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-carboxy with N-chlorosuccinimide

• Published in: Tetrahedron Vol. 56; no. 40; pp. 7915 - 7921
• Main Authors: Ikemoto, T, Kawamoto, T, Tomimatsu, K, Takatani, M, Wakimasu, M
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 29.09.2000
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; 4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one derivative; IMIDAZO<1,2-A>PYRIDINES; N-chlorosuccinimide; ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxylate; regioselective chlorination
• ISSN: 0040-4020
• DOI: 10.1016/S0040-4020(00)00709-2

A convenient synthesis of the chronic renal disease agent, trifluoro-N-[4-(3-oxo-3,5-dihydro-4H-1,4,8b-triazaacenaphthylen-4yl)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-carboxlate (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. (C) 2000 Elsevier Science Ltd. All rights reserved.