To a solution of N-(4-(4-hydroxy-2,6-dimethylphenyl)-thiazol-2-yl)isonicotinamide (5-3, 325 mg, 1.0 mmol) in DMF (15 mL) were added cesium carbonate (650 mg, 2.0 mmol, 2.0 equiv) and Cu (19.5 mg, 0.30 mmol, 0.30 equiv). The mixture was stirred at 80-90° C. for 60 min. 5-Bromo-2-hydroxypyridine (261 mg, 1.5 mmol) was added to the solution and the reaction mixture was stirred at 100° C. for additional 24 hr. The solution was quenched with water (40 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on (NH silica gel, hexane/ethyl acetate=3/1-1/3) to give 5 (0.75 g) in 18% yield: 1H NMR (500 MHz, CDCl3) δ 8.31 (d, J=5.0 Hz, 2 H), 8.29 (d, J=5.0 Hz, 2 H), 7.23 (d, J=9.5 Hz, 1 H), 6.81 (s, 1 H), 6.60 (d, J=4.76 Hz, 1 H), 6.49 (s, 2 H), 5.42 (s, 1 H), 2.04 (s, 6 H), ESI-MS=m/z 417.2 (M−H)−.
