Sodium hydride → HCID 17942763, compound

HRID 855685Notes

Reaction equation

HRID 855685 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][C:11](=[O:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1>CN(C=O)C.[Cl-].[NH4+].CCOCC>[ClH:16].[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][N:10]=[C:11]([O:13][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]5[CH2:34][CH2:35][O:36][CH2:37][CH2:38]5)=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:12]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 47787925-(4-Fluorophenyl)-2,4-dihydro-3H-pyrazol-3-oneHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 17942763HCID 17942763, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

3-(4-Fluorophenyl)-4,5-dihydro-1H-pyrazol-5-one (222 mg, 1.25 mmol) was added in portions over 10 minutes to a suspension of sodium hydride (50 mg, 1.25 mmol, prewashed with hexane) in DMF (3 ml) under nitrogen. After stirring for 20 minutes at ambient temperature, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (169 mg, 0.5 mmol), (prepared as described for the starting material in Example 2), was added and the mixture was heated at 60° C. for 1 hour. After cooling, the mixture was diluted with aqueous ammonium chloride solution and ether was added. The precipitate was collected by filtration, washed with water, and dried under vacuum. The solid was dissolved in methylene chloride/methanol (1/1) and 4M ethereal hydrogen chloride (0.5 ml) was added. After removal of the solvent by evaporation, the solid was triturated with ether, collected by filtration and dried under vacuum to give 4-(5-(4-fluorophenyl)pyrazol-3-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (115 mg, 48%).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 60° C. for 1 hour
  3. temperatureAfter cooling
  4. additionwas added
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried under vacuum
  8. dissolutionThe solid was dissolved in methylene chloride/methanol (1/1)
  9. addition4M ethereal hydrogen chloride (0.5 ml) was added
  10. customAfter removal of the solvent
  11. customby evaporation
  12. customthe solid was triturated with ether
  13. filtrationcollected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-0c7f3ab9561641c2a32dfeeb8e5c34fd
Source dataset
uspto-grants-2007_08
Patent number
US07262201B1

Reaction notes

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