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

HRID 591817Notes

Reaction equation

HRID 591817 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)=[CH:25][C:26]=3[O:31][CH3:32])[N:21]=2)[CH:17]=[C:16]([CH3:34])[N:15]=1.O>CS(C)=O>[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]([O:10][CH2:9][CH2:8][O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:25][C:26]=3[O:31][CH3:32])[N:21]=2)[CH:17]=[C:16]([CH3:34])[N:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 31236PhenoxyethanolHCID 1363480402-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one

Product 1

HCID 1359390692-(2,6-Dimethylpyridin-4-yl)-5-methoxy-7-(2-phenoxyethoxy)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2-phenoxy-ethanol (0.90 g, 6.50 mmol) in DMSO (5 mL) was added sodium hydride (60% in mineral oil, 0.16 g, 4.00 mmol) in small portions. The reaction mixture was stirred at room temperature under nitrogen for 1 hour. 2-(2,6-Dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one (0.20 g, 0.67 mmol) was added and stirring continued at 90° C. for 17 hours. The reaction was then cooled to room temperature, water (100 mL) was added, and was extracted with ethyl acetate (200 mL). The organic phase was washed with brine and dried over anhydrous Na2SO4. Solvent was removed and the crude compound was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in CH2Cl2 as eluent) to give the title compound as a white solid. Yield: 70 mg (25%). MP 223-224° C. 1H NMR (400 MHz, CDCl3): δ 11.35 (s, 1H), 7.75 (s, 2H), 7.32 (t, J=8.0 Hz, 2H), 7.02-6.97 (m, 3H), 6.91 (d, J=2.0 Hz, 1H), 6.60 (d, J=1.6 Hz, 1H), 4.49-4.47 (m, 2H), 4.41-4.39 (m, 2H), 3.97 (s, 3H), 2.67 (s, 6H). MS (ES+) m/z: 418.08 (M+1).

Workup

  1. stirringstirring
  2. waitcontinued at 90° C. for 17 hours
  3. temperatureThe reaction was then cooled to room temperature
  4. extractionwas extracted with ethyl acetate (200 mL)
  5. washThe organic phase was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. customSolvent was removed
  8. customthe crude compound was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-05707544abc948bfa19330d269eaa4d4
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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