Water → HCID 22228173, compound

HRID 1744583Notes

Reaction equation

HRID 1744583 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:23][C:24]([C:26]2[CH:27]=[N:28][N:29]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[C:30]=2[CH3:31])=[O:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([O:15][Si](C(C)(C)C)(C)C)[CH2:11][CH2:10]1)#[N:2].[H-].[Na+].[CH3:41]I.O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([N:23]([CH3:41])[C:24]([C:26]2[CH:27]=[N:28][N:29]([C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)[C:30]=2[CH3:31])=[O:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22227885HCID 22227885, compound

Product 1

HCID 22228173HCID 22228173, compoundYield 65.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-[3-Cyano-4-(4-tert-butyldimethylsilyloxypiperidin-1-yl)phenyl]-1-(4-fluorophenyl)-5-methylpyrazole-4-carboxamide (1.5 g) and sodium hydride (60% content, 0.2 g) were reacted in dimethylformamide (10 ml) under ice-cooling for 1 h. Dimethylformamide solution (1 ml) containing methyl iodide (0.6 g) was added and the mixture was stirred under ice-cooling for 1 h and, after allowed to warm to room temperature, stirred for another 1 h. The reaction mixture was added into water and extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. Tetrabutylammonium fluoride (1.4 g), tetrahydrofuran (10 ml) and acetonitrile (10 ml) were added to the residue, and the mixture was stirred at 80° C. for 2 h. The reaction mixture was added into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. A mixed solvent of ethyl acetate-n-hexane was added to the residue to allow crystallization. The crystals were recrystallized from a mixed solvent of ethyl acetate-ethanol to give the title compound (0.8 g), melting point: 211–212° C.

Workup

  1. temperaturecooling for 1 h
  2. additionwas added
  3. temperaturecooling for 1 h
  4. stirringstirred for another 1 h
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with dilute hydrochloric acid and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customafter which the solvent was evaporated under reduced pressure
  9. additionTetrabutylammonium fluoride (1.4 g), tetrahydrofuran (10 ml) and acetonitrile (10 ml) were added to the residue
  10. stirringthe mixture was stirred at 80° C. for 2 h
  11. additionThe reaction mixture was added into water
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customafter which the solvent was evaporated under reduced pressure
  16. additionA mixed solvent of ethyl acetate-n-hexane was added to the residue
  17. customcrystallization
  18. customThe crystals were recrystallized from a mixed solvent of ethyl acetate-ethanol

Sources & evidence

ORD record
ord-4171329c4389497cb5e9af8f276b27d2
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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