JPS6143173A - Novel pyrimidine drivative and preparation thereof - Google Patents

Abstract

NEW MATERIAL:A pyrimidine derivative expressed by formula I (R1 is H, phenyl group-substituted methyl or lower alkoxycarbonyl; R2 and R3 are H, lower alkyl, etc., provided that at least one of R2 and R3 is other than H; X is OR4 or formula II; R4 is H or lower aklyl; R5 and R6 are H, alkyl, halogen-substituted lower alkyl, phenyl group-substituted lower alkyl, etc., or 4-6C alkylene in which R5 and R6 are linked; n is 2 or 3). EXAMPLE:Methyl 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylate. USE:Useful as a herbicide, and effective against weeds in paddy field, e.g. barnyard grass or smallflower umbrella-lant, and weeds in upland field, e.g. Deccan grass or large crabgrass. PREPARATION:For example, a guanidine derivative expressed by formula III (R1 is phenyl group-substituted methyl, etc. is reacted with a compound expressed by formula IV (R7 is lower alkyl) to give the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel pyrimidine derivative useful as a herbicide and a method for producing the same.

[Conventional technology]

As a compound having a piperazinylpyrimidine structure,
Chemical Abst Clara (Chem.

Abstr, ) Volume 72 55401y, Volume 76 14
However, the usefulness of these compounds for agricultural applications has not been elucidated at all.

[Problem that the invention seeks to solve]

While conducting research on pyrimidine derivatives, the present inventors discovered that the piperazinylbilimidine compound of the present invention, which is different from those described in the prior art documents, has novel and excellent herbicidal activity, and completed the present invention. I was able to do that.

[Means to solve the invention]

[Summary of the Invention] The present invention is based on ■-General formula 1. ) [In the formula, R represents hydrogen, a phenyl-substituted methyl group, or a lower alkoxycarbonyl group, and 1. R2 and R3 are hydrogen,
It is a lower alkyl group or a phenyl-substituted lower alkyl group, and at least one of Mr. and R8 is a lower alkyl group or a phenyl-substituted lower alkyl group, and X is represented by the general formula (
n) or flush with OR, (It) (wherein, ``R'' is hydrogen or a lower alkyl group, and ``Y'' and ``A'' are hydrogen, an alkyl group, a halogen-substituted lower alkyl group,
Lower alkyl group substituted with phenyl group, phenyl group, amino group, lower alkyl group substituted amino group, hydroxyl group, acyl group, lower alkoxycarbonyl group, lower alkokene group, lower alkoxyoxalyl group, lower alkyloxy group substituted with phenyl group, cyclo It is an alkyl group, a lower alkyl group substituted with a hydroxyl group, a lower alkyl group substituted with a lower alkoxy group, a lower alkyl group substituted with a tetrahydropyranooxy group, or an alkylene group having 4 to 6 carbon atoms in which a reptile and a bird are bonded. )
It is a group represented by, and n is 2 or 6. same as below.

] The present invention also provides a method for producing the novel pyrimidine derivatives as follows: (1) of the general formula σ (wherein is a phenyl-substituted methyl group or a lower alkoxycarbonyl A guanidine derivative (hereinafter the same applies hereinafter) or an addition of the guanidine derivative (wherein is a lower alkyl group). same as below. ] The general formula (1) is characterized by reacting a ketoester derivative represented by
-1) Method for producing a new pyrimidine derivative represented by the general formula (1)
-11"l ) (CH2)n (wherein R: is a lower alkyl group. The same applies hereinafter to 0). The general formula ([-■) represented by λ is characterized in that it hydrolyzes a pyrimidine derivative represented by Method for producing new pyrimidine/derivatives, ■ General formula (1
-It) A pyrimidine derivative represented by the chemical formula (CL)n and the general formula (in the formula, R3 and bird are hydrogen, an alkyl group), a rogene-substituted lower alkyl group, a phenyl-substituted lower alkyl group, a phenyl group, an amino group , lower alkyl substituted amino group, hydroxyl group, lower alkoxy group, phenyl group substituted lower alkyloxy group, cycloalkyl group, hydroxyl group substituted lower alkyl group, lower alkyl group substituted with 7 lower alkyl groups, lower alkyl group substituted with tetrahydropyranooxy group or an alkylene group having 4 to 6 carbon atoms in which Mr. and Bird are combined. same as below. )
A method for producing a novel pyrimidine derivative represented by general formula (1-IV) (CH2)n, characterized by reacting an amine compound represented by
1-I[1-1') (CH2)n Pyrimidine derivatives represented by the general formula group, amine group, lower alkyl group-substituted amino group, cycloalkyl group, hydroxyl group-substituted lower alkyl group, lower alkoxy group-substituted lower alkyl group, tetrahydropyranooxy group-substituted lower alkyl group, or the number of carbon atoms bonded to A method for producing a novel pyrimidine derivative represented by the general formula (1-IV-11), which comprises reacting an amine compound represented by 4 to 6 alkylene groups (the same applies hereinafter) in the presence of a dehydrating agent. ■-General formula 1
-Ill-1), the pyrimidine derivative represented by the general formula (
(2) (In the formula, Y is chlorine or bromine. The same applies hereinafter.) Convert the pyrimidine derivative (
■) A method for producing a novel pyrimidine derivative represented by general formula (1-IV-1), which is characterized by reacting an amine compound represented by general formula (Vl) with general formula (1-V). pyrimidine derivative and general formula (IX) Ra-”
-Z (IX) (In the formula, the bird is hydrogen, a lower alkyl group, a lower alkoxy group, or a lower alkoxycarbonyl group, and zh is a dimethylamine group, a lower alkoxy group, chlorine, or bromine. The same applies hereinafter.) A method for producing a novel pyrimidine derivative represented by the general formula (1-Vl)(CH2)n, characterized by reacting an acylating agent, ■General formula■ (CH2)n (wherein IR9 is a halogen, an alkoxy group, a nitro These include a methyl group, an alkoxycarbonyl group, and an aralkyloxycarbonyl group which are polysubstituted with a phenyl group which may be substituted with a group selected from the group consisting of cylindrical groups.

same as below. ) A method for producing a novel pyrimidine derivative represented by the general formula (I-■) & Gpeng)n, characterized by hydrogenation or acid decomposition of the pyrimidine derivative represented by the formula (■-General formula X)
I) (wherein R8° is a methyl group or hydrogen substituted with a phenyl group which may be substituted with a cynuclear group selected from the group of halogen, alkoxy group, and nitro group.

same as below. ) and compounds represented by the general formula (Kari) R,," Q (Xll) (wherein R3 is a lower alkyl group and J and Q are chlorine or bromine. The same applies hereinafter) The present invention provides a method for producing a novel pyrimidine derivative represented by the general formula (I-■), which is characterized by reacting the following.

[Description of the claimed substance]

The substance of the present invention is represented by the general formula [I].

In the formula, the methyl group substituted with a phenyl group in the form of a bird includes a benzyl group, a diphenylmethyl group, and a triphenylmethyl group, among which a benzyl group is preferable, and the lower alkoxycarbonyl group in a form of a bird includes a methoxycarbonyl group and an ethoxycarbonyl group. , a propoxycarbonyl group, an isopropoquine carbonyl group, a butoxycarbonyl group, and among them, a methoxycarbonyl group and an ethoxycarbonyl group are preferred. In addition, the lower alkyl group of bird or Rs (hereinafter sometimes abbreviated as R2 etc.) in the formula includes methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, inbutyl group, 5ec-butyl group, Examples include tert-butyl group, among which methyl group and ethyl group are preferred; examples of phenyl-substituted lower alkyl groups include those exemplified as phenyl-substituted methyl group, 2-phenylethyl group, 1-phenylethyl group, etc. , 1.1-diphenylethyl group, s 1,2y phenylethyl group, 2.2-diphenylethyl group, and the like, of which 2-phenylethyl group is preferred. In the formula (■) representing Examples of the group include, in addition to those listed as lower alkyl groups such as R7, pentyl groups such as n-pentyl group, hexyl groups such as n-hexyl group, and lower alkyl groups are particularly preferred. Examples of the halogen-substituted lower alkyl group include trifluoromethyl group, 2-fluoroethyl group, 2,2,2. -trifluoroethyl group, 2,2,3,3.3-h:,y
Tafluoroprovir L 2-chloroethyl group natowo,
As the phenyl group-substituted lower alkyl group, the same as those mentioned above are used, and as the lower alkyl group-substituted amine group, methylamine group, ethylamino group, n-propylamino group, isopropylamine group, dimethylamino group, diethylamino group, Di-n-propylamine group, diimpropylamino group, etc., and the acyl group includes aliphatic acyl groups such as formyl group, acetyl group, propionyl group, butyryl group, and valeryl group, and aromatic groups such as benzoyl group and toluoyl group. Examples of lower alkoxycarbonyl groups include methoxy, ethoxy, propoxy, isopropoxy, and lower alkoxy groups.
butoxy group, etc., lower alkoxyoxalyl group such as methoxyoxalyl group, ethoxyoxalyl, propoxyoxalyl group, etc., phenyl group-substituted lower alkyloxy group such as benzyloxalyl group, 2-phenylethoxy group, etc. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups; examples of lower alkyl groups substituted with hydroxyl groups include methylol and ethylol groups; examples of lower alkyl groups substituted with lower alkoxy groups include methoxymethyl, Ethoxymethyl group, methoxyethyl group, ethoxyethyl group, etc., as the lower alkyl group substituted with tetrahydropyranooxy group, 2-tetrahydropyranooxyethyl group, 3-tetrahydropyranooxyethyl group, etc.
-tetrahydropyranooxyprobyl group and the like.

