Reaction Steps
A mixture of tert-butyl 2-(2-chloro-3-quinolinyl)-5-hydroxy-1H-indole-1-carboxylate (1-8, 1.50 g, 3.80 mmol, 1 equiv), 2-chloro-N-(2-methoxyethyl)-N-methylethanamine (720 mg, 4.75 mmol, 1.25 equiv), and cesium carbonate (3.09 g, 9.50 mmol, 2.50 equiv) in N, N-dimethylformamide (20 mL) was heated at 70° C. for 5 hours. The reaction mixture was concentrated, and the residue was partitioned between water and ethyl acetate. The organic layer was washed with water then brine, dried over magnesium sulfate, and concentrated to give a brown gum. The gum was dissolved in a 1:1 mixture of water and acetic acid (60 mL), and the resulting solution was heated at 100° C. for 18 hours. The reaction mixture was concentrated, and the residue was partitioned between aqueous saturated sodium bicarbonate solution and ethyl acetate. The organic layer was washed with water then brine, dried over magnesium sulfate, and concentrated to give a yellow solid. Purification by flash column chromatography (5% ethanol saturated with ammonia/CH2Cl2, grading to 10% ethanol saturated with ammonia/CH2Cl2) provided 3-(5-{2-[(2-methoxyethyl)(methyl)amino]ethoxy}-1H-indol-2-yl)quinolin-2(1H)-one (1-9) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.10 (s, 1H), 9.72 (s, 1H), 8.32 (s, 1H), 7.68 (br d, 1H, J=7.8 Hz), 7.53 (br t, 1H, J=7.6 Hz), 7.35 (d, 1H, J=8.8 Hz), 7.29 (br t, 1H, J=7.8 Hz), 7.24 (br d, 1H, J=8.2 Hz), 7.09 (d, 1H, J=2.2 Hz), 6.97 (d, 1H, J=1.4 Hz), 6.89 (dd, 1H, J=8.6, 2.2 Hz), 4.16 (t, 2H, J=5.9 Hz), 3.54 (t, 2H, J=2.67 (t, 3H, J=5.7 Hz), 3.38 (s, 3H), 2.92 (t, 3H, J=6.0 Hz), 2.73 (t, 3H, J=5.8 Hz), 2.44 (s, 3H).
