反应详情

To a solution of 5-chloro-N2-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (Example 6; 2.46 g, 6.28 mmol) in methanol (25 ml) was added a solution of phosphoric acid (85 wt % in water, 724 mg, 6.28 mmol) in methanol (10 ml). The resulting precipitate was heated to reflux and more methanol (25 ml) was added. The precipitate was allowed to stir at reflux for 1 hour before cooling down to room temperature. The solution was filtered and filter cake obtained was washed with methanol and transferred to a round bottomed-flask for recrystallization. A suspension of the salt in methanol (50 ml) was then heated to reflux. At reflux, methanol (125 ml) was added where dissolution occurred. The excess solvent was removed by distillation to a final volume of 75 ml. The flask was removed from the heat and the solution was allowed to cool to room temperature. The resulting precipitate was filtered, washed with methanol, and vacuum dried under N2 atmosphere (16 h) to afford 1.43 g (57% isolated yield) of the title compound. 1H NMR: 9.63 (s, 1H), 8.49 (s, 1H), 7.87-8.10 (m, 2H), 7.65 (t, J=8.67 Hz, 1H), 7.41 (dd, J=8.29, 4.52 Hz, 1H), 5.52 (s, 1H), 5.03 (br s, 1H), 4.65 (br s, 1H), 1.44 (d, J=6.78 Hz, 3H), 1.26 (d, J=6.03 Hz, 6H).

1. temperatureThe resulting precipitate was heated
2. temperatureto reflux
3. temperatureat reflux for 1 hour
4. filtrationThe solution was filtered
5. filtrationfilter cake
6. customobtained
7. washwas washed with methanol
8. customtransferred to a round bottomed-flask for recrystallization
9. additionA suspension of the salt in methanol (50 ml)
10. temperaturewas then heated to reflux
11. temperatureAt reflux
12. additionmethanol (125 ml) was added
13. dissolutionwhere dissolution
14. customThe excess solvent was removed by distillation to a final volume of 75 ml
15. customThe flask was removed from the
16. temperatureheat
17. temperatureto cool to room temperature
18. filtrationThe resulting precipitate was filtered
19. washwashed with methanol, and vacuum
20. customdried under N2 atmosphere (16 h)
21. customto afford