Note that it is preferable that one of the melon and the bird is hydrogen.

Specific examples of these compounds are shown in Table 1.

Table 1 [Manufacturing process invention] [Process for manufacturing the compound of general formula (1-1)] Among the claimed substances, the compound represented by general formula (1-1) is one in which R is R8, that is, the compound represented by the formula (1-1). It is a phenyl-substituted methyl group or a lower alkoxycarbonyl group, and can be produced by reacting a guanidine derivative represented by the general formula (IV) or an addition salt thereof with a ketoester derivative represented by the general formula (IV). Here, in the general formula M, the lower alkyl group for R7 may be the same as that of Karasu. Also, the general formula (I
Addition salts of V) include sulfates, hydrochlorides, nitrates, carbonates, acetates and the like, with sulfates and hydrochlorides being particularly preferred.

The reaction is carried out by suspending the compound of general formula (IV) in an alcohol such as methanol or ethanol, adding an alcoholic solution of caustic alkali to this, and then gradually adding the compound of general formula M in an equimolar amount to compound (IV). Add dropwise and react while stirring. The reaction is usually completed at a temperature of 0 to 100° C. in 1 to 30 hours.

After the reaction, the compound of general formula (I-1) can be obtained by removing salts such as sodium sulfate generated when using the salt of formula (IV), removing the solvent, and then purifying. can. Specifically, it can be carried out by the operations described in the examples (the same applies to the following production methods) 0 [general formula (
1-111)] Among the substances of the present application, the pyrimidine carboxylic acid represented by the general formula (1-1) is obtained by hydrolyzing the corresponding ester, a compound represented by the general formula CI=t[-1]. You can get it by doing. Hydrolysis of the compound of formula (1-11-I) can be carried out in a mixed solution of alcohol such as methanol or ethanol and water using an alkali such as caustic soda as a catalyst. In this case, it is preferable to use about 1 to 2 mol of alkali per 1 mol of ester of formula (I-11-1), and the reaction temperature is 20 to 100°C, and about 0.1 mol of alkali is used.
or i[lHR reaction. After the reaction is completed, the precipitated crystals may be filtered out after neutralization with a mineral acid such as hydrochloric acid or sulfuric acid, or extracted with a solvent such as chloroform or dichloromethane. ] Among the substances of the present application, the pyrimidine derivative represented by the general formula (1-1'/) can be obtained by reacting the pyrimidine carboxylic acid or its ester derivative of the general formula (J-It) with the amine compound of the general formula (Vi). It can be manufactured by Here, examples of each group such as "a" and the alkyl group of Ra in the general formula (Vl) include those exemplified by the chicken or R6 of the formula (ID, etc.).

The reaction is carried out on a compound of formula (1-It) with formula (VI)
The reaction is carried out in the presence of a strong basic catalyst such as sodium methoxide or potassium methoxide. The reaction temperature is near the boiling point of the amine compound, and the reaction is carried out while distilling off the alcohol.
In the case of low point amine compounds, under pressure in a pressure vessel,
It is also possible to react at high temperatures above the boiling point.

The reaction time is 1 to several hours, depending on the temperature.

After the reaction, the desired product is obtained by purification and separation by conventional methods such as washing.

[Process for producing compound of general formula (1-IV-11)] Of the compounds represented by general formula (1-IV) of the substance of the present application, compounds of general formula (
1-IV-n) is represented by the general formula (■-nl-
It can be produced by reacting a pyrimidine derivative having a carboxyl group represented by 1) with an amine compound represented by general formula (Vii). Here, examples of each group such as the alkyl group of t and R in the general formula (■) include those exemplified by the bird or bird in the general formula (II). .

In the reaction, a dehydrating agent such as N,N-dicyclohexylcarpodiide is added to the compound of formula (1-IV), and an amine compound of general formula (1) is added thereto for reaction.

As a reaction solvent, dichloromethane, dichloroethane,
Using a halogenated hydrocarbon such as chloroform, at room temperature,
The reaction may be carried out for one to several hours under normal pressure.

[Production method of compound of general formula (1-r@-1)] Among those represented by general formula (1-!V) of the substance of the present application, compounds of general formula (1-r@-1)
-IV-1) is the formula (1-IV-
Produced by halogenating the carboxyl group of the compound represented by formula (1-m-1) to the acid halogen derivative represented by formula () in the same way as the compound of 11), and then reacting with the amine compound of formula (Vl). can do.

For conversion to the acid halogen derivative of formula (■), a halogenating agent such as thionyl chloride, phosphorus trichloride, phosphorus oxytrichloride, etc. can be used in a conventional manner. The reaction is consistent
This can be carried out in a solvent such as pyridine or triethylamine at room temperature. After the reaction, the raw acid is purified and separated using a conventional method.

[Process for producing compound of general formula (1-Vl)] The substance of the present application represented by general formula (1-Vl) is a pyrimidine derivative represented by general formula (1-V) represented by general formula (IX). It can be produced by reacting an acylating agent. Here, in the general formula (IX), as the lower alkyl group of R8 or 2, R4, R5-'' of the general formula
Examples of e can be mentioned.

As a catalyst for the reaction, sodium hydride, alkyllithium such as butyllithium, methyllithium, sodium amide, lithium diimpropylamide, etc. are used.
As a reaction solvent, an acylating agent of general formula (IX) can be used as a general formula (1-V). It is preferable to use 1 to 100 times the mole of the compound.When 2 in general formula (iX) is halogen, the reaction temperature is usually -20 to 100°C and the reaction time is 0.5 to 10 hours. When 2 is other than halogen, the reaction temperature is usually 70 to 170°C and the reaction time is 1 to several hours.After the reaction, the product is purified by a conventional method.
To separate.

[Process for producing the compound of general formula (1-■)] The claimed substance represented by the general formula (I-■) can be produced by hydrogenolysis or acid decomposition of the pyrimidine derivative represented by the general formula (■). can do.

Here, one of s R9 in the formula (■) is a methyl group di-substituted with a phenyl group which may be substituted with a group selected from the group consisting of halogen, alkoxy group, and nitro group. . Preferred is be/zyl group.

Other examples include alkoxycarbonyl as exemplified in the above, and aralkyloxycarbonyl such as hapendyloxycarbonyl and nitrotunzyloxycarbonyl. The compound represented by formula (1) can be one synthesized according to the method for producing the compound of general formula (1-1).

Hydrocracking catalysts include Pd-carbon, Raney Ni,
Pt-C, i'do, etc. can be used. The reaction solvent is usually an alcohol such as methanol, ethanol or isopropanol, a carboxylic acid such as formic acid, acetic acid or propionic acid, etatruformic acid or a mixed solvent such as ethanol-acetic acid, and hydrogen is added at normal pressure to 10 kg/-. and react at 10 to 100° C. for 0.1 to 10 hours.

On the other hand, in the case of acid decomposition of the compound of formula (1), it is preferable to use hydrochloric acid, hydrobromic acid, or the like as the acid, and to carry out the reaction in an acetic acid solvent. Usually, the reaction is carried out at a reaction temperature of 0 to 100°C for 0.5 to 10 hours.

[Production method of compound of general formula (■-■)]

The substance of the present application represented by the general formula (I-■) can be produced by reacting the compound represented by the general formula (XI) with the acylating agent represented by the general formula (■).

Here, in the general formula (M), Rlo is the same as the optionally substituted phenyl group of FiRe, and in the general formula (XU), the lower alkyl of R1, The groups are the same as those exemplified for chicken.

The reaction is carried out using a compound of general formula (M) dissolved in a solvent such as THF, ether, dichloromethane, or chloroform.
Usually 1 to 6 moles of the compound of the general formula (Shu) is added and allowed to react at room temperature for 1 to several tens of hours. The desired compound is separated and purified from the reaction mixture by a conventional method.

[Usefulness of the claimed substance]

The substance of the present application has excellent activity as a herbicide. That is, the substance of the present invention can be used as a herbicide for paddy fields and upland fields. The herbicides are particularly effective against paddy field weeds such as Japanese grasshopper, Japanese grasshopper, Japanese grasshopper, Japanese fireweed, and Japanese grasshopper, as well as upland weeds such as Japanese barnyard grass, Japanese grasshopper, Japanese grasshopper, and Japanese grasshopper.

In order to use the claimed substance as a herbicide, the claimed substance alone or in combination with a carrier, a surfactant, a dispersant, an adjuvant, etc., is formulated into an aquarium, an emulsion, a fine granule, a granule, etc.
It can be diluted to an appropriate concentration and sprayed, or it can be applied directly.

