PL160991B1 - Method of obtaining novel 2-anilinopyrimidine derivatives - Google Patents

Abstract

Method for the preparation of new 2-anilinopyrimidine derivatives of general formula I, wherein R1 and R2 are independently they represent a hydrogen atom, a halogen atom, C1-C3-alkyl radical, C1-C2-haloalkyl radical, a C1-C3 alkoxy group or a C1-C3 haloalkoxy group, R3 represents a hydrogen atom, the radical C1-C4- alkyl optionally substituted with halogen, a group hydroxyl or cyano, cyclopropyl radical possibly up to three times, equally or differently substituted with methyl and / or halogen, and R4 is a C3-C6-cycloalkyl radical or optionally co up to three times, equally or differently substituted a methyl group and / or a halogen, characterized in that the salt phenylguanidines of formula IIa or matrix guanidine o the formula 2b is reacted with the dichotone of formula 3 in environment or without a solvent at a temperature of 60- 160 ° C, or the guanidine salt of formula IV with dichoton o formula 3 without solvent at 100-160 ° C or in an inert solvent at temperature 30-140 ° C cyclizes to the pyrimidine compound of formula 5 and the resulting compound of formula 5 are subjected to treatment is reacted with a compound of formula 6 under conditions cleavage of HY in the presence of a proton acceptor w environment of aprotic solvents at temperature 30-140 ° C, while in formulas 2-6 symbols R1-R4 have the meanings given in the discussion of formula 1, A® is an acid anion and Y is a halogen atom.

Description

The subject of the invention is a process for the preparation of new 2-anilinopyrimidine derivatives.

The new, highly pesticidally active 2-anilinopyrimidine derivatives are encompassed by the general formula 1, in which R1 and R2 independently represent a hydrogen atom, a halogen atom, a C1-C3-alkyl radical, a C1-C2-haloalkyl radical, a C1-C3-alkoxy group or a C1-C3 haloalkoxy group, R3 is a hydrogen atom, a C1-C4-alkyl radical optionally substituted by halogen, hydroxy or cyano, a cyclopropyl radical optionally up to three times, equally or differently substituted with a methyl and / or halogen group, and R4 is a C3- radical C6-cycloalkyl optionally up to three times, equally or differently substituted with methyl and / or halogen, including their acid addition salts and metal salt complexes.

The term alkyl radical alone or as a component of another substituent, such as a haloalkyl, alkoxy or haloalkoxy group, should be understood, depending on the number of carbon atoms, to be understood e.g. as a methyl, ethyl, propyl, butyl radical and isomers thereof, such as isopropyl, isobutyl radicals , Two-order butyl or second-order butyl. Halogen, also called Hal, is a fluorine, chlorine, bromine or iodine atom. Haloalkyl and haloalkoxy groups are once to fully halogenated radicals such as CHCb, CH2F, CC13, CH2C1, CHF2, CF3, CH2CH2Br, C2C15, CHBr, CHBrCl and the like, preferably CF3. A cycloalkyl radical is, for example, a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical according to the number of carbon atoms indicated.

The N-pyrimidinylaniline compounds are already known. Thus, in published European patent application No. 0 224 339 and in German Democratic Republic Patent No. 151 404 there are compounds having a Ν-2-pyrimidinyl structure which are described as being effective against plant damaging fungi. However, these known compounds have so far not been able to fully meet the practical requirements. The novel compounds of the formula I differ from the known compounds in a characteristic manner by introducing at least one cycloalkyl radical and other substituents into the anilinopyrimidine structure, whereby these novel compounds achieve surprisingly high fungicidal and insecticidal activity.

The compounds of the formula I are stable oils, resins or solids at room temperature, which have valuable microbicidal properties. They can be used in the agrarian sector or in related fields as a preventive or curative treatment to combat microorganisms that damage plants. The new active compounds of the formula I are not only distinguished by a very strong insecticidal and fungicidal action at low application concentrations, but also by a particularly good plant tolerance.

The new salts are in particular the addition salts with physiologically acceptable inorganic or organic acids, e.g. with hydrohalic acids such as chloro-, bromo- or hydroiodic acid, with sulfuric, phosphoric, phosphorous, nitric acid, or with organic acids such as acetic acid. , trifluoroacetic, trichloroacetic, propionic, glycol, thiocyanic, lactic, amber, citric, benzoic, cinnamic, oxalic, formic, benzenesulfonic, p-toluenesulfonic, methanesulfonic, salicylic, paminosalicylic, 2-phenoxyulfoxy-benzoic acid .

The complexes of the compound of formula I with metal salts consist of an organic base molecule and an inorganic or organic metal salt, e.g., halides, nitrates, sulfates, phosphates, acetates, trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates, etc. salts of main group II elements, such as calcium and magnesium, and elements of main group II and IV, such as clay, tin or lead, and elements of sub-group I-VIII, such as chromium, manganese, iron, cobalt, nickel, copper , zinc, etc. The elements of the subgroups of period 4 are preferred. These metals can also be present with different valencies as appropriate. These metal complexes can be single or multi-core, ie they can contain one or more proportions of organic molecules as ligands.

Particularly preferred individual substances are, for example, 2-phenylamino-4-methyl-6-cyclopropylpyrimidine (compound No. 1.1), 2-phenylamino-4-ethyl-6-cyclopropylpyrimidine (compound No. 1.6), 2-phenylamino-4-methyl-6/2 -methylcyclopropyl) -pyrimidine (compound No. 1.14), 2 - ^^ i ^; ^ lc ^; ^ i ^ ii ^ <^ '^ - ^ ,, ^ - ^ is - / ^^ l ^ l <^] ^: ^ i3py ^ 1 ^^ - pyrimidine (compound No. 1.236), 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine (compound No. 1.48), 2-phenylamino-4-fluoromethyl-6-cyclopropylpyrimidine (compound No. 1.59), 2-phenylamino- 4-hydroxymethyl-6- (2-methylcyclopropyl) -pyrimidine (compound No. 1.13), 2-fei ^; ^^ <^ and ^: ^^ and ^ <^ '^' ^ - ^ and ^ (^ t; ^ 11 ^ - (^ - / ^^ ifl ^ <^ i ^ oc: ^ l ^] ^ <^ j ^: crude ^ i ^> / pyrimidine (compound No. 1.66), 2-phenylamino-4-methyl --- (2-chlorocyclopropyl) -pyrimidine (compound No. 1.69), 2-phenylamino-4-methyl-6- (2-difluorocyclopropyl) -pyrimidine (compound No. 1.84), 2-phenylamino-4-fluoromethyl-6- (2-Ωuo-cyclopropyl) / -pyrimidine (compound No. 1.87), 2-phenylamino-4-ifuoromethyl-6- (2-chlorocyclopropyl) -pyrimidine (compound No. 1.94), 2-phenylamino-4- ^ 1f ^ and ^ <^] ^ o- (6 ^ - (2-methyl [beta]) (^ ^ <^ <13> propyl) -pyrimidine (compound No. 1.108), 2-phenylamino -4-ethyl-6- (2-methylcyclopropyl) -pyrimidine (compound No. 1.131) and 2- (p-fluorophenes-Coamino) -4-methyl-6-cyclopropylpyrimidine (compound No. 1.33).

