One-pot regioselective synthesis of 2,6,9-trisubstituted adenines

Abstract

A series of 2,6,9-substituted adenines were obtained from the easily accessible 5-amino-4-cyanoformimidoyl imidazoles 1, acetic and benzoic anhydrides and primary alkyl amines in a three-steps sequence. Acylation of 1 followed by addition of the amine led to the intermediates 5-amino-4-(N-acyl)formamidino imidazoles 4/5, under mild conditions. Cyclization of 4/5 under reflux in ethanol led to the desired substituted adenine. A preliminary stepwise study led to the development of three general and efficient one-pot methods for the synthesis of adenine derivatives. The one-pot three-step reaction in the presence of DMAP was the most convenient syn-thetic approach.