Ammonium Chloride → HCID 71209333, compound

Participants

Reaction Steps

A solution of methyl 2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)isonicotinate (I129) (70.0 mg, 0.120 mmol), and LiOH.H2O (15 mg, 0.36 mmol) in THF (5 mL), water (1 mL) and MeOH (0.5 mL) was stirred at room temperature for 4 hours. The volatiles were evaporated under reduced pressure to give a yellow solid which was dissolved in dry DMF (4 mL). HATU (133 mg, 0.350 mmol), DIPEA (60 μL, 0.034 mmol) and ammonium chloride (187 mg, 3.50 mmol) were added and the resulting mixture was stirred at room temperature overnight. The volatiles were evaporated under reduced pressure and the residue diluted with ethyl acetate. The resulting solution was washed with 10% aqueous NaHCO3, then the organic layer was dried (MgSO4) and volatiles removed by evaporation under reduced pressure. The residue was adsorbed onto silica gel and purified by chromatography (SiO2, 0-100% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I130) (50 mg, 50%) as a colourless solid; 1H NMR (400 MHz, CDCl3) δ 8.67 (dd, J=5.1, 0.7 Hz, 1H), 8.51 (s, 1H), 7.60 (s, 1H), 7.55 (s, 1H), 7.53 (d, J=8.6 Hz, 2H), 7.44 (dd, J=5.1, 1.6 Hz, 1H), 7.18 (d, J=8.5 Hz, 2H), 6.37-6.20 (m, 1H), 6.18-5.96 (m, 1H), 4.22 (s, 2H), 3.34 (tt, J=10.4, 5.0 Hz, 4H), 2.63 (s, 1H), 1.81 (d, J=12.7 Hz, 2H), 1.73 (s, 2H), 1.60 (dd, J=12.7, 4.1 Hz, 2H), 1.48 (s, 9H). LCMS Method C: rt 6.04 min; m/z 571.2 [M+1C, 569.2 [M−1]−, 515.2 [M−t-Bu+2]+.

Provenance & Evidence