient. [3] (a) reacting aniline represented by the following general formula (4) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (5) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1):

[0011] [ka]

[0012] (b) reacting aniline or a derivative thereof represented by the following general formula (4) with a fluorine-containing pyrimidine compound represented by the following general formula (6) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2):

[0013] [ka]

[0014] or (c) reacting aniline represented by the following general formula (4) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (7) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3):

[0015] [ka]

[0016] In the above general formulas (1) to (7), W, X, Y, Z and n are as defined above, 1 represents a halogen atom.) The present invention relates to a method for producing a fluorine-containing pyrimidine compound. [4] (d) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (9) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1):

[0017] [ka]

[0018] (e) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (10) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2):

[0019] [ka]

[0020] or (f) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (11) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3):

[0021] [ka]

[0022] (In the above general formulas (1) to (3) and (8) to (11), W, X, Y, Z and n are as defined above, 2 represents a halogen atom.) The present invention relates to a method for producing a fluorine-containing pyrimidine compound. Effect of the Invention

[0023] According to the present invention, it is possible to provide a novel fluorine-containing pyrimidine compound and a method for producing the same. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] [Fluorine-containing pyrimidine compounds] The fluorine-containing pyrimidine compound of the present invention is represented by the following general formula (1), (2) or (3).

[0025] [ka]

[0026] (In the above general formulas (1) to (3), W and X each independently represent a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C m F 2m+1 (m is an integer from 1 to 10), a nitro group, -OA 1 , -SO l A 1 (l is an integer from 1 to 3), -SA 1 , -NA 1 A 2 , -B(OA 1 )(OA 2 ), -COA 1 , -COOA 1 or -CONA 1 A 2 represents Y is a halogen atom or -OA 3 represents Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C m F 2m+1 (m is an integer from 1 to 10), a nitro group, -OA 1 , -SO l A 1 (l is an integer from 1 to 3), -SA 1 or -NA 1 A 2 represents A 1 and A 2 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, A 3 represents a hydrocarbon group having 1 to 12 carbon atoms, n represents an integer of 0 to 3; In W, X and Z, each A 1 , A 2 , m and l may be the same or different; When there are multiple Z's, each of the multiple Z's may be the same or different.

[0027] When Y is a halogen atom, the halogen atom is F, Cl, Br or I, preferably F or Cl.

[0028] Y-OA 3 If A 3 represents a hydrocarbon group having 1 to 12 carbon atoms. 3 The alkyl group is not particularly limited as long as it is a hydrocarbon group having 1 to 12 carbon atoms and composed of carbon atoms and hydrogen atoms, and examples thereof include a chain hydrocarbon group, an aromatic hydrocarbon group, and an alicyclic hydrocarbon group. The chain hydrocarbon group is not particularly limited as long as it has a total of 1 to 12 carbon atoms, and may be a straight chain hydrocarbon group or a branched chain hydrocarbon group. The aromatic hydrocarbon group is not particularly limited as long as it has a total of 6 to 12 carbon atoms, and may be an aromatic hydrocarbon group having a substituent or an aromatic hydrocarbon group having no substituent. The aromatic hydrocarbon group may have a condensed polycyclic structure. The alicyclic hydrocarbon group is not particularly limited as long as it has a total of 3 to 12 carbon atoms, and may be an alicyclic hydrocarbon group having a substituent or an alicyclic hydrocarbon group having no substituent. The alicyclic hydrocarbon group may have a bridged ring structure.

[0029] A 3 Examples of the chain hydrocarbon group represented by the formula (I) include alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl; alkenyl groups such as ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl; and alkynyl groups such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, and dodecynyl.

[0030] A 3 Examples of the aromatic hydrocarbon group represented by include a phenyl group, a benzyl group, a tolyl group, a naphthyl group, etc. The tolyl group may be any of an o-tolyl group, an m-tolyl group, and a p-tolyl group, with a p-tolyl group being preferred.

[0031] A 3The alicyclic hydrocarbon group represented by the formula (I) includes saturated or unsaturated cyclic hydrocarbon groups. Examples of the cyclic hydrocarbon group include a cyclopropyl group, a cyclobutyl group, a cyclohexyl group, a cyclopentyl group, an adamantyl group, and a norbornyl group.

[0032] Each of W and X is preferably a hydrogen atom, a halogen atom, or a hydrocarbon group having 1 to 10 carbon atoms, and more preferably a hydrogen atom. Each of W and X may be the same or different. It is particularly preferable that both of W and X are hydrogen atoms. Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C m F 2m+1 (wherein m is an integer of 1 to 10) or a nitro group.

[0033] When there are multiple Z's and all of the multiple Z's are hydrocarbon groups, the total number of carbon atoms in the hydrocarbon groups of the multiple Z's may be 5 or more. In this case, n is an integer of 1 to 3.

[0034] In W, X and Z, the halogen atom is F, Cl, Br or I, and is preferably F or Cl.

[0035] In W, X and Z, the hydrocarbon group having 1 to 10 carbon atoms is not particularly limited as long as it is a hydrocarbon group having 1 to 10 carbon atoms and consisting of carbon atoms and hydrogen atoms. 3 Among the hydrocarbon groups mentioned in the explanation of the above, hydrocarbon groups having 1 to 10 carbon atoms can be mentioned.

[0036] In W, X and Z, -C m F 2m+1 is not particularly limited as long as it is a perfluoroalkyl group consisting of carbon atoms and fluorine atoms. m F 2m+1 m may be linear or branched. m is an integer of 1 to 10, and preferably an integer of 1 to 3.

[0037] -OA in W, X and Z 1 , -SOl A 1 , -SA 1 , -NA 1 A 2 , and -B(OA 1 )(OA 2 ), -COA 1 , -COOA 1 , -CONA 1 A 2 In A 1 and A 2 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms. 1 and A 2 may be the same or different. Examples of the hydrocarbon group having 1 to 10 carbon atoms include the above A 3 Among the hydrocarbon groups mentioned in the explanation of the above, examples include hydrocarbon groups having a carbon number of 1 to 10. l is an integer of 1 to 3, and is preferably 1.

[0038] [Harmful fungus control agent] The harmful fungi control agent of the present invention contains the fluorine-containing pyrimidine compound or a salt thereof of the present invention as an active ingredient. The harmful fungi control agent of the present invention may contain one or more of the fluorine-containing pyrimidine compounds or salts thereof.

[0039] When the harmful fungi control agent of the present invention contains a salt of the fluorine-containing pyrimidine compound of the present invention, examples of the salt of the fluorine-containing pyrimidine compound of the present invention include hydrochloride, hydrobromide, acetate, sulfate and the like.

[0040] The harmful fungal control agent of the present invention is particularly suitable for controlling numerous fungi on various cultivated plants such as wheat, rye, barley, oats, rice, corn, pasture grass, bananas, cotton, soybeans, coffee plants, sugarcane, grape vines, fruit trees and ornamental plants; vegetables such as cucumbers, beans, tomatoes, potatoes and gourds; and the seeds of these plants.

[0041] The harmful fungi control agent of the present invention is particularly suitable for controlling the following plant diseases caused by harmful fungi: Rice blast disease (Primularia oryzae), brown spot disease (Cochliobolus miyabeanus), sheath blight disease (Rizoctonia solani), etc.; Powdery mildew (Erysiphe graminis), Gibberella zeae, (red) rust (Puccinia striiformis, P.graminis, P.recondita, P.hordei), snow rot (Typhula sp., Micronectriella nivalis), naked smut (Ustilago tritici, U. nuda), Tilletia caries, Pseudocercosporella herpotrichoide, Rhynchosporium secalis, Septoria tritici, Leptosphaeria nodorum, Pyrenophora teres, Helminthosporium zonatum Ikata) etc; Citrus black spot (Diaporthe citri), common scab (Elsinoe fawcetti), fruit rot (Penicillium digitatum, P. italicum), brown rot (Phytophthora citrophthora, P.nicotianae), black spot (Phyllostictina citricarpa), canker (Xanthomonas citri), etc.; Monilinia mali, canker (Valsa mali), powdery mildew (Podosphaera leucotricha), leaf spot (Alternaria mali), black spot (Venturia inaequalis), black spot (Mycospherella pomi), anthracnose (Colletotrichum acutatum), ring spot (Botryosphaeria berengeriana), red spot (Gymnosporangium yamadae), brown spot (Monilinia fructicola), etc. of apple; Pear black spot (Venturia nashicola, V. pirina), black spot (Alternaria kikuchiana), red spot (Gymnosporangium haraeanum), brown spot (Monilinia fructicola), etc.; Peach brown spot (Monilinia fructicola), black spot (Cladosporium caepophilum), Phomopsis rot (Phomopsis sp.), etc.; Grape rot (Elinoe ampelina), late rot (Colletotrichum acutatum), powdery mildew (Uncinula necaator), rust (Phakopsora ampelopsidis), black rot (Guignardia bidwellii), downy mildew (Plasmopara viticola), gray spot (Monilinia fructigena), black spot (Cladosporium viticolum), gray mold (Botrytis cinerea), etc.; Anthracnose of persimmon (Gloeosporium kaki), leaf spot (Cercospora kaki, Mycoshaerella nawae), anthracnose of cucurbits (Colletotrichum lagenarium), powdery mildew (Sphaerotheca fuliginea, Oidiopsis taurica), vine wilt (Didymella bryoniae), vine splitting (Fusarium oxysporum), downy mildew (Pseudoperonospora cubensis), late blight (Phytophthora sp.), damping-off (Pythium sp.), etc.; Tomato leaf spot disease (Alternaria solani), leaf mold disease (Cladosporium fulvum), late blight (Phytophthora infestans), etc.; Brown spot of eggplant (Phomopsis vexans), powdery mildew (Erysiphe cichoracearum), etc.; Black spot disease (Alternaria japonica), white spot disease (Cercosporella brassicae), soft rot disease (Erwinia carotovora) of cruciferous vegetables; Onion rust (Puccinia allii), etc.; Soybean purple spot (Cercospora kikuchii), black rot (Elsinoe glycines), black spot (Diaporthe phaseolorum var. sojae), etc.; Anthracnose of beans (Colletotrichum lindemthianum), etc.; Black spot disease (Cercospora personata) and brown spot disease (Cercospora arachidicola) of peanut; Powdery mildew of pea (Erysiphe pisi), etc.; Potato summer blight (Alternaria solani), late blight (Phytophthora infestans), leaf rot fungus (Rhizoctonia solani), etc.; Powdery mildew of strawberry (Sphaerrotheca humuli), etc.; Tea net blight (Exobasidium reticulatum), white spot (Elsinoe leucospila), etc.; Tobacco red spot (Alternaria longipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), late blight (Phytophthora nicotianae), wildfire blight (Pseudomonus syringae), etc; Brown spot disease (Cercospora beticola) and damping-off disease (Aphanomyces cochliodes) of sugar beet; Rose black spot (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa), etc.; Chrysanthemum brown spot (Septoria chrysanthemi-indici), white rust (Puccinia horiana), etc.; Gray mold (Botrytis cinerea) and stem rot (Sclerotinia sclerotiorum) of various crops.

