Acetonitrile--water (1/1) → 3-(6-Amino-2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)piperidine-2,6-dione

HRID 453013

Reaction equation

HRID 453013 reaction equation
[CH3:1][C:2]1[N:11]([CH:12]2[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]2=[O:19])[C:10](=[O:20])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:21]([O-])=O)[CH:8]=2)[N:3]=1.CC#N.O>C1CCCCC=1.CN(C=O)C.[OH-].[OH-].[Pd+2]>[NH2:21][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH3:1])[N:11]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:10]2=[O:20]

Participants

6

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 687281433-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

Product 1

HCID 252357313-(6-Amino-2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)piperidine-2,6-dioneYield 31%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolventHCID 8079CyclohexeneSolvent

Conditions

Temperature
125 °C

Procedure

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.

Workup

  1. filtrationThe suspension was filtered
  2. washwashed with DMF (30 mL)
  3. filtrationThe suspension was filtered
  4. customThe solvent was removed in vacuo
  5. additionTo the residue, was added DMF (20 mL)
  6. customwater (80 mL) to give a suspension
  7. filtrationThe suspension was filtered
  8. washwashed with water (50 mL), ethyl acetate (50 mL) and water (50 mL)
  9. customto give a brown solid, which
  10. customwas purified with preparative HPLC (C18 5/95 for 2 minutes
  11. waitthen gradient to 50/50 in 18 min

Sources & evidence

ORD record
ord-c71bff9adb6b4905b041628ce3084dc5
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Linked notes

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