反应详情

To a stirred solution of 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylic acid (60 mg, 0.13 mmol) in 10 ml of anhydrous DMF were added HATU (61 mg, 0.16 mmol) and N,N-diisopropylethylamine (52 mg, 0.40 mmol). The mixture was stirred at room temperature for 10 minutes, followed by addition of 5-methyl L-glutamate (32 mg, 0.20 mmol). The mixture was heated at 60° C. for 1 hour, cooled to room temperature and poured into 100 ml of water with vigorous stirring. 2M HCl was added slowly until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give 2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-methoxy-5-oxopentanoic acid as white solid. Yield: 30 mg, 38%.

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