Hereinafter, the present invention will be specifically explained using Examples, Test Examples, etc.

1-amidino-4-benzylpiperazine sulfate 26.8
Ii (0, Imol) Nometa/- suspension (6ONl)
1M sodium hydroxide in methanol solution 100ml
/, then α-methoxymethyleneacetoacetic acid mef
15.8 ji (0.1 mol) of Rues fl was added dropwise. After stirring overnight at room temperature, the precipitated sodium sulfate was filtered and washed with methanol. Solution F and washing solution were combined, and methanol was distilled off under reduced pressure, and the resulting residue was dissolved in 500 d of ethyl acetate and washed twice with 100 d of water.

The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and ethyl acetate was distilled off under reduced pressure to obtain the desired product as an orange oil (yield: 88%). It crystallized when left at room temperature.

Boiling point = 205-b Melting point: 68-40°C Infrared absorption spectrum (neat; cm') 1
710.1580.1520 1H-Nuclear Magnetic Resonance Spectrum (CD CI, ; pp
m) 2.50 (4H,m), 2.63 (3H,s
), 6.54 (2H,S), 3.83 (3H,s
), 3.94 (4H, m) 7.32 (5H, s )
, 8゜78(IH,s) Synthesized in the same manner as in Example 1 except that α-methoxymethyleneacetoacetic acid ethyl ester was used in place of α-methoxymethyleneacetoacetic acid methyl ester (yield 85%). Yellow crystal melting point: 36-68.5°G Infrared absorption spectrum (KBr tablet; cm-1) 17
10.1585.1520 1H-nuclear magnetic resonance spectrum (CDCl2; ppm)
1°35 (3H, t, J=7.0Hz), 2.
49 (4H, rn) 2.63 (3H, s), 3.54
(2H,s), 3.94 (4H.

m), 4.30 (2H, q, J = 7.0Hz)
, 7.32 (5H.

S), 8.79 (1H, s) Same method as Example 1 except that 2-methoxymethylene-6-oxo-n-valerate methyl ester was used instead of α-methoxymethyleneacetoacetic acid methyl ester. (yield 88%).

Yellow oil infrared absorption spectrum (neat; cf 1) 17
13.1583.1525 'H-Nuclear Magnetic Resonance Spectrum/l/ (CD C1,;
ppm) 1.22 (3H, t, J=7.4Hz), 2.
50 (4H, m), 3.04 (2H, q, J=
7.4f(z), 3.54(2H,s), 3.83
(3H,s), 3.95 (4H,rn), 7.32
(5H.

8), 8.78 (IH,s) 3-oquinone n-valeric acid methyl ester 1.95 g (1
5mmol, J, Amer, Cbcrn, Soc
, vol. 96, 1082Jj, 1974), methyl orthoformate 3, 18 g (30 mmol
) and 4.5i (45 mmol) of acetic anhydride were heated under reflux for 8 hours, and then boiled at normal pressure (bath temperature: 100°C).
) was distilled off. The obtained residue was distilled under reduced pressure to obtain the target product as a yellow oil. ! (yield 76%).

Boiling point: 86-b Infrared absorption spectrum k (neat; cm-')
1710.1625 In=Nuclear magnetic co-S spectrum/l/ (CD CI, ;
ppm) 1.07 and 1.08 (total
3H, t, J=7.0Hz) 2.68and 2.
71 (total 2H, q, J=7.QHz)3
．． 74 and 3.81 (total 3H,s
), 3.96 and 4.00 (total 3H
,s), 7.51 and 7.56 (total
IH) Absolute ethanol 33 mA in a 100 Wll eggplant flask under nitrogen! and sodium 0.121 (5,2rnrn
ol ) or lanium ethoxide was made. Under water cooling, 1.44% of 1-amidino-4-benzylpiperazine sulfate was added to the sodium ethoxide solution. ! i'(5,4rn
mol) and ethyl α-ethoxyethylideneacetoacetate 1
．． 00g (5.0 mmol) was added, and after stirring for 60 minutes, the reaction was carried out at room temperature for 14 hours. The reaction mixture was distributed door to door, r
The liquid was dried to dryness under reduced pressure to obtain 1.41 g of the target product as an oil.

(Yield 79%).

Infrared absorption spectrum (KBr tablet; 11) 1705,
1560.1505 1H-Nuclear Magnetic Resonance Spectrum/l/ (CD CI,;
pprn) 136 (3H, t, J=7.2Hz), 2.
4. '4 (6H, 8) 2.48 (4H, m), 3.54
(2H,s), 3.90 < oi.

m), 4.34 (2H1q, j=7.2Hz), 7.3
4 (5B.

S) Practical Example 5 Ethyl 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylate 40.9 (0,12
8 mol), KOH11F,)120, and 500 ml of EtOH were added to flask 11 and stirred at 100°C for 5 hours.Then the solvent was distilled off under reduced pressure)1
2011 was added and the pH was adjusted to 4 with concentrated hydrochloric acid.

The precipitated crystals were filtered and dried under reduced pressure to obtain 36N of the target product as a white solid (yield 98%) 0 Melting point: 19
2°C Mass spectrometry spectrum m/z 312 (molecular ion peak) Infrared absorption spectrum (KBr tablet; m') 3424%
1700.1652.15761H-nuclear magnetic resonance spectrum (DMSO-d, ; ppm) 2.56 (3H
, s), 2.77 (4H, rn>, 3.87 (2H.

S), 4.00 (4Fi, m), 7.36 (5H
,s), 8.71 (1H,5) 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidi7 5-carboxylic acid 2.0 g (6,4 mr
no l ) and 10% Pd/C400Q to AcOH2Q
The mixture was dissolved in WL1 O and 20 d of EtOH, and heated and stirred at 80° C. for 3 hours while bubbling H2. After the reaction,
Pd/C was passed through the mouth, and the mouth liquid was dried under reduced pressure to obtain 1.4 g of the target product as a white solid (yield 98%).

Mass spectrometry spectrum rn/Z222 (molecular ion peak) 1H-nuclear magnetic resonance spectrum (DMSO-d, ; p
pm) 2.64 (3H, s), 3.18 (4H, m)
, 4.14 (4h.

m), a81 (IH, 8), 10°8 (2H, br,
s) Reference Example 7 2-(4-benzyl-1-piperazinyldiisopropylamine 1.44.!i'(14,3rn
mol) in anhydrous THF solution (100 WLl),
Under water cooling, 14.0 ml of IM-nBuLi hexane solution (
14.0 mmol) was added and stirred for 5 hours. Then, it was cooled to -70°C and 2-(4-benzyl-1-piperazinyl)-4-methylbilimicin-5-carboxylic acid ethyl ester 4.73. A solution of F (13.9 mmol) in anhydrous THF (20 ml) was added dropwise over 0.5 hr.
Furthermore, 1. Stirred for 1 hour.

Next, benzyl bromide 2.4 & (14, Ornm
An anhydrous THF solution (2Qml) of ol') was added dropwise at -50°C, and then the temperature was gradually raised to 20°C and stirred for 2 hours. After that, the solvent was distilled off and purified by silica gel column chromatography, yielding 4.79 g of the target product as a pale yellow oil.
(yield 80%).

Mass spectrometry spectrum m/z 430 (molecular ion peak) In-nuclear magnetic resonance spectrum /l/ (CD C13;
pprn) 1.34 (3H, t, J = 6.QJi
z), 2.48 (4H, m), 2.92-3.10
(2H,rn), 3.22-3.40 (2H.

m), 3.55 (21-1,8), 3.92 (4H, m
), 4.60 (2H, q, J=6.0Hz), 7.24
(5)1. B), 7.35 (5H,s), 8.82
(IH, 8) Example 8 2-(4-benzyl-1-piperazinyl-2-(4-benzyl-1-piperazinyl)-4
-Methylpyrimidine-5-carboxylic acid ethyl 2-(4-benzyl-1-piperazinyl)-4-(2-
Synthesis was performed in the same manner as in Example 5, except that ethyl pyrimidine-5-carboxylate (722-ethyl)pyrimidine-5-carboxylate was used (yield: 99%).

Oil mass spectrometry spectrum m/z 402 (molecular ion peak) Infrared absorption spectrum (KBr tablet; 11) 3425.
1688.1580 1H-Nuclear Magnetic Resonance Spectrum (CD C13i pp”
) 2.56 (4H, br, s), 2.82-2.94
(2H, m), 3.15-3.40 (2H, m),
3.60 (2H, s), 3.90 (4H, br, s),
7.22 (5H, s), 7.62 (5H, s), 8.1
2 (IH, br, s ), 8.72 (H, 5) 1-amidino-4-benzylpiperazine sulfate 16.1 g (
60 mmol) methanol suspension ('iQQm) under water cooling, 2.4 g (6 (Jm
iooml of methanol solution of α-ethoxymethyleneacetoacetanilide 14. Of!
(60 mmol) of methanol solution was added dropwise. After stirring overnight at room temperature, the precipitated salt was filtered and washed with methanol.

