JPS63216877A - Fluorine-containing pyrimidine derivative - Google Patents

Abstract

NEW MATERIAL:The fluorine-containing pyrimidine derivative of formula I [R<1> is 1-5C alkyl, 3-6C cycloalkyl, benzyl which may be substituted with methyl, ethyl or Cl, phenyl which may be substituted with methyl, methoxy or Cl, -OR<4> or group of formula II (R<4>, R<5> and R<6> are H or lower alkyl); R<2> is halogen or amino which may be substituted with lower alkoxy, lower alkylthio or lower alkyl; R<3> is halogen, hydroxyl, group of formula III or formula IV; X is lower alkyl]. EXAMPLE:6-Fluoro-2-methyl-5-trifluoromethyl-4-pyrimidone. USE:Useful as pharmaceuticals such as carcinostatic agent or agricultural chemicals such as herbicide and insecticide and their synthetic intermediates. PREPARATION:The compound of formula I can be produced e.g. by reacting a compound of formula V (R is H, etc.) with a compound of formula VI (R<7> is 1-5C alkyl, etc.; X is halogen, etc.).

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a novel fluorine-containing pyrimidine compound and a method for producing the same. It is useful as pharmaceuticals, herbicides, insecticides, acaricides, fungicides, and other agricultural chemicals, or as intermediates in their production.

[Conventional technology]

1,1.3.3.3-pentafluoro-1-methoxy-
A method for synthesizing 2-methyl-1 or 2-7enyl-4-fluoro-5-trifluoromethyl-6-medoxypyrimidine from 2-trifluoromethylpropane and acetamidine or benzamidine is described in J. Pluorin.
e Chem, Vol. 27, p. 231 (1985).

[Problem that the invention seeks to solve]

Conversion of fluorine-containing 6-medoxypyrimidine obtained by the method of the above-mentioned literature to 6-hydroxypyrimidine (6-pyrimidone), which is more widely available, is generally difficult due to the cleavage of chemically stable ether bonds. Not yet successful. Therefore, the present inventors have intensively studied the synthesis of pyrimidines having a hydroxyl group from the beginning, and have further discovered that a wide variety of new fluorine-containing pyrimidine derivatives can be produced from the obtained fluorine-containing pyrimidone.

[Means for solving problems]

The present inventor used readily available 2-trifluoromethyl-3,3,3-)lifluoropropionic acid and its ester, or perfluoroacrylic acid or its ester dehydrogenated from it as a starting material, When these were reacted with amidines, guanidines, and isothioureas, it was found that pyrimidines that had a hydroxyl group from the beginning, i.e., pyridones, could be easily obtained under mild conditions and in high yields. I found it. Furthermore, they discovered that this hydroxyl group can be converted into a chlorine or fluorine atom, or converted into a derivative such as a phosphoric acid ester or an oxycarboxylic acid ester.

That is, in the general formula L, R1 is a C, -C, alkyl group, a cycloalkyl group of 03 to C6, a methyl group, an ethyl group, or a benzyl group optionally substituted with a chlorine atom, a methoxy group, or a chlorine atom. Substituent at an atom (R', R', R' each independently represents a hydrogen atom or a lower alkyl group)
, R2 represents a halogen atom or an amino group optionally substituted with a lower alkoxy group, a lower alkylthio group, or a lower alkyl group, and R3 represents a halogen atom or a hydroxyl alkyl group. It has been found that a new fluorine-containing pyrimidine derivative represented by the following formula can be obtained.

The present invention will be explained in detail below.

The compound of general formula +13 of the present invention can be produced by the following methods (1) to (2).

A compound represented by the formula 0 (wherein R is a hydrogen atom, a lower alkyl group or an alkali metal atom), preferably in an organic solvent,
In the presence of an excess aqueous solution of a basic substance, a phase transfer catalyst is present if necessary, and the formula [wherein R7 is a C1-C3 alkyl group, a 03-C6 cycloalkyl group, an optionally substituted or -SR
'(R',R',R',R' each independently represents a hydrogen atom or a lower alkyl group, and X represents a halogen or (SO4) pot)] Amidines, guanidines, inureas and isothioureas, preferably at a temperature of O to the boiling point of the organic solvent, preferably for 1 to 24 hours, under stirring or reflux, to obtain the compound represented by the formula.

