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【结 构 式】 
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【分子编号】65952 【品名】 【CA登记号】 |
【 分 子 式 】C25H27FN4O6 【 分 子 量 】498.5111432 【元素组成】C 60.23% H 5.46% F 3.81% N 11.24% O 19.26% |
合成路线1
该中间体在本合成路线中的序号：(VII)Coupling of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (I) with (4aS,7aS)-octahydropyrrolo[3,4-b][1,4]oxazine (II) in the presence of triethylamine in acetonitrile and subsequent treatment of the resulting adduct (III) with hydrochloric acid in water gives finafloxacin hydrochloride (1, 2). Alternatively, condensation of the ethyl ester (IV) with the Boc-protected pyrrolo-oxazine (V) by means of DIPEA in dimethylphthalate (DMP) at 100 °C gives adduct (VI), which is hydrolyzed with lithium hydroxide to yield the corresponding free carboxylic acid (VII). Finally, acid (VII) is deprotected by treatment with hydrochloric acid in ethanol/ether (3). Scheme 1.
| 【1】 Matzke, M., Petersen, U., Schenke, T. et al. (Bayer Healthcare AG). Use of 7-(2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-quinolone carboxylic acid and naphthyridon carboxylic acid derivatives for the treatment of Helicobacter pylori infections and associated gastroduodenal diseases. CA 2274894, DE 19652239, EP 0946176, JP 200351781, JP 2000514825, US 6133260, US 6432948, WO 1998026779. |
| 【2】 Wohlert, S.E., Jaetsch, T., Gallenkamp, B. et al. New fluoroquinolone finafloxacin HCI (FIN): Route of synthesis, physicochemical characteristics and activity under neutral and acid conditions. 48th Annu Intersci Conf Antimicrob Agents Chemother (ICAAC) Infect Dis Soc Am (IDSA) Annu Meet (Oct 25-28, Washington, D.C.) 2008, Abst F1-2036. |
| 【3】 Hong, J., Zhang, Z., Lei, H. et al. A novel approach to finafloxacin hydrochloride (BAY35-3377). Tetrahedron Lett 2009, 50(21): 2525-8. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 65946 | 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid | C14H8ClFN2O3 | 详情 | 详情 | |
| (II) | 65947 | (4aS,7aS)-octahydropyrrolo[3,4-b][1,4]oxazine | C6H12N2O | 详情 | 详情 | |
| (III) | 65948 | C20H19FN4O4 | 详情 | 详情 | ||
| (IV) | 65949 | C16H12ClFN2O3 | 详情 | 详情 | ||
| (V) | 65950 | C11H20N2O3 | 详情 | 详情 | ||
| (VI) | 65951 | C27H31FN4O6 | 详情 | 详情 | ||
| (VII) | 65952 | C25H27FN4O6 | 详情 | 详情 |