Sodium Carbonate → 6-(3-Fluorophenyl)pyrazin-2-amine

HRID 1710676Notes

Reaction equation

HRID 1710676 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4](Cl)[N:3]=1.[F:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[F:9][C:10]1[CH:15]=[C:14]([C:4]2[N:3]=[C:2]([NH2:1])[CH:7]=[N:6][CH:5]=2)[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 1184582-Amino-6-ChloropyrazineHCID 27339863-Fluorophenylboronic acid

Product 1

HCID 457883426-(3-Fluorophenyl)pyrazin-2-amineYield 95.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a stirred solution of 2-amino-6-chloropyrazine (2.0 g, 15.43 mmol) in a mixture of toluene (90 mL) and ethanol (8.5 mL) was added 3-fluorophenyl boronic acid (2.60 g, 18.51 mmol) and a 2M aqueous solution of sodium carbonate (16.2 mL, 32.40 mmol). The mixture was subjected to three cycles of evacuation-backfilling with argon, and tetrakis(triphenylphosphine)palladium (0.713 g, 0.617 mmol) was added. The mixture was subjected again to three cycles of evacuation-backfilling with argon the flask was capped and placed in a 110° C. oil bath. After 4 h, the mixture was cooled, partitioned between dichloromethane and water the organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was purified by silica gel flash chromatography (33% ethyl acetate in hexanes to 50% ethyl acetate in hexanes). Concentration in vaccuo of the product-rich fractions provided the titled compound (2.79 g, 95%) as a yellowish solid (2.79 g, 95%).

Workup

  1. additionwas added
  2. customwas capped
  3. customplaced in a 110° C.
  4. temperaturethe mixture was cooled
  5. custompartitioned between dichloromethane and water the organic layer
  6. washwas washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by silica gel flash chromatography (33% ethyl acetate in hexanes to 50% ethyl acetate in hexanes)
  10. concentrationConcentration in vaccuo of the product-rich fractions

Sources & evidence

ORD record
ord-7050240071ad40968653655cc854aedb
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

Loading…