According to the invention, the process for the preparation of the new 2-anSCinopSrimidine derivatives of the general formula 1, in which R 1, R 2, R 3 and R 4 are as defined above, consists in reacting the phenylguanidine salt of the formula 2a or the matrix guanidine of the formula 2b with the dicetone of the formula 3 without solvent or in an aprotic, preferably protic solvent at a temperature of 60-16 ° C, preferably at a temperature of 60-110 ° C, or a guanidine salt of formula 4 with a dichotone of formula 3 without solvent at a temperature of 100-160 ° C, preferably at a temperature of 120-150 ° C, or in an inert solvent at a temperature of 30-140 ° C, preferably at a temperature of 60-120 ° C, cyclized to a pyrimidine compound of formula 5 and the resulting compound of formula 5 is reacted with a compound of for formula 6 under conditions for cleavage of HY in the presence of a proton acceptor in an aprotic solvent medium at a temperature of 30-140 ° C, preferably at a temperature of 60-120 ° C, where in formulas 2-6 the symbols R1-R4 have has the meaning given in the discussion of formula 1, A @ is the anion of the acid and Y is the halogen atom.

In the methods described for compounds of formulas 2a and 4 for the acid anion ^Α θ are, for example. Residues following salts: carbonate, bicarbonate, nitrate, halide, sulfate or hydrogen sulfate.

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The acids used are, in particular, inorganic acids, such as hydrohalic acids, for example hydrofluoric, hydrochloric or hydrobromic acid, and sulfuric, phosphoric or nitric acid; however, suitable organic acids such as acetic acid, toluenesulfonic acid and the like can also be used.

Proton acceptors are, for example, inorganic or organic bases, such as, for example, alkali or alkali metal compounds, e.g. lithium, sodium, potassium, magnesium, calcium, strontium and barium hydroxides, oxides or carbonates, and also hydrides such as sodium hydride. As organic bases, there should be mentioned, for example, tertiary amines such as triethylamine, triethylenediamine or pyridine.

In the previously discussed processes, in addition to some of the solvents mentioned, for example, the following solvents can be used according to the reaction conditions: halogenated hydrocarbons, in particular chlorohydrocarbons, such as tetrachlorethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, chloronaphthalene, carbon tetrachloride, trichlorethane, trichlorethylene, trichlorethane, difluorobenzene, 1,2-dichloroethane, 1,1-dichloroethane, 1,2-cis-dichloroethylene, chlorobenzene, fluorobenzene, bromobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlorotoluene; ethers such as ethyl propyl ether, tertiary butyl methyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexyl methyl ether, diethyl glycol diethyl ether , tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether; nitrocarbons such as nitromethane, nitroethane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; nitriles such as acetonitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cycloaliphatic hydrocarbons such as heptane, hexane, octane, nonane, cymene, gasoline fractions within the range with a boiling point of 70-190 ° C, cyclohexane, methylcyclohexane, decalin, petroleum ether, ligroin, trimethylpentane such as 2,3, 3-trimethylpentane; esters such as ethyl acetate, acetoacetate, isobutyl acetate; amides such as formamide, methylformamide, dimethylformamide; ketones such as acetone, methyl ethyl ketone; alcohols, especially lower aliphatic alcohols such as methanol, ethanol, n-propanol, isopropanol, and butanol isomers; possibly also water. Mixtures of the solvents and diluents mentioned are also possible.

Synthetic methods analogous to the previously discussed preparation methods are discussed in the literature in the following publications: Method 1- A. Kreutzberger and J. Gillessen, J. Heterocyclic Chem. 22, 101 (1985); method 2, step 2.1 - O. Stark, Ber, Drsch.Chem.Ges. 42, 699 (1909),

J. Hale, J.Am.Chem. Soc. 36, 104 (1914), G.M. Kosolapoff, J.Org. Chem. 26, 1895 (1961); stage 2.2 - St. Angerstein, Ber.Dtsch.Chem.Ges. 34, 3956 (1901), G.M. Kosolapoff, J.Org. Chem. 26, 1985 (1961); stage 2.3 - M.P.V. Boarland and J.F.W. McOmie, J.Chem. Soc. 1951 1218, T. Matsukawa i

K. Shirakuwa, J. Harm. Soc. Japan 71, 933 (1951), Chem. Abstr. 46, 4549 (1952); method 3 A. Combes and C. Combes, Bull.Soc.Chem. (3), 7,791 (1892), W.J. Hale and F.C. Vibrans, J.AM.Chem. Soc. 40, 1046 (1918).

It has surprisingly been found that the compounds of formula I have, for practical purposes, a very favorable biocidal range against insects and phytopathogenic microorganisms, in particular against Fungi. These compounds show very beneficial curative, preventive and, in particular, systemic properties, so they can be used to protect many crops. By means of the active compounds of the formula I, it is possible to suppress or destroy existing pests on plants or plant parts (fruit, flowers, foliage, stems, clusters, roots) from various utility crops, while the plant parts which grow later, e.g. by phytopathogenic microorganisms.

