Cesium carbonate → 2,6-difluoro-N-[1-({2-methyl-4-[(2-pyridinylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]benzamide

HRID 1946390Notes

Reaction equation

HRID 1946390 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]=2[CH3:20])[N:8]=1)=[O:5].C(=O)([O-])[O-].[Cs+].[Cs+].Br.Br[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1>CS(C)=O>[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[CH:15][C:14]=2[CH3:20])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 595479572,6-Difluoro-N-{1-[(4-hydroxy-2-methylphenyl)methyl]-1H-pyrazol-3-yl}benzamide

Product 1

HCID 595480092,6-difluoro-N-[1-({2-methyl-4-[(2-pyridinylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]benzamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2,6-difluoro-N-{1-[(4-hydroxy-2-methylphenyl)methyl]-1H-pyrazol-3-yl}benzamide (for a preparation see Example 48)(103 mg, 0.30 mmol) in dimethyl sulfoxide (1 ml) was added cesium carbonate (195 mg, 0.60 mmol) and then 2-(bromomethyl)pyridine hydrobromide (107 mg, 0.423 mmol, Aldrich). The resulting red solution was stirred at ambient temperature under nitrogen overnight. The mixture was filtered using a hydrophobic frit and the filtrate diluted with methanol (1 ml). The filtrate was purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier (Method B). The solvent was evaporated in vacuo to give the title compound as an orange gum (28.3 mg); LCMS: (System 4) MH+=435, tRET=2.27 min.

Workup

  1. filtrationThe mixture was filtered
  2. additionthe filtrate diluted with methanol (1 ml)
  3. customThe filtrate was purified by MDAP on Sunfire C18 column
  4. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-d5774108eab8414da932f49114114620
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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