Purines. LXXVII. An alternative synthesis of N6-demethylcaissarone from 9-methyl-8-oxoadenine by regioselective N(3)-methylation: Utilization of the N(7)-benzyl and N(1)-benzyloxy groups as control synthons

Article abstract of DOI:10.1248/cpb.45.1601

An alternative synthesis of 3,9-dimethyl-8-oxoadenine (N⁶- demethylcaissarone) hydrochloride (5a-HCI) starting from 9-methyl-8- oxoadenine (17) is described. The synthesis proceeded through N(7)- benzylation, N(1)-oxidation, and O-benzylation to afford the 1-benzyloxy derivative 25, which afforded the ring-opened formamide derivative 26 on treatment with dilute aqueous NaOH. Methylation of the monocycle 26 with MeI in the presence of K₂CO₃, followed by acid-catalyzed cyclization and subsequent catalytic hydrogenolysis afforded 5a·HCl. The key intermediate 25 was alternatively prepared from 17 by N-oxidation and subsequent O,N(7)- dibenzylation with PhCH₂Br in the presence of K₂CO₃.