Sodium hydride → 2,6-Dichloro-4-cyano-N-(3,5-difluoropyridin-4-yl)-benzamide

HRID 2366275Notes

Reaction equation

HRID 2366275 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([F:11])[C:9]=1[NH2:10].[Cl:12][C:13]1[CH:21]=[C:20]([C:22]#[N:23])[CH:19]=[C:18]([Cl:24])[C:14]=1[C:15](Cl)=[O:16]>CN(C=O)C>[Cl:12][C:13]1[CH:21]=[C:20]([C:22]#[N:23])[CH:19]=[C:18]([Cl:24])[C:14]=1[C:15]([NH:10][C:9]1[C:8]([F:11])=[CH:7][N:6]=[CH:5][C:4]=1[F:3])=[O:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27376543,5-Difluoro-4-pyridinamine2×HCID 866489562,6-Dichloro-4-cyanobenzoyl chloride

Product 1

HCID 668013412,6-Dichloro-4-cyano-N-(3,5-difluoropyridin-4-yl)-benzamideYield 53.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (461 mg, 11.54 mmol) was added portionwise to a solution of 3,5-difluoropyridin-4-ylamine (1.0 g, 7.69 mmol) in DMF (20 mL) at 0° C. under a nitrogen atmosphere. A solution of 2,6-dichloro-4-cyano-benzoyl chloride (1.98 g, 8.46 mmol) in DMF (15 mL) was then added whilst maintaining the internal temperature below 10° C. Stirring was continued for 1.5 hours. The reaction mixture was quenched by addition of a saturated solution of NH4Cl and partitioned between water and EtOAc. The aqueous phase was further extracted with EtOAc (×2) and the combined organic layers were washed with water, then with brine, dried (MgSO4) and concentrated under reduced pressure. The resultant residue was combined with the crude reaction mixture obtained following the same method starting from 3,5-difluoro-pyridin-4-ylamine (100 mg, 0.77 mmol) and purified by column chromatography on silica gel eluting with 0-50% EtOAc in cyclohexane to afford the title compound as an off-white solid (1.35 g, 49% yield). LCMS (Method D): RT=3.02 min, m/z: 328 [M+H+].

Workup

  1. temperaturewhilst maintaining the internal temperature below 10° C
  2. customThe reaction mixture was quenched by addition of a saturated solution of NH4Cl
  3. custompartitioned between water and EtOAc
  4. extractionThe aqueous phase was further extracted with EtOAc (×2)
  5. washthe combined organic layers were washed with water
  6. dry with materialwith brine, dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customreaction mixture
  9. customobtained
  10. custompurified by column chromatography on silica gel eluting with 0-50% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-7a98e87a245e483cab4d2bfd11a19b0d
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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