Reaction Steps
A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.50 g, 1.6 mmol), 3-chloro-4-methylphenyl isocyanate (0.26 g, 1.6 mmol), and diisopropylethylamine (0.40 g, 3.1 mmol) in 10 mL pyridine was warmed to 40° C. with stirring under N2, and the resulting solution was stirred at the same temperature for 2 hours. The mixture was cooled, and the solvent was evaporated under vacuum. The residue was chromatographed, eluting with 95:5 methylene chloride-methanol, to provide 0.63 g of the product in 90% yield: mp 238-240° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.22 (s, 3H), 2.49-2.65 (m, 2H), 2.84-2.97 (m, 1H), 4.70 (d, J=6.0 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.3 Hz, 1H), 6.81 (t, J=6.0 Hz, 1H), 7.10 (dd, J=8.3 Hz, J=2.0 Hz, 1H), 7.18 (d, J=8.3 Hz, 1H), 7.65 (d, J=2.0 Hz, 1H), 7.75-7.85 (m, 3H), 8.90 (s, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 18.7, 22.0, 30.9, 38.7, 48.9, 116.4, 117.6, 121.9, 127.2, 127.5, 131.0, 131.6, 133.0, 133.7, 134.7, 139.5, 140.1, 155.1, 167.0, 167.6, 169.8, 172.8; Anal. calcd. for C22H19ClN4O5.0.25H2O: C, 57.52; H, 4.27; N, 12.19. Found: C, 57.80; H, 4.33; N, 11.83.
