Oxalyl chloride → 4-[(5-Acetyl-2-propoxybenzoyl)amino]-5-propyl-1-(pyridin-2-yl methyl)-1H-pyrazole-3-carboxamide

HRID 1837554Notes

Reaction equation

HRID 1837554 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH3:22])=[C:14]([CH:18]=1)[C:15]([OH:17])=O)(=[O:9])[CH3:8].[NH2:23][C:24]1[C:25]([C:39]([NH2:41])=[O:40])=[N:26][N:27]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[C:28]=1[CH2:29][CH2:30][CH3:31]>CN(C)C=O.ClCCl>[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH3:22])=[C:14]([CH:18]=1)[C:15]([NH:23][C:24]1[C:25]([C:39]([NH2:41])=[O:40])=[N:26][N:27]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[C:28]=1[CH2:29][CH2:30][CH3:31])=[O:17])(=[O:9])[CH3:8]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 226781155-Acetyl-2-n-propoxybenzoic acidHCID 226781324-amino-5-propyl-1-(pyridin-2-ylmethyl)-1H-pyrazole-3-carboxamide

Product 1

HCID 226781254-[(5-Acetyl-2-propoxybenzoyl)amino]-5-propyl-1-(pyridin-2-yl methyl)-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (1.6 ml, 18 mmol) was added to an ice-cooled solution of 5-acetyl-2-n-propoxybenzoic acid (WO 9312095) (2 g, 9 mmol) in N,N-dimethylformamide (0.2 ml) and dichloromethane (200 ml) under nitrogen. Once addition was complete the solution was allowed to warm to room temperature for 3 hours and the solvent was removed under reduced pressure. The intermediate acid chloride was dissolved in pyridine (50 ml) and 4-amino-5-propyl-1-(pyridin-2-ylmethyl)-1H-pyrazole -3-carboxamide (WO 9954333) (1.5 g, 5.8 mmol) and the reaction was stirred at reflux for 3 hours, then at room temperature for 18 hours. The mixture was partitioned between dilute sodium carbonate solution and dichloromethane, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using dichloromethane:methanol (100:0 changing to 98:2 then 92:8) to afford the title compound as a beige solid, 1.5 g.

Workup

  1. additionOnce addition
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe intermediate acid chloride was dissolved in pyridine (50 ml)
  4. temperatureat reflux for 3 hours
  5. customThe mixture was partitioned between dilute sodium carbonate solution and dichloromethane
  6. dry with materialthe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-a76715d3aa0d462ca37d1f0bbca9afb5
Source dataset
uspto-grants-2004_08
Patent number
US06784185B2

Reaction notes

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