反应详情

Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I55) (476 mg, 0.906 mmol) and LiOH.H2O (113 mg, 2.71 mmol) in a mixture of THF (20 mL), water (4 mL) and MeOH (2 mL) were stirred at room temperature for 24 hours. The volatiles were evaporated under reduced pressure to give a light yellow solid which was dissolved in dry DMF (10 mL) and dry THF (10 mL), HOBT (171 mg, 1.26 mmol), EDCI (196 mg, 1.26 mmol), ammonium carbonate (458 mg, 4.87 mmol) and DIPEA (829 μL, 4.87 mmol) were added and the resulting mixture was stirred at room temperature for 16 hours. The volatiles were evaporated under reduced pressure and the residue taken up in ethyl acetate. The resulting solution was washed with 10% NaHCO3, the layers separated and the organic layer was dried (MgSO4). The volatiles were evaporated under reduced pressure and the residue chromatographed (SiO2, 0-100% MeOH/DCM) to give the title compound (12) (358 mg, 52%) as a cream solid; 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.58 (d, J=89 Hz, 1H), 7.34 (s, 1H), 7.28-7.19 (m, 4H), 7.14-7.09 (m, 2H), 5.66 (s, 1H), 5.49 (s, 1H), 3.65 (s, 2H), 3.13-3.04 (m, 4H), 3.04-2.97 (m, 2H), 2.54-2.41 (m, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 2.08 (td, J=11.3, 3.8 Hz, 2H), 1.88-1.80 (m, 4H). LCMS Method C: rt 4.91 min; m/z 512.2 [M+1]+, 510.2 [M−1]−.

1. customThe volatiles were evaporated under reduced pressure
2. customto give a light yellow solid which
3. stirringthe resulting mixture was stirred at room temperature for 16 hours
4. customThe volatiles were evaporated under reduced pressure
5. washThe resulting solution was washed with 10% NaHCO3
6. customthe layers separated
7. dry with materialthe organic layer was dried (MgSO4)
8. customThe volatiles were evaporated under reduced pressure
9. customthe residue chromatographed (SiO2, 0-100% MeOH/DCM)