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 o-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 overnight. The reaction was quenched with methanol (1 mL), and the mixture was concentrated. The residue was stirred with 1N HCl (30 mL) and filtered. The solid was slurried with ethanol (15 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-methoxy-benzamide (0.8 g, 94%) as a white solid: mp 236-238° C.; 1H NMR (DMSO-d6) δ 2.01-2.06 (m, 1H), 2.32-2.66 (m, 2H), 2.86-3.01 (m, 1H), 3.88 (s, 3H, OCH3), 4.39-4.61 (m, 4H, 2CH2), 5.12-5.19 (dd, J=4.9 and 13.1 Hz, 1H, CH), 7.02 (t, J=7.4 Hz, 1H, Ar), 7.16 (d, J=8.3 Hz, 1H, Ar), 7.44-7.72 (m, 5H, Ar), 8.77 (t, J=5.6 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.60, 31.17, 46.20, 51.55, 55.82, 111.93, 120.41, 121.51, 123.10, 128.24, 130.22, 130.43, 131.57, 132.17, 134.89, 139.94, 156.87, 165.34, 168.09, 171.00, 172.83; Anal. calcd. for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C, 64.59; H, 5.01; N, 10.17.
