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【结 构 式】 
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【分子编号】17011 【品名】(E)-2-(3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indol-5-yl)ethenyl phenyl sulfone; 3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-5-[(E)-2-(phenylsulfonyl)ethenyl]-1H-indole 【CA登记号】180637-89-2 |
【 分 子 式 】C22H24N2O2S 【 分 子 量 】380.51084 【元素组成】C 69.44% H 6.36% N 7.36% O 8.41% S 8.43% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of N-(benzyloxycarbonyl)-D-proline (I) with oxalyl chloride in dichloromethane/DMF gives the corresponding acyl chloride (II), which is condensed with 5-bromoindole (III) by means of ethylmagnesium bromide in ether yielding 3-(N-benzyloxycarbonyl-D-prolyl)-5-bromoindole (IV). The reduction of the carbonyl group of (IV) with LiAlH4 in THF affords 5-bromo-3-[1-methylpyrrolidin-2(R)-ylmethyl]indole (V), which is condensed with phenyl(vinyl)sulfone (VI) by means of tri-p-tolylphosphine, palladium acetate and triethylamine in refluxing acetonitrile giving the substituted (E)-vinyl sulfone (VII). Finally, this compound is hydrogenated with H2 over Pd/C in ethanol/HCl.
| 【1】 Ngo, J.; Rabasseda, X.; Castañer, J.; Eletriptan. Drugs Fut 1997, 22, 3, 221. |
| 【2】 Harding, V.D.; Macrae, R.J.; Ogilvie, R.J. (Pfizer Inc.); Salts of an anti-migraine indole deriv. EP 0776323; JP 1997512283; US 6110940; WO 9606842 . |
| 【3】 Macor, J.E.; Wythes, M.J. (Pfizer Inc.); Indole derivs. EP 0592438; JP 1993507288; JP 1997003063; US 5545644; WO 9206973 . |
| 【4】 Perkins, J.F. (Pfizer Inc.); Process for the preparation of 3-acyl-indoles. EP 1088817 . |
| 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) | 17005 | (2R)-1-[(benzyloxy)carbonyl]tetrahydro-1H-pyrrole-2-carboxylic acid | C13H15NO4 | 详情 | 详情 | |
| (II) | 17006 | benzyl (2R)-2-(chlorocarbonyl)tetrahydro-1H-pyrrole-1-carboxylate | C13H14ClNO3 | 详情 | 详情 | |
| (III) | 13309 | 5-Bromo-1H-indole; 5-Bromoindole | 10075-50-0 | C8H6BrN | 详情 | 详情 |
| (IV) | 17008 | benzyl (2R)-2-[(5-bromo-1H-indol-3-yl)carbonyl]tetrahydro-1H-pyrrole-1-carboxylate | C21H19BrN2O3 | 详情 | 详情 | |
| (V) | 17009 | 5-bromo-3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indole | C14H17BrN2 | 详情 | 详情 | |
| (VI) | 17010 | phenyl vinyl sulfone; dioxo(phenyl)vinyl-lambda(6)-sulfane; Benzene, (ethenylsulfonyl)- | 5535-48-8 | C8H8O2S | 详情 | 详情 |
| (VII) | 17011 | (E)-2-(3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indol-5-yl)ethenyl phenyl sulfone; 3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-5-[(E)-2-(phenylsulfonyl)ethenyl]-1H-indole | 180637-89-2 | C22H24N2O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)
| 【1】 Macor JE, Wythes MJ.1992.Preparation of 3-(heterocyclylmethyl) indoles as drugs W0 9206973 |
| 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) | 13309 | 5-Bromo-1H-indole; 5-Bromoindole | 10075-50-0 | C8H6BrN | 详情 | 详情 |
| (II) | 17006 | benzyl (2R)-2-(chlorocarbonyl)tetrahydro-1H-pyrrole-1-carboxylate | C13H14ClNO3 | 详情 | 详情 | |
| (III) | 17008 | benzyl (2R)-2-[(5-bromo-1H-indol-3-yl)carbonyl]tetrahydro-1H-pyrrole-1-carboxylate | C21H19BrN2O3 | 详情 | 详情 | |
| (IV) | 17009 | 5-bromo-3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indole | C14H17BrN2 | 详情 | 详情 | |
| (V) | 17011 | (E)-2-(3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indol-5-yl)ethenyl phenyl sulfone; 3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-5-[(E)-2-(phenylsulfonyl)ethenyl]-1H-indole | 180637-89-2 | C22H24N2O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)
| 【1】 Furlong PJ,Kelly CJ,el d.2005. Preparation of α-polymotphic eletriptan hydrobromide.US 2005020663 |
| 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) | 66299 | (R,E)-1-(3-((1-methylpyrrolidin-2-yl)methyl)-5-(2-(phenylsulfonyl)vinyl)-1H-indol-1-yl)ethanone | C24H26N2O3S | 详情 | 详情 | |
| (II) | 17011 | (E)-2-(3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-1H-indol-5-yl)ethenyl phenyl sulfone; 3-[[(2R)-1-methyltetrahydro-1H-pyrrol-2-yl]methyl]-5-[(E)-2-(phenylsulfonyl)ethenyl]-1H-indole | 180637-89-2 | C22H24N2O2S | 详情 | 详情 |