反应详情

温度

20 °C

7-(1-ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (11.64 mmoles) is charged into a 100 mL 3-necked round bottomed flask followed by addition of 2-propanol (16 mL, 3.72 volumes). The yellowish brown slurry is stirred at about 20° C. for 5 min. Then morpholine (3.3 g, 37.84 mmoles) is added over 2-5 minutes. Contents are refluxed for 6 hr. The slurry is cooled to 25° C. 2-Propanol (32 mL, 7.44 volumes) and water (8.6 mL, 2.0 volumes) are added and the mixture warmed to 70-75° C., filtered and concentrated to ˜9 volumes at atmospheric pressure. The clear solution is gradually cooled to 55° C., seeded with 0.06 g of crystalline 7-(1-ethyl-propyl)-3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine slurried in 0.5 mL 2-propanol, rinsed with additional 0.5 mL 2-propanol and added to crystallization flask. The slurry is cooled to 0-5° C., maintained for 1 hr., filtered and the product rinsed with 2-propanol (9 mL, 2.1 volumes). Suctioned dried under vacuum at 60° C. to afford 4.6 g of dry 7-(1-ethyl-propyl)-3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (88.8% yield, purity by HPLC assay is 99.88%). MS (ES)=420 (M+1).

1. temperatureContents are refluxed for 6 hr
2. temperatureThe slurry is cooled to 25° C
3. temperaturethe mixture warmed to 70-75° C.
4. filtrationfiltered
5. concentrationconcentrated to ˜9 volumes at atmospheric pressure
6. temperatureThe clear solution is gradually cooled to 55° C.
7. washrinsed with additional 0.5 mL 2-propanol
8. additionadded to crystallization flask
9. temperatureThe slurry is cooled to 0-5° C.
10. temperaturemaintained for 1 hr
11. filtration, filtered
12. washthe product rinsed with 2-propanol (9 mL, 2.1 volumes)
13. customSuctioned dried under vacuum at 60° C.