반응 #540183

반응 방정식

3-amino-piperidine-2,6-dione hydrogen chloride

imidazole

triphenyl phosphite

2-amino-5-fluorobenzoic acid

imidazole

acetyl chloride

→

3-(6-fluoro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

수율 53.9%

용매

acetonitrile

반응 조건

후처리

1. 1
   온도heated
2. 2
   온도to reflux for 22 hours
3. 3
   여과The suspension was filtered
4. 4
   세척washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL)

실험 절차

To a stirred mixture of 2-amino-5-fluorobenzoic acid (1.2 g, 7.8 mmol) and imidazole (0.63 g, 9.3 mmol) in acetonitrile (15 mL), was added acetyl chloride (0.66 mL, 9.3 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (1.3 g, 7.7 mmol), imidazole (1.2 g, 17 mmol) and triphenyl phosphite (2.2 mL, 8.5 mmol) and heated to reflux for 22 hours. The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give 3-(6-fluoro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.2 g, 53% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 5.99 min (99.3%); mp: 273-275° C.; 1H NMR (DMSO-d6) δ 2.13-2.23 (m, 1H, CHH), 2.57-2.71 (m, 5H, CH3, 2CHH), 2.75-2.95 (m, 1H, CHH), 5.30 (dd, J=6, 11 Hz, 1H, NCH), 7.70-7.73 (m, 3H, Ar), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.31, 30.58, 56.63, 110.54 (d, JC-F=23 Hz), 121.40 (d, JC-F=8 Hz), 123.24 (d, JC-F=24 Hz), 129.47 (d, JC-F=8 Hz), 143.75, 154.45, 159.83 (d, JC-F=245 Hz), 159.86 (d, JC-F=3 Hz), 169.37, 172.58; LCMS: MH=290; Anal Calcd for C14H12N3O3F+1.3H2O: C, 53.78; H. 4.71; N, 13.44. Found: C, 53.75; H, 4.61; N, 13.50.

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