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【结 构 式】 
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【分子编号】32478 【品名】ethyl 3-(2-aminoethyl)-5-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C20H26N4O4 【 分 子 量 】386.451 【元素组成】C 62.16% H 6.78% N 14.5% O 16.56% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of 2-(4-nitrophenyl)ethanol (I) with 5,5-dimethylimidazolidine-2,4-dione (II) by means of PPh3 and DIAD in THF gives 5,5-dimethyl-3-[2-(4-nitrophenyl)ethyl]imidazolidine-2,4-dione (III), which is reduced with H2 over Pd/C in ethanol yielding the 4-aminophenyl derivative (IV). The condensation of (IV) with 2-(3-chloropropyl)malonic acid diethyl ester (V) by means of NaNO2 and NaOAc in water affords the hydrazone (VI), which is isomerized and cyclized in refluxing butanol giving the indolecarboxylic ester (VII). The methylation of the free amino group of (VII) with formaldehyde and NaCNBH3 yields the dimethylamino derivative (VIII), which is transesterified with benzyl alcohol and titanium tetraisopropoxide affording the benzyl ester (IX). The debenzylation of (IX) with H2 over Pd/C gives the free acid (X), which is finally converted into the target amide with benzylamine, TBTU and DIPEA in DMF.
| 【1】 Robertson, A.D.; Dodsworth, S.; Sang, P.Y.; Glen, R.; Moloney, G.P.; Mathews, N.; Martin, G.R.; MacLennan, S.; Knight, C.; A novel series of 2,5-substituted tryptamine derivatives as vascular 5HT(1B/1D) receptor antagonists. J Med Chem 1997, 40, 15, 2347-62. |
| 【2】 Mathews, N.; Martin, G.R.; Moloney, G.P.; et al.; Synthesis and serotonergic activity of substituted 2,N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives: Novel antagonists for the vascular 5-HT1B-like receptor. J Med Chem 1999, 42, 14, 2504. |
| 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) | 32472 | 2-(4-nitrophenyl)-1-ethanol | 100-27-6 | C8H9NO3 | 详情 | 详情 |
| (II) | 32473 | 5,5-dimethyl-2,4-imidazolidinedione | 77-71-4 | C5H8N2O2 | 详情 | 详情 |
| (III) | 32474 | 5,5-dimethyl-3-(4-nitrophenethyl)-2,4-imidazolidinedione | C13H15N3O4 | 详情 | 详情 | |
| (IV) | 32475 | 3-(4-aminophenethyl)-5,5-dimethyl-2,4-imidazolidinedione | C13H17N3O2 | 详情 | 详情 | |
| (V) | 32476 | diethyl 2-(3-chloropropyl)malonate | 18719-43-2 | C10H17ClO4 | 详情 | 详情 |
| (VI) | 32477 | ethyl 5-chloro-2-((Z)-2-[4-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]phenyl]hydrazono)pentanoate | C20H27ClN4O4 | 详情 | 详情 | |
| (VII) | 32478 | ethyl 3-(2-aminoethyl)-5-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate | C20H26N4O4 | 详情 | 详情 | |
| (VIII) | 32479 | ethyl 3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate | C22H30N4O4 | 详情 | 详情 | |
| (IX) | 32480 | benzyl 3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate | C27H32N4O4 | 详情 | 详情 | |
| (X) | 32481 | 3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylic acid | C20H26N4O4 | 详情 | 详情 |