Sodium Iodide → N-[1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

HRID 1946365Notes

Reaction equation

HRID 1946365 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)=[O:5].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C=O)C>[Cl:33][C:31]1[CH:30]=[CH:29][C:28]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[C:27]([CH2:26][N:9]2[CH:10]=[CH:11][C:7]([NH:6][C:4](=[O:5])[C:3]3[C:12]([F:16])=[CH:13][CH:14]=[CH:15][C:2]=3[F:1])=[N:8]2)[CH:32]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 221055531-(Benzyloxy)-2-(bromomethyl)-4-chlorobenzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 46947749N-[1-({5-chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(174 mg, 0.78 mmol) was dissolved in DMF (2.5 ml). Sodium iodide (33 mg, 0.22 mmol) and potassium carbonate (164 mg, 1.19 mmol) were added followed by 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (synthesised according to WO2006066968) (233 mg, 0.75 mmol) washed in with further DMF (2.5 ml). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then stirred and heated to 80° C. for 3 h under a nitrogen atmosphere and allowed to cool. Further 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (51 mg) was added, and the reaction was stirred and heated to 80° C. under a nitrogen atmosphere for 3 h. The reaction mixture was concentrated in vacuo. The crude material was treated with water (50 ml) and extracted with EtOAc (3×50 ml). The extracts were combined, dried (MgSO4) and concentrated in vacuo. The residue was purified on silica (50 g) using 0-100% EtOAc-cyclohexane. Appropriate fractions were concentrated in vacuo to give the title compound as a colourless gum (20 mg);

Workup

  1. washwashed in with further DMF (2.5 ml)
  2. stirringThe reaction mixture was then stirred
  3. temperatureheated to 80° C. for 3 h under a nitrogen atmosphere
  4. temperatureto cool
  5. additionFurther 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (51 mg) was added
  6. stirringthe reaction was stirred
  7. temperatureheated to 80° C. under a nitrogen atmosphere for 3 h
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. additionThe crude material was treated with water (50 ml)
  10. extractionextracted with EtOAc (3×50 ml)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified on silica (50 g)
  14. concentrationAppropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-45424256b1e14e3db125388b0c25499d
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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