Examples of organic solvents include halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, ethers such as diethyl ether, T)(F), and aromatic hydrocarbons such as benzene, toluene, and monochlorobenzene. .

Examples of basic substances include NaHCO3, KI (CO
s.

Na, COs, K2CO3, NaOH, KOH, Li
Examples include tertiary amines such as OH or triethylamine.

Also, as a phase transfer catalyst, for example, butylammonium,
Tetra-n-butylammonium chloride, hensyltriethylammonium chloride, benzyltriethylammonium bromide, benzyltrimethylammonium chloride, methyl chloride), IJ-2-methyl-phenylammonium, etc.), sulfonium compounds (tetramethylphosphonium iodide, bromide, etc.) tetra-n-butylphosphonium, etc.)
and sulfate compounds (such as methyldinonylsulfonium methylsulfate and benzyltriethylammonium sulfate).

0 (wherein R' represents a hydrogen atom, a lower alkyl group, or an alkali metal atom) in the presence of an excess aqueous solution of a basic substance in a preferably inert organic solvent,
A phase transfer catalyst is allowed to coexist if necessary, and amidines, guanidines, isoureas, and isothioureas represented by the formula (wherein R' and X have the same meanings as above) and preferably 00 ~The compound represented by (wherein R1 means the same as above) can be obtained by reacting at the boiling point temperature of a common organic solvent, preferably for 1 to 24 hours, with stirring or rapid flow. .

Here, as the organic solvent, basic substance, or phase transfer catalyst, the same ones as used in the method (2) above can be used.

■ The compound represented by formula (1) is reacted with excess phosphorus oxychloride, phosphorus trichloride, or phosphorus pentachloride, preferably in the presence of a basic substance if necessary, at 100 to 120°C for 5 to 15 hours; (wherein R2 and R? have the same meanings as above) can be obtained.

Examples of the basic substance used here include N,N-dimethylaniline and 4-(N,N-dimethyl)pyridine.

(2) A compound represented by formula (3), a suitable fluorinating agent (eg, KF, C8F, etc.), and an aprotic polar solvent (eg, DMF, DMAc, DMSO, DMSO).

TMSO, sulfolane, etc.), preferably 100 to 2
The reaction was carried out at 50°C for 0.5 to 10 hours, and (in the formula, nt
, nt means the same as in the previous section).

■ A compound represented by formula (2) and a base (for example, a tertiary amine such as triethylamine, Na, Co, K, Co,
, NaOH, KOH, MeONa.

(EtONa, etc.), R'OM, CR' are lower alkyl groups, M is an alkali metal), R''SM (R'D or lower alkyl group), [wherein R7 is the same as above] and R'' and R y have the same meanings as above.

■ The formula R”C00M is added to the pyrimidine represented by the formula (4).
(10) [In the formula, R14 is a lower alkyl group, M represents an alkali metal] in an aprotic polar solvent (for example, DMF, D
MAc, NMP, DMSO, sulfolane, etc.),
Preferably, the reaction is carried out in the range of 50° to the boiling point of the solvent for 1 to 5 hours, followed by further hydrolysis to obtain a compound represented by the formula (wherein It' and R'' are the same as above). be able to.

■ A base (e.g. Na
In the presence of a tertiary amine such as H, KH, NaOH, KOH or tri-
” is a lower alkyl group or a phenyl group, Y is O or S
, X represents a halogen atom) in a suitable organic solvent, preferably at room temperature to 100 °C.

A compound represented by the formula 0 and an amidine in the presence of a base, (wherein Z is +CFt + 4 or -(CH2)
A cyclic ether represented by t -0(CHz)-, for example, THF or dioxane, is preferably reacted at room temperature to the boiling point of the cyclic ether for 1 to 10 hours (wherein R7 means the same as in the previous section, R” bar (CH,), -CH=
CH, also represented by (CH2)tOcH=CHt) can be obtained.

〔Effect of the invention〕

The fluorine-containing pyrimidines of the present invention are extremely useful as intermediates for medicines and agrochemicals, and the method of the present invention has made it possible to easily produce a wide variety of these pyrimidine derivatives in high yields.

Example 1. Preparation of 6-fluoro-2-methyl-5-trifluoromethyl-4-pyrimidone Second, 330 g of Co
Dissolve it in water 1001117, cool it to -5'CK, and add chloroform 1001111TEBAC50■
Add and stir.

