A PROCESS FOR THE SYNTHESIS OF 3:8- DISUBSTITUTED 4-OXO-PERHYDRO (1,2-C)-PIPERAZINOPYRIMIDINES.

摘要

A process for the synthesis of 3,8-disubstituted-4-oxo-perhydro(l,2-c)piperazinopyrimidines of the general formula IX shown in the accompanying draw-ing wherein R and R" are alkyl, aryl or araikyl groups like methyl, ethyl, phenyl, benzyl or phenethyl by (a) condensing N-substituted benzyloxycarbonyigly-cines of the general formula I of the drawing in which K is alkyl, arvl or araikyl group like methyl, ethyl, phenyl, benzyl or phenethyl with dimethyl aspartate (II) by standard methods of peptide synthesis using active esters of the carboxyl component such as p-nitrophenylesters or through anhydride formation with ethyl chloroformate or by the use of agents which cause direct peptide synthesis like dicyclohexylcarbo-diimide, to give N-substituteol benEyloxycarbonylgly-cyl-aspartic acid dimethyl ester of the general formu-la III of the drawing, (b) catalytically hydrogenating the peptide of the general formula III of the drawing using noble metal catalysts or treating with acid re-agents like hydrobromic acid in acetic acid and subse-quent liberation of the free base with chloroformic ammonia to get a compound of the general formula rv of the drawing, which then cyclised to get a com-pound of the general formula V of the drawing by keeping in vacuum over phosphorus pentoxide, (c) treating the compound of the general formula V of the drawing with a primary amine of the general formula VI in ethanolic solution to get a compound of the general formula -VII in which R" is an alkyl, aryl or araikyl group like methyl, ethyl, phenyl, benzyl or phenethyl, (d) reducing the compound of the general formula VII electrolytic ally or with metal hydrides like lithium aluminium hydride in solvents like ether or tetrahydrofuran to get 1-substituted 3-[B-(N-sub-stituted)aminoethyl]-piperazines of the formula VIII of the drawing and (e) treating these amines or their hydrochlorides with ethyl chloroformate to get 1-sub-stituted-N-ethyl carbonyl-3-[6-{N-substituted)amino-ethyl] -piperazines, and tlien treating with methoxides or ethoxides of sodium or potassium in solvents like methanol or ethanol to get 3,8-disubstituted-4-oxo-perhydro (1,2-c) piperazinopyrimidines of the general formula IX shown in the accompanying drawing.