Sodium Carbonate → 5-Bromo-3-(4-chloro-phenyl)-6-trifluoromethyl-pyrazin-2-ylamine

HRID 416472Notes

Reaction equation

HRID 416472 reaction equation
Br[C:2]1[C:3]([NH2:13])=[N:4][C:5]([C:9]([F:12])([F:11])[F:10])=[C:6]([Br:8])[N:7]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:6]1[N:7]=[C:2]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)[C:3]([NH2:13])=[N:4][C:5]=1[C:9]([F:12])([F:11])[F:10]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 578993203,5-Dibromo-6-(trifluoromethyl)pyrazin-2-amine

Product 1

HCID 866347035-Bromo-3-(4-chloro-phenyl)-6-trifluoromethyl-pyrazin-2-ylamineYield 66.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 6.08 g 3,5-dibromo-6-trifluoromethyl-pyrazin-2-ylamine, 3.25 g 4-chlorophenylboronic acid and 1.095 g tetrakis(triphenylphosphine)palladium(0) in 60 ml 1,2-dimethoxyethane was added a solution of 4.016 g sodium carbonate in 22.74 ml water and the mixture was heated to reflux for 18 h. The reaction mixture was cooled to room temperature and partitioned between 10% aqueous citric acid and ethyl acetate, the phases were separated and the organic phase was purified by chromatography on silica gel with a gradient of 9:1 heptane: dichloromethane to 1:1 heptane: dichloromethane to yield 4.45 g of the title compound as white solid. MS (M−H) at 352.0 and 350.1.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 18 h
  3. custompartitioned between 10% aqueous citric acid and ethyl acetate
  4. customthe phases were separated
  5. customthe organic phase was purified by chromatography on silica gel with a gradient of 9:1 heptane

Sources & evidence

ORD record
ord-273bec9c387d474881a92d34194f04c7
Source dataset
uspto-grants-2012_01
Patent number
US08088920B2

Reaction notes

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