There, acetamidine hydrochloride 19.8 F (0,21
mol) in 100 ml of water was added, and 21.3 t (0.10 mol) of methyl 2-trifluoromethyl-3,3,3-)lifluoropropionate was added dropwise, and the mixture was reacted overnight at room temperature. Dilute hydrochloric acid was added to apply weak acidic pressure, extraction was performed with chloroform, and the extract was dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was recrystallized from chloroform to obtain the desired 6-fluoro-2-methyl-5-trifluoromethyl-4-pyrimidone (15.5 PC yield: 78 cm). ml) 157-159°C0IR
(cm″) ; 1690,167ONMR(CD
Ct, + DMSO-d, ); δ2.42 (a,
3H.

CHs), 10,0 (br, s, IH, OH) MS;
mlz 196 (M”), 181 (M+CHs), 1
77 (M”-F) 168.155.136.135.
126.116.91calcd for C6H4F
4N1(), M” 196.105 Example 2゜NaOH10,75y-(0,25 mol) in water 100
Acetamidine hydrochloride dissolved in 7.1'il
(0,075 mol) was added, stirred well, and a solution of 10.5 P (0.05 mol) of methyl 2-trifluoromethyl-3,3,3-)lifluoroglopionate in 39 ml of methylene chloride was added dropwise. and allowed to react overnight at room temperature. Water was added and the organic layer was separated while maintaining alkalinity. After neutralizing the aqueous layer with hydrochloric acid, the precipitated crystals were filtered and n-
mP 157-1 after recrystallization from hexane-ethyl acetate
0-2-Methyl-5-trifluoromethyl-4-pyrimidone (5.2PC yield 53%) at 59 °C 6-7
I got it.

The organic layer was washed with saturated brine and then dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was distilled under reduced pressure to obtain 6-fluoro-4-methoxy-2-methyl-5-trifluoromethylpyrimidine 2, IP (yield 20%).

bp68-70°C/17mmHg (literature value) bp
6 row 67'C/18mmHg), IR (crn-
'), 1610. HNMR (CDCts); δ2.
65 (s, CHs), 4.20 (a, OCHs)
MS; mlz 210 (M+),
calcd for C, H6F4N! 0210
．． 132 1) Y, Inouye and Y,
Higuchi, J., Fluorine
('hem,.

27, 231 (1985) Example 3 Preparation of oro-2-ingrobyl-5-trifluoromethyl-4-pyrimidone in 6-7; Propionamidine hydrochloride 1.13ji' (9.2m/).

A mixture of 3 ml of water and 5 ml of chloroform
Cool to 2,995' KK2COs (
21.6 mmol) and TEBAC20711P,
Then methyl 2-trifluoromethyl-3,3,3-)lifluoropropionate 1.02PC4, 9mmol)
was dripped. After stirring overnight at room temperature, the mixture was made weakly acidic with dilute hydrochloric acid, extracted with chloroform, and the extract was dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the desired 6-fluoro-2-isopropyl-5-trifluoromethyl-4.
-pyrimide 70.951 (yield 87) was obtained.

mp 135-136°C (n-hex f7-ethyl acetate) IR (ffi-li; 1690.1660'HNMR (
CDCts); δ1.37 (d, J = 6.8 H
z, 6H.

(CHs)*CH)3.02(hept, J=6.8H
z, IH.

"F NMR (CDCz3. C6H, CFs internal standard); δ3.7 (d, J-24Hz, 3F, CFs), 8
．． 1 (Q, J = 24H2, IF, F on pyrimidine ring) MS; mlz 224 (M”), 20
9(M”CHs)-205°204, 203.1
96. 189. 181. 156. 136°91
, 71. 54 Calcd, for c8H, p, N, o, 224
, 159 2-substituted-6-fluoro synthesized in the same manner as
-5-trifluoromethyl/L; The results for -4-pyrimidone are summarized in Table 1.