Combine the washing liquid and the washing liquid, and after distilling off methanol under reduced pressure,
The obtained residue was recrystallized from chloroform/hexane to obtain 17.26.9% of the target product as colorless crystals (yield 74%).

Melting point: 176-177°C Infrared absorption spectrum (KBr tablet; cm) 3300.
1653.1595, In-Nuclear Magnetic Resonance Spectrum/l/ (CD C1,;
pprn) 2.48 (4H, rn), 2.53 (3H,
8).

3.54 (2H,s), 3.89 (4H,rn
), 7.1-7.6 (5H, rn), 7.32 (5H,
s), 7.70 (IH, br ), 8.39 (IH,
S) Reference example Synthesis of α-ethoxymethyleneacetoacetanilide Acetoacetanilide 26.6,! i' (0,15r
No, ethyl orthoformate 44.5,! i' (0,
3mol) ,,,acetic anhydride 45.9g (0.3m0
The mixture of 1) was heated under reflux for 2 hours. After cooling to room temperature, hexane was added, and the precipitated crystals were separated and dried to obtain 14.1 of the target product in the form of light brown needle-like crystals (yield: 41
%).

Melting point: 88-89°C Infrared absorption spectrum (KBr tablet; 11) 3160.
1660.1585. 1H-nuclear magnetic resonance spectrum (CDC13; ppm) 1
．． 46 (3H,' t, J=7.3Hz), 2
．． 50 (3H,s), 4.37 (2H1q+ J
=7.0Hz), 7.0-7.7 (6H), 8.4
6(IH,s) 8.16 g (25
mmol), ethylamide 75.64. ! i' (12
5rnmol) and 21.5rnmol of sodium methoxide.
8wt% methanol solution 1.24.51 (5rnmo
l) in a 50m#, t-) crepe and heated at 100℃ for 6
．． The reaction was allowed to proceed for 5 hours.

The resulting reaction mixture was poured into 150ml of water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over magnesium sulfate, and then ethyl acetate was distilled off under reduced pressure. The resulting residue was recrystallized from ethyl acetate-hexane to give the desired product as pale yellow crystals with 7.71. ! iT was obtained (yield 91%).

Melting point: 110-111°C Infrared absorption spectrum (KBr tablet; c+n-1) 32
90.1625.1585 1H-Nuclear Magnetic Resonance Spectrum (CD CI, ; pp
m) 1.22 (3H, t, J=7.QHz), 2
．． 49 (4H, m).

2.51 (3H,s), 3.42 (2H,rll)
, 3.55 (2H.

S), 3.88 (4H, m), 5.76 (IH, I
T+), Otsuro 2 (5H, 8), 8.30 (1H, 5) 1-amidino-4-benzylpiperazine sulfate 1.34
．． 9 (5 mmol) in methanol suspension (5 mg)
Sodium hydroxide 2 Q Omg (5 m
mol ) of methanol solution (5 m
N-ethyl-α-ethoxymethylene/acetoacetamide 9
A methanol solution (5 mQ) of 30 μm (5 rnmol) was added dropwise.

After stirring overnight at room temperature, the precipitated salt was filtered and washed with methanol. The P solution and the washing solution were combined, methanol was distilled off under reduced pressure, and the resulting residue was quantitatively determined by gas chromatography (GC), and the yield of the same target product as in Example 10 was 64%.

GC quantitative conditions packing material: Diasolid ZS glass column 2m Column temperature = 180°C, after holding for 4 minutes, 250 at 8°C/#I
Carrier gas: Nitrogen (flow rate 30 w/min) Internal standard: 0-terphenyl GC retention time of target substance: 125% 2-(4-benzyl-1-piperazinyl)-4-methylpyri is gin-5 -carboxylic acid 9.37i30rnmol
) was suspended in 150 mA' of dicoupromethane, stirred, and N,N-dicyclohexylcarbodiimide 6.
19. ! 9 (30rllrTIO1) of Jinoo methane solution 3Qm# was added dropwise. After stirring at 20°C for 16 hours, anhydrous ethylamide 13.5. ! i' (300 mmol
) was added dropwise and further stirred for 6 hours. 600 d of ethyl acetate was added to the reaction mixture, the precipitated N,N-dicyclohexylurea was removed by filtration, and the p solution was concentrated under reduced pressure. When the residue was purified by silica gel column chromatography (elution solvent: ethyl acetate), 2.35.9 of the target product as pale yellow crystals as in Example 10 was obtained (yield 26%).
.

- Using 2-(4-benzyl-1-homohyherazinyl)-4-methylpyrimidine-5-carboxylic acid instead of 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid. It was synthesized in the same manner as in Example 12, except for the following (yield: 25%).

Mass spectrometry spectrum: m/Z353 (molecular ion peak) 1H-nuclear magnetic resonance spectrum (CD CI, p
pm) 1.23 (3H, t+ J=6.5Hz), 1.
76-2.07 (2H, m), 2.52 (3H, s)
, 2.56-2.84 (4H, m), 3.42 (2) (
, q, J = 6.5H2), 3.63 (2H,s
), 3.70-4.00 (4H, yn) 5.67 (IH
, br, ), 7.25 (5H,s ), 8.52 (I
H,S) do 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid methyl
Synthesis was performed in the same manner as in Example 10, except that ethyl -benzyl-1-piperazinyl)-4,6-dimethylpyrimidine-5-carboxylate was used (yield: 6%).

Melting point: 155-158°C Infrared absorption spectrum (Nujol; cm')
3260.1630'H-Nuclear Magnetic Resonance Svekle (CD C13; pp
rn) 1.22 (3H, t, J=7.0H2), 2.3
2 (6H, s ), 2.46 (4H, rn), 6.44
(2H, rn), 3.54 (2H.

S), 3.84 (4H, m), 5.70 (IH, br,
s), 7.32 (5H,s) 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid methyl
Synthesis was performed in the same manner as in Example 10, except that methyl -benzyl-1-piperazinyl)-4-ethylpyrimidine-5-carboxylate was used (yield: 48%).

Melting point: 161-162°C Infrared absorption spectrum (KBr tablet; c+++1) 32
70.1623.1580 'H'a magnetic resonance spectrum (deuterochloroform; ppm
) 1.22 (6H, t+ J=7.0Hz), 2.49 (
4H, rn), 2.85 (2H, q, J=7.0Hz)
, 3.40 (2H,rn), 3.54 (2H,s
), 3.88 (4H,m >, 5.68 (IH.

br), 7.32 (5H, S), 8.30 (IH, S)
It was synthesized in the same manner as in Example 10, except that methylamine was used instead of ethylamine (yield: 81%).

Oily 1H-Nuclear Magnetic Resonance Spectrum/L/ (CD C13;
p pm ) 2.48 (4H, rn), 2.52 (3H
, s), 2.96 (5H.

d, J=6.0Hz), 3.54 (2H,s), 3
．． 88 (4H.

m), 5.68 (IH, rn), 7.32 (5H, S)
, 8.30 (1H・S) Example 17 2-(4-benzyl-1-piberazimi
Synthesized in the same manner as in Example 10 except that n-propylamine was used instead of doethylamine (yield 54%)
.

Melting point: 166°C (recrystallized from dichloromethane-hexane) Infrared absorption spectrum (KBr tablet; Cm) 6245.
1628.1590 1H-Nuclear Magnetic Resonance Spectrum/l/ (CD C13;
ppm) 0.91 (3H, t, J=7.2Hz),
1.61 (2H, rn).

2.50 (4H, m), 2.53 (RoH, s), 2.
36 (2H.

q, J = 7.2H2), 3.56 (2H, 8), 3
．． 89 (4H.

m), 5.74 (IH, bs), 7.34 (5H, S)
, 8.32 (IH, 8) Synthesized in the same manner as in Example 10, except that isopropylamine was used instead of tyrpyrimidine-5-carboxylic acid amidoethylamine (yield: 54
%).

Melting point: 152°C Infrared absorption spectrum (KBr tablet; cm-1) 630
5.1628.1594 1H-Nuclear Magnetic Resonance Spectrum (CD C13; pp
rn) 1.23 (6H, d, J=7.2Hz)
, 2.47 (4H, rn), 2.51 (3H, s),
3.53 (2H, s), 3.87 (4H.

m), 4.19 (IH, m), 5.48 (IH, br,
d, J=7.2Hz), 7.32 (5H,s)
, 8.28 (IH, 8) was synthesized in the same manner as in Example 10 except that cyclopropylamine was used instead of amidoethylamine (yield 58%).
).

White powder melting point: 145-147°C Infrared absorption spectrum (KBr tablet; cm-1) 330
0.1660.1580, 'H-Nuclear Magnetic Resonance, <hex) (CD C13; ppm
)0.5-1.0 (4H,m), 2.49 (4H
, m ), 2.52 (3H, s), 2.7-3.0 (
IH,rn), 3.56 (2H.

s), 3.88 (4H, rn), 5.87 (I
H, br; s).

Synthesis was carried out in the same manner as in Example 10, except that cyclohexylamine was used instead of 7.34 (5H, s) and 8.28 (IH, 8) acid amidoethylamine (yield: 11
%).

