Potassium Carbonate → HCID 66612439, compound

HRID 2174617Notes

Reaction equation

HRID 2174617 reaction equation
Br[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[Cl:16].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:65][C:66]1[CH:72]=[C:71]([O:73][CH3:74])[CH:70]=[C:69]([F:75])[C:67]=1[NH2:68]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[C:3]1[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=1[NH:68][C:67]1[C:69]([F:75])=[CH:70][C:71]([O:73][CH3:74])=[CH:72][C:66]=1[F:65]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 51857632,6-Difluoro-4-methoxyanilineHCID 666126355-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole2×

Product 1

HCID 66612439HCID 66612439, compound

Reagents, catalysts & solvents 2

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

Procedure

5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step A) (0.20 g, 0.66 mmol), palladium(II) acetate (15 mg, 0.066 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.13 mmol) and powdered potassium carbonate (1.8 g, 13 mmol) were combined in anhydrous 1,4-dioxane (3 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,6-Difluoro-4-methoxyaniline (0.22 g, 1.3 mmol) was added in one portion, and the reaction mixture was heated at reflux for 22 h. The reaction mixture was filtered through Celite® diatomaceous filter aid, and the filter pad was washed with ethyl acetate (20 mL). The filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a semisolid residue. This residue was purified by column chromatography through 5 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound, a compound of the present invention, as a light-brown solid (48 mg).

Workup

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

Sources & evidence

ORD record
ord-7bcf5e9fdd9d4d95b3cd08ec032d10a9
Source dataset
uspto-grants-2015_06
Patent number
US09062005B2

Reaction notes

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