Sodium Carbonate → 2-Amino-5-(4-trifluoromethylphenyl)pyrazine

HRID 1427485Notes

Reaction equation

HRID 1427485 reaction equation
[NH2:1][C:2]1N=[CH:6][C:5](I)=[CH:4][N:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15]C(B(O)O)=[CH:13][CH:12]=1.[C:22](=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+:29]>CC#N>[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:6]([C:5]2[N:29]=[CH:22][C:2]([NH2:1])=[N:3][CH:4]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 2411022-Amino-5-iodopyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 205670592-Amino-5-(4-trifluoromethylphenyl)pyrazineYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 100 mL round bottom flask was charged with 2-amino-5-iodopyrimidine (3.66 g, 21.1 mmol), (4-(trifluoromethyl)phenyl)boronic acid (4.00 g, 21.1 mmol) and MeCN (84 mL). Stirred 15 minutes at room temperature until a nice clear solution is obtained. The resulting solution is then treated with 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (508 mg, 695 μmol) was added followed by the sodium carbonate 1M aq. (52.7 mL, 52.7 mmol). Reaction refluxed for 2 hours. Reaction cooled down to room temperature and dissolved with ammonium chloride solution (aq. sat.). Aqueous layer extracted with ethyl acetate (3×). Combined organic layers washed with brine (1×), dried over sodium sulfate, filtered and concentrated to give the crude material. Purification by silica gel flash chromatography (Ethyl Acetate/DCM) provide the title compound as a light yellow solid (4.4 g, 87%). 1H NMR (400 MHz, DMSO-d6) δ 6.76 (s, 2H) 7.76 (d, J=8.41 Hz, 2H) 7.99 (d, J=1.57 Hz, 1H) 8.14 (d, J=8.22 Hz, 2H) 8.62 (d, J=1.37 Hz, 1H). MS (M+1): 240.2.

Workup

  1. customis obtained
  2. additionThe resulting solution is then treated with 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (508 mg, 695 μmol)
  3. additionwas added
  4. customReaction
  5. temperaturerefluxed for 2 hours
  6. customReaction
  7. temperaturecooled down to room temperature
  8. extractionAqueous layer extracted with ethyl acetate (3×)
  9. washCombined organic layers washed with brine (1×)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give the crude material
  14. customPurification by silica gel flash chromatography (Ethyl Acetate/DCM)

Sources & evidence

ORD record
ord-65405edc7dc540788ccfc4b7e4e47453
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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