WO1996006086A1

WO1996006086A1 - 4-cyclohexylaminopyrimidine derivative, process for producing the same, and agrohorticultural pest control drug

Info

Publication number: WO1996006086A1
Application number: PCT/JP1995/001665
Authority: WO
Inventors: Tokio Obata; Katsutoshi Fujii; Kiyoshi Tsutsumiuchi; Yoshinori Yamanaka
Original assignee: Ube Industries, Ltd.
Priority date: 1994-08-23
Filing date: 1995-08-23
Publication date: 1996-02-29

Abstract

A 4-cyclohexylaminopyrimidine derivative represented by general formula (1), wherein: R1 represents halogen, C¿2?-C5 acyloxy, hydroxy, C1-C4 alkoxy or C1-C4 alkylthio; Q represents a substituent represented by general formula (Qa), etc.: (wherein R?2¿ represents C¿1?-C8 alkyl, phenyl, pyrimidinylamino, C1-C6 alkoxy, COOR?3¿, amino or NHCOR4); and the asterisked carbon atom represents an asymmetric carbon atom.

Description

O 96/0

Specification

4-Cyclohexylaminovirimidine derivative, its production method and pesticides for agricultural and horticultural use

The present invention relates to a novel 4-cyclohexylaminopyrimidine derivative which is a pesticide for agricultural and horticultural use useful as an insecticide, acaricide, fungicide and the like. Background art

As a 4-cyclohexylaminopyrimidine derivative similar to the present invention, there is a compound disclosed in DE 428 08 54 A1.

However, there is no disclosure of a 4-cyclohexylaminopyrimidine derivative having a substituent at the 6-position ethyl group of the pyrimidine ring as in the present invention.

Therefore, since the 4-cyclohexylaminopyrimidine derivative of the present invention is a novel compound, it is also known that it has a pest control activity for agricultural and horticultural use which is useful as an insecticide, acaricide, fungicide and the like. Absent.

An object of the present invention is to provide a novel 4-cyclohexylaminovirimidine derivative, a process for producing the same, and a pesticide for agricultural and horticultural use containing the same as an active ingredient, which are useful as insecticides, acaricides, and fungicides. To provide. Disclosure of the invention

The present inventors have conducted studies to solve the above-mentioned problems. As a result, a novel 4-cyclohexylaminovirimidine derivative is useful as an insecticide, acaricide, fungicide, etc. The present inventors have found that they have a remarkable controlling activity as an agent, and have completed the present invention.

That is, the present invention is as follows.

The first invention has the following formula (1):

Each substituent in the formula is as follows.

R ¹ represents a halogen atom, an alkoxy group having 2 to 5 carbon atoms, a hydroxyl group, an alkoxy group having 1 ^ 4 carbon atoms, or an alkylthio group having 1 to 4 carbon atoms.

Q is the following equation (Qa):

In the formula, R ² is an alkyl group having 1 to 8 carbon atoms, a phenyl group, a pyrimidinylamino group, an alkoxy group having 1 to 6 carbon atoms, a C00 R ³ group,

Here, R ³ represents an alkyl group having 1 to 4 carbon atoms or a hydrogen atom.

Amino group or NHC0 R ⁴ groups

Here, R ⁴ represents an alkyl group having 1 to 8 carbon atoms or an alkoxy group having 1 to 8 carbon atoms.

Represents;

Or the following formula (Qb):

The following formula (Qc)

Wherein n represents 2 or 3;

Represents a substituent represented by: Carbon atoms marked with * indicate asymmetric carbon atoms:

The second invention relates to a 4-cyclohexylaminovirimidine derivative represented by the following formula (2):

In the formula, R ¹ and * are as defined above. X represents a halogen atom,

And a pyrimidine derivative represented by

The following equation (3-1):

H ₂ N-Qac (3-1) In the formula, Qac represents a substituent represented by the above formula (C) or the formula (Qc), and cyclohexylamines represented by the following formula [Compound (3-1) Wherein Q is represented by the formula (Qa) or the formula (Qc) in the above formula (1), and a method for producing the 4-cyclohexylaminopyrimidine derivative.

The third invention has the following formula (lc):

H ₃ C (lc)

R

In the formula, R ′, n and * are as defined above,

Wherein the compound (lc) represented by the formula (1) is hydrolyzed under acidic conditions, wherein Q is a 4-cyclohexylaminovirimidine derivative represented by the formula (Qb): is there.

The fourth invention relates to a pesticidal composition for agricultural and horticultural use, comprising a 4-cyclohexylaminovirimidine derivative represented by the above formula (1) as an active ingredient. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail.

R ¹ and Q represented by the target compound, a novel 4-cyclohexylaminopyrimidine derivative [compound (1)] and its raw materials [compound (2) and compound (3-1)] are as follows: It is.

[R ¹ ]

Examples of R ¹ include a halogen atom, an alkoxy group having 2 to 5 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and an alkylthio group having 1 to 4 carbon atoms.

Examples of the halogen atom include a chlorine atom, an iodine atom, a bromine atom, a fluorine atom and the like; a fluorine atom, a chlorine atom and a bromine atom are preferred.

Examples of the acyloxy group include those having a linear or branched alkyl group; those having 2 to 4 carbon atoms are preferred; and acetyloxy groups are more preferred.

Examples of the alkoxy group include linear or branched ones; those having 1 to 4 carbon atoms are preferred; and methoxy and ethoxy groups are preferred.

Examples of the alkylthio group include those having a linear or branched alkyl group; a methylthio group and an ethylthio group are preferred.

C Q]

Examples of Q include a substituent represented by the above formula (Qa), (Qb), or (Qc).

The compound (1) in which the substituent Q is represented by the formula (Cia), (Qb), or (CLc) is referred to as a compound (la), a compound (lb), or a compound (lc), respectively.

[R ² ]

The R ² in formula (C), a 1-8C alkyl group having a carbon Fuweniru group, pyrimidinyl § amino group, alkoxy groups having 1-6 carbon atoms, C 00 R ³ groups, Amino group, NHC 0 group And the like.

Examples of the alkyl group include straight-chain or branched ones; those having 1 to 5 carbon atoms are preferable; and methyl, ethyl, t-butyl and n-alkyl groups. Pentyl groups are preferred.

Examples of the phenyl group include unsubstituted or substituted ones. The pyrimidinylamino group preferably has the following formula (Qa-1):

Wherein R ¹ and * are as defined above,

Is a substituent (Qa-1) represented by

R ¹ in the substituent (Qa-1) is preferably a halogen atom, an acyloxy group having 2 to 5 carbon atoms, a hydroxyl group, or the like; More preferable substituent (Qa-l) is described in Table 2 below. And the substituents R ² corresponding to the compounds (la-42) to (la-48) described in (1).

Examples of the alkoxy group include straight-chain or branched ones; those having 1 to 4 carbon atoms are preferred; and methoxy, ethoxy and n-butoxy groups are preferred.

As R ³ is the C00 R ³ groups, linear or branched having 1-4 § alkyl group carbon and hydrogen atoms can be mentioned; as the alkyl group, Echiru group, is t one-butyl group preferable.

Examples of R ⁴ in the NH COR ⁴ group include a linear or branched alkyl group having 1 to 8 carbon atoms, and a linear or branched alkoxy group having 1 to 8 carbon atoms. As an alkyl group, a methyl group and a t-butyl group are preferable; and as an alkoxy group, a t-butoxy group is preferable.

n represents 2 or 3.

Examples of the compound (1) include compounds obtained by combining the above-mentioned various substituents. Preferred compounds from the viewpoint of drug efficacy are as follows.

(a) Compound Ua) in which R ¹ is a halogen atom and R ² is an alkyl group having 1 to 8 carbon atoms. (b) Compound (la) in which R ¹ is a halogen atom and R ² is a phenyl group.

(c) The compound (la) in which R ¹ is an acyloxy group having 2 to 5 carbon atoms and R ² is a phenyl group.

(d) Compound (la) in which R ¹ is a hydroxyl group and R ² is a phenyl group.

(e) A compound (la) in which R ¹ is an alkoxy group having 1 to 4 carbon atoms and R ² is a phenyl group.

(f) Compound (la) in which R ¹ is a halogen atom and R ² is a pyrimidinylamino group

(g) Compound in which R ¹ is a halogen atom (lb).

(h) Compound (lc) wherein R ¹ is a halogen atom and n is 2.

As R ¹ and R ² in the compounds (la), (lb) and (lc) shown in (a) to (h), preferred are those described in the explanation of R ′ and R ² above. Preferred ones can be exemplified.

Specific examples of these compounds (1) include compounds ((la-1). (La-7), (la-8), (la-11), and (la-13) described in Table 2 below. ) To (la-19), (la-21), (la-22), (la-25), (la-26), (la-29), (la-30), (la-40), (la-41), (la-47), (la-48)}, compound (lb-4), compound (lc-4) and the like.

Since compound (1) of the present invention has an amino group, acid addition salts derived therefrom are also included in the present invention.

Examples of the acid that forms an acid addition salt include inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid; formic acid, oxalic acid, fumaric acid, adipic acid, stearic acid, maleic acid, and aconic acid. Carboxylic acids such as (1); organic sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, and P-toluenesulfonic acid;

In the compound (1) of the present invention, the carbon atom marked with * is an asymmetric carbon atom, and any optical isomer, racemate, diastereomer compound or a mixture thereof is included in the present invention. .

Preferred embodiments for producing the 4-cyclohexylaminovirimidine derivative represented by the above formula (1) include the synthesis methods 1 and 2 described as the second and third inventions. In addition, the following five production methods (synthesis methods 3 to 7) can be mentioned.

(Synthesis method 3)

The following equation (1-1):

NH-Q

H ₃ C (1-1)

In the formula, Q and * have the same meanings as described above, and R ⁶ represents a halogen atom, and a 4-cyclohexylaminopyrimidine derivative represented by

The following equation (4):

R ⁷ One H (4)

In the formula, R ⁷ represents an acyloxy group having 2 to 5 carbon atoms;

Wherein, in the above formula (1), R ¹ is a 4-cyclohexylamino pyrimidine derivative [compound (1-2) Name. ] Manufacturing method.

(Synthesis method 4)

The following equation (1-2):

NH-Q

^C "^ N (1-2)

Ju OS

In the formula, Q, * and R ⁷ are as defined above.

A 4-cyclohexylaminopyrimidine derivative represented by

The following equation (5):

M-0 H (5)

Where M represents alkali gold,

In the above formula (1), characterized by reacting with an inorganic base represented by 4-cyclohexylaminovirimidine derivative in which R ¹ is represented by a hydroxyl group [referred to as compound (1-3)] ] Manufacturing method.

(Synthesis method 5)

A 4-cyclohexylaminopyrimidine derivative represented by the above formula (1-1) and the following formula (6):

R ⁵ Y-H (6)

In the formula, R ⁵ represents a lower alkyl group; Y represents an oxygen atom or a sulfur atom, and is reacted with an alcohol (or a mercaptan) represented by the following formula (1): In which R ¹ is a lower alkoxy group (or a lower alkyl group), a 4-cyclohexylaminovirimidine derivative [referred to as compound (1-4)]. ] Manufacturing method.

(Synthesis method 6)

A 4-cyclohexylaminopyrimidine derivative represented by the above formula (1-1) and the following formula (7):

M-F (7)

Wherein M is as defined above,

A 4-cyclohexylaminopyrimidine derivative wherein R ¹ is a fluorine atom in the above formula (1), characterized by reacting with an alkali metal fluorine compound represented by the formula (1): Name. ] Manufacturing method.

(Synthesis method 7)

The following equation (1-3):

(1-3,

In the formula, Q and * are as defined above,

A 4-cyclohexylaminopyrimidine derivative represented by

The following equation (8): H ₅ C

N-S-Fa (8)

H ₅ C

A method for producing a 4-cyclohexylaminovirimidine derivative [compound (1-5)] wherein R ¹ is a fluorine atom in the above formula (1), wherein the compound is reacted with a fluorinating agent represented by the following formula (1).

