Potassium Carbonate → N-[1-({4-Chloro-2-[(phenylmethyl)oxy]phenyl]methyl)-1H-pyrazol-3-yl}-2,6-difluorobenzamide

HRID 1946362Notes

Reaction equation

HRID 1946362 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(=O)([O-])[O-].[K+].[K+].Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C=O)C>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][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)=[C:26]([O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:27]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 667254251-(Bromomethyl)-4-chloro-2-[(phenylmethyl)oxy]benzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547907N-[1-({4-Chloro-2-[(phenylmethyl)oxy]phenyl]methyl)-1H-pyrazol-3-yl}-2,6-difluorobenzamideYield 17.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for as preparation see Intermediate 9) (76 mg, 0.340 mmol) and potassium carbonate (96 mg, 0.692 mmol) was added a solution of 1-(bromomethyl)-4-chloro-2-[(phenylmethyl)oxy]benzene (0.106 g, 0.340 mmol) in DMF (1 ml). The reaction was stirred overnight, at ambient temperature and under nitrogen. The suspension was filtered using a hydrophobic frit and the residue washed with methanol (1 ml). The filtrate was purified by MDAP (supelcosil ABZ+Plus column) eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid) (Method A). The solvent was evaporated in vacuo to give the title compound as a white solid (27 mg); LCMS: (System 1) MH+=454, tRET=3.68 min.

Workup

  1. filtrationThe suspension was filtered
  2. washthe residue washed with methanol (1 ml)
  3. customThe filtrate was purified by MDAP (supelcosil ABZ+Plus column)
  4. washeluting with solvents A/B (A: Water+0.1% Formic acid, B
  5. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-354a4c80a678449992d4bf4bcda519d1
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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