Potassium Carbonate → HCID 46871835, compound

HRID 514230Notes

Reaction equation

HRID 514230 reaction equation
Br[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[C:14]([F:15])=[CH:13][C:12]([O:16][CH3:17])=[CH:11][C:10]=1[F:18].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[F:67][C:68]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[C:69]=1[NH2:70]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:10]1[CH:11]=[C:12]([O:16][CH3:17])[CH:13]=[C:14]([F:15])[C:9]=1[C:3]1[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=1[NH:70][C:69]1[C:68]([F:67])=[CH:74][C:73]([F:75])=[CH:72][C:71]=1[F:76]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 677652,4,6-TrifluoroanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66613416HCID 66613416, compound2×

Product 1

HCID 46871835HCID 46871835, compound

Reagents, catalysts & solvents 2

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

Procedure

5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step D) (0.30 g, 0.94 mmol), palladium(II) acetate (20 mg, 0.090 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.11 g, 0.19 mmol) and powdered potassium carbonate (2.6 g, 19 mmol) were combined in anhydrous 1,4-dioxane (4 mL), and the resulting mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,4,6-Trifluoroaniline (0.28 g, 1.9 mmol) was added in one portion, and the reaction mixture was heated at reflux under nitrogen for 22 h. The reaction mixture was cooled, then filtered through Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (20 mL), and the filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a semisolid residue. The residue was purified by column chromatography through 12 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound as a semisolid (73 mg).

Workup

  1. customthe resulting mixture was sparged with a subsurface stream of N2 gas for 10 min
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux under nitrogen for 22 h
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered through Celite® diatomaceous filter aid
  6. washThe filter pad was washed with ethyl acetate (20 mL)
  7. washthe filtrate was washed with water (10 mL) and brine (10 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customto leave a semisolid residue
  11. customThe residue was purified by column chromatography through 12 g of silica gel
  12. washeluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3)

Sources & evidence

ORD record
ord-dfce4549d4a148008582f610943836e4
Source dataset
uspto-grants-2015_08
Patent number
US09107412B2

Reaction notes

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