反应详情

To a solution of 2-(2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamide 56 (1.14 g, 2.33 mmol) in MeOH (40 mL) was added formaldehyde solution (37% in water, 0.52 mL, 7.0 mmol) and sodium triacetoxyborohydride (1.98 g, 9.33 mmol) under a nitrogen atmosphere. The mixture was stirred at room temperature for 4 hours before concentrating under reduced pressure. The mixture was diluted with sat. aq. NaHCO3 (75 mL) and the aqueous phase was extracted with EtOAc (3×50 mL). The combined organics were washed with brine and dried (MgSO4) before the solvent was removed in vacuo to give the product as a white solid (1.05 g, 90%). 1H NMR (400 MHz, d6-DMSO) δ 10.22-10.09 (m, 1H), 8.69-8.55 (m, 1H), 8.04-7.95 (m, 1H), 7.58 (s, 1H), 7.43-7.35 (m, 1H), 7.29-7.12 (m, 4H), 6.96-6.84 (m, 1H), 4.13-4.01 (m, 1H), 3.90-3.79 (m, 1H), 3.27-2.88 (m, 4H), 2.83 (d, J=10.0 Hz, 2H), 2.19 (s, 3H), 2.07-1.87 (m, 6H), 1.33 (d, J=6.8 Hz, 3H). LCMS-D: rt 3.03 min; m/z 502 [M+H]+.

1. concentrationbefore concentrating under reduced pressure
2. additionThe mixture was diluted with sat. aq. NaHCO3 (75 mL)
3. extractionthe aqueous phase was extracted with EtOAc (3×50 mL)
4. washThe combined organics were washed with brine
5. dry with materialdried (MgSO4) before the solvent
6. customwas removed in vacuo