To a solution of N-(4-(4-Hydroxy-2,6-dimethylphenyl)-thiazol-2-yl)isonicotinamide (5-3, 0.98 g, 3.0 mmol) in DMF (10 mL) were added cesium carbonate (1.95 g, 6.0 mmol, 2.0 equiv) and Cu (58.5 mg, 0.90 mmol, 0.3 equiv). The mixture was stirred at 100-110° C. for 1.0 h and added with 5-bromo-2-(2-methoxyethoxy)pyridine (17-2, 1.04 g, 4.5 mmol). The solution heated at 130° C. for 24 h. The reaction mixture was added with water (40 mL) and extracted with EtOAc. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3) to give 17 (0.94 g) in 66% yield: 1H NMR (500 MHz, CDCl3) δ 8.81 (d, 2 H), 7.93 (d, 1 H), 7.88 (d, 2 H), 7.32 (m, 1 H), 6.82 (d, 2 H), 6.57 (s, 2 H), 4.45 (t, 2 H), 3.75 (t, 2 H), 3.44 (s, 3 H), 1.99 (s, 6 H), ESI-MS=m/z 477.2 (M+H)+.
