Sodium hydride → HCID 17942744, compound

HRID 855686Notes

Reaction equation

HRID 855686 reaction equation
[C:1]1([C:7]2[CH2:11][C:10](=[O:12])[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:23][CH:24]=2)[N:19]=[CH:18][N:17]=1>CN(C=O)C.[Cl-].[NH4+]>[ClH:15].[CH3:30][O:29][CH2:28][CH2:27][O:26][C:22]1[CH:21]=[C:20]2[C:25]([C:16]([O:12][C:10]3[CH:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[NH:8][N:9]=3)=[N:17][CH:18]=[N:19]2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 785775-Phenyl-4H-pyrazol-3-olHCID 10681434HCID 10681434, compound

Product 1

HCID 17942744HCID 17942744, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

3-Phenyl-4,5-dihydro-1H-pyrazol-5-one (270 mg, 1.68 mmol), (J. Org. Chem., 1967, 32, 3321-3324), was added in portions over 10 minutes to a suspension of sodium hydride (70 mg, 1.68 mmol, prewashed with pentane) in DMF (3 ml) under nitrogen. After stirring for 1 hour at ambient temperature 4-chloro-7-(2-methoxyethoxy)quinazoline (160 mg, 0.67 mmol) was added and the mixture was heated for 1 hour at 60° C. After cooling, the mixture was diluted with saturated aqueous ammonium chloride solution and partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methanol/methylene chloride (5/95). The volatiles were removed by evaporation, the residual solid was dissolved in methylene chloride and 3M ethereal hydrogen chloride (0.5 ml) was added. After removal of the solvent by evaporation, the residue was triturated with ether, collected by filtration and dried under vacuum to give 7-(2-methoxyethoxy)-4-(5-phenylpyrazol-3-yloxy)quinazoline hydrochloride (120 mg, 46%).

Workup

  1. additionwas added
  2. temperatureAfter cooling
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methanol/methylene chloride (5/95)
  9. customThe volatiles were removed by evaporation
  10. dissolutionthe residual solid was dissolved in methylene chloride
  11. addition3M ethereal hydrogen chloride (0.5 ml) was added
  12. customAfter removal of the solvent
  13. customby evaporation
  14. customthe residue was triturated with ether
  15. filtrationcollected by filtration
  16. customdried under vacuum

Sources & evidence

ORD record
ord-e7b3927441af45798ca0159fef8f533b
Source dataset
uspto-grants-2007_08
Patent number
US07262201B1

Reaction notes

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