Synthesis of Furo[2,3-c]pyridazines via Tandem Transition-Metal Catalysis

Abstract

A general and efficient catalytic approach to synthesis of the furo[2,3-c]pyridazine ring system is reported. Building on the easily accessible 2-bromo-3-aminopyridizinone skeleton, a tandem Sonogashira coupling-cycloisomerization provides ready access to functionalized furopyridazines. A wide functional group tolerance was observed in the tandem reaction, which proceeds in high yield in 1-3 h. The structure of the heterocyclic ring system was confirmed through single-crystal X-ray crystallography.

Synthesis of Substituted 6,7-Dihydro-5H-pyrrolo[2,3-c]pyridazines/pyrazines via Catalyst-Free Tandem Hydroamination–Aromatic Substitution

“…Synthetic routes to access fused bicyclic pyridazines are less common. Strategies for the synthesis of furo­[2,3- c ]­pyridazines, tetrahydropyridopyridazines, and pyrimido­[4,5- d ]­pyridazines have been described, and recently, Herdewijn and colleagues disclosed a report detailing a comprehensive synthesis of many other fused pyridazines …”

“…6 Synthetic routes to access fused bicyclic pyridazines are less common. Strategies for the synthesis of furo[2,3-c]pyridazines, 7 tetrahydropyridopyridazines, 8 and pyrimido[4,5-d]pyridazines 9 have been described, and recently, Herdewijn and colleagues disclosed a report detailing a comprehensive synthesis of many other fused pyridazines. 10 Although the vast majority of fused pyridazine-containing drug-like molecules feature an imidazo[1,2-b]pyridazine scaffold, 11 we required direct access to substituted 6,7dihydro-5H-pyrrolo[2,3-c]pyridazines in an ongoing drugdiscovery program in our laboratory.…”