The compounds of formula I are effective against phytopathogenic fungi belonging to the following classes: Fungi imperfecti (especially Botrytis, hereinafter Pyricularia, Helminthosporium Fusarium, Sepstoria, Cercospora and Alternaria); Basidiomycetes (e.g. the genera Hemileia, Rhizoctonia, Puccinia). They are also active against Ascomycetes (e.g. Venturia, Podosphaera, Erysiphe, monilinia, Uncinula) and Oomycetes (Perenosporales), Phytophthora, Plasmopara, Pythium). In addition, the compounds of formula I can be used as dressings for the treatment of seeds (fruit, tubs, grains) and cuttings to protect against fungal contamination and against phytopathogenic

160 991 5 soil fungi. The compounds of the formula I are also effective against insect damaging insects, for example against cereal pests such as rice.

The following plant species are, for example, the target crops for the disclosed field of plant protection: cereals such as wheat, barley, rye, oats, rice, maize, sorghum and the like; beet, such as sugar beet and fodder beet; pome trees, stone trees and berry shrubs, such as apple trees, pear trees, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries; legumes such as beans, lentils, peas, soybeans; oil crops such as rape, mustard, poppy seed, olives, sunflowers, coconut palms, castor, cocoa shrubs and groundnuts; cucurbits such as squash, cucumbers and melons; fiber crops such as cotton, linen, hemp, and jute; citrus fruits such as oranges, lemons, grapefruit, and mandarins; vegetable species such as spinach, head lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes and peppers; root crops such as Lingon, Ceylon cinnamon, camphor cinnamon; or plants such as tobacco, nuts, coffee, sugarcane, tea, pepper, grapevines, hops, bananas, rubber trees, and ornamentals.

The active compounds of the formula I are usually used in the form of preparations and can be applied simultaneously or sequentially one after the other together with other active substances to the surfaces or plants to be treated. These further active substances can be both fertilizers, micronutrient enrichants or other preparations which exert an influence on plant growth. They can also be selective herbicides and insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these agents, together with possible further formulating techniques known in the art of carriers, surface-active substances or other additives promoting the application of the preparations.

The carriers and additives used can be solid or liquid and correspond to the intended substances in the preparation technique, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, adhesion promoters, thickeners, binders or fertilizers.

A preferred method of spreading the active ingredient of the formula I or the agrochemical containing at least one of these active ingredients is by application to the foliage (application to the leaves). The frequency of applications and the number of doses are selected according to the paralytic pressure for a given pathogen. The active substances of the formula I can also enter the plants via the soil and via the root system (systemic action) by saturating the habitat of the plants with a liquid preparation or by introducing solid active substances into the soil, e.g. in the form of granules (application to soil). In the case of aquatic rice cultivation, such granules can be dosed into a flooded rice field. The compounds of the formula I can also be applied to seed grains (coating) by either impregnating the grains with a liquid formulation of the active ingredient or by coating them with a solid formulation.

The compounds of formula I are used in unchanged form or, preferably together with auxiliaries known in the preparatory technique, and then processed in a known manner, e.g. into emulsion concentrates, paint pastes, ready-to-spray solutions or diluent solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules or by encapsulation, e.g. in polymeric substances. The methods of application, such as mist spraying, nebulizing, dusting, broadcasting, painting or drenching, are selected from the type of agents depending on the intended purpose and the given conditions. The preferred doses generally correspond to an amount of 50 g to 5 kg of active compound per ha, preferably 100 g to 2 kg of active compound per ha, in particular 200 to 600 g of active compound per ha.

The formulations, i.e. compositions, compositions and mixtures containing the active ingredient of the formula I and, if appropriate, a solid or liquid excipient, are prepared in a known manner, for example by thoroughly mixing and / or grinding the active ingredients with diluents such as solvents, solid carriers and possibly surfactants (surfactants).

As solvents are aromatic hydrocarbons, preferably the fractions C ₈ -C _2, such as xylene mixtures and substituted naphthalenes, phthalates such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or para6

160 991 fins, alcohols and glycols and their ethers and esters such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methylpyrrolidone-2, dimethyl sulphoxide or dimethylformamide, and optionally epoxidized vegetable oils such as epoxidized coconut oil or soybean oil, and water.

As solid carriers, for example for dusts and dispersible powders, natural rock meals such as calcite, talcum, kaolin, montmorillonite or attapulgite are usually used. In order to improve the physical properties, it is also possible to add highly disperse silica or highly disperse absorbent polymers. Suitable granular adsorptive granulator support are porous types, e.g. pumice, brick crumble, sepiolite or bentonite, and non-sorptive carrier substances, e.g. calcite or sand. In addition, it is possible to use a wide range of pre-granulated substances of inorganic origin, such as in particular dolomite or comminuted plant residues. In addition, natural (animal or plant) or synthetic phospholipids from the kephalin and lecithin series, which can be obtained, for example, from soybean, are particularly advantageous application-promoting additives which can lead to a significant reduction in dosage.

Depending on the active compound of the formula I to be processed, the surface-active compounds are nonionic, cationic and / or anionic surfactants with high emulsifying, dispersing and wetting properties. The term tensides also includes mixtures of surfactants.

Suitable anionic surfactants can be both water-soluble soaps, and water-soluble synthetic surfactants.

As soaps, mention may be made of alkali metal salts, calcium salts and optionally substituted ammonium salts of higher fatty acids (with 10-22 carbon atoms), such as the sodium or potassium salt of oleic or stearic acid, or those of mixtures of natural fatty acids which can be obtained e.g. from coconut or tallow oil. In addition, methyl taurine fatty acid salts should be mentioned.

However, the so-called synthetic surfactants, especially alkanesulfonates, fatty alcohol sulfates, sulfonated benzimidazole derivatives or alkyl sulfonates.

The fatty alcohol sulphonates or sulphates are usually in the form of alkali metal salts, calcium salts or optionally substituted ammonium salts and have an alkyl radical with 8-22 carbon atoms, the alkyl radical also comprising the alkyl part of the acyl radicals, e.g. the sodium or calcium salt of the acid lignin sulfonic acid, dodecyl sulfuric acid ester or a mixture of fatty alcohol sulfate, made from natural fatty acids. Also included are salts of sulfuric acid esters of sulfonic acids with fatty alcohol-ethylene oxide adducts. The sulfonated benzimidazole derivatives preferably contain 2 sulfo groups and a fatty acid group with 8-22 carbon atoms. The alkylarylsulfonates are, for example, the sodium, calcium or triethanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphthalenesulfonic acid or the condensation product naphthalenesulfonic acid formaldehyde.

