Dimethylformamide → 3-[2-(2-Chloro-3,6-difluoro-phenyl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester

HRID 1512061Notes

Reaction equation

HRID 1512061 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:9]=1[CH2:16][C:17]([OH:19])=O.CN(C)C=O.[CH3:25][O:26][C:27]([C:29]1[C:34]([NH2:35])=[N:33][CH:32]=[CH:31][N:30]=1)=[O:28]>ClCCl.C(#N)C>[CH3:25][O:26][C:27]([C:29]1[C:34]([NH:35][C:17](=[O:19])[CH2:16][C:9]2[C:10]([F:15])=[CH:11][CH:12]=[C:13]([F:14])[C:8]=2[Cl:7])=[N:33][CH:32]=[CH:31][N:30]=1)=[O:28]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 72669Methyl 3-aminopyrazinecarboxylateHCID 27735662-Chloro-3,6-difluorobenzeneacetic acid

Product 1

HCID 579988233-[2-(2-Chloro-3,6-difluoro-phenyl)-acetylamino]-pyrazine-2-carboxylic acid methyl esterYield 244.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (1.30 ml) was added dropwise to a solution of (2-chloro-3,6-difluoro-phenyl)-acetic acid (3.151 g) in dichloromethane (20 ml) and a drop of N,N-dimethylformamide was added to initiate the reaction. The reaction mixture was stirred at ambient temperature for 1 hour. The solvent was evaporated to produce a colourless oil which was dissolved in acetonitrile (30 ml). This solution was then divided into three portions and each portion was added to a slurry of 3-amino-pyrazine-2-carboxylic acid methyl ester (0.76 g) in acetonitrile (15 ml). The reaction mixtures were heated in the microwave at 130° C. for 40 minutes to produce dark red solutions that was stored at ambient temperature for 16 hours. The samples were combined and concentrated to produce 3-[2-(2-chloro-3,6-difluoro-phenyl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester as a dark orange solid (4.15 g). 1H-NMR (400 MHz, CDCl3): 4.02 (s, 3H), 4.22 (s, 2H), 7.02-7.10 (m, 1H), 7.11-7.17 (m, 1H), 8.41 (d, 1H), 8.61 (d, 1H), 10.8 (s, 1H) ppm.

Workup

  1. customthe reaction
  2. customThe solvent was evaporated
  3. customto produce a colourless oil which
  4. customThe reaction mixtures
  5. temperaturewere heated in the microwave at 130° C. for 40 minutes
  6. customto produce dark red solutions that
  7. waitwas stored at ambient temperature for 16 hours
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-68abd114d0944e62b54fc2ccfb014b3e
Source dataset
uspto-grants-2012_07
Patent number
US08217055B2

Reaction notes

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