A general method for the preparation of 2,3,5-trisubstituted-furo[3,2-b]pyridines

The preparation of 2,3,5-trisubstituted-furo3,2-b]pyridines via a Pd(0)-catalyzed intramolecular cyclization of methyl 4-(6-chloro-2-iodopyridin-3-yloxy)-substituted-butenoates 9a-f is described. This approach was both efficient and general, and provided the highly functionalized heterocyclic ring system in high yield. Among the several examples provided is the preparation of 3-2-(N,N-dimethylamino)ethyl]-5-(4-fluorobenzoyl)amino-2-methylfuro3,2-b]pyridine 4, a selective 5-HT_1F receptor agonist.