The above-mentioned synthesis methods 1 to 7 of the compound (1 \\) of the present invention will be described in more detail.

(Synthesis method 1)

In the synthesis method 1, as shown below, the compound (2) and the compound (3-1) are reacted in a solvent or without a solvent to obtain a compound (la) or a compound (lc) [Q in the compound (1) Or a compound represented by Qc), wherein the reaction can be promoted by reacting in the presence of a base.

(3-1)

(2)

(1) In the formula, R ¹ , X, * and Qac are as defined above.

The type of the solvent is not particularly limited as long as it does not directly participate in the reaction. For example, benzene, toluene, xylene, methylnaphthalene, petroleum ether, ligroin, hexane, chlorobenzene, dichlorobenzene, Chlorinated or non-chlorinated aromatic, aliphatic and cycloaliphatic hydrocarbons such as methylene chloride, chloroform, dichloroethane, trichloroethylene, cyclohexane; Ethers such as ter, tetrahydrofuran and dioxane; ketones such as acetone and methylethylketone; amides such as N, N-dimethylformamide, N, N-dimethylacetamide; acetonitrile, propio Nitriles such as nitril; organic bases such as triethylamine, pyridine, N, N-dimethylaniline; 1,3-dimethyl-2-imidazolidone; dimethyl sulfoxide; a mixture of the above solvents; it can.

The solvent can be used in such an amount that the compound (2) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.

The type of the base is not particularly limited. For example, organic bases such as triethylamine, pyridin, N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-indene (DBU) Alkali metal alkoxides such as bases, sodium methoxide, sodium ethoxide, inorganic hydrides such as sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, and potassium carbonate Bases may be mentioned; organic bases are preferred.

The amount of the base to be used is 0.001 to 5 moles, preferably 0.8 to 2 moles, relative to compound (2).

The reaction temperature is not particularly limited, but is in the range of from room temperature to the boiling point of the solvent used or less; C is preferred.

The reaction time varies depending on the above concentration and temperature; it is usually 0.3 to 4 hours.

The amount of the starting compound used is 0.5 to 2 times mol of compound (3-1) relative to compound (2); preferably 1.0 to 1.2 times mol.

The raw material compound (2) in which R ¹ is represented by X is usually prepared by compound (7-1) and compound (7-1) as shown below, as in the method described in JP-A-5-94417. (8-1) with a solvent in a solvent.

(7-1) (8-1)

(2) In the formula, when R ¹ = X, X and * are as defined above.

Examples of the solvent include the above-mentioned solvents; the amount of the solvent can be used such that the amount of the compound (7-1) is 5 to 80% by weight.

The reaction temperature is not particularly limited, but is in the range of room temperature to the boiling point of the solvent used or lower.

The reaction time varies depending on the above concentration and temperature; it is usually 2 to 10 hours.

The amount of the starting compound to be used is 0.5 to 3 times mol of compound (8-1) relative to compound (7-1); preferably 0.9 to 1.2 times mol.

The starting compound (2) when R ¹ is other than X can be produced by the method described in JP-A-5-320141.

Compound (7-1) can be produced, for example, according to the method described in Journal of Chemical ♦ Society (JC S) 3478-3481 (1955) as shown in the following formula. Can be.

(7-2) (8-2) (7-1) In the formula, X has the same meaning as described above.

After the completion of the reaction, the compound (2) produced as described above is subjected to ordinary post-treatments such as extraction, concentration, and filtration, and if necessary, appropriately by known means such as recrystallization and various types of chromatography. It can be purified.

Examples of the compound (2) include the compounds (2-1) to (2-7) shown in Table 1 below.

Compound (3-1) used in the present invention can be produced by carrying out a reaction as shown in the following formula. _Λ "NH2_rei _ττ _^. _Τ"

0 = Qac "HON = Q _ac

L i A £ H 4 H ₂ N-Q _ac

(3-1)

In the formula, Qac is as defined above.

As the compound (3-1), the types of the substituents corresponding to the compounds (la-l) to (la-149) and the compounds (lc_l) to (lc-4) shown in Table 2 below [Compound (3-1) ( _la- to (3-1) and Compound (3-1) ( _lc ) to]

(3-1) _Called ( _lc - ₄ ). For example, in compound (3) or a-,), R ^{2 in the} formula represented by compound (3-1) is a t-butyl group. ].

The target compound (1) synthesized as described above includes the compounds (la-l) to (la-149) and the compounds (lc-l) to (lc-4) shown in Table 2 below. [For example, in the compound (la-1), R ^{1 in the} formula represented by the compound (la) is a chlorine atom, and R ² is a t-butyl group. ].

(Synthesis method 2)

In the synthesis method 2, as shown below, the compound (lc) is hydrolyzed under acidic conditions to obtain the compound (lb) [Q in the compound (1) is a compound represented by Qb]. .

2) n

R

(lc) acid

R

(lb) In the formula, R ¹ , η, and * are as defined above.

Examples of the acid used for the hydrolysis include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, carboxylic acids such as acetic acid, oxalic acid, and tartaric acid, methanesulfonic acid, benzenesulfonic acid, and ρ-toluene. Examples thereof include organic sulfonic acids such as sulfonic acid; hydrochloric acid and acetic acid are preferred.

The amount of the acid to be used is 0.1 to 5 moles to compound (lc); preferably 0.1 to 2 moles.

Examples of the type of the solvent include ketones, amides, and ethers described in Synthesis Method 1, alcohols (such as methanol, ethanol, propanol, and butanol), water, and a mixture of the above solvents. But preferably a mixture of alcohols and water.

The solvent can be used in such an amount that the compound (lc) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.

The reaction temperature is not particularly limited, but is in the range of room temperature to the boiling point of the solvent used or lower; room temperature to 5 O'C is preferred.

The reaction time varies depending on the concentration and the temperature described above; After completion of the reaction, the compound (lb) produced as described above is subjected to ordinary post-treatments such as extraction, shrinkage, and thigh, and if necessary, appropriately by known means such as recrystallization and various types of chromatography. It can be purified.

Examples of compound Ub) include compounds Ub-l) to (lb-4) shown in Table 2 below.

(Synthesis method 3)

In the synthesis method 3, as described below, the compound (1-1) and the compound (4) are reacted in a solvent or without a solvent to give the compound (II) [R ′ in the compound (1) is a lower acyloxy group. A certain compound] can be obtained by reacting in the presence of a base.

(1-1)

(1-2) In the formula, CI, R ⁶ , R ⁷ and * are as defined above.

Examples of the type of the solvent include aliphatic carboxylic acids such as acetic acid and propionic acid, and mixtures thereof in addition to the solvents described in Synthetic Method 1. N, N-dimethylformamide and the introduced The same aliphatic carboxylic acid as the acyloxy group is preferred.

The amount of the solvent used can be such that the compound (1-1) is 5 to 80% by weight; it is preferably 10 to 70% by weight.

Examples of the type of the base include the bases described in Synthesis method 1; an inorganic base is preferred.

The amount of the base to be used is 1 to 5 moles relative to compound (1-1); preferably 2 to 5 moles.

The reaction temperature is not particularly limited, be at a temperature within range of the boiling point of the solvent used at room temperature; 60~; 120 ^e C is preferred.

As the compound (4), a commercially available product can be used.

After completion of the reaction, the target compound (1-2) produced as described above is subjected to ordinary post-treatments such as extraction, concentration, filtration and the like, and, if necessary, recrystallization and various chromatographies. It can be appropriately purified by a known means such as one.

As the compound (1-2), the compounds shown in Table 2 below ((la-3), (la-4), (la-13), (la-14), (la-35), ( (la-36), (la-38), (la-43), (la-44), (la-51), (la-52), (la-59), (la-60), (la- 68)-(la-70). (La-80)-(la_82), (la-104)-(la-106), (la-116)-(la-118), (la-128)-( la-130), (la-140) to (la-142)}. Compound (lb-2), compound (lc-2) and the like. (Synthesis method 4)

In the synthesis method 4, as described below, the compound (1-2) and the compound (5) are reacted in a solvent to form the compound (1-3) {the compound in which R ¹ in the compound (1) is a hydroxyl group]. This is a method of obtaining a compound, and the reaction can be promoted by reacting in the presence of a base. H

R

(1-2)

NH-Q

H ₃ C * oy

ゝ N

OH

(1-3) In the formula, R ⁷ , * and M are as defined above.

Examples of the solvent include, in addition to the ethers, ketones, and amides described in Synthesis Method 1, alcohols (such as methanol, ethanol, propanol, and butanol), water, and a mixture of the above solvents. But a mixture of alcohols and water is preferred.

The solvent can be used in such an amount that the compound (1-2) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.

Examples of the type of the base include the inorganic bases described in Synthesis Method 1; sodium hydroxide and potassium hydroxide are preferred.

The amount of the base to be used is 1 to 5 moles relative to compound (1-2); preferably 2 to 5 moles.

The reaction temperature is not particularly limited, but is in the range of room temperature to the boiling point of the solvent to be used or lower; preferably room temperature to 5 CTC.

The reaction time varies depending on the concentration and the temperature as described above; is there.

As the compound (5), a commercially available product can be used.

After completion of the reaction, the target compound (1-3) produced as described above is subjected to ordinary post-treatments such as extraction, concentration, rupturing, etc., and, if necessary, recrystallization and various chromatographic methods. It can be appropriately purified by known means such as.

As the compound (1-3), the compounds shown in Table 2 below ((la-5), (la-6), (la-15), (la-16), (la-39), ( (la-45), (la-46), (la-53), (la-54), (la-61), (la-62), (la-71)-(la-73), (la- 83)-(la-85), (la-89)-(la-91), (la-107)-(la-109), (la-119)-(la-121), (la-131) ~ (La-133), (la-143) ~ a-145)}, compound (lb-3), compound (lc-3) and the like.

(Synthesis method 5)

In the synthesis method 5, the compound (1-1) and the compound (6) are reacted in a solvent or without a solvent as follows to obtain a compound (1-4) [R ¹ in the compound (1) has ¹ carbon atom. Or a compound having 4 to 4 alkoxy groups or an alkylthio group having 1 to 4 carbon atoms]. The reaction can be promoted by reacting in the presence of a base.

^H 3

(1-1)

(1-4)

In the formula, Q, R ⁵ , R ⁶ , * and Y are as defined above.

Examples of the type of the solvent include ethers, ketones, amides and a mixture of the above-mentioned solvents described in Synthesis Method 1. Ketones and amides are preferred. The amount of the solvent used should be such that the compound (1-1) accounts for 5 to 80% by weight. But preferably 10-70% by weight.

The amount of the base used is 1 to 5 moles per 1 mole of the compound; 1 to 3 moles is preferable.

The reaction temperature is not particularly limited, but is in the temperature range from room temperature to the boiling point of the solvent used or less; room temperature to 6O'C is preferred.

The reaction time varies depending on the above concentration and temperature, but is usually 0.3 to 2 hours.

As the compound (6), a commercially available product can be used.

After completion of the reaction, the target compound (1-4) produced as described above is subjected to ordinary post-treatments such as extraction, concentration, and filtration, and if necessary, recrystallization and various chromatographic methods. It can be appropriately purified by known means such as.

As compound U-4), compounds {(la-9), (la-10), (la-19) to (la-22), (la-31) to (la- -34), (la-148), (la-149)}.

(Synthesis method 6)

In the synthesis method 6, as described below, the compound (1-1) and the compound (7) are reacted in a solvent to obtain the compound (1-5) {the compound in which R ¹ in the compound (1) is a fluorine atom] The reaction can be promoted by heating and reacting.

NH-Q

N + M-F

^H 3C * 9 (7)

(1-1)

NH-Q

N

H ₃ C, *, N

F

(1-5 In the formula, Q, R ⁶ , * and M are as defined above.

Examples of the type of the solvent include amides such as N, N-dimethylformamide and N, N-dimethylacetamide; 1.3-dimethyl-2-imidazolidone; dimethyl sulfoxide; sulfolane; Can be mentioned.

