Reaction Steps
A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.50 g, 1.6 mmol), 3,4-dichlorophenyl isocyanate (0.29 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 using a methylene chloride-methanol gradient, eluting with 97:3 methylene chloride-methanol, to provide 0.60 g of the product in 82% yield: mp 241-243° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.54-2.64 (m, 2H), 2.84-2.97 (m, 1H), 4.71 (d, J=6.0 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.4 Hz, 1H), 6.92 (t, J=6.0 Hz, 1H), 7.25 (dd, J=8.8 Hz, J=2.5 Hz, 1H), 7.45 (d, J=8.8 Hz, 1H), 7.75-7.88 (m, 4H), 9.15 (s, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.8, 48.9, 117.8, 118.8, 121.9, 122.4, 127.2, 130.4, 130.9, 131.6, 133.7, 134.8, 139.9, 140.5, 154.9, 167.0, 167.6, 169.8, 172.8; Anal. calcd. for C21H16Cl2N4O5.0.25H2O: C, 52.57; H, 3.47; N, 11.68. Found: C, 52.78; H, 3.41; N, 11.37.
