A Practical Synthesis of the Chronic Renal Disease Agent,4,5-Dihydro-3H-1,4,8b-triazaacenaphthylen-3-one Derivatives,Using Regioselective Chlorination of Ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxylate with N-Chlorosuccinimide

摘要

A convenient synthesis of the chronic renal disease agent,trifluoro-N-[4-(3-oxo-3,5-dihydro-4H-1,4,8b-triazaacenaphthylen-4-yl)butyl]methanesulfonamide (1a),for large scale has been developed via ethyl 5-(chloromethyl)imidazo[1,2-a]pyridine-3-carboxylate (3),which was given by the regioselective chlorination of ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxylate (6) with N-chlorosuccinimide (NCS) using AcOEt as a solvent in 83% yield.The condensation of 3 and primary amines gave 4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one derivatives (1)in good yields.The present synthesis of 1a was accomplished in five steps from 2-amino-6-methylpyridine (4)without requiring a chromatographic method.