Imidazole → 3-(2,7-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione

HRID 509496

Reaction equation

HRID 509496 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:16]=[CH:15]N=C1.C(Cl)(=O)C.Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:15][C:16]1[N:22]([CH:23]2[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]2=[O:30])[C:4](=[O:6])[C:3]2[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][CH:7]=2)[N:1]=1

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 753164-Methylanthranilic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 252358703-(2,7-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dioneYield 67.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-4-methylbenzoic acid (2.0 g, 13 mmol) and imidazole (1.1 g, 16 mmol) in acetonitrile (20 mL), was added acetyl chloride (1.1 mL, 16 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 (2.2 g, 13 mmol), imidazole (2.0 g, 30 mmol) and triphenyl phosphite (4.2 mL, 16 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-(2,7-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (2.52 g, 67% yield): HPLC: Waters Symmetry C13, 5 μM, 3.9×150 mm, 1 mL/min. 240 nm, 20/80 CH3CN/0.1% H3PO4, 5.13 min (99.9%); mp: 305° C. (decomp); 1H NMR (DMSO-d6) δ 2.08-2.24 (m, 1H, CHH), 2.45 (s, 3H, CH3), 2.56-2.75 (m, 5H, 2CHH), 2.81-2.91 (m, 1H, CHH), 5.24 (dd, J=6, 11 Hz, 1H, NCH), 7.32 (dd, J=1.8 Hz 1H, Ar), 7.43 (s, 1H, Ar), 7.91 (d, J=8 Hz, 1H, Ar), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.00, 21.35, 23.45, 30.61, 56.43, 117.94, 125.80, 126.10, 127.97, 145.21, 146.98, 154.96, 160.34, 169.56, 172.62; LCMS: MH=286; Anal Calcd for C15H15N3O3: C, 63.15; H, 5.21; N, 14.73. Found: C, 63.14; H, 5.21; N, 14.76.

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-f7e95840ca7240c4a41283bc4334a971
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Linked notes

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