Reaction Steps
1,8-Diazabicyclo[5,4,0]undec-7-ene (0.7 g, 4.3 mmol) was added to a stirred suspension of 3-[4-(aminomethyl)-1-oxo-1,3-dihydro-isoindol-2-yl]piperidine-2,6-dione hydrochloride (0.6 g, 1.9 mmol) in acetonitrile (50 mL). After stirring for 30 minutes, phenylacetyl chloride (0.4 g, 2.3 mmol) was added. The mixture was stirred at room temperature for 17 hours. Solvent was removed and the residue was stirred with water (40 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-phenyl-acetamide (0.41 g, 54%) as a white solid: mp 236-238° C.; 1H NMR (DMSO-d6) δ 1.94-1.98 (m, 1H, CH2), 2.15-2.19 (m, 1H, CH2), 2.49-2.63 (m, 1H, CH2), 2.85-2.99 (m, 1H, CH2), 3.47 (s, 2H, CH2), 4.23-4.43 (m, 4H, 2CH2), 5.07-5.14 (dd, J=5.1 and 13.2 Hz, 1H, CH), 7.18-7.33 (m, 5H, Ar), 7.46-7.64 (m, 3H, Ar), 8.61 (t, J=5.6 Hz, 1H, NH), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.51, 31.14, 42.23, 46.08, 51.47, 121.70, 126.34, 128.22, 128.95, 130.73, 131.69, 134.49, 136.16, 140.09, 167.99, 170.18, 170.87, 172.81; Anal. calcd. for C22H21N3O4+0.07H2O: C, 67.29; H, 5.43; N, 10.70. Found: C, 66.94; H, 5.22; N, 10.63.
