反应详情

温度

5 °C

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 p-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 (30 mL). The mixture was filtered, and 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]-4-methoxy-benzamide (0.8 g, 90%) as a white solid: mp 289-291° C.; 1H NMR (DMSO-d6) δ 2.01-2.05 (m, 1H), 2.32-2.65 (m, 2H), 2.86-3.00 (m, 1H), 3.81 (s, 3H, OCH3), 4.40-4.60 (m, 4H, 2CH2), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 7.02 (d, J=8.6 Hz, 2H, Ar), 7.46-7.64 (m, 3H, Ar), 7.85 (d, J=8.7 Hz, 2H, Ar), 8.93 (t, J=5.3 Hz, 1H, NH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.58, 31.17, 46.28, 51.59, 55.32, 113.51, 121.57, 126.25, 128.27, 129.06, 130.64, 131.58, 134.93, 140.07, 161.63, 165.81, 168.07, 170.98, 172.81; Anal. calcd. for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C, 64.51; H, 5.04; N, 10.09.

1. concentrationThe mixture was concentrated
2. stirringthe residue was stirred with 1N HCl (30 mL)
3. filtrationThe mixture was filtered