Phosphorus oxychloride → 3-Amino-6-bromopyrazine-2-carbonitrile

HRID 1959395Notes

Reaction equation

HRID 1959395 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH2:11])=O)=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>N1C=CC=CC=1.CCOC(C)=O>[NH2:1][C:2]1[C:3]([C:9]#[N:11])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 4708993-Amino-6-bromopyrazine-2-carboxamideHCID 516892Sodium Bicarbonate

Product 1

HCID 110526113-Amino-6-bromopyrazine-2-carbonitrileYield 43%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-amino-6-bromo-pyrazine-2-carboxamide (500 mg, 2.304 mmol) was dissolved in pyridine (5 mL) and treated with POCl3 (666 μL, 7.145 mmol) dropwise at 0° C. After the addition was complete the reaction was allowed to warm to ambient temperature and stirred for 1.5 hours. The solvent was removed in vacuo and the reaction carefully treated with NaHCO3 to basify. The mixture was diluted with EtOAc and the layers separated. The aqueous layer was further extracted with EtOAc (1×) and the combined organics washed with brine (1×), 0.1 M HCl (1×) and water (1×), dried (MgSO4), filtered and concentrated to furnish the product as a brown solid (197 mg, 43% Yield). 1H NMR (DMSO) d 7.62 (2H, br s), 8.45 (1H, s) ppm

Workup

  1. additionAfter the addition
  2. customThe solvent was removed in vacuo
  3. customthe reaction
  4. customthe layers separated
  5. extractionThe aqueous layer was further extracted with EtOAc (1×)
  6. washthe combined organics washed with brine (1×), 0.1 M HCl (1×) and water (1×)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-38767d77cbc440b9bdcab6569a0ad6f6
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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