Sodium hydride → 4-(5-(3,4-Dimethoxyphenyl)pyrazol-3-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinazoline

HRID 855700Notes

Reaction equation

HRID 855700 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:13]2[CH2:17][C:16](=[O:18])[NH:15][N:14]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:32][CH2:33][CH2:34][CH2:35][N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[C:27]([O:30][CH3:31])[CH:28]=2)[N:23]=[CH:22][N:21]=1>CN(C=O)C.[Cl-].[NH4+]>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:13]2[NH:14][N:15]=[C:16]([O:18][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:32][CH2:33][CH2:34][CH2:35][N:36]5[CH2:37][CH2:38][O:39][CH2:40][CH2:41]5)=[C:27]([O:30][CH3:31])[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH:17]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 152835193-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-5-one

Product 1

HCID 179427524-(5-(3,4-Dimethoxyphenyl)pyrazol-3-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinazolineYield 57.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Sodium hydride (40 mg, 1 mmol, prewashed with THF) was added to a suspension of 3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-5-one (220 mg, 1 mmol) in DMF (3 ml) under nitrogen. After stirring for 20 minutes at ambient temperature, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (134 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), was added and the mixture was heated for 30 minutes at 60° C. After cooling, the mixture was diluted with saturated aqueous ammonium chloride solution and partitioned between methylene chloride and water. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate/methanol (1/10 followed by 5/4/1). The volatiles were removed by evaporation and the residual solid was collected by filtration, washed with ether and dried under vacuum to give 4-(5-(3,4-dimethoxyphenyl)pyrazol-3-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (120 mg, 57%).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated for 30 minutes at 60° C
  3. temperatureAfter cooling
  4. custompartitioned between methylene chloride and water
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried (MgSO4)
  7. customthe volatiles were removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methylene chloride/ethyl acetate/methanol (1/10 followed by 5/4/1)
  10. customThe volatiles were removed by evaporation
  11. filtrationthe residual solid was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-5c4116051303449c9909f51b3d67d043
Source dataset
uspto-grants-2007_08
Patent number
US07262201B1

Reaction notes

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