反应详情

温度

60 °C

To a stirred suspension of 7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid (100 mg, 0.22 mmol) in 10 ml of anhydrous tetrahydrofuran were added HATU (100 mg, 0.26 mmol) and N,N-diisopropylethylamine (85 mg, 0.66 mmol). The mixture was heated at 60° C. for 10 minutes, followed by addition of L-glutamic acid dimethyl ester hydrochloride (55 mg, 0.26 mmol). The mixture was heated at 60° C. for another 20 minutes, cooled to room temperature and poured into 100 ml of water with vigorous stirring. 1M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give dimethyl (2S)-2-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]pentanedioate as white solid. Yield: 126 mg, 94%.

1. temperatureThe mixture was heated at 60° C. for another 20 minutes
2. temperaturecooled to room temperature
3. filtrationThe precipitates were filtered
4. washwashed with water
5. customdried in vacuo