【结 构 式】 |
【分子编号】32150 【品名】ethyl 4,6-dichloro-3-[(E)-3-oxo-3-(2-pyridinylsulfanyl)-1-propenyl]-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C19H14Cl2N2O3S 【 分 子 量 】421.30324 【元素组成】C 54.17% H 3.35% Cl 16.83% N 6.65% O 11.39% S 7.61% |
合成路线1
该中间体在本合成路线中的序号:(XIII)The precursor ethyl ester (X) was also prepared from the unprotected indole carboxylic acid (XII). Conversion into amide (XIV) was carried out using activation of the carboxyl group via formation of the corresponding 2-pyridyl thioester (XIII) and then coupling with aniline (VI). Trifluoroacetic acid-promoted cleavage of the N-Boc group of (XIV) provided amine (XV). This was converted to urea (X) by means of trimethylsilyl isocyanate.
【1】 Provera, S.; Rovatti, L.; Sabbatini, F.M.; Reggiani, A.; Di Fabio, R.; De Magistris, M.; Conti, N.; Barnaby, R.J.; Feriani, A.; Substituted analogues of GV150526 as potent glycine binding site antagonists in animal models of cerebral ischemia. J Med Chem 1999, 42, 18, 3486. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 35549 | tert-butyl 4-aminobenzylcarbamate | C12H18N2O2 | 详情 | 详情 | |
(X) | 35553 | ethyl 3-[(E)-3-(4-[[(aminocarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C22H20Cl2N4O4 | 详情 | 详情 | |
(XII) | 32149 | (E)-3-[4,6-dichloro-2-(ethoxycarbonyl)-1H-indol-3-yl]-2-propenoic acid | C14H11Cl2NO4 | 详情 | 详情 | |
(XIII) | 32150 | ethyl 4,6-dichloro-3-[(E)-3-oxo-3-(2-pyridinylsulfanyl)-1-propenyl]-1H-indole-2-carboxylate | C19H14Cl2N2O3S | 详情 | 详情 | |
(XIV) | 35554 | ethyl 3-[(E)-3-(4-[[(tert-butoxycarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C26H27Cl2N3O5 | 详情 | 详情 | |
(XV) | 35555 | ethyl 3-[(E)-3-[4-(aminomethyl)anilino]-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C21H19Cl2N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XIII)In a more direct route, 4-aminobenzyl amine (V) was treated with trimethylsilyl isocyanate to yield amino urea (XVI). This was subsequently coupled with pyridyl thioester (XIII) to furnish the previously described intermediate (X).
【1】 Conti, N.; Di Fabio, R.; De Magistris, E.; Feriani, A. (Glaxo Wellcome plc); Indole derivs. as EAA antagonists. EP 0813524; JP 1999501041; US 5919811; WO 9627588 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(V) | 35548 | 4-(aminomethyl)aniline; 4-aminobenzylamine | 4403-71-8 | C7H10N2 | 详情 | 详情 |
(X) | 35553 | ethyl 3-[(E)-3-(4-[[(aminocarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C22H20Cl2N4O4 | 详情 | 详情 | |
(XIII) | 32150 | ethyl 4,6-dichloro-3-[(E)-3-oxo-3-(2-pyridinylsulfanyl)-1-propenyl]-1H-indole-2-carboxylate | C19H14Cl2N2O3S | 详情 | 详情 | |
(XVI) | 35556 | N-(4-aminobenzyl)urea | C8H11N3O | 详情 | 详情 |