Pyridine → N-(3-cyano-2,4-difluorophenyl)-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide

HRID 1500064Notes

Reaction equation

HRID 1500064 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[C:12]([C:13]([OH:15])=O)=[C:11]([C:16]([F:19])([F:18])[F:17])[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])=[N:9]1.N1C=CC=CC=1.[NH2:33][C:34]1[C:35]([F:43])=[C:36]([C:39]([F:42])=[CH:40][CH:41]=1)[C:37]#[N:38]>CN(C=O)C.ClCCl.C1COCC1>[C:37]([C:36]1[C:35]([F:43])=[C:34]([NH:33][C:13]([C:12]2[N:8]([CH3:7])[N:9]=[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[C:11]=2[C:16]([F:18])([F:17])[F:19])=[O:15])[CH:41]=[CH:40][C:39]=1[F:42])#[N:38]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 80271533-Amino-2,6-difluorobenzonitrileHCID 866600921-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 89651058N-(3-cyano-2,4-difluorophenyl)-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamideYield 44.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Oxalyl chloride (0.85 ml, 1.2 g, 9.8 mmol) followed by DMF (3 drops) were added to 1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (2.03 g, 6.50 mmol) in dichloromethane (15 ml), and the mixture was heated to 50° C. After 5 h at 50° C., the mixture was concentrated under reduced pressure, THF (15 ml) and pyridine (1.1 ml, 1.0 g, 13 mmol, 2 eq.) were added, followed by 3-amino-2,6-difluorobenzonitrile (1.0 g, 6.5 mmol, 1.0 eq.) in THF (3 ml). The mixture was left at room temperature for 24 h, HC10N aq. solution) was added, the mixture was extracted with ethyl acetate and the extract was washed with HC10N aq. solution) and NaOH (2N aq. solution). The extract was dried over MgSO4 and filtered through silica gel. After concentration under reduced pressure, the product was purified by column chromatography on silica gel (hexane/ethyl acetate), giving N-(3-cyano-2,4-difluorophenyl)-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (1.29 g, 44%).

Workup

  1. additionwere added
  2. waitThe mixture was left at room temperature for 24 h
  3. additionHC10N aq. solution) was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washthe extract was washed with HC10N aq. solution) and NaOH (2N aq. solution)
  6. dry with materialThe extract was dried over MgSO4
  7. filtrationfiltered through silica gel
  8. concentrationAfter concentration under reduced pressure
  9. customthe product was purified by column chromatography on silica gel (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-fc66944b5a31497d8e811ec208772c6f
Source dataset
uspto-grants-2015_12
Patent number
US09204645B2

Reaction notes

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