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【结 构 式】 
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【药物名称】Lintitript, SR-27897 【化学名称】1-(Carboxymethyl)-N-[4-(2-chlorophenyl)thiazol-2-yl]indole-2-carboxamide 【CA登记号】136381-85-6 【 分 子 式 】C20H14ClN3O3S 【 分 子 量 】411.86988 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】METABOLIC DRUGS, Oncolytic Drugs, Pancreatic Cancer Therapy, Treatment of Eating Disorders, Treatment of Nutritional Disorders, CCK1 (CCKA) Antagonists |
合成路线1
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 |