반응 #540195

반응 방정식

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

CH3CN H2O

→

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

수율 31.0%

용매

cyclohexene

DMF

반응 조건

후처리

1. 1
   여과The suspension was filtered
2. 2
   세척washed with DMF (30 mL)
3. 3
   여과The suspension was filtered
4. 4
   기타The solvent was removed in vacuo
5. 5
   workup.ADDITIONTo the residue, was added DMF (20 mL)
6. 6
   기타water (80 mL) to give a suspension
7. 7
   여과The suspension was filtered
8. 8
   세척washed with water (50 mL), ethyl acetate (50 mL) and water (50 mL)
9. 9
   기타to give a brown solid, which
10. 10
    기타was purified with preparative HPLC (C18 5/95 for 2 minutes
11. 11
    workup.WAITthen gradient to 50/50 in 18 min

실험 절차

A suspension of 3-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (4.1 g, 13 mmol) and 20% Pd(OH)2/C (0.9 g) in cyclohexene (20 mL) and DMF (60 mL) was heated in a 125° C. oil bath overnight. The suspension was filtered thru a pad of Celite, and washed with DMF (30 mL). The DMF solution and Charcoal (4 g) were stirred at room temperature for 5 hours. The suspension was filtered thru a pad of Celite. The solvent was removed in vacuo. To the residue, was added DMF (20 mL), and then water (80 mL) to give a suspension. The suspension was filtered and washed with water (50 mL), ethyl acetate (50 mL) and water (50 mL) to give a brown solid, which was purified with preparative HPLC (C18 5/95 for 2 minutes then gradient to 50/50 in 18 min CH3CN/H2O) to give 3-(6-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.15 g, 31% yield): HPLC: Waters Xterra C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% NH4HCO2, 5.31 min (99.8%); mp: 314-316° C.; 1H NMR (DMSO-d6) δ2.08-2.14 (m, 1H, CH—H), 2.54 (s, 3H, CH3), 2.55-2.67 (m, 2H, 2CHH), 2.75-2.90 (m, 1H, CHH), 5.16 (dd, J=5, 11 Hz, 1H, NCR), 5.59 (brs, 2H, NH2), 7.04-7.08 (m, 2H, Ar), 7.31-7.34 (m, 1H, Ar), 10.97 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.06, 22.96, 30.62, 56.22, 105.89, 121.34, 122.61, 127.35, 137.89, 147.63, 149.24, 160.39, 169.68, 172.66; LCMS: MH=287; Anal Calcd for C14H14N4O3+1H2O: C, 55.26; H, 5.30; N, 18.41. Found: C, 54.99; H, 5.22; N, 18.35.

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