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 (200 mg, 0.19 mmol) was added to a solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 6-[(4-acetyl-1-piperazinyl)carbonyl]-13-cyclohexyl-N-[(dimethylamino)sulfonyl]- (79 mg, 0.13 mmol) in MeOH (10 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 3 d, 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, 6-[(4-acetyl-1-piperazinyl)carbonyl]-13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro- (16 mg, 0.03 mmol, 20%) as a white powder. Mixture of atrope diastereomers: 1HNMR (500 MHz, CD3OD) δ 8.09 (s. 0.3H), 7.99 (s. 0.7H), 7.91 (d, J=8.6 Hz, 0.3H), 7.89 (d, J=8.6 Hz, 0.7H), 7.63 (d, J=7.9 Hz, 0.3H), 7.59 (d, J=7.9 Hz, 0.7H), 7.52-7.28 (m, 4H), 4.64-4.56 (m, 0.7H), 4.50 (dd, J=6.1, 14.0 Hz, 0.3H), 4.14-4.05 (m, 0.3H), 3.94-3.57 (m, 9H), 3.02 (s, 4H), 3.01 (s, 2H), 2.98-2.91 (m, 1H), 2.88-2.68 (m, 2H), 2.19 (s, 2H), 2.11 (s, 1H), 2.16-1.91 (m, 4H), 1.87-1.76 (m, 2H) 1.67-1.22 (m, 4H). LCMS: m/e 618 (M−H)−, ret time 1.59 min, column A, 3 minute gradient.

Provenance & Evidence