Practical Synthesis of T-3761,(S)-10-(1-Aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic Acid

概要

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An economical 11-step synthesis of T-3761 (1), a new quinolone antibacterial agent discovered by us, has been developed. Commercially available 2,3,4,5-tetrafluorobenzoic acid (2) has been transformed to 4-(1-acetaminocyclopropyl)-2,3,5-trifluorobenzoic acid (10) in 6 steps (68% yield), including cyclopropane-ring formation of the 4-cyanomethylbenzoate intermediate (6) at its side chain. Conversion of 10 to the β-keto ester 11 and a subsequent 2-step pyridoxazine annulation procedure afforded 13 (80% yield), which, on N, O-deprotection, provided 1 (48% overall yield from 2). The overall reaction sequence can be carried out without chromatographic purification of intermediates.
社団法人日本薬学会の論文
1994-12-15