INNOVATIVE APPROACHES TO THE IMIDAZO[4,5-B]PYRIDINE RING-SYSTEM - DEVELOPMENT OF AN EFFICIENT PROCESS FOR INDUSTRIAL-SCALE PRODUCTION OF A KEY INTERMEDIATE FOR POTENT ANGIOTENSIN-II RECEPTOR ANTAGONISTS

Two syntheses of 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (3), a n important intermediate for the synthesis of several potent angiotens in II antagonists, have been investigated. The first route involves co nversion of 1,1-bis(methylthio)-2-nitroethene (17) to 2-amino-4,6-dime thyl-3-nitropyridine (6); catalytic hydrogenation of 6 in propionic ac id gave 3 in high yield. In the second synthesis, propionitrile is con verted to imidate hydrochloride 15 . HCl which is neutralised and reac ted with aminoacetonitrile in the presence of acetylacetone to give 3 in 55% overall yield. The propionitrile route was scaled up to produce 3 in the pilot plant.