Reaction Steps
Triethylamine (0.5 g, 5.0 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) and m-toluoyl chloride (0.4 g, 2.8 mmol) in THF (30 mL) at 5-10° C. After stirring at 5° C. for 10 minutes, the mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (20 mL). The residue was dissolved in CH2Cl2 (80 mL), washed with H2O (30 mL) and brine (30 mL), and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (silica gel) to N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3 dihydro-1H-isoindol-4-ylmethyl]-3-methyl-benzamide (0.5 g, 66%) as a white solid: mp 218-220° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.37 (s, 3H, CH3), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 4.94 (d, J=5.7 Hz, 2H, CH2), 5.14-5.21 (dd, J=5.4 and 12.7 Hz, 1H, CH), 7.37-7.41 (m, 2H, Ar), 7.72-7.86 (m, 5H, Ar), 9.10 (t, J=5.6 Hz, 1H, NH), 11.14 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.91, 21.98, 30.93, 38.30, 48.87, 121.82, 124.42, 127.10, 127.83, 128.24, 131.52, 131.98, 132.99, 133.92, 134.77, 137.64, 139.39, 166.71, 166.96, 167.53, 169.81, 172.73; Anal. calcd. for C22H19N3O5+0.04H2O: C, 65.06; H, 4.74; N, 10.35. Found: C, 64.75; H, 4.68; N, 10.02.
