Benzylamine → 1-(4-fluoro-phenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid benzylamide

HRID 268637Notes

Reaction equation

HRID 268637 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]=[O:14])=[C:11]([CH:15]([CH3:17])[CH3:16])[C:10]([C:18]([OH:20])=O)=[N:9]2)=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[CH2:44]([NH2:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C(Cl)Cl>[CH2:44]([NH:51][C:18]([C:10]1[C:11]([CH:15]([CH3:16])[CH3:17])=[C:12]([CH:13]=[O:14])[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]=1)=[O:20])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 247549741-(4-fluoro-phenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 247545241-(4-fluoro-phenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid benzylamideYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-(4-fluoro-phenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid (1.25 g, 4.52 mmol) in CH2Cl2 (50 mL) at 25° C. was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.30 g, 6.79 mmol; commercially available from Sigma Aldrich) followed by 1-hydroxybenzotriazole hydrate (1.04 g, 6.79 mmol; commercially available from Sigma Aldrich) and the reaction was stirred for 5 min at 25° C. Subsequently, benzyl amine (0.533 g, 4.98 mmol; commercially available from Sigma Aldrich) was added and the reaction was stirred for an additional 4 hrs as a fine white precipitate developed. The organic layer was washed with 1 N HCl, saturated NaHCO3 and brine. After drying and concentration, the product was purified by silica gel chromatography (20% EtOAc/Hex) to provide 1-(4-fluoro-phenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid benzylamide (0.65 g, 39%): MS(APCI+): m/z366.1 (M+H).

Workup

  1. additioncommercially available from Sigma Aldrich) was added
  2. stirringthe reaction was stirred for an additional 4 hrs as a fine white precipitate
  3. washThe organic layer was washed with 1 N HCl, saturated NaHCO3 and brine
  4. customAfter drying
  5. concentrationconcentration
  6. customthe product was purified by silica gel chromatography (20% EtOAc/Hex)

Sources & evidence

ORD record
ord-fcfdbfcf656644949ea3b35fb04eba89
Source dataset
uspto-grants-2008_11
Patent number
US07446121B2

Reaction notes

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