8-Hydroxyquinoline → tert-butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-fluorobenzyloxy)pyridin-2(1H)-one (95 mg, 0.43 mmol), tert-butyl 8-bromo-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate (180 mg, 0.47 mmol), 8-hydroxyquinoline (13 mg, 0.086 mmol) and Cs2CO3 (154 mg, 0.47 mmol) in DMSO (10 mL) was degassed under reduced pressure for 40 min. CuI (98 mg, 0.52 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 2×5 min. The reaction mixture was then heated at 135° C. under nitrogen overnight. The reaction 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, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was dissolved in DCM and stirred with charcoal for 10 min. The suspension was filtered, concentrated and purified to afford the title compound (0.12 g, 54%) as a mixture of rotamers: 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=8.5 Hz, 0.4H), 7.53 (d, J=8.0 Hz, 0.6H), 7.41 (dd, J=8.0, 6.0 Hz, 2H), 7.33-7.26 (m, 2H), 7.10 (t, J=8.5 Hz 2H), 7.00 (d, J=8.0 Hz, 1H), 6.07 (s, 1H), 6.02 (d, J=5.5 Hz, 1H), 5.01 (s, 2H), 4.71 (s, 0.7H), 4.63 (s, 1.3H), 3.76 (br s, 1.3H), 3.68 (br s, 0.7H), 3.65 (s, 3H), 2.97 (br s, 2H), 2.05-2.03 (m, 2H), 1.44 (s, 3.1H), 1.37 (s, 5.9H).

Provenance & Evidence