Reaction Steps
A suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) and triethylamine (0.3 g, 2.6 mmol) in THF (30 mL) was cooled to 5° C. 3-Methoxyphenyl isocyanate (0.4 g, 2.6 mmol) was added, and the mixture was stirred at room temperature 5 hours. The mixture was concentrated, and the residue was dissolved in CH2Cl2 (80 mL). The CH2Cl2 solution was washed with 1N HCl (40 mL), water (40 mL), and brine (40 mL), and dried (MgSO4). Solvent was removed, and the solid was slurried with ethanol (20 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3 dihydro-1H-isoindol-4-ylmethyl]-3-(3-methoxy-phenyl)-urea (0.7 g, 80%) as a white solid: mp 160-162° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.50-2.65 (m, 2H), 2.85-2.99 (m, 1H), 3.69 (s, 3H, OCH3), 4.69 (d, J=5.2 Hz, 2H, CH2), 5.14-5.20 (dd, J=4.6 and 12.1 Hz, 1H, CH), 6.49 (d, J=7.9 Hz, 1H, Ar), 6.76-6.86 (m, 2H, Ar), 7.08-7.14 (m, 2H), 7.76-7.85 (m, 3H, Ar), 8.81 (s, 1H, NH), 11.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.94, 38.72, 48.87, 54.82, 103.44, 106.70, 110.05, 121.86, 127.19, 129.36, 131.61, 133.62, 134.72, 140.23, 141.51, 155.15, 159.62, 167.01, 167.60, 169.82, 172.76; Anal. calcd. for C22H20N4O6: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.18; H, 4.42; N, 12.63.
