Polysubstituted and ring-fused pyridazine systems from tetrafluoropyridazine

Abstract

Tetrafluoropyridazine 1 reacts with a range of oxygen-, nitrogen-, sulfur- and carbon-centred nucleophiles to give, in general, products 2 arising from substitution of fluorine para to ring nitrogen. Subsequent reaction of the trifluoropyridazine derivatives 2 gave a range of 4,5-di- and tri-substituted products 3 and 6. Related reactions of tetrafluoropyridazine 1 with difunctional nucleophiles gave [6,6]-, [5,6]- and [6,5,6]-polycyclic ring fused pyridazine scaffolds 4 and 9. Further functionalisation of scaffolds 4 by nucleophlic aromatic substitution processes involving displacement of fluorine atoms at activated sites ortho to ring nitrogen provide an indication of the synthetic possibilities offered using tetrafluoropyridazine as a starting material for the preparation of polysubstituted pyridazine and novel polyfunctional ring fused pyridazine systems with potential applications in the drug discovery arena.