7H-indolo[2,1-a][2]benzazepine-10-carboxamide → 5H-indolo[2,1-a][2]benzazepine-10-carboxamide

Participants

Reaction Steps

10% Palladium on carbon (84 mg, 0.08 mmol) was added to a solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl]- (84 mg, 0.14 mmol) in MeOH (6 mL) and the reaction mixture was vacuum flushed with nitrogen (3×) and then with hydrogen (3×). The reaction mixture was stirred under a balloon of hydrogen for 1 d. Additional 10% palladium on carbon (100 mg, 0.9 mmol) was added and the reaction mixture was vacuum flushed with nitrogen (3×), with hydrogen (3×) and then stirred under a balloon of hydrogen for 3 d. The reaction mixture was filtered through a pad of celite and concentrated. The residue was purified by preparative HPLC (MeOH/H2O with an NH4OAc buffer) to yield 5H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl]- (39 mg, 0.06 mmol, 44%) as a yellow solid. Mixture of atrope diastereomers: 1HNMR (500 MHz, CD3OD) δ 8.10 (s. 0.3H), 8.02 (s. 0.7H), 7.92 (d, J=8.6 Hz, 0.3H), 7.90 (d, J=8.6 Hz, 0.7H), 7.63 (d, J=8.5 Hz, 0.3H), 7.58 (d, J=8.5 Hz, 0.7H), 7.53-7.31 (m, 4H), 4.64-4.47 (m, 1H), 4.15-3.64 (m, 5H), 3.55-3.27 (m, 5H), 3.04-2.96 (m, 9H), 2.94-2.76 (m, 3H), 2.19-1.23 (m, 10H). LCMS: m/e 654 (M−H)−, ret time 1.73 min, column A, 3 minute gradient.

Provenance & Evidence