反应详情

温度

40 °C

2-Bromoethyl methyl ether (22 μl) and potassium carbonate (43 mg) were added to a mixture of 4-[3-chloro-4-fluoroanilino]-5-{[(2R)-1-glycoloylpyrrolidin-2-yl]-methoxy}-quinazolin-7-ol (70 mg) in DMF and the reaction mixture was heated at 40° C. for 16 hours. The reaction mixture was cooled to room temperature and then water (5 ml) was added to leave a white precipitate. The precipitate was filtered, washed with water and then purified by column chromatography using 2-5% methanol in DCM as eluent to give the title compound as a white solid (51 mg, 64%); NMR Spectrum (DMSO-d6 at 373 K) 9.80 (br s, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.65 (m, 1H), 7.33 (m, 1H), 6.80 (m, 2H), 4.60 (m, 1H), 4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.0 (m, 2H), 3.75 (t, 2H), 3.50-3.37 (m, 2H), 3.35 (s, 3H), 2.10-1.85 (m, 4H); Mass spectrum MH+ 505.

1. temperatureThe reaction mixture was cooled to room temperature
2. customto leave a white precipitate
3. filtrationThe precipitate was filtered
4. washwashed with water
5. custompurified by column chromatography