Reaction Steps
Dimethylamine/THF (2M, 6.1 mL, 12.3 mmol) was added to a stirred solution of 2-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (1.0 g, 3.1 mmol) in DMF (30 mL). The resulting solution was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with CH2Cl2 (15 mL). The mixture was filtered, and the solid was dissolved in H2O (10 mL). 4N HCl (1.5 mL) was added and stirred for 30 minutes. The resulting solution was concentrated, and the residue was evaporated with ethanol (3×10 mL). The residue was slurried with ether (15 mL) and ethanol (5 mL). The mixture was filtered to give 2-dimethylamino-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide hydrochloride (0.7 g, 54%) as a white solid: mp 273-275° C.; 1H NMR (DMSO-d6) δ 2.00-2.04 (m, 1H), 2.33-2.65 (m, 2H), 2.81 (s, 6H, 2CH3), 2.87-3.01 (m, 1H), 4.02 (s, 2H, CH2), 4.36 (d, J=17.4 Hz, 1H), 4.43 (d, J=4.6 Hz, 2H, CH2), 4.55 (d, J=17.4 Hz, 1H), 5.12-5.19 (dd, J=5.0 and 13.1 Hz, 1H, CH), 7.48-7.67 (m, 3H, Ar), 9.41 (t, J=5.7 Hz, 1H, NH), 10.08 (s, 1H, NH), 11.04 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.60, 31.16, 39.06, 43.05, 46.19, 51.55, 57.07, 121.95, 128.32, 130.87, 131.72, 133.59, 140.25, 164.43, 167.93, 170.94, 172.84; Anal. calcd. for C18H23N4O4Cl+0.34H2O: C, 53.92; H, 5.95; N, 13.94; Cl, 8.84. Found: C, 54.06; H, 6.08; N, 13.72; Cl, 9.06.
