Imidazole → HCID 24967231, compound

HRID 1409602Notes

Reaction equation

HRID 1409602 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4]([OH:6])=O.N1[CH:17]=[CH:16]N=C1.C(Cl)(=O)C.Cl.[NH2:23][CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:12][O:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]2[C:3]=1[C:4](=[O:6])[N:23]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:16]([CH3:17])=[N:1]2

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 27353572-Amino-6-methoxybenzoic Acid

Product 1

HCID 24967231HCID 24967231, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-6-methoxybenzoic acid (2.0 g, 12 mmol) and imidazole (1.0 g, 14 mmol) in acetonitrile (20 mL), was added acetyl chloride (1.0 mL, 14 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 (2.0 g, 12 mmol), imidazole (1.8 g, 26 mmol) and triphenyl phosphite (3.8 mL, 14 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), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL) to give 3-(5-methoxy-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.3 g, 35% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 15/85 CH3CN/0.1% H3PO4, 3.37 min (99.4%); mp: 274-276° C.; 1H NMR (DMSO-d6) δ 2.09-2.16 (m, 1H, CHH), 2.51-2.63 (m, 5H, CH3, 2CHH), 2.72-2.89 (m, 1H, CHH), 3.83 (s, 3H, CH3), 5.14 (dd, J=6, 11 Hz, 1H, NCH), 6.98 (d, J=8 Hz, 1H, Ar), 7.12 (d, J=8 Hz, 1H, Ar), 7.69 (t, J=8 Hz, 1H, Ar), 10.96 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.84, 23.36, 30.55, 55.85, 56.16, 107.96, 109.91, 118.26, 134.98, 149.24, 155.30, 158.13, 159.42, 169.63, 172.63; LCMS: MH=302; Anal Calcd for C15H15N3O4+1.6H2O: C, 54.57; H, 5.56; N, 12.73. Found: C, 54.19; H, 5.42; N, 12.55.

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), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL)

Sources & evidence

ORD record
ord-27a02edd934b4594aea91d54ee8e7bd1
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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