Water → N-(5-Cyano-3-methyl-1-propyl-1H-pyrazol-4-yl)acetamide

HRID 2417683Notes

Reaction equation

HRID 2417683 reaction equation
[CH3:1][C:2]1[C:6]([N+:7]([O-])=O)=[C:5]([C:10]([NH2:12])=O)[N:4]([CH2:13][CH2:14][CH3:15])[N:3]=1.[N+]([C:19]1[CH:23]=CNN=1)([O-])=O.[OH2:24]>P(Cl)(Cl)(Cl)=O.C(O)(=O)C.[Fe]>[C:10]([C:5]1[N:4]([CH2:13][CH2:14][CH3:15])[N:3]=[C:2]([CH3:1])[C:6]=1[NH:7][C:23](=[O:24])[CH3:19])#[N:12]

Participants

7

Reactant 3

HCID 962WaterHCID 542536793-Methyl-4-nitro-1-propyl-1H-pyrazole-5-carboxamideHCID 178526745HCID 178526745, compound

Product 1

HCID 13338440N-(5-Cyano-3-methyl-1-propyl-1H-pyrazol-4-yl)acetamide

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

A solution of 46 g (0.2 mol) of 3-methyl-4-nitro-1-n-propyl-pyrazole-5-carbonyl chloride [J. Med. Chem., 16 1346 (1973)] in 50 ml of acetone is added slowly to 250 ml of cold (5° C.) concentrated ammonium hydroxide. The mixture is filtered to give 33 g (79%) of 3-methyl-4-nitro-1-n-propylpyrazole-5-carboxamide, mp 136°-138° C. The amide (33 g, 0.15 mol) is stirred under reflux in 100 ml of phosphorus oxychloride for 2.5 hours and evaporated in vacuo. The residue is stirred in 250 ml of ice water to give, after filtering, 25.5 g (86%) of 5-cyano-3-methyl-4-nitro-1-n-propylpyrazole. This nitropyrazole (25 g, 0.013 mol) is dissolved in 350 ml of glacial acetic acid and treated at 95° C. portionwise with 12 g iron filings and 20 ml of water. After stirring under reflux three hours the mixture is filtered and the filtrate is concentrated in vacuo. The concentrate is extracted with methylene dichloride and the organic extract is treated with 20 ml of acetic anhydride and refluxed for two hours. The cooled mixure is stirred with saturated aqueous NaHCO3 solution, the organic layer is dried (MgSO4), and evaporated in vacuo to give 16.5 g of N-(5-cyano-3-methyl-1-n-propylpyrazol-4-yl)acetamide, mp 129°-131° C.

Workup

  1. customevaporated in vacuo
  2. customto give
  3. filtrationafter filtering
  4. stirringAfter stirring
  5. temperatureunder reflux three hours the mixture
  6. filtrationis filtered
  7. concentrationthe filtrate is concentrated in vacuo
  8. extractionThe concentrate is extracted with methylene dichloride
  9. extractionthe organic extract
  10. additionis treated with 20 ml of acetic anhydride
  11. temperaturerefluxed for two hours
  12. stirringThe cooled mixure is stirred with saturated aqueous NaHCO3 solution
  13. dry with materialthe organic layer is dried (MgSO4)
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-debd75fb9ac94a3486eea53899126c84
Source dataset
uspto-grants-1984_09
Patent number
US04469868

Reaction notes

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