반응 #540180

반응 방정식

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

imidazole

triphenyl phosphite

2-amino-5-methylbenzoic acid

imidazole

acetyl chloride

→

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

수율 38.0%

용매

DMF

acetonitrile

water

water

반응 조건

후처리

1. 1
   온도heated
2. 2
   온도to reflux for 22 hours
3. 3
   여과The suspension was filtered
4. 4
   세척washed with water (2×100 mL), ethyl acetate (2×100 mL), sodium hydrogen carbonate (sat, 100 mL) and water (100 mL)
5. 5
   기타to give a white solid, which
6. 6
   여과The suspension was filtered
7. 7
   세척washed with DMF (5 mL)
8. 8
   기타to give a white solid
9. 9
   기타at room temperature
10. 10
    기타overnight
11. 11
    여과The suspension was filtered
12. 12
    세척washed with water (2×50 mL)

실험 절차

To a stirred mixture of 2-amino-5-methylbenzoic acid (4.8 g, 32 mmol) and imidazole (2.6 g, 38 mmol) in acetonitrile (100 mL), was added acetyl chloride (2.7 mL, 38 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 (5.2 g, 32 mmol), imidazole (4.7 g, 70 mmol) and triphenyl phosphite (9.9 mL, 38 mmol) and heated to reflux for 22 hours. To the mixture, was added water (100 mL). The suspension was filtered and washed with water (2×100 mL), ethyl acetate (2×100 mL), sodium hydrogen carbonate (sat, 100 mL) and water (100 mL) to give a white solid, which was stirred in DMF (40 mL) overnight. The suspension was filtered and washed with DMF (5 mL) to give a white solid. The solid was stirred in water (100 mL) at 60° C. for 2 hours, then at room temperature overnight. The suspension was filtered and washed with water (2×50 mL) to give 3-(2,6-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (3.4 g, 38% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 5.37 min (99.8%); mp: 270-272° C.; 1H NMR (DMSO-d6) δ 2.10-2.22 (m, 1H, CHH), 2.43 (s, 3H, CH3), 2.56-2.72 (m, 5H, CH3, 2CHH), 2.76-2.92 (m, 1H, CHH), 5.24 (dd, J=6, 11 Hz, 1H, NCH), 7.52 (d, J=8 Hz, 1H, Ar), 7.64 (dd, J=2, 8 Hz, 1H, Ar), 7.82 (s, 1H, Ar), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.76, 20.95, 23.34, 30.60, 56.47, 120.05, 125.20, 126.39, 135.96, 136.19, 144.87, 153.99, 160.40, 169.53, 172.62; LCMS: MH=286; Anal Calcd for C15H15N3O3+2H2O: C, 56.07; H, 5.96; N, 13.08. Found: C, 55.73; H, 5.75; N, 13.01.

출처