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【结 构 式】 
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【分子编号】17006 【品名】benzyl (2R)-2-(chlorocarbonyl)tetrahydro-1H-pyrrole-1-carboxylate 【CA登记号】 |
【 分 子 式 】C13H14ClNO3 【 分 子 量 】267.7118 【元素组成】C 58.33% H 5.27% Cl 13.24% N 5.23% O 17.93% |
合成路线1
该中间体在本合成路线中的序号：(II)The title compound has been prepared by two related procedures. Treatment of N-carbobenzoxy-D-proline (I) with oxalyl chloride provided the corresponding acid chloride (II). This was condensed with 5-methoxyindolyl magnesium bromide, generated from 5-methoxyindole (III) and ethylmagnesium bromide, to afford the indolyl ketone (IV). Reduction of both keto and carbamate groups of (IV) by means of LiAlH4 in refluxing THF then furnished the target compound.
| 【1】 Schmidt, A.W.; Macor, J.E.; Blake, J.; Ryan, K.; Fox, C.B.; Zorn, S.H.; Morrone, J.M.; Koe, B.K.; Johnson, C.; Schulz, D.W.; Lebel, L.A.; Synthesis and serotonergic pharmacology of the enantiomers of 3-[(N-methylpyrrolidin-2-yl)methyl]-5-methoxy-1H-indole: Discovery of stereogenic differentiation in the aminoethyl side chain of the neurotransmitter serotonin. J Med Chem 1992, 35, 23, 4503. |
| 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) | 25902 | 1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole | 1006-94-6 | C9H9NO | 详情 | 详情 |
| (IV) | 31540 | benzyl (2R)-2-[(5-methoxy-1H-indol-3-yl)carbonyl]-1-pyrrolidinecarboxylate | C22H22N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)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3
该中间体在本合成路线中的序号：(II)
| 【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 |