4-((3S,4S)-3-amino-4-hydroxypyrrolidin-1-yl)-3-bromo-N-(4-(chlorodifluoromethoxy)phenyl)benzamide (Stage 245.1, 60 mg, 0.121 mmol), 5-pyrimidineboronic acid (22.46 mg, 0.181 mmol) and Na2CO3 aq. (0.181 mL, 0.362 mmol) were added to a vial containing DME (1.5 mL) under argon atmosphere. PdCl2(dppf)-(CH2Cl2) (5.92 mg, 7.25 μmol) was added. The RM was stirred at 80° C. for 2 h, then filtered through Hyflo® and the solvent was evaporated off under reduced pressure to give the crude product which was purified by preparative HPLC (Condition 14). Fractions containing the product were combined, treated with sat. aq. Na2CO3 and the MeCN was removed. The aq. residue was extracted with DCM and the combined extracts were dried over Na2SO4, filtered and the filtrate was evaporated off under reduced pressure to give a residue that was suspended in DCM/n-hexane. The obtained solid was filtered off and washed with n-hexane then purified by SFC. The residue diluted with sat. aq. Na2CO3 (20 mL) and DCM (20 mL). Aq. phase was extracted with DCM (2×10 mL) and with EtOAc (3×10 mL). The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to afford the title product as a beige solid. HPLC (Condition 10) tR=5.77 min, UPLC-MS (Condition 3) tR=0.79 min, m/z=476.1/478.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.65-2.73 (m, 2H) 3.09-3.15 (m, 1H) 3.21-3.30 (m, 2H) 3.71-3.79 (m, 1H) 5.00 (d, J=3.50 Hz, 1H) 6.95 (d, J=8.99 Hz, 1H) 7.34 (d, J=8.20 Hz, 2H) 7.83-7.90 (m, 3H) 7.94 (dd, J=8.60, 2.30 Hz, 1H) 8.86 (d, J=0.78 Hz, 2H) 9.17 (d, J=1.17 Hz, 1H) 10.10 (s, 1H).
