Reaction Steps
A suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) and m-anisoyl chloride (0.4 g, 2.5 mmol) in THF 30 mL) was cooled to 5° C. Triethylamine (0.5 g, 4.8 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The mixture was concentrated, and the residue was stirred with 1N HCl (40 mL). The mixture was filtered, and the solid was slurried with hot ethanol (20 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-methoxy-benzamide (0.8 g, 93%) as a white solid: mp 244-246° C.; 1H NMR (DMSO-d6) δ 2.01-2.07 (m, 1H), 2.36-2.65 (m, 2H), 2.86-3.00 (m, 1H), 3.80 (s, 3H, CH3), 4.41-4.61 (m, 4H, 2CH2), 5.12-5.19 (dd, J=5.1 and 13.2 Hz, 1H, CH), 7.08-7.12 (m, 1H, Ar), 7.35-7.65 (m, 6H, Ar), 9.09 (t, J=5.6 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.59, 31.17, 46.29, 51.59, 55.24, 112.41, 117.19, 119.44, 121.65, 128.31, 129.46, 130.67, 131.61, 134.68, 135.46, 140.12, 159.18, 166.08, 168.06, 171.00, 172.82; Anal. calcd. for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C, 64.62; H, 5.06; N, 10.23.
