Into a 250-mL 3-necked round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-nitrophenylboronic acid (500 mg, 2.99 mmol, 1.00 equiv) in ethylene glycol dimethyl ether (30 mL), N-(3-(trifluoromethyl)benzyl)-2-bromoisonicotinamide 21a (1.08 g, 3.01 mmol, 1.00 equiv), Pd(PPh3)4 (334.7 mg, 0.30 mmol, 0.10 equiv), and a solution of sodium carbonate (1.6 g, 15.09 mmol, 5.00 equiv) in water (4 mL). The resulting solution was stirred for 1.5 h at 80° C. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:1). The resulting solution was diluted with 50 mL of water. The resulting solution was extracted with 2×100 mL of ethyl acetate and the organic layers combined and dried over magnesium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/EtOAc (20:1-5:1). The product was obtained as 1.0 g (83%) of a light yellow solid.