[0042] The harmful fungi control agent of the present invention is particularly suitable for controlling fungi and molds that cause plant diseases such as late blight of tomatoes, brown rust of wheat, powdery mildew of cucumbers, gray mold of cucumbers and kidney beans, and leaf rot of kidney beans.

[0043] When the harmful fungus control agent of the present invention is actually applied, the fluorine-containing pyrimidine compound of the present invention or its salt may be used in a pure form without adding other components, or may be used in the form that general agricultural chemicals can take, that is, in the form of solids such as granules, powders, broad-area spraying agents or dusting products; or in the form of liquids such as wettable powders, emulsifiable concentrates, water-soluble concentrates, solutions, pastes, oil dispersions, dispersion preparations, emulsion preparations, oil solutions, aerosols, sprays or flowable preparations.The application form is determined by its specific purpose, but in each case, it is preferable that the fluorine-containing pyrimidine compound of the present invention or its salt is finely and uniformly dispersed.

[0044] The harmful fungi control agent of the present invention can be prepared by a known method, for example, by applying the fluorine-containing pyrimidine compound of the present invention or a salt thereof to a solvent and / or onto a solid carrier, if necessary, using an auxiliary such as an emulsifier or a dispersant.

[0045] Examples of the solvent include water, aromatic solvents (e.g., toluene, xylene, etc.), paraffins (e.g., mineral oil fractions, etc.), alcohols (e.g., methanol, butanol, pentanol, benzyl alcohol, etc.), ketones (e.g., cyclohexanone, γ-butyrolactone, etc.), pyrrolidones (e.g., NMP, NOP, etc.), acetates (e.g., glycol diacetate, etc.), glycols, fatty acid dimethylamides, fatty acids, and fatty acid esters. Two or more types of solvents may be mixed and used.

[0046] Solid carriers include mineral earths (e.g., silica gel, silicates, talc, kaolin, attaclay, limestone, lime, chalk, bolus, loess, clay, dolomide, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, and the like), ground synthetic materials, fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, or urea, and the like), products of vegetable origin (e.g., flour, bark meal, wood meal, nut meals, and the like), cellulose powders, and the like.

[0047] The emulsifiers include nonionic or anionic emulsifiers (e.g., polyoxyethylene fatty alcohol ethers, alkyl or aryl sulfonates), etc. The dispersants include lignosulfite waste liquor, and methylcellulose, etc.

[0048] The harmful fungi control agent of the present invention may contain a surfactant. Suitable surfactants include alkali metal salts, alkaline earth metal salts, or ammonium salts of compounds selected from the group consisting of lignosulfonic acid, naphthalenesulfonic acid, phenolsulfonic acid, dibutylnaphthalenesulfonic acid, alkylarylsulfonic acid, alkylsulfuric acid, alkylsulfonic acid, fatty alcohol sulfuric acid, fatty acid, and sulfated fatty alcohol glycol ether; condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde; condensation products of naphthalene or naphthalenesulfonic acid with phenol and formaldehyde; polyoxyethylene octylphenyl ether; ethers, ethoxylated isooctylphenol, octylphenol, nonylphenol, alkylphenyl polyglycol ethers, tributylphenyl polyglycol ethers, tristearylphenyl polyglycol ethers, alkylaryl polyether alcohols; alcohol and fatty alcohol / ethylene oxide condensates; ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetals, sorbitol esters, lignosulfite waste liquor, and methylcellulose.

[0049] When the harmful fungus control agent of the present invention is a directly sprayable solution, emulsion, paste, oil dispersion, etc., it is preferable that the harmful fungus control agent of the present invention contains a medium to high boiling mineral oil fraction (e.g., kerosene or diesel oil); coal tar oil; oil of vegetable or animal origin; aliphatic, alicyclic or aromatic hydrocarbon (e.g., toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalene or derivatives thereof); methanol, ethanol, propanol, butanol, cyclohexanol, cyclohexanone, isophorone; or a strongly polar solvent (e.g., dimethyl sulfoxide, N-methylpyrrolidone, water, etc.).

[0050] When the harmful fungus control agent of the present invention is a dust, a broad-area spray agent, a dustable product, or the like, the harmful fungus control agent of the present invention can be produced by mixing the fluorine-containing pyrimidine compound or a salt thereof of the present invention with the solid carrier or by grinding it simultaneously with the solid carrier.

[0051] When the harmful fungus control agent of the present invention is a granule such as a coated granule, an impregnated granule or a homogeneous granule, the harmful fungus control agent of the present invention can be produced by binding the fluorine-containing pyrimidine compound or a salt thereof of the present invention to the solid carrier.

[0052] The content of the fluorine-containing pyrimidine compound or its salt of the present invention in the harmful fungi control agent of the present invention varies depending on the formulation form, application method and other conditions. The harmful fungi control agent of the present invention may contain only the fluorine-containing pyrimidine compound or its salt of the present invention in some cases. However, the content of the fluorine-containing pyrimidine compound or its salt of the present invention in the harmful fungi control agent of the present invention is usually 0.2 to 95 mass%, preferably 0.5 to 70 mass%.

[0053] The harmful fungus control agent of the present invention has an excellent control effect when sprayed on foliage, and is applied at a concentration of, for example, 10 to 4000 ppm. Although it varies depending on the method, time and other conditions, when used as an agricultural and horticultural agent, an agent for controlling forest pests, and an agent for controlling pasture pests, it is preferably applied at a concentration of 10 to 4000 ppm. 2 The amount of active ingredient used per unit is usually 10 to 300 mg, preferably 15 to 200 mg. 2 The amount of active ingredient used is usually 2 to 200 mg, preferably 5 to 100 mg per ml. 2 The amount of active ingredient is usually 15 to 120 mg per tablet, and 1 ml per tablet when used as granules. 2 The amount of active ingredient per tablet is usually 30 to 240 mg, and when used as an emulsion, it is 1 ml. 2The amount of active ingredient per dose is usually 40 to 250 mg. However, in special cases, the amount may be less than the above range, and sometimes must be less than the above range.

[0054] Examples of methods for producing each form of the harmful fungi control agent of the present invention are shown below.

[0055] 1. Products that are diluted with water Water-soluble The fluorine-containing pyrimidine compound or a salt thereof of the present invention is dissolved in water or a water-soluble solvent, and optionally a wetting agent or other auxiliary agent may be added.

[0056] Dispersion formulation The fluorine-containing pyrimidine compound of the present invention or a salt thereof is dissolved in cyclohexanone to which a dispersant (such as polyvinylpyrrolidone) has been added, and then diluted with water to obtain a dispersion preparation.

[0057] ·emulsion The fluorine-containing pyrimidine compound or a salt thereof of the present invention is dissolved in xylene to which calcium dodecylbenzenesulfonate and castor oil ethoxylate have been added, and then diluted with water to obtain an emulsion.

[0058] Emulsion formulations The fluorine-containing pyrimidine compound or its salt of the present invention is dissolved in xylene to which calcium dodecylbenzenesulfonate and castor oil ethoxylate have been added. This mixture is introduced into water using an emulsifying device to form a homogeneous emulsion. An emulsion is obtained by diluting with water.

[0059] Flowable formulation The fluorine-containing pyrimidine compound or its salt of the present invention is milled in a ball mill under stirring with the addition of a dispersant or wetting agent and water or an organic solvent to obtain a fine suspension of the active compound. Dilution with water gives a stable suspension.

[0060] Water dispersible granules and water soluble granules The fluorine-containing pyrimidine compound or its salt of the present invention is finely pulverized with a dispersant and a wetting agent, and then made into a water dispersible granule or a water-soluble granule using a dedicated device (e.g., an extruder, a spray tower, a fluidized bed, etc.). A stable dispersion or solution is obtained by diluting with water.

[0061] Water-dispersible powder and water-soluble powder In a rotor-stator mill, the fluorine-containing pyrimidine compound or its salt of the present invention is milled with the addition of a dispersant, a wetting agent and silica gel. By diluting with water, a stable dispersion or solution is obtained.

[0062] 2. Products to be applied undiluted Powder The fluorine-containing pyrimidine compound or a salt thereof of the present invention is finely ground and thoroughly mixed with finely ground kaolin to obtain a dust product.

[0063] Granules The fluorine-containing pyrimidine compound or a salt thereof of the present invention is finely ground and combined with a carrier. In this case, the extrusion method, the spray drying method, or the fluidized bed method can be used. This gives granules that can be applied without dilution.

[0064] ·Solution (ULV solution) The fluorine-containing pyrimidine compound or a salt thereof of the present invention is dissolved in an organic solvent (e.g., xylene, etc.), thereby obtaining a product that can be applied without dilution with water.

[0065] The harmful fungi control agent of the present invention can be used by spraying, atomizing, dusting, wide-area spraying, watering, etc. The form in this case can be selected from the above-mentioned forms according to the purpose. In any case, it is preferable to use the fluorine-containing pyrimidine compound or its salt of the present invention in a form that can be reliably and as finely dispersed as possible.

[0066] Aqueous application forms can be prepared by adding water to emulsifiable concentrates, pastes or wettable powders (e.g., dusting powders, oil-based dispersions). Emulsifiable concentrates, pastes or wettable powders can be prepared by homogenizing the fluorine-containing pyrimidine compound of the present invention or its salt with a wetting agent, tackifier, dispersant or emulsifier, either directly or after dissolving in oil or a solvent. Alternatively, a concentrate can be prepared consisting of the fluorine-containing pyrimidine compound of the present invention or its salt, a wetting agent, tackifier, dispersant or emulsifier, and, if necessary, a solvent or oil, and such a concentrate is suitable for dilution with water.

[0067] When the harmful fungus control agent of the present invention is used as a ready-to-use preparation, the concentration of the fluorine-containing pyrimidine compound or a salt thereof of the present invention can be set within a relatively wide range, but is generally 0.0001 to 10 mass%, preferably 0.01 to 1 mass%.

[0068] If necessary, various types of oils, wetting agents, adjuvants, etc. may be added to the harmful fungi control agent of the present invention immediately before use (tank mix). These can be added in an amount of, for example, 0.1 to 10 parts by mass per part by mass of the harmful fungi control agent of the present invention.

[0069] The harmful fungus control agent of the present invention is sufficiently effective even when used alone in the application form as a harmful fungus control agent. However, in addition to the harmful fungus control agent of the present invention, other drugs such as herbicides, insecticides, attractants, growth regulators, disease control agents (fungicides, etc.), fertilizers, etc. can also be present together. Therefore, the harmful fungus control agent of the present invention may be used in combination with the fluorine-containing pyrimidine compound or its salt of the present invention and at least one other drug such as herbicide, insecticide, attractant, growth regulator, disease control agent (fungicide, etc.), fertilizer, etc. In particular, the fluorine-containing pyrimidine compound or its salt of the present invention tends to have a broadened fungicidal activity spectrum by combining with other fungicides.

