Cesium carbonate → N-{4-Methyl-3-[1-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-1H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide

HRID 220081Notes

Reaction equation

HRID 220081 reaction equation
[CH3:1][NH:2][C:3]1[C:7]([C:8]2[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[CH:10][N:9]=2)=[CH:6][NH:5][N:4]=1.Br[C:17]1[CH:18]=[C:19]([NH:24][C:25](=[O:36])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)[CH:20]=[CH:21][C:22]=1C.[C:37](=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[CH3:21][C:22]1[CH:17]=[CH:18][C:19]([NH:24][C:25](=[O:36])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=2)=[CH:20][C:1]=1[NH:2][C:3]1[C:7]([C:8]2[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[CH:10][N:9]=2)=[CH:6][N:5]([CH3:37])[N:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 58601069N-(3-Bromo-4-Methylphenyl)-3-(Trifluoromethyl)BenzamideHCID 178482506HCID 178482506, compound

Product 1

HCID 59173322N-{4-Methyl-3-[1-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-1H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-1H-pyrazol-3-ylamine (61 mg, 0.27 mmol) is mixed with N-(3-Bromo-4-methyl-phenyl)-3-trifluoromethyl-benzamide (161 mg, 0.45 mmol), palladium acetate (20 mg, 0.089 mmol), Xantophos (78 mg, 0.135 mmol) and cesium carbonate (280 mg, 0.86 mmol). 2 mL anhydrous 1,4-dioxane is added under nitrogen environment and the mixture is subjected to microwave irradiation to 150° C. for 45 minutes. The reaction mixture is then cooled to room temperature, treated with 100 mL THF, passed through a celite column and concentrated. The crude product is purified by ISCO chromatography eluting with ethyl acetate in hexanes from 10% to 100% to afford N-{4-Methyl-3-[1-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-1H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide.

Workup

  1. customirradiation to 150° C. for 45 minutes
  2. concentrationconcentrated
  3. customThe crude product is purified by ISCO chromatography
  4. washeluting with ethyl acetate in hexanes from 10% to 100%

Sources & evidence

ORD record
ord-2b2645fe431d46b1bfcebabaa488dfc5
Source dataset
uspto-grants-2012_06
Patent number
US08202876B2

Reaction notes

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