Purines. IXXVII. An Alternative Synthesis of N 6 -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

An alternative synthesis of 3, 9-dimethyl-8-oxoadenine (N6-demethylcaissarone) hydrochloride (5a·HCl) 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.