Specific inhibitors in vitamin biosynthesis. Part 10. Synthesis of 7- and 8-substituted 7-deazaguanines

Versatile syntheses of 7- and 8-substituted 7-deazaguanines including N-alkyl derivatives have been developed by identifying selective annulation reactions with 2,6-diaminopyrimidin-4(3H)-one as substrate and β-halocarbonyl compounds as electrophiles. A new synthesis of 8-substituted 7-deazaguanines using nitrosoalkenes as electrophiles is described. With some combinations of reactants, furo[2,3-d]pyrimidines are significant products in place of or in addition to the required 7-deazaguanines [pyrrolo[2,3-d]-pyrimidin-4(3H)-ones]. When 2,4-diamino-6-chloropyrimidine was used as a substrate, imidazo-pyrimidines were produced.