The solvent can be used in such an amount that the compound (1-1) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.

Examples of the compound (7) include an alkali metal fluorine compound; preferred are cesium fluoride and potassium fluoride.

The ratio of the solvent to be used is 1 to 5 moles relative to compound (1-1); preferably, it is 1.2 to 3 moles.

The reaction temperature is not particularly limited, be at a temperature within range of the boiling point of the solvent used at room ^{temperature; 1 0 0~ 1 4 0 e} C is preferred.

The reaction time varies depending on the concentration and temperature as described above; it can be usually carried out for 1 to 8 hours.

(Synthesis method 7)

Compound U-5) can be synthesized by reacting compound (1-3) with a fluorinating agent in a solvent, in addition to synthesis method 6, as follows.

Synthesis method 7 is a method of reacting compound (1-3) with a fluorinating agent in a solvent to obtain compound U-5).

+ Fluorinating agent

O H

( 13)

F

(1 -5) 1 5

In the formula, Q and * are as defined above.

Examples of the solvent include chlorinated or non-chlorinated aromatic, aliphatic, and alicyclic hydrocarbons described in Synthesis Method 1; ethers such as getyl ether, tetrahydrofuran, and dioxane; And the like.

The amount of the solvent to be used may be such that the compound (1-3) is 5 to 80% by weight; however, it is preferably 10 to 70% by weight.

The fluorinating agent is not particularly limited,

The following formula:

Getyl aminosulfur trifluorofluoride (DAST), etc. represented by

The amount to be used is 1 to 5 moles relative to compound (1-3); preferably 1 to 2 moles relative to compound (1-1).

The reaction temperature is not particularly limited, but is in a range of from the ice-cooling temperature to the boiling point of the solvent used or lower; preferably from the ice-cooling temperature to room temperature.

The reaction time varies depending on the concentration and temperature, but is usually 0.3 to 2 hours.

After completion of the reaction, the target compound (1-5) produced by Synthetic Methods 6 and 7 is subjected to ordinary post-treatments such as extraction, concentration, and filtration, and if necessary, recrystallization, various chromatographies, etc. Can be appropriately purified by known means.

Compound U-5) includes the compounds ((la-7), (la-8), (la-17), (la-18), (la-25), (la -26), (la-29), (la-30), (la-40), (la-41), (la-47), (la-48), (la-55), (la-56 ), (la-63), (la-64), (la-74) to (la-76), (la-86 to (la-88), (la-92) to (la-97), ( (la-110)-(la-112), (la-122)-(la-124), (la-134)-(la-136), (la-147)}, compound (lb-4), compound (Lc-4) and the like.

Examples of pests in agricultural and horticultural activities in which the compound (1) of the present invention has a controlling effect include agricultural and horticultural pests [for example, Hemiptera (Pteromorpha, Lepidoptera, Aphids, Whitefly) and the like. Eyes (Lepidoptera, Convolvulus, Coleoptera, Mephides, Beetles, cabbage beetles, etc.); , Flies, powers, cockroaches, etc.), storage pests (such as terrestrial mushrooms, beetles, etc.), mosquitoes in the soil, pine woods, ticks, etc., and agricultural and horticultural pathogens (eg, Wheat rust, barley powdery mildew, cucumber downy mildew, rice blast, tomato blight, etc.).

The pesticidal composition for agricultural and horticultural use of the present invention has a remarkable insecticidal, acaricidal and bactericidal effect, and contains at least one compound (1) as an active ingredient.

The compound (1) can be used alone, but it is usually compounded with a carrier, a surfactant, a dispersant, an auxiliary agent and the like (for example, powders, emulsions, fine granules, granules IJ, It is preferably used as a composition such as a wettable powder, an oily suspension, or an aerosol).

Carriers include, for example, solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, cake sand, ammonium sulfate, urea, etc .; hydrocarbons (kerosene, mineral oil, etc.), aromatic hydrocarbons (Benzene, toluene, xylene, etc.), chlorinated hydrocarbons (chloroform, carbon tetrachloride, etc.), ethers (dioxane, tetrahydrofuran, etc.), ketones (acetone, cyclohexanone, isophorone) ), Esters (ethyl acetate, ethylene glycol acetate, dibutyl maleate, etc.), alcohols (methanol, n-hexanol, ethylene glycol, etc.), polar solvents (dimethylformamide, dimethyl sulfoxide, etc.), Liquid carrier such as water; air, nitrogen , Carbon dioxide, gaseous carriers such as Freo emissions (in this case, can be mixed jet), etc. can and Ageruko.

Examples of surfactants and dispersants that can be used to improve the performance of this agent, such as adhesion to animals and plants, improved absorption, and dispersion, emulsification, and spreading of drugs, include alcohol sulfates and alkyl sulfones. Acid salts, lignin sulfonates, polyoxyethylene glycol ethers, and the like. In order to improve the properties of the preparation, for example, carboxymethylcellulose, polyethylene glycol Cole, gum arabic and the like can be used as adjuvants.

In the production of the present agent, the above-mentioned carrier, surfactant, dispersant and auxiliary agent can be used alone or in appropriate combination, respectively, depending on the purpose of each.

When the compound (1) of the present invention is formulated, the concentration of the active ingredient is usually from 1 to

50% by weight, usually 0.3 to 25% by weight for powders, 1 to 90% for wettable powders

%, Usually 0.5 to 5% by weight for granules, 0.5 to 5% by weight for oils and 0.1 to 5% by weight for aerosols.

These preparations can be diluted to an appropriate concentration and applied to various uses by spraying them onto plant foliage, soil, or the surface of paddy fields, or directly applying them, depending on the purpose. Example

Hereinafter, the present invention will be described specifically with reference examples and examples. Note that these examples do not limit the scope of the present invention.

Reference Example 1 [Synthesis of Compound (2)]

(1) Synthesis of 6- (1-chloroethyl) -1,4,5-dichloropyrimidine [Compound (2-1)]

4, 5-dichloro-6-Echirupiri spermidine a (2 70 g) was dissolved in dichloromethane (750 meters l), warmed to 30 to 35 ^e C, elaborate blown 2 hours with chlorine gas under搰拌.

Nitrogen gas was blown into the reaction solution to remove excess dissolved chlorine gas. Then, the solvent was distilled off under reduced pressure, and the obtained residue was distilled under reduced pressure to obtain 240 g of the target substance as a pale yellow liquid.

(2) Synthesis of 4,5-dichloro-6- (1-fluoroethyl) pyrimidine [compound (2-4)]

Dissolve 4,5-dichloro-1-6- (1-hydroxyxethyl) pyrimidine (2.1) in dichloromethane (15 ml), cool with ice, and search for getylaminosulfur trifluoride (2.0 g). ) Was added dropwise, and the mixture was further stirred at room temperature for 1 hour to complete the reaction. Cold water (20 ml) was added to the reaction solution, the dichloromethane layer was separated, washed with water and dried over anhydrous sodium sulfate. Then, the solvent is distilled off under reduced pressure, and the obtained residue is purified by column chromatography (Pelcogel C-200, elution with chloroform) to give the target compound as a pale yellow oily liquid 1.3 g was obtained.

• bp 229-231 ^e C

Ή-NMR (C D C 1 a, 5 p pm)

1.64 to 1.81 (d-d, 3 H), 5.84 to 6.19 (d-q, 1 H), 8.92 (s, 1 H)

(3) Synthesis of 5-chloro-4-fluoro-6- (1-fluoroethyl) pyrimidine [Compound (2-5)]

4,5-Dichloro-6- (1-fluoroethyl) pyrimidine (1.3 g) is dissolved in N, N-dimethylformamide (1Om 1), and cesium fluoride (4.0 ε) is added. For 1.5 hours to complete the reaction.

Cold water (10 ml) was added to the reaction solution, and the separated oil was extracted with toluene, washed with water, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (Pelcogel C-200, eluting with chloroform) to obtain the target compound as a pale yellow oily liquid. Og was obtained.

• b. P. 192-194. C

Ή-NM R (C DC 1 a, 5 p pm)

1.66 to 1.82 (d-d, 3H), 5.85 to 21 (d-q, 1H), 8.83 (s, 1H)

(4) Synthesis of 6— (1-acetoxyshethyl) —4,5-dichloropyrimidine [Compound (2-6)]

6- (1-Chloroethyl) 1,4-Dichloropyrimidine (10.2 g) is dissolved in N, N-dimethylformamide (150 ml), and potassium acetate (12.0 g) is dissolved. And potassium carbonate (3.0 g) were added, and the mixture was stirred at about 6 CTC for 3 hours.

Water (200 ml) was added to the reaction solution, and the separated oil was extracted with toluene, washed with water, and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to column chromatography (Co-gel C-200, toluene: acetate). Purification by chill = 10: 1 elution) gave 5.2 g of the desired product as a pale yellow liquid.

-NMR (C D C 13, δ p pm)

1.55 ~: I.62 (d, 3H), 2.15 (s, 3H),

6.00 to 6.12 (q, 1H), 8.84 (s, 1H)

(5) Synthesis of 4,5-dichloro-6- (1-hydroxyxethyl) pyrimidine [compound (2-7)]

6- (1-acetoxitytyl) 1,4-dichloropyrimidine (4.0 g) was dissolved in tetrahydrofuran (50 ml), and a 1N aqueous sodium hydroxide solution (30 ml) was added with stirring. It was made and dropped. After the addition, the mixture was further stirred at room temperature for 1 hour to complete the reaction. Next, the desired product was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained oily product was purified by column chromatography (Co-gel C-200, toluene: ethyl acetate = 5: 1 elution) to obtain 2.8 g of the target compound as a pale yellow liquid. Was.

1.47 ~; I. 52 (d, 3H), 3.76 ~ 3.85 (d, 1H), 5.17 ~ 5.25 (m, 1H), 8.88 (s, 1 H)

(6) Synthesis of other starting compounds (2) in Table 1

Other starting compounds (2) in Table 1 were synthesized in the same manner as in the above (1) to (5).

R

Example 1 [Synthesis of Compound (1)]

Using the compound (2) obtained in Reference Example 1, the target compound (1) was synthesized.

(1) 4-(4-cis-tert Kishiruamino to Buchirushikuro) Single 5 black opening one 6- (1 - Kuroroechiru) pyrimidine [Compound (l _a -l)] and

4-Synthesis of (4-trans-tert-butylcyclohexylamino) — 5-chloro-6- (1-chloroethyl) pyrimidine [compound (la-2)]

4-tert-butylcyclohexylamine (3.6 g of a mixture of cis and rans isomers) and triethylamine (3 g) are dissolved in toluene (20 ml). Then, 4,5-dichloro-6- (1-chloroethyl) pyrimidine (6.3 g) was added, and the mixture was heated and stirred at about 60 for 4 hours.

After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with toluene, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluted with toluene) to obtain 1.3 g of a colorless oily compound (la-1) (cis form) from the second fraction. From the first fraction, 0.9 g of a colorless crystalline compound (la-2) (trans form) was obtained.

[Compound (la-l)]

Ή-N R (C D C 1 a, δ p pm)

0.85 (s9H), 1.08-128 (m, 2H),

1.52 to 178 (m, 5H), 180 to; I.82 (d, 3H),

1.93—205 (m, 2H), 4 30-4.39 (m, 1H),

5.35 ~ 5 46 (q, 1H), 5 64 ~ 5.78 (m, 1H),

8.50 (s1H)

[Compound (la-2)]

¹ H-NM R (CDC 1 δ ppm)

0.90 (s, 9H), 1.15-123 (m, 5H),

1.82-1.85 (d, 3H), 179-: L.94 (m, 2H),

2.12 to 2.20 (m, 2H), 386 to 4.00 (m, 1H),

5.22 ~ 5.3 1 (m, 1 H), 5 32 ~ 5.4 1 (q, 1 H),

8.50 (s, 1 H)

(2) Synthesis of 6- (1-acetoxitytyl) -4-1 (4-cis-tert-butylcyclohexylamino) -1-5-cyclopyrimidine [Compound (la-3)] Compound (la-1) (1.1 g) is dissolved in N, N-dimethylformamide (30 ml), and potassium acetate (0.5 g) and anhydrous potassium carbonate (0.7 g) are added. For 4 hours.