Table 1. 2-Substituted-6-fluoro-5-trifluoromethyl-4-pyrimidone Example 4゜6-fluoro-2-methyl-5-trifluoromethyl-
Production of 4-pyrimidone: Acetamidine hydrochloride 14.2P (0.15 mol)
was dissolved in 80 ml of methylene chloride and cooled on ice. Methyl perfluorometaacrylate 19.051' (0,
1 mol) of methylene chloride 10 me bath solution was added dropwise,
In addition, 3,1 liters of triethylamine (0,3 m
After adding ol) and reacting at room temperature for 10 hours, the mixture was washed with water. The methylene chloride layer was separated and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent: n-hexane-ethyl acetate mixed solvent) to obtain the desired pyrimidone 10.8P C
A yield of 55 cm was obtained. mp158-160°C Example 5 Preparation of 2-dimethylamino-6-fluoro-5-trifluoromethyl-4-pyrimidone 22N,N-dimethylamino 71,185' (9,5mm
ol).

3 ml of water, 5 ml of riooform. TEBAC20Q and methyl 2-trifluoromethyl-3,3,3-)lifluoropropionate 1.05' (4,76 mmol
) was reacted and post-treated in the same manner as in the examples to obtain 2-dimethylamine-6-fluoro- as an alkali-soluble product.
5-trifluoromethyl-4-pyrimidone 0.241 (
A yield of 24 cm) was obtained. Recrystallize from ethyl acetate and mp
210-213°CIn(crn-'); 166
0. 1615. 1585'HNMR (CDC13+
DMSO-d6); δ3.12 (s.

Me, N) Products insoluble in alkali were purified by column chromatography (Sin, n-hexane/ethyl acetate) to give 2-dimethylamine-6-
0.7055 L (yield: 62 L) of fluoro-4-methoxy-5-trifluoromethylpyrimidine was obtained.

IR (Bei-'); 1635. 1620. 157
5. 1525'HNMR (CDC2s); δ 3.
17(s+ 6H@Me2N−) 3.99(s,
3H, OMe) + MS; mlZ 239 (M).

High MS, 239.151Calcd f
or C, H, F, N, 0. 239.174 Example 6゜6-chloro-4-fluoro-2-methyl-3) I77#
Production of olomethylpyrimidine = 6-fluoro-2-methyl-5-trifluoromethyl-4-pyrimidone 19.8
5'(0,10mo+) as phosphorus oxychloride 158 mt
51m of N,N-dimethyl-aniline was dissolved in
1 was added and reacted at 110-120°C for 7.5 hours.

Excess phosphorus oxychloride was distilled off under reduced pressure, and the residue was poured into water and extracted twice with ether. The extract was washed with dilute hydrochloric acid and saturated brine, and then dried over magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is distilled under reduced pressure to obtain the desired 6-chloro-4-fluoro-2-methyl-pyrimidine 16. 1 (yield: 80%).

bp89-91°C/65 mmHg IR (crn''''); NMR for 1595 (CD
Cz, ) ; δ 2,75 (S, CH3) In the same manner, more 2-substituted-4-chloro0-6-fluoro-5-trifluoromethylpyrimidines summarized in Table 2 were synthesized.

Table 2. 2-Substituted-4-chloro-6-fluoro-5-trifluoromethylpyrimidine (Formula (3)) %Formula% Production of trifluoromethylpyrimidine: Add 21 ml of toluene to 52 ml of sulfolane, and add toluene at normal pressure. is distilled off, the dried sulfolane is returned to the adjusted room temperature, and 719.15'
(73,3mrr)01), spray-dried potassium fufluoride 7.545' (130mmol) was added, and 180-1
Stirred at 95°C for 2 hours. After cooling, add water, extract with ether, wash the extract with water, then with saturated saline,
'Dried with magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was distilled under reduced pressure to obtain the desired 4,6-difluoro-2-ethylthio-5-trifluoromethylpyrimidine (12.3PC yield: 70%).

hp 113-114°C/s8mmE (g.

1(crn-');1615'HNMR(CDCz3); δ1.43(t, J=7
．． 4Hz, 3HCHs), 3.19 (Q, J=7.
4Hz, 2H0CHt) I9FNMR (CDCz
,, C6H,CF, internal standard); δ6.0(t,
JP-F: 181 (Z, 3F, CF 8.0 (
Q+Jr-r-18Hz, 2F, 4.6-position F
) Example 8 Evolution of 4.6-difluoro-2-methylthio-5-trifluoromethylpyrimidine: From 6,-chloro-2-ethylthio-4-fluoro-5-trifluoromethyl-pyrimidine 7.741 Reaction, post-treatment and purification were carried out in the same manner as in Example 6 to obtain bp 105-10
7°C/66 mmHg 4.6-Di7A/Olow 2
-methylthio-5-trifluoromethylpyrimidine 3,
91ff (yield 54%) was obtained.

