반응 #540187

반응 방정식

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

imidazole

triphenyl phosphite

HCl

2-amino-5-hydroxybenzoic acid

imidazole

acetyl chloride

→

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

수율 31.3%

용매

water

methanol

acetonitrile

반응 조건

후처리

1. 1
   온도heated
2. 2
   온도to reflux for 22 hours
3. 3
   기타The solvent was removed in vacuo
4. 4
   workup.ADDITIONTo the residue, was added water (50 mL)
5. 5
   추출The aqueous layer was extracted with ethyl acetate (50 mL)
6. 6
   workup.ADDITIONTo the aqueous layer, was added ethyl acetate (50 mL)
7. 7
   workup.STIRRINGthe mixture was stirred at room temperature
8. 8
   기타to give a suspension
9. 9
   여과The suspension was filtered
10. 10
    기타to give a solid, which
11. 11
    여과The suspension was filtered
12. 12
    세척washed with methanol (2×30 mL) and water

실험 절차

To a stirred mixture of 2-amino-5-hydroxybenzoic acid (5.1 g, 33 mmol) and imidazole (5.0 g, 73 mmol) in acetonitrile (60 mL), was added acetyl chloride (5.2 mL, 73 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 (6.0 g, 37 mmol), imidazole (5.0 g, 73 mmol) and triphenyl phosphite (10.5 mL, 40 mmol) and heated to reflux for 22 hours. To the mixture, was added water (100 mL) and conc HCl until pH ˜1. The solvent was removed in vacuo. To the residue, was added water (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). To the aqueous layer, was added ethyl acetate (50 mL), and the mixture was stirred at room temperature to give a suspension. The suspension was filtered to give a solid, which was stirred in methanol (50 mL) overnight. The suspension was filtered and washed with methanol (2×30 mL) and water to give 3-(6-hydroxy-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (2.97 g, 31% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 5/95 grad 95/5 in 5 min CH3CN/0.1% H3PO4, 4.50 min (96.8%); mp: 315-317° C.; 1H NMR (DMSO-d6) δ 2.13-2.18 (m, 1H, CH—H), 2.58 (s, 3H, CH3), 2.62-2.71 (m, 2H, 2CH—H), 2.78-2.91 (m, 1H, CH—H), 5.22 (dd, J=6, 11 Hz, 1H, NCH), 7.24-7.32 (m, 2H, Ar), 7.49 (d, J=9 Hz, 1H, Ar), 10.07 (s, 1H, OH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.97, 23.10, 30.59, 56.36, 108.59, 121.24, 124.13, 128.19, 140.14, 151.39, 155.89, 160.24, 169.58, 172.63; LCMS: MH=288; Anal Calcd for C14H13N3O4+1H2O: C, 55.08; H, 4.95; N, 13.76. Found: C, 54.82; H, 4.74; N, 13.54.

출처