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

HRID 509473

Reaction equation

HRID 509473 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:18]=[CH:17]N=C1.C(Cl)(=O)C.Cl.[NH2:24][CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:17][C:18]1[N:24]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:4](=[O:6])[C:3]2[C:2](=[CH:10][CH:9]=[C:8]([N+:11]([O-:13])=[O:12])[CH:7]=2)[N:1]=1

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 120322-Amino-5-nitrobenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 687281433-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-5-nitrobenzoic acid (5.0 g, 28 mmol) and imidazole (2.2 g, 33 mmol) in acetonitrile (50 mL), was added acetyl chloride (2.3 mL, 33 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 (4.5 g, 28 mmol), imidazole (4.1 g, 60 mmol) and triphenyl phosphite (8.7 mL, 33 mmol) and heated to reflux for 22 hours. To the mixture, was added water (60 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give 3-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (5.3 g, 61% yield): 1H NMR (DMSO-d6) δ 2.19-2.26 (m, 1H, CHH), 2.60-2.69 (m, 2H, 2CHH), 2.72 (s, 3H, CH1), 2.79-2.87 (m, 1H, CHH), 5.37 (dd, J=5, 11 Hz, 1H, NCH), 7.83 (d, J=9 Hz, 1H, Ar), 8.56 (dd, J=3, 9 Hz, 1H, Ar), 8.74 (dt, J=3 Hz 1H, Ar), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.69, 23.82, 30.57, 56.98, 119.46, 120.20, 122.21, 128.45, 128.74, 144.90, 150.85, 159.13, 159.78, 169.12, 172.53.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL)

Sources & evidence

ORD record
ord-cefaf94f73724d438e40a7c22e47af6a
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Linked notes

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