After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.5 g of the target compound as colorless crystals.

0.87 (s, 9H), 1.05 to 121 (m, 2H),

1.54 ~; I.56 (d, 3H), 157 ~ 1.75 (m, 5H),

1.90 to 2.02 (m, 2H), 213 (s, 3H),

4.29 to 4.39 (m, 1H), 562 to 5.82 (m, 1H),

5.99-6.05 (q, 1H), 847 (s, 1H)

(3) Synthesis of 6- (1-acetoxitytyl) 1-41 (4_trans-tert-butylcyclohexylamino) -5-chloropyrimidine [Compound (la-4)] Compound (la-2) (0. 69 g) was dissolved in N, N-dimethylformamide (30 ml), potassium acetate (0.3 g) and anhydrous potassium carbonate (0.4 _g ) were added, and the mixture was heated at about 60 ^eC for 4 hours. Stirred.

After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (ヮ -gel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.68 g of the target compound as colorless crystals.

0.87 (s, 9 9), 1.12 to 1.26 (m, 5Η),

1.52 to 1 55 (d, 3 Η), 179 to 1.91 (m, 2 Η),

2.13 (s3Η), 2.10 ~ 2 2 1 (m, 2Η),

3.82 ~ 3 99 (m, 1Η), 5 22 ~ 5.32 (m, 1Η),

5.99 ~ 607 (q, 1Η), 846 (s, 1Η)

(4) 4- (4-cis-t-e-rt-butylcyclohexylamino) 1-5-clo

-6-Synthesis of (1-hydroxyethyl) pyrimidine [compound (la-5)] Dissolve compound (la-3) (0.15 g) in ethanol (1 Om1) and add 1 N An aqueous sodium chloride solution (5 ml) was added, and the mixture was heated with stirring at about 40 rpm for 2 hours. After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate == 10 _: 1 elution) to obtain 0.10 g of the target compound as colorless crystals.

Ή-NMR (C D C 1 a, δ p pm)

0.87 (s, 9H) 1.05 to 131 (m.2H),

1. 4 1—1.44 (d, 3 H), 1 52-: 1.79 (m, 5 H),

1.92 ~ 2.05 (m, 2 H), 4 1 2 ~ 4.18 (d, 1 H),

4.30-4.39 (m, 1H), 429-5.05 (q, 1H),

5.61 to 5.72 (m, 1H), 846 (s, 1H)

(5) Synthesis of 4- (4-trans-tert-butylcyclohexylamino) -15-chloro-6- (1-hydroxyethyl) pyrimidine [Compound (la-6)] Compound (la-4) (0 68 g) was dissolved in ethanol (20 ml), a 1N aqueous solution of sodium hydroxide (5 ml) was added, and the mixture was heated with stirring at about 40 ^eC for 2 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.60 g of the target compound as a colorless oily liquid.

¹ H-NM R (CDC 1 a, δ p pm)

0.87 (s, 9H), 1.1 1 to 137 (m, 5H),

L. 43 (d, 3H), 172 to 1.95 (m, 2H),

2.08-2.22 (m, 2H), 382-4.00 (m, 1H),

4.12 to 4.18 (d, 1H), 492 to 5.02 (q, 1H),

5.20 ~ 5.33 (m, 1H), 844 (s, 1H)

(6) Synthesis of 4- (4-cis-tert-butylcyclohexylamino) -5-chloro-1-6- (1-fluoroethyl) virimidine [Compound (la-7)] Compound Ua-5) (0.15) g) was dissolved in black-mouthed form (10 ml) and stirred on ice. Below, getylaminosulfur trifluoride (DAST) (0.1 g) was added dropwise, and the mixture was stirred at room temperature for 4 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, and the form layer was collected and washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.10 g of the target compound as a colorless oily liquid.

¹ H-NR (CDC 1, δ p pm)

0.89 (s, 9H), 1.02 to 130 (m, 2H),

1.62 ~ 1.73 (d-d, 3H) 1, 42 ~ 丄 .79 (m, 5H),

1.9 to 2.05 (m, 2 H), 4 30 to 4.40 (m, 1 H),

5.65 ~ 5.76 (m, 1H), 576 ~ 6.02 (d-q, 1H),

8.52 (s, 1 H)

(7) Synthesis of 4- (4-I "fc rans-tert-butylcyclohexylamino) 15-chloro- 1 6- (1-fluoroethyl) pyrimidine [Compound (la-8)] Compound (la-6) (0 60 g) was dissolved in methylene chloride (1 Om 1), DAST (0.4 g) was added dropwise under ice cooling and stirring, and the mixture was stirred at room temperature for 4 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, a methylene chloride layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.23 g of the target compound as a colorless oily liquid.

¹ H-NM R (CDC 1, δ p pm)

0.87 (s, 9Η), 0.98-: .32 (m, 5Η),

1.60-1.71 (d-d, 3H), 1.72-; L.93 (m, 2H), 2.02-2.24 (m, 2H), 3.81-4 0 1 (m, 1 H), 5.2 to 5.37 (m, 1 H), 5.75 to 6.02 (d-q, 1 H), 8.51 (s, 1H)

(8) 6- (1-Chloroethyl) -1-5-chloro-4-1 (4-1cS-phenylsyloxyhexylamino) pyrimidine [Compound (la-11) and

Synthesis of 6- (1-Chloroethyl) -1-5-Chloro-41- (41-trans-phenylcyclohexylamino) pyrimidine [compound (la-12)]

4-Funylcyclohexylamine (a mixture of cis- and trans-forms, 4.0 g) and triethylamine (3 g) are dissolved in toluene (20 ml) to give 4,5-dichloro-6- (1-chloroethyl). Pyrimidine (6.0 g) was added, and the mixture was heated and stirred at about 60 for 4 hours.

The residue obtained was purified on a silica gel column (Pecogel C-200, eluted with toluene) to obtain 2.6 g of a colorless oily compound 11 (cis form) from the second fraction. From this, 1.9 _{g of} colorless crystalline compound 12 (trans form) was obtained.

[Compound (la-11)]

1.67 ~; I. 90 (m, 6H), 183 186 (d, 3H),

2.0 1-2.06 (m, 2H), 2.62 267 (m, 1H),

4.40 to 4.50 (m, 1 H), 5.39 5 46 (q, 1 H),

5.78-5.82 (m, 1H), 7.16 736 (m, 5H),

8.54 (s, 1H)

[Compound (la-12)]

Ή-NM R (C D C 1 a, δ p pm)

1.34 to 1.48 (m, 2H), 1.61 177 (m, 2H),

1.83 ~: L.85 (d, 3H), 1.97202 (m, 2H),

2.22 ~ 2.27 (m, 2 H), 2.50 2 60 (m, 1 H),

4.04 to 4.15 (m, 1 H), 5.35 5 45 (m, 1 H),

5.37 to 5.45 (q, 1H), 7.17733 (m, 5H), 8.54 (s, 1 H)

(9) 6- (1-acetoxitytyl) -1-5-chloro-4-1 (4-1cis-phenylcyclohexylamino) pyrimidine [compound (la-13)] and

Synthesis of 6- (1-acetoxitytyl) -1-5-chloro-4-1 (4-trans-phenylcyclohexylamino) pyrimidine {compound (la-14)]

4-phenylcyclohexylamine (4.0 g of a mixture of cis and trans isomers) and triethylamine (3 g) are dissolved in toluene (20 ml), and 6- (1-acetoxicetyl) -1,4 is dissolved. 5-Dichloropyrimidine (5.4 g) was added, and the mixture was heated with stirring at about 60 ° C for 4 hours.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 5: 1 elution) to give a pale yellow oily liquid of Compound 13 (cis form) from the second fraction. .8 g, and 2.0 g of colorless compound 14 (trans form) was obtained from the first fraction.

[Compound (la-13)]

1.55 ~: L.57 (d, 3H), 1.60 ~ 194 (m, 6H),

2.00—2.09 (m, 2H), 2.12 (s3H),

2.58 to 2.74 (m, 1 H), 4.35 to 4 45 (m, 1 H),

5.68 to 5.78 (m, 1H), 6.00 to 608 (q, 1H),

7.12 to 7.32 (m, 5H), 8.50 (s1H)

[Compound (la-14)]

¹ H-NMR (CDC 1 a, δ p pm)

1.3 1 to 1.50 (m, 2 H), 1.52 to 1 55 (d, 3 H),

1.59-1, 80 (m, 2 H), 1.89-204 (m, 2 H),

2.12 (s, 3H), 2.17 to 2.31 (m2H),

2.48-2.62 (m, 1H), 4.00-4 19 (m, 1H),

5.28-5.37 (m, 1H), 5.98-606 (q, 1H), 7.10 to 7.32 (m, 5H), 8.54 (s, 1H)

(10) 5-chloro-6- (1-hydroxyethyl) 1-41 (4-1cis-phenylcyclohexylamino) pyrimidine [compound (la-15)] and

Synthesis of 5-chloro-6- (1-hydroxyethyl) 1-41 (4-trans-phenylcyclohexylamino) pyrimidine [(la-16)]

4-Phenylcyclohexylamine (4.0 g of a mixture of cis and trans forms) and triethylamine (3 g) were dissolved in toluene (20 ml), and the mixture was dissolved in 4,5-dichro-6- (1-hydroxydene). (Chill) pyrimidine (4.4 g) was added, and the mixture was heated and stirred at about 60 ° C for 4 hours.

The resulting residue was purified by a silica gel column (ヮ -gel C-200, toluene: ethyl acetate = 5: 1 elution) to give a colorless oily liquid compound 15 (cis form) from the second fraction. 4 g were obtained, and 1.5 g of colorless crystalline compound 16 (trans form) was obtained from the first fraction.

[Compound (la-15)]

1.43 to 1.45 (d, 3H), 156 • 190 (m, 6H),

1.98-2.12 (m, 2H), 2.63 267 (m.1H),

4.17 to 4.20 (d, 1 H), 4.42 4 45 (m, 1 H),

4.96—5.04 (m, 1 H), 5.65 5 78 (m, 1 H),

7.16 to 36.m (5H), 8.48 (s1H)

[Compound (la-16)]

Ή-NMR (C D C 1 a, δ p pm)

1.39-1.48 (m, 2 H), 1.42 ■ 144 (d, 3 H),

1.62 ~; 1.76 (m, 2H), 1.98 • 202 (m, 2H),

2.23 to 2.30 (m, 2 H), 2.5 1 2 60 (m, 1 H),

4.08-4.14 (m, 1H), 4.17 '420 (d, 1H),

4.95 ~ 5 Q 5 (m, 1 H), 5.30 5 33 (m, 1 H), 7.18 to 7.34 (m, 5H), 8.47 (s, 1H)

(11) Synthesis of 5-chloro-6- (1-fluoroethyl) 1-41- (4-cis-phenylcyclohexylamino) pyrimidine [compound (la-17)]

Compound (la-11) (1.8 g) was dissolved in N, N-dimethylformamide (20 _ml ), cesium fluoride (1 · 4 _g ) was added, and 100 to 12 CTC for 6 hours The mixture was heated and stirred.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 1.1 g of the target compound as a colorless oily liquid.

Ή-NMR (C D C 1 a, δ p pm)

1.61-: L.95 (m, 6H), 171-; L.76 (d-d, 3H),

2.02 to 2.06 (m, 2H), 2 64 to 2.68 (m, 1H),

4.42 to 4.45 (m, 1 H), 5 78 to 5.81 (m, 1 H),

5.81-6.03 (d-q, 1H) 7.19-7.36 (m, 5H), 8.54 (s, 1H)

(12) Synthesis of 4- (1-cis-phenylcyclohexylamino) -1-6- (1-methoxyhexyl) pyrimidine [compound (la-19)]

Compound (la-11) (0.7 g) was dissolved in methanol (3 Om 1), 28% sodium methylate (methanol solution) (0.5 g) was added, and the mixture was heated at about 60 ° C for 3 hours. Stirred hot.