[0070] Representative examples of other drugs that can be contained in the harmful fungi control agent of the present invention are shown below. However, the following descriptions are intended to exemplify other drugs that can be combined with the fluorine-containing pyrimidine compound or a salt thereof of the present invention, and the other drugs are not limited to these.

[0071] Disease control agents: Copper disease control agents such as basic copper chloride, cupric hydroxide, basic copper sulfate, anhydrous copper sulfate, copper oxine, copper nonylphenol sulfonate, DEBDC, and quicklime; Inorganic agents such as sulfur, lime polysulfide, zinc sulfate, sodium bicarbonate, potassium bicarbonate, and sodium hypochlorite; Organosulfur agents such as zineb, maneb, manzeb, ambam, polycarbamates, organosulfur nickel salts, propineb, ziram, thiuram, and thiadiazines; Organophosphates such as IBP, EDDP, tolclofos-methyl, and fosetyl; Melanin synthesis inhibitors such as fthalide, tricyclazole, pyroquilon, carpropamid, diclocymet, and fenoxanil; Benzimidazoles such as benomyl, thiophanate methyl, and thiazendazole; Dicarboximides such as iprodione and procymidone; Carboxanilides such as oxycarboxin, mepronil, flutolanil, furametpyr, and thifluzamide; Phenylamide agents such as metalaxyl and oxadixyl; Sterol biosynthesis inhibitors such as triadimefon, bitertanol, fenbuconazole, myclobutanil, hexaconazole, tebuconazole, propiconazole, difenoconazole, ipconazole, imibenconazole, cyproconazole, triflumizole, prochloraz, pefurazoate, oxpoconazole fumarate, fenarimol, pyrifenox, triforine, tetraconazole, simeconazole; Strobilurins such as azoxystrobin, kresoxim-methyl, trifloxystrobin, metoinostrobin, pyraclostrobin, orysastrobin, picoxystrobin, and fluoxastrobin; Anilinopyrimidines such as pyrimethanil, mepanipyrim, and diprodinil; synthetic antibacterials such as tecloftalam, oxolinic acid; Other synthetic disease control agents such as probenazole, acimenzolar-S-methyl, isoprothiolane, ferimzone, diclomedine, pencycuron, fluorimide, captan, dichlofluanid, tolylfluanid, chlorothalonil, dithianone, quinomethionate, dinocap, dimethirimol, diflumetrim, fludioxonil, benthiazole, triazine, fluazinam, cymoxanil, famoxadone, iminoctadine triacetate, iminoctadine albesilate, propamocarb hydrochloride, dimethomorph, diazofamid, fenhexamid, diethoxyfencarb, thiadinil, benthiavalicarb isopropyl, ethaboxam; Antibiotics such as blasticidin S, kasugamycin, polyoxin, validamycin A, streptomycin, oxytetracycline, and mildiomycin; Natural product-based agents such as machine oil, rapeseed oil, and soy lecithin; Biological agents such as Lentinula edodes mycelium extract, live Trichoderma fungus, Agrobacterium radiobacter, non-pathogenic Erwinia carotovora subsp., Bacillus subtilis, Talaromyces flavus, Pseudomonas fluorescens, Pseudomonas CAB-2, non-pathogenic Fusarium oxysporum, etc.; Soil disease control agents such as flusulfamide, hydroxyisoxazole, eclumezole, dazomet, chloroneb, metasulfocarb, methyl isothiocyanate, DD, methyl bromide, chloropicrin, and carbam.

[0072] Insecticides (insect and mite control agents): Organophosphate insecticides such as cyanophos, fenthion, fenitrothion, diclofenthion, pirimiphos-methyl, diazinon, quinalphos, isoxathion, pyridaphenthion, chlorpyrifos-methyl, chlorpyrifos, vamidothion, malathion, phenthoate, dimethoate, thiometon, disulfoton, phosalone, methidathion, prothiofos, sulprofos, profenofos, pyraclofos, dichlorvos, monocrotophos, naled, tetrachlorvinphos, dimethylvinphos, chlorfenvinphos, propaphos, acephate, isofenphos, trichlorfon, EPN, ethion; Carbamate insect control agents such as carbaryl, isoprocarb, fenobucarb, propoxur, XMC, ethiofencarb, pirimicarb, bendiocarb, carbosulfan, benfuracarb, furathiocarb, methomyl, oxamyl, thiodicarb, and alanycarb; Pyrethroid insect control agents such as allethrin, resmethrin, permethrin, cymermethrin, cyhalothrin, cyfluthrin, tralomethrin, fenpropathrin, bifenthrin, fenvalerate, flucythrinate, fluvalinate, acrinathrin, cycloprothrin, etofenprox, silafluofen, and tefluthrin; Nereistoxin-based insect control agents such as cartap, thiocyclam, and bensultap; Neochycotinoid insect control agents such as imidacloprid, acetamiprid, nitenpyram, thiacloprid, thiamethoxam, clothianidin, and dinotefuran; Insect growth regulators such as buprofezin, isoprothionlan, diflubenzuron, teflubenzuron, hexaflumuron, lufenuron, flufenoxuron, chlorfluazuron, tebufenozide, chromafenozide, and cyromazine; Other synthetic pest control agents such as benzoepin, fipronil, pymetrozine, chlorfenapyr, diafenthiuron, indoxacarb, emamectin benzoate, sodium oleate, potassium oleate, DBEDC, metaldehyde, adhesives, methoxyfenozide, tolfenpyrad; Natural pest control agents such as pyrethrins, rotenone, nicotine, machine oil, rapeseed oil, soy lecithin, starch, fatty acid glycerides, propylene glycol mono-fatty acid esters, and diatomaceous earth; Acaricides such as Kelthane, Phenisobromorate, Tetradifon, Propargite, Quinomethionate, Amitraz, Fenothiocarb, Hexythiazox, Fenbutatin Oxide, Dienochlor, Fenpyroximate, Tebufenpyrad, Fluazinam, Pyridaben, Pyrimidifen, Clofentezine, Etoxazole, Dinocap, Halfenprox, Polynactin Complex, Milbemectin, Bialaphos, Acequinocyl, Bifenazate, Fluacrypyrim; Nematocides such as DD, DCIP, dazomet, benomyl, ethoprophos, fosthiazate, mesulfenphos, morantel tartrate, cadusafos, ensallevamisole, and nemadectin; Fumigants such as methyl bromide, chloropicrin, carbam, sodium carbam, hydrocyanic acid, hydrogen phosphide, aluminum phosphide, ethylene oxide, carbon dioxide, methyl isothiocyanate, and sulfuryl fluoride; Biological pest control agents such as BT, spinosad, Beauveria brongniartii, Beauveria bassiana, Verticillium lecanii, Steinernema carpocapsae, Steinernema kushidai, Steinernema glacerai, Monacrosporium phymatopagum, Pasteuria penetrans, Pecilomyces fumosoroseus, and natural enemies (Phytoseiulus persimmon, Phytoseiulus cucumeris, Aphelenchus koremani, Aphelenchus vulgaris, Aphelenchus desertis, Aphelenchus isaea, Aphididae, Orius punctatus, Orius strifegus, and Chrysophyllaceae).

[0073] Attractant: Insect sex pheromone attractants such as Litrur, Beetarmylure, Diamolure, Peachflua, Tetradecenyl acetate, Tortrilua, Pirimalure, Orifleur, Cheritrur, Bulwellua, Roukarua, Fisirua, Ochimeranorua, Sachimeranorua, Sweetbilua, Fallwebulua; Other attractants such as pinene oil, methyl eugenol, protein hydrolysates, curua, and methyl phenyl acetate; Rodenticides such as monofluoroacetate, coumarolaryl, warfarin, chlorophacinone, diphacinone, zinc phosphide, and thallium sulfate; Lime nitrogen, etc.

[0074] Herbicides: Phenoxy herbicides such as 2,4-PA, MCPA, MCPB, MCPP, triclopyr, clomeprop, naproanilide, fenoxaprop-ethyl, cyhaloprop-butyl, fluazipop, and quizalop-ethyl; Carbamate herbicides such as IPC, phenmedipham, desmedipham, benthiocarb, orthobencarb, esprocarb, molinate, dimepiperate, and pyributicarb; Acid amide herbicides such as DCPA, alachlor, pretilachlor, metolachlor, butachlor, dimethenamid, thenylchlor, bromobutide, etobenzanide, diflufenican, mefenacet, napropamide, cafenstrole, propyzamide, isoxaben, and asulam; urea herbicides such as DCMU, linuron, siduron, dymuron, cumyluron, carbutilate, isouron, and tebuthiuron; Sulfonylurea agents such as bensulfuron methyl, ethoxysulfuron, pyrazosulfuron ethyl, azimsulfuron, halosulfuron methyl, flazasulfuron, cinosulfuron, nicosulfuron, rimsulfuron, thifensulfuron methyl, imazosulfuron, metsulfuron methyl, and cyclosulfamuron; Pyrimidyloxybenzoic acid herbicides such as pyriminobac-methyl and bispyribac-sodium; Triazine herbicides such as CAT, atrazine, simetryn, ametryn, prometryn, dimethametryn, cyanazine, triaziflam, and metribuzin; Diazine herbicides such as terbacil, bromacil, butafenacil, lenacil, PAC, bentazon, and pyridate; diazole herbicides such as pyrazolate, pyrazoxyfen, benzofenap, and pyraflufen-ethyl; Bipyridylium herbicides such as paraquat and diquat; Dinitroaniline herbicides such as trifluralin, beslosin, prodiamine, pendimethalin, and oryzalin; Aromatic carboxylic acid herbicides such as MDBA, imazapyr, imazaquin, imazaquin ammonium salt, dithiopyr, TCTP, imazamox ammonium salt, and fentrazamide; Aliphatic herbicides such as pelargonic acid, DPA, and tetrapion; Organophosphate herbicides such as piperophos, amiprophos-methyl, butamiphos, and SAP; Amino acid based herbicides such as glyphosate isopropylamine salt, glyphosate ammonium salt, glyphosate trimesium salt, glyphosate potassium salt, bialaphos, glufosinate; Other organic herbicides such as ioxynil, bifenox, DBN, DCBN, sethoxydim, clethodim, tepraloxydim, CAN, indanofan, chlorphthalim, endothal disodium salt, benfuresate, florasulam, pentoxazone, oxaziclomefone, carfentrazone-ethyl, flumioxazin, benzobicyclon; Inorganic herbicides such as cyanates.

[0075] The other agents are preferably added in an amount that allows each agent to fully exert the desired effect, depending on the type of the agent and the type of the harmful fungi control agent of the present invention to be used in combination. For example, the other agents are added in an amount of, for example, 0.1 to 1000% by mass, preferably 0.5 to 500% by mass, based on the mass of the harmful fungi control agent.

