Sodium Iodide → N-[1-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-4-yl]-2,6-difluorobenzamide

HRID 1746111Notes

Reaction equation

HRID 1746111 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:8]=[N:9][NH:10][CH:11]=1)=[O:5].ClC1C=CC=C(Cl)C=1C(NC1C=NN(CC2C=CC(Cl)=CC=2Cl)C=1)=O.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Br[CH2:51][C:52]1[CH:57]=[C:56]([Cl:58])[CH:55]=[CH:54][C:53]=1[O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C=O)C>[Cl:58][C:56]1[CH:55]=[CH:54][C:53]([O:59][CH2:60][C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)=[C:52]([CH2:51][N:10]2[CH:11]=[C:7]([NH:6][C:4](=[O:5])[C:3]3[C:2]([F:1])=[CH:15][CH:14]=[CH:13][C:12]=3[F:16])[CH:8]=[N:9]2)[CH:57]=1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 221055531-(Benzyloxy)-2-(bromomethyl)-4-chlorobenzene2×HCID 434306572,6-Difluoro-N-1H-pyrazol-4-ylbenzamideHCID 569674692,6-Dichloro-N-{1-[(2,4-dichlorophenyl)methyl]-1H-pyrazol-4-yl}benzamide

Product 1

HCID 67518335N-[1-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-4-yl]-2,6-difluorobenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,6-Difluoro-N-1H-pyrazol-4-ylbenzamide (for a preparation see Intermediate 2; 86 mg, 0.385 mmol) was dissolved in DMF (2.5 ml), sodium iodide (21 mg, 0.140 mmol), potassium carbonate (169 mg, 1.22 mmol) and 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (synthesised according to Bioorganic & Medicinal Chemistry Letters (2009), 19, 2599-2603; 121 mg, 0.388 mmol) were then added using further DMF (2.5 ml). The reaction was then stirred overnight. Further 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (125 mg) was added and the reaction was stirred for 4 h. The reaction was concentrated in vacuo. The crude material was treated with water (50 ml) and the aqueous solution was extracted with ethyl acetate (3×50 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The sample was loaded in ethyl acetate and purified on silica (20 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound (70 mg) as a colourless gum; LCMS (System 1): MH+=454, tRET=3.59 min.

Workup

  1. stirringthe reaction was stirred for 4 h
  2. concentrationThe reaction was concentrated in vacuo
  3. additionThe crude material was treated with water (50 ml)
  4. extractionthe aqueous solution was extracted with ethyl acetate (3×50 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified on silica (20 g)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-261b298dd2d14b539f1033007d8946c8
Source dataset
uspto-grants-2015_10
Patent number
US09149462B2

Reaction notes

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