1-Bromo-2-methylpropane → N-[1-({2-Chloro-6-[(2-methylpropyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

HRID 1946355Notes

Reaction equation

HRID 1946355 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[CH2:9][N:10]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[N:11]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][CH:34]([CH3:36])[CH3:35]>CN(C=O)C.CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:33][CH:34]([CH3:36])[CH3:35])[C:3]=1[CH2:9][N:10]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[N:11]1

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 11430Potassium Carbonate2×HCID 59547909HCID 59547909, compound2×

Product 1

HCID 59547912N-[1-({2-Chloro-6-[(2-methylpropyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamideYield 9.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{1-[(2-chloro-6-hydroxyphenyl)methyl]-1H-pyrazol-3-yl}-2,6-difluorobenzamide (for as preparation see Intermediate 11)(37 mg, 0.102 mmol) in DMF (1 ml) was added potassium carbonate (18 mg, 0.13 mmol) and then 1-bromo-2-methylpropane (0.014 ml, 0.132 mmol, Aldrich). The suspension was stirred at ambient temperature overnight. A further amount of potassium carbonate (7 mg, 0.05 mmol) and then 1-bromo-2-methylpropane (0.014 ml, 0.132 mmol, Aldrich) was added to the suspension. The suspension was stirred at ambient temperature for a further 4 h. The suspension was diluted with methanol (0.5 ml) and then filtered through a cotton wool plug. 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 colourless gum (4 mg); LCMS: (System 1) MH+=420, tRET=3.63 min.

Workup

  1. stirringThe suspension was stirred at ambient temperature for a further 4 h
  2. filtrationfiltered through a cotton wool plug
  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-6659d02a7c284adabc3ac25d17c9a5d5
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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