Reaction Steps
To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.16 mmol) in CH2Cl2 (60 ml), was added diisopropylethylamine (0.94 mL, 5.4 mmol) and piperonyloyl chloride (0.5 g, 2.8 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched by the addition of MeOH (1 mL). The suspension was filtered, and the solid was rinsed with CH2Cl2 (10 mL) to afford benzo[1,3]dioxole-5-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide as a white solid (0.8 g, 85%): mp, 231-233° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.7 (99%); 1H NMR (DMSO-d6): δ 2.06-2.10 (m, 1H), 2.53-2.64 (m, 2H), 2.86-2.97 (m, 1H), 4.92 (d, J=5.6 Hz, 2H), 5.14-5.20 (dd, J=5, 12 Hz, 1H), 6.11 (s, 2H), 7.03 (d, J=8.1 Hz, 1H), 7.45-7.85 (m, 5H), 9.00 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.33, 48.85, 101.68, 107.34, 107.90, 121.81, 122.35, 127.08, 127.88, 131.50, 133.01, 134.77, 139.44, 147.36, 149.87, 165.70, 166.96, 167.52, 169.82, 172.74. Anal Calcd for C22H17N3O7+0.2H2O: C, 60.19; H, 4.00; N, 9.57. Found: C, 60.15; H, 3.71; N, 9.46.
