SU403179A1 - METHOD OF OBTAINING PRODUCTION [X [1] BENZOTIENO [2,3-th] PYRIMIDINE - Google Patents

Description

The invention relates to the field of obtaining a new group of compounds possessing valuable pharmacological properties.

The first is based on a well known reaction of reacting an ester with amines to obtain derivatives of 1 benzothieno 2,3-é pyrimidine of the general formula

which, in the carbocyclic ring, have at least one carbocyclic aromatic residue and in position 4 is an amino-lower alkylamino group, or their 5,6,7,8-tetrahydropro-derivatives, or their salts.

The method consists in the fact that the corresponding 4-Y-1 beisotheno 2,3-d pyrimidine, which has in the carbocyclic ring, at least one aromatic carbocyclic residue and in which Y is a reactive esterified ester into hydroxyl ether or ester, ammonium.

a mercapto or sulfonyl group, or its 5,6,7,8-tetrahydro derivative, is subjected to an exchange reaction with an amino lower alkylamine, which contains at least one

a hydrogen atom at the nitrogen atom, with the following, if necessary, substitution of the amino groups in the amino with alkylamine and release of the target product in a free form, as a mixture of isomers, optical antipodes

or in the form of salts known methods. The exchange reaction is expediently carried out in the presence of a base.

Example 1. A mixture of 9 g of 4-.chloro-6,8-difepil5, 6,7,8 - tetrahydro-1 benzo-2,3-pyrimidine and 25 ml of fi-diptylampnoethylamine is heated for 2 hours at 140 ° C. The reaction mixture, while hot, is added, with stirring, to ice-cold water, and the crystals obtained are filtered on a putt and recrystallized from methanol.

4 (p-Diethylamino-ethylamino) -6,8-diphenyl 5, 6,7,8 - tetrahydro 1 benzothieno 2,, 3 - dynthyl imidine melts at 154-155 ° C. Example 2. 8 g of 4-chloro-6,8-diphenyl-5,6,7,8 tetrahydro - 1 bessojepio 2,3-d pyrimidine and 25 ml of y-DI tytaminopropylampia are heated for 2 hours at 140 ° C. Excess amine is distilled under vacuum; the residue is washed with water.

and filtered on suction. Thus obtained 4- (y-dimethylaminopropylamino) -6,8-dipheiyl-5, b, 7,8-tetrahydro-1 benzothieno 3,2c; J pyrimidine is dissolved in isopropanol. By introducing hydrogen chloride, the dihydrochloride is precipitated, which melts after recrystallization from ethanol at 256 ° C.

In a similar way, it is possible to obtain from 4-chloro-6,8-G) IS- (and-chlorophenyl) - 5,6,7,8 - tetrahydro-1 j Oenzo-yeno 2,3-d pyrimidine 4- (| 3 diethylamioethylamio) -6 , 8 bis - (p - chlorophenyl) - 5,6,7,8 - tetrahydro - 1 beisothieno 3,2dj pyrimidine and 4- (p-dimethylamioethylamino) t /, 8 - iis (p - chlorophenyl) - 5,6 , 7,8 - tetrahydro l-benzoate leno 3, 2-d pyrimidine or their hydrochlorides.

PR and measures 3. 9 g of 4-chloro-6,8-diphenyl-5,6,7,8 tetrahydro-1 6en3OTneHo 2,3-d pyrimidine and 25 ml of 4-amino-1-diethylaminopentane are heated for 2 hours at. The hot oil is poured into 100 ml of ice water and crystallization occurs. After several hours, the base is filtered on suction, dissolved in isopropiaol, and dry hydrochloric acid is added to the solution. 4- (4-diethylamino-1-methylbutylamido) -6,8-diphenyl-5,6,7,8-tetrahydro-1 benzothieno 2,3-d pyrimidine dihydrochloride precipitates and can be recrystallized from isopropanol; m.p. 225-230 ° C.

Example 4. 4.5 g of 4-chloro-6,8-bis (d-chlorophenyl) -5,6,7,8-tetrahydro-1 benzothieno 2,3dj pyrimidine and 25 ml of p-diethylaminoethylamine are heated for 1 hour at 140 ° WITH. The excess amine is then distilled off, the crystalline residue is stirred in water, filtered off under suction and recrystallized from a mixture of ethanol and water. 4- (p-Diethylaminoethylamino) -6.8bis- (he-chlorophenyl) -5,6,7,8-tetrahydro-1 benzothio 2, 3-d nirimidine melts at 172-174 ° C.

