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【结 构 式】 
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【药物名称】 【化学名称】9-Cyclopropyl-6,8-difluoro-7-piperazino-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-dione methanesulfonate 【CA登记号】 【 分 子 式 】C18H20F2N4O5S2 【 分 子 量 】474.5087 |
【开发单位】Abbott (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA Topoisomerase II Inhibitors |
合成路线1
The cyclization of 2-(2,4-dichloro-3,5-difluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-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 isothiazoloquinoline (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) | 43200 | ethyl 3-(2,4-dichloro-3,5-difluorophenyl)-3-oxopropanoate | C11H8Cl2F2O3 | 详情 | 详情 | |
| (II) | 43201 | 1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene | C10H10ClNS | 详情 | 详情 | |
| (III) | 43202 | ethyl 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-3-quinolinecarboxylate | C21H16ClF2NO3S | 详情 | 详情 | |
| (IV) | 43203 | ethyl 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfinyl)-1,4-dihydro-3-quinolinecarboxylate | C21H16ClF2NO4S | 详情 | 详情 | |
| (V) | 43204 | 7-chloro-9-cyclopropyl-6,8-difluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione | C13H7ClF2N2O2S | 详情 | 详情 | |
| (VI) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |