Cesium carbonate → HCID 25054172, compound

HRID 220085Notes

Reaction equation

HRID 220085 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH2:15])[N:5]([C:7]2[CH:12]=[C:11]([S:13][CH3:14])[N:10]=[CH:9][N:8]=2)[N:6]=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:15][C:4]1[N:5]([C:7]2[CH:12]=[C:11]([S:13][CH3:14])[N:10]=[CH:9][N:8]=2)[N:6]=[C:2]([CH3:1])[CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 58601069N-(3-Bromo-4-Methylphenyl)-3-(Trifluoromethyl)BenzamideHCID 591733685-Methyl-2-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamine

Product 1

HCID 25054172HCID 25054172, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

5-Methyl-2-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamine (90 mg, 0.40 mmol) is mixed with N-(3-Bromo-4-methyl-phenyl)-3-trifluoromethyl-benzamide (228 mg, 0.64 mmol), palladium acetate (20 mg, 0.089 mmol), Xantophos (75 mg, 0.13 mmol) and cesium carbonate (420 mg, 1.28 mmol). 4 mL anhydrous 1,4-dioxane is added under a nitrogen environment and the mixture is subjected to microwave irradiation to 150° C. for 30 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 0% to 40% to afford N-{4-Methyl-3-[5-methyl-2-(6-methylsulfanyl-pyrimidin-4-yl)-2H-pyrazol-3-ylamino]-phenyl}-3-trifluoromethyl-benzamide: 1H NMR 400 MHz (d6-DMSO) δ 10.65 (s, 1H), 10.46 (s, 1H), 8.89 (s, 1H), 8.30-8.25 (m, 2H), 7.98 (d, J=7.5 Hz, 1H), 7.89 (s, 1H), 7.80 (t, J=7.5 Hz, 1H), 7.67 (s, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.25 (d, J=8.2 Hz, 1H), 6.12 (s, 1H), 2.61 (s, 3H), 2.34 (s, 3H), 2.25 (s, 3H); MS m/z 499.14 (M+1).

Workup

  1. customirradiation to 150° C. for 30 minutes
  2. concentrationconcentrated
  3. customThe crude product is purified by ISCO chromatography
  4. washeluting with ethyl acetate in hexanes from 0% to 40%

Sources & evidence

ORD record
ord-8049ec9228b844419068099866b521d5
Source dataset
uspto-grants-2012_06
Patent number
US08202876B2

Reaction notes

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