【结 构 式】 |
【药物名称】 【化学名称】4,6-Dichloro-3-(2,4-dioxo-3-phenylimidazolidin-1-ylmethyl)-1H-indole-2-carboxylic acid 【CA登记号】 【 分 子 式 】C19H13Cl2N3O4 【 分 子 量 】418.23916 |
【开发单位】Johannes Gutenberg-Universität Mainz (Originator) 【药理作用】Antiepileptic Drugs, NEUROLOGIC DRUGS, Drugs Acting on Glutamate Receptors (Ionotropic) |
合成路线1
Diazotization of 3,5-dichloroaniline (I), followed by reduction of the resultant diazonium salt provides hydrazine (II). Subsequent reaction of 3,5-dichlorophenylhydrazine (II) with ethyl pyruvate (III) under Fischer reaction conditions gives rise to indole (IV). Vilsmeier formylation of (IV) using N-methylformanilide and phosphoryl chloride produces aldehyde (V). This is reductively aminated with methyl glycinate and NaBH(OAc)3 to afford aminoester (VI). Condensation of (VI) with phenyl isocyanate, followed by cyclization in the presence of Et3N leads to hydantoin (VII). Finally, ester (VII) is hydrolyzed employing LiOH to furnish the target indolecarboxylic acid.
【1】 Jansen, M.; Potschka, H.; Brandt, C.; Loscher, W.; Dannhardt, G.; Hydantoin-substituted 4,6-dichloroindole-2-carboxylic acids as ligands with high affinity for the glycine binding site of the NMDA receptor. J Med Chem 2003, 46, 1, 64. |
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) | 26542 | 3,5-dichloroaniline | 626-43-7 | C6H5Cl2N | 详情 | 详情 |
(II) | 28066 | 1-(3,5-dichlorophenyl)hydrazine | 39943-56-1 | C6H6Cl2N2 | 详情 | 详情 |
(III) | 12135 | ethyl 2-oxopropanoate; Ethyl pyruvate | 617-35-6 | C5H8O3 | 详情 | 详情 |
(IV) | 32142 | ethyl 4,6-dichloro-1H-indole-2-carboxylate | C11H9Cl2NO2 | 详情 | 详情 | |
(V) | 32144 | ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate | C12H9Cl2NO3 | 详情 | 详情 | |
(VI) | 64389 | ethyl 4,6-dichloro-3-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1H-indole-2-carboxylate | C15H16Cl2N2O4 | 详情 | 详情 | |
(VII) | 64390 | ethyl 4,6-dichloro-3-[(2,4-dioxo-3-phenyl-1-imidazolidinyl)methyl]-1H-indole-2-carboxylate | C21H17Cl2N3O4 | 详情 | 详情 |