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【结 构 式】 
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【分子编号】44716 【品名】5-chloro-6-(4-methyl-1-piperazinyl)indoline 【CA登记号】 |
【 分 子 式 】C13H18ClN3 【 分 子 量 】251.75884 【元素组成】C 62.02% H 7.21% Cl 14.08% N 16.69% |
合成路线1
该中间体在本合成路线中的序号：(XII)Catalytic hydrogenation of 1-acetyl-6-nitroindoline (V) afforded amine (VI). Condensation of (VI) with mechlorethamine hydrochloride (VIII) in the presence of K2CO3 in refluxing n-butanol produced piperazinylindoline (X). Alternatively, intermediate (X) was obtained by Sandmeyer reaction of amine (VI) in the presence of CuBr, followed by condensation of the resulting bromide (VII) with N-methylpiperazine (IX). Chlorination of (X) with N-chlorosuccinimide provided (XI). The acetamide function of (XI) was then hydrolyzed in refluxing 2M HCl to give amine (XII). Finally, coupling of (XII) with isocyanate (IV) gave rise to the corresponding urea.
| 【1】 Evans, M.; Gaster, L.M.; Gordon, l.; et al.; Mixed 5-HT1A/1B/1D receptor antagonists as novel antidepressants. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PB-77. |
| 【2】 Gaster, L.M.; Rami, H.K.; Wyman, P.A. (SmithKline Beecham plc); Indole derivs. having combined 5HT1A, 5HT1B and 5HT1D receptor antagonist activity. EP 0975593; WO 9850358 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 44709 | 4-(4-pyridinyl)-1-naphthyl isocyanate; 4-(4-isocyanato-1-naphthyl)pyridine | C16H10N2O | 详情 | 详情 | |
| (V) | 44710 | 1-(6-nitro-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C10H10N2O3 | 详情 | 详情 | |
| (VI) | 44711 | 1-(6-amino-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C10H12N2O | 详情 | 详情 | |
| (VII) | 44712 | 1-(6-bromo-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C10H10BrNO | 详情 | 详情 | |
| (VIII) | 44713 | 2-chloro-N-(2-chloroethyl)-N-methyl-1-ethanamine; N,N-bis(2-chloroethyl)-N-methylamine | C5H11Cl2N | 详情 | 详情 | |
| (IX) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (X) | 44714 | 1-[6-(4-methyl-1-piperazinyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone | C15H21N3O | 详情 | 详情 | |
| (XI) | 44715 | 1-[5-chloro-6-(4-methyl-1-piperazinyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone | C15H20ClN3O | 详情 | 详情 | |
| (XII) | 44716 | 5-chloro-6-(4-methyl-1-piperazinyl)indoline | C13H18ClN3 | 详情 | 详情 |