Hexahydroimidazo[1,5-a]pyrazine. I. Synthesis of 7-methyl-1,5,6,7,8a-hexahydroimidazo[1,5-a]pyrazin-3(2H)-one and derivatives]

The synthesis and pharmacological activity of a series of 2-aryl or alkyl substituted 7-methyl-1,5,6,7,8,8a-hexahydroimidaso[1,5-a]pyrazin-3(2H)-ones, are reported. The 2-aryl derivatives (VI) have been prepared by reaction of 3-(arylaminomethyl)-1-methylpiperazines (IV) have been prepared by reaction of 3-(arylaminomethyl)-1-methylpiperazines (IV) with N,N'-carbonyldiimidazole. Reaction of various anilines with 3-carbomethoxy-1-methylpiperazine (II) and subsequent reduction of the amides (III) afforded the bases (IV). The synthesis of the unsubstituted compound (XII) has been accomplished either by cyclization with sodium methoxide of methyl (1-me-thylpiperazin-3-yl)methylcarbamate (XI) or by reaction of 3-aminomethyl-1-methylpiperazine (XV) with N,N'-carbonyldiimidazole. Reduction of 1-benzyl-2-cyano-4-methylpiperazine (VII) followed by reaction with methyl chloroformate and debenzylation afforded the urethane (XI). The 2-alkyl and 2-alkenyl derivatives (XIII) have been prepared by alkylation of the sodium salt of (XII) in DMF. The compounds of these series have been tested for antiinflammatory, coronary dilator and C.N.S. depressant activities.