Cesium carbonate → 2-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-1-methyl-4-phenyl-1H-pyrazol-3-yl)oxy]ethyl acetate

HRID 1368645Notes

Reaction equation

HRID 1368645 reaction equation
[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12](I)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2].[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 222818952-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino)-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate

Product 1

HCID 222820392-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-1-methyl-4-phenyl-1H-pyrazol-3-yl)oxy]ethyl acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

2-[(5-{{[4-(tert-Butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate (Preparation 14) (1.95 g), benzeneboronic acid (0.78 g) and cesium carbonate (5.26 g) were suspended in 1,4-dioxane (50 ml) and water (5 ml). The mixture was degassed (vacuum and nitrogen atmosphere×5) and then tetrakis(triphenylphosphine)palladium(0) (50 mg) was added and the mixture degassed again. The mixture was heated at reflux for 2 hours and cooled to room temperature overnight. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (20 ml×3). The combined organics were washed with saturated aqueous sodium bicarbonate solution, dried with magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica eluting with a gradient elution of ethyl acetate:hexane (1:2 to 2:1) yielded the desired product as an off white solid (1.112 g).

Workup

  1. customThe mixture was degassed (vacuum and nitrogen atmosphere×5)
  2. additiontetrakis(triphenylphosphine)palladium(0) (50 mg) was added
  3. customthe mixture degassed again
  4. temperatureThe mixture was heated
  5. temperatureat reflux for 2 hours
  6. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
  7. extractionextracted with ethyl acetate (20 ml×3)
  8. washThe combined organics were washed with saturated aqueous sodium bicarbonate solution
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. washChromatography on silica eluting with a gradient elution of ethyl acetate:hexane (1:2 to 2:1)

Sources & evidence

ORD record
ord-757fd8b1c027466a8f55f18d8f8eb0f7
Source dataset
uspto-grants-2003_06
Patent number
US06573270B1

Reaction notes

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