[0076] [Method of producing fluorine-containing pyrimidine compound] Specific examples of the method for producing the fluorine-containing pyrimidine compound of the present invention include the following methods (a) to (f).

[0077] (a) A method comprising the step of reacting aniline represented by the following general formula (4) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (5) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1):

[0078] [ka]

[0079] (In the above general formula, W, X, Y, Z and n are as defined above, and X 1 represents a halogen atom.)

[0080] (b) A method comprising the step of reacting aniline represented by the following general formula (4) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (6) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2):

[0081] [ka]

[0082] (In the above general formula, W, X, Y, Z, X 1 and n is as defined above.

[0083] (c) A method comprising the step of reacting aniline represented by the following general formula (4) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (7) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3):

[0084] [ka]

[0085] (In the above general formula, W, X, Y, Z, X 1and n is as defined above.

[0086] (d) A method comprising the step of reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (9) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1):

[0087] [ka]

[0088] (In the above general formula, W, X, Y, Z and n are as defined above, and X 2 represents a halogen atom.)

[0089] (e) A method comprising a step of reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (10) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2):

[0090] [ka]

[0091] (In the above general formula, W, X, Y, Z, X 2 and n is as defined above.

[0092] (f) A method comprising a step of reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (11) in an organic solvent in the presence of a basic substance to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3):

[0093] [ka]

[0094] (In the above general formula, W, X, Y, Z, X 2 and n is as defined above.

[0095] The compound represented by the general formula (4) is aniline when n = 0, and is an aniline derivative when n = 1 to 3. The compound represented by the general formula (8) is an aryl halide when n = 0, and is an aryl halide derivative when n = 1 to 3.

[0096] The fluorine-containing pyrimidine compounds represented by the above general formulae (5) to (7) can be obtained by reacting a fluoroisobutylene derivative represented by the following general formula (12) or a fluoroisobutane derivative represented by the following general formula (13) with an amidine derivative represented by the following general formulae (14) to (16), as shown in the following reaction formula. The reaction temperature in the reaction is preferably 0 to 100° C., more preferably 5 to 50° C., and even more preferably 10 to 20° C. The reaction time is preferably 0.5 to 48 hours, more preferably 1 to 36 hours, and even more preferably 2 to 12 hours.

[0097] [ka]

[0098] [ka]

[0099] [ka]

[0100] (In the above general formula, W, X, Y and X 1 is as defined above, and Z 1 is a halogen atom, -OA 1 , -SO p A 1 (p is an integer from 0 to 3), or -NA 1A 2 A stands for 1 , A 2 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms.)

[0101] The fluorine-containing pyrimidine compounds represented by the above general formulas (9) to (11) each have a halogen atom (X) located at the 6-position of the pyrimidine ring of the fluorine-containing pyrimidine compound represented by the above general formulas (5) to (7), as shown in the following reaction formula: 1 ) with ammonia as a nucleophilic agent to replace it with an amino group (-NH2). The reaction temperature during the reaction is preferably 20 to 150°C, and the reaction time is preferably 1 to 24 hours. A base such as triethylamine may be used as a reaction aid.

[0102] [ka]

[0103] (In the above general formula, W, X, Y and X 1 is as defined above.)

[0104] Examples of organic solvents that can be used in the above methods (a) to (f) include ethers such as tetrahydrofuran, diethyl ether, dioxane, monoglyme, diglyme, triglyme, and tetraglyme; aromatic hydrocarbons such as benzene, toluene, and xylene; nitriles such as acetonitrile; and aprotic polar solvents such as dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethyleneurea, tetramethylurea, dimethylsulfoxide, and sulfolane.

[0105] Examples of basic substances that can be used in the above methods (a) to (f) include alkali metal / alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, magnesium hydroxide, barium hydroxide, etc.; alkali metal / alkaline earth metal carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.; metal hydrides such as sodium hydride, potassium hydride, calcium hydride, etc.; and tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, diazabicycloundecene, N,N-dimethylaniline, etc.

[0106] The reaction temperature in the above methods (a) to (f) is preferably −20° C. or higher and lower than the boiling point of the organic solvent, more preferably 25 to 100° C., and even more preferably 80 to 90° C. The reaction time in the above methods (a) to (f) is preferably 0.5 to 48 hours, more preferably 1 to 36 hours, and even more preferably 20 to 25 hours.

[0107] Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment, and includes all aspects included in the concept of the present invention and the scope of the claims, and can be modified in various ways within the scope of the present invention. EXAMPLES

[0108] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0109] Example 1 <Production of 6-methoxy-N-phenyl-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.5g (1.8mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 6ml of acetonitrile, 0.2g (2.4mmol) of aniline and 0.4g (4.1mmol) of triethylamine were added, and the mixture was stirred for 22.3 hours under heating and reflux. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.3g (1.0mmol) of 6-methoxy-N-phenyl-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 52.2%.

[0110] [ka]

[0111] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.81-8.83(m,1H),8.32(d,J=8.0Hz,1H),7.81(ddd,J=7.6,7 .6,1.2Hz,1H),7.63(d,J=7.6Hz,2H),7.38-7.44(m,4H),7.16-7.21(m,1H),4.22(s,3H) APCI-MS(m / z):347.7[M+H] +

[0112] Example 2 <Production of 6-methoxy-N-(3-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> Dissolve 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.2 g (2.2 mmol) of m-toluidine and 0.4 g (4.1 mmol) of triethylamine, and stir at reflux for 19.5 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.4 g (1.1 mmol) of 6-methoxy-N-(3-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 58.1%.

[0113]

Chemical formula

[0114] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.81 - 8.83 (m, 1H), 8.32 - 8.35 (m, 1H), 7.78 - 7.83 (m, 1H), 7.45 - 7.48 (m, 2H), 7.35 - 7.41 (m, 2H), 6.98 - 7.02 (m, 1H), 4.22 (s, 3H), 2.41 (s, 3H) APCI-MS (m / z): 361.6 [M + H] +

[0115] (Example 3) <Synthesis of N-(4-butylphenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> 0.5g (1.8mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 6ml of acetonitrile, 0.4g (2.5mmol) of 4-butylaniline and 0.4g (4.4mmol) of triethylamine were added, and the mixture was stirred for 19.5 hours under heating and reflux. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.4g (1.1mmol) of N-(4-butylphenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 59.4%.

[0116] [ka]

[0117] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.81(ddd,J=4.6,1.8,0.9Hz,1H),8.32(ddd,J=8.0,1.2,1.2H z,1H),7.80(ddd,J=8.0,7.3,1.8Hz,1H),7.52(d,J=8.3Hz,2H),7.39(ddd,J=7.6,4.6,1. 2Hz,1H),7.23-7.39(m,1H),7.21(d,J=8.3Hz,2H),7.64(d,J=7.6Hz,2H),4.21(s,3H),2. 63(t,J=7.6Hz,2H),1.58-1.66(m,2H),1.38(tq,J=7.3,7.3Hz,2H),0.95(t,J=7.3Hz,3H) APCI-MS(m / z):403.6[M+H] +

[0118] Example 4 <Production of 6-methoxy-N-(3,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.5 g (1.9 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine was dissolved in 6 ml of acetonitrile, 0.3 g (2.2 mmol) of 3,4-xylidine and 0.4 g (4.3 mmol) of triethylamine were added, and the mixture was stirred under heating reflux for 28.6 hours. After air-cooling to room temperature, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then subjected to column purification to obtain 0.5 g (1.3 mmol) of 6-methoxy-N-(3,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 68.0%.

[0119]

Chemical formula

[0120] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.81 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.31 - 8.34 (m, 1H), 7.80 (ddd, J = 8.0, 7.6, 1.8 Hz, 1H), 7.36 - 7.40 (m, 3H), 7.30 - 7.35 (m, 1H), 7.16 (d, J = 8.0, 1H), 4.21 (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H) APCI-MS (m / z): 375.5 [M + H] +

[0121] (Example 5) (Production of N-(2-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine) Dissolve 0.5 g (1.9 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.3 g (2.5 mmol) of 2-fluoroaniline and 0.4 g (4.3 mmol) of triethylamine, and stir at reflux for 28.6 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.1 g (0.2 mmol) of N-(2-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 10.4%.

[0122]

Chemical formula

[0123] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.83 (ddd, J = 4.6, 1.8, 0.9 Hz, 1H), 8.47 (d, J = 8.3, 8.0, 1.5 Hz, 1H), 8.32 - 8.35 (m, 1H), 7.83 (ddd, J = 8.0, 7.6, 1.8 Hz, 1H), 7.67 (br, 1H), 7.41 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.20 - 7.26 (m, 1H), 7.08 - 7.19 (m, 2H), 4.22 (s, 3H) APCI-MS (m / z): 365.6 [M + H] +

[0124] (Example 6) (Preparation of N-(3-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine) Dissolve 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.3 g (2.3 mmol) of 3-fluoroaniline and 0.4 g (4.3 mmol) of triethylamine, and stir at reflux for 28.6 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.2 g (0.5 mmol) of N-(3-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 26.1%.

[0125]

Chemical Structure

[0126] The analysis results were as follows. 1 H NMR(400MHz,CDCl3)δppm:8.84(ddd,J=4.6,1.8,0.9Hz,1H),8.34 - 8.37(m,1H),7.84(ddd,J=8.0,7.6,1.8Hz,1H),7.77(ddd,J=11.3,2.5,2.1Hz,1H),7.43 - 7.49(m,1H),7.42(ddd,J=7.6,4.9,1.2Hz,1H),7.32(m,1H),7.24(dd,J=8.2,1.2Hz,1H),6.87(ddd,J=8.3,2.5,0.9Hz,1H),4.22(s,3H) APCI-MS(m / z):365.5[M + H] +

[0127] (Example 7) <Synthesis of N-(4-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine was dissolved in 6 ml of acetonitrile, 0.3 g (2.3 mmol) of 4-fluoroaniline and 0.4 g (4.3 mmol) of triethylamine were added, and the mixture was stirred under heating reflux for 28.6 hours. After air-cooling to room temperature, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, the filtrate was concentrated, and column purification was performed to obtain 0.2 g (0.5 mmol) of N-(4-fluorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 26.1%.

[0128] [Chemical formula]

[0129] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.81 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.26 (ddd, J = 8.0, 8.0, 0.9 Hz, 1H), 7.80 (ddd, J = 7.6, 7.6, 1.8 Hz, 1H), 7.54 - 7.59 (m, 2H), 7.40 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.30 - 7.37 (m, 1H), 7.10 (dd, J = 8.9, 8.6 Hz, 2H), 4.22 (s, 3H) APCI-MS (m / z): 365.6 [M + H] +

[0130] (Example 8) [Production of N-(2,6-dichloro-4-nitrophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine] 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine was dissolved in 6 ml of acetonitrile, 0.5 g (2.2 mmol) of 2,6-dichloro-4-nitroaniline and 0.6 g (4.2 mmol) of DBU were added, and the mixture was stirred under heating to reflux for 22.3 hours. After air-cooling to room temperature, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, the filtrate was concentrated, and column purification was carried out to obtain 0.06 g (0.1 mmol) of N-(2,6-dichloro-4-nitrophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 7.6%.

