1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 1750341Notes

Reaction equation

HRID 1750341 reaction equation
[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[C:8]([C:17]([OH:19])=O)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].CC[N:22]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl-].[NH4+]>CN(C=O)C.O>[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[C:8]([C:17]([NH2:22])=[O:19])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 534225981-Tert-butyl-5-(4-fluorophenyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 867211791-tert-butyl-5-(4-fluorophenyl)-1H-pyrazole-4-carboxamideYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (16.87 g, 64.32 mmol) obtained in step 2, WSC (16.03 g, 83.62 mmol), HOBt (11.30 g, 83.62 mmol), TEA (11.65 mL, 83.62 mmol) and ammonium chloride (4.47 g, 83.62 mmol) in DMF (200 mL) was stirred at room temperature for 2 days. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5→85% ethyl acetate/hexane) to give 1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (14.72 g, 56.3 mmol, 88%) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 5→85% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5c402c2ac0b7421f88cfbd185ffaa0e4
Source dataset
uspto-grants-2015_10
Patent number
US09156837B2

Reaction notes

Loading…