A HIGH CHEMICAL-REACTIVITY OF 5-AZIDOURACILS AND ITS SYNTHETIC APPLICATION - NOVEL SYNTHESIS OF 8-SUBSTITUTED 1,3-DIMETHYLXANTHINE DERIVATIVES

A novel method for the preparation of 8-substituted 1,3-dimethylxanthi ne derivatives (7 or 8) is described: treatment of 6-alkylamino-5-brom o-1,3-dimethyluracils (6a-e), easily prepared by bromination of the co rresponding 6-alkylamino-1, 3-dimethyluracils (5), with sodium azide i n DMF at ambient temperature allowed the direct formation of the 8-sub stituted 1,3-dimethylxanthines (7) proceeding via a transient formatio n of the corresponding 5-azido-1 ,3-dimethyluracils. The 5-bromo-1,3-d imethyluracils (6f, g) possessing an ct-branched alkylamino group at t he 6-position similarly react with sodium azide to afford 8,8-disubsti tuted 1,3-dimethyl-8H-xanthines (8,8-disubstituted 1,3-dimethyl-3,g-di hydropurine-2,6-diones)(8).