Example 9 6-Fluoro-2-methyl-3-) IJ Fluoromethyl-4-pyrimidone 1.96 fP (0,000 ml) was dissolved in methanol lO++/, and a methanol solution of 28 thimetrium methoxide was added thereto. Drop ml,
After reacting at room temperature for 10 hours, the mixture was poured into water, neutralized with hydrochloric acid, and extracted with ether. After washing the extract with saturated saline,
Dry with magnesium sulfate. The solvent was distilled off under reduced pressure,
The residue was recrystallized from n-hexane-ethyl acetate to give m
6-medoxy 2-methyl-5 at p198-199°C
-Trifluoromethyl-4-pyrimidone 1.51 (yield 72%) was obtained.

ll((cWl-'); 3400(br) 16
60'HNMR (CDCz, +DMSO-da); δ
2.41(a, 3H.

CHs), 4.01(s, 3H,0CHs)-12,8
(br.

IH, OH).

MS; m/z 208 (M+), 207,189,
188°179, 178. 137. 109. 8
9゜Ca1cd for C7H, F3N202.
208,141 Example 10゜6-fluoro-2-methyl-3-) +7 fluoromethyl-4-pyrimidone4. Of (0.02mol) was dissolved in 20mt of ethanol, and a solution of 3.4PC0.05mol of sodium ethoxide in 30ml of ethanol was added dropwise at room temperature, and the reaction and post-treatment were carried out as in Example 8. Recrystallize to mp153-156°
6-nitoxy-2-methyl-5-trifluoromethyl-4-pyrimidone (3.4 PC yield 77%) was obtained.

IR (Confucian-'); 1685. 1670IHNMR
(CD(δ3); δ1.37(t, 3H, CH3
).

2.45 (s, 3H, CHs), 4,48 (Q
, 2H, CHJ.

11. 0(br, L)I, OH)
.

Example 11゜6-fluoro-2-methyl-5-trifluoromethyl-
4-pyrimidone 2.05' (0.01ml) in THF
40% dimethylamine aqueous solution 2
．． 51 was added dropwise, and the mixture was allowed to react at room temperature for 3 hours. After the solvent was distilled off under reduced pressure, the residue was neutralized with pentahydrochloric acid and extracted with ether. The extract was washed with saturated brine and then dried over magnesium sulfate.

The solvent was distilled off under reduced pressure to give 1.6% of 6-dimethylamino-2-methyl-5-trifluoromethyl-4-pyrimidone.
P (yield 72%) was obtained. Recrystallized from ethyl acetate
P 181-183°CIR (1 near F+-');
1630'HNMR (CDCta + DMSO-δ6
); δ2,28(a, 3H.

CHs), 3.14(s, 6H2CCHs) x N),
12.1 (br.

s, IH, OH).

Example 12 Sodium hydride (60%, 2.45', 0.
06 mol) and DMAc 30 m/i-butyl mercaptan 2.75' (0,03 mo+) of DMAc.
10 ml of solution was added dropwise and stirred for a while until gas evolution stopped. There 6-fluoro-2-methyl-5-trifluoromethyl-4-pyrimidone 4.0FC0,02
mol) and reacted at 50 to 60°C for 10 hours.

After confirming the disappearance of the raw materials by TLC, the reaction mixture was poured into water, substances insoluble in water were removed by dissolving in ether, and the aqueous layer was neutralized with hydrochloric acid. Extraction was performed with ethyl acetate, and the extract was washed with saturated brine and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, recrystallization from n-hexane gave mp
6-Inptylthio-2-methyl-5-trifluoromethyl-4-pyrimidone at 162-164°C 3.81 (
A yield of 71 cm) was obtained.

IR("-'); 3400(br, OH), 16
65NMR (CDCl5); δ1.01 (d,
6HCCH3)tcH).

1.92 (m, IH,,,cH), 2.46 (
1! , 3H, CHs).

