Reaction Steps
1,8-Diazabicyclo[5,4,0]undec-7-ene (0.2 g, 2.2 mmol) was added to a stirred suspension of 4-aminomethyl-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.3 g, 1.0 mmol) in acetonitrile (40 mL). After stirring for 30 minutes, ethyl isocyanate (0.09 g, 1.3 mmol) was added, and the mixture was stirred at room temperature for 24 hours. The mixture was concentrated and the residue was dissolved in methylene chloride (60 mL). The methylene chloride solution was washed with water (2×30 mL) and brine (30 mL), and dried (MgSO4). Solvent was removed and purified by chromatography (silica gel) to give 1-ethyl-3-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.2 g, 55%) as a white solid: mp 220-222° C.; 1H NMR (DMSO-d6) δ 0.99 (t, J=7.1 Hz, 3H, CH3), 1.90 (s, 3H, CH3), 2.03-2.09 (m, 1H), 2.50-2.74 (m, 3H), 2.97-3.07 (m, 2H), 4.59 (d, J=5.8 Hz, 2H), 6.09 (t, J=5.0 Hz, 1H), 6.41 (t, J=5.6 Hz, 1H), 7.65-7.82 (e, 3H, Ar), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 15.59, 21.01, 28.58, 29.11, 34.16, 38.65, 58.69, 121.25, 126.64, 131.37, 133.26, 134.46, 140.79, 157.92, 167.78, 168.41, 172.14, 172.22; Anal. calcd. for C18H20N4O5+0.08H2O: C, 57.83; H, 5.44; N, 14.99. Found: C, 57.26; H, 5.21; N, 14.79.
