Potassium Carbonate → 1-(4-Fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

HRID 83547Notes

Reaction equation

HRID 83547 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.[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][C:5]([N:8]2[C:12]([C:18]3[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]=3)=[CH:11][C:10]([NH2:14])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 71287745HCID 71287745, compoundHCID 86680375HCID 86680375, compound

Product 1

HCID 712878641-(4-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

Procedure

To a solution of 1-(4-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (38 mg) prepared in Preparation 18 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) and a 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 an aqueous layer of the reaction mixture, an organic layer was filtered through silica gel (5 g), and subjected to elution with ethyl acetate. The filtrate was concentrated under reduced pressure, 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 an aqueous layer of the reaction mixture
  3. filtrationan 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-158d20d586b04150bcad82643a916212
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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