Water → HCID 21018330, compound

HRID 1744589Notes

Reaction equation

HRID 1744589 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:23][C:24]([C:26]2[C:27]([CH3:38])=[N:28][N:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH:30]=2)=[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+].Br[CH2:42][C:43]([O:45]CC)=[O:44].O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([N:23]([C:24]([C:26]2[C:27]([CH3:38])=[N:28][N:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH:30]=2)=[O:25])[CH2:42][C:43]([OH:45])=[O:44])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:10][CH2:11][CH:12]([OH:15])[CH2:13][CH2:14]1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 22227957HCID 22227957, compound

Product 1

HCID 21018330HCID 21018330, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Cyano-4-(4-tert-butyldimethylsilyloxypiperidin-1-yl)phenyl)-1-(4-fluorophenyl)-3-methylpyrazole-4-carboxamide (2.1 g) and sodium hydride (60% content, 0.2 g) were reacted in dimethylformamide (30 ml) under ice-cooling for 1 h. Dimethylformamide solution (10 ml) containing ethyl bromoacetate (1.0 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 saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. To the residue were added tetrabutylammonium fluoride (2.0 g), tetrahydrofuran (20 ml) and acetonitrile (20 ml) and the mixture was stirred at 80° C. for 1 h. The solvent was evaporated under reduced pressure. To the residue was added dilute hydrochloric acid, and the mixture was 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 toluene-ethyl acetate was added to the residue to allow crystallization. The crystals were recrystallized from hydrous isopropanol to give the title compound (0.2 g), melting point: 124–125° 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 saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customafter which the solvent was evaporated under reduced pressure
  9. additionTo the residue were added tetrabutylammonium fluoride (2.0 g), tetrahydrofuran (20 ml) and acetonitrile (20 ml)
  10. stirringthe mixture was stirred at 80° C. for 1 h
  11. customThe solvent was evaporated under reduced pressure
  12. additionTo the residue was added dilute hydrochloric acid
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customafter which the solvent was evaporated under reduced pressure
  17. additionA mixed solvent of toluene-ethyl acetate was added to the residue
  18. customcrystallization
  19. customThe crystals were recrystallized from hydrous isopropanol

Sources & evidence

ORD record
ord-21a8ca34d7aa452fbc9ea5d6c4b8e5fb
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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