Reaction Steps
AcCl (0.01 mL, 0.2 mmol) was added to a solution of 4-((5-fluoropyridin-2-yl)methoxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-one hydrochloride (49 mg, 0.11 mmol), DMAP (3 mg, 0.03 mmol), and Et3N (0.03 mL, 0.3 mmol) in CH2Cl2 (10 mL) under N2, and the resulting solution was stirred at 25° C. for 4 h. H2O was added and the resulting phases were separated. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography on silica gel ((1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded 39 mg (78%) of the title compound as a white solid as a mixture of rotomers: mp 88-94° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=3.0 Hz, 1H), 7.84 (ddd, J=9.0, 9.0, 3.0 Hz, 1H), 7.66 (dd, J=8.5, 4.5 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.38 (dd, J=3.0, 1.5 Hz, 1H), 6.92-6.88 (m, 1H), 6.12 (dd, J=7.5, 3.0 Hz, 1H), 5.96 (d, J=2.5 Hz, 1H), 5.22 (s, 2H), 3.82-3.76 (m, 2H), 3.75-3.63 (m, 5H), 3.10 (t J=5.5, 1H), 3.05-2.98 (m, 2H), 2.93 (t, J=5.5, 1H), 2.13 (s, 1.5H), 2.08 (s, 1.5H); ESI MS m/z 461 [M+H]+.
