Phthaloyl chloride → 2-(6-(Bis(4-methoxybenzyl)amino)-2,7-naphthyridin-1-yl)isoindoline-1,3-dione

Participants

Reaction Steps

To a stirred mixture of crude 4-5 (10.9 g, <19.3 mmol), triethylamine (8.05 mL, 57.8 mmol), and dichloromethane (75.0 mL) at 0° C. under an atmosphere of nitrogen gas was added phthaloyl dichloride (90%; 3.75 mL, 23.4 mmol). The resulting mixture was stirred at ambient temperature for 15 hours under an atmosphere of nitrogen gas. The reaction mixture was quenched with saturated aqueous NH4Cl (200 mL) and the resulting mixture was extracted with dichloromethane (1000 mL, 500 mL×2). The combined organic extracts were washed with brine (200 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel 200 g, step gradient eluting with 50:1, 40:1, 30:1, 20:1, 10:1, and 5:1 dichloromethane/ethyl acetate) followed by recrystallization from dichloromethane to give 3.94 g (39% in 3 steps) of 4-6 as yellow crystals: 1H NMR (400 MHz, CDCl3) δ 8.94 (1H, br s), 8.33 (1H, d, J=6.0 Hz), 8.02 (2H, m), 7.84 (2H, m), 7.31 (1H, dd, J=6.0, 0.8 Hz), 7.15 (4H, m), 6.85 (4H, m), 6.52 (1H, br s), 4.81 (4H, br s), 3.79 (6H, s); ESI-MS m/z 531 [C32H26N4O4+H]+.

Provenance & Evidence