Melting point: 172-173°C (recrystallized from ethyl acetate-hexane) Infrared absorption spectrum (KBr tablet; cnvl) 328
0.1628.1586, IH-Nuclear Magnetic Resonance Spectrum (CD C13; pp”
)0.9~1.2 (10H), 2.4 (4H,rr
l ), 2.46 (3H1S), 3.54 (2H,s)
, 3.87 (4H, rn), 3.9 (IH, rrl)
, 5.5 (IH, br), 7.32 (5H.

S), 8.30 (IH,s) Synthesized in the same manner as in Example 10 except that 2-methoxyethylamine was used instead of ethylamine (yield 2
1%).

Melting point: 95-96°C Infrared absorption spectrum (KBr tablet; cm-') 6
310.1627.1587 1H-Nuclear Magnetic Resonance Spectrum # (CD C13; pp
m) 2.48 (4H, m), 2.51 (3H, a)
, 5.55 (3H, s), 3.54 (6H, s),
3.88 (4H, m ), 6.2 (IHlbr), 7.
31 (5H, B), 8.34 (IH.

2-(4-Benzyl-1-piperazinyl)-4-methylpyrimidine-5-carbo/methyl acid s, i6. y(25
mrnol), benzylamine: / 13.4.9 (1
, 2'5 mmol) and 2 of sodium methoxide.
i, 8 wt% methanol solution 1.24' (5 m
rnol) was placed in a reaction vessel and reacted at 185°C for 6.5 hours while methanol was distilled off.

The resulting reaction mixture was poured into 3001d of water and extracted with ethyl acetate.

The ethyl acetate layer was washed with saturated brine and dried over magnesium sulfate, and then ethyl acetate and excess benzylamine were distilled off under reduced pressure. The resulting residue was recrystallized from ethyl acetate-hexane to yield 7.77 g of the desired product as pale yellow crystals.
(yield 77%).

Melting point: 116-117°C Infrared absorption spectrum (KBr tablet; cIn) 6280
．． 1623.1587 1H-nuclei 1 [tK resonance scheme)/I/(CDCl2; p
pm) 2.47 (4H, m), 2.52 (3H, s),
6.56 (2H, s), 3.87 (4H, rn>, 4.
56 (2H.

a, J=5.7Hz), 6.06 (IH, br, t)
-7,31 (10H, s), 8.33 (IH, 5) 2-
(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid ethyl 0.336g (1rnm
ol) and hydrazihydrate y3.9 (60 mmol) to 16
The reaction was carried out at 0°C for 4 hours. 5Qml of water was added, and the precipitated crystals were filtered and washed with water. When recrystallized with ethanol,
0.2 g of the target product as white crystals was obtained (yield 62%).

Melting point: 147°C Infrared absorption spectrum (KBr tablet; 11) 3265.
6160.1624.1588IH-Nuclear Magnetic Resonance Spectrum (CD C1s; pprn) 2.49 (4H,
m ), 2.52 (3H, a ), 6,55 (2H, E
+), 3.89 (4E(,m), 4.05 C2H.

btus), 7.05 (IH, br, s), 7.32
<5H.

8), 8.31 (IH, 5) Ethyl 2-(4-be/zi-1-piperazinyl)-4-methylpyrimidine-5-carboxylate 0.33.1 (1 m
rnol) and 71.22 g of ethanolamide (20 mrn
ol) was reacted at 170°C for 1.5 hours. Water 5Qm/
' was added and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and then dried over magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was recrystallized from ethyl acetate-hexane to obtain 0.2 El of the desired product as white crystals (yield 72%).

Melting point: 123°C Infrared absorption spectrum (KBr tablet; cm') 3
280, 1630.1594, IH-Nuclear Magnetic Resonance Spectronov CD CI,; ppm
) 2.48 (4H, m'), 2.51 (3H, s)
, 2.46-2.62 (4H, m), 2.73-2.8
3 (6H, m > 6.39 (IH, br, s ), 7
．． 32 (5H,s), 8.35 (1n, 5) 2-(4-benzyl-1-piperazinyl)-N-(2-
6.52.9 (77.5 mmol) of 2,3-dihydropyran and P in an ethyl acetate solution (160 me) of 2.76 ji (7.75 mmol) of −
Toluenesulfonic acid monohydrate 1.77 (9 (9,30r
nrnol) was added and stirred at room temperature for 2 days. The resulting reaction mixture was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, and then ethyl acetate was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography (elution solvent:
When purified with ethyl acetate), the desired product was obtained as pale yellow crystals as 3.
24 g was obtained (yield 95%).

Melting point: 87-88℃ Infrared absorption spectrum (KBr tablet; cm 1) 32
80.1622.1588 IH-Nuclear Magnetic Resonance Spectrum/l/ (CD C13;
pprn) 1.3-2.0 (6H), 2.48 (4H
, m), 2.52 (5H, s), 3.54 (2H, s
), 3.5-3.9 (6H) 3.89 (4H, m
), 4.56 (IH, m), 6.54 (IH, rn),
7.31 (5H,s), 8.35 (IH,s) amide 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid 4.69. ! 9 (15rn
mol) was suspended in pyridine/80ml, 5OC
Add 124,45,F (37,5rnmol),
Stirred at room temperature for 1 hour. Then, 4.62 g (37.5 mrnol) of O-benzylhydroxylamine was added and stirred overnight at room temperature. After pyridine in the reaction mixture was distilled off under reduced pressure, 200 Wg of water was added, the pH was adjusted to 8 with K2CO3, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over magnesium sulfate, and then ethyl acetate was distilled off under reduced pressure.

The resulting residue was recrystallized from ethyl acetate-hexane to yield the desired product as colorless crystals. '95g was obtained (yield 66
%).

Melting point: 150-151°C Mass spectrometry spectrum: rn/Z417 (molecular ion peak) Infrared absorption spectrum (KBr tablet; cm') 3
190.1668.1588. 1H-nuclear magnetic resonance spectrum (CD ci3; ppr
n) 2.45 (3H, s), 2.50 (4H, m)
, 3.53 (2H.

S), 3.86 (4H, m), 4.98 (2H, s),
7.31 (5H, s), 7.38 (5H, S), 8.1
4(IH,s)8.25(IH,br) was synthesized in the same manner as in Example 26 except that 60% aqueous ammonia was used instead of 0-benzylhydroxylamine (yield 25%).

8 points: 195-196°C (recrystallized from chloroform-hexane) Mass spectrometry spectrum: rn/Z 311 (molecular ion peak) Infrared absorption spectrum (KBr tablet; cm-1) 349
7.6367.1661.15771H-Nuclear magnetic resonance spectrum (CD C13; ppm) 2.48 (4H,
m), 2.56 (3H, s), 6.54 (2H, 8)
, 3.90 (4H, m), 7.31 (5H, S ) 8
．． 43(IH,!ribonic acid amide O-benzylhydroxylamine was synthesized in the same manner as in Example 26 except that a 70% aqueous ethylamine solution was used (yield: 47%).

Melting point: 161-132°C Infrared absorption spectrum (KBr tablet; Crn″1) 62
85.1624,1582 In-nuclear magnetic resonance spectrum (CD C13; ppm
) 1, 15 (3H, t+ J = 7.OHz), 2.
48 (4H, m) 2.90-3.15 (4H, m),
3.32 (2H, q, J=7, QHz), 3.52
(2H,s), 3.83 (4H,m)7.22 (
5H, s), Otsu 37 (5H, s), 8.60 (1H
, s) Example 29 2-(4-be/zi-1-piperadiamide) Synthesized in the same manner as in Example 26 except that pyrrolidine was used instead of 0-benzylhydroxylamine (yield 43%).

Melting point = 164-165°C Mass spectrometry spectrum: m/Z 365 (molecular ion peak) 1H-nuclear magnetic resonance spectrum (CD C1s i Pp
m) 1.96 (4H, br, s), 2.37 (3H,
s ), 2.49 (4H, m), 3.29 (4H, b
r, s), 3.56 (2H.

S), 6.87 (4H, m), 7.33 (5) (, s
), 8.16 (IH, s) Synthesized in the same manner as in Example 26 except that diethylamine was used instead of mido-0-benzylhydroxylamine (yield 43%).

Melting point: 121-122°C Infrared absorption spectrum (KBr tablet; cm) 1624.
1594'H-Nuclear Magnetic Resonance Vector (CD CI, ; pp
rn) 1.16 (6H, t, J=7.2Hz), 2
．． 13 (3H, s), 2.49 (4H, rn), 5.5
8C4H, br, s), 3.55 (2H, s'), 3
．． 86 (4H, m), 7.37 (5H, s), 8.
09(IH,S) Methyl-n in place of 0-benzylhydroxylamine
Synthesis was carried out in the same manner as in Example 26 except that -hexylamine/ was used (yield 69%).

