Acetyl chloride → 1-(6-Acetyl-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one

Participants

Reaction Steps

Triethylamine (40 μL, 0.28 mmol), DMAP (3.5 mg, 0.028 mmol) and acetyl chloride (15 μL, 0.21 mmol) were added to a solution of 1-(9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one hydrochloride (80 mg, 0.14 mmol) in CH2Cl2 (8 mL) and the resulting solution was stirred at ambient temperature for 3 h under N2. The resulting solution was concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes, increased to 0:100 over 20 column volumes and held for 14 column volumes) gave the title compound (51 mg, 77%) as a yellow solid and a mixture of rotomers: mp 238-242° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.20 (d, J=2.0 Hz, 1H), 8.50 (dd, J=8.0, 2.0 Hz, 1H), 8.11-8.04 (m, 3H), 7.44-7.37 (m, 1H), 7.03 (d, J=1.5 Hz, 1H), 6.86-6.83 (m, 1H), 4.73-4.68 (m, 2H), 3.90-3.83 (m, 2H), 3.71-3.69 (m, 3H), 3.01-2.86 (m, 2H), 2.16-2.12 (m, 3H); ESI MS m/z 468 [M+H]+; HPLC (Method A)>99% (AUC), tR=17.8 min.

Provenance & Evidence