Also suitable are the corresponding phosphates, such as salts of phosphoric acid esters with a p-nonylphenol-ethylene oxide adduct (4-14 oxide units).

Non-ionic surfactants include, in particular, derivatives of polyethylene glycol ethers with aliphatic or cycloaliphatic alcohols, with saturated or unsaturated fatty acids and alkylphenols, containing 3-30 glycol ether groups and 8-20 carbon atoms in the (aliphatic) hydrocarbon radical and 6-18 carbon atoms in the alkyl radical of an alkylphenol.

Further suitable nonionic surfactants are the water-soluble 20-250 ethylene glycol ether groups and 10-100 propylene glycol ether groups containing poly-adducts of ethylene oxide with polypropylene glycol, ethylene diamine polypropylene glycol and alkyl polypropylene glycol having 1-10 carbon atoms in the alkyl chain. These compounds usually contain 1 to 5 ethylene glycol units per propylene glycol unit.

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Examples of nonionic surfactants include nonylphenol polyethoxyethanols, polyethylene glycol castor oil ethers, polypropylene polyethylene oxide adducts, tributylphenoxypolyethoxyethanol, polyethylene glycol and octylphenoxypolyethoxyethanol.

Also contemplated are polyoxyethylene anhydrosorbitan fatty acid esters, such as polyoxyethylene anhydrosorbitan trioleate.

The cationic surfactants are, above all, quaternary ammonium salts which contain at least one alkyl radical with 8 to 22 carbon atoms as the nitrogen substituent and which have lower, optionally halogenated, alkyl, benzyl or hydroxyalkyl radicals as further substituents. These salts are preferably in the form of halides, methylsulfates or ethylsulfates, such as stearyltrimethylammonium chloride or benzyldi (2-chloroethyl) ethyl ammonium bromide.

Further, the usual surfactants in the formulation art are known to the person skilled in the art or can be taken from the relevant specialist literature.

The agrochemical preparations generally contain from 0.1 to 99%, preferably from 0.1 to 95%, of active compound of the formula I; 99.9-1%, preferably 99.8% -5%, of a solid or liquid additive and 0-25%, preferably 0.1-25%, of a surfactant.

While a concentrated agent is preferred as a commercial product, as a rule, the end user uses dilute agents.

These agents may also contain further additives, such as stabilizers, antifoams, viscosity regulators, tackifiers, adhesion promoters, and synthetic fertilizers or other active ingredients to achieve special effects.

Example 1 below illustrates the process according to the invention in more detail without limiting its scope. In the table below, the abbreviation mt. is the melting point and the symbol nD is the refractive index at the given temperature.

Example I. Preparation of 2-phenylamino-4-methyl-6-cyclopropylpyrimidine (compound No.

1.1) 10 g (51 mmoles) of phenylguanidine bicarbonate and 9.7 g (77 mmoles) of 1,3-cyclopropylbutanedione are heated for 6 hours with stirring at 110 ° C, the evolution of carbon dioxide begins with the progress of the reaction ceases. After cooling to room temperature, the dark brown-colored emulsion is mixed with 50 ml of diethyl ether, washed twice with 20 ml of water each time, dried over sodium sulphate, filtered and the solvent is evaporated off. As the residue, the dark brown-colored oil obtained (= 13.1 g) was purified by column chromatography on silica gel (ethyl ether: toluene = 5: 3). After evaporation of the recycle medium mixture, the brown-colored oil is crystallized and recrystallized from ethyl ether / petroleum ether at 30-50 ° C. 8.55 g (38 mmol, 74.5% of theory) of light brown colored crystals, mp 67-69 ° C, are obtained.

Further novel compounds of formula I can be prepared analogously in which R1-R4 have the meanings given in the table below.

Table

Relationship no R, Ra Ra R « Physical data 1 2 3 4 5 6 1 1 H. H. CH3 cyclopropyl mp 67-69 ° C 1 2 2-C1 H. CH3 cyclopropyl 1 3 H. H. H. cyclopropyl mp 53-56 ° C 1 4 H. H. -CHzBr cyclopropyl mp. 77.5-79.5 ° C 1 5 3-CI H. CH3 cyclopropyl mp 104-105 ° C 1 6 H. H. -C2H5 cyclopropyl mp 42-45 ° C 1 7 4-CI H. -CH3 cyclopropyl mp. 86-87 ^on C 1 8 H. H. -CHzBr 1-methylcyclopropyl 1 9 H. H. -CHzCl 2-methylcyclopropyl mp 50-52 ° C

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1 2 3 4 5 6 1 10 4-CHa Η -CH3 cyclopropyl mp 53-56 ° C 1 11 Η Η -CF3 2-methylcyclopropyl 1 12 Η Η -CaH7-n cyclopropyl mp 44-46 ° C 1.13 Η Η -CHjOH 2-methylcyclopropyl mp 111-113 ° C 1 14 Η Η -CH3 2-methylcyclyopropyl mp 73-74 ° C 1.15 4-OCH3 Η CH3 cyclopropyl mp 48-50 ° C 1.16 Η Η -CH2CH2OH cyclohexyl 1 17 Η Η -CH ₂ Br 2-methylcyclopropyl 1 18 Η Η -CdHg-n cyclopropyl dark brown oil No. ²⁴ : 15992 1 19 Η Η -ch ₂ oh cyclohexyl 1 20 Η II CH3 cyclopropyl mp 33-36 ° C 1.21 Η Η H. 2-methylcyclopropyl 1 22 Η Η -CH2Br cyclopentyl 1 23 Η Η -CH2Br cyclobutyl 1.24 Η Η H. cyclobutyl 1.25 Η Η -CaHsII-n cyclopropyl oil n _D ²⁴ .1.6002 1 26 Η Η -CH2OH 1-methylcyclopropyl 1 27 4-Br Η -CH3 cyclopropyl mp 94-98 ° C 1 28 Η Η -CH3 cyclohexyl mp 97-98 ° C 1 29 Η Η -CF3 cyclohexyl 1 30 Η Η -CiHglII-n cyclopropyl 1 31 Η Η -CH3 cyclobutyl mp. 50-52 ° C 1 32 Η Η -CF3 1-methylcyclopropyl 1 33 4-F Η -CH3 cyclopropyl mp. 89-91 ° C 1 34 Η Η H. cyclohexyl 1 35 Η Η -CH2C1 cyclopropyl mp 55-57 ° C 1 36 Η Η -CF3 cyclobutyl 1 37 4-OCHF ₂ Η -CH3 cyclopropyl oil n® ²⁵ .1.5763 1 38 Η Η -C2H5 1-methylcyclopropyl 1 39 Η Η -CHCI2 cyclopropyl mp. 56-58 ° C 1.40 3-C1 5-C1 -CH3 cyclopropyl 1.41 Η Η -CHCI2 cyclopentyl 1 42 Η Η -CH3 1-methylcyclopropyl mp 63-65 ° C 1.43 Η Η -CH2OH cyclobutyl 1 44 3-OCaHs 4-OC2H5 -CH3 cyclopropyl oil no ²⁵ 1.5498 1 45 Η Η -CF3 cyclopropyl mp 66-69 ° C 1.46 4-OCFa Η -CH3 cyclopropyl 1.47 Η Η -CH2OH cyclopentyl 1.48 Η Η -CH2OH cyclopropyl mp. 123-125 ° C 1 49 3-CF ₃ 4- (01 -CH3 cyclopropyl mp 128-130 ° C 1 50 Η Η H. cyclopentyl 1.51 Η Η FI 1-methylcyclopropyl 1 52 Η Η -CH2C1I2OH cyclopropyl

