Synthesis of novel 6-enaminopurines

• Author(s): Carvalho, M. Alice ; Zaki, M. ; Proença, M. Fernanda R. P. ; Booth, Brian L. ; Álvares, Yolanda
• Date: 2004
• Persistent ID: http://hdl.handle.net/1822/2199
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): 6-enaminopurines; Imidazoles; Ethoxymethylenemalononitrile; Ethoxymethylenecyanoacetate; 6-methoxyformimidoyl purines; Malononitrile
• Document Type: Article
• Language: English

Description

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.