Hydrochloric Acid → (S)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)-6-(pyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Participants

Reaction Steps

2-(4-Chloro-2-methoxypyridin-3-yl)-6-(pyridine-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dione (0.60 g, 1.48 mmol) was dissolved in 10 mL of 1,4-dioxane and 5 mL of concentrated HCl at rt. The reaction mixture was stirred at rt overnight. Then, the volatile was removed to give a yellow-brown solid. This solid was mixed with (S)-1-(2,3,5,6-tetrafluorophenyl)propan-2-amine (0.46 g, 2.22 mmol), N,N-diisopropylethylamine (1.32 mL, 7.40 mmol) and n-butanol (30 mL) in a flask. The reaction mixture was stirred and heated to reflux overnight under argon. Then, volatiles were removed under reduced pressure. The residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a yellow-brown solid product, 0.65 g, 78.3% yield. MS: 560.8 [M−H]−. 1H NMR (DMSO-d6, 500 MHz): δ 13.48 (s, 1H), 11.35 (d, 1H, J=4.5 Hz), 10.91 (d, 1H, J=8.0 Hz), 8.73-8.72 (m, 1H), 8.63-8.61 (m, 1H), 8.25 (s, 1H), 8.03 (s, 1H), 7.95 (dd, 1H, J=8.0 Hz, J2=2.0 Hz), 7.77-7.70 (m, 1H), 7.62-7.58 (m, 1H), 7.41 (t, 1H, J=4.5 Hz), 6.18 (d, 1H, J=7.5 Hz), 4.25 (m, 1H), 3.18-3.10 (m, 2H), 1.93 (d, 3H, J=6.0 Hz).

Provenance & Evidence