4-Chloroaniline → HCID 59570661, compound

HRID 1961724Notes

Reaction equation

HRID 1961724 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[C:13]([N:14]2[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[N:15]2)=[N:12][C:11](Br)=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[C:13]([N:14]2[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[N:15]2)=[N:12][C:11]([NH:28][C:27]2[CH:29]=[CH:30][C:24]([Cl:23])=[CH:25][CH:26]=2)=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 78124-ChloroanilineHCID 10796Cesium carbonateHCID 59570667HCID 59570667, compound

Product 1

HCID 59570661HCID 59570661, compoundYield 43.4%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of give [5-bromo-3-(3,5-dimethyl-pyrazol-1-yl)-pyrazin-2-yl]-carbamic acid tert-butyl ester (511 mg, 1.25 mmol), 4-chloroaniline (223 mg, 1.75 mmol) and cesium carbonate (822 mg, 2.5 mmol) in dioxane (35 mL) was degassed with argon for 15 min. Tris(dibenzylideneaceton)dipalladium (0) 29 mg, 0.03 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (57 mg, 0.1 mmol) were added followed by degassing for 5 min. The reaction mixture was heated to 120° C. for overnight. Ethyl acetate, water and brine were added and the phases were separated. The aqueous phase was extracted with ethyl acetate (5×50 mL). The combined organic phases were washed with brine, dried over sodium sulphate, filtrated and concentrated in vacuo. The crude product purified by flash chromatography (ethyl acetate/heptane as eluent) to give [5-(4-chloro-phenylamino)-3-(3,5-dimethyl-pyrazol-1-yl)-pyrazin-2-yl]-carbamic acid tert-butyl ester (225 mg, 43%) as an yellow solid.

Workup

  1. customwas degassed with argon for 15 min
  2. customby degassing for 5 min
  3. additionEthyl acetate, water and brine were added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (5×50 mL)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltrated
  9. concentrationconcentrated in vacuo
  10. customThe crude product purified by flash chromatography (ethyl acetate/heptane as eluent)

Sources & evidence

ORD record
ord-271c661d2386426984c60499bfb20056
Source dataset
uspto-grants-2013_04
Patent number
US08415358B2

Reaction notes

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