Triethylamine → 4-[(5-acetyl-2-propoxybenzoyl)amino]-5-ethyl-1H-pyrazole-3-carboxamide

HRID 1837553Notes

Reaction equation

HRID 1837553 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].C(N(CC)CC)C.[NH2:30][C:31]1[C:32]([CH2:39][CH3:40])=[N:33][NH:34][C:35]=1[C:36]([NH2:38])=[O:37]>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:30][C:31]1[C:35]([C:36]([NH2:38])=[O:37])=[N:34][NH:33][C:32]=1[CH2:39][CH3:40])=[O:17])(=[O:9])[CH3:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 226781155-Acetyl-2-n-propoxybenzoic acidHCID 178438044HCID 178438044, compound

Product 1

HCID 226781184-[(5-acetyl-2-propoxybenzoyl)amino]-5-ethyl-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (5.45 ml, 46.4 mmol) was added to a solution of 5-acetyl-2-n-propoxy-benzoic acid (WO 9312095) (11.1 g, 30.9 mmol) in N,N-dimethylformamide (0.1 ml) and dichloromethane (200 ml) under nitrogen at room temperature. Once addition was complete the solution was stirred for 1 hour. The solution was concentrated under reduced pressure and azeotroped with toluene, and the intermediate acid chloride was dissolved in dichloromethane (200 ml). Triethylamine (10.4 ml, 46.4 mmol) was added followed by 4-amino-3-ethyl-1H-pyrazole-5-Carboxamide (WO 9849166) (7.7 g, 30.9 mmol) and the reaction was stirred at room temperature for 16 hours. The mixture was washed with 1N hydrochloric acid (2×100 ml), 10% sodium bicarbonate solution (100 ml) and brine (100 ml), dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was recrystallised from acetonitrile to afford the title compound as a crystalline solid, 14.8 g.

Workup

  1. additionOnce addition
  2. concentrationThe solution was concentrated under reduced pressure
  3. customazeotroped with toluene
  4. dissolutionthe intermediate acid chloride was dissolved in dichloromethane (200 ml)
  5. stirringthe reaction was stirred at room temperature for 16 hours
  6. washThe mixture was washed with 1N hydrochloric acid (2×100 ml), 10% sodium bicarbonate solution (100 ml) and brine (100 ml)
  7. dry with materialdried over Na2SO4
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was recrystallised from acetonitrile

Sources & evidence

ORD record
ord-09c46aa1fd624eedafd9eb5d9297d030
Source dataset
uspto-grants-2004_08
Patent number
US06784185B2

Reaction notes

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