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【结 构 式】 
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【分子编号】32931 【品名】4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-amine; 4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-ylamine 【CA登记号】 |
【 分 子 式 】C19H25ClN2O2S 【 分 子 量 】380.93848 【元素组成】C 59.91% H 6.61% Cl 9.31% N 7.35% O 8.4% S 8.42% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)4-Cyclohexylbutyric acid (XVIII) was converted to the corresponding acid chloride (XIX) with SOCl2. Subsequent Friedel-Crafts condensation with 2,5-dimethoxychlorobenzene (XX) yielded ketone (XXI). After bromination of (XXI) in CH2Cl2, the resulting bromoketone (XXII) was condensed with thiourea (XXIII), providing aminothiazole (XXIV). This amine was coupled with indole acid (XV) by means of BOP to give amide (XXV). The title compound was then obtained by deprotection of the tert-butyl ester with trifluoroacetic acid. In a related alternative procedure, coupling of aminothiazole (XXIV) with indole acid (XVII) gave amide (XXVI). The methyl ester was then deprotected by hydrolysis with K2CO3 in aqueous butanol.
| 【1】 Brodin, R.; Boigegrain, R.; Molimard, J.-C.; Bignon, E.; Olliero, D. (Sanofi-Synthelabo ); Carboxamidothiazole derivs., preparation, pharmaceutical compsns. containing them. EP 1017693; FR 2768737; FR 2777887; WO 9915525 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 32923 | 1-[2-(tert-butoxy)-2-oxoethyl]-5,7-dimethyl-1H-indole-2-carboxylic acid | C17H21NO4 | 详情 | 详情 | |
| (XVII) | 32925 | 1-(2-methoxy-2-oxoethyl)-5,7-dimethyl-1H-indole-2-carboxylic acid | C14H15NO4 | 详情 | 详情 | |
| (XVIII) | 32926 | 4-cyclohexylbutyric acid | 4441-63-8 | C10H18O2 | 详情 | 详情 |
| (XIX) | 32927 | 4-cyclohexylbutanoyl chloride | C10H17ClO | 详情 | 详情 | |
| (XX) | 32928 | 2-chloro-1,4-dimethoxybenzene; 2-chloro-4-methoxyphenyl methyl ether | 2100-42-7 | C8H9ClO2 | 详情 | 详情 |
| (XXI) | 32929 | 1-(4-chloro-2,5-dimethoxyphenyl)-4-cyclohexyl-1-butanone | C18H25ClO3 | 详情 | 详情 | |
| (XXII) | 32930 | 2-bromo-1-(4-chloro-2,5-dimethoxyphenyl)-4-cyclohexyl-1-butanone | C18H24BrClO3 | 详情 | 详情 | |
| (XXIII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (XXIV) | 32931 | 4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-amine; 4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-ylamine | C19H25ClN2O2S | 详情 | 详情 | |
| (XXV) | 32932 | tert-butyl 2-[2-([[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]amino]carbonyl)-5,7-dimethyl-1H-indol-1-yl]acetate | C36H44ClN3O5S | 详情 | 详情 | |
| (XXVI) | 32933 | methyl 2-[2-([[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]amino]carbonyl)-5,7-dimethyl-1H-indol-1-yl]acetate | C33H38ClN3O5S | 详情 | 详情 |