Hydrochloric Acid → 4-(2,4-Dichlorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-one

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A suspension of 4-(2,4-dichlorobenzyloxy)pyridin-2(1H)-one (103 mg, 0.381 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (131 mg, 0.347 mmol), CuI (79 mg, 0.42 mmol), 8-hydroxyquinoline (10 mg, 0.069 mmol) and Cs2CO3 (124 mg, 0.381 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 135° C. for 48 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. Activated carbon was added to the resulting solution, and the resulting suspension was filtered. The filtrate was dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH), 100:0 to 0:100) afforded a tan solid. 2 N HCl in Et2O (100 mL) was added to a solution of the tan solid in CH2Cl2 (5 mL) under N2, and the resulting suspension was stirred at 25° C. for 17 h. The suspension was filtered, and the solid was washed with Et2O and freeze dried to afford 66 mg (38%) of the title compound as a white powder: 1H NMR (500 MHz, DMSO-d6) δ 9.02 (br s, 2H), 7.74 (d, J=2.0 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.54-7.50 (m, 2H), 7.45 (d, J=1.5 Hz, 1H), 6.96 (dd, J=8.5, 2.0 Hz, 1H), 6.10 (dd, J=7.5, 3.0 Hz, 1H), 6.00 (d, J=3.0 Hz, 1H), 5.19 (s, 2H), 3.69 (s, 3H), 3.42-3.31 (m, 4H), 3.26-3.22 (m, 2H), 3.13-3.09 (m, 2H); ESI MS m/z 468 [M+H]+.

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