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

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A suspension of 4-((3,5-dichloropyridin-2-yl)methoxy)pyridin-2(1H)-one (103 mg, 0.380 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (131 mg, 0.345 mmol), Cs2CO3 (124 mg, 0.380 mmol), CuI (79 mg, 0.41 mmol) and trans-1,2-bis(methylamino)cyclohexane (33 mg, 0.23 mmol) in toluene (10 mL) was degassed by bubbling N2 through the suspension for 45 min. The suspension was put under N2 and heated at reflux for 2 d. 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) afforded a viscous oil. 2 N HCl in Et2O (100 mL) was added to a solution of the viscous oil in CH2Cl2 (10 mL) under N2, and the resulting suspension was stirred at 25° C. for 16 h. The suspension was filtered, and the solid was washed with Et2O and put in a vacuum oven at 40° C. for 3 h to afford 59 mg (34%) of the title compound as a white powder: mp 178-180° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.14 (br s, 2H), 8.69 (s, 1H), 8.37 (s, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.09 (dd, J=7.5, 2.5 Hz, 1H), 6.01 (s, 1H), 5.30 (s, 2H), 3.69 (s, 3H), 3.42-3.30 (m, 4H), 3.28-3.22 (m, 2H), 3.17-3.09 (m, 2H); ESI MS m/z 469 [M+H]+.

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