Sodium Carbonate → HCID 89907349, compound

Participants

Reaction Conditions

Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 2 g, 4.48 mmol), pyrimidin-5-ylboronic acid (0.666 g, 5.38 mmol), Pd(PPh3)2Cl2 (0.315 g, 0.448 mmol) and Na2CO3 (1.425 g, 13.45 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon, and DME (12.55 mL), water (3.59 mL), EtOH (1.793 mL) were added. The RM was stirred at 80° C. for 3.5 h, diluted with THF (4 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 1.765 g, 2.241 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 120 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 60% to 90% EtOAc-EtOH+0.1% NH4OH (9:1)). Crystallization from a toluene/EtOH mixture yielded the title compound as a white amorphous solid. HPLC Chiral (CHIRALPAK® AD-H, 250×4.6 mm, eluent: EtOH, 0.5 mL/min, UV 210 nm) tR=18.58 min, UPLC-MS (condition 1) tR=2.07 min, m/z=446.1 [M+H]+, m/z=444.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.80 (m, 1H) 1.81-1.92 (m, 1H) 2.89 (d, J=11.25 Hz, 1H) 3.18-3.28 (m, 2H) 3.35-3.44 (m, 1H) 4.22 (br. s, br. s, 1H) 4.89 (d, J=3.42 Hz, 1H) 7.35 (d, J=9.05 Hz, 2H) 7.85 (d, J=9.05 Hz, 2H) 8.10 (d, J=2.45 Hz, 1H) 8.80 (d, J=2.20 Hz, 1H) 8.89 (s, 2H) 9.20 (s, 1H) 10.17 (s, 1H).

Provenance & Evidence