8-Hydroxyquinoline → 4-(4-Chlorobenzyloxy)-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-chlorobenzyloxy)pyridin-2(1H)-one (91.0 mg, 0.38 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate (160 mg, 0.42 mmol), 8-hydroxyquinoline (11 mg, 0.072 mmol) and Cs2CO3 (137 mg, 0.42 mmol) in DMSO (10.0 mL) was degassed under reduced pressure for 40 min. CuI (87 mg, 0.46 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 2×5 min. The reaction mixture was heated at 135° C. under nitrogen overnight. 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 5 min. Celite was added, and the suspension was stirred for 5 min. The suspension was filtered through Celite, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in dichloromethane (1.0 mL), and HCl (2M in diethyl ether, 5.0 mL) was added. The resulting slurry was stirred at room temperature overnight and concentrated under reduced pressure. Purification by preparative HPLC followed by preparative TLC (DCM/MeOH/concentrated ammonia 96:3.6:0.4) and preparative HPCL afforded the title compound (41 mg, 23%) as a white solid: 1H NMR (500 MHz, CD3OD) δ 7.58 (d, J=8.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.47 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.39 (d, J=1.5 Hz, 1H), 7.01 (dd, J=8.5, 2.0 Hz, 1H), 6.28 (dd, J=8.0, 3.0 Hz, 1H), 6.11 (d, J=2.5 Hz, 1H), 5.17 (s, 2H), 3.74 (s, 3H), 3.54 (t, J=5.5 Hz, 2H), 3.48 (t, J=5.5 Hz, 2H), 3.35-3.33 (m, 2H), 3.23 (t, J=5.5 Hz, 2H); ESI MS m/z 434 [M+H]+.

Provenance & Evidence