After completion of the reaction, the solvent was distilled off under reduced pressure, water was added to the obtained residue, the target compound was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by silica gel column (Ecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 0.5 g of the target compound as a colorless liquid.

'H—NMR (CDC 1, δ p pm) 1.46-: 1.48 (d, 3H), 162-: L98 (m, 6H),

2.00-2.12 (m, 2H), 260-2.72 (m, 1H),

3.33 (s, 3H), 4.37-449 (m, 1H),

4.73 to 4.80 (q, 1 H), 5 68 to 575 (m, 1 H),

7.19 to 7.36 (m, 5H), 855 (s, 1H)

(13) 5-Chloro-4-1 (4-trans-phenylcyclohexylamino)

Synthesis of 6— (1-Methoxyxyl) pyrimidine {compound (la-20)] Compound (la-12) (1.0 g) is dissolved in methanol (30 ml), and 28% sodium methylate (methanol (0.7 _g ) was added and the mixture was heated and stirred at about 60 C for 3 hours.

The resulting residue was purified by a silica gel column (Peco-gel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 0.5 g of the target compound as colorless crystals.

¹ H-NM R (CDC 1 a, δ p pm)

13 :! ~; I. 57 (m, 2 H), 145-1.48 (d, 3 H),

1 62 to 181 (m, 2 H), 195 to 2.06 (m, 2 H),

2 20 to 2 32 (m, 2 H), 250 to 2.74 (m, 1 H),

3 32 (s1H), 4.08-420 (m, 1H),

4 72 ~ 4 79 (q, 1 H), 5 27 ~ 5.38 (m, 1 H),

7 20-7 33 (m, 5H), 854 (s, 1H)

(14) 5—Chloro 6— (1—Fluoroethyl) 1 4 1 (4 1 cis—

Synthesis of oral hexylamino) pyrimidine [compound (la-25)]

5—Black mouth— 6— (1-Hydroxitytyl) 1-41 (4-1 cis-methylcyclohexylamino) Pyrimidine compound (0.3 g) is dissolved in dichloromethane (20 ml) and stirred under ice-cooling. Then, getylaminosulfur trifluoride (DAST) (0.3 g) was added dropwise, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, a dichloromethane layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (ヮ -gel C-200, elution with ethyl acetate: toluene = 10: 1) to obtain 0.25 g of the target compound as colorless crystals.

Ή-NMR (C D C 13, δ p pm)

0.95-0.98 (d, 3H), 1.19-126 (m, 3H),

1.61 ~; I.72 (d-d, 3H), 1.36 1.89 (m, 6H),

4.15 to 4.34 (m, 1H), 5.53 to 570 (m, 1H),

5.77 to 6.02 (d-q, 1 H), 8.52 (s, 1 H)

(15) Synthesis of 5-chloro-6- (1-fluoroethyl) 1-4-1 (4-trans-methylcyclohexylamino) pyrimidine [compound (la-26)]

5-Chloro-6- (1-hydroxyethyl) 1-41 (4-1 "brans-methylcyclohexylamino) Pyrimidine compound (1.3 g) is dissolved in dichloromethane (20 ml) and stirred under ice-cooling. Then, DAST (1.0 g) was added dropwise, and the mixture was stirred at room temperature for 4 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, a dichloromethane layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (ヮ -gel C-200, elution with ethyl acetate: toluene = 1: 10) to obtain 0.87 g of the target compound as colorless crystals.

0.92-0.98 (d, 3H), 1.10--160 (m, 9H),

1.69 to 2.06 (d-d, 3H), 1.65 2.06 (m, 2H)

2.02 to 2.16 (m, 2H), 3.89 to 405 (m, 1H),

5.23 to 5.38 (m, 1 H), 5.76 to 60 1 (d—q, 1 H)

8.5 1 (s, 1 H) (16) 5-chloro-6- (1-fluoroethyl) 1-4-1 (4-cis-n-pentylcyclohexylamino) pyrimidine [compound (la-29)] and

5-Chloro-6- (1-fluoroethyl) -4-1- (4-trans-n-pentylcyclohexylamino) pyrimidine [Compound (la-30)] Synthesis of compound (la-143) (0.5 g) in dichloromethane (50 ml), DAST (0.5 g) was added dropwise under ice-cooling stirring, and the mixture was stirred at room temperature for 4 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooled stirring, dichloromethane was separated and washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The residue obtained was purified by a silica gel column (ヮ -gel C-200, eluting with ethyl acetate: toluene = 1: 10) to give the target compound (la-29) as a colorless oil from the second fraction. ) (cis-isomer) was obtained in an amount of 0.05 g, and the first fraction was obtained as a colorless oil (0.13 g) as a target compound (la-30) (trans-isomer).

[Compound (la-29)〗

_{Ή-NMR (CDC 1 3,} δ ρ pm)

0.86-0.92 (m, 3Η), 100-1.50 (m, 13H),

1.59- 丄 .70 (d-d, 3Η), 1.51--: L.89 (m, 4H), 4.2-4.37 (m, 1H), 5.60- 5.72 (m, 1H),

5.89 to 6.13 (d-q, 1H), 8.52 (s, 1H)

[Compound (la-30)]

_{Ή - NMR (CDC 1 3,} δ p pm)

0.73 ~; I. 00 (m, 3H), 1.00 to 1.49 (m, 13H),

1 60-1.72 (d- d, 3 H), 1.72-1.90 (m, 2 H),

192-2.18 (m, 2H), 3.85-4.04 (m, 1H),

5 20 to 5.39 (m, 1H), 5.76 to 6.02 (d—q, 1H), 851 (s1H)

(17) Synthesis of 5-chloro-4- (4-cis-tert-butylcyclohexylamino) -6- (1-methylthioethyl) virimidine [compound a-31)] Compound (la-11) (1.0 g) ) Is dissolved in tetrahydrofuran (20 ml), An aqueous solution (1.6 g) of 15% -methylmercaptane sodium was added, and the mixture was stirred at room temperature for 6 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 20: 1 elution) to give 1.0 g of the target compound as a colorless liquid.

(18) Synthesis of 5-chloro-41- (4-trans-ter-butylcyclohexylamino) -16- (1-methylthioethyl) pyrimidine {compound (la-32)] Compound (la-12) (1 .0 g) was dissolved in tetrahydrofuran (20 ml), a 15% aqueous solution of methylmercaptane sodium (1.6 g) was added, and the mixture was stirred at room temperature for 6 hours.

The resulting residue was purified by a silica gel column (Ecogel C-200, toluene: ethyl acetate = 20: 1 elution) to obtain 0.5 g of the target compound as a colorless liquid.

(19) Synthesis of 5-chloro-1- (1-chloroethyl) 141- (4-ethylcyclohexylamino) pyrimidine [compound (la-37)]

4-Ethylcyclohexylamine (2.0 g) is dissolved in a mixture of toluene (20 ml) and triethylamine (10 ml), and 4,5-dichloro-6- (1-chloroethyl) pyrimidine (14 _g ) is dissolved. And stirred at about 60 ° C. for 4 hours. After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with toluene, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 3.0 g of the target compound as a colorless oily liquid. (20) Synthesis of 6- (1-acetoxitytyl) -1-5-chloro-4-1 (4-ethylcyclohexylamino) pyrimidine [compound (la-38)]

Compound (la-37) (3. O g) N, N- dimethyl dissolved in formamide (1 00 m 1), potassium acetate (5 g) and anhydrous potassium carbonate and (3 g) was added, about 60 ^e C was searched for 6 hours.

The obtained residue was purified by silica gel column (Ecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 2.5 g of the target compound as a colorless oily liquid.

(21) Synthesis of 5-chloro-41- (4-ethylcyclohexylamino) -1-6- (1-hydroxyxethyl) pyrimidine [compound (la-39)]

The compound (la-38) (2.5 g) was dissolved in ethanol (100 ml), a 1 N aqueous solution of sodium hydroxide (50 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 1.9 g of the target compound as a colorless oily liquid.

(22) Synthesis of 5- (1-ethylcyclohexylamino) -1-6- (1-furethyl lotyl) pyrimidine 〖compound (la-40)]

The compound (la-39) (1.9 g) was dissolved in chloroform (50 ml), DAST (2.0 g) was added dropwise with ice cooling and stirring, and the mixture was stirred at room temperature for 5 hours.

After the completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, and the foam layer was separated, washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 1.5 g of the target compound as a colorless oily liquid. (23) Synthesis of 4- (4-cis-tert-butylcyclohexylamino) -15-chloro-16- (1-fluoroethyl) pyrimidine hydrochloride [Compound (la-41)]

4- (4-cis-tert-butylcyclohexylamino) 5-chloro-6- (1-fluoroethyl) Pyrimidine (0.4 g) is dissolved in getyl ether (50 ml), and the mixture is stirred under ice-cooling with stirring. Gas was blown.

The obtained colorless crystals were washed with hexane to obtain 0.22 g of the target compound as colorless crystals.

Elemental analysis

_{_{- Calcd for C 16 H 25 N}} 3 C1F; C. 54.89: H. 7.14: N. 12.00

• Foun d; C. 54.38: H. 7.49: N. 11.85

(24) 4- [4- (5-Chloro-6- (1-chloroethyl) pyrimidine-1-4-luamino) cyclohexylamino] -5-chloro-6- (1-chloroethyl) pyrimidine [compound (la-42) ] Synthesis

1,4-Six-hexandiamine (10 g) was dissolved in a mixture of toluene (100 ml) and triethylamine (10 ml) to give 4,5-dichloro-6- (1-chloroethyl) pyrimidine (10-ml). 10 g) and stirred at room temperature for 4 hours.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluting with ethyl acetate) to give 8.0 g of the target compound as a colorless viscous liquid.

(25) 6- (1-acetoxityl) -5-chloro-4-1 [4- (5-chloro-6-1 (1-chloroethyl) pyrimidine-4-ylamino) cyclohexylaminopyrimidine [compound (la-43)] as well as

6— (1-acetoxitytyl) 5-chloro-4-1 [4— (5-chloro-6- (1-acetoxitytyl) pyrimidine-14-yl-amino] cyclohexylamino] pyrimidine [compound (la- 44)]

Compound (la-42) (0.15 g) was dissolved in N, N-dimethylformamide (20 ml), and potassium acetate (0.16 g) and anhydrous potassium carbonate (0.1 g) were added. And stirred at about 60 ° C. for 6 hours. After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (ヮ -gel C-200, eluting with ethyl acetate) to obtain 0.06 g of the target compound (la-43) as a colorless viscous liquid from the first fraction. From the second fraction, 0.08 g of the target compound (la-44) as a colorless liquid was obtained.

(26) 5-Chloro-4-1 [4- (5-Chloro-6- (1-chloroethyl) pyrimidine-1-4-ylamino) cyclohexylamino] 16- (1-hydroxyethyl) pyrimidine [Compound (la-45)] Synthesis

The compound (la-43) (0.06 g) was dissolved in ethanol (2 Om 1), a 1 N aqueous solution of sodium hydroxide (20 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The resulting residue was purified by a silica gel column (Peco-gel C-200, eluting with ethyl acetate) to obtain 0.06 g of the target compound as a glassy solid.

(27) 5-chloro-1,4- [4- (5-chloro-6- (1-hydroxyethyl) pyrimidine-1-4-ylamino) cyclohexylamino] 6- (1-hydroxyshetyl) pyrimidine [compound (la -46)]

The compound (la-44) (0.08 g) was dissolved in ethanol (2 Om 1), an aqueous solution of IN-sodium hydroxide (20 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The obtained residue was purified by a silica gel column (ヮ -gel C-200, eluting with ethyl acetate) to obtain 0.08 g of the objective compound as a glassy solid.

