Purines. LXXVI. Alkylation of 8-Oxoadenine Derivatives : Syntheses of 3,7-Dialkyl-, 3,9-Dialkyl-, and 3,7,9-Trialkyl-8-oxoadenines

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3-Alkyl-8-hydroxyadenines (5) have been shown to undergo regioselective methylation at the 7- or 9-position depending on the reaction conditions. Thus, treatment of 5a, c with dimetyl sulfate in aqueous NaOH provided 3-alkyl-7-methyl-8-oxoadenines (6b, h) in 48-60% yields, together with 3-alkyl-8-methoxyadenines 4d, h), whereas treatment of 5a-c with MeI in AcNMe_2 at 40℃ for 48h and subsequent anion exchange afforded 3-alkyl-9-methyl-8-oxoadenine hydrochlorides (7d, g, h・HCl) in 50-59% yieds. However, the reactions of 5a, c with EtI or PhCH_2Br took place slowly, giving complex mixtures of products.Compounds 6d, h were alternatively prepared in 51% and 31% yields, respectively, together with 3-alkyl-7,9-dimethyl-8-oxoadenine hydrochlorides (11d, h・HCl), by treatment of 3-alkyl-8-methoxyadenines (4d, h) with MeI in AcNMe_2 at room temperature for 6 h, followed by hydrolysis with boiling aqueous HCl. This method was applicable to ethylation with EtI, and 7-ethyl-3-methyl-8-oxoadenine (6e) was obtained in 70% yield from 8-ethoxy-3-methyladenine (4e). Compound 11h was shown to be obtainable through futher methylation of 6h. Thus, 11d, h were prepared in good yields by treatment of 6d, h with MeI in AcNMe_2.Compounds 7,to which zwitterionic structures were assigned, were stable in 0.1 N aqueous NaOH at room temperature, whereas 11d, h were no longer stable under such conditions.
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1997-10-15