Brown liquid infrared absorption spectrum (Nujol; cm) 1
625.1585 In-Nuclear Magnetic Resonance Spectrum (CDC1,; ppm
)0.90 (3H, t+ J=7.0Hz), 1.10
~1.80 (8H, m), 2.34 (3H, s), 2.
50 (4H.

m), 2.98 (3H, s), 3.56 (2H, s)
, 3.88 (6H, m), 7.35 (5H, a), 8.
11(IH,5) In place of 0-benzylhydroxylamine, 2.2.
2-) Synthesized in the same manner as in Example 26 except for using IJ fluoroethylamine hydrochloride (yield 6%) Melting point: 156-157°C Infrared absorption spectrum (KBr tablet; cm-1) 6000 .1644.1595. 1H-Nuclear Magnetic Resonance Spectrum (CD C13i p p
rn )2.50 (4H,m), 2.52 (3H
,s), 3.55(2H,s), 3.90(4H,m
), 4.11 (2H, dq.

J=9.2 and 6.6Hz), 6.00(IH
, br, t ), 7.32 (5H, s), 8.36 (
IH, 5) Synthesis was performed in the same manner as in Example 26, except that 0-methylhydroxylamine was used in place of 0-benzylhydroxylamine (yield: 86%).

Melting point: 131-133°G Infrared absorption spectrum (KBr tablet i Cl711) 1
630.1590 1H-Nuclear Magnetic Resonance Spectrum (CD C13i pp”
) 2.52 (3H, S), 2.52 (4H, m),
3.56 (2H.

S), 3.84 (3H, s), 3.88 (4H, m
), 7.33 (5H, s), a28 (IH, s) Example 34 2-(4-benzyl-1-piperazinyl)-N
-dimethylamino-4-methylpyrimidine-5-carboxylic acid amide 0-pene dihydroxylamine, 1°1
- Synthesized in the same manner as in Example 26 except for using dimethylhydrazine (yield 48%) 0 Melting point: 157-1
58°C infrared absorption spectrum (KBr tablet; 0) 1645.
1586'H-Nuclear Magnetic Resonance Spectrum (CD C13; pp
m) 2.48 (3H, s ), 2.56 (4H, m>
, 2.63 (6H, 8), 3.55 (2H2S), 3
．． 88 (4H, m>, 7.33 (5H, s ), 8.
27(IH, 5)-5-carboxylic acid amide 2-(4-benzyl-1-piperazi)-N-ethyl-4-methylpyrimidine-5-carbo/acid amide 0.
Ro35. A 5me solution of ji+ (1 mmol) in tetrahydrofuran was cooled in a water bath, and 0.048 ml of sodium hydride was added.
g (60% in oil, 1.2 rnmol) was added and stirred for 10 minutes.

Then ethyloxalyl chloride 0.15 f/(1,
1 mmol) of tetrahydrofuran solution was added dropwise to the mixture, and the mixture was reacted at room temperature for 1 hour and then at 70° C. for 4 hours. The resulting reaction mixture was poured into 50 g of ice water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/hexane-3/2) to obtain the desired product as a light blue oil with 0.306. F was obtained (yield 71%)
.

=1 Infrared absorption spectrum (neat; cm) 1740.
1712.1672.1590"H-nuclear magnetic resonance spectrum (CD C13; ppm) 1.18 (3H, t, J
=7.2Hz), 1.24(3H,t.

J=7.2Hz), 2.47 (3,H,s),
2.51 (4H.

m), 3.58 (2, H, s), 3.72-4.16
(8H.

m), 7.34 (5H, s), 8,23 (IH, 8) Synthesized in the same manner as in Example 35 except that acetyl chloride was used instead of ethyloxalyl chloride (yield 68%)
.

Pale yellow oily In-nuclear magnetic resonance spectrum/l/ (CD C13i
pp") 1.17 (3H, t, J=7.2Hz),
2.23 (RoH, s), 2.48 (3H, s), 2.5
3 (4H,rn), 3.54 (2H.

S), 3.76 (2H, q, J = 7.2Hz)
, 3.94 (4H.

m), 7.33 (5H, s), 8.24 (IH, S) 2
-(4-benzyl-1-piperazinyl)-N-ethyl-
4-methylpyrimidine-5-carboxylic acid amide 0.50
g (1,47 mmol) Te), J He)'o7u7
Add n-butyllithium hexane solution (1,56M) to the 5mg solution under water cooling.1. OmJ was added and stirred at 0°C for 5 minutes. Add 0.18i of ethyl chlorocarbonate to the mixture.
I! (1.88 rnmol) and stirred for 2 hours under water cooling, then 20 ml of water and 20 m/+ of chloroform were added. The organic layer was separated, the aqueous layer was extracted three times with 20 tal of chloroform, the organic layers were combined, dried over sodium sulfate, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (developing solvent: ethyl acetate) to obtain 0.55.9% of the target product as a colorless oil (yield: 86%).
%).

1H-Nuclear Magnetic Resonance Spectrum/I/ (CD C13p
ppm ) 1, 12 (3H, t, J=7.0Hz
), 1.28 (3H, t.

J=7. QHz), 2.40 (3H, s), 2.50
(4H, rn) 3.55 (2H, s ), 3.82 (
2H2Q, J=7.0Hz)3.90(4H,rTl
), 4.13 (2H, (1, J=7.OHz)7.
31 (5H, s), 8.13 (IH, s) Example 38
N-amino-2-(4-benzyl-4-methylpyrimidine-5-carboxylic acid amide sodium hydride 0.048 g (60% in oil,
1.2rnmol) was washed with ether, 2.5ml of dimethylformamide was added, and 0.326I (1mmol) of 2-(4-benzyl-1-piperacyl)-4-methylpyrimidine-5-carboxylic acid hydrazide was added in dimethyl. 2.5 d of formamide solution was added dropwise at room temperature. Next, the temperature was raised to 150°C and the reaction was carried out for 4 hours. After cooling to room temperature, 50F ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and then the solvent was distilled off under reduced pressure.

The resulting residue was subjected to silica gel column chromatography -
- (developing solvent: ethyl acetate/acetone - 4/1) to obtain 0.159.9 of the desired product as white crystals (yield: 45 yen).

Melting point = 193°C Mass spectrometry spectrum: m/Z 354 (molecular ion peak) Infrared absorption spectrum (KBr tablet; crIVl) 61
95.1678.1594 1H-Nuclear Magnetic Resonance Spectrum (CD CI, +DMS
O-de; ppm) 2.51 (4H, m), 2.54 (3H, s)
, 2.94 (2H.

br, s), 3.55 (2H, s), 3.89 (4
H,m), 7.33 (5H,s), 8. 'l 4(I
H,s), 8.47(1)LS) Example 69 4-Methyl-2-(1-piperazinyl)pyrimidine-5-carboxylic acid amide 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine -5-Carbonamide 0.75F and 10%
pd-CD, 20. ! 1/l was placed in a 100 ml Nitro flask, and the atmosphere was replaced with nitrogen under reduced pressure. 2 Qtul of absolute ethanol and 10 ml of glacial acetic acid were added thereto, and hydrogen reduction was performed at 60 to 65° C. under normal pressure for 65 minutes. The reaction mixture was distributed and the catalyst was washed with ethanol. After drying all the colorless furnace liquid, it was dissolved in aqueous sodium bicarbonate solution to make p) (=13 to 9) and extracted with chloroform.The aqueous layer was dried under reduced pressure and extracted with chloroform.
Heated extraction was performed with an ethanol mixed solvent. After separating the organic layer, it was dried under reduced pressure. The dried product was extracted with chloroborm, and the chloroform layer was dried under reduced pressure to give colorless crystals in a yield of 0.12. ! 9 (yield 23%).

Melting point: 210-212°C Infrared absorption spectrum (KBr tablet; cm') 6360
．． 3180.1640.15851H-nuclear magnetic resonance spectrum (, DMSO-d, ;pprn) 2.46 (3
H,s), 2.70 (4H,m), 3.70 (4H
.

m), 7.20 (IH, br, s ), 7.66 (IH
,br,s)8.42(IH,5) 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid amide
-benzyl-1-piperazinyl)-N-cyclohexyl-4-methylpyrimidine-5-carboxylic acid amide was used in the same manner as in Example 69 (yield: 91
%).

Melting point -180-182°C (recrystallized from ethyl acetate) Infrared absorption spectrum (KBr tablet; cln) 3250.
1617.1582 1H-nuclear magnetic resonance spectrum (CDC13; ppm) 1
．． 0-2.2 (10H), 2.51 (3H,s),
6.03 (4H, m), 4.00 (4H, rll),
4.0 (IH, m), 5.7 (IH, brd), C
32(IH,s) Example 41 N-benzyl-4-
Methyl-2-(1-piperazinyl)pyrimidine-5- KN-benzyl-2-(4-benzyl- 1-piperazinyl)-4-
It was synthesized in the same manner as in Example 69 except that methylpyrimidine-5-carboxylic acid amide was used (yield 95%).

