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【结 构 式】 
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【药物名称】Sparfloxacin, CP-103826, RP-64206, CI-978, PD-131501, AT-4140, Zagam, Spara 【化学名称】5-Amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 【CA登记号】110871-86-8, 111542-93-9 (undefined stereoch.) 【 分 子 式 】C19H22F2N4O3 【 分 子 量 】392.40899 |
【开发单位】Dainippon Pharmaceutical (Originator), Aventis Pharma (Licensee), Bertek (Licensee) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, DNA Gyrase Inhibitors, DNA Topoisomerase IV Inhibitors, Quinolones |
合成路线1
The reaction of ethyl pentafluorobenzoylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with cyclopropylamine (II) in ether gives the aminomethylene derivative (III), which is cyclized by means of NaH in THF yielding ethyl 5,6,7,8-tetrafluoro-1-cyclopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (IV). The reaction of (IV) with benzylamine (V) by means of K2CO3 in refluxing acetonitrile affords the benzylamino derivative (VI), which is deprotected by hydrogenation with H2 over Pd/C in ethanol giving ethyl 5-amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (VII). The hydrolysis of (VII) with hot H2SO4 yields the free acid (VIII), which is finally condensed with cis-2,6-dimethylpiperazine (IX) in DMF.
| 【1】 Matsumoto, J.; Miyamoto, T.; Egawa, H.; Nakamura, S. (Dainippon Pharm. Co.; Ltd.); Novel quinoline derivatives and processes for preparation thereof. AU 8664277; EP 0221463; JP 87277362 . |
| 【2】 Prous, J.; Castaner, J.; AT-4140. Drugs Fut 1989, 14, 5, 413. |
| 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) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
| (III) | 20842 | ethyl 2-[(cyclopropylamino)methyl]-3-oxo-3-(2,3,4,5,6-pentafluorophenyl)propanoate | C15H14F5NO3 | 详情 | 详情 | |
| (IV) | 20843 | ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C15H11F4NO3 | 详情 | 详情 | |
| (V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (VI) | 20845 | ethyl 5-(benzylamino)-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C22H19F3N2O3 | 详情 | 详情 | |
| (VII) | 20846 | ethyl 5-amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C15H13F3N2O3 | 详情 | 详情 | |
| (VIII) | 19819 | 4-[(benzyloxy)carbonyl]-3,4-dihydro-2H-1,4-benzothiazine-7-carboxylic acid | C17H15NO4S | 详情 | 详情 | |
| (IX) | 20848 | (2R,6S)-2,6-dimethylpiperazine | C6H14N2 | 详情 | 详情 |