Reaction Steps
m-Tolyl isocyanate (0.4 g, 3.0 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.8 g, 2.3 mmol) and triethylamine (0.3 g, 3.2 mmol) in THF (40 mL) at 5° C. After stirring for 10 minutes at 5° C., the mixture was warmed to room temperature and stirred overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (30 mL) for 30 minutes. The solid was collected and slurried with ether (20 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-m-tolyl-urea (0.7 g, 76%) as a white solid: mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.23 (s, 3H), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 4.71 (d, J=6.0 Hz, 2H), 5.13-5.20 (dd, J=5.4 and 12.6 Hz, 1H), 6.70-6.77 (m, 2H), 7.05-7.17 (m, 2H), 7.25 (s, 1H), 7.75-7.88 (m, 3H), 8.70 (s, 1H), 11.16 (s, 1H); 13C NMR (DMSO-d6) δ 21.19, 21.99, 30.93, 38.71, 48.86, 114.90, 118.25, 121.85, 121.95, 127.18, 128.46, 131.60, 133.66, 134.71, 137.73, 140.18, 140.30, 155.22, 167.01, 167.59, 169.82, 172.76; Anal. calcd. for C22H20N4O5+0.5H2O: C, 61.53; H, 4.93; N, 13.05. Found: C, 61.87; H, 4.72; N, 12.92.
