Phenylboronic Acid → HCID 89907909, compound

Participants

Reaction Conditions

Reaction Steps

(R)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 89.0 mg) and phenylboronic acid (48.8 mg) were dissolved in DME (0.8 mL). A solution of 2M NaHCO3 (0.3 mL, 0.6 mmol) was added, the RM was flushed with argon, heated to 90° C., and treated with Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol). The RM was stirred under argon at 95° C. for 2 h in a capped 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 5% MeOH) and treated with Si-Thiol (80 mg) in MeOH to afford the title compound as an off-white powder. HPLC (Condition 4) tR=5.09 min, UPLC-MS (Condition 3) tR=1.14 min, m/z=444.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.62-1.73 (m, 1H) 1.74-1.85 (m, 1H) 2.85 (d, J=11.34 Hz, 1H) 3.10-3.26 (m, 2H) 3.32-3.45 (m, 1H) 4.15 (m, J=2.30 Hz, 1H) 4.80 (d, J=3.13 Hz, 1H) 7.25-7.51 (m, 7H) 7.78-7.88 (m, 2H) 7.96 (d, J=2.35 Hz, 1H) 8.72 (d, J=2.30 Hz, 1H) 10.15 (s, 1H).

Provenance & Evidence