Aniline → 6-chloro-N-phenylpyrazin-2-amine

HRID 2192679Notes

Reaction equation

HRID 2192679 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C>C(OC(O)C)C>[Cl:8][C:4]1[N:3]=[C:2]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 785042,6-DichloropyrazineHCID 81531Diisopropylethylamine

Product 1

HCID 103529206-chloro-N-phenylpyrazin-2-amine

Reagents, catalysts & solvents 1

HCID 101298981-EthoxyethanolSolvent

Procedure

A solution of 2,6-dichloropyrazine (1 g, 62 mmol) and aniline (1.25 g, 13.4 mmol) in ethoxyethanol (20 mL) containing DIPEA (2.5 mL, 13.4 mmol) was heated at reflux for 3 days under N2. The solution was concentrated under reduced pressure and the residue dissolved in EtOAc (50 mL) and washed successively with H2O (50 mL), 1M HCl (2×50 mL), H2O (50 mL) and brine (50 mL). After drying (Na2SO4) the solvent was removed under reduced pressure and the residue chromatographed eluting with EtOAc-hexane (20:80-50:50) to separate pure product from the lower fractions (230 mg, 17%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 days under N2
  3. concentrationThe solution was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in EtOAc (50 mL)
  5. washwashed successively with H2O (50 mL), 1M HCl (2×50 mL), H2O (50 mL) and brine (50 mL)
  6. dry with materialAfter drying (Na2SO4) the solvent
  7. customwas removed under reduced pressure
  8. customthe residue chromatographed
  9. washeluting with EtOAc-hexane (20:80-50:50)
  10. customto separate pure product from the lower fractions (230 mg, 17%)

Sources & evidence

ORD record
ord-f78e4dcdbf01460e82d5477238a7fca4
Source dataset
uspto-grants-2012_12
Patent number
US08329737B2

Reaction notes

Loading…