JPS59104364A - Novel pyrimidine derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A pyrimidine derivative shown by the formula I (R is alkyl; R' is hydrocarbon group). EXAMPLE:2-Phenyl-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 an amidine 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 relates to novel pyrimidine derivatives and methods for their production. More specifically, the present invention relates to a novel pyrimidine derivative synthesized from perfluoroisobutylene and a method for producing the same.

Perfluoroisobutylene is obtained in relatively large quantities as the main by-product when producing perfluoropropylene by thermally decomposing tetraphnoreoloethylene, but an effective method for using this compound has not yet been established. . Also,
This compound is highly toxic and difficult to handle, so alcohol adducts such as methanol [(OF,)20HOF20
R ], 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, the dehydrofluorinated product [(CF3 ) 20-OFOR ] with amidine or its salt, the present inventors found that a novel pyrimidine derivative was obtained, and this pyrimidine derivative has a fluorine substituted at the 41-position of the pyrimidine nucleus. Due to the electron-withdrawing properties of the atom and the trifluoromethyl group substituted at the 5-position, unique medicinal efficacy is exhibited as an anti-inflammatory agent and an anti-tumor agent.

Accordingly, the present invention relates to novel pyrimidine derivatives, which are represented by the general formula where R is an alkyl group and R' is a hydrocarbon group.

The present invention also relates to a method for producing such a novel pyrimidine derivative, and the novel pyrimidine derivative includes a perfluoroisobutylene derivative represented by the formula NH
- by reacting an amidine or stream thereof represented by OR'NH2 (where R' is a hydrocarbon group).

The perfluoroisobutylene derivative represented by the above general formula can be obtained by absorbing perfluoroisobutylene in an alcohol such as methanol, ethanol, n-propanol, isopropanol, or n-butamer, and then dehydrofluorinating it. Since it is easily obtained as a crystal, it can be used in the reaction as an alkoxy derivative depending on the type of alcohol used for absorption.

In addition, the amidine represented by the above general formula includes alkylamidine such as methylamidine and ethylamidine;
Arylamidines such as phenylamidine are used, and the hydrocarbon group of the arylamidine may be further substituted with an alkyl group, an alkoxy group, or the like. These amidines are also used in the form of salts such as hydrochloride, sulfate, carbonate, and acetate.

The reaction is performed for perfluoroisobutylene derivatives from about 1 to
Dichloromethane, 1,1.1-trichloroethane, 1,1,2-trichloroethane, 1.1.2-trifluoro-1.2.2- is used to dissolve the former using 50 molar ratio of amidine or its salts. Halogenated solvents such as trichloroethane, carbon tetrachloride, chloroform, benzene,
Aromatic solvents such as toluene and xylene, ethyl acetate,
Ester solvents such as butyl acetate, ethyl benzoate, propyl benzoate, butyl benzoate, diethyl ether,
diisopropyl ether, diglyme, triglyme,
Since it is carried out in a heterogeneous system using an ether solvent such as tetraglyme, it is preferably carried out using a phase transfer catalyst such as a quaternary ammonium salt at a reaction temperature of about -10 to +50°C.

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

Example 3.2 g (22.46 mmol) of phenylamidine hydrochloride was dissolved in 5 rnl of water, 5 ml of an aqueous solution of 0.8 g of sodium hydroxide dissolved in 5 ml of water was added, and 1-methoxy- 2.1 units of 2-trifluoromethylperfluoropropylene (9.906 mmol)
A solution prepared by dissolving the above in 10 ml of dichloromethane and 0.1 g of penzyltrimethylammonium chloride were added. After standing at room temperature for 24 hours, the mixture is separated, and the diqualmethane solution phase is dehydrated over anhydrous magnesium sulfate and evaporated to dryness. Since 1.55 g of crystals with a melting point of 39 to 50°C was obtained,
This was purified using a silica gel/n-hexane column.

The purified crystals have a melting point of 62-66°C.

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

Elemental analysis (as 0,2H5F4N30)゜Calculated value a
: 56.25%, H: 3.13%, N: 10.94% Actual value 0: 56.01%, H: 3.52%, N: 10.9
7%'H-NMR (oDoz,): 4.20ppm3H 8.52-7.40ppm5H "F-NMR (aDa, g3): Mass spectrum: 272M 271M-1 241M-OF 172M-02F4 Attorney Toshio Yoshida

Claims (1)

[Claims] 1. A novel pyrimidine derivative represented by the general formula (wherein R is an alkyl group and R' is a carbon hydrogen group). The novel pyrimidine derivative according to claim 1, which is 2,2-phenyl-4-fluoro-5-trifluoromethyl-6-methoxypyrimidine. 3. Perfluoroisobutylene derivatives represented by the general formula (wherein R is an alkyl group) and general formula NH=OR'NH2 (wherein R'
is a hydrocarbon group) or a salt thereof. Law. 4. The method for producing a novel pyrimidine derivative according to claim 3, wherein a dehydrofluorinated alcohol adduct of perfluoroisobutylene is used as the perfluoroisobutylene derivative.