(28) 5- (1-chloro-5- (1-chloroethyl) pyrimidin-4-ylamino) cyclohexylamino] 1-6- (1-fluoroethyl) pyrimidine 〖compound (la-47) ] Synthesis

The compound (la-45) (0.06 g) was dissolved in chloroform (1 Om 1), and DAST (0.1 g) was added dropwise with stirring under ice-cooling, followed by stirring at room temperature for 5 hours. After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, and the chloroform layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (Pelcogel C-200, toluene: ethyl acetate = 1: 1 elution) to obtain 0.06 g of the target compound as a colorless viscous liquid.

(29) 5-Crosin-4- [4-(5-Cross-6- (1-fluoroethyl) birimidine-1-4-ylamino) cyclohexylamino] 1-6— (1fluoroethyl) pyrimidine [compound (la -48)]

Compound (la-45) (0.08 g) was dissolved in chloroform (10 ml), and DAST (0.1 g) was added dropwise under ice-cooling with stirring, followed by stirring at room temperature for 5 hours. .

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, and the chloroform layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 1: 1 elution) to obtain 0.08 g of the target compound as a colorless viscous liquid.

(30) Synthesis of 4- (4-n-butoxycyclohexylamino) -1-chloro-6- (1-1-chloroethyl) pyrimidine {compound (la-65)]

4-n-Butoxycyclohexylamine (1.4 g) is dissolved in a mixture of toluene (20 ml) and triethylamine (10 ml), and 4,5-dichloro mouth-6- (1-chloroethyl) Add pyrimidine (2 g) and add about 60. The mixture was stirred at C for 4 hours. After completion of the reaction, water was added to the reaction mixture, the target compound was extracted with toluene, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 1.1 g of the target compound as a colorless liquid.

(31) Synthesis of 6- (1-acetoxyshethyl) — 5-chloro-4- (4-n-butoxysic hexylamino) pyrimidine [compound (la-68)] Compound (la-65) (1.1 g) was dissolved in N, N-dimethylformamide (50 ml), and potassium acetate (1.8 g) and anhydrous potassium carbonate (0.9 g) were added. I searched for 60 hours at 60 days.

The obtained residue was purified by silica gel column (Pecogel C-200, toluene: ethyl acetate = 5: 1 elution) to obtain 1.2 g of the target compound as a colorless oily liquid.

(32) Synthesis of 4- (4-N-butoxycyclohexylamino) -1-5-chloro-6- (1-hydroxyethyl) pyrimidine [compound (la-71)]

Compound (la-68) (1.2 g) was dissolved in ethanol (3 Om 1), an aqueous solution of IN-sodium hydroxide (30 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The resulting residue was purified by a silica gel column (Pelcogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 0.5 g of the target compound as a colorless oily liquid.

(33) Synthesis of 4- (4-n-butoxycyclohexylamino) -1-chloro-6- (1-fluoroethyl) pyrimidine [compound (la-74)]

The compound (la-71) (0.5 g) was dissolved in chloroform (30 ml), DAST (0.3 g) was added dropwise under ice-cooling and stirring, and the mixture was stirred at room temperature for 5 hours.

The obtained residue was purified by silica gel column (Pecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 0.5 g of the target compound as a colorless oily liquid.

(34) Synthesis of 4- [4-chloro-6- (1-chloroethyl) pyrimidine-14-ylamino] cyclohexanecarboxylic acid ethyl ester [compound (la-77)] 4-ethylaminocyclohexanecarboxylate (2.0 g) was dissolved in a mixture of toluene (30 ml) and triethylamine (10 ml), and the mixture was dissolved in 4,5-dichloro-6- (1-chloroethyl). ) Pyrimidine (3 g) was added, and the mixture was stirred at about 6 CTC for 4 hours.

The resulting residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 2.8 g of the target compound as a colorless liquid.

(35) Synthesis of 4- [6- (1-acetoxitytyl) -4-4-pyrimidine-14-ylamino] cyclohexanecarboxylic acid ethyl ester [compound (la-80)]

Compound (la-77) (2.8 g) was dissolved in N, N-dimethylformamide (100 ml), and potassium acetate (4.8 g) and anhydrous potassium carbonate (2.2 g) were added. Then, the mixture was stirred at about 6 O'C for 6 hours.

The obtained residue was purified by silica gel column (Pecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 1-2 g of the target compound as a colorless oily liquid.

(36) Synthesis of 4- [4-chloro-6- (1-hydroxyethyl) pyrimidine-4-ylamino] cyclohexanecarboxylic acid [compound (la-8.9)]

The compound (la-80) (1.2 _g ) was dissolved in ethanol (50 _ml ), an IN-sodium hydroxide aqueous solution (50 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluting with ethyl acetate) to obtain 1.2 g of the target compound as a colorless oily liquid.

(37) 4— [4-Chloro-6— (1-Fluoroethyl) pyrimidine 4-yl- Synthesis of [Mino] cyclohexanecarboxylic acid [Compound (la-92)]

Compound (la-89) (1.2 g) was dissolved in dichloromethane (30 ml), and DAST (0.8 g) of dichloromethane (10 ml) was slowly added dropwise with ice cooling and stirring, and the mixture was cooled with ice. For 5 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling stirring, the dichloromethane layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluted with ethyl acetate) to give 0.8 g of the target compound as a colorless oily liquid.

(38) Synthesis of 4- [4-chloro-6- (1-fluoroethyl) pyrimidine-14-ylamino] cyclohexanecarboxylic acid- "tert-butyl ester {compound (la-95)]

Compound (la-92) (0.8 g) was dissolved in a mixture of cyclohexane (5 ml) and dichloromethane (3 ml), and tert-butyl-2,2,2,2-trichloroacetimidate (1.1 lg) was dissolved. )) And a catalytic amount of poly (trifluorotrifluoroethyl) ether complex were added, and the mixture was stirred at room temperature for 12 hours.

After completion of the reaction, water was slowly added to the reaction mixture, the dichloromethane layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Ecogel C-200, toluene: ethyl acetate = 2: 1 elution) to obtain 0.8 g of the target compound as a colorless oily liquid.

(39) Synthesis of 4- (4-aminocyclohexylamino) -1-chloro-6- (1-chloroethyl) pyrimidine [compound (la-98)]

1,4-Cyclohexanediamine (10 g) is dissolved in acetonitrile (100 ml), and ice-cooled solution of 4,5-dichloro-6- (1-chloroethyl) pyrimidine (3.7 g) in acetonitrile (50 ml) was added dropwise, and the mixture was stirred at room temperature for 5 hours.

After completion of the reaction, the solvent was distilled off under reduced pressure, and water was added to the obtained residue. The target compound was extracted with ter and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluted with ethyl acetate) to give 5.0 g of the target compound as a colorless oily liquid.

(40) Synthesis of N- [4- (5-chloro-6- (1-chloroethyl) pyrimidine-14-ylamino) cyclohexyl] -12,2-dimethylpropanamide [compound (la-113)]

Compound (la-98) (2.0 g) was dissolved in a mixture of toluene (50 ml) and triethylamine (10 ml), and a solution of pivaloyl chloride (0.8 g) in toluene was cooled under ice-cooling. (10 ml) was slowly added dropwise, and the mixture was stirred at room temperature for 3 hours.

The resulting residue was purified by a silica gel column (Pelcogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 1.5 g of the target compound as colorless crystals.

(41) N- [4- (6- (1-acetoxicetyl) -15-clovirimidine-14-ylamino) cyclohexyl] -1,2,2-dimethylpropaneamide [compound (la-116 )]

Compound (la-113) (1.5 g) was dissolved in N, N-dimethylformamide (50 ml), and potassium acetate (2 g) and anhydrous potassium carbonate (1.2 _g ) were added. The mixture was stirred at about 60 for 4 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 1.5 g of the target compound as a colorless oil.

(42) N— [4- (5-chloro-1- (1-hydroxyhexyl) pyrimidine-1-ylamino) cyclohexyl] -2,2-dimethylpropanamide [compound (la-119)] Synthesis of The compound (la-116) (1.5 g) was dissolved in ethanol (50 ml), an IN-sodium hydroxide aqueous solution (50 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The resulting residue was purified by a silica gel column (Pecogel C-200, eluted with ethyl acetate) to give 1.5 g of the target compound as colorless crystals.

(43) Synthesis of N— [4- (5-chloro-6- (1-fluoroethyl) pyrimidine-14-ylamino) cyclohexyl] -12,2-dimethylpropanamide [compound (la-122)]

Compound (la-119) (1.5 g) was dissolved in dichloromethane (30 ml), and DAST (1.0 g) was added dropwise with ice-cooling stirring, followed by stirring at room temperature for 4 hours.

The obtained residue was purified by silica gel column (Ecogel C-200, elution with ethyl acetate: toluene = 2: 1) to give 0.6 g of the target compound as colorless crystals.

(44) N— [4 -— (5-chloro-6- (1-chloroethyl) pyrimidine—4-yl-amino) cyclohexyl] 1 "tert-butyloxycarboxamide [la- 125)]

The compound (la-98) (1.0 g) was dissolved in a solution consisting of 1,4-dioxane (20 ml) and water (20 ml), and anhydrous sodium carbonate (0.5 g) and di-tert. —Butyl dicarbonate (lg) was added, and the mixture was stirred at room temperature for 3 hours.

After completion of the reaction, water was added to the reaction mixture, the desired product was extracted with toluene, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 0.6 _g of the target compound as colorless crystals.

(45) N-f 4-(6— (1—acetoxicetil) — 5—pyrimidine— 41 Synthesis of (ylamino) cyclohexyl] -tert-butyloxycarboxamide [compound (la-128)]

Compound (la-125) (0.6 g) was dissolved in N, N-dimethylformamide (30 ml), and potassium acetate (0.9 g) and anhydrous potassium carbonate (0.4 g) were added. The mixture was stirred at 6 O'C for 4 hours.

The obtained residue was purified by silica gel column (Pecogel C-200, toluene: ethyl acetate = 1: 1 elution) to obtain 0.4 g of the target compound as a colorless oil.

(46) N- [4- (5-chloro-6- (1-hydroxyethyl) pyrimidine-1 4-ylamino) cyclohexyl] -1 "fc ert-butyloxycarboxamide

Synthesis of Compound (la-131)

The compound (la-128) (0.4 g) was dissolved in ethanol (30 ml), a 1 N aqueous solution of sodium hydroxide (30 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, eluted with ethyl acetate) to give 0.3 _g of the target compound as colorless crystals.

(47) N— [4 -— (5-chloro-6— (1-fluoroethyl) pyrimidine-1-4-amino) cyclohexyl-1-tert-butyloxycarboxamide

Synthesis of [Compound (la-134)]

The compound (la-131) (0.3 g) was dissolved in dichloromethane (20 ml), and DAST (0.4 g) was added dropwise with stirring under ice-cooling, followed by stirring at room temperature for 4 hours.

The resulting residue is purified by a silica gel column (ヮ -gel C-200, eluting with ethyl acetate: toluene = 2: 1) to give the target compound as colorless crystals. 0.3 g was obtained.

(48) Synthesis of 5-chloro-6- (1-chloroethyl) 1-41 (4-1n-pentylcyclohexylamino) pyrimidine [compound (la-137)]

41: n-Pentylcyclohexylamine (1.1 g) is dissolved in a mixture of N, N-dimethylformamide (20 ml) and triethylamine (10 ml), and 4,5-dichloro-6 - a (1 one Kuroroechiru) pyrimidine (1. 7 g) was added and stirred for 4 hours at about 60 ^e C.

The obtained residue was purified by silica gel column (Ecogel C-200, eluted with toluene) to give 1.6 g of the target compound as a colorless liquid.

(49) Synthesis of 6- (1-acetoxyshethyl) 1-5-chloro-4-1 (4-n-bentylsic hexylamino) pyrimidine [compound (la-140)]

Compound (la-137) (1.5 g) was dissolved in N, N-dimethylformamide (50 ml), and potassium acetate (2.3 g) and anhydrous potassium carbonate (1.4 _g ) were added. The mixture was stirred at 60 ^eC for 4 hours.