[0131]

Chemical formula

[0132] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.76 - 8.78 (m, 1H), 8.34 (s, 2H), 7.95 (d, J = 8.0 Hz, 1H), 7.74 (ddd, J = 8.0, 7.6, 1.5 Hz, 1H), 7.37 (ddd, J = 7.8, 4.9, 1.4 Hz, 1H), 7.26 (br, 1H), 4.26 (s, 3H) APCI-MS (m / z): 460.5 [M] +

[0133] (Example 9) <Production of N-[2-nitro-4-(trifluoromethyl)phenyl]-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> Dissolve 0.5 g (1.9 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.5 g (2.2 mmol) of 4-amino-3-nitrobenzotrifluoride and 0.4 g (4.1 mmol) of triethylamine, and stir at reflux for 20.3 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.1 g (0.2 mmol) of N-[2-nitro-4-(trifluoromethyl)phenyl]-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 12.6%.

[0134]

Chemical formula

[0135] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 10.95 - 11.01 (m, 1H), 9.22 (d, J = 8.9 Hz, 1H), 8.85 (ddd, J = 4.6, 1.8, 0.9 Hz, 1H), 8.53 (d, J = 1.5 Hz, 1H), 8.39 - 8.42 (m, 1H), 7.93 (dd, J = 9.2, 2.1 Hz, 1H), 7.89 (ddd, J = 8.0, 7.6, 1.8 Hz, 1H), 7.47 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 4.25 (s, 3H) APCI-MS (m / z): 460.7 [M + H] +

[0136] (Example 10) <Production of N-(2,4-dinitrophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> Dissolve 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.4 g (2.3 mmol) of 2,4-dinitroaniline and 0.5 g (4.7 mmol) of triethylamine, and stir at reflux for 20.3 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.1 g (0.3 mmol) of N-(2,4-dinitrophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 16.8%.

[0137]

Chemical formula

[0138] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 11.20 - 11.25 (m, 1H), 9.39 (d, J = 9.5 Hz, 1H), 9.17 (d, J = 2.5 Hz, 1H), 8.86 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.54 (dd, J = 9.5, 2.8 Hz, 1H), 8.41 - 8.44 (m, 1H), 7.90 (ddd, J = 8.0, 7.6, 1.8 Hz, 1H), 7.49 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 4.27 (s, 3H) APCI-MS (m / z): 437.4 [M + H] +

[0139] (Example 11) <Production of N-[5-chloro-2-nitro-4-(trifluoromethyl)phenyl]-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> 0.5g (1.9mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 6ml of acetonitrile, 0.5g (2.2mmol) of 5-chloro-2-nitro-4-(trifluoromethyl)aniline and 0.4g (4.4mmol) of triethylamine were added, and the mixture was stirred for 66.4 hours under heating and reflux. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.2g (0.4mmol) of N-[5-chloro-2-nitro-4-(trifluoromethyl)phenyl]-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 20.6%.

[0140] [ka]

[0141] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:10.16-11.21(m,1H),9.74(s,1H),8.88(ddd,J=4.6,1.5,0.9Hz,1H),8.62(s,1H),8.4 5(ddd,J=8.0,0.9,0.9Hz,1H),7.91(ddd,J=7.6,7.6,1.5Hz,1H),7.49(ddd,J=7.6,4.9,1.2Hz,1H),4.26(s,3H) APCI-MS(m / z):494.8[M+H] +

[0142] Example 12 <Production of 6-methoxy-N-(2,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 6 ml of acetonitrile, 0.3 g (2.3 mmol) of 2,4-dimethylaniline and 0.4 g (4.2 mmol) of triethylamine were added, and the mixture was stirred under heating reflux for 25.4 hours. After air-cooling to room temperature, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, the filtrate was concentrated, and column purification was carried out to obtain 0.1 g (0.3 mmol) of 6-methoxy-N-(2,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 14.1%.

[0143]

Chemical formula

[0144] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.78 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.16 (ddd, J = 8.0, 8.0, 1.8 Hz, 1H), 7.75 (ddd, J = 8.0, 1.2, 0.9 Hz, 1H), 7.59 - 7.61 (m, 2H), 7.36 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.12 - 7.17 (m, 1H), 7.12 - 7.06 - 7.11 (m, 2H), 4.22 (s, 3H), 2.36 (s, 3H), 2.24 (s, 3H) APCI-MS (m / z): 375.8 [M + H] +

[0145] (Example 13) <Production of N-(4-chlorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> Dissolve 0.5 g (1.8 mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)pyrimidine in 6 ml of acetonitrile, add 0.3 g (2.3 mmol) of 4-chloroaniline and 0.4 g (4.1 mmol) of triethylamine, and stir at room temperature for 18.6 hours, at 70 °C for 2.7 hours, and under reflux heating for 19.6 hours. After air-cooling to room temperature, add water to the reaction solution, extract with ethyl acetate, and dry the organic phase over sodium sulfate. Filter the dried organic phase, concentrate the filtrate, and perform column purification to obtain 0.3 g (0.8 mmol) of N-(4-chlorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 43.8%.

[0146] [Chemical Formula]

[0147] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.82 (ddd, J = 4.6, 1.8, 0.9 Hz, 1H), 8.30 (ddd, J = 8.0, 0.9, 0.9 Hz, 1H), 7.83 (ddd, J = 8.0, 7.6, 1.8 Hz, 1H), 7.58 - 7.62 (m, 2H), 7.42 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.35 - 7.39 (m, 3H), 7.21 (d, J = 8.3 Hz, 2H), 4.22 (s, 3H) APCI-MS (m / z): 381.6 [M + H] +

[0148] (Example 14) [Production of N-(2,4-dichlorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine] 0.5g (1.8mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 6ml of acetonitrile, 0.4g (2.3mmol) of 2,4-dichloroaniline and 0.4g (6.9mmol) of sodium hydride were added, and the mixture was stirred for 19.2 hours under heating and reflux. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.1g (0.3mmol) of N-(2,4-dichlorophenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 17.1%.

[0149] [ka]

[0150] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.83(ddd,J=4.6,1.8,0.9Hz,1H),8.58(d,J=8.9Hz,1H),8.32-8.35(m,1H),7.95 -8.01(m,1H),7.85(ddd,J=8.0,7.6,1.8Hz,1H),7.42-7.45(m,2H),7.35(dd,J=8.9,2.5Hz,1H),4.22(s,3H) APCI-MS(m / z): 416.5[M+H] +

[0151] Example 15 <Production of 6-methoxy-N-(4-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.24g (2.22mmol) of p-toluidine was dissolved in 6.1ml of DMF, 0.09g (2.27mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. Then, 0.50g (1.83mmol) of 6-fluoro-4-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at 100°C for 18.8 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.31g (0.87mmol) of 6-methoxy-N-(4-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 48%.

[0152] [ka]

[0153] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.81(m,1H),8.31(d,J=8.0Hz,1H),7.80(ddd,J=7.6,7.6,1.8Hz,1 H),7.49(d,J=8.2Hz,2H),7.32-7.40(m,2H),7.21(d,J=8.3Hz,2H),4.21(s,3H),2.37(s,3H) APCI-MS(m / z):360.1[M+H] +

[0154] (Example 16) <Production of 6-chloro-N-phenyl-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.05g (0.2mmol) of 6-chloro-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine was dissolved in 2ml of acetonitrile, 0.02g (0.2mmol) of chlorobenzene and 0.01g (0.3mmol) of sodium hydride were added, and the mixture was stirred at 50°C for 19.2 hours. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.01g (0.02mmol) of 6-chloro-N-phenyl-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure. The yield was 12.5%.

[0155] [ka]

[0156] The analysis results were as follows: APCI-MS(m / z):451.7[M+H] +

[0157] (Example 17) <Production of 6-methoxy-N-phenyl-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.04g (0.39mmol) of aniline was dissolved in 5.0ml of DMF, 0.02g (0.58mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 1 hour. Then, 0.10g (0.37mmol) of 4-fluoro-6-methoxy-2-(4-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 16.7 hours and at 70°C for 8 hours, and further stirred at room temperature for 16 hours, and then stirred at 70°C for 8 hours and at 100°C for 10.5 hours. After cooling to room temperature, water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.03g (0.08mmol) of 6-methoxy-N-phenyl-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structural formula. The yield was 22%.

[0158] [ka]

[0159] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.73(m,2H), 8.14(dd,J=4.8,1.6Hz,2H), 7.41-7.55(m,4H), 7.21-7.25(m,1H), 4.16(s,3H) APCI-MS(m / z): 346.6[M+H] +

[0160] (Example 18) <Production of 6-methoxy-N-(4-methylphenyl)-2-(3-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 1.89g (17.60mmol) of p-toluidine was dissolved in 49.0ml of DMF, 0.72g (17.98mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. Then, 4.02g (14.73mmol) of 4-fluoro-6-methoxy-2-(3-pyridyl)-5-trifluoromethylpyridine was added, and the mixture was stirred at 100°C for 24 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.71g (1.98mmol) of 6-methoxy-N-(4-methylphenyl)-2-(3-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure. The yield was 13%.

[0161] [ka]

[0162] The analysis results were as follows: 1H NMR(400MHz,CDCl3) δppm: 9.52(m,1H), 8.68(dd,J=4.6,1.2Hz,1H), 8.54(ddd,J=8.0,1.5,1.5Hz,1H), 7.40(d,J=8.3Hz,2H), 7.35(dd,J=8.0,4.9Hz,1H), 7.31(br,1H), 7.21(d,J=8.3Hz,2H), 4.13(s,3H), 2.38(s,3H) APCI-MS (m / z): 360.0[M+H] +

[0163] (Example 19) <Production of 6-methoxy-N-(4-methylphenyl)-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.24g (2.27mmol) of p-toluidine was dissolved in 6.1ml of DMF, 0.09g (2.30mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. Then, 0.50g (1.82mmol) of 4-fluoro-6-methoxy-2-(4-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at 100°C for 24 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.24g (0.65mmol) of 6-methoxy-N-(4-methylphenyl)-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 36%.

[0164] [ka]

[0165] The analysis results were as follows: 1H NMR(400MHz,CDCl3) δppm: 8.73(dd,J=4.3,1.4Hz,2H), 8.13(dd,J=4.3,1.8Hz,2H), 7.41(d,J=8.3Hz,2H), 7.33(br,1H), 7.23(d,J=8.3Hz,2H), 4.16(s,3H), 2.40(s,3H) APCI-MS (m / z): 360.0[M+H] +

[0166] (Example 20) <Production of 6-chloro-N-(4-methylphenyl)-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.04g (0.36mmol) of p-toluidine was dissolved in 1.1ml of DMF, 0.02g (0.45mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. Then, 0.10g (0.34mmol) of 4,6-dichloro-2-(4-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 18.3 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.11g (0.30mmol) of 6-chloro-N-(4-methylphenyl)-2-(4-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 89%.

