Sodium Bicarbonate → HCID 118195158, compound

Participants

Reaction Conditions

Reaction Steps

(S)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 33.1, 60 mg, 0.134 mmol) and (6-methylpyridin-3-yl)boronic acid (36.8 mg, 0.19 mmol) were dissolved in DME (0.5 mL). A solution of 2 M aq. NaHCO3 (0.2 mL, 0.6 mmol) was added, the RM was flushed with argon, heated to 90° C., and then treated with Pd(PPh3)2Cl2 (9.44 mg, 0.013 mmol). The RM was stirred under argon at 90° C. for 2 h in a sealed pressure safe tube. After cooling at RT, the RM was dissolved in EtOAc, and washed with brine. The organic phase was dried over Na2SO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 10% MeOH) and treated with Si-Thiol (50 mg) in MeOH to afford the title compound as an off-white amorphous solid. HPLC (Condition 4) tR=4.09 min, UPLC-MS (Condition 7) m/z=459.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.75 (m, 1H) 1.76-1.87 (m, 1H) 2.52 (s, 3H) 2.86 (d, J=11.73 Hz, 1H) 3.11-3.24 (m, 2H) 3.27-3.43 (m, 1H) 4.17 (br. s, br. s, 1H) 4.83 (br. s, br. s, 1H) 7.28-7.39 (m, 3H) 7.69 (dd, J=7.82, 1.96 Hz, 1H) 7.79-7.89 (m, 2H) 7.98 (d, J=2.35 Hz, 1H) 8.48 (d, J=2.35 Hz, 1H) 8.73 (d, J=2.35 Hz, 1H) 10.15 (s, 1H).

Provenance & Evidence