2-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione → 2-(4-(1-(2,5-Difluorophenyl)propan-2-ylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)-6,7-dihydroimidazo[4,5-f]isoindol-5(1H)-one

Participants

Reaction Steps

2-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (0.40 g, 0.74 mmol) and zinc powder (1.16 g, 17.7 mmol) were suspended in acetic acid (30 mL). The reaction mixture was stirred and heated to reflux overnight under argon. Then, the solvent was removed under reduced pressure. The residue solid was stirred in 100 mL of saturated K2CO3 solution. The white solid was filtered out, dried under vacuum and extracted with CH2Cl2/MeOH (7/3 v/v) three times (300 mL). The extracts were concentrated to dryness. The residue was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a white solid product, 0.29 g, 74.6% yield. MS: 527 [M−H]−. 1H-NMR (DMSO-d6, 300 MHz): δ 13.06 (s, 1H), 11.18 (s, 1H), 11.06-11.05 (m, 1H), 7.96 (s, 0.5H), 7.86 (s, 0.5H), 7.81 (s, 0.5H), 7.70 (s, 0.5H), 7.29-7.28 (m, 1H), 7.23-7.19 (m, 1H), 7.14-7.12 (m, 1H), 6.89-6.85 (m, 1H), 6.14-6.11 (m, 1H), 4.48 (s, 2H), 4.17-4.13 (m, 1H), 4.03-3.99 (m, 1H), 3.01-2.98 (m, 2H), 2.88-2.85 (m, 2H), 2.35 (d, 3H, J=4.5 Hz), 2.20 (s, 3H), 2.03-1.99 (m, 2H), 1.86-1.83 (m, 3H), 1.70-1.68 (m, 2H), 1.33 (d, 3H, J=6.5 Hz).

Provenance & Evidence