Sodium hydride → HCID 22614874, compound

HRID 842678Notes

Reaction equation

HRID 842678 reaction equation
[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].[H-].[Na+].[Cl:8][C:9]1[C:10]([N:24]2[C:28]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[N:27][N:26]=[C:25]2[C:35](OCC)=O)=[C:11]2[C:16](=[CH:17][C:18]=1[Cl:19])[N:15]=[C:14]([O:20][CH3:21])[C:13]([O:22][CH3:23])=[N:12]2>C1(C)C=CC=CC=1>[Cl:8][C:9]1[C:10]([N:24]2[C:28]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[N:27][N:26]=[C:25]2[C:35]2[O:5][N:4]=[C:1]([CH3:2])[N:3]=2)=[C:11]2[C:16](=[CH:17][C:18]=1[Cl:19])[N:15]=[C:14]([O:20][CH3:21])[C:13]([O:22][CH3:23])=[N:12]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 22614908HCID 22614908, compound

Product 1

HCID 22614874HCID 22614874, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Acetamide oxime (120 mg, 1.62 mmol) followed by sodium hydride (80% w/w dispersion in oil, 8 mg, 0.27 mmol) were added to a stirred suspension of 6,7-dichloro-2,3-dimethoxy-5-[3-ethoxycarbonyl-5-(3-pyridyl)-4H-1,2,4-triazol-4-yl]quinoxaline (Preparation 94, 250 mg, 0.53 mmol) in dry toluene (15 mL) at room temperature under nitrogen. The mixture was heated under reflux for 3.5 hours, cooled and the solution partitioned between ethyl acetate and brine. The aqueous phase was extracted with ethyl acetate (2×20 mL), the combined organic extracts dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, by gradient elution using hexane:ethyl acetate (7:3 changing to 1:1, by volume) to give the title compound (210 mg, 82%) as a white solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 3.5 hours
  3. temperaturecooled
  4. customthe solution partitioned between ethyl acetate and brine
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×20 mL)
  6. dry with materialthe combined organic extracts dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel, by gradient elution

Sources & evidence

ORD record
ord-432491f726494a4aa6249eade175e92c
Source dataset
uspto-grants-2002_04
Patent number
US06376490B1

Reaction notes

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