Acetic acid methylene chloride → 4-(Benzyloxy)-1-(2-isopropyl-6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride

Participants

Reaction Steps

Acetone (2.81 mL) and picoline borane complex (59 mg, 0.55 mmol) were added to a suspension of 4-(benzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (80 mg, 0.18 mmol) in 10:1 CH2Cl2/AcOH (3.1 mL) and the resulting solution was stirred at reflux for 18 h. Acetone (1.0 mL) and picoline borane complex (50 mg, 0.46 mmol) were added to the solution and the resulting mixture was stirred for 48 h. The mixture was partitioned with H2O (5 mL) and CH2Cl2 (20 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes to 0:100 over 20 column volumes) followed by preparative TLC (Analtech, 20×20 cm, 1000 microns, 50:50 (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH) provided a white solid that upon concentration with 1.25 M HCl in MeOH (2.0 mL) afforded the title compound (33 mg, 38%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 9.92 (br s, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.50-7.35 (m, 6H), 7.02 (dd, J=8.0, 1.5 Hz, 1H), 6.10 (dd, J=7.5, 2.5 Hz, 1H), 5.97 (d, J=3.0 Hz, 1H), 5.15 (s, 2H), 4.65-4.53 (m, 2H), 3.72 (s, 3H), 3.57-3.47 (m, 3H), 3.11 (t, J=6.0 Hz, 2H), 2.24-2.07 (m, 2H), 1.34-1.30 (m, 6H); ESI MS m/z 442 [M+H]+; HPLC (Method A, 223 nm) 98.4% (AUC), tR=15.7 min.

Provenance & Evidence