Synthesis and reactions of 2-and 4-substituted furo[3,2-c]pyridines

Substituted furopropenoic acids were prepared from appropriate aldehyde under the Doebner’s conditions. Obtained acids were converted to the corresponding azides, which were cyclized by heating in Dowtherm to furopyridones. These compounds were aromatized with phosphorus oxychloride to chloro derivatives of furo3,2-c]pyridine (Va, Vb). Chloro derivative Vb was reduced with hydrazine hydrate to 2-(4-aminophenyl)furo3,2-c]pyridine in ethanol and Pd/C as a catalyst. Chloro derivative Va was converted to 4-amino-2-(3-pyridyl)furo3,2-c]pyridine under the same conditions. The chlorine atom in other chloro derivatives (VIIa, VIIb) was replaced by nucleophilic substitution with alkoxides (sodium ethoxide, propoxide, and isopropoxide) and the corresponding alkoxy derivatives were formed. By reaction of VII with cyclic secondary amines (morpholine, piperidine, and pyrrolidine) 4-substituted furopyridines were prepared.