反应详情

温度

55 °C

1-{5-[1-(1,3-Dimethoxypropan-2-yl)-4-oxo-3-(piperazin-1-ylcarbonyl)-1,4-dihydroquinolin-6-yl]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-2-yl}-3-ethylurea (Example 140, 180 mg, 0.267 mmol) was dissolved in acetonitrile (15 mL). Potassium carbonate (73.7 mg, 0.53 mmol) was added, followed by the addition of 2-bromoethanol (40 mg, 0.32 mmol) and the mixture was heated to 55° C. for 16 h. The reaction mixture was filtered, and the filtrate was concentrated and dried to give the crude compound. The crude was dissolved in water (10 mL) and the pH was adjusted to 2. The aqueous solution was washed with ethyl acetate, then basified to pH˜8 with saturated sodium bicarbonate solution, then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford 65 mg (34%) of 1-{5-[1-(1,3-dimethoxypropan-2-yl)-3-{[4-(2-hydroxyethyl)piperazin-1-yl]carbonyl}-4-oxo-1,4-dihydroquinolin-6-yl]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-2-yl}-3-ethylurea as an off-white solid.

1. filtrationThe reaction mixture was filtered
2. concentrationthe filtrate was concentrated
3. customdried
4. customto give the crude compound
5. washThe aqueous solution was washed with ethyl acetate
6. extractionextracted with ethyl acetate
7. dry with materialThe organic layer was dried over anhydrous sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure