6-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 223.1, 150 mg, 0.380 mmol) was suspended in iPrOH (0.6 mL). tert-Butyl[3-(trifluoromethylpyrrolidine-3-yl)]carbamate (193 mg, 0.760 mmol) and DIPEA (0.265 mL, 1.520 mmol) were added at RT. The pink/red suspension was stirred at 140° C. for 22 h. The orange reaction solution was diluted with EtOAc (50 mL) then washed with a 2 N citric acid solution (20 mL) and water (3×20 mL). Aq. phases were back-extracted with EtOAc (40 mL). The combined organic phases were dried over Na2SO4, filtered, and the solvent was evaporated off under reduced pressure to give a crude product that was purified by flash chromatography (RediSep® Silica gel column, 40 g, DCM/EtOAc 7:3). The resulting intermediate (135 mg, 0.22 mmol) was suspended in DCM (2 mL). TFA (0.679 mL, 8.82 mmol) was added at RT and the resulting light yellow solution was stirred for 2 h at RT. The RM was diluted with EtOAc (50 mL), washed with an aq. sat. solution of NaHCO3 (2×20 mL) and water (2×20 mL). Aq. phases were back-extracted with EtOAc (40 mL). The combined organic phases were dried over Na2SO4, filtered, and the solvent was evaporated off under reduced pressure to give a crude product that was suspended in MeCN (2 mL). The white suspension was stirred for 30 min at RT then filtered. The solid was washed with MeCN (2 mL) and dried under reduced pressure to give the title product as a white solid. HPLC (Condition 10) tR=5.748 min, UPLC-MS (Condition 3) tR=1.03 min, m/z=513.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.75-1.85 (m, 1H) 1.96-2.08 (m, 1H) 2.24-2.35 (m, 2H) 3.13-3.26 (m, 2H) 3.36-3.52 (m, 2H) 7.36 (d, J=8.99 Hz, 2H) 7.86 (d, J=8.99 Hz, 2H) 8.14 (d, J=2.35 Hz, 1H) 8.81 (d, J=2.35 Hz, 1H) 8.92 (s, 2H) 9.22 (s, 1H) 10.22 (s, 1H).