The obtained residue was purified by a silica gel column (ecogel c-200, toluene: ethyl acetate = 3: 1 elution) to give the target compound as a colorless oil (1.5).

(50) Synthesis of 5- (1-hydroxyethyl) 1-41- (4-n-pentylcyclohexylamino) pyrimidine [compound (la-143)]

The compound (la-140) (1.5 g) was dissolved in ethanol (2 Om 1), 1N—water / aqueous sodium hydroxide solution (20 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The obtained residue was purified by silica gel column (Ecogel C-200, toluene: ethyl acetate = 3: 1 elution) to give the target compound as a colorless oil. 0.5 g was obtained.

(51) Synthesis of 5-chloro-6- (1-fluoroethyl) 1-4-1 (4-cyclohexylhexamino) pyrimidine 〖compound (lb-4)]

Compound (lc-4) (1.1 g) was dissolved in methanol (20 ml), 1 N hydrochloric acid (10 ml) was added, and the mixture was stirred at room temperature for 5 hours.

After completion of the reaction, the solvent is distilled off under reduced pressure, the target compound is extracted from the residue with ethyl acetate, washed with a saturated aqueous solution of sodium carbonate, washed with water, dried over anhydrous sodium sulfate, and then the solvent is distilled off under reduced pressure did.

The resulting residue was purified by a silica gel column (Ecogel C-200, toluene: ethyl acetate = 1: 1 elution) to obtain 0.4 g of the target compound as a colorless oily liquid.

1.60 ~ 1.75 (d-d, 3H), 1.75 1.91 (m, 2H),

2.22 to 2.58 (m, 6H), 4.41 to 461 (m, 1H),

5.28 to 5.61 (m, 1H), 5.78 to 604 (d—q, 1H),

8.55 (s, 1H)

(52) Synthesis of 5-chloro-6- (1-chloroethyl) 1-41 (1,4-dioxaspiro (4,5) decane-1-ylamino) pyrimidine [compound (lc-l)]

1,4-Dioxaspiro (4,5) decane-1-ylamine (8.5 g) is dissolved in triethylamine (20 ml), and 4,5-dichloro-6- (1-chloroethyl) pyrimidine (14 g) is added. In addition, the mixture was stirred at about 60 ° C for 4 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 8.5 g of the target compound as colorless crystals.

1.61-: I.85 (m, 6H), 1.82-1.85 (d, 3H), 2.04-2.13 (m, 2H), 3.95-3 97 (m, 4H), 4.03-4.22 (m, 1H), 5.36-5.44 (m, 1H),

5.39 to 5.41 (m, 1 H), 8.52 (s, 1 H)

(53) Synthesis of 6- (1-acetoxitytyl) -1-5-chloro-4-1 (1,4-dioxasubi (4,5) decane-18-ylamino) pyrimidine [compound (lc-2)]

Compound (lc-1) (8.4 g) was dissolved in N, N-dimethylformamide (100 ml), and potassium acetate (12 g) and carbon dioxide anhydride (7 g) were added. And stirred for 6 hours.

The obtained residue was purified by a silica gel column (Pecogel C-200, toluene: ethyl acetate = 10: 1 elution) to obtain 8.0 of the target compound as a colorless oily liquid.

1.41-: L.43 (d, 3H), 141-; I.83 (m, 6H),

2.0 1 to 2.15 (m, 2 H), 2 15 (s, 3 H),

3.97 to 4.00 (m, 4H), 402 to 4.20 (m, 1H), 5.3 to 5.40 (m, 1H), 599 to 6.02 (m, 1H) 1 H), 8.47 (s, 1 H)

(54) Synthesis of 5-chloro-41- (1,4-dioxaspiro (4,5) decane-8-ylamino) -16- (1-hydroxyethyl) pyrimidine [compound (lc-3)]

The compound (lc-2) (8.0 g) was dissolved in ethanol (10 Om 1), a 1N aqueous solution of sodium hydroxide (50 ml) was added, and the mixture was stirred at room temperature for 2 hours.

The obtained residue was purified by silica gel column (Pelcogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 6.2 g of the target compound as a colorless oily liquid. _{Ή-NMR (CDC 1 3,} δ p pm)

1.41 1.43 (d, 3 H), 1.65 1 89 (m, 6 H),

2.05 ~ 2 14 (m, 2 H), 3 97 ~ 4 1 2 (m, 4 H),

4.12 to 4 21 (m, 1 H), 4 97 to 4 99 (m, 1 H),

5.30 ~ 5 41 (m, 1 H), 5 41 ~ 5 52 (m, 1 H),

8.46 (s1H)

(55) 5-Chloro-41- (1.4-dioxaspiro (4,5) decane-1-8-ylamino) -16- (1-Fluoroethyl) pyrimidine [Compound (lc-4)] Compound (lc-3) (6.2 g) was dissolved in chloroform (100 ml), and DAS-cho (4 g) was added dropwise under ice-cooling and stirring, followed by stirring at room temperature for 5 hours.

After completion of the reaction, water was slowly added to the reaction mixture under ice-cooling and stirring, and the foam layer was separated, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.

The obtained residue was purified by silica gel column (Ecogel C-200, toluene: ethyl acetate = 3: 1 elution) to obtain 5.2 g of the target compound as a colorless oily liquid.

1.51-1.89 (m, 6H), 1.70-1178 (d-d, 3H)

2.02—2.14 (m, 2H), 3.92 to 408 (m, 4H),

4.08 to 4.25 (m, 1 H), 5-28 to 5 48 (m, 1 H),

5.74-6.02 (d-q, 1H), 8.53 (s, 1H)

(56) Synthesis of other compounds (1) in Table 2

Other compounds (1) in Table 2 were synthesized according to the methods described in the above (1) to (55).

Table 2 shows the compounds synthesized as described above.

0 Table 2

Table 2 (continued)

Table 2 (continued)

Table 2 (continued)

Table 2 (continued)

NH-SV

Sun

≠ 0 ^ 2 Table 2 (continued)

Table 2 (continued)

NH-HV R2

¾ N (l a)

R ¹

Table 2 (continued)

〇

D〇2

-NH ^ H

Compound R ¹ R2) -R ² site

Stereoisomers of physical properties

la- 81 -COOC ₂ H ₅ cis

〇

la-82 1! -COOC2H5 rans

-0CCH ₃

c i s / t rans

la-83 OH -COOC2H5

La-84 OH -COOC2H5 cis la-85 OH -COOC2H5 trans ci sZt rans

la- 86 F -COOC2H5

Mixed ^) la - 87 F -COOC2H5 cis la- 88 F one _{_{COOC 2 H 5 rans cis / t}} rans

la-89 OH -COOH

Mixed ^)

I

la-90 OH -COOH c is 1

1 Table 2 (continued)

-NH- <H) -R ² sites

Compound Ri R2 Properties

Stereoisomer of

la-91 OH -COOH rans c i s / 1 r a n s

la- 92 F -COOH n ²⁰ ° 1.5212 mixed ^) D la- 93 F -COOH cis la-94 F -COOH trans G

c i s / t rans o o

la- 95 F -COO-t-CiHgo

Mixed ^!

M C

la-96 F -COC t-C ^ Hg c i s O C

O C la-97 F -COCM-C4H9 trans c i s "t r a n s

la- 98 C £ NH ₉

Mixture la- 99 cr NH ₂ cis

ί la- 100 NH ₂ t rans Table 2 (continued)

Table 2 (continued)

Table 2 (continued)

Table 2 (continued)

Cl a

Ko

Le VIII l -NH ^ H) -R ² site

Compound R ¹ Physical isomerism

〇 X cis / t rans m .p.

la-131 OH

-NHC-0-t-C4H ₉ mixed ^) 180 to 181 ° C

0

la-132 OH c i s

-NHC-0-t-C4H ₉

0

la-133 OH t r ans

-NHC-O-t- Hg

0 cis / transm.p.

la-134 F

-NHC-0-t-C4H ₉ mixed ^) 170 ~ 171 ° C

0

la- 135 F c i s 0

-NHC-0-tC ₄ H ₉ 0

0

la-136 F t r ans

-NHC-0-t-C H9

c i sZt r ans

-137 C £ nC 5 ^H 11

Mixed ^) la-138 C £ c i s la- 139 C £ t r an s

0 c 1 s / trans _nn

la- 140 C 5 ^H 11 -one n J. ^Q 1.5158

-OCC¾ mixture '' Table 2 (continued)

Table 2 (continued)

Compound 〇 R l Physical properties o〇 =

lb- 1 lb- 2 lb- 3 OH m.p.

lb-4 F

119 to 121 ° C lb-5 Br

Table 2 (continued)

Compound Rln physical properties m.p.

lc-1 2

84 to 86 ° C

〇

lc-2 2

-OCCHs

m.p.

lc-3 OH 2

148 to 150 ° C m.p.

lc-4 F 2

102 to 105 ° C lc-5 Br 2

Example 2 Preparation of formulation)

(1) Preparation of granules

5 parts by weight of compound Ua-l). 35 parts by weight of bentonite, 57 parts by weight of talc, 1 part by weight of Neo Perex powder (trade name, manufactured by Kao Corporation) and 2 parts by weight of sodium ligninsulfonate are mixed uniformly. After adding and kneading a small amount of water, the mixture was granulated and dried to obtain granules.

(2) Preparation of wettable powder

10 parts by weight of compound (la-1), 70 parts by weight of kaolin, 18 parts by weight of white carbon, Neobelex powder (trade name; manufactured by Kao Corporation) 1.5 parts by weight and demosol (trade name: Kao) And 0.5 part by weight, and then pulverized to obtain a wettable powder.

(3) Emulsion preparation

Toxane (trade name; manufactured by Sanyo Chemical Industries, Ltd.) (10 parts by weight) was added to compound (la-1) (20 parts by weight and xylene (70 parts by weight)), mixed uniformly, and dissolved to obtain an emulsion.

(4) Preparation of powder

5 parts by weight of the compound (la-1), 50 parts by weight of talc, and 45 parts by weight of potassium chloride were uniformly mixed to obtain a powder.

Example 3 (Efficacy test)

(1) Efficacy test for lotus beetle

Each wettable powder of the compound (1) shown in Table 2 prepared according to Example 2 was diluted to 500 ppm with water containing a surfactant (0.01%). The soybean leaves were immersed for 30 seconds, placed one by one into each plastic cup, and air-dried. In each of these cups, release 10 moss montouts (2nd instar larvae), cover them, and leave them in a constant temperature room at 25 ° C. After 2 days, count the number of live and dead insects in each cup to obtain the kill rate. Was.

The evaluation of the insecticidal effect was shown in four stages (A: 100%, B: less than 100 to 80%, C: less than 80 to 60%, D: less than 60%) according to the range of the insecticidal rate. Table 3 shows these results. Table 3 Efficacy test on Lotus officinalis

(2) Potency test for Conaga

Each wettable powder of the compound (1) shown in Table 2 prepared according to Example 2 was diluted to 300 ppm with water containing a surfactant (0.01%), and the cabbage was added to each of these chemical solutions. Leaf pieces (5 x 5 cm) were soaked for 30 seconds, placed one at a time in each plastic cup, and air-dried.

Next, release 10 moths (3rd instar larvae) into each of these tubs, cover them, and leave them in a constant temperature room at 25 ° C. The mortality was determined by counting.

The results of the evaluation of the insecticidal effect are shown in Table 4 using the four-step evaluation method described in (1) above.

Table 4 Efficacy test compounds for Conaga

1 a— 1 B

1 a-7 A

1 a-1 1 A

1 a-13 A

1 a-15 A

1 a-1 7 A

1 a-1 9 A

1 a-2 1 A

1 a-29 A

1 a-30 A

1 a-40 A

1 a-4 1 A

1 a-47 A

1 a-48 A

1 c-4 B (3) Test for potency

Each wettable powder of the compound (1) shown in Table 2 prepared according to Example 2 was diluted to 300 ppm with water containing a surfactant (0.01%). Rice seedlings were immersed for 30 seconds, air-dried, and inserted into each glass cylinder. Next, release 10 mosquitoes (4th instar larvae) into each cylinder, plug them with a porous plug, leave them in a constant temperature room at 25'C, and count the number of live and dead insects 4 days later to calculate the insecticidal rate. .

