反应详情

Alternatively, Example 2 was prepared by treating a suspension of 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.1, 68.3 g, 132 mmol) in DCM (1 L) with TFA (305 mL, 3959 mmol) at RT for 5.5 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in EtOAc (2 L), washed with a sat. solution of NaHCO3 (3×500 mL) and brine (2×500 mL), and dried over Na2SO4. The solvent was evaporated off under reduced pressure and the residue was suspended in DCM (300 mL) and stirred at RT for 15 min. The crystalline material was filtered, washed with DCM (200 mL), dried under reduced pressure, dissolved in MeOH (500 mL) and treated with Si-Thiol (Biotage, 10.0 g, 13 mmol) for 15 h at 30° C. The mixture was filtered and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel, 2 kg, DCM/MeOH 95:5) and crystallized from MeCN to afford the title compound as a white crystalline solid.

1. customAlternatively, Example 2 was prepared
2. additionby treating
3. customThe solvent was evaporated off under reduced pressure
4. dissolutionthe residue was dissolved in EtOAc (2 L)
5. washwashed with a sat. solution of NaHCO3 (3×500 mL) and brine (2×500 mL)
6. dry with materialdried over Na2SO4
7. customThe solvent was evaporated off under reduced pressure
8. filtrationThe crystalline material was filtered
9. washwashed with DCM (200 mL)
10. customdried under reduced pressure
11. dissolutiondissolved in MeOH (500 mL)
12. filtrationThe mixture was filtered
13. customthe solvent was evaporated off under reduced pressure
14. customto give the crude product which
15. customwas purified by flash chromatography (Silica gel, 2 kg, DCM/MeOH 95:5)
16. customcrystallized from MeCN