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【结 构 式】 
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【分子编号】39110 【品名】Sodium 1-ethanethiolate; Sodium ethylmercaptide 【CA登记号】811-51-8 |
【 分 子 式 】C2H5NaS 【 分 子 量 】84.117468 【元素组成】C 28.56% H 5.99% Na 27.33% S 38.12% |
合成路线1
该中间体在本合成路线中的序号：(A)The condensation beta-tetralone (I) with phenyl 4-methoxybenzoate (II) by means of NaNH2 in THF gives 3,4-dihydro-1-(4-methoxybenzoyl)-2(1H)-naphthalenone (III), which is then submitted to a Grignard reaction with 4-methoxyphenylmagnesium bromide (IV) in hot THF yielding 3,4-dihydro-2-(4-methoxyphenyl)-1-naphthyl-4-methoxyphenyl ketone (V). The cleavage of one methoxy group of (V) with sodium ethylmercaptide (A) in dry DMF affords 3,4-dihydro-2-(4-methoxyphenyl)-1-naphthyl-4-hydroxyphenyl ketone (VI), which is finally condensed with N-(2-chloroethyl)pyrrolidine (VII) by means of K2CO3 in refluxing 2-butanone.
| 【1】 Jones, C.D.; et al.; Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxyphenyl]methanone]methane sulfonic acid salt. J Med Chem 1979, 22, 8, 962-966. |
| 【2】 Castaner, J.; Hillier, K.; Trioxifene mesylate. Drugs Fut 1980, 5, 5, 259. |
| 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) | 39106 | 3,4-Dihydro-2(1H)-naphthalenone; beta-Tetralone | 530-93-8 | C10H10O | 详情 | 详情 |
| (II) | 39107 | Phenyl 4-methoxybenzoate | C14H12O3 | 详情 | 详情 | |
| (III) | 39108 | 1-(4-Methoxybenzoyl)-3,4-dihydro-2(1H)-naphthalenone; 3,4-Dihydro-1-(4-methoxybenzoyl)-2(1H)-naphthalenone | C18H16O3 | 详情 | 详情 | |
| (IV) | 37674 | Bromo(4-methoxyphenyl)magnesium; 4-Methoxyphenylmagnesium bromide | 352-13-6 | C7H7BrMgO | 详情 | 详情 |
| (V) | 39109 | (4-Methoxyphenyl)[2-(4-methoxyphenyl)-3,4-dihydro-1-naphthalenyl]methanone; 3,4-Dihydro-2-(4-methoxyphenyl)-1-naphthyl-4-methoxyphenyl ketone | C25H22O3 | 详情 | 详情 | |
| (VI) | 39111 | (4-Hydroxyphenyl)[2-(4-methoxyphenyl)-3,4-dihydro-1-naphthalenyl]methanone; 3,4-Dihydro-2-(4-methoxyphenyl)-1-naphthyl-4-hydroxyphenyl ketone | C24H20O3 | 详情 | 详情 | |
| (VII) | 33922 | 1-(2-Chloroethyl)pyrrolidine; N-(2-Chloroethyl)pyrrolidine | C6H12ClN | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(A)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 N-methylcarbamic acid and CDI yielding the monoester (III). Finally this compound is esterified again at the remaining OH with isobutyric anhydride (IV) and TEA or DMAP affording the target diester. The selective monoesterification of (II) can also be performed with N-methylcarbamic anhydride and TEA or DMAP, with N-methylcarbamoyl chloride and DBU, or with N-methylisocyanate and K2CO3.
| 【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) | 41230 | (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 methylcarbamate | C18H22N2O4 | 详情 | 详情 | |
| (IV) | 22334 | 1-methylpropionic anhydride | 97-72-3 | C8H14O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(A)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 |