Reaction Steps
To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.55 g, 4.8 mmol) in CH3CN (15 ml), was added triethyl amine (1.67 mL, 11.98 mmol) and 5-phenyl-1,3,4-oxadiazole-2-carbonyl-chloride (1.0 g, 4.8 mmol). The mixture was stirred at room temperature for 21 hours and a suspension was obtained. The reaction mixture was filtered, and the solid was rinsed with CH3CN (20 mL), water (2×20 mL), EtOAc (20 mL) and MeOH (20 mL) to afford 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethylamide as a white solid (1.34 g, 61%): mp, 279-281° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=4.90 min. (99%); 1H NMR (DMSO-d6): δ 2.08-2.10 (m, 1H), 2.53-2.64 (m, 2H), 2.86-2.98 (m, 1H), 4.98 (d, J=5 Hz, 1H), 5.18 (dd, J=5, 13 Hz, 1H), 7.62-7.72 (m, 3H), 7.85 (broad, 3H), 8.09-8.12 (m, 2H). 9.97 (t, J=5 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.90, 30.85, 38.24, 48.82, 122.07, 122.70, 126.98, 127.16, 129.46, 131.49, 132.58, 133.03, 134.77, 137.63, 153.51, 158.29, 164.94, 166.84, 167.42, 169.74, 172.67. Anal Calcd for C23H17N5O6: C, 60.13; H, 3.73; N, 15.24. Found: C, 56.69; H, 3.34; N, 15.41.
