反应详情

温度

60 °C

A mixture 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), HATU (91 mg, 0.24 mmol) and N,N-diisopropylethylamine (62 mg, 0.48 mmol) in anhydrous tetrahydrofuran (10 ml) was heated at 60° C. for 10 minutes, followed by addition of ethyl piperazinoacetate (57 mg, 0.33 mmol). Heating was continued at 60° C. for 30 minutes and the mixture was poured into 100 ml of water. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 3˜5% methanol in chloroform to give ethyl [4-({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)piperazin-1-yl]acetate as white solid. Yield: 73 mg, 54%.

1. temperatureHeating
2. filtrationThe precipitates were filtered
3. washwashed with water
4. customdried in vacuo
5. customto give the crude, which
6. customwas purified by silica gel chromatography
7. washeluting with 3˜5% methanol in chloroform