Efficient conversion of 6-cyanopurines into 6-alkoxyformimidoyl purines

Abstract

An extremely simple method for the selective synthesis of 9-aryl and 9-alkyl 6-alkoxy or 6-alkoxyformimidoyl purines from the corresponding 6-cyanopurines is described. The reaction is carried out with methanol or ethanol in the presence of DBU. At room temperature, nucleophilic attack by the primary alcohol occurs selectively on the cyano carbon atom, leading to 6-alkoxyformimidoyl purines in good yields. Heating the reaction mixture at a temperature greater than or equal to 78 °C leads to nucleophilic substitution of the substituent in the 6-position by the alkoxy group, generating the corresponding 6-alkoxypurines, also in excellent yields. The 6-alkoxyformimidoyl purines were used as intermediates in the synthesis of 6-carboxamidinopurines by reaction with methylamine (for 9-methylpurine 5a) or methyl ammonium chloride (for 9-arylpurines 5b and 5c).