Water → HCID 68014935, compound

HRID 1747823Notes

Reaction equation

HRID 1747823 reaction equation
[CH3:1][O:2][C:3]1[C:4]([OH:20])=[C:5]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[CH:11][CH:10]=2)[N:6]=[N:7][CH:8]=1.[H-].[Na+].[F:23][C:24]([F:34])([F:33])[C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27]Br.O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:1][O:2][C:3]1[C:4](=[O:20])[C:5]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[CH:11][CH:10]=2)=[N:6][N:7]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=2[C:24]([F:23])([F:33])[F:34])[CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1230571-(Bromomethyl)-2-(trifluoromethyl)benzeneHCID 178493808HCID 178493808, compound

Product 1

HCID 68014935HCID 68014935, compoundYield 32.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4-ol (21 mg) in DMF (0.5 mL) were added tetra n-butylammoniumiodide (9 mg) and 60% NaH oil mixture (4 mg) at 0° C., and the mixture was stirred as it was for 20 min. To the reaction mixture was added 2-(trifluoromethyl)benzyl bromide (24 mg), and the mixture was stirred at room temperature for 60 hr. To the reaction mixture was added water (0.5 mL), and the mixture was extracted with ethyl acetate (2 mL×2) (the extract was separated by an organic layer-separation filter). The extract was distilled by blowing air at 60° C., and the residue was dissolved in DMSO, and purified by preparative HPLC (column: YMC combiprep pro C18 RS, solvent: 10 mM NH4HCO3/MeCN). The obtained eluate containing the title compound was concentrated by blowing air at 60° C. to give the title compound (10.8 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 60 hr
  2. extractionthe mixture was extracted with ethyl acetate (2 mL×2) (the extract
  3. customwas separated by an organic layer-separation
  4. filtrationfilter)
  5. distillationThe extract was distilled
  6. customat 60° C.
  7. dissolutionthe residue was dissolved in DMSO
  8. custompurified by preparative HPLC (column: YMC combiprep pro C18 RS, solvent: 10 mM NH4HCO3/MeCN)
  9. additionThe obtained eluate containing the title compound
  10. concentrationwas concentrated
  11. customat 60° C.

Sources & evidence

ORD record
ord-74eb23bdd747406183253bf47a50e1cc
Source dataset
uspto-grants-2015_10
Patent number
US09150588B2

Reaction notes

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