Synthesis of novel 6-enaminopurines

Abstract

Two different approaches have been used for the synthesis of 6-enaminopurines 6 from 5-amino-4-cyanoformimidoyl imidazoles 1. In the first approach imidazoles 1 were reacted with ethoxymethylenemalononitrile or ethoxymethylenecyanoacetate under mild experimental conditions and this led to 9-substituted-6-(1-amino-2,2-dicyanovinyl) purines 6a–f or 9-substituted-6-(1-amino-2-cyano-2-methoxycarbonylvinyl) purines 6g–k. These reactions are postulated to occur through an imidazo-pyrrolidine intermediate 7, which rapidly rearranges to the 6-enaminopurine 6.

In the second approach 6-methoxyformimidoyl purines 3, prepared in two efficient steps from 5-amino-4-cyanoformimidoyl imidazoles 1, were reacted with malononitrile and methylcyanoacetate with a mild acid catalysis (ammonium acetate or piperidinium acetate) to give 6-enaminopurines 6a, 6d, 6f, 6g and 6k in very good yields. Only low yields were obtained for the 6-enaminopurine 6j, as competing nucleophilic attack on C-8 of either 3d or 6j causes ring opening with formation of pyrimido-pyrimidines 11 and 10a respectively.