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【结 构 式】 
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【药物名称】 【化学名称】6-O-Demethyl-3-O-(isopropoxycarbonyl)-6-O-(pivaloyl)galanthamine hydrochloride 【CA登记号】 【 分 子 式 】C25H34ClNO6 【 分 子 量 】480.00583 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Acetylcholinesterase Inhibitors |
合成路线1
The demethylation of galanthamine (I) with ethyl mercaptane sodium salt in hot DMF gives 6-demethylgalanthamine (II), which is selectively monoesterified at the phenolic OH with pivalic acid and CDI yielding the monoester (III). Finally this compound is esterified again at the remaining OH with isopropyl dicarbonate (IV) and TEA or DMAP affording the target diester. The selective monoesterification of (II) can also be performed with pivalic anhydride and TEA or DMAP, or with pivaloyl chloride and DBU.
| 【1】 Bores, G.M.; Kosley, R.W. Jr.; Galanthamine derivatives for the treatment of Alzeimer's disease. Drugs Fut 1996, 21, 6, 621. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 39110 | Sodium 1-ethanethiolate; Sodium ethylmercaptide | 811-51-8 | C2H5NaS | 详情 | 详情 |
| (I) | 41226 | (4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol | 357-70-0 | C17H21NO3 | 详情 | 详情 |
| (II) | 41227 | (4aS,6R,8aS)-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepine-3,6-diol | C16H19NO3 | 详情 | 详情 | |
| (III) | 41228 | (4aS,6R,8aS)-6-hydroxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-3-yl pivalate | C21H27NO4 | 详情 | 详情 | |
| (IV) | 41229 | C8H14O5 | 详情 | 详情 |