1-Bromo-3-chlorobenzene → HCID 67135368, compound

HRID 2174616Notes

Reaction equation

HRID 2174616 reaction equation
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:49][C:50]1[CH:55]=[C:54]([F:56])[CH:53]=[CH:52][C:51]=1[C:57]1[C:58]([CH3:64])=[N:59][N:60]([CH3:63])[C:61]=1[NH2:62].Br[C:66]1[CH:71]=[CH:70][CH:69]=[C:68]([Cl:72])[CH:67]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:72][C:68]1[CH:67]=[C:66]([NH:62][C:61]2[N:60]([CH3:63])[N:59]=[C:58]([CH3:64])[C:57]=2[C:51]2[CH:52]=[CH:53][C:54]([F:56])=[CH:55][C:50]=2[F:49])[CH:71]=[CH:70][CH:69]=1

Participants

7

Reactant 4

HCID 79281-Bromo-3-chlorobenzene2×HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 64558935HCID 64558935, compound2×

Product 1

HCID 67135368HCID 67135368, compound

Reagents, catalysts & solvents 2

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

Procedure

Palladium(II) acetate (90 mg, 0.40 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (460 mg, 0.80 mmol) and powdered potassium carbonate (5.5 g, 40 mmol) were combined in anhydrous 1,4-dioxane (20 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (i.e. the product of Step B) (0.89 g, 4.0 mmol) was added in one portion, and 1-bromo-3-chlorobenzene (0.47 mL, 4.0 mmol) was added via a syringe. The reaction mixture was heated at reflux under a nitrogen atmosphere for 3 h. Additional 1-bromo-3-chlorobenzene (0.09 mL, 0.8 mmol) was added, and heating was continued for 1 h. The reaction mixture was allowed to cool to room temperature, and then partitioned between water (40 mL) and ethyl acetate (40 mL). The organic phase was washed with additional water (40 mL), brine (40 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography through 10 g of silica gel eluted with hexanes/ethyl acetate (1:1) to give the title compound, a compound of the present invention, as a solid (0.41 g).

Workup

  1. customthe mixture was sparged with a subsurface stream of N2 gas for 10 min
  2. additionwas added via a syringe
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux under a nitrogen atmosphere for 3 h
  5. temperatureheating
  6. custompartitioned between water (40 mL) and ethyl acetate (40 mL)
  7. washThe organic phase was washed with additional water (40 mL), brine (40 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography through 10 g of silica gel
  11. washeluted with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-5d8e23d974d94f588be65f1e22742be2
Source dataset
uspto-grants-2015_06
Patent number
US09062005B2

Reaction notes

Loading…