The results of the evaluation of the insecticidal effect are shown in Table 5 using the four-step evaluation method described in (1) above.

Table 5 Efficacy test for flying iron

(4) Efficacy test for black leafhopper

Each wettable powder of the compound (1) shown in Table 2 prepared according to Example 2 was diluted with water containing a surfactant (0.01%) to 3◦0 ppm, and each of these chemical solutions was diluted. The rice seedlings were immersed in them for 30 seconds, air-dried, and inserted into each glass cylinder.

Next, 10 cylinders of 4th instar larvae (4th instar larvae) were released into each cylinder, plugged with a porous plug, and allowed to stand in a constant temperature room at 25 ° C. The results of the evaluation of the insecticidal effect are shown in Table 6 using the four-step evaluation method described in (1) above. Table 6 Efficacy test for black leafhopper

(5) Efficacy test for two female adults

Each wettable powder of the compound (1) shown in Table 2 prepared according to Example 2 was diluted to 300 ppm with water containing a surfactant (0.01%), and 1 Each bean leaf piece (2 Omm in diameter) in which 0 female female adults were infested was immersed for 15 seconds.

Next, each leaf piece was left in a constant temperature room at 25 ^eC , and three days later, the number of live and dead insects in each leaf piece was counted to determine the acaricidal rate.

The evaluation of the acaricidal effect was shown in four stages (A: 100%, B: less than 100 to 80%, C: less than 80 to 60%, D: less than 60%) according to the range of the acaricidal rate.

Table 7 shows the results of the evaluation of the acaricidal effect. Table 7 Efficacy test for two female adults

(6) Testing efficacy against rice blast (preventive effect)

10 rice plants (cultivar: Nipponbare) were grown per pot in plastic flower pots with a diameter of 6 cm. The seedlings at the 1.5 leaf stage were prepared as shown in Table 2 and prepared according to Example 2. Each wettable powder of the product (1) was diluted to 500 ppm with water containing a surfactant (0.01%) and sprayed at a rate of 20 ml per pot.

After spraying, the plants were cultivated in a glass greenhouse for 2 days, and then a conidia spore suspension of the rice blast fungus prepared from the diseased leaves was spray-inoculated uniformly on the plant leaves.

After inoculation, they were grown in a humid chamber for 5 days, and the degree of rice blast lesions that appeared on the leaves was examined.

The evaluation of the bactericidal effect was performed in 6 stages (0: whole disease, 1: lesion area about 60%, 2 _: lesion area about 40%, 3 : Lesion area is about 2 °%, 4: Lesion area is 10% or less, 5: No lesion).

Table 8 shows the results. Table 8 Efficacy test for rice blast

(Preventive effect)

(7) Efficacy test for prevention of wheat rust (preventive effect)

Wheat (cultivar: Kobushi wheat) was grown in plastic flower pots with a diameter of 6 cm per pot, and seedlings of 1.5-leaf stage were prepared according to Example 2 and shown in Table 2. The wettable powder of the compound (1) was diluted to 500 ppm with water containing a surfactant (0.01%) and sprayed at 2 Om 1 per pot.

After spraying, the plants were cultivated in a glass greenhouse for 2 days, and then a spore suspension (7 × 1 spores Zm 1) of wheat rust was uniformly spray-inoculated on the plants.

After inoculation, they were grown in a glass greenhouse for one week, and the degree of wheat leaf rust spots on the first leaf was investigated.

The results are shown in Table 9 using the six-step evaluation method described in (S) above.

Table 9 Efficacy test for wheat rust

(Preventive effect)

Industrial applicability

INDUSTRIAL APPLICABILITY The novel 4-cyclohexylaminovirimidine derivative of the present invention has excellent effects such as insecticide, killing, and sterilization, and is useful as a pesticide for agricultural and horticultural use.

Claims

The scope of the claims

1. The following equation (1):

In the formula, R ¹ represents a halogen atom, an alkoxy group having 2 to 5 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, or an alkylthio group having 1 to 4 carbon atoms; And the following equation (Qa):

In the formula, R ² is an alkyl group having 1 to 8 carbon atoms, a phenyl group, a pyrimidinylamino group, an alkoxy group having 1 to 6 carbon atoms, a C00 R ³ group

Here, R ³ represents an alkyl group having 1 to 4 carbon atoms or a hydrogen atom, an amino group, or an NHCO R ⁴ group

Here, represents an alkyl group having 1 to 8 carbon atoms or an alkoxy group having 1 to 8 carbon atoms.

Represents;

Or the following formula (Qb):

Or the following formula (Qc)

Wherein n represents 2 or 3;

Represents a substituent represented by;

Carbon atoms marked with * indicate asymmetric carbon atoms;

A 4-cyclohexylaminopyrimidine derivative represented by the formula:

2. R ¹ is selected from a chlorine atom, an iodine atom, a bromine atom, a fluorine atom, an acyloxy group having 2 to 4 carbon atoms, a hydroxyl group, a methoxy group, an ethoxy group, a methylthio group and an ethylthio group 4. The 4-cyclohexylaminopyrimidine derivative according to claim 1.

3. R ¹ forces a chlorine atom, a bromine atom, a fluorine atom, Asechiruokishi group, hydroxyl group, main butoxy group, an ethoxy group, a methylthio group and according Ru der those selected from Echiruchio groups range as set forth in claim 1, wherein 4-cyclopropyl Hexylaminopyrimidine derivatives.

4. The 4-cyclohexylaminopyrimidine derivative according to claim 1, wherein Q is a compound represented by the formula (Qa).

5. R ² force Alkyl group having 1 to 5 carbon atoms, phenyl group, the following formula (Q a-1):

Wherein R ′ and * are as defined above,

In pyrimidinyl § amino group represented, 1-4 alkoxy group having a carbon number, C 00 R ³ groups, an amino group, or NH CO R ⁴ group

Wherein R ³ and FT are as defined above,

4. The 4-cyclohexylaminopyrimidine derivative according to item 4, wherein the derivative is selected from the group consisting of:

6. R ² force Methyl group, ethyl group, t-butyl group, n-pentyl group, phenyl group, methoxy group, ethoxy group, n-butyloxy group, ethoxycarbonyl group, carboxyl group, t-butoxycarbonyl group, 5. The 4-cyclohexylaminopyrimidine derivative according to claim 4, which is selected from an amino group, an acetamido group, a t-butylamide group, and a t-butyloxyamide group.

7. The 4-cyclohexylaminopyrimidine derivative according to claim 1, wherein Q is a compound represented by the formula (Qb).

8. The 4-cyclohexylaminopyrimidine derivative according to claim 1, wherein Q is a compound represented by the formula (Clc).

9. The 4-cyclohexylaminopyrimidine derivative according to claim 1, wherein the compound is selected from the following group.

(a) a compound in which R ¹ is a halogen atom and R ² is an alkyl group having 1 to 8 carbon atoms (la),

(b) a compound (la) wherein R ¹ is a halogen atom and R ² is a phenyl group,

(c) a compound (la) wherein R ¹ is an acyloxy group having 2 to 5 carbon atoms and R ² is a phenyl group;

(d) a compound (la) in which R ′ is a hydroxyl group and R ² is a fuunyl group,

(e) a compound (la) wherein R ¹ is an alkoxy group having 1 to 4 carbon atoms and R ² is a phenyl group

(f) a compound wherein R ¹ is a halogen atom and R ² is a pyrimidinylamino group (la),

(g) a compound in which R ¹ is a halogen atom (lb), and

(h) Compound (lc) wherein R ¹ is a halogen atom and n is 2.

10. The 41-cyclohexylaminopyrimidine derivative according to claim 1, wherein said compound is selected from the following group.

4-1 (4-1 cis-t e rt-butylcyclohexylamino) 1-5-chloro-

7F 6— (1-Chloroethyl) birimidine,

4- (4-cis-tert-butylcyclohexylamino) 5-chloro-6- (1-fluoroethyl) pyrimidine,

4- (4-trans-tert-butylcyclohexylamino) 5-chloro-6- (1-fluoroethyl) pyrimidine,

6— (1-Chloroethyl) -1-5-Chloro-4- (4-cis-phenylcyclohexylamino) pyrimidine,

6— (1-acetoxicetyl) 1—5-chloro-4-1 (4-1cis—phenylcyclohexylamino) bilimidine,

6— (1-acetoxitytyl) 1—5-chloro-4-1 (41-trans-phenylcyclohexylamino) pyrimidine,

5—Black mouth— 6— (1-Hydroxyethyl) 1-41 (4-1 cis-phenylcyclohexylamino) pyrimidine,

5-chloro-6- (1-hydroxyethyl) 1-41 (4-trans-phenylcyclohexylamino) pyrimidine,

5—Chloro 6— (1—full-year roetil) 1-41 (41 cis—Fenirsik mouth hexylamino) pyrimidine,

5-chloro-6- (1-fluoroethyl) -4-1 (4-trans-phenylcyclohexylamino) pyrimidine,

5-chloro-4- (4-cis-phenylcyclohexylamino) 1-6- (1-methoxethyl) pyrimidine,

6-(1-ethoxyxyl) 1-5-black mouth-4-1 (4-1 cis-fenirushik mouth hexylamino) pyrimidine,

6— (1-Ethoxyshetyl) -1-5-Chloro-4 -— (4-Trans—Phenylcyclohexylamino) pyrimidine,

5—Chloro-6— (1-Fluoroethyl) 1-4— (4-1Cis—methylcyclohexylamino) pyrimidine,

5-chloro-6- (1-fluoroethyl) 1-4-1 (4-trans-methylcyclohexylamino) pyrimidine, 5—Chloro-6— (1—Fluoroethyl) 1—4 (4—cis—n—pentyl cyclohexylamino) bilimidine,

5—Chloro 6— (1—Fluoroethyl) 1-41 (4—1 ”tran s—n—Pentylcyclohexylamino) pyrimidine

5-chloro-4-1- (4-ethylcyclohexylamino) -1-6- (1-fluoroethyl) pyrimidine,

4- (4-cis-tert-butylcyclohexylamino) 5-chloro- 6- (1-fluoroethyl) pyrimidine HC salt,

5-Chloro-4-1 [4-(5-Chloro-6- (1-chloroethyl) pyrimidine-14-ylamino) cyclohexylamino] -1-6- (1-fluoroethyl) pyrimidine,

5- (1-chloro-1- (1-fluoroethyl) pyrimidine-41-ylamino) cyclohexylamino] 1-6- (1-fluoroethyl) pyrimidine,

5—Chloro 6— (11-Fluoroethyl) 1-41 (4-year-old oxocyclohexylamino) pyrimidine and

5—Black mouth—41 (1,4,1 dioxassubi) (4.5) Decane—8—Ilamino—1—6— (1—Fluoroethyl) Pyrimidine.

1 1. The following equation (2):

In the formula, R ¹ and * have the same meanings as described in claim 1, and X represents a halogen atom.

The following equation (3-1):

H ₂ N-Qac (3-1) In the formula, Qac represents a substituent represented by the formula (Qa) or the formula (Qc) described in claim 1;

Wherein Q is a 4-cyclohexylamino represented by the formula (Qa) or the formula (Qc), wherein the cyclohexylamine is reacted with a cyclohexylamine represented by the formula: Production method of bilimidine derivatives.

1 2. The following equation (lc):

In the formula, R ¹ .n and * have the same meanings as described in claim ¹ .

Wherein Q is a 4-cyclohexylaminobilimidine derivative represented by the formula (Qb), wherein the compound represented by the formula (Qb) is hydrolyzed under acidic conditions. Manufacturing method.

1 3. A pesticide for agricultural and horticultural use comprising a 4-cyclohexylaminobilimidine derivative represented by the formula (1) according to claim 1 as an active ingredient.