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

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-chloro-2-fluorobenzyloxy)pyridin-2(1H)-one (87 mg, 0.34 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (143 mg, 0.380 mmol), CuI (78 mg, 0.41 mmol), 8-hydroxyquinoline (10 mg, 0.068 mmol) and Cs2CO3 (124 mg, 0.38 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 22 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) afforded an off-white powder. 2 N HCl in Et2O (100 mL) was added to a solution of the yellow residue in CH2Cl2 (5 mL) under N2, and the resulting suspension was stirred at 25° C. for 22 h. The suspension was filtered, and the solid was washed with Et2O and put in a vacuum oven at 40° C. for 2 h to afford 48 mg (29%) of the title compound as a white powder: 1H NMR (500 MHz, DMSO-d6) δ 9.21 (br s, 2H), 7.63 (dd, J=8.0, 8.0 Hz, 1H), 7.57-7.50 (m, 3H), 7.43 (d, J=1.5 Hz, 1H), 7.39 (dd, J=8.5, 2.0 Hz, 1H), 6.95 (dd, J=8.5, 2.0 Hz, 1H), 6.08 (dd, J=7.5, 3.0 Hz, 1H), 6.02 (d, J=2.5 Hz, 1H), 5.18 (s, 2H), 3.69 (s, 3H), 3.41-3.31 (m, 4H), 3.28-3.22 (m, 2H), 3.16-3.09 (m, 2H); ESI MS m/z 452 [M+H]+.

Provenance & Evidence