Ammonia → 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxamide

HRID 2372396Notes

Reaction equation

HRID 2372396 reaction equation
C(O[C:4](=[N:14][CH3:15])[CH2:5][C:6]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=1[F:13])C.[C:16]([NH2:22])(=[O:21])[C:17]([NH:19][NH2:20])=O.N>CN1CCOCC1.ClCCl>[F:12][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]([F:13])[C:6]=1[CH2:5][C:4]1[N:14]([CH3:15])[C:17]([C:16]([NH2:22])=[O:21])=[N:19][N:20]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 68200Oxamic acid hydrazideHCID 199042321-ethoxy-2-(2,6-difluorophenyl)-1-(N-methylimino)-ethane

Product 1

HCID 199042355-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 79724-MethylmorpholineSolvent

Procedure

320 mg (1.5 mmol) of 1-ethoxy-2-(2,6-di-fluorophenyl)-1-(N-methylimino)-ethane and 155 mg (1.5 mmol) of oxalic acid monoamide monohydrazide are dissolved under a nitrogen atmosphere in 5 ml of N-methylmorpholine and the whole is heated under reflux for 41 hours After cooling, the reaction mixture is diluted with 20 ml of dichloromethane and extracted by shaking in succession twice with water, twice with 2N hydrochloric acid and again with water. The last three acidic aqueous phases obtained are combined, rendered alkaline with concentrated ammonia solution and extracted three times with dichloromethane. The combined organic phases are dried over magnesium sulphate and concentrated. Recrystallisation of the crude product from ethanol yields 102 mg (27% of the theoretical yield) of the desired 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxamide which melts at 189-190°.

Workup

  1. temperaturethe whole is heated
  2. temperatureunder reflux for 41 hours
  3. temperatureAfter cooling
  4. extractionextracted
  5. customThe last three acidic aqueous phases obtained
  6. extractionextracted three times with dichloromethane
  7. dry with materialThe combined organic phases are dried over magnesium sulphate
  8. concentrationconcentrated
  9. customRecrystallisation of the crude product from ethanol
  10. customyields 102 mg (27% of the

Sources & evidence

ORD record
ord-f0c7dd9575124ad7b62dfe1b077f302b
Source dataset
uspto-grants-1992_03
Patent number
US05098922

Reaction notes

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