Potassium Carbonate → 1-(2-Fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

HRID 83541Notes

Reaction equation

HRID 83541 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12](I)=[CH:11][C:10]([NH2:14])=[N:9]1.[F:15][C:16]1[CH:17]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:18]2[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=[C:16]([F:15])[CH:17]=2)=[CH:11][C:10]([NH2:14])=[N:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 71287745HCID 71287745, compoundHCID 866803721-(2-Fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine

Product 1

HCID 866803741-(2-Fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 1-(2-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (38 mg) in 1,4-dioxane (0.4 ml) were sequentially added 2-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (52 mg) prepared according to the same procedures as Preparation 15, palladium (II) acetate (3 mg), tricyclohexylphosphine (7 mg), 2M aqueous solution of potassium carbonate (0.2 ml) at room temperature, and the mixture was stirred at 105° C. for 4 hours. After removing the aqueous layer of this reaction mixture, the organic layer was filtered through silica gel (5 g), and subjected to elution with ethyl acetate. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel thin-layer chromatography (eluent: n-hexane/ethyl acetate 1/1) to give the titled compound.

Workup

  1. customprepared
  2. customAfter removing the aqueous layer of this reaction mixture
  3. filtrationthe organic layer was filtered through silica gel (5 g)
  4. washsubjected to elution with ethyl acetate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica gel thin-layer chromatography (eluent: n-hexane/ethyl acetate 1/1)

Sources & evidence

ORD record
ord-58b730552709451e872d74d35a7cb538
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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