To a solution of 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, 0.3 equiv). The solution was stirred at 100-110° C. for 60 min and added with 5-bromo-N-(2-methoxyethyl)pyridin-2-amine (29-2, 347 mg). The reaction mixture was stirred at 140° C. for 48 h. The reaction was quenched with water (40 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3) to give 29 (96 mg) in 16% yield: 1H NMR (500 MHz, CDCl3) δ 8.81 (d, 1 H), 7.72 (d, 1 H), 7.71 (d, 1H), 7.24 (m, 1 H), 6.81 (s, 1 H), 6.72 (d, 1 H), 6.49 (s, 1 H), 3.59 (t, 1 H), 3.51 (t, 1 H), 3.35 (s, 3 H), 2.01 (s, 6 H), ESI-MS=m/z 447.5 (M+H)+.
