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【结 构 式】 
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【分子编号】34573 【品名】benzyl 1-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C19H17NO4 【 分 子 量 】323.34832 【元素组成】C 70.58% H 5.3% N 4.33% O 19.79% |
合成路线1
该中间体在本合成路线中的序号：(IV)The esterification of indole-2-carboxylic acid (I) with benzyl alcohol and CDI gives the corresponding benzyl ester (II), which is alkylated with methyl bromoacetate (III) by means of NaH in DMF yielding 1-(methoxycarbonylmethyl)-1H-indole-2-carboxylic acid benzyl ester (IV). The debenzylation of (IV) with H2 over Pd/C in ethanol/DMF affords the free acid (V), which is condensed with 4-(2-chlorophenyl)thiazol-2-amine (VI) by means of benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) in DMF to give the carboxamide (VII). Finally, the ester group of (VII) is hydrolyzed with NaOH or KOH in methanol/water.
| 【1】 Bras, J.-P.; Frehel, D.; Gully, D.; Valette, G. (Sanofi-Synthélabo ); Heterocyclic derivs. of acylaminothiazole, their preparation and pharmaceutical compsns. containing them. EP 0432040; FR 2655344; FR 2661677; JP 1991279374; JP 1998130147; US 5189049 . |
| 【2】 Radisson, J. (Sanofi-Synthelabo ); Method for preparing lintitript potassium salt. FR 2781227; WO 0005233 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 | |
| (I) | 25226 | 1H-Indole-2-carboxylic acid; Indole-2-carboxylic acid | 1477-50-5 | C9H7NO2 | 详情 | 详情 |
| (II) | 34572 | benzyl 1H-indole-2-carboxylate | C16H13NO2 | 详情 | 详情 | |
| (III) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
| (IV) | 34573 | benzyl 1-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylate | C19H17NO4 | 详情 | 详情 | |
| (V) | 34574 | 1-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylic acid | C12H11NO4 | 详情 | 详情 | |
| (VI) | 34575 | 4-(2-chlorophenyl)-1,3-thiazol-2-ylamine; 4-(2-chlorophenyl)-1,3-thiazol-2-amine | C9H7ClN2S | 详情 | 详情 | |
| (VII) | 34576 | methyl 2-[2-([[4-(2-chlorophenyl)-1,3-thiazol-2-yl]amino]carbonyl)-1H-indol-1-yl]acetate | C21H16ClN3O3S | 详情 | 详情 | |
| (VIII) | 34577 | 2-bromo-1-(2-chlorophenyl)-1-ethanone | C8H6BrClO | 详情 | 详情 | |
| (IX) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |