反应详情

温度

50 °C

To a clean, dry, nitrogen-purged 2 L hydrogenation reactor were charged 20 wt % Pd(OH)2/C (24.0 g, 50% water wet), water (160 ml), isopropanol (640 ml), (1-benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (160.0 g, 0.48 mol), and acetic acid (28.65 g, 0.48 mol). The reactor was purged with three times at 50 psi with nitrogen and three times at 50 psi with hydrogen. Once purging was complete, the reactor was heated to 45-55° C. and pressurized to 50 psi with hydrogen through a continuous feed. The hydrogen uptake was monitored until no hydrogen was consumed for 1 hour. The reactor was cooled to 20-30° C. and purged three times at 50 psi with nitrogen. The reaction mixture was filtered through wet Celite and the filtrate was sent to a clean, dry, nitrogen-purged vessel. A solution of sodium hydroxide (39.33 g) in water (290 ml) was charged and the mixture was stirred for a minimum of 1 hour then heated to 75-90° C. The isopropanol was removed by distillation. The reaction mixture was cooled to 20-30° C. and 2-methyltetrahydrofuran (1.6 L) was added. The aqueous layer was drained off and the 2-methyltetrahydrofuran was displaced with toluene (1.6 L). The distillation was continued until the final volume was 800 ml. The slurry was cooled to 20-30° C. and held for a minimum of 7 hours. The resulting solids were isolated by filtration and washed with toluene (480 ml). After drying under vacuum between 40-50° C. for a minimum of 24 hours with a slight nitrogen bleed 102.3 g (87.3%) of the title compound were isolated.

1. customTo a clean, dry
2. customnitrogen-purged 2 L hydrogenation reactor
3. customThe reactor was purged with three times at 50 psi with nitrogen and three times at 50 psi with hydrogen
4. customOnce purging
5. customwas consumed for 1 hour
6. temperatureThe reactor was cooled to 20-30° C.
7. custompurged three times at 50 psi with nitrogen
8. filtrationThe reaction mixture was filtered through wet Celite
9. customdry
10. customnitrogen-purged vessel
11. additionA solution of sodium hydroxide (39.33 g) in water (290 ml) was charged
12. temperaturethen heated to 75-90° C
13. customThe isopropanol was removed by distillation
14. temperatureThe reaction mixture was cooled to 20-30° C.
15. addition2-methyltetrahydrofuran (1.6 L) was added
16. distillationThe distillation
17. temperatureThe slurry was cooled to 20-30° C.
18. customheld for a minimum of 7 hours
19. customThe resulting solids were isolated by filtration
20. washwashed with toluene (480 ml)
21. customAfter drying under vacuum between 40-50° C. for a minimum of 24 hours with a slight nitrogen
22. customwere isolated