Direct SNAr amination of fluorinated imidazo[4,5-c]pyridine nucleosides: efficient syntheses of 3-fluoro-3-deazaadenosine analogs

This paper describes the ready preparation of 3,6-difluoro-3-deazapurine (4,7-difluoroimidazo4,5-c]pyridine). This novel base was glycosylated under mild conditions using three different ribose sugar analogs. 3,6-Difluoro-3-deazapurine ribonucleoside analogs underwent direct S_NAr amination reactions with liquid ammonia to give 3-fluoro-3-deazaadenosine analogs in excellent yield; in contrast, 6-chloro-3-fluoro-3-deazapurine nucleosides were inert under similar reaction conditions.