Potassium Carbonate → N-{3-Cyano-4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl}-1-(2,4-difluorophenyl)-5-methylpyrazole-4-carboxamide

HRID 1744591Notes

Reaction equation

HRID 1744591 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([CH3:14])=[C:12]([C:15]([OH:17])=O)[CH:11]=[N:10]1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([N:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][OH:35])[CH2:29][CH2:28]2)=[C:23]([CH:26]=1)[C:24]#[N:25].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:24]([C:23]1[CH:26]=[C:19]([NH:18][C:15]([C:12]2[CH:11]=[N:10][N:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[C:13]=2[CH3:14])=[O:17])[CH:20]=[CH:21][C:22]=1[N:27]1[CH2:28][CH2:29][N:30]([CH2:33][CH2:34][OH:35])[CH2:31][CH2:32]1)#[N:25]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 167739411-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acidHCID 176095935-Amino-2-[4-(2-hydroxyethyl)piperazin-1-yl]benzonitrile

Product 1

HCID 22227961N-{3-Cyano-4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl}-1-(2,4-difluorophenyl)-5-methylpyrazole-4-carboxamideYield 52.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(2,4-Difluorophenyl)-5-methylpyrazole-4-carboxylic acid (2.4 g), 5-amino-2-[4-(2-hydroxyethyl)piperazin-1-yl]benzonitrile (2.4 g), 1-hydroxybenzotriazole (1.6 g) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (2.3 g) were added to dimethylformamide (25 ml) and the mixture was stirred at room temperature for 5 h. The reaction mixture was treated with aqueous potassium carbonate solution 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. The residue was purified by silica gel column chromatography (mobile phase:chloroform:methanol=100:1). Diisopropyl ether was added to the obtained oily substance to allow crystallization. The crystals were recrystallized from isopropyl alcohol to give the title compound (2.4 g), melting point: 193–194° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customafter which the solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (mobile phase:chloroform:methanol=100:1)
  6. additionDiisopropyl ether was added to the obtained oily substance
  7. customcrystallization
  8. customThe crystals were recrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-6f401677ee29412d8a6260702fb2eaa6
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

Loading…