A New Strategy toward Fused-Pyridine Heterocyclic Scaffolds: Bischler−Napieralski-type Cyclization, Followed by Sulfoxide Extrusion Reaction

Method development was completed for a new strategy to obtain fused-pyridine heterocyclic scaffolds. The synthetic route entails a Bischler-Napieralski-type reaction as the key step, followed by a sulfoxide extrusion reaction. The reactions of 3-amino-2-arylthiopyridines or 3-amino-4-arylthiopyridines and carboxylic acids promoted by a Lewis acid such as SnCl4 yielded novel tricyclic pyridobenzothiazepines, which could be readily converted to their corresponding oxidized products via a sequence of sulfur oxidations and eventually to benzonaphthyridines via a sulfoxide extrusion. The synthetic strategy provides an efficient way to access libraries of novel structurally diversified heterocyclic compounds with potential pharmaceutical or biological activities.