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 2-chlorobenzoyl chloride (0.5 g, 2.8 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (1 mL) and then washed with H2O (40 mL), 1N HCl (40 mL), brine (40 mL), and dried over MgSO4. The organic layer was concentrated in vacuo, and the resulting oil was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2 for 10 min, then 5% MeOH in CH2Cl2 for 10 min):) to afford 2-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide as a white solid (0.55 g, 60%): mp, 209-211° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.0 min (99%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.87-2.93 (m, 1H), 4.92 (d, J=5.9 Hz, 2H), 5.14-5.20 (dd, J=5, 12 Hz, 1H), 7.39-7.57 (m, 4H), 7.82-7.89 (m, 3H), 9.12 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.96, 30.91, 38.10, 48.86, 121.95, 127.15, 128.97, 129.62, 129.83, 130.94, 131.54, 133.10, 134.80, 136.49, 138.74, 166.77, 166.93, 167.48, 169.80, 172.74. Anal Calcd for C21H16ClN3O5: C, 59.23; H, 3.79; N, 9.87; Cl, 8.33. Found: C, 59.24; H, 3.45; N, 9.71; Cl, 8.32.
