Reaction Steps
Triethylamine (0.5 g, 5.0 mmol) was added to a stirred 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 methoxyacetyl chloride (0.3 g, 2.7 mmol) in THF (30 mL) at room temperature. The mixture was stirred at room temperature overnight. Reaction mixture was quenched with methanol (1 mL) and then concentrated. The residue was stirred with 1N HCl (30 mL) for 30 minutes 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-acetamide (0.4 g, 57%) as a white solid: mp 232-234° C.; 1H NMR (DMSO-d6) δ 2.00-2.04 (m, 1H), 2.32-2.64 (m, 2H), 2.85-3.00 (m, 1H), 3.31 (s, 3H, CH3), 3.87 (s, 2H, CH2), 4.35 (d, J=6.2 Hz, 2H, CH2), 4.41 (d, J=17.3 Hz, 1H), 4.49 (d, J=17.3 Hz, 1H), 5.10-5.17 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.45-7.64 (m, 3H, Ar), 8.46 (t, J=5.8 Hz, 1H, NH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.57, 31.16, 38.42, 46.18, 51.54, 58.61, 71.46, 121.60, 128.23, 130.69, 131.56, 134.65, 140.01, 168.03, 169.20, 170.97, 172.82, Anal. calcd. for C17H19N3O5: C, 59.12; H, 5.55; N, 12.17. Found: C, 59.10; H, 5.51; N, 12.05.
