Practical Synthesis and Molecular Structure of a Potent Broad-Spectrum Antibacterial Isothiazoloquinolone
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- 作者：Akihiro Hashimoto ; Godwin C. G. Pais ; Qiuping Wang ; Edlaine Lucien ; Christopher D. Incarvito ; Milind Deshpande ; Barton J. Bradbury ; Jason A. Wiles
- 刊名：Organic Process Research & Development
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：11
- 期：3
- 页码：389 - 398
- 全文大小：349K
- 年卷期：v.11,no.3(May 2007)
- ISSN：1520-586X
文摘
We report the synthesis of the new 2-sulfonylquinolone ethyl1-cyclopropyl-6,7-difluoro-2-methanesulfonyl-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (5). Sulfone 5 is a keyintermediate used in the optimized synthesis of the isothiazoloquinolone 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4-b]quinoline-3,4-dione (1), a potentbroad-spectrum antibacterial agent that is effective againstclinically important resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA). Our synthetic methodis free of chromatographic purification and amenable to large-scale synthesis. The molecular structures of 1, 9-cyclopropyl-6,7-difluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione (4), 5, and ethyl 2-cyclopropylamino-6,7-difluoro-8-methoxy-4-oxo-4H-thiochromene-3-carboxylate (10) were establishedunambiguously using multinuclear NMR spectroscopy andX-ray crystallography.