Sodium Carbonate → 1-Phenyl-5-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

HRID 83588Notes

Reaction equation

HRID 83588 reaction equation
I[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([NH2:13])[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[CH:23]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])O.[Na+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:7]1([N:6]2[C:2]([C:26]3[CH:27]=[CH:22][CH:23]=[C:24]([CH2:28][O:29][CH2:30][C:31]([F:32])([F:33])[F:34])[CH:25]=3)=[CH:3][C:4]([NH2:13])=[N:5]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 516892Sodium BicarbonateHCID 71287843HCID 71287843, compoundHCID 86680350HCID 86680350, compound

Product 1

HCID 712878771-Phenyl-5-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-1H-pyrazol-3-ylamineYield 95.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 5-iodo-1-phenyl-1H-pyrazol-3-ylamine (221 mg) prepared according to the same procedures as Preparation 2 in 1,2-dimethoxyethane (2.2 ml) were sequentially added 4,4,5,5-tetramethyl-2-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-[1,3,2]dioxaborolane (269 mg) prepared in Preparation 28, a 2M aqueous solution of sodium carbonate (1.1 ml), tricyclohexylphosphine (43.4 mg) and palladium (II) acetate (17.4 mg) at room temperature, and the mixture was stirred at 100° C. for 12 hours. To this reaction mixture was added a saturated aqueous solution of sodium hydrogen carbonate at room temperature, and then the mixture was filtered through Celite, and subjected to elution with ethyl acetate. The filtrate was extracted with ethyl acetate, the resulting organic layer was washed with was a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1) to give the titled compound (258 mg).

Workup

  1. customprepared in Preparation 28
  2. filtrationthe mixture was filtered through Celite
  3. washsubjected to elution with ethyl acetate
  4. extractionThe filtrate was extracted with ethyl acetate
  5. washthe resulting organic layer was washed
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-82108d5c481947b389da4572ff719a22
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

Loading…