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【结 构 式】 
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【药物名称】A-70826 【化学名称】(±)-1-(2,4-Difluorophenyl)-6-fluoro-7-[3-(L-norvalyl-L-norvalylamino)pyrrolidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid hydrochloride 【CA登记号】129670-72-0 (free base;non-specified stereoch.), 129671-30-3 (undefined stereoch.) 【 分 子 式 】C29H34ClF3N6O5 【 分 子 量 】639.07973 |
【开发单位】Abbott (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Naphthyridines |
合成路线1
Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II). Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III). Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV). Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI). Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.
| 【1】 Chu, D.T.W.; A-70826. Drugs Fut 1992, 17, 3, 179. |
| 【2】 Chu, D.T.W.; Pernet, A.G.; Plattner, J.J.; Hallas, R.; Shipkowitz, N.; Marsh, K.C.; Synthesis and biological properties of A-70826: A prodrug of tosufloxacin. 31st Intersci Conf Antimicrob Agents Chemother (Sept 29-Oct 2, Chicago) 1991, Abst 1440. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 19462 | 2,4-difluoroaniline; 2,4-difluorophenylamine；2,4-Difluoro-benzenamine;1-Amino-2,4-difluorobenzene | 367-25-9 | C6H5F2N | 详情 | 详情 | |
| (I) | 15228 | ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxopropanoate | C10H8Cl2FNO3 | 详情 | 详情 | |
| (II) | 15229 | ethyl (Z)-2-[(2,6-dichloro-5-fluoro-3-pyridinyl)carbonyl]-3-(2,4-difluoroanilino)-2-propenoate | C17H11Cl2F3N2O3 | 详情 | 详情 | |
| (III) | 15230 | ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate | C17H10ClF3N2O3 | 详情 | 详情 | |
| (IV) | 15231 | 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid | C15H6ClF3N2O3 | 详情 | 详情 | |
| (V) | 15232 | tert-butyl N-[(1S)-1-[([(1S)-1-[(tetrahydro-1H-pyrrol-3-ylamino)carbonyl]butyl]amino)carbonyl]butyl]carbamate | C19H36N4O4 | 详情 | 详情 | |
| (VI) | 15233 | 7-(3-[[(2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]pentanoyl]amino)pentanoyl]amino]-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid | C34H41F3N6O7 | 详情 | 详情 |