1H-Nuclear Magnetic Resonance Spectrum # (CD C13; pp
rn) 2.53 (3H, s ), 3.12 (4H, r
n), 4.07 (4H.

m), 4.56 (2H, d, J-6, 3Hz), 6
．． 47 (IH.

br, s), 7.33 (5H, s), 8.68 (I
H,S) Example 42 4-methyl-N-phenyl-2-
(2-(2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid amide)
4-be/giru-1-piperazinyl)-4-methyl-N-
Synthesized in the same manner as in Example 39 except for using phenylpyrimidine-5-carboxylic acid amide (yield 98%)
.

1H-nuclear magnetic resonance spectrum (CD C13; ppr
n) 2.47 (3H, s), 2.74 (4H, m)
, 3.76 (4H.

m), 7.00-7.48 (3H, m), 7.60-7
．． 80 (2 am), 8.48 (IH,s) Example 43 N,N-diethyl-4-methyl-2-
5-Carboxylic acid amide 2-L(
'4-benzyl-1-piperazinyl), N.

It was synthesized in the same manner as in Example 69 except that N-diethyl-4-methylpyrimidine-5-carboxylic acid amide was used (yield: 62%).

1H-Nuclear Magnetic Resonance Spectrum (CD C13; I)l
) m) 1.1'8 (6H, m), 2.34 (3H, s
), 3.19 (4H.

m), 3.5 (5H, rn), 4.11 (4H, rn)
, 8.15(1H,s') thyl-N-tetramethylenepyrimidine-5-carboxylic acid amide 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid amide instead of 2- (4
-benzyl-1-piperazinyl)-4-methyl-N-tetramethylenepyrimidine-5-carboxylic acid amide was used in the same manner as in Example 39 (yield: 99
%).

Melting point: 228°C (recrystallized from ethanol ether) Mass spectrometry spectrum: m/Z 275 (molecular ion beak) Infrared absorption spectrum (KBr tablet; an') 3
416.3300.1626.15821H-nuclear magnetic resonance spectrum (DMSO-d, ; ppm) 1.83
(4H, br, s), 2.26 (3H, s), 2
．． 72 (4H, m), 3.24 (4H, br, s)
, 3.69 (4H.

m), 8.20 (IH, s) Example 45 4-methyl-2-(1-piperazinyl)
-N-(2,2,2-)pyrimidine-5-carboxylic acid amide Instead of 2-(4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid amide, 2 −(
4-Benzyl-1-piperazinyl)-4-methyl-N-
(2,2,27)lifluoroethyl)pyrimidi/-5-
Synthesis was carried out in the same manner as in 39, except that carboxylic acid amide was used (yield: 91%).

Melting point: 148-150°C 1H-nuclear magnetic resonance spectrum/l/(CD 013 ;
ppm ) 2.53 (3H, s), 2.96 (4H,
rn'), 6.83 (4H, rn), 4.06 (2H,
ciq, J=9.2and 6.6Hz), 6.20
(IH, br ), 8.37 (1H,s ) 2-(4
Example 3 except that -benzyl-1-piperazinyl)-4-methylpyrimidi/-5-carboxylic acid hydrazide was used.
Synthesized in the same manner as 9 (yield 47%) 0 Melting point: 176°C Mass spectrometry spectrum: m/Z 236 (molecular ion peak) Infrared absorption spectrum (KBr tablet: cm) 3280.
1626.1590 1H-Nuclear Magnetic Resonance Spectrum (DMSO-d, ; p
pm) 2.27 (3H, 8), 2.84 (4H, rn)
, 3.5 (3H.

bs), 3.80 (4H, m), 8.33 (IH, s)
, 9.31 (IH,br,s) Example 47 N-dimethylamino-4-methyl-2-
Instead of (4-benzyl-1-piperazinyl)-4-methylpyrimidine-5-carboxylic acid amide, 2-(4-
Synthesized in the same manner as in Example 39 except for using benzyl-1-piperazinyl)-N-dimethylamino-4-methylpyrimidine-5-carboxylic acid amide (yield 5
9%).

'H-nuclear magnetic resonance vector (CDC13; ppm) 2
．． 38 (3H, s), 2.55 (6H, S), 2.78
(4H.

m), 3.78 (4H, rn), 8.17 (IH, 8)
Acid amide 2-(4-benzyl-1-piperazinyl)-N-ethyl-4-methylpyrimidine-5-carboxylic acid amide 0.5
g(1,5mrnol) to tetrahuman 07u71Qt
rtl and 0.3 g of ethyl chlorocarbonate (2,
8 mmol) was added thereto, and the mixture was stirred at room temperature for 12 hours. 5 Qrttl of water and 50 Illl of chloroform were added to the reaction mixture, and the chloroform layer was separated. The aqueous layer was extracted twice with chloroform at 50 tnlC, and the chloroform layers were combined, dried over sodium sulfate, and concentrated under reduced pressure to obtain the desired product as colorless crystals. 9 was obtained (yield 96%).

Melting point: 128-130'C Infrared absorption spectrum (KBr tablet; crn) 1712
．． 1630.1590, 1548.15001H-MW
mki ebsuhe/toru (CD C13; ppm) 1
．． 23 (3H, t+J=7.2Hz), 1.30
(3H, t+, r=7.2Hz), 2.52 (3H,
s), 3.42 (2H.

(1, J=7.2H2), 3.50 (4H, m), 3.
90 (4H.

m), 4.19 (2H, q, J=7.2Hz), 5
．． 78 (IH.

br, s), 8.35 ('IH, s ) Synthesized in the same manner as in Example 48 using benzyl chlorocarbonate in place of ethyl chlorocarbonate.

Yield 87% Infrared absorption spectrum (KBr tablets) 1710.
1625 In-Nuclear Magnetic Resonance Spectrum (CD C13p p p
m ) 1.20 (6H, m), 2.50 (3H, s
), 3.42 < 4H.

m), 3.63 (4)L rn), 3.88 (4H
, m ), 5.20 (2H, s), 7.35 (5H,
s), 8.33 (IH,s)-5-carboxylic acid amide 2-(4-benzyloxycarbonyl-1-piperazinyl)-N,N-diethyl-4-methylpyrimidine-5-carboxylic acid amide 0.50 ．． ! 9 (1.2 mmol) in 10 ml of 25% hydrogen bromide in acetic acid at room temperature for 2.
Ohr reaction was performed. After the reaction mixture was dried under reduced pressure, water was added and neutralized with potassium carbonate. After extraction with chloroform, it was dried over anhydrous sodium sulfate. The chloroform layer was dried under reduced pressure to obtain the compound shown in Example 43, N,N-diethyl-4-methyl-2-(1-piperazinyl)pyriε.
Zin-5-carboxylic acid amide 0.25. ! i+ (yield 7
4%).

Example of formulation as a herbicide Next, examples of blending the compounds of the present invention will be explained.

In addition, the numbers indicate weight centipedes.

Formulation example (wettable powder) Compound of the present invention 10% higher alcohol sulfate ester sodium salt 3% kaolin
87% or more is mixed and pulverized uniformly to make an irrigation agent.

Test Example 1 The mixture was dispersed in 1 ml of water and sprayed over the entire surface of the soil using a small sprayer from above the remaining soil. After treatment, place it in a greenhouse for 20 days.
The herbicidal efficacy was investigated. The evaluation criteria are as follows.

Weeding effect 5 Complete withering 4 High weeding effect 3. Weeding effect medium 2 Weeding effect small 1. Weeding effect: slight 0 Invalid (normal) The results are shown in Table 2.

