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 4-fluorobenzoyl chloride (0.45 g, 2.8 mmol). The mixture was stirred at room temperature overnight followed by addition of MeOH (1 mL). After filtration, the resulting solid was washed with CH2Cl2 then recrystallized in CH3OH to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-benzamide as a white solid (0.5 g, 59%): mp, 233-235° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.6 (96%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.86-2.98 (m, 1H), 4.95 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.30-7.38 (m, 2H), 7.72-7.86 (m, 3H), 7.96-8.03 (m2H), 9.18 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.35, 48.86, 115.15, 115.44, 121.87, 127.12, 129.91, 130.03, 130.37, 131.52, 133.05, 134.80, 139.21, 162.35, 165.54, 165.64, 166.95, 167.52, 169.82, 172.74. Anal Calcd for C21H16FN3O5: C, 66.61; H, 3.94; N, 10.26; F, 4.64. Found: C, 61.53; H, 3.82; N, 10.20; F, 4.72.
