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【结 构 式】 
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【分子编号】61102 【品名】3-(6-fluoro-2-methyl-1H-indol-3-yl)-1-{4-hydroxy-4-[3-(trifluoromethyl)phenyl]-1-piperidinyl}-1-propanone 【CA登记号】 |
【 分 子 式 】C24H24F4N2O2 【 分 子 量 】448.4604528 【元素组成】C 64.28% H 5.39% F 16.95% N 6.25% O 7.14% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of 6-fluoro-2-methylindole (I) with beta-chloropropionitrile (II) by means of ethylmagnesium iodide (that forms the magnesium salt of (I)) in refluxing ether gives 3-(6-fluoro-2-methyl-3-indolyl)propionitrite (III), which is hydrolyzed with KOH in refluxing water yielding 3-(6-fluoro-2-methyl-3-indolyl)propionic acid (IV) (1). The condensation of (IV) with 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (V) by means of ethyl chloroformate and triethylamine in refluxing THF affords 1-[3-(6-fluoro-2-methyl-3-indolyl)propionyl]-4-hydroxy-4-(3-trifluromethylphenyl)piperidine (VI), which is reduced with LiAlH4 in refluxing THF giving 1-[3-(6-fluoro-2-methyl-3-indolyl)propyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (VII). The ozonolysis of (VII) in HOAc affords 1-[3-(2-acetamido-4-fluorobenzoyl)propyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (VIII), which is finally hydrolyzed with concentrated HCl in refluxing EtOH
| 【1】 (Sumitomo Chemical Co., Ltd.); FR 2196153 . |
| 【2】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); DE 2065311; JP 754670; JP 754671 . |
| 【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Owen, R.T.; ID - 4708. Drugs Fut 1979, 4, 7, 492. |
| 【4】 Honma, T.; et al.; The XIAP antisense compound AEG35156/GEM640 demonstrates significant antitumor activity in multiple human cancer xenograft models. Arzneim-Forsch 1974, 24, 9, 1248. |
| 【5】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); 3-Hetero-substd.-N-benzyl-indoles. US 3907812 . |
| 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) | 61098 | 6-fluoro-2-methyl-1H-indole | C9H8FN | 详情 | 详情 | |
| (II) | 30744 | 3-chloropropanenitrile | 542-76-7 | C3H4ClN | 详情 | 详情 |
| (III) | 61099 | 3-(6-fluoro-2-methyl-1H-indol-3-yl)propanenitrile | C12H11FN2 | 详情 | 详情 | |
| (IV) | 61100 | 3-(6-fluoro-2-methyl-1H-indol-3-yl)propanoic acid | C12H12FNO2 | 详情 | 详情 | |
| (V) | 61101 | 4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C12H14F3NO | 详情 | 详情 | |
| (VI) | 61102 | 3-(6-fluoro-2-methyl-1H-indol-3-yl)-1-{4-hydroxy-4-[3-(trifluoromethyl)phenyl]-1-piperidinyl}-1-propanone | C24H24F4N2O2 | 详情 | 详情 | |
| (VII) | 61103 | 1-[3-(6-fluoro-2-methyl-1H-indol-3-yl)propyl]-4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C24H26F4N2O | 详情 | 详情 | |
| (VIII) | 61104 | N-[5-fluoro-2-(4-{4-hydroxy-4-[3-(trifluoromethyl)phenyl]-1-piperidinyl}butanoyl)phenyl]acetamide | C24H26F4N2O3 | 详情 | 详情 |