JPS59104366A - Novel pyrimidine derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A pyrimidine derivative shown by the formula I (R is alkyl; R' is H, or hydrocarbon group). EXAMPLE:2-Amino-4-fluoro-5-trifluoromethyl-6-methoxypyrimidine. USE:Exhibiting specific medicinal effects as an antiphlogistic agent and an antitumor agent by electron attractive properties of F replaced at the 4-position and CF3 replaced at the 5-position of pyrimidine nucleus. PROCESS:Perfluoroisobutylene is absorbed in an alcohol such as methanol, etc., and dehydrofluorinated to give a perfluoroisobutylene derivative shown by the formula II, which is reacted with a guanidine shown by the formula III or its salt dissolved in an ether solvent in the presence of a phase transfer catalyst such as preferably a quaternary ammonium salt, etc. at -10-50 deg.C, to give a compound shown by the formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel pyrimidine-inducing 15 and 1<4
Regarding the manufacturing method. More specifically, we will discuss novel pyrimidine derivatives synthesized from perfluoroisobutylene;
ll Regarding the 7W method.

Perfluoroisobutylene is the main H11 product in the production of perfluoropropylene by thermal decomposition of tetrafluoroethylene, and is readily available at a relatively low cost. It has not been established.Also, because this compound is highly toxic and difficult to handle, alcohol adducts such as methanol [(ar3)2
cHar2oR], but there are only a few reactions using this alcohol adduct as a raw material, and the reality is that there are even fewer effective ways to use it.

By the way, such low 7) can be obtained by adding about an equimolar amount of alkali such as sodium hydroxide or potassium hydroxide to the alcohol adduct and heating it to about 30 to 40°C.
,=shic7. )IIG7.7 Hydrogen tsuride 4'rA't
) [(OF3), 0=OFOR], guanidine 79
The present inventors discovered that a :6i-order ηC pyrimidine induction tree was obtained by reacting the pyrimidine;
,i+;! ! (11 °C of the trifluoromethyl group substituted at the 5-position! J'tTh
When 'j I 'i<t, the anti-inflammatory agent and anti-tumor agent exhibit a unique effect.

Therefore, the present invention relates to a novel pyrimidine derivative, which has the general formula (where R
is an alkyl group, and R' is a hydrocarbon group the size of a rice atomic bomb.

The present invention also relates to a method for producing such a novel pyrimidine derivative, and this novel pyrimidine conductor has the general formula (OF3).
20-Cri. Perfluoroisobutylene derivatives represented by A (wherein R is an alkyl group) and guanidines represented by the general formula NH-CNH2, (wherein R' is water, a hydrogen atom, or a hydrocarbon group) or its salts.

The perfluoroisobutylene derivative represented by the above general formula is produced by absorbing perfluoroisobutylene into an alcohol such as methanol, ethanol, n-propanol, isopropanol, or n-butanol, and then de7ing it.
Since it can be easily obtained as a crystal by accumulating tsulfide water, it can be subjected to the reaction as an alkoxy derivative depending on the type of alcohol used for absorption.

Further, as guanidine 41'1 represented by the above general formula, in addition to guanidine, its N-hydrocarbon substituted products such as N-alkyl, N-aryl, N-aralkyl, and N-allyl, and carbonates thereof , nitrate, americ salt, perchlorate, thiocarbonate, acetate, α, β-dibromopropionate, monoethyl oxalate, benzene sulfonate, alizarin disulfonate, picrin salt etc. are used.

Reaction c. Approximately 1 to 1 for perfluoroisobutylene derivative
Dichloromethane, 1°1.1-) dichloroethane, 1,1.2-) dichloroethane, 1,1.2-) dichloroethane, 1,1.2-) dichloromethane, 1.1.
2-) Norogen-based solvents such as refluoro-1,2,2-)dichloroethane, carbon tetrachloride, and chloroform; aromatic solvents such as benzene, toluene, and xylene; ethyl acetate, butyl acetate, and ethyl benzoate; Since it is carried out in a heterogeneous system using an ester solvent such as propyl benzoate or butyl benzoate, or an ether solvent such as diethyl ether, diisopropyl ether, diglyme, triglyme, or tetraglyme, it is preferable to use a quaternary ammonium salt. About -10 to +50℃ using a phase transfer catalyst such as
The reaction is carried out at a humidity of .

