反应详情

To a fine suspension of 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride (Example 62, 50.2 mg, 0.107 mmol) in 2:1 MeOH/acetic acid (0.60 mL) was added (1-ethoxycyclopropoxy)trimethylsilane (94.2 mg, 0.535 mmol) and the mixture was stirred at ambient temperature for 5 minutes. Sodium cyanoborohydride (42.5 mg, 0.642 mmol) was added in one portion and the mixture was stirred at 50° C. for 3 hours. The mixture was cooled to ambient temperature and concentrated to dryness. The residual white solid was partitioned into DCM and 1M K2CO3 (3 mL each) and the mixture was stirred until both layers were homogeneous. The DCM layer was removed and the aqueous layer was extracted with DCM. The combined DCM extracts were dried over Na2SO4, filtered through a Celite pad and concentrated to give a colorless glass. The glass was purified on a silica gel column eluting with a step gradient of EtOAc, 5% MeOH/EtOAc, and 10% MeOH/EtOAc to furnish the title compound (35 mg, 82% yield) as a white solid. MS (apci) m/z=400.2 (M+H).

1. stirringthe mixture was stirred at 50° C. for 3 hours
2. temperatureThe mixture was cooled to ambient temperature
3. concentrationconcentrated to dryness
4. customThe residual white solid was partitioned into DCM and 1M K2CO3 (3 mL each)
5. stirringthe mixture was stirred until both layers
6. customThe DCM layer was removed
7. extractionthe aqueous layer was extracted with DCM
8. dry with materialThe combined DCM extracts were dried over Na2SO4
9. filtrationfiltered through a Celite pad
10. concentrationconcentrated
11. customto give a colorless glass
12. customThe glass was purified on a silica gel column
13. washeluting with a step gradient of EtOAc, 5% MeOH/EtOAc, and 10% MeOH/EtOAc