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

摘要

WE CLAIM:   1. A process for the synthesis of 3, 8-disubs timled-4-oxo-perhydro (1,2-C) piperazinopyrimidines of the general formula V, VII, IX and XI as shown in the accompanying drawing, wherein R1 and R3 are alkyl, aryl or aralkyl groups like methyl, ethyl, phenyl or benzyl and R3 is alkyl, aralkyl, acyl, or aroyl groups such as methyl, ethyl, benzyl, acetyl or benzoyl by (a) condensing N-monosubsituted ethylene-diamines of the general formula I with N-monosubstituted maleamic acids of the general formula II, shown in the drawing, in which R! and R2 are alky], aryl or aralkyl groups like methyl, ethyl , phenyl or benezyl, by heating the two reactants under reflux in solvents like dioxan, pyridine tertrahydrofuran, glymeor diglyme forming 1-slbstiiuted 2- oxop,peiazire-3-N-acetarnides of the general formula III as shown in drawing ; (b) subject g the amide of the general formula 111 to electrolytic reduction or to the treatment with a metal hydride such as lithium aluminium hydride in the presence of solvents like ether and tertrahydrofuran to yield l-Subsotuted-3-[/3-(N-substituted)-amino ethyl]-piperazines of the general formula IV as shown in the drawing; (c) treating the amines of the general formula IV first with ethylchloroformate and then with sodium ethoxide, as described in our earlier patent application No, 113616, or with ca bonyl- diimidazole, thus obtaming 3, 8-disubstituted-4-oxo-perhydro (1, 2-C)-piperaztnopyrimi- dmes of the general formula V as shown m the drawing; (d) catalytically hydrogenating with noble metal catalysts like palladium on carbon in solvents like acetic acid, compounds of the general formula in which R2 is benzyl and R1 is alkyl, aryl or aralkyl, or R1 is benzyl and R1 is alkyl, aryl or aralkyl and R1 and R2, are benzyl, yielding the respective substituted, 3-substituttd or unsubstituted-4-oxi -perhydro (], 2-C ) - piperazinopyrimidines of the general formula VI, VIII and X respective and finally (e) alkylating, aralkylating, acylating or aroylating the compounds of the general formulae VI, VIII and X using formic acid and formaldehyde for methylation or reaction withalkylhalioes, aralkylhalides, acylhalides or aroylhalides such as ethyl iodide, phenyl- ethyl bromide, acetyl chloride or benzoyl chloride in the presence of bases like sodium ethoxide, potassium carbonate or sodium bicarbonate in the solvents such as benzene, toluene, or acetone.