Next, the present invention will be explained with reference to examples.

Example guanidine carbonate 2.09 (11.11 mmol)
Dissolve 5- in water and add 0.8! 7 hydroxide)
5 ml of an aqueous solution of IJum dissolved in 5 ml of water!
was added, and a solution of 1 ml (4,717 mmol) of 1-methoxy-2-trifluoromethylperfluoropropylene dissolved in 20 ml of dichloromethane and 0.19 ml of benzyltrimethylammonium chloride were added.

After standing at room temperature for 1 hour, the layers are separated, and the dichloromethane solution phase is dehydrated over anhydrous magnesium sulfate and evaporated to dryness. When this was purified through a silica gel column (ether), 0.78 g of crystals with a melting point of 122-130°C (yield 7
9%) was obtained. When this was further recrystallized from carbon tetrachloride-benzene, the melting point was 137-138°C.

It is clear from the following identification data that this crystal is 2-amino-4-fluoro-5-trifluoromethyl-6-medoxypyrimidine.

Elemental analysis (as 06H574N, O): 'H-NMR
(dimethyl sulfoxide-d6) = 5.88 ppm
(br) C area ratio) Nl (222,99 ppm
(br) OHs 3 Purchase Analysis Spectrum 211 M+ 10M-1 18Q M-OF Infrared Absorption Spectrum; Attorney Yoshi 1) Toshio Proceedings Amendment (Spontaneous) June 2, 1980, 1988 Patent Application No. 212525 2, Title of the invention: New pyrimidine derivatives and their production method 3, Relationship with the case of the person making the amendment Patent applicant name: ￥Sake Mectron Co., Ltd. 4, Agent address: 1- Shiba Daimon, Minato-ku, Tokyo 2-7 Ato Building 5
No. 01 No. 5, Claims of the specification to be amended and Detailed Description of the Invention 6, Contents of amendment (1) The claims are corrected as shown in the attached sheet.

(2) Correct "1 correlation" in the first line directly below No. 5 to "correlation".

〔Attachment〕

2. Claim 1: A novel pyrimidine derivative represented by the general formula (wherein R is an alkyl group and R/ is a hydrogen atom or a hydrocarbon group).

2. Claim 1 which is 2-amino-4-fluoro-5-trifluoromethyl-6-medoxypyrimidine
Novel pyrimidine derivatives described in .

3. General formula (OF,)2c=a. Perfluoroisobutylene derivatives represented by R (wherein R is an alkyl group) and general formula NH=CriN crystals, (Kokote)R
' is a hydrocarbon group spanning a hydrogen atom)) (where R and R' are 411 < of the above a6 constant) A method for producing a novel pyrimidine derivative represented by:

4. Patent n? in which a defluorinated water-containing product of perfluoro-f-sobutylene with alcohol is used as a perfluoroin-butylene conductor. l desired range 3rd erotic description n
Method for producing a primary pyrimidine derivative.

Claims (1)

[Claims] 1. A novel pyrimidine derivative represented by the general formula (wherein R is an alkyl group and R' is a hydrogen atom or a carbon hydrogen group). 2. Claim 1 which is 2-amino-4-fluoro-5-trifluoromethyl-6-medoxypyrimidine
Novel pyrimidine derivatives described in . 3. General formula (CF3)2C=Cri. Perfluoroisobutylene derivatives represented by R (wherein R is an alkyl group) and general formula NH-0 (where R' is a hydrogen atom or a hydrocarbon group) A general formula characterized by reacting a guanidine or a salt thereof (where R and R' are
A new pi IJ represented by <) 11.5)
Or body fl, μ sludge. 4. Perfluoroin butylene derivative W (4r and shite, perfluoroisobutylene alcohol adduct defluorinated water poxide is used)
A suppressor slag of the novel pyrimidine compound described in Section 1.