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【结 构 式】 
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【药物名称】Orbifloxacin, AT-4526, Victas 【化学名称】1-Cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-5,6,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid 【CA登记号】113617-63-3 【 分 子 式 】C19H20F3N3O3 【 分 子 量 】395.38475 |
【开发单位】Dainippon Pharmaceutical (Originator), Schering-Plough (Licensee) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Quinolones |
合成路线1
The reaction of pentafluorobenzoylacetic acid ethyl ester (I) with triethyl orthoformate in refluxing acetic anhydride, followed by condensation with cyclopropylamine, gives 2-(pentafluorobenzoyl)-3-(cyclopropylamino)acrylic acid ethyl ester (II), which is cyclized by means of NaH in THF to yield 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III). The hydrolysis of (III) with H2SO4 /HOAc in refluxing water affords the corresponding carboxylic acid (IV), which is finally condensed with cis-2,6-dimethylpiperazine (V) in DMF to provide the target quinolone.
| 【1】 Matsumoto, J.-I.; Miyamoto, T.; Egawa, H.; Nakamura, S. (Dainippon Pharmaceutical Co., Ltd.); Quinoline derivs., pharmaceutical compsn. and method of use. EP 0242789; US 4886810 . |
| 【2】 Miyamoto, T.; Matsumoto, J.; Chiba, K.; et al.; Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency. J Med Chem 1990, 33, 6, 1645. |
| 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) | 20840 | ethyl 3-oxo-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C11H7F5O3 | 详情 | 详情 | |
| (II) | 55231 | ethyl (Z)-3-(cyclopropylamino)-2-(2,3,4,5,6-pentafluorobenzoyl)-2-propenoate | C15H12F5NO3 | 详情 | 详情 | |
| (III) | 20843 | ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C15H11F4NO3 | 详情 | 详情 | |
| (IV) | 55232 | 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C13H7F4NO3 | 详情 | 详情 | |
| (V) | 20848 | (2R,6S)-2,6-dimethylpiperazine | C6H14N2 | 详情 | 详情 |