Water → HCID 58243554, compound

HRID 389151Notes

Reaction equation

HRID 389151 reaction equation
C1C=CC2N(O)N=NC=2C=1.[CH:11]([NH:13][NH2:14])=[O:12].[C:15]([C:17]1[CH:18]=[CH:19][C:20]([O:26][C:27]([CH3:45])([C:29]2[N:33]([CH3:34])[C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]([F:44])([F:43])[F:42])=[N:31][N:30]=2)[CH3:28])=[C:21]([CH:25]=1)[C:22](O)=O)#[N:16].O>CN(C=O)C>[CH3:45][C:27]([C:29]1[N:33]([CH3:34])[C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]([F:43])([F:44])[F:42])=[N:31][N:30]=1)([O:26][C:20]1[CH:19]=[CH:18][C:17]([C:15]#[N:16])=[CH:25][C:21]=1[C:22]1[O:12][CH:11]=[N:13][N:14]=1)[CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 12229HydrazinecarboxaldehydeHCID 757711-HydroxybenzotriazoleHCID 58244139HCID 58244139, compound

Product 1

HCID 58243554HCID 58243554, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

WSC•monohydrochloride (81 mg), HOBt (57 mg) and formic hydrazide (30 mg) were sequentially added to a solution of 5-cyano-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzoic acid (140 mg) in DMF (2 ml), followed by stirring at room temperature for 2 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting solid (130 mg) was dissolved in dichloromethane (2 ml) and pyridine (0.090 ml) was added thereto, followed by cooling to −78° C. Trifluoromethanesulfonic acid (0.090 ml) was added to the reaction solution and was elevated to room temperature, followed by stirring for 30 minutes. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1). The resulting solid was washed with diisopropylether to obtain, as a white solid, 4-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)-3-(1,3,4-oxadiazol-2-yl)benzonitrile (65 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting solid (130 mg) was dissolved in dichloromethane (2 ml)
  6. additionpyridine (0.090 ml) was added
  7. temperatureby cooling to −78° C
  8. additionTrifluoromethanesulfonic acid (0.090 ml) was added to the reaction solution
  9. customwas elevated to room temperature
  10. stirringby stirring for 30 minutes
  11. additionSaturated aqueous sodium bicarbonate was added to the reaction solution
  12. extractionfollowed by extraction with ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customthe solvent was evaporated under reduced pressure
  16. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1)
  17. washThe resulting solid was washed with diisopropylether

Sources & evidence

ORD record
ord-b051aa3cdf9842b48beab2494e1a6fa3
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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