Reaction of enamines with semicarbazone-based amidoalkylating reagents: A straightforward synthesis of annulated 1-aminopyrimidin-2-one derivatives

Abstract

An efficient synthesis of 1-arylideneamino-substituted hexahydro-1H-cyclopenta[d]pyrimidin-2-ones and octahydroquinazolin-2-ones has been developed. The synthesis involves a stereo- and regioselective cascade reaction of the corresponding 4-(tosylmethyl)semicarbazones with 1-morpholinocyclopentene or 1-morpholinocyclohexene to give predominantly bicyclic pyrimidines with an exocyclic CC double bond (80–97%). The later undergo rapid isomerization when heated in THF in the presence of TsOH to form bicyclic pyrimidines with a significant predominance of those with an endocyclic CC double bond (90–97%).