反应详情

温度

46 °C

A 1 L, 4-neck, round-bottom flask equipped with a mechanical stirrer, a thermometer, heating/cooling capacity, and an addition funnel was charged in sequence with 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide free base (10 g), methanol (250 mL), and 37% hydrochloric acid (1.85 g) under nitrogen purge. The mixture was heated to 42-50° C. and stirred for an additional 15 minutes. The resulting solution was filtered through a polypropylene pad, while maintaining the batch temperature above 40° C. The clear solution was transferred under nitrogen atmosphere to another 1 L, 4-neck, and round-bottom flask equipped with a mechanical stirrer, a thermometer, and heating/cooling capacity. The batch was stirred and cooled to 30° C. over a period of 30 minutes. Seeds (20 mg) were added at this temperature, and the batch was cooled to 23° C. over a period of 45 minutes. The batch was stirred for an additional 3 hours to obtain a thick white suspension. The suspension was cooled to −10° C. over a period of 1.5 hours and stirred for an additional 30 minutes. Any solid was collected by filtration and rinsed with cold (−10° C.) methanol (20 mL). The solid was dried at 50-55° C./10-20 torr for 8-16 hours to obtain 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide monohydrochloride monohydrate salt (9.8 g) as a white solid.

1. customA 1 L, 4-neck, round-bottom flask equipped with a mechanical stirrer
2. temperaturea thermometer, heating/cooling capacity, and an addition funnel
3. custompurge
4. filtrationThe resulting solution was filtered through a polypropylene pad
5. temperaturewhile maintaining the batch temperature above 40° C
6. custom4-neck, and round-bottom flask equipped with a mechanical stirrer
7. temperaturea thermometer, and heating/cooling capacity
8. stirringThe batch was stirred
9. temperaturecooled to 30° C. over a period of 30 minutes
10. additionSeeds (20 mg) were added at this temperature
11. temperaturethe batch was cooled to 23° C. over a period of 45 minutes
12. stirringThe batch was stirred for an additional 3 hours
13. customto obtain a thick white suspension
14. temperatureThe suspension was cooled to −10° C. over a period of 1.5 hours
15. stirringstirred for an additional 30 minutes
16. filtrationAny solid was collected by filtration
17. washrinsed with cold (−10° C.) methanol (20 mL)
18. customThe solid was dried at 50-55° C./10-20 torr for 8-16 hours