Water → 2-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-phenoxyethoxy)-3H-quinazolin-4-one

HRID 591821Notes

Reaction equation

HRID 591821 reaction equation
[O:1]([CH2:8][CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:13][C:14]1[CH:19]=[C:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]([F:32])=[CH:25][C:26]=3F)[N:21]=2)[CH:17]=[C:16]([CH3:33])[N:15]=1.O>CN(C=O)C.C(O)(=O)C>[CH3:13][C:14]1[CH:19]=[C:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]([F:32])=[CH:25][C:26]=3[O:10][CH2:9][CH2:8][O:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[N:21]=2)[CH:17]=[C:16]([CH3:33])[N:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 31236PhenoxyethanolHCID 1363480062-(2,6-dimethylpyridin-4-yl)-5,7-difluoro-3H-quinazolin-4-one

Product 1

HCID 1363480192-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-phenoxyethoxy)-3H-quinazolin-4-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-phenoxyethanol (4.81 g, 34.8 mmol) in DMF (20 mL) was added sodium hydride (60% suspension in mineral oil, 0.70 g, 17.4 mmol) in portions and the reaction mixture was stirred at room temperature for 1 hour. To this mixture was added 2-(2,6-dimethylpyridin-4-yl)-5,7-difluoro-3H-quinazolin-4-one (0.50 g, 1.74 mmol) and the reaction mixture was stirred at room temperature for 16 hours. Water (1 mL) was added, neutralized to pH approximately 6-7 with acetic acid, concentrated, dissolved in ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (eluted with 50% ethyl acetate in hexanes, then 5% methanol in DCM) to give 2-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-phenoxyethoxy)-3H-quinazolin-4-one as a light yellow solid. Yield: 0.59 g (83%).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 hours
  2. concentrationconcentrated
  3. dissolutiondissolved in ethyl acetate
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (
  8. washeluted with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-65cdceff2f5a493dbc31f99d75428bf9
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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