Acetyl chloride → 1-(2-Acetyl-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)-4-phenethylpiperazin-2-one

Participants

Reaction Steps

1-(5-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)-4-phenethylpiperazin-2-one dihydrochloride (170 mg, 0.368 mmol), acetyl chloride (˜120 μL, 1.5 mmol) and i-PrNEt2 (400 μL, 2.23 mmol) were combined in methylene chloride (20 mL) and stirred for 16 h. Sodium bicarbonate solution (4 mL) was added and the organics removed and concentrated. The residue was purified by flash chromatography (12 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 85% methylene chloride over 30 min) to provide the title compound as a white solid; 1H NMR (500 MHz, DMSO-d6) δ 11.86 (m, 1H), 7.50-7.48 (dd, J=8.3, 5.0 Hz, 1H), 7.40-7.31 (m, 5H), 7.31-7.26 (m, 1H), 6.98-6.95 (overlapping ddd, J=4.0, 1.5 Hz, 1H), 4.65 (d, J=11.2 Hz, 2H), 4.23-3.97 (m, 3H), 3.97-3.75 (m, 3H), 3.64-3.61 (m, 3H), 3.57-3.42 (m, 4H), 3.19-3.08 (m, 2H), 2.93-2.87 (m, 1H), 2.82-2.77 (m, 1H), 2.13-2.11 (2×s, 3H); ESI MS m/z 431 [M+H]+; HPLC (Method B)>99% (AUC), tR=13.8 min.

Provenance & Evidence