Imidazopyridine and pyrimidinopyridine systems from perfluorinated pyridine derivatives

Annelation of pentafluoropyridine via an intramolecular nucleophilic aromatic substitution process with benzamidine gave an imidazopyridine system in high yield in a two step process whilst alkyl amidines gave 4-aminotetrafluoropyridine by a competing elimination reaction. 4-Phenylsulfonyl tetrafluoropyridine reacts with amidines to give the corresponding imidazo[4,5-b]pyridine systems. In contrast, 4-cyanotetrafluoropyridine gave a [6,6]-fused pyrimidinopyridine system arising from initial nucleophilic substitution at the C-3 position of the pyridine ring followed by intramolecular cyclization onto the pendant cyano group. The systems prepared by this annelation methodology further demonstrate the utility of perfluorinated heterocyclic substrates for the synthesis of heterocyclic scaffolds that possess multiple functionality and have potential applications in the drug discovery arena.