反应详情

温度

60 °C

To a stirred suspension of 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 (150 mg, 0.24 mmol) in 10 ml of anhydrous tetrahydrofuran were added HATU (109 mg, 0.29 mmol) and N,N-diisopropylethylamine (93 mg, 0.72 mmol). The mixture was heated at 60° C. for 15 minutes and cooled to room temperature, followed by addition of 2M ethylamine solution in THF (0.18 ml, 0.36 mmol). The mixture was stirred for another 5 minutes 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 the crude, which was purified by silica gel chromatography eluting with 3˜5% methanol in chloroform to give tert-butyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate as white solid. Yield: 100 mg, 64%.

1. temperaturecooled to room temperature
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