|
【结 构 式】 
|
【药物名称】 【化学名称】9-Cyclopropyl-6-fluoro-7-(1-piperazinyl)isothiazolo[5,4-b][1,8]naphthyridine-3(2H),4(9H)-dione 【CA登记号】 【 分 子 式 】C16H16FN5O2S 【 分 子 量 】361.40062 |
【开发单位】Abbott (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Naphthyridines |
合成路线1
The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V), which is finally condensed with piperazine in pyridine to furnish the target compound.
| 【1】 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317. |
| 【2】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101. |
| 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) | 15228 | ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxopropanoate | C10H8Cl2FNO3 | 详情 | 详情 | |
| (II) | 43201 | 1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene | C10H10ClNS | 详情 | 详情 | |
| (III) | 43205 | ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro[1,8]naphthyridine-3-carboxylate | C20H16ClFN2O3S | 详情 | 详情 | |
| (IV) | 42306 | methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate | C21H25N3O2 | 详情 | 详情 | |
| (V) | 43027 | tert-butyl (1S)-1-isobutyl-3-methyl-2-oxo-3-butenylcarbamate | C14H25NO3 | 详情 | 详情 | |
| (VI) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |