Pyridine → HCID 59226944, compound

HRID 1943115Notes

Reaction equation

HRID 1943115 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([F:12])[C:4]=1[F:13])#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:20][C:21]1[CH:27]=[C:26]([C:28]([F:37])([C:33]([F:36])([F:35])[F:34])[C:29]([F:32])([F:31])[F:30])[CH:25]=[C:24]([CH3:38])[C:22]=1[NH2:23].N1C=CC=CC=1.C(=O)([O-])O.[Na+]>CN(C)C=O.ClCCl.O1CCCC1>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:23][C:22]2[C:24]([CH3:38])=[CH:25][C:26]([C:28]([F:37])([C:29]([F:30])([F:31])[F:32])[C:33]([F:34])([F:35])[F:36])=[CH:27][C:21]=2[CH3:20])=[O:9])=[C:5]([F:12])[C:4]=1[F:13])#[N:2]

Participants

9

Reactant 5

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 98824254-(1,1,1,2,3,3,3-Heptafluoropropan-2-yl)-2,6-dimethylanilineHCID 592269714-Cyano-2,3-difluorobenzoic acid

Product 1

HCID 59226944HCID 59226944, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-cyano-2,3-difluoro-benzoic acid (623 mg, 3.4 mmol) (Example I10) and N,N-dimethylformamide (2 drops) in dichloromethane (17 ml) under a nitrogen atmosphere was added oxalyl chloride (0.3455 ml, 4.08 mmol). The reaction mixture was stirred for one hour at ambient temperature and then at 60° C. for 1.5 hours. The reaction mixture was concentrated and the residue dissolved in tetrahydrofuran (5 ml). The solution was added drop-wise to a solution of 2,6-dimethyl-4-(heptafluoroprop-2-yl)aniline (prepared according to EP 1,006,102) (787 mg, 2.72 mmol) and pyridine (547 μl, 6.8 mmol) in tetrahydrofuran (12 ml). The reaction mixture was stirred at ambient temperature for 16 hours. Then the reaction mixture was poured into aqueous sodium hydrogen carbonate (1M) and the mixture extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase chromatography (eluent: trifluoroacetic acid/water/acetonitrile 1:4:5 to 1:1:8) to give 4-cyano-2,3-difluoro-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide (0.675 g, 44% yield). 1H-NMR (400 MHz, CDCl3): 2.35 (6H, s), 7.38 (2H, s), 7.57 (1H, m), 7.79 (1H, d), 8.03 (1H, m) ppm.

Workup

  1. waitat 60° C. for 1.5 hours
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue dissolved in tetrahydrofuran (5 ml)
  4. stirringThe reaction mixture was stirred at ambient temperature for 16 hours
  5. extractionthe mixture extracted three times with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by reverse-phase chromatography (eluent: trifluoroacetic acid/water/acetonitrile 1:4:5 to 1:1:8)

Sources & evidence

ORD record
ord-0f702ee44c9f43689f4867f9043032a2
Source dataset
uspto-grants-2013_03
Patent number
US08389766B2

Reaction notes

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