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1 2 3 4 5 6 1.53 3-C1 4-C1 -CH3 cyclopropyl mp. 85-87 ° C 1 54 Η Η -CH3 1-fluorocyclopropyl mp 73-74 ° C 1 55 2-F Η -CH3 cyclopropyl mp 51-54 ° C 1.56 Η Η -CH3 1-bromo-2-methylcyclopropyl 1 57 Η Η H. 1-fluorocyclopropyl 1 58 Η Η -CH3 1-chlorocyclopropyl mp 58-61 ° C 1 59 Η Η -CHzF cyclopropyl mp 48-52 ° C 1.60 3-C1 4-CH3 -CH3 cyclopropyl 1.61 Η Η H. 1-chlorocyclopropyl 1 62 Η Η -CH3 1-bromocyclopropyl 1 63 3-F Η -CH3 cyclopropyl 11. 87-89 ° C 1 64 II Η -CH3 1-chloro-2,2-dimethylcyclopropyl 1 65 2-CH3 3-C1 -CH3 cyclopropyl 1 66 Η Η -CH3 2-fluorocyclopropyl mp 81-84 ° C 1 67 Η Η CHzF 1-fluorocyclopropyl mp 63-65 ° C 1.68 2-C1 5-CH3 -CH3 cyclopropyl 1 69 Η Η -CH3 2-chlorocyclopropyl 1 1. 67-69 ° C 1.70 2-Βγ Η -CH3 cyclopropyl 1 71 2-CHs 4-C1 -CH3 cyclopropyl 1 72 Η Η -CH cyclopentyl mp. 64-66 ° C 1.73 2-C1 6-CH3 -CH3 cyclopropyl 1 74 Η Η -CHzF 1-chlorocyclopropyl mp 43-45 ° C 1 75 Η Η -CHzF 1-bromocyclopropyl 1 76 3-Βγ Η -CH3 cyclopropyl 1 77 Η Η cyclopropyl 1-bromocyclopropyl 1.78 Η Η -CH3 1-bromocyclopropyl mp 51-53 ° C 1.79 2-C11 4-CH3 -CH3 cyclopropyl 1.80 Η Η cyclopropyl 1-methyl-2,2-dichlorocyclopropyl oil ²⁵ 1.6101 1 81 Η Η -CHzF 1-mctylcyclopropyl 1 82 3-CI 4-F -CH3 cyclopropyl 1 83 Η Η -C3H7-1ZO 1-chlorocyclopropyl 1.84 Η Η -CFI3 2,2-difluorocyclopropyl mp 81-84 ° C 1 85 Η Η -C3H7-1ZO 2-methylcyclopropyl 1.86 4-J Η -CH3 cyclopropyl 1.87 Η Η -CHzF 2-fluorocyclopropyl mp. 63-65 ° C 1.88 Η Η -CqHg-n 1-chlorocyclopropyl 1 89 2-CHs Η -CH3 cyclopropyl 190 Η Η -C3H7-IZO cyclopropyl oil _D 2 '' 1.6074 1.91 Η Η -CH3 2,2-dichlorocyclopropyl mp 65-68 ° C 1 92 2-CH3 5-CI -CH3 cyclopropyl 1 93 Η Η -CH3 1-methylcyclohexyl 1 94 Η Η -CHzF 2-chlorocyclopropyl mp 48-50 ° C 1 95 2-OH 5-C1 -CH3 cyclopropyl 1 96 3-C1 4-OH -CH3 cyclopropyl

