Sodium Bicarbonate → 2,6-Difluoro-N-(1-{[2-methyl-6-(methyloxy)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946429Notes

Reaction equation

HRID 1946429 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].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:28][C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:37].C(=O)(O)[O-].[Na+]>C1COCC1>[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][N:9]([CH2:28][C:29]2[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:37])[N:8]=1)=[O:5]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 103532222-(Bromomethyl)-1-methoxy-3-methylbenzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 595478822,6-Difluoro-N-(1-{[2-methyl-6-(methyloxy)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(50 mg, 0.224 mmol) in dry THF (1.75 ml) under nitrogen was added 1.0 lithium bis(trimethylsilyl)amide in THF (0.2 ml, 0.2 mmol) dropwise and the solution stirred for 30 min. To the solution was added a solution of 2-(bromomethyl)-1-methyl-3-(methyloxy)benzene (for a preparation see intermediate 57)(48 mg, 0.224 mmol) in THF (1.75 ml). The solution was stirred for 1.5 h and then allowed to stand overnight. The solvent was blown down using a stream of nitrogen and aqueous sodium bicarbonate added to the residue. The aqueous phase was then extracted with chloroform. The organic extract was removed in vacuo to give a gum (84 mg). The residue was purified on MDAP (Method B). The solvent was removed and the residue dried at −45° C. under high vacuum to give the title compound as a white solid; LCMS (System 4) MH+=358, tRET=2.77 min.

Workup

  1. stirringThe solution was stirred for 1.5 h
  2. waitto stand overnight
  3. additionadded to the residue
  4. extractionThe aqueous phase was then extracted with chloroform
  5. extractionThe organic extract
  6. customwas removed in vacuo

Sources & evidence

ORD record
ord-efa263d39ff6450c8b722cf66a86b939
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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