Cesium carbonate → HCID 25056505, compound

HRID 220091Notes

Reaction equation

HRID 220091 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][CH3:14])[CH:8]=2)[N:5]=[CH:4][CH:3]=1.Br[C:16]1[CH:17]=[C:18]([NH:23][C:24](=[O:42])[C:25]2[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[CH:26]=2)[CH:19]=[CH:20][C:21]=1[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[CH3:22][C:21]1[CH:20]=[CH:19][C:18]([NH:23][C:24](=[O:42])[C:25]2[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=[C:27]([N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[CH:26]=2)=[CH:17][C:16]=1[NH:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([NH:13][CH3:14])[N:10]=[CH:11][N:12]=2)[N:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 59173460HCID 59173460, compoundHCID 68702811N-(3-Bromo-4-methylphenyl)-3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)benzamide

Product 1

HCID 25056505HCID 25056505, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

[6-(5-Amino-pyrazol-1-yl)-pyrimidin-4-yl]-methyl-amine (200 mg, 1.05 mmol) is mixed with N-(3-bromo-4-methyl-phenyl)-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide (640 mg, 1.40 mmol), palladium acetate (60 mg, 0.27 mmol), Xantophos (235 mg, 0.41 mmol) and cesium carbonate (1.03 g, 3.15 mmol). 10 mL of anhydrous 1,4-dioxane is added under nitrogen environment and the mixture is subjected to microwave irradiation to 160° C. for 25 minutes. The reaction mixture is treated with 150 mL THF, passed through a celite column and condensed. The crude product is purified by ISCO chromatography eluting with THF and methanol (v/v=1:1) in methylene chloride from 0% to 10% to afford N-{4-Methyl-3-[2-(6-methylamino-pyrimidin-4-yl)-2H-pyrazol-3-ylamino]-phenyl}-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide.

Workup

  1. customirradiation to 160° C. for 25 minutes
  2. custompassed through a celite column and condensed
  3. customThe crude product is purified by ISCO chromatography
  4. washeluting with THF and methanol (v/v=1:1) in methylene chloride from 0% to 10%

Sources & evidence

ORD record
ord-b470a8b04c2b40d3b84c28606006a11e
Source dataset
uspto-grants-2012_06
Patent number
US08202876B2

Reaction notes

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