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 (150 mg, 0.33 mmol) in 10 ml of anhydrous DMF were added HATU (150 mg, 0.39 mmol) and N,N-diisopropylethylamine (128 mg, 0.99 mmol). The mixture was stirred at room temperature for 10 minutes, followed by addition of L-Glutamic acid 5-tert-butyl ester (102 mg, 0.50 mmol). The mixture was heated at 60° C. for 30 minutes, cooled to room temperature, and poured into 100 ml of water. 2M HCl was added dropwise with vigorous stirring until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give 5-tert-butoxy-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoic acid as white solid. Yield: 185 mg, 87%.

1. temperatureThe mixture was heated at 60° C. for 30 minutes
2. temperaturecooled to room temperature
3. stirringwith vigorous stirring until pH=4
4. filtrationThe precipitates were filtered
5. washwashed with water
6. customdried in vacuo