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【结 构 式】 
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【分子编号】56737 【品名】3-[3-amino-1-(2-fluorophenyl)-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl]propanenitrile 【CA登记号】 |
【 分 子 式 】C18H16FN3O2 【 分 子 量 】325.3424632 【元素组成】C 66.45% H 4.96% F 5.84% N 12.92% O 9.84% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 3-amino-1-(2-fluorophenyl)-6-methoxyindolin-2-one (I) with acrylonitrile (II) by means of K2CO3 in DMSO gives the propionitrile derivative (III), which was submitted to optical resolution with (+)-dibenzoyl tartaric acid to yield enantiomer (IV). The condensation of (IV) with isoquinoline-3-carboxylic acid (V) by means of DEC and HOBt in DMF affords the carboxamide (VI), which is treated with HCl in methanol to provide the propionic ester (VII). Finally, this compound is hydrolyzed with NaOH in methanol/water to furnish the target sodium propionate derivative as a pure enantiomer.
| 【1】 Yamada, K.; Hikota, M.; Shikano, T.; Nagasaki, M. (Tanabe Seiyaku Co., Ltd.); 2-Oxoindoline deriv.. EP 0731091; US 5807883; WO 9514668 . |
| 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) | 52869 | 3-amino-1-(2-fluorophenyl)-6-methoxy-1,3-dihydro-2H-indol-2-one | C15H13FN2O2 | 详情 | 详情 | |
| (II) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (III) | 56737 | 3-[3-amino-1-(2-fluorophenyl)-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl]propanenitrile | C18H16FN3O2 | 详情 | 详情 | |
| (IV) | 56738 | 3-[(3S)-3-amino-1-(2-fluorophenyl)-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl]propanenitrile | C18H16FN3O2 | 详情 | 详情 | |
| (V) | 56739 | 3-isoquinolinecarboxylic acid | 203626-75-9 | C10H7NO2 | 详情 | 详情 |
| (VI) | 56740 | N-[(3S)-3-(2-cyanoethyl)-1-(2-fluorophenyl)-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl]-3-isoquinolinecarboxamide | C28H21FN4O3 | 详情 | 详情 | |
| (VII) | 56741 | methyl 3-{(3S)-1-(2-fluorophenyl)-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl}propanoate | C29H24FN3O5 | 详情 | 详情 |