Cesium carbonate → N-{4-Methyl-3-[2-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide

HRID 220078Notes

Reaction equation

HRID 220078 reaction equation
[CH3:1][N:2]1[C:6]([NH2:7])=[C:5]([C:8]2[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[CH:10][N:9]=2)[CH:4]=[N:3]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]=1[CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[CH3:23][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:21]=1[NH:7][C:6]1[N:2]([CH3:1])[N:3]=[CH:4][C:5]=1[C:8]1[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 58601069N-(3-Bromo-4-Methylphenyl)-3-(Trifluoromethyl)BenzamideHCID 591733022-Methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamine

Product 1

HCID 59173636N-{4-Methyl-3-[2-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2-Methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamine (120 mg, 0.54 mmol) is mixed with N-(3-Bromo-4-methyl-phenyl)-3-trifluoromethyl-benzamide (290 mg, 0.81 mmol), palladium acetate (25 mg, 0.1 mmol), Xantophos (100 mg, 0.17 mmol) and cesium carbonate (530 mg, 1.63 mmol). 10 mL of anhydrous 1,4-dioxane is added under a nitrogen environment and the mixture is subjected to microwave irradiation to 150° C. for one hour. 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-[2-methyl-4-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide: MS m/z 499.1 (M+1).

Workup

  1. customirradiation to 150° C. for one hour
  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-e666274769674ed785f5d9ad4ef36895
Source dataset
uspto-grants-2012_06
Patent number
US08202876B2

Reaction notes

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