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【结 构 式】 
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【药物名称】Sercloremine hydrochloride, CGP-4718A 【化学名称】4,5-(Chloro-2-benzofuranyl)-1-methylpiperidine hydrochloride 【CA登记号】54403-20-2, 54403-19-9 (free base) 【 分 子 式 】C14H17Cl2NO 【 分 子 量 】286.20369 |
【开发单位】Novartis (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
The condensation of 5-chlorosalicyialdehyde (I) with 4-chloromethylpyridine (II) by means of K2CO3 / KI in hot DMF gives 5-chloro-2-[(4-pyridyl)methoxy]benzaldehyde (III), which is cyclized by heating at 300 C to afford 5-chloro-2-(4-pyridyl)benzofurane (IV). Quaternization of (IV) with methyl iodide in hot methanol yields 1-methyl-4-(5-chloro-2-benzofuranyl)pyridinium iodide (V), which is hydrogenated with NaBH4 in methanol giving 5-chloro-2-(1-methyl-1,2,3,6-tetrahydro-4-pyridyl)benzofurane (VI). Finally, this compound is hydrogenated further with H2 over PtO2 in methanol.
| 【1】 Bernasconi, R.; Schenker, K. (Novartis Corp.); Anti-depressant benzofuranyl piperidines. CH 592656; CH 605926; DE 2408476; FR 2219781; JP 49117474; JP 58004781; US 210655 . |
| 【2】 Castaner, J.; Serradell, M.N.; Sercloremine Hydrochloride. Drugs Fut 1986, 11, 2, 126. |
| 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) | 26408 | 5-chlorosalicylaldehyde; 5-chloro-2-hydroxybenzaldehyde | 635-93-8 | C7H5ClO2 | 详情 | 详情 |
| (II) | 10844 | 4-(Chloromethyl)pyridine | 10445-91-7 | C6H6ClN | 详情 | 详情 |
| (III) | 28844 | 5-chloro-2-(4-pyridinylmethoxy)benzaldehyde | C13H10ClNO2 | 详情 | 详情 | |
| (IV) | 28845 | 4-(5-chloro-1-benzofuran-2-yl)pyridine | C13H8ClNO | 详情 | 详情 | |
| (V) | 28846 | 4-(5-chloro-1-benzofuran-2-yl)-1-methylpyridinium iodide | C14H11ClINO | 详情 | 详情 | |
| (VI) | 28847 | 4-(5-chloro-1-benzofuran-2-yl)-1-methyl-1,2,3,6-tetrahydropyridine | C14H14ClNO | 详情 | 详情 |