A Convenient Synthetic Method of a 5,7-Diarylcyclopenteno-[1,2-b]pyridine-6-carboxylate: A Key Intermediate for Potent Endothelin Receptor Antagonists Original Research Article

A convenient method for the synthesis of the title intermediate 4 was described. The key steps of this synthesis involved: (1) regioselective addition reaction of arylzinc reagent to quinolic anhydride in 42% isolated yield, (2) conversion of a ketoacid to an enone , which was achieved in 65% yield by intramolecular Knoevenagel reaction of β-ketoester generated by condensation of an acid imidazolide with an ester enolate, followed by dehydration assisted with silica gel, and (3) stereoselective reduction of an allyl alcohol in 75% yield with zinc under acidic conditions. This synthesis enabled us to provide hundreds of grams of without chromatographic purification.