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 p-toluoyl chloride (0.43 g, 2.8 mmol). The mixture was then stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched with MeOH (1 mL) and washed with H2O (40 mL), 1N HCl (40 mL) and brine (40 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting mixture was purified by ISCO silica gel flash chromatography (eluent: 3% MeOH in CH2Cl2) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide as a white solid (0.5 g, 61%): mp, 218-220° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.3 (97%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.36 (s, 3H), 2.54-2.64 (m, 2H), 2.85-2.93 (m, 1H), 4.94 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 9.07 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 20.93, 31.97, 30.92, 38.26, 48.85, 121.81, 127.08, 127.30, 128.87, 131.11, 131.51, 132.98, 134.77, 139.47, 141.35, 166.47, 166.97, 167.54, 169.83, 172.74. Anal Calcd for C22H19N3O5: C, 65.18; H, 4.72; N, 10.36. Found: C, 64.78; H, 4.72; N, 10.07.