[0167] [ka]

[0168] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.74(dd,J=4.6,1.5Hz,2H), 8.10(dd,J=4.3,1.8Hz,2H), 7.51(br,1H), 7.39(d,J=8.3Hz,2H), 7.27(d,J=8.3Hz,2H), 2.42(s,3H) APCI-MS (m / z): 365.1[M+H] +

[0169] Example 21 <Production of 6-chloro-N-(4-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.36g (3.34mmol) of p-toluidine was dissolved in 4.0ml of DMF, 0.17g (4.25mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. 0.98g (3.34mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine dissolved in 7.0ml of DMF was added, and the mixture was stirred at room temperature for 21.7 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.89g (2.44mmol) of 6-chloro-N-(4-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 73%.

[0170] [ka]

[0171] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.84(ddd,J=4.6,1.8,0.9Hz,1H), 8.24(ddd,J=8.0,0.9,0.9Hz,1H), 7.80(ddd,J=8.0,7.6,1.8Hz,1H), 7.52(br,1H), 7.45(dd,J=8.3,1.8,1.8Hz,2H), 7.41(ddd,J=7.6,4.9,1.2Hz,1H), 7.25(d,J=9.2Hz,2H), 2.40(s,3H) APCI-MS (m / z): 365.0[M+H] +

[0172] Example 22 <Production of 6-chloro-N-(4-methylphenyl)-2-(3-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.23g (2.17mmol) of p-toluidine was dissolved in 2.0ml of DMF, 0.11g (2.63mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. 0.63g (2.16mmol) of 4,6-dichloro-2-(3-pyridyl)-5-trifluoromethylpyrimidine dissolved in 8.0ml of DMF was added, and the mixture was stirred at room temperature for 21.5 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.51g (1.40mmol) of 6-chloro-N-(4-methylphenyl)-2-(3-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure. The yield was 65%.

[0173] [ka]

[0174] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 9.45(dd,J=2.1,0.6Hz,1H), 8.72(dd,J=4.9,1.5Hz,1H), 8.56(ddd,J=8.0,2.1,1.8Hz,1H), 7.49(br,1H), 7.36-7.40(m,3H), 7.25(d,J=9.5Hz,2H), 2.40(s,3H) APCI-MS (m / z): 365.1[M+H] +

[0175] Example 23 <Production of 6-methoxy-N-(4-methylphenyl)-2-(6-n-propyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.4g (3.3mmol) of p-toluidine was dissolved in 2.0ml of DMF, 0.13g (3.3mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 35 minutes. 0.9g (2.7mmol) of 4-fluoro-6-methoxy-2-(6-n-propyl-2-pyridyl)-5-trifluoromethylpyrimidine dissolved in 7.0ml of DMF was added, and the mixture was stirred at room temperature for 51.7 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.7g (1.7mmol) of 6-methoxy-N-(4-methylphenyl)-2-(6-n-propyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 61%.

[0176] [ka]

[0177] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.14(d,J=7.6Hz,1H), 7.70(dd,J=8.0,7.6Hz,1H), 7.64(d,J=8.6Hz,2H), 7.36(br,1H), 7.25(d,J=8.3Hz,1H), 7.18(d,J=8.3Hz,2H), 4.18(s,3H), 2.90(t,J=7.6Hz,1H), 2.36(s,3H), 1.92(tq,J=7.3,7.3Hz, 2H), 1.05(t,J=7.3Hz,3H) APCI-MS(m / z): 403.0[M+H] +

[0178] (Example 24) <Production of 6-methoxy-2-(2-methoxy-5-pyridyl)-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.03g (0.3mmol) of p-toluidine was dissolved in 1.0ml of DMF, 0.02g (0.6mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. Then, 0.1g (0.3mmol) of 4-fluoro-6-methoxy-2-(2-methoxy-5-pyridyl)-5-trifluoromethylpyrimidine was added and stirred at room temperature for 25 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.002g (0.005mmol) of 6-methoxy-2-(2-methoxy-5-pyridyl)-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 2%.

[0179] [ka]

[0180] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 9.14(d,J=1.8Hz,1H), 8.44(dd,J=2.5,8.6Hz,1H), 7.40(d,J=8.3Hz,2H), 7.26(br,1H), 7.21(d,J=8.3Hz,1H), 6.78(d,J=8.3Hz,2H), 4.11(s,3H), 4.00(s,3H), 2.38(s,3H) APCI-MS (m / z): 390.5[M] +

[0181] (Example 25) <Production of 6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-2-(2-trifluoromethyl-5-pyridyl)-4-pyrimidinamine> 0.04g (0.4mmol) of p-toluidine was dissolved in 5.0ml of DMF, 0.02g (0.6mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes, then cooled to 0°C, 0.1g (0.4mmol) of 4-fluoro-6-methoxy-5-trifluoromethyl-2-(2-trifluoromethyl-5-pyridyl)pyrimidine was added, and the mixture was stirred at room temperature for 26.8 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.001g (0.002mmol) of 6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-2-(2-trifluoromethyl-5-pyridyl)-4-pyrimidineamine having the following structure. The yield was 1%.

[0182] [ka]

[0183] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 9.59(s,1H), 8.72(dd,J=8.3,1.2Hz,1H), 7.75(d,J=8.0Hz,1H), 7.36(d,J=8.3Hz,2H), 7.34(br,1H), 7.22(d,J=8.3Hz,2H), 4.15(s,3H), 2.39(s,3H) APCI-MS (m / z): 428.4[M] +

[0184] (Example 26) <Production of 6-methoxy-N-(4-methylphenyl)-2-(4-methylthio-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.02g (0.1mmol) of p-toluidine was dissolved in 1.0ml of DMF, 0.01g (0.3mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. The mixture was then cooled to 0°C, and 0.05g (0.1mmol) of 4-fluoro-6-methoxy-2-(4-methylthio-2-pyridyl)-5-trifluoromethylpyrimidine dissolved in 2ml of DMF was added, and the mixture was stirred at room temperature for 22.6 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain a trace amount of 6-methoxy-N-(4-methylphenyl)-2-(4-methylthio-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0185] [ka]

[0186] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.56(d,J=5.5Hz,1H), 8.14(d,J=2.1,1H), 7.46(d,J=8.6Hz,2H), 7.32-7.54(m,1H), 7.18-7.21(m,3H), 4.22(s,3H), 2.48(s,3H), 2.37(s,3H) APCI-MS (m / z): 406.3[M] +

[0187] Example 27 <Production of 2-(2-bromo-5-pyridyl)-6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.03g (0.2mmol) of p-toluidine was dissolved in 3.0ml of DMF, 0.01g (0.4mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. The mixture was then cooled to 0°C, 0.09g (0.3mmol) of 2-(2-bromo-5-pyridyl)-4-fluoro-6-methoxy-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 22 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column chromatography to obtain a trace amount of 2-(2-bromo-5-pyridyl)-6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure.

[0188] [ka]

[0189] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 9.23(ddd,J=2.5,0.6Hz,1H), 8.38(dd,J=8.3,2.5Hz,1H), 7.54(dd,J=8.3,0.6Hz,1H), 7.36(d,J=11.0Hz,2H), 7.30-7.32(m,1H), 7.20(d,J=8.0Hz,1H), 4.13(s,3H), 2.38(s,3H) APCI-MS (m / z): 440.3[M+H] +

[0190] (Example 28) <Production of 2-(2-dimethylamino-4-pyridyl)-6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.03g (0.3mmol) of p-toluidine was dissolved in 3.0ml of DMF, 0.02g (0.4mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes, then cooled to 0°C, 0.08g (0.3mmol) of 2-(2-dimethylamino-4-pyridyl)-4-fluoro-6-methoxy-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 41.4 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried with sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified with a column to obtain 0.008g (0.02mmol) of 2-(2-dimethylamino-4-pyridyl)-6-methoxy-N-(4-methylphenyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 8%.

[0191] [ka]

[0192] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.27(d,J=5.5,1H), 7.48(s,1H), 7.45(d,J=8.3Hz,2H), 7.41(dd,J=5.2,1,2Hz,1H), 7.30-7.32(m,1H), 7.19(d,J=8.6Hz,2H), 4.40(s,3H), 3.14(s,6H), 2.37(s,3H) APCI-MS (m / z): 403.3[M] +

[0193] (Example 29) <Production of methyl 2-[6-methoxy-4-[(4-methylphenyl)amino]-5-(trifluoromethyl)-2-pyrimidinyl]-4-pyridinecarboxylate> 0.07g (0.6mmol) of p-toluidine was dissolved in 6.0ml of DMF, 0.03g (0.7mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. The mixture was then cooled to 10°C, and 0.2g (0.6mmol) of methyl 2-[(4-fluoro-6-methoxy-5-trifluoromethyl)-2-pyrimidinyl]-4-pyridinecarboxylate was added, followed by stirring at room temperature for 62.6 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain 0.02g (0.05mmol) of methyl 2-[6-methoxy-4-[(4-methylphenyl)amino]-5-(trifluoromethyl)-2-pyrimidinyl]-4-pyridinecarboxylate having the following structure. The yield was 8%.

[0194] [ka]

[0195] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.96(dd,J=4.9,0.9Hz,1H), 8.87(dd,J=1.5,0.9,1H), 7.94(dd,J=4.9,1.5Hz,1H), 7.53(d,J=8.3Hz,2H), 7.38-7.41(m,1H), 7.23(d,J=8.3Hz,2H), 4.22(s,3H), 4.00(s,3H), 2.38(s,3H) APCI-MS (m / z): 418.6[M] +

[0196] (Example 30) <Production of 6-methoxy-N-(4-methylphenyl)-2-(3-methyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.02g (0.2mmol) of p-toluidine was dissolved in 1.0ml of DMF, 0.02g (0.4mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. The mixture was then cooled to 0°C, and 0.05g of crude 4-fluoro-6-methoxy-2-(3-methyl-2-pyridyl)-5-trifluoromethylpyrimidine dissolved in 2.0ml of DMF was added, and the mixture was stirred at room temperature for 17.1 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column purification to obtain a trace amount of 6-methoxy-N-(4-methylphenyl)-2-(3-methyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0197] [ka]

[0198] The analysis results were as follows: APCI-MS (m / z): 374.3[M] +

[0199] (Example 31) <Production of 6-methoxy-N-(4-methylphenyl)-2-(5-methyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.09g (0.8mmol) of p-toluidine was dissolved in 6.0ml of DMF, 0.03g (0.9mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes. The mixture was then cooled to 0°C, 0.2g (0.7mmol) of 6-fluoro-4-methoxy-2-(5-methyl-2-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 64 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.07g (0.18mmol) of 6-methoxy-N-(4-methylphenyl)-2-(5-methyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 26%.