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1 2 3 4 5 6 1.97 Η Η -CH ₂ CH ₂ OH 1-methyl-2,2-dimethylcyclopro- dust 1 98 Η Η -CH3 2,2-dibromocyclopropyl 1 99 2-Br 4-Βγ -CH3 cyclopropyl 1.100 Η Η -CH ₂ F 2-bromocyclopropyl mp. .38-41 ° C 1.101 3-CH ₃ Η -CH3 cyclopropyl 1 102 Η Η -CiHg-n 2-methylcyclopropyl 1 103 3-CHs 4-Βγ -CH3 cyclopropyl 1 104 Η Η -C3H7-n 1-methyl-2,2-dichlorocyclopro- dust 1.105 Η Η -CH3 2-bromo-2-methylcyclopropyl 1 106 Η Η -CH2CH2OH 2-methylcyclopropyl 1.107 2-C ₂ H ₅ Η -CH3 cyclopropyl 1.108 Η Η -CH2F 2-methylcyclopropyl mp. 55-57 ° C 1.109 Η Η H. 1-bromocyclopropyl 1.110 Η Η -C3H7-n 2-methylcyclopropyl 1.111 3-C ₂ Hs Η -CH3 cyclopropyl 1 112 Η Η -CH2F 2,2-dimethylcyclopropyl 1.113 Η Η -CH3 2-bromo-2-chloro- mp 83-85 ° C 1 114 2-Br 5-Βγ -CH3 cyclopropyl 1.115 2-CHa 4-Βγ -CH3 cyclopropyl 1 116 Η Η -C4H9-1I-th 1-chlorocyclopropyl 1.117 2-CH ₃ 5-F -CH3 cyclopropyl 1 118 4-C ₂ H _s Η -CH3 cyclopropyl 1 119 Η Η H. 2-fluorocyclopropyl 1.120 Η Η -CH3 2,2-dimethylcyclopropyl mp 51-54 ° C 1 121 2-Br 4-CHa -CH3 cyclopropyl 1.122 Η Η -CH2F 1-methyl-2,2-dichlorocyclopropyl 1.123 Η Η -CF3 2-bromocyclopropyl 1.124 Η Η -CF3 2-chlorocyclopropyl 1 125 2-C3H7-1ZO Η -CH3 cyclopropyl 1 126 Η Η -CH2F cyclobutyl mp 44-47 ° C 1 127 Η Η -CH3 1-methyl-2-chlorocyclopropyl 1.128 Η Η cyclopropyl 1-methylcyclopropyl mp 54-56 ° C 1.129 2-C1 4-Βγ -CH3 cyclopropyl 1 130 Η Η -C4H9-1I-th. 1-methylcyclopropyl 1 131 Η Η -C2H ₅ 2-methylcyclopropyl mp. 57-59 ° C 1 132 4-C3H7-1ZO Η -CH3 cyclopropyl 1 133 2-OH ₃ 5-CH ₃ -CH3 cyclopropyl 1.134 Η Η -CH3 1-methyl-2-bromocyclopropyl 1.135 Η Η -CH2CI 2-fluorocyclopropyl 1 136 3-CFa 5-CF ₃ -CH3 cyclopropyl 1.137 Η Η -CF3 2-fluorocyclopropyl 1 138 Η Η -C2H ₅ 2-bromocyclopropyl 1 139 2-CFo Η -CH3 cyclopropyl mp. 56-58 ° C

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1 2 3 4 5 6 1 140 Η Η Η 2-chlorocyclopropyl 1.141 Η Η -CH3 1,2-dimethylcyclopropyl 1 142 Η Η -CH ₂ C1 1-chlorocyclopropyl 1 143 2-C1 3-C1 -CH3 cyclopropyl 1 144 Η Η -C4H9-IIIrd row 1-chlorocyclopropyl 1 145 Η Η -C ₂ H ₅ 2-chlorocyclopropyl mp. 55-60 ° C 1.146 2-CFs 4-C1 -CH3 cyclopropyl 1 147 2-C1 4-C1 -CH3 cyclopropyl 1 148 Η Η -CH3 1-fluoro-2-methylcyclopropyl 1 149 Η Η -CHzCl 1-bromocyclopropyl 1.150 3-CFs Η -CH3 cyclopropyl mp 81-83 ° C 1 151 Η Η -ΟΗ-ΙΙΙ-γζ. 1-methylcyclopropyl 1 152 4-CFa Η -CH3 cyclopropyl mp. 60-62 ° C 1 153 2-C1 5-CF3 -CH3 cyclopropyl 1.154 Η Η -CHjCI 2-fluorocyclopropyl mp. 63-66 ° C 1 155 Η Η -CH3 1-methyl-2,2-dichlorocyclopropyl mp 99-109 ° C 1.156 2-C1 5-0 -CH3 cyclopropyl 1.157 4-OC3H7-1ZO Η -CH3 cyclopropyl 1.158 Η Η -C ₂ H ₅ 2-fluorocyclopropyl mp. 58-61 ° C 1.159 2-C1 6C1 -CH3 cyclopropyl 1 160 Η Η -C2H5 1-chlorocyclopropyl 1 161 Η Η -CH3 1-methyl-2,2-dibromocyclopro- dust 1.162 Η Η -CH ₂ C1 2-chlorocyclopropyl mp 55-57 ° C 1 163 2-OCH3 Η -CH3 cyclopropyl 1 164 Η Η -CH ₂ CH ₂ CH ₂ C1 cyclopropyl 1165 Η Η H. 2-bromocyclopropyl 1.166 2-F 3-F -CH3 cyclopropyl mp 65-67 ° C 1 167 Η Η -C2H5 1-fluorocyclopropyl 1 168 Η Η -CH3 1,2-dimethyl-2-bromocyclopropyl 1 169 Η Η -CH2CI 2-bromocyclopropyl 1 170 3-OCH3 Η -CH3 cyclopropyl mp 47-50 ° C 1.171 Η Η -CH2CI 1-methyl-2,2-dichlorocyclopro- dust 1 172 2-CH3 4-OCH3 -CH3 cyclopropyl 1 173 2-F 4-F -CH3 cyclopropyl mp 73-73.5 ° C 1 174 Η Η -CH2CHzCH2C1 2-methylcyclopropyl 1.175 Η Η -CH3 1,2,2-trimethylcyclopropyl 1.176 Η Η -CH ₂ C1 1 ifluoro-2-methylcyclopropyl 1 177 -OCH F ₂ Η -CH3 cyclopropyl 1.178 Η Η -ch ₂ oh 1-methyl-2,2-dichlorocyclopropyl 1.179 Η Η H. 1-methyl-2,2-dichlorocyclopropyl 1 180 2-F 5-F -CH3 cyclopropyl mp 77-79 ° C

