Water → HCID 21018331, compound

HRID 1744584Notes

Reaction equation

HRID 1744584 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+].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[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])[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 22227885HCID 22227885, compound

Product 1

HCID 21018331HCID 21018331, compoundYield 10.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Cyano-4-(4-tert-butyldimethylsilyloxypiperidin-1-yl) phenyl)-1-(4-fluorophenyl)-5-methylpyrazole-4-carboxamide (3.3 g) and sodium hydride (60% content, 0.3 g) were reacted in dimethylformamide (30 ml) under ice-cooling for 1 h. Dimethylformamide solution (10 ml) containing ethyl bromoacetate (1.4 g) was added and the mixture was stirred under ice-cooling for 1 h and, after allowed to warm to roan 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. Tetrabutylammonium fluoride (3.0 g), tetrahydrofuran (20 ml) and acetonitrile (20 ml) were added to the residue 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 (0.3 g), melting point: 155–158° C.

Workup

  1. temperaturecooling for 1 h
  2. additionwas added
  3. temperaturecooling for 1 h
  4. temperatureto warm
  5. stirringstirred for another 1 h
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customafter which the solvent was evaporated under reduced pressure
  10. additionTetrabutylammonium fluoride (3.0 g), tetrahydrofuran (20 ml) and acetonitrile (20 ml) were added to the residue
  11. stirringthe mixture was stirred at 80° C. for 1 h
  12. customThe solvent was evaporated under reduced pressure
  13. additionTo the residue was added dilute hydrochloric acid
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe organic layer was washed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. customafter which the solvent was evaporated under reduced pressure
  18. additionA mixed solvent of toluene-ethyl acetate was added to the residue
  19. customcrystallization
  20. customThe crystals were recrystallized from hydrous isopropanol

Sources & evidence

ORD record
ord-64131bd4a5a342e984163e31cdbfab34
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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