Sodium Carbonate → 5-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamine

HRID 83555Notes

Reaction equation

HRID 83555 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.[Cl: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.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:10]([NH2:14])[CH:11]=2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:26])([F:27])[F:28])[CH:21]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 71287834HCID 71287834, compoundHCID 86680375HCID 86680375, compound

Product 1

HCID 712878655-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamineYield 115.7%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 1-(4-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (50 mg) prepared according to the same procedures as Preparation 18 in 1,2-dimethoxyethane (0.5 ml) were sequentially added 2-[3-chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (72 mg) prepared according to the same procedures as Preparation 22, a 2M aqueous solution of sodium carbonate (0.25 ml), tricyclohexylphosphine (9.3 mg) and palladium (II) acetate (3.7 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 magnesium 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 (79 mg).

Workup

  1. customprepared
  2. customaccording to the same procedures as Preparation 22
  3. filtrationfiltered through Celite
  4. washsubjected to elution with ethyl acetate
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washthe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-7c484ac6613c4ebead43f7c570939f8f
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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