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 3-fluorobenzoyl chloride (0.45 g, 2.8 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched with MeOH (1 mL) and concentrated in vacuo. 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 N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-fluoro-benzamide as a white solid (0.7 g, 77%): mp, 215-217° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.2 min. (99%); 1H NMR (DMSO-d6): δ 2.07-2.12 (m, 1H), 2.54-2.65 (m, 2H), 2.87-2.93 (m, 1H), 4.96 (d, J=5.8 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.39-7.84 (m, 7H), 9.26 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.40, 48.86, 114.29, 118.49, 121.92, 123.50, 127.15, 130.62, 131.52, 133.09, 134.82, 136.31, 138.97, 163.69, 165.31, 166.94, 167.51, 169.83, 172.74. Anal Calcd for C21H16FN3O5: C, 61.61; H, 3.94; N, 10.26; F, 4.64. Found: C, 61.36; H, 3.84; N, 10.00; F, 4.74.