Example 5. 10 g of 4-chloro-6,8-bis- (l-chlorophenyl) -5,6,7,8 - tetrahydro - 1 bepzotieno 2,3d pyrimidine and 50 ml of p-dimethylamio-ethylamine are heated for 1 hour at 140 ° C . Excess ammoniums are then distilled, the crystalline residue is stirred in water, filtered on an iatch, and recrystallized from a mixture of ethanol and water. 4- (p-Dimethylaminoethylamino) -6,8-bis - (/ g-chlorophenyl) -5,6,7,8 - tetrahydro l 6eH3OTHeHo 2, 3-d pyrimidine nlava at 199-200 ° C. The dihydrochloride salt of this compound melts at 236-238 ° C.

Example 6. 3.6 g of 4-chloro-6,8-diphenyl-5,6,7,8 tetrahydro-1 beisotheno 2,3-d pyrimidine and 30 ml of p-morpholinoethylamine are heated for 1 hour at 190 ° C. The excess amine is distilled under vacuum, stir the crystalline residue in ethanol and filter on suction. The 4- (p-morpholinoethylamino) -6,8-diphenyl-5,6,7,8-tetrahydro-1 bepzotieno 2,3-d pyrimidium thus obtained melts at 182-184 ° C.

P R.Im ep 7. 7 g of 4-chloro-6,8-bis- (l-chlorfell) -5,6,7,8 - tetrahydro - 1 benzothieno 2,3d pyrimidine and 40 ml of y-dimethyl amiopropylamine are heated 1 hour at 140 ° C. Then the excess amine is distilled, the crystalline residue is stirred up, filtered off under suction and recrystallized from a mixture of ethanol and

water. 4- (y-Dimethylaminopropylamino) -6,8bis- ((g-chlorfeiyl) -5,6,7,8-tetrahydro-1 benzothieno 2, 3-d pyrimidia nlavis at 175-

76 ° C.

Example 8. 8.3 g of 4-chloro-6,8-bis- (p-chlorophenyl) -l benzoethio 2,3-d pyrimidine and 25 ml of p-dimethylamio-ethylamine are heated for 1 hour at 140 ° C. Then the excess amine is distilled, the residue is stirred in water, filtered on an iatch, and recrystallized from dimethylformamide. 4- (p-Dimethylaminoethylamino) -6,8-bis (-chlorfeiyl) -1 benzothieno 2,3d pyrimidine melts at 202-203 ° C.

Example 9. 15 g of 4-chloro-6,8-bis- (72-chlorophenyl) -5,6,7,8 - tetrahydro - 1 benzotethio 2,3d pyrimidine and 20 g of 1M-methyl-M-benzylethylenediamine are heated together 1 hour at 140 ° C. The excess amine is then distilled, the residue is shaken in water, filtered under suction and recrystallized from dimethylformamide water. (Benzylmethylamio) -ethylamino-6,8-bis- (p-chlorophenyl) -5,6,7,8-tetrahydro-1 benzothioio 2,3-d nirimidine melts at 171 - 172 ° C. Example 10. 8 g of 2-methyl-4-chloro-6,8-bis - (/ ghlorfeiil) - 5,6,7,8-tetrahydro-1 benzothio 2, 3-d pyrimidine and 30 ml of p-dimethylaminoethylamine are heated together 1 hour at 140 ° C. The excess amine is distilled under vacuum, the residue is triturated with water, filtered

They must also be recrystallized from a mixture of ethanol and water. Thus obtained 2-methyl-4- (p-dimethylaminoethylamino) -6.8bis- (l-chlorophenyl) -5,6,7,8-tetrahydro-1 benzothioio 2, 3-d pyrimidine ylavites at 202-

203 ° C.

Example 11. Described in the preceding irimery method, you can get 4- (p-methyamio, ethylamino) -6,8-bis- (p-chloroethiyl) 5, 6,7,8-tetrahydro-1 beisothieno 2,3-d pyrimidine hydrochloride, m.p. 178-182 ° C; and (p-dimethylamioethyl) - methylamino-6,8-bis (p-chlorfeiyl) -5,6,7,8 - tetrahydro-I beisothieno 2, 3-d pyrimidine, m.p. 150-153 ° C.

Subject invention

Claims (2)

1. The method of obtaining the derivatives of 1 benzothieno 2, 3-d pyrimidine of the general formula which in the carbocyclic ring, at least one carbocyclic aromatic residue and in position 4 of the amionization alkylamino group, or their 5,6,7,8-tetrahydroproducts, or their salts. characterized in that the corresponding 4-Y-1 benzothieno 2,3-d pyrimidine, which has in the carbocyclic ring, at least one aromatic carbocyclic residue and in which Y is a hydroxyl, ammonium esterified reactive ester or ester, mercapto or sulfonyl a group, or its 5,6,7,8-tetrahydro derivative is subjected to an exchange reaction with an amino-lower alkylamine, which contains at least one hydrogen atom at the nitrogen atom, followed, if necessary, by replacing the amino groups in the amino lower alkylamine and isolating the desired product in free form, as a mixture of isomers, optical antipodes or as a salt by known techniques. 2. A method according to claim 1, characterized in that the exchange reaction is carried out in the presence of a base.