反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 0 °C
PROCEDURE
实验过程
A solution of tert-butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate A66 (3.41 g, 5.80 mmol) in DCM (50 mL) was cooled to 0° C. and treated with TFA (4.44 mL, 0.058 mol). The mixture was stirred at 0° C. for 1 hour and then at room temperature for 3 hours. An extra aliquot of TFA (2.2 mL, 0.029 mol) was added to the mixture and stirring was continued for 2 hours at room temperature. Sat. aq. NaHCO3 (˜50 mL) was carefully added, followed by aq. NaOH (2 M, ˜50 mL). DCM was removed in vacuo and the resultant aqueous mixture was diluted with H2O (˜50 mL). The white suspension was sonicated for 10 minutes and vacuum filtered. The isolated solid was washed with water and air dried to give the title compound 56 as a white solid (2.8 g, 99%). 1H NMR (400 MHz, d6-DMSO) δ 10.20-10.08 (m, 1H), 8.69-8.56 (m, 1H), 8.02-7.93 (m, 1H), 7.58 (s, 1H), 7.44-7.35 (m, 1H), 7.27-7.14 (m, 4H), 6.92-6.80 (m, 1H), 4.21-4.08 (m, 1H), 3.91-3.79 (m, 1H), 3.18-2.91 (m, 6H), 2.61-2.50 (m, 2H), 1.92-1.86 (m, 2H), 1.81-1.68 (m, 2H), 1.33 (d, J=6.9 Hz, 3H). LCMS-A: rt 4.79 min; m/z 488 [M+H]+.
WORKUP
后处理
- waitat room temperature for 3 hours
- stirringstirring
- waitwas continued for 2 hours at room temperature
- customDCM was removed in vacuo
- additionthe resultant aqueous mixture was diluted with H2O (˜50 mL)
- customThe white suspension was sonicated for 10 minutes
- filtrationvacuum filtered
- washThe isolated solid was washed with water and air
- customdried