反应详情

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide (0.60 g, 2.2 mmol), trimethyl orthoformate (3 mL, 26.8 mmol), and p-toluene sulfonic acid (0.060 g) in acetonitrile (20 mL) was heated to reflux for 30 hours. The mixture was cooled to room temperature. To the mixture, water (75 mL) and ether (20 mL) were added, and the resulting mixture was stirred for 2 hours. The suspension was filtered and washed with water and ether (50 mL each) to give 3-(5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (0.28 g, 47% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.08 min (99%); mp: 262-264° C.; 1H NMR (DMSO-d6) δ 2.09-2.16 (m, 1H, CHH), 2.62-2.84 (m, 6H, CH2, CH3, CHH), 5.42 (brs, 1H, NCH), 7.32 (d, J=7 Hz, 1H, Ar), 7.52 (d, J=8 Hz, 1H, Ar), 7.69 (t, J=8 Hz, 1H, Ar), 8.30 (s, 1H, CH), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ22.35, 22.62, 30.88, 58.00, 119.81, 125.36, 129.57, 133.72, 140.15, 147.08, 149.07, 160.21, 169.91, 172.33, 172.44; LCMS: MH=272; Anal. Calcd. for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49. Found: C, 61.67; H, 4.40; N, 15.41.

1. temperatureto reflux for 30 hours
2. filtrationThe suspension was filtered
3. washwashed with water and ether (50 mL each)