[0200] [ka]

[0201] The analysis results were as follows: 1 H NMR(400MHz,CDCl3) δppm: 8.63(m,1H), 8.20(d,J=8.0,1H), 7.58-7.61(m,1H), 7.49(d,J=8.3Hz,2H), 7.33(br,1H), 7.20(d,J=8.3Hz,2H), 4.21(s,3H), 2.41(s,3H), 2.37(s,3H) APCI-MS (m / z): 374.8[M] +

[0202] Example 32 <Production of 6-chloro-N-(4-methylphenyl)-2-(6-n-propyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.04g (0.3mmol) of p-toluidine was dissolved in 3.0ml of DMF, 0.02g (0.2mmol) of sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes, then cooled to 0°C, 0.1g (0.3mmol) of 4,6-dichloro-2-(6-n-propyl-2-pyridyl)-5-trifluoromethylpyrimidine was added, and the mixture was stirred at room temperature for 15.8 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.09g (0.2mmol) of 6-chloro-N-(4-methylphenyl)-2-(6-n-propyl-2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 26%.

[0203] [ka]

[0204] The analysis results were as follows: 1H NMR(400MHz,CDCl3) δppm: 8.11(dd,J=8.0,0.9Hz,1H), 7.71(dd,J=8.0,7.6Hz,1H), 7.59(d,J=8.3Hz,2H), 7.53(br,1H), 7.28(dd,J=7.6,0.9Hz,1H), 7.22(d,J=8.0Hz,2H), 2.92(t,J=8.1Hz,2H), 2.38(s,3H), 1.88(tq,J=7.6,7.3Hz,2H), 1.03(t,J=7.3Hz,3H) APCI-MS (m / z): 406.9[M] +

[0205] (Example 33) <Production of 6-chloro-N-[2,4-dinitro-6-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 6-chloro-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine was dissolved in 1.2ml of acetonitrile, 0.1g (1.0mmol) of triethylamine was added, and the mixture was stirred at room temperature for 1.1 hours. Then, 0.2g (0.6mmol) of 2-chloro-3,5-dinitrobenzotrifluoride was added, and the mixture was stirred at room temperature for 16.8 hours. The reaction solution was purified by column chromatography to obtain a trace amount of 6-chloro-N-[2,4-dinitro-6-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure.

[0206] [ka]

[0207] The analysis results were as follows: APCI-MS (m / z): 509.2[M] +

[0208] (Example 34) <Production of 6-chloro-N-(3-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1 g (0.3 mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1 ml of acetonitrile, 0.05 g (0.5 mmol) of m-toluidine and 0.08 g (0.8 mmol) of triethylamine were added, and the mixture was stirred at room temperature for 16.8 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column chromatography to quantitatively obtain 0.1 g (0.4 mmol) of 6-chloro-N-(3-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine having the following structure.

[0209] [Chemical formula]

[0210] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.85 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.27 (ddd, J = 8.0, 0.9, 0.9 Hz, 1H), 7.81 (ddd, J = 7.6, 7.6, 1.5 Hz, 1H), 7.51 - 7.58 (m, 1H), 7.39 - 7.45 (m, 3H), 7.34 (t, J = 8.0 Hz, 1H), 7.34 (d, J = 7.3 Hz, 1H), 2.42 (s, 3H) APCI-MS (m / z): 365.7 [M + H] +

[0211] (Example 35) <Production of N-(4-butylphenyl)-6-chloro-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.07g (0.4mmol) of 4-butylaniline and 0.08g (0.8mmol) of triethylamine were added, and the mixture was stirred at room temperature for 24 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g (0.3mmol) of N-(4-butylphenyl)-6-chloro-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 92.3%.

[0212] [ka]

[0213] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.85 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.25 (ddd, J=8.0, 1.2, 0.9 Hz, 1H), 7.80 (ddd, J=8.0, 8.0, 1.8 Hz, 1H), 7.50-7.56 (m, 1H), 7.45-7.50 (m, 2H), 7.41 (ddd, J=7.6, 4.9, 1.2 Hz, 1H), 7.24-7.27 (m, 2H), 2.66 (dd, J=7.6, 7.6 Hz, 2H), 1.64 (m, 2H), 1.39 (tq, J=7.6, 7.3 Hz, 2H), 0.95 (t, J=7.3 Hz, 3H) APCI-MS(m / z):407.8[M+H] +

[0214] (Example 36) <Production of 6-chloro-N-(3,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.05g (0.4mmol) of 3,4-xylidine and 0.09g (0.9mmol) of triethylamine were added, and the mixture was stirred at room temperature for 24.3 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g (0.3mmol) of 6-chloro-N-(3,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 82.8%.

[0215] [ka]

[0216] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.85 (ddd, J=4.9, 1.8, 0.9 Hz, 1H), 8.27 (ddd, J=8.0, 1.2, 0.9 Hz, 1H), 7.80 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.46-7.53 (m, 1H), 7.41 (ddd, J=7.6, 4.9, 1.2 Hz, 1H), 7.33-7.36 (m, 2H), 7.18-7.22 (m, 2H), 2.32(s, 3H), 2.30(s, 3H) APCI-MS(m / z):379.9[M+H] +

[0217] (Example 37) <Production of 6-chloro-N-(2-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.06g (0.5mmol) of 2-fluoroaniline and 0.08g (0.8mmol) of triethylamine were added, and the mixture was stirred at room temperature for 22.6 hours. Water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified by column chromatography to obtain 0.006g (0.02mmol) of 6-chloro-N-(2-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 4.4%.

[0218] [ka]

[0219] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.86 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.24-8.29 (m, 2H), 7.83 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.73-7.82 (m, 1H), 7.44 (ddd, J=7.6, 4.9, 1.2 Hz, 1H), 7.18-7.30 (m, 3H) APCI-MS(m / z):369.8[M+H] +

[0220] (Example 38) <Production of 6-chloro-N-(3-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.06g (0.5mmol) of 3-fluoroaniline and 0.09g (0.9mmol) of triethylamine were added, and the mixture was stirred at room temperature for 17 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.08g (0.2mmol) of 6-chloro-N-(3-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 66.2%.

[0221] [ka]

[0222] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.87 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.31 (ddd, J=8.0, 1.2, 0.9 Hz, 1H), 7.85 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.66 (ddd, J=10.7, 2.5, 2.1 Hz, 1H), 7.57-7.65 (m, 2H), 7.45 (ddd, J=7.3, 4.9, 1.2 Hz, 1H), 7.39 (ddd, J=8.3, 8.3, 6.4 Hz, 1H), 7.23-7.26 (m, 1H), 7.69 (ddd, J=8.3, 2.5, 0.9 Hz, 1H) APCI-MS(m / z):369.9[M+H] +

[0223] (Example 39) <Production of 6-chloro-N-(4-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.05g (0.4mmol) of 4-fluoroaniline and 0.08g (0.7mmol) of triethylamine were added, and the mixture was stirred at room temperature for 16.3 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g (0.3mmol) of 6-chloro-N-(4-fluorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 99.9%.

[0224] [ka]

[0225] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.84 (ddd, J=4.9, 1.8, 0.9 Hz, 1H), 8.19 (ddd, J=8.0, 0.9, 0.9 Hz, 1H), 7.81 (ddd, J=7.6, 7.6, 1.8 Hz, 1H), 7.48-7.56 (m, 3H), 7.42 (ddd, J=7.6, 4.9, 1.2 Hz, 1H), 7.13-7.17 (m, 2H) APCI-MS(m / z):370.0[M+H] +

[0226] (Example 40) <Production of 6-chloro-N-(2,6-dichloro-4-nitrophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.09g (0.4mmol) of 2,6-dichloro-4-nitroaniline and 0.03g (0.7mmol) of sodium hydride were added, and the mixture was stirred at room temperature for 22.5 hours. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.004g of a crude product of 6-chloro-N-(2,6-dichloro-4-nitrophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0227] [ka]

[0228] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.82 (ddd, J=4.6, 1.5, 0.6 Hz, 1H), 8.38 (s, 2H), 7.89 (ddd, J=8.0, 0.9, 0.9 Hz, 1H), 7.76 (ddd, J=7.6, 7.6, 1.8 Hz, 1H), 7.43-7.37 (br, 1H), 7.41 (ddd, J=7.3, 4.6, 1.2 Hz, 1H) APCI-MS(m / z):465.1[M] +

[0229] (Example 41) <Production of 6-chloro-N-[2-nitro-4-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.09g (0.4mmol) of 4-amino-3-nitrobenzotrifluoride and 0.04g (0.9mmol) of sodium hydride were added, and the mixture was stirred at room temperature for 16.7 hours. Water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g of a crude product of 6-chloro-N-[2-nitro-4-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0230] [ka]

[0231] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:11.09 (br, 1H), 9.13 (d, J=9.2 Hz, 1H), 8.88 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.56 (d, J=1.5 Hz, 1H), 8.39 (ddd, 1H) APCI-MS(m / z):465.2[M+H] +

[0232] (Example 42) <Production of 6-chloro-N-(2,4-dinitrophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.08g (0.4mmol) of 2,4-dinitroaniline and 0.08g (0.8mmol) of triethylamine were added, and the mixture was stirred for 16.1 hours under heating and reflux. After cooling to room temperature, water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.03g of a crude product of 6-chloro-N-(2,4-dinitrophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0233] [ka]

[0234] The analysis results were as follows: APCI-MS(m / z):441.9[M+H] +

[0235] (Example 43) <Production of 6-chloro-N-[5-chloro-2-nitro-4-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.1g (0.4mmol) of 5-chloro-2-nitro-4-(trifluoromethyl)aniline and 0.03g (0.9mmol) of sodium hydride were added, and the mixture was stirred at room temperature for 22.6 hours. Water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g (0.2mmol) of 6-chloro-N-[5-chloro-2-nitro-4-(trifluoromethyl)phenyl]-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 57.9%.

[0236] [ka]

[0237] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:11.32 (br, 1H), 9.65 (s, 1H), 8.91 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.65 (s, 1H), 8.46 (ddd, J=8.0, 0.9, 0.9 Hz, 1H), 7.93 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.52 (ddd, J=7.3, 4.6, 0.9 Hz, 1H) APCI-MS(m / z):499.0[M+H] +

[0238] (Example 44) <Production of 6-chloro-N-(2,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.4mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.05g (0.4mmol) of 2,4-dimethylaniline and 0.08g (0.8mmol) of triethylamine were added, and the mixture was stirred at room temperature for 16.5 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.08g (0.2mmol) of 6-chloro-N-(2,4-dimethylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 57.1%.

