Reaction Steps
To a stirred solution of [2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylamino]acetic acid (0.73 g, 2.2 mmol) in DMF (20 mL), were successively added HOBt (0.32 g, 2.4 mmol), DBU (0.38 g, 2.5 mmol), methylamine (0.062 g, 2.0 mmol) and EDC-Cl (0.58 g, 3.0 mmol). The solution was stirred overnight at room temperature. The solvent was evaporated in vacuo, giving a yellow oil. The oil was dissolved in CH2Cl2 (100 mL), washed with water (3×50 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo to give a yellow solid. This material was triturated with diethyl ether for 1 hour and then filtered, and the resulting solid was recrystallized from ethanol, and the recrystallized solid was rinsed with diethyl ether, providing 0.45 g (65%) of the product as a yellow solid: mp 239-241° C.; 1H NMR (DMSO-d6) δ 2.01-2.05 (m, 1H), 2.47-2.56 (m, 2H), 2.62 (d, J=4.5 Hz, 3H), 2.97-2.82 (m, 1H), 3.91 (d, J=5.6 Hz, 2H), 5.07 (dd, J=12.5 Hz, J=5.4 Hz, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.95 (t, J=5.5 Hz, 1H), 7.07 (d, J=7.1 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 8.00 (d, J=4.5 Hz, 1H), 11.10 (s, 1H); 13C NMR (DMSO-d6) δ 22.14, 25.53, 30.95, 45.16, 48.53, 109.87, 110.92, 117.38, 132.02, 136.19, 145.80, 167.28, 168.65, 168.87, 169.99, 172.76; Anal. calcd. for C16H16N4O5.0.15H2O.0.03Et2O: C, 55.44; H, 4.79; N, 16.04. Found: C, 55.31; H, 4.56; N, 15.65.
