Hydrochloric Acid → HCID 86712651, compound

Participants

Reaction Steps

LiOH.H2O (0.063 g, 1.5 mmol) was added to a solution of tert-butyl 4-(2-fluoro-4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A31) (0.30 g, 0.49 mmol) in THF (10 mL), water (2 mL) and MeOH (1.5 mL) and the resulting mixture was stirred at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4) and the volatiles removed in vacuo to give a white solid. The solid was dissolved in dry THF (12 mL) and dry DMF (2 mL) under an atmosphere of nitrogen and HOBt (0.086 g, 0.64 mmol), EDCl.HCl (0.12 g, 0.64 mmol) and DIPEA (0.43 mL, 2.4 mmol) were added. After 10 minutes ammonium carbonate (0.24 g, 2.4 mmol) was added in one portion and the resulting mixture was stirred at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organic layers were washed with brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo to afford a pale yellow oil which was purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A32 as a white solid (0.209 g, 69%); 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.44 (s, 1H), 7.61 (dd, J=12.8, 2.2 Hz, 1H), 7.30-7.18 (m, 5H), 7.09 (t, J=8.4 Hz, 1H), 6.31 (s, 1H), 5.69 (s, 1H), 4.39-4.16 (m, 2H), 3.72 (s, 2H), 3.14-3.00 (m, 4H), 2.94 (tt, J=12.1, 3.3 Hz, 1H), 2.81 (t, J=11.4 Hz, 2H), 1.78 (d, J=12.2 Hz, 2H), 1.69-1.53 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 6.710 min; m/z 602.3 [M+H]+.

Provenance & Evidence