[0239] [ka]

[0240] The analysis results were as follows: 1 H NMR(400MHz,CDCl3)δppm:8.82 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.07 (ddd, J=8.0, 1.2, 0.9 Hz, 1H), 7.74 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.38 (ddd, J=7.6, 4.6, 1.2 Hz, 1H), 7.32 (br, 1H), 7.09-7.13 (m, 2H), 2.38 (s, 3H), 2.23 (s, 3H) APCI-MS(m / z):380.0[M+H] +

[0241] (Example 45) <Production of 6-chloro-N-(4-chlorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (1.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.07g (0.5mmol) of 4-chloroaniline and 0.08g (0.8mmol) of triethylamine were added, and the mixture was stirred at room temperature for 17.5 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.1g (0.3mmol) of 6-chloro-N-(4-chlorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 88.9%.

[0242] [ka]

[0243] The analysis results were as follows: 1H NMR(400MHz,CDCl3)δppm:8.86 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.24 (ddd, J=8.0, 0.9, 0.9 Hz, 1H), 7.83 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.50-7.57 (m, 3H), 7.40-7.46 (m, 3H) APCI-MS(m / z):385.9[M+H] +

[0244] (Example 46) <Production of 6-chloro-N-(2,4-dichlorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.07g (0.4mmol) of 2,4-dichloroaniline and 0.03g (0.7mmol) of sodium hydride were added, and the mixture was stirred at room temperature for 21.9 hours. Water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.01g of a crude product of 6-chloro-N-(2,4-dichlorophenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0245] [ka]

[0246] The analysis results were as follows: 1H NMR(400MHz,CDCl3)δppm:8.86 (ddd, J=4.6, 1.8, 0.9 Hz, 1H), 8.39 (d, J=8.9 Hz, 1H), 8.28 (ddd, J=8.0, 1.2, 0.9 Hz, 1H), 8.06 (br, 1H), 7.85 (ddd, J=8.0, 7.6, 1.8 Hz, 1H), 7.50 (d, J=2.5 Hz, 1H), 7.45 (d, J=7.6, 4.9, 1.2 Hz, 1H), 7.39 (dd, J=8.9, 2.5 Hz, 1H) APCI-MS(m / z):420.0[M] +

[0247] (Example 47) <Production of 6-chloro-N-(4-chloro-2-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidinamine> 0.1g (0.3mmol) of 4,6-dichloro-2-(2-pyridyl)-5-trifluoromethylpyrimidine was dissolved in 1.1ml of acetonitrile, 0.07g (0.5mmol) of 4-chloro-2-methylaniline and 0.07g (0.5mmol) of triethylamine were added, and the mixture was stirred at room temperature for 21.6 hours. Water was added to the reaction solution, which was extracted with ethyl acetate and the organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then purified using a column to obtain 0.04g of a crude product of 6-chloro-N-(4-chloro-2-methylphenyl)-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure.

[0248] [ka]

[0249] The analysis results were as follows: 19 F NMR(400MHz,CDCl3)δppm:-56.11 (s, 3F) APCI-MS(m / z): 400.1[M+H] +

[0250] (Example 48) <Production of N-(4-chloro-2-methylphenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine> Dissolve 0.1 g (0.4 mmol) of 4-fluoro-6-methoxy-2-(2-pyridyl)-5-trifluoromethylpyrimidine in 1.1 ml of acetonitrile, add 0.07 g (0.5 mmol) of 4-chloro-2-methylaniline and 0.1 g (0.9 mmol) of triethylamine, and stir at reflux for 22.2 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulfate. The dried organic phase was filtered, and the filtrate was concentrated and then subjected to column purification to obtain 0.01 g (0.02 mmol) of N-(4-chloro-2-methylphenyl)-6-methoxy-2-(2-pyridyl)-5-(trifluoromethyl)-4-pyrimidineamine having the following structure. The yield was 5.7%.

[0251] [Chemical formula]

[0252] The analysis results were as follows. 1 H NMR (400 MHz, CDCl3) δ ppm: 8.80 (ddd, J = 4.6, 1.8, 0.9 Hz, 1H), 8.16 (ddd, J = 8.0, 1.2, 0.9 Hz, 1H), 7.76 - 7.80 (m, 2H), 7.38 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.24 - 7.28 (m, 2H), 7.15 (br, 1H), 4.22 (s, 3H), 2.27 (s, 3H) APCI-MS (m / z): 396.1 [M + H] +

[0253] (Evaluation test for cucumber powdery mildew (500 ppm)) The fluorine-containing pyrimidine compounds prepared in Examples 12, 13 and 15 were dissolved in acetone and diluted to a concentration of 500 ppm. Next, a cucumber leaf disk (diameter 20 mm) was placed in the diluted acetone solution and completely wetted, and then the cucumber leaf disk was placed so that the back side of the cucumber leaf disk was in contact with a plain agar medium prepared separately, and air-dried. After air-drying, a spore suspension of cucumber powdery mildew was uniformly sprayed on the cucumber leaf disk and air-dried. Thereafter, the cucumber leaf disk was placed in an incubator (25°C, 12 hours of light), and the lesion area was examined after 12 days, and the control value was calculated. The results are shown in Table 1. The control value was calculated according to the following formula. In the following formula, "untreated" means that the cucumber leaf disk was wetted with only acetone as the test liquid, and "untreated area" means the area.

[0254] [Table 1]

[0255] (Evaluation test against cucumber powdery mildew (100ppm)) The fluorine-containing pyrimidine compounds prepared in Examples 12, 13 and 15 were dissolved in acetone and diluted to a concentration of 100 ppm. Next, a cucumber leaf disk (diameter 20 mm) was placed in the diluted acetone solution and completely wetted, and then the cucumber leaf disk was placed so that the back side of the cucumber leaf disk was in contact with a plain agar medium prepared separately, and air-dried. After air-drying, a spore suspension of cucumber powdery mildew was uniformly sprayed on the cucumber leaf disk and air-dried. Thereafter, the cucumber leaf disk was placed in an incubator (25°C, 12 hours of illumination), and the lesion area was examined after 12 days, and the control value was calculated. The results are shown in Table 2. The control value was calculated according to the following formula. In the following formula, "untreated" means that the cucumber leaf disk was wetted with only acetone as the test liquid, and "untreated area" means the area.

[0256] [Table 2]

[0257] Control value = {(average diseased area in untreated areas - average diseased area in treated areas) / average diseased area in untreated areas} x 100

[0258] (Evaluation test against gray mold (500ppm)) The fluorine-containing pyrimidine compounds prepared in Examples 1, 2, 3, 4, 12 and 16 were dissolved in DMSO and diluted to a concentration of 50,000 ppm. 30 μL of the diluted DMSO solution was added to 3 ml of dissolved PDA medium, stirred with a pipette, and placed in a well of a 6-well plate to solidify (final concentration 500 ppm, 3 replicates each). Botrytis cinerea, strain 2018105, grown in PDA medium was cut out together with the medium with a 0.4 cm diameter Seiken punch, and these were placed in the center of the PDA medium of a 6-well plate containing DMSO solution and grown at 27 ° C. The diameter of the mycelium was measured after 2 days, and the control value was calculated. The average is shown in Table 3. The control value was calculated according to the following formula. In the following formula, "untreated" refers to PDA medium to which only DMSO was added as the test solution.

[0259] [Table 3]

[0260] Control value = {(untreated hypha diameter - treated hypha diameter) / untreated hypha diameter} x 100

[0261] From the above, it is seen that the fluorine-containing pyrimidine compound of the present invention exhibits a fungicidal effect against pathogens of cucumber powdery mildew and gray mold, and is effective as a compound exhibiting biological activity, particularly as an agent for controlling harmful fungi. [Industrial Applicability]

[0262] The fluorine-containing pyrimidine compound of the present invention can be suitably used mainly as an active ingredient of an agent for controlling harmful fungi in the agricultural field.

Claims

1. A fluorine-containing pyrimidine compound represented by the following general formula (1), (2) or (3): 【Chemistry 1】 (In the above general formulas (1) to (3), W and X each independently represent a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ , -NA １ A ２ , -B(OA １ ) (OA ２ ), -COA １ , -COOA １ Or -CONA １ A ２ represents Y is a halogen atom or -OA ３ represents Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ or -NA １ A ２ represents A １ and A ２ each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, A ３ represents a hydrocarbon group having 1 to 12 carbon atoms, n represents an integer of 0 to 3; In W, X and Z, each A １ , A ２ , m and l may be the same or different; When there are multiple Z's, the multiple Z's may be the same or different.

2. 2. A harmful fungus control agent comprising the fluorine-containing pyrimidine compound or a salt thereof according to claim 1 as an active ingredient.

3. (a) reacting aniline or a derivative thereof represented by the following general formula (4) with a fluorine-containing pyrimidine compound represented by the following general formula (5) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1); 【Chemistry 2】 (b) reacting aniline or a derivative thereof represented by the following general formula (4) with a fluorine-containing pyrimidine compound represented by the following general formula (6) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2): 【Chemistry 3】 or (c) reacting aniline or a derivative thereof represented by the following general formula (4) with a fluorine-containing pyrimidine compound represented by the following general formula (7) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3): 【Chemistry 4】 (In the above general formulas (1) to (7), W and X each independently represent a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ , -NA １ A ２ , -B(OA １ ) (OA ２ ), -COA １ , -COOA １ Or -CONA １ A ２ represents X １ represents a halogen atom, Y is a halogen atom or -OA ３ represents Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ or -NA １ A ２ represents A １ and A ２ each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, A ３ represents a hydrocarbon group having 1 to 12 carbon atoms, n represents an integer of 0 to 3; In W, X and Z, each A １ , A ２ , m and l may be the same or different; When there are multiple Z's, the multiple Z's may be the same or different. The present invention relates to a method for producing a fluorine-containing pyrimidine compound.

4. (d) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (9) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (1): 【Chemistry 5】 (e) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (10) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (2): 【Chemistry 6】 or (f) reacting an aryl halide represented by the following general formula (8) or a derivative thereof with a fluorine-containing pyrimidine compound represented by the following general formula (11) to obtain a fluorine-containing pyrimidine compound represented by the following general formula (3): 【Chemistry 7】 (In the above general formulas (1) to (3) and (8) to (11), W and X each independently represent a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ , -NA １ A ２ , -B(OA １ ) (OA ２ ), -COA １ , -COOA １ Or -CONA １ A ２ represents X ２ represents a halogen atom, Y is a halogen atom or -OA ３ represents Z is a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C ｍ F ２ｍ＋１ (m is an integer of 1 to 10), a nitro group, —OA １ , -SO ｌ A １ (l is an integer of 1 to 3), -SA １ or -NA １ A ２ represents A １ and A ２ each independently represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, A ３ represents a hydrocarbon group having 1 to 12 carbon atoms, n represents an integer of 0 to 3; In W, X and Z, each A １ , A ２ , m and l may be the same or different; When there are multiple Z's, the multiple Z's may be the same or different. The present invention relates to a method for producing a fluorine-containing pyrimidine compound.

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