Reaction Steps
1,8-Diazabicyclo[5,4,0]-unded-7-ene (0.8 g, 5.3 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) in acetonitrile (100 mL). The mixture was stirred for 30 minutes. Propyl isocyanate (0.3 g, 3.2 mmol) was added, and the mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with CH2Cl2 (60 mL) and 2N HCl (30 mL). The mixture was filtered and the solid was slurried with methanol (40 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-propyl-urea (0.3 g, 31%) as a white solid: mp 298-300° C.; 1H NMR (DMSO-d6) δ 0.82 (t, J=7.3 Hz, 3H, CH3), 1.32-1.41 (m, 2H), 1.99-2.04 (m, 1H), 2.37-2.65 (m, 2H), 2.86-2.99 (m, 3H), 4.29 (d, J=6.0 Hz, 2H), 4.37 (d, J=17.3 Hz, 1H), 4.45 (d, J=17.3 Hz, 1H), 5.11-5.18 (dd, J=5.1 and 13.2 Hz, 1H, CH), 6.00 (t, J=5.5 Hz, 1H, NH), 6.38 (t, J=5.9 Hz, 1H, NH), 7.47-7.62 (m, 3H, Ar), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 11.31, 22.62, 23.24, 31.18, 41.16, 46.13, 51.50, 121.36, 128.19, 130.24, 131.58, 136.29, 139.80, 157.97, 168.13, 171.01, 172.87; Anal. calcd. for C18H22N4O4: C, 60.32; H, 6.19; N, 15.63. Found: C, 59.93; H, 6.27; N, 15.40.