Table 2 Test example 2 Rice field test

Claims (9)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1 is hydrogen, a phenyl group-substituted methyl group, or a lower alkoxycarbonyl group, R_2 and R_3
is hydrogen, a lower alkyl group, or a phenyl-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl-substituted lower alkyl group, and X is of general formula (II) or (III) -OR_4 (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R_4 is hydrogen or a lower alkyl group, and R_
5 and R_6 are hydrogen, an alkyl group, a halogen-substituted lower alkyl group, a phenyl-substituted lower alkyl group, a phenyl group, an amino group, a lower alkyl-substituted amino group, a hydroxyl group,
Acyl group, lower alkoxycarbonyl group, lower alkoxy group, lower alkoxyoxalyl group, phenyl group-substituted lower alkyloxy group, cycloalkyl group, hydroxyl group-substituted lower alkyl group, lower alkoxy group-substituted lower alkyl group,
It is a lower alkyl group substituted with a tetrahydropyranooxy group, or an alkylene group having 4 to 6 carbon atoms in which R_5 and R_6 are bonded. ), where n is 2 or 3. ] A novel pyrimidine derivative. (2) General formula (IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (IV) (In the formula, R_1' is a phenyl-substituted methyl group or a lower alkoxycarbonyl group, and n is 2 or 3.)
A guanidine derivative represented by or an addition salt of the guanidine derivative and the general formula (V) ▲ Numerical formula, chemical formula, table, etc. ▼ (V) [In the formula, R_2 and R_3 are hydrogen, a lower alkyl group, or a phenyl group-substituted lower alkyl group. group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl-substituted lower alkyl group, and X is represented by general formula (II) or (
III) -OR_4 (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R_4 is hydrogen or a lower alkyl group, and R_
5 and R_6 are hydrogen, an alkyl group, a halogen-substituted lower alkyl group, a phenyl-substituted lower alkyl group, a phenyl group, an amino group, a lower alkyl-substituted amino group, a hydroxyl group,
Acyl group, lower alkoxycarbonyl group, lower alkoxy group, lower alkoxyoxalyl group, phenyl group-substituted lower alkyloxy group, cycloalkyl group, hydroxyl group-substituted lower alkyl group, lower alkoxy group-substituted lower alkyl group,
It is a lower alkyl group substituted with a tetrahydropyranooxy group, or an alkylene group having 4 to 6 carbon atoms to which R_5R_6 is bonded. ), and R_7 is a lower alkyl group. ] General formula (I - I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I - I) (In the formula, R_1', R_2, R_3, n and is the same as above.) A method for producing a novel pyrimidine derivative. (3) General formula (I-II-I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I-II-I) (In the formula, R_1 is hydrogen, a phenyl group-substituted methyl group, or a lower alkoxycarbonyl group, R_2 and R_3
is hydrogen, a lower alkyl group, or a phenyl-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl-substituted lower alkyl group, R_4' is a lower alkyl group, and n is 2 or It is 3. ) General formula (I-III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I-III) (In the formula, R_1, R_2, R_3 and n are The method for producing a new pyrimidine derivative shown in (4) General formula (I-II) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I-II) (In the formula, R_1 is hydrogen, a phenyl group-substituted methyl group, or a lower alkoxycarbonyl group, R_2 and R_3
is hydrogen, a lower alkyl group, or a phenyl group-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group substituted with a phenyl group,
R_4 is hydrogen or a lower alkyl group, and n is 2 or 3
It is. ) and the general formula (VI) ▲Mathematical formulas, chemical formulas, tables, etc.▼(VI) (In the formula, R_5' and R_6' are hydrogen, alkyl groups,
Halogen-substituted lower alkyl group, phenyl-substituted lower alkyl group, phenyl group, amino group, lower alkyl-substituted amino group, hydroxyl group, lower alkoxy group, phenyl-substituted lower alkyloxy group, cycloalkyl group, hydroxyl-substituted lower alkyl group, lower alkyl group substituted with lower alkoxy group,
A lower alkyl group substituted with a tetrahydropyranooxy group or having 4 to 6 carbon atoms with which R_5' and R_6' are bonded
is an alkylene group. ) General formula (I-IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I-IV) ′
and n are the same as above. ) A method for producing a new pyrimidine derivative. (5) General formula (I-III-I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I-III-I) (In the formula, R_1' is a phenyl group-substituted methyl group or lower alkoxycarbonyl group, and R_2 and R_3 is hydrogen, a lower alkyl group, or a phenyl-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl-substituted lower alkyl group, and n
is 2 or 3. ) Pyrimidine derivatives and general formula (VII) ▲Mathematical formulas, chemical formulas, tables, etc. are available▼(VII) (In the formula, R_5″ and R_6″ are hydrogen, alkyl groups,
halogen-substituted lower alkyl group, phenyl-substituted lower alkyl group, phenyl group, amino group, lower alkyl-substituted amino group, cycloalkyl group, hydroxyl-substituted lower alkyl group,
A lower alkyl group substituted with a lower alkoxy group, a lower alkyl group substituted with a tetrahydropyranooxy group, or R_5''
and R_6'' are an alkylene group having 4 to 6 carbon atoms bonded together. General formula (I-IV-II) characterized by reacting an amine compound represented by (I-IV-II) ▲Mathematical formula, chemical formula , there are tables, etc.▼( I −IV-II)
'' and n are the same as above.) A method for producing a novel pyrimidine derivative. (6) General formula (I-III-I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I-III-I) (In the formula, R_1' is a phenyl group-substituted methyl group or lower alkoxycarbonyl group, and R_2 and R_3 is hydrogen, a lower alkyl group, or a phenyl-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl-substituted lower alkyl group, and n
is 2 or 3. ) The pyrimidine derivative represented by the general formula (VIII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (VIII) In the formula, R_1', R_2, R_3 and n are as described above, and Y is chlorine or bromine. . ) is halogenated to the pyrimidine derivative (VII
General formula (VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VI) (In the formula, R_5' and R_6' are hydrogen, alkyl groups,
Halogen-substituted lower alkyl group, phenyl-substituted lower alkyl group, phenyl group, amino group, lower alkyl-substituted amino group, hydroxyl group, lower alkoxy group, phenyl-substituted lower alkyloxy group, cycloalkyl group, hydroxyl-substituted lower alkyl group, lower alkyl group substituted with lower alkoxy group,
A lower alkyl group substituted with a tetrahydropyranooxy group or having 4 to 6 carbon atoms with which R_5' and R_6' are bonded
is an alkylene group. ) General formula (I -IV- I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼( I -IV- I) (In the formula, n, R_1', R_2 , R_3, R_5' and R_6' are the same as above.) A method for producing a novel pyrimidine derivative. (7) General formula (I -V) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I -V) (In the formula, R_1' is a phenyl group-substituted methyl group or lower alkoxycarbonyl group, and R_2 and R_3 are hydrogen , is a lower alkyl group or a phenyl group-substituted lower alkyl group, and at least one of R_2 and R_3 is a lower alkyl group or a phenyl group-substituted lower alkyl group, and n
is 2 or 3, and R_5' is hydrogen, alkyl group, halogen-substituted lower alkyl group, phenyl-substituted lower alkyl group, phenyl group, amino group, lower alkyl-substituted amino group, hydroxyl group, lower alkoxy group, phenyl group-substituted These include a lower alkyloxy group, a cycloalkyl group, a hydroxyl-substituted lower alkyl group, a lower alkoxy-substituted lower alkyl group, and a tetrahydropyranooxy-substituted lower alkyl group. )
Pyrimidine derivatives and general formula (IX) ▲Mathematical formulas, chemical formulas, tables, etc.▼(IX) (In the formula, R_8 is hydrogen, lower alkyl group, lower alkoxy group, or lower alkoxycarbonyl group, and Z is dimethylamino General formula (I-VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I-VI) ( In the formula, R_1', R_2, R_3, R_5', R_8
, n are the same as above. ) A method for producing a new pyrimidine derivative. (8) General formula (X) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (X) [In the formula, R_9 is a phenyl group which may be nuclear-substituted with a group selected from the group of halogen, alkoxy group, and nitro group. is a methyl group, alkoxycarbonyl group, or aralkyloxycarbonyl substituted with It is a substituted lower alkyl group, and X is represented by the general formula (II) or (III)-OR_4 (
II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R_4 is hydrogen or a lower alkyl group, and R_
5 and R_6 are hydrogen, an alkyl group, a halogen-substituted lower alkyl group, a phenyl-substituted lower alkyl group, a phenyl group, an amino group, a lower alkyl-substituted amino group, a hydroxyl group,
Acyl group, lower alkoxycarbonyl group, lower alkoxy group, lower alkoxyoxalyl group, phenyl group-substituted lower alkyloxy group, cycloalkyl group, hydroxyl group-substituted lower alkyl group, lower alkoxy group-substituted lower alkyl group,
It is a lower alkyl group substituted with a tetrahydropyranooxy group, or an alkylene group having 4 to 6 carbon atoms in which R_5 and R_6 are bonded. ), where n is 2 or 3. General formula (I - VII) characterized by hydrogenolysis or acid decomposition of a pyrimidine derivative represented by and n are the same as above.)
A method for producing a novel pyrimidine derivative shown in (9) General formula (X I ) ▲Mathematical formula, chemical formula, table, etc.▼(X I) [In the formula, R_1_0 may be nuclear-substituted with a group selected from the group of halogen, alkoxy group, and nitro group. a methyl group or hydrogen substituted with a phenyl group, R_2 and R_3 are hydrogen, a lower alkyl group, or a phenyl-substituted lower alkyl group, and R_2 and R_3
at least one of is a lower alkyl group or a phenyl-substituted lower alkyl group, and X is represented by general formula (II) or (III)
-OR_4 (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R_4 is hydrogen or a lower alkyl group, and R_
5 and R_6 are hydrogen, an alkyl group, a halogen-substituted lower alkyl group, a phenyl-substituted lower alkyl group, a phenyl group, an amino group, a lower alkyl-substituted amino group, a hydroxyl group,
Acyl group, lower alkoxycarbonyl group, lower alkoxy group, lower alkoxyoxalyl group, phenyl group-substituted lower alkyloxy group, cycloalkyl group, hydroxyl group-substituted lower alkyl group, lower alkoxy group-substituted lower alkyl group,
It is a lower alkyl group substituted with a tetrahydropyranooxy group, or an alkylene group having 4 to 6 carbon atoms in which R_5 and R_6 are bonded. ), where n is 2 or 3. ] The pyrimidine derivative shown and the general formula (XI
I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (XII) A general formula characterized by reacting a compound represented by (in the formula, R_1_1 is a lower alkyl group and Q is chlorine or bromine) ( I - VIII) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ ( I - VIII) A method for producing a novel pyrimidine derivative represented by (in the formula, R_2, R_3, R_1_1, X and n are the same as above).