反应详情

温度

35 °C

Method To a 50 mL flask was added a solution of the free base (1-3) of Compound I in isopropyl acetate (13.9 mL at 160 g/L). The solution was heated to 35° C., and HCl in isopropyl alcohol (1.33 N, 6.1 mL, 1 eq) was added in one portion. The resulting solution was heated to 60° C. and a second equivalent of 1.33N HCl in isopropyl alcohol (6.1 mL) was added in one portion. To the resulting solution at 60° C. was added seed of the bis HCl Form II of Compound I (25.2 mg). After seeding, the mixture was cooled to 20 C. over at least 1 hour, and then aged at 20° C. for a minimum of 12 hours. The mixture was filtered, and washed with isopropyl acetate (5.6 mL) to give the bis HCl salt Form II 2-propanol/isopropyl acetate co-solvate of compound I (1-9).

1. temperatureThe resulting solution was heated to 60° C.
2. temperaturethe mixture was cooled to 20 C
3. waitover at least 1 hour
4. customaged at 20° C. for a minimum of 12 hours
5. filtrationThe mixture was filtered
6. washwashed with isopropyl acetate (5.6 mL)