反应详情

A mixture of 2-amino-5-methylbenzoic acid (1.0 g, 6.6 mmol) and CDI (1.0 g, 6.1 mmol) in acetonitrile (15 mL) was stirred at room temperature for 1.5 hours. To the suspension, was added 3-amino-piperidine-2,6-dione hydrogen chloride (1.0 g, 6.1 mmol) and sodium hydrogen carbonate (0.45 g, 3.6 mmol), and the mixture was heated at 50° C. for 21 hours. The suspension was cooled to room temperature for 1 hour. The suspension was filtered and washed with acetonitrile (20 mL), water (2×20 mL) and ethyl acetate (20 mL) to give 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-methyl-benzamide as a blue solid (1.1 g, 63% yield): 1H NMR (DMSO-d6) δ 1.91-1.98 (m, 1H, CHH), 2.05-2.14 (m, 1H, CHH), 2.17 (s, 3H, CH3), 2.50-2.56 (m, 1H, CHH), 2.73-2.85 (m, 1H, CHH), 4.69-4.77 (m, 1H, NCH), 6.20 (br, 2H, NH2), 6.63 (d, J=9 Hz, 1H, Ar), 7.00 (dd, J=2, 8 Hz, 1H, Ar), 7.34 (d, J=2 Hz, 1H, Ar), 8.43 (d, J=8 Hz, 1H, NH), 10.84 (s, 1H, NH); 13C NMR (DMSO-d6) δ 19.89, 24.13, 30.92, 48.93, 113.87, 116.48, 122.81, 127.87, 132.72, 147.40, 168.55, 172.40, 172.97.

1. temperaturethe mixture was heated at 50° C. for 21 hours
2. temperatureThe suspension was cooled to room temperature for 1 hour
3. filtrationThe suspension was filtered
4. washwashed with acetonitrile (20 mL), water (2×20 mL) and ethyl acetate (20 mL)