Sodium Carbonate → 1-(4-Fluorophenyl)-5-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

HRID 83568Notes

Reaction equation

HRID 83568 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](I)=[CH:11][C:10]([NH2:14])=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][O:30][CH2:31][C:32]([F:35])([F:34])[F:33])[CH:24]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:27]3[CH:28]=[CH:23][CH:24]=[C:25]([CH2:29][O:30][CH2:31][C:32]([F:33])([F:34])[F:35])[CH:26]=3)=[CH:11][C:10]([NH2:14])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 71287843HCID 71287843, compoundHCID 86680375HCID 86680375, compound

Product 1

HCID 712877501-(4-Fluorophenyl)-5-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-1H-pyrazol-3-ylamineYield 51%

Reagents, catalysts & solvents 2

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

Procedure

Under argon atmosphere, to a solution of 1-(4-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (70 mg) prepared in Preparation 18 in 1,2-dimethoxyethane (0.7 ml) were sequentially added 4,4,5,5-tetramethyl-2-[3-(2,2,2-trifluoroethoxymethyl)phenyl]-[1,3,2]dioxaborolane (80 mg), a 2M aqueous solution of sodium carbonate (0.35 ml), tricyclohexylphosphine (13.0 mg) and palladium (II) acetate (5.2 mg) at room temperature, and the mixture was stirred at 100° C. for 2 hours. This reaction mixture was cooled to room temperature, filtered through Celite, and subjected to elution with ethyl acetate. The filtrate was extracted with ethyl acetate, the resulting organic layer was washed with 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=1/1) to give the titled compound (43 mg).

Workup

  1. filtrationfiltered through Celite
  2. washsubjected to elution with ethyl acetate
  3. extractionThe filtrate was extracted with ethyl acetate
  4. washthe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-91d311e57b334d3aab7ee8511953fae3
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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