, 3.10(d, 2H,CH2), 13.4(
br, 8', IH, OH) Example 13゜Sodium acetate A 1.64P (0.02 mol) in DM
Dissolve in F20at and add 6-fluoro-4
-Medoxy 2-methyl-5-trifluoromethylpyrimidine 72.15' (0, Olmol) was added and 100
The reaction was carried out at 0C for 5 hours. After cooling, the mixture was poured into water, 5-thihydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure and recrystallized from n-hexane-ethyl acetate to give m
6-medoxy2-methyl-5- at p198-199°C
2.0 n (yield: 97%) of trifluoromethyl-4-pyrimidone was obtained, and it was confirmed from IR comparison that it was the same as that obtained in Example 8.

Example 14゜60 Sodium thihydride 0.92PC0,0225mo
l) and DMF 20at, 6-medoxy 2
-Methyl-5-trifluoromethyl-4-pyrimide 73
．． 121 (0,015 mo) was added, and after the gas evolution stopped, 5.43 PCs of ethyl 2-promopropionate was added.
0.03 mol was added thereto, and the mixture was reacted at room temperature for 24 hours.

The reaction mixture was poured into water, extracted with ethyl acetate, and the extract was thoroughly washed with water and dried over magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent n-hexane/ethyl acetate = 3/1) to obtain 2-(6-medoxy-2-methyl-5-trifluoromethyl- 4.077 ml of ethyl 4-pyrimidyloxy)propionate (yield: 88%) was obtained.

nDl, 4462 ■1 ((crn-'); 1740.1580.15
55 INMR (CDCJs); δ1.24 (t,
3H, CH, CH,).

1.60 (d, 3H, CH2Cl), 2.44 (s
, 3H,CH,).

4.00 (s, 3H1CHaO), 4.16 (Q, 2H
-CHtO) 15.36 (Q, IH, -δt) Example 15゜0 in place of ethyl 2-bromopropionate in Example 13
,0-diethylphosphorochloride thioate 4.255
0225 mol of NO) was added, the reaction and post-treatment were carried out in the same manner, and silica gel column chromatography (eluent n-
Purify with hexane/ethyl acetate = 5/1 to 2/l),
0,0-diethyl0-(6-medoxy2-methyl-5
-trifluoromethyl-4-pyrimidinyl)phosphothioate 3,61? (yield 67%). nDl, 47
11) 1((crn-'); 1585. 1555
'HNMR (CDCLs); δ1.40 (t, 6
H, CI, X2).

2.56(st 3H+ eH3L 4.02(15*
3H,0CI-I3).

4.3 (m, 4H, CI (,
05moJ) was dissolved in 40ml of THF, 12.6PC0.125mol of triethylamine) was added thereto, and the mixture was reacted under boiling reflux for 4 hours. After cooling, put it in water,
Extracted with ether. The extract was washed with saturated brine, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 6-
7.7p (yield 62%) of (3-butenyloxy)-2-mef-5-trifluoromethyl-4-pyrimidone was obtained. Recrystallized from ethyl acetate, mp199-200°
C71((crn-');1670.1600'
HNMR (CDC15); δ 2.10
(m, 4H1(CI-12)2).

2.54 (8,3H,CH,), 4.04,4,2
0,5.28 (each IH, hinyl group), 13.3 (hr
, IH, OH) MS; m/z 248 (M”)
, 205. 192. 144. 91°71,
Ca1cd for C+oH11F3N202 2
48.206 Patent Applicant H Honka Kuwa Co., Ltd. Company Procedures Amendment January 22, 1986

Claims (1)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) [In the formula, R^1 is an alkyl group of C^1 to C^5, C^3 to
C^6 cycloalkyl group, methyl group, ethyl group, or benzyl group optionally substituted with a chlorine atom, or phenyl group optionally substituted with a methyl group, methoxy group, or chlorine atom, -OR^4 or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ represents a group (R^4, R^5, R^6 each independently represents a hydrogen atom or a lower alkyl group), R^2
represents a halogen atom or an amino group which may be substituted with a lower alkoxy group, a lower alkylthio group, or a lower alkyl group, R^3 is a halogen atom, a hydroxyl group, ▲ is a mathematical formula, chemical formula, table, etc. ▼ or ▲ is a mathematical formula, There are chemical formulas, tables, etc. ▼ indicates, and X indicates a lower alkyl group. ] A fluorine-containing pyrimidine derivative.