Potassium Carbonate → (R)-4'-Cyano-2-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

(R)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 100 mg, 0.224 mmol) was dissolved in DMF (1.5 mL). 4-Cyanopyridine-3-boronic acid pinacol ester (77 mg, 0.336 mmol), K2CO3 (0.224 mL, 0.448 mmol) and Pd(PPh3)4 (12.95 mg, 0.011 mmol) were added at RT. The vial was evacuated/purged with argon and sealed. The light yellow solution was stirred at 130° C. for 4 h. The yellow reaction solution was diluted with EtOAc (50 mL) and washed with water (3×30 mL). the combined extracts were dried over Na2SO4, filtered, the solvent was evaporated off under reduced pressure to give a crude that was purified by flash chromatography (RediSep® Silica gel column, 24 g, DCM/MeOH 95:5). The fractions containing product were evaporated to dryness under reduced pressure and the residue was dissolved in hot MeOH (2 mL). The yellow solution was allowed to cool down to RT under stirring and the resulting suspension was stirred at RT for 1 h then filtered. The solid was washed with MeOH (1 mL) and dried to afford the title product as a white solid. HPLC (Condition 10) tR=5.91 min, UPLC-MS (Condition 3) tR=0.95 min, m/z=470 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.97 (m, 2H) 2.84 (d, J=10.95 Hz, 1H) 3.07-3.18 (m, 1H) 3.19-3.30 (m, 1H) 3.32-3.45 (m, 1H) 4.21 (br. s, 1H) 4.82-5.00 (m, 1H) 7.36 (d, J=8.99 Hz, 2H) 7.85 (d, J=8.99 Hz, 2H) 7.94-8.05 (m, 1H) 8.12 (d, J=6.26 Hz, 1H) 8.80-8.90 (m, 2H) 9.03 (s, 1H) 10.21 (s, 1H).

Provenance & Evidence