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1 2 3 4 5 6 1 181 Η Η -CH2OH 2,2-dichlorocyclopropyl 1.182 Η Η -CH3 1-bromo-2,2-dichlorocyclopro- 1 183 Η Η -CHC12 2-methylcyclopropyl 1.184 4-OCF ₂ CHF ₂ Η -CH cyclopropyl 1 185 Η Η -CH2C1 1-bromo-2-methylcyclopropyl 1 186 Η Η Η cyclobutyl 1.187 Η Η 2-methylcyclopropyl 1-fuorocyclopropyl Oil 1 188 Η Η 1-fluorocyclopropyl 1-fluorocyclopropyl 1.189 Η Η -CH 1-bromo-2,2-dichlorocyclopropyl 1.190 4-OCF ₂ CHCIF Η -CH3 cyclopropyl 1 191 Η Η -CH2C1 cyclobutyl 1.192 2-F 6-F -CH cyclopropyl mp. 135-137 ° C 1 193 Η Η 2-methylcyclopropyl 1-chlorocyclopropyl 1 194 4-OC3H7-n Η -CH cyclopropyl 1 195 Η Η 1-fuorocyclopropyl 1-chlorocyclopropyl 1 196 Η Η -CH 1,2,2-trichlorocyclopropyl 1.197 Η Η 1-Fluorocyclopropyl 2-chlorocyclopropyl 1.198 4-OCF ₂ CHCl2 Η -CH cyclopropyl 1 199 Η Η 1-fluorocyclopropyl 2-methylcyclopropyl 1,200 3-F 4-F -CH cyclopropyl mp. 91-93 ° C 1 201 Η Η -CC1F2 cyclopropyl mp. 68-70 ° C 1.202 3-OC ₂ H _s Η -CH cyclopropyl 1 203 Η Η -CH 1,2,2-tribromocyclopropyl 1.204 Η Η -CH ₂ Br 1-fluorocyclopropyl 1.205 4-OCF2CFCI2 Η -CH cyclopropyl 1.206 2-OH 5-OH -CH cyclopropyl 1207 Η Η -CH2OH 2-bromocyclopropyl 1 208 Η Η -CCIFj 2-methylcyclopropyl 1 209 Η Η -CH2Br 1-chlorocyclopropyl 1.210 2-OH 4-OH -CH cyclopropyl 1 211 Η Η 2-methylcyclopropyl 2-fuorocyclopropyl Oil 1 212 Η Η -CH ₂ Br 1-bromocyclopropyl 1.213 Η Η 2-chlorocyclopropyl 1-fluorocyclopropyl 1.214 Η Η -CH ₂ OH 1-chlorocyclopropyl 1.215 Η Η 2-methylcyclopropyl 2-chlorocyclopropyl 1 216 3-OH 5-OH -CH cyclopropyl 1.217 Η Η -CH ₂ Br 2-fluorocyclopropyl 1 218 Η Η 2-methylpropyl cyclopropyl mp 44-46 ° C 1.219 2-CHa 3-CHa -CH cyclopropyl 1 220 Η Η -CHzOH 2-fuorocyclopropyl 1 221 Η Η 2-methylcyclopropyl 2-bromocyclopropyl 1 222 Η Η 2-methylpropyl 2-methylcyclopropyl

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1 2 3 4 5 6 1.223 2-CH3 4-CH3 -CHs cyclopropyl 1 224 H. H. -CHzBr 2-chlorocyclopropyl 1.225 H. H. cyclopropyl 2-bromocyclopropyl 1.226 2-CH3 5-CH3 -CH3 cyclopropyl 1 227 H. H. -CH2OH 1-bromocyclopropy1 1 228 H. H. -CF2CF3 cyclopropyl mp 50-52'C 1 229 H. H. -CH2OH 1-chlorocyclopropyl 1 230 H. 11 cyclopropyl 1-chlorocyclopropyl 1.231 2-CH3 6-CH3 -CHs cyclopropyl mp. 122-12.3 ° C ' 1232 H. H. -CHzBr 2-bromocyclopropyl 1.233 H. H. -CFzCFs 2-methylcyclopropyl 1 234 H. H. 1-fluorocyclopropyl 1-methyl-2,2-dichlorocyclopropyl 1.235 H. H. 2-methylcyclopropyl 2-m ^^ yll ^^^ y ^^ and ^^ ropyl mp 58-60 ° C 1.236 H. H. cyclopropyl cyclopropyl mp 75-77 ° C 1 237 3-CHa 4-CH3 -CH3 cyclopropyl 1 238 H. H. -CH2OH 1-fluorocyclopropyl Oil 1 239 H. H. -CzBr 1-fluoro-2-methylcyclopropyl 1.240 H. H. cyclopropyl 2-chlorocyclopropyl 1 241 H. H. cyclopropyl 1-fluorocyclopropyl 1 242 H. H. 2-chlorocyclopropyl 1-chlorocyclopropyl 1 243 H. H. CHzBr 1-methyl-2,2-dichlorocyclopro- dust 1 244 H. H. 1-chlorocyclopropyl 1-methyl-2,2-dichlorocyclopro- dust 1 245 3-CHa 5-CH3 -CHs cyclopropyl 1 246 H. H. cyclopropyl 2-methylcyclopropyl oil nD ⁵ . 16232 1.247 3-H 4-CH3 -CHs cyclopropyl 1 248 H. H. cyclopropyl 2-fluorocyclopropyl 1.249 H. H. -CHzBr cyclopropyl 1.250 2-OCHF2 4-CH3 -CH3 cyclopropyl mp 85-87 ° C 1.251 3-C1 4-OCHFz -CHs cyclopropyl rn / ⁵ 1.5898 1 252 3-OCH3 4-OCH3 -CHs cyclopropyl mp. 74-76 ° C 1 253 H. H. -CHs 1-chloro-1-fluorocyclopropyl mp 97-99 ° C 1 254 3-F 5-F -CHs cyclopropyl mp. 1O5-107 ° C

The following Examples 2 to 7 illustrate the biological properties of the novel compounds of formula I in more detail.

Example II. Action against Venturia inaequalis on apple shoots - residual preventive action.

Apple seedlings 10-20 cm long of fresh shoots were sprayed with a spraying broth (0.006% active ingredient), prepared from a wettable active ingredient powder. After 24 hours, the treated plants are infected with a conidia suspension of the fungus. These plants were then incubated for 5 days at 90-100% relative air humidity and kept in a greenhouse at 20-24 ° C for a further 10 days. Scab infection was assessed 15 days after infection.

The compounds in the table showed strong activity against Venturia fungi (infection: less than 20%). Etc. compounds nr. Ll, 1.6,1.13,1.14,1.59,1.66,1.69,1.84,1.87, 1.94,1.108,1126,1145,

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1,158, 1,180, 1,200 and 1,236 reduced the infestation with Venturia to 0-10%. In contrast, untreated but infected control plants showed 100% Venturia scab infestation.

Example III. Action against Botrytis cinerea on apple fruit - residual preventive action.

