反应详情

温度

55 °C

7-(2-Methyl-2H-pyrazol-3-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide (step 3) (480 g) was suspended in ethanol (2300 mL) in a 5000 mL four-necked flask equipped with thermometer, reflux condenser and a nitrogen inlet. The mixture was heated to 55° C. and the suspension gradually became clear. A solution of citric acid (180 g) in acetone (2.4 L) was added over 1 h and the internal temperature was controlled at 45-50° C. The clear solution was stirred at 50° C. for 2 h. A crystal seed (1 g) was added to the reactor and the internal temperature was cooled to 20° C. at a speed of 8° C./h. The mixture was stirred at 20° C. for 60 h. The resulting solid was filtered and the filter cake was washed with acetone (1 L) and dried in vacuum (under 4 mbar at 55° C.) for 24 h to afford the title compound;

1. customequipped with thermometer
2. temperaturereflux condenser and a nitrogen inlet
3. customwas controlled at 45-50° C
4. additionA crystal seed (1 g) was added to the reactor
5. temperaturethe internal temperature was cooled to 20° C. at a speed of 8° C./h
6. stirringThe mixture was stirred at 20° C. for 60 h
7. filtrationThe resulting solid was filtered
8. washthe filter cake was washed with acetone (1 L)
9. customdried in vacuum (under 4 mbar at 55° C.) for 24 h