The artificially damaged apples are treated in such a way that the spray broth (0.002% active ingredient), prepared from the wettable active ingredient powder, is sprinkled on the damaged sites. The treated fruits are then inoculated with the spore suspension of this fungus and incubated for 1 week at approximately 20 ° C and high relative humidity. In the evaluation, rotten lesions are counted and the fungicidal activity of the test substance is estimated from this.

The compounds in the table show a strong activity (infection less than 20%) against Botrytis; and so, for example, compounds Nos. 1.1,1.6,1.13,1.14,1.31,1.33,1.35,1.48,1.59,1.66-, 1.69,1.84,1.94, 1.87, 1.108, 1.126, 1.131, 1.145, 1.158, 1.180, and 1.236 reduced Botrytis infestation to 0-10. In contrast, untreated but infected control plants showed a 100% Botrytis infection.

Example IV. Action against Erysiphae graminis on barley - residual preventive action.

Barley plants approximately 8 cm in height were sprayed with a spraying broth (0.006 active ingredient) made from a wettable active ingredient powder. After 3-4 hours, the treated plants were dusted with conidia of this fungus. The contaminated barley plants were kept in a greenhouse at a temperature of about 22 ° C and the fungus infestation was assessed after 10 days.

The compounds in the table showed strong activity against Erysiphae; for example, compounds Nos. 1.1,1.6,1.13,1.14,1.3,1.48,1.59,1.6611.69> 1.84.1.87,1.94,1.108,1131,1158 and 1,236 reduced the Erysiphae infection to 0-10%. In contrast, untreated but infected control plants showed a 100% Erysiphae infection.

Example 5: Action against Helminthosporium gramineum.

Wheat grains are contaminated with a spore suspension of this fungus and dried again. The contaminated grains are treated with a suspension of the test substance (600 ppm of active ingredient, based on the weight of the seed), prepared from a wettable powder. After two days, these grains are placed in appropriate agar plates and, after a further 4 days, the development of fungal colonies around the grains is assessed. The number and size of the fungal colonies are taken into account in the evaluation of the test substance. The compounds in the table significantly reduced the fungal infection (0-10%).

Example VI. Action against Colletotrichum lagenarium on cucumbers.

After a 2-week cultivation, the cucumber plants were sprayed with a spraying broth (concentration 0.002) prepared from a wettable active ingredient powder. After 2 days, the plants were infected with a spore suspension [1.5.10. spores / ml] of this fungus and incubated for 36 hours at 23 ° C and high relative air humidity. Incubation was continued at normal atmospheric humidity at about 22-23 ° C. The resulting fungal infestation was assessed 8 days after infection. Untreated leGz, the infected control plants showed 100% fungus infestation.

The compounds in the table showed a strong effect and limited the spread of the disease. Fungus infestation was suppressed to 20% or less.

Example VII. a / Contact insecticidal action against Nephotettix cincticeps and Nilaparvata lugens / nymphs-larvae /.

The test was carried out on growing rice plants. For this purpose, 4 plants were planted each time (14-20 days old / about 15 cm high in a pot / 5.5 cm in diameter).

These plants were sprayed on a turntable with 100 ml of an aqueous emulsion preparation containing 400 ppm of the active ingredient in question. After the spray layer had dried on, each plant was colonized with 20 nymphs of the third-stage insect. In order to prevent the singers from leaving, a glass cylinder which was opened on both sides was slid over the planted plants and covered with a gauze cover. Until maturity, the nymphs were kept on the treated plants. Estimation of percent mortality was postponed

160,991 days from settlement. This temperature was carried out at about 277 ° C and 60% relative humidity for 16 hours.

b / Systemic insecticidal action against Nilspsrvsts lugens / in water /.

Rice plants about 10 days old (about 10 cm tall) were placed in a plastic cup containing 150 ml of an aqueous emulsion formulation of the active substance to be tested at a concentration of 100 ppm and closed with a multi-perforated plastic lid. The roots of the rice plant were inserted into the aqueous test formulation through an opening in the plastic lid. The rice plant was then infested with a group of 20 Nilspsrvsta lugens nymphs at the N2-N3 stage and covered with a plastic cylinder. The test was carried out at a temperature of about 26 ° C, 60% relative air humidity, and an exposure period of 16 hours. After 5 days, the number of test animals killed is assessed in comparison to the untreated control animals. It was thus determined whether the active substance absorbed by the roots killed the test animals on the aerial parts of the plant.

The compounds in the table showed strong killing of rice pests both in the contact test a / and in the system test b /. Mortality was above 80%. Compounds Nos. 1.1, 1.6, 1.14, 1.59, 1.66, 1.87, 1.94, 1.108, and 1.236 resulted in almost complete extermination (98-100%) of the insects.

Ο ο

II ιι

Rs-C-CH ^ C-R ,.

Formula 3

H2N-C χ

Ν = /

R4

Formula 5

Publishing Department of the UP RP. Circulation of 90 copies

Price: PLN 10,000

Claims (1)

Patent claim The method for the preparation of the new 2-anilinopyrimidine derivatives of the general formula I, in which Ri and R2 independently represent a hydrogen atom, a halogen atom, a C1-C3-alkyl radical, a C1-C2-haloalkyl radical, a C1-C3-alkoxy group or a C1-C3 group. -C3-haloalkoxy, R3 is a hydrogen atom, a C1-C4-alkyl radical optionally substituted with halogen, hydroxy or cyano, a cyclopropyl radical optionally up to three times, equally or differently substituted with a methyl and / or halogen group, and R4 is a C3-C6 radical - cycloalkyl optionally up to three times, equally or differently substituted with methyl and / or halogen, characterized in that the phenylguanidine salt of the formula 2a or the matrix guanidine of the formula 2b is reacted with the dicetone of the formula 3 in the medium or without solvent at a temperature of 60- 160 ° C, or a salt of guanidine of formula 4 with dicetone of formula 3 without solvent at a temperature of 100-160 ° C or in an inert solvent at a temperature of from 30-140 ° C it is cyclized to the pyrimidine compound of formula 5 and the obtained compound of formula 5 is reacted with the compound of formula 6 under HY cleavage conditions in the presence of a proton acceptor in an aprotic solvent medium at a temperature of 30-140 ° C, in Formulas 2-6, R1-R4 have the meanings given in the discussion of Formula 1, A @ is the anion of the acid and Y is the halogen atom.