Dimethylformamide → 5-{[2-Fluoro-5-methoxy-3-(2-methoxyethoxy)phenyl]-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-(3-nitropyridin-2-yl)-2,4-dihydro-[1,2,4]triazol-3-one

HRID 1161569Notes

Reaction equation

HRID 1161569 reaction equation
CN(C=O)C.CO[C:8](=[O:44])[N:9]=[C:10](SC)[C:11]([C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[C:30]([O:36][CH2:37][CH2:38][O:39][CH3:40])[C:29]=1[F:41])=[N:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[O:21][N:20]=2)=[CH:15][CH:14]=1.[N+:45]([C:48]1[C:49]([NH:54][NH2:55])=[N:50][CH:51]=[CH:52][CH:53]=1)([O-:47])=[O:46]>C(N(CC)CC)C>[F:41][C:29]1[C:30]([O:36][CH2:37][CH2:38][O:39][CH3:40])=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:28]=1[CH:11]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[O:21][N:20]=2)=[CH:15][CH:14]=1)[C:10]1[NH:9][C:8](=[O:44])[N:54]([C:49]2[C:48]([N+:45]([O-:47])=[O:46])=[CH:53][CH:52]=[CH:51][N:50]=2)[N:55]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 35789352-Hydrazinyl-3-nitropyridineHCID 72312810{2-[2-Fluoro-5-methoxy-3-(2-methoxyethoxy)phenyl]-1-methylsulfanyl-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]ethylidene}carbamic acid methyl ester

Product 1

HCID 1363892825-{[2-Fluoro-5-methoxy-3-(2-methoxyethoxy)phenyl]-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-(3-nitropyridin-2-yl)-2,4-dihydro-[1,2,4]triazol-3-oneYield 56.4%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

To 3 ml of a DMF solution containing 86 mg of {2-[2-fluoro-5-methoxy-3-(2-methoxyethoxy)phenyl]-1-methylsulfanyl-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]ethylidene}carbamic acid methyl ester, 25 mg of (3-nitropyridin-2-yl)hydrazine and 0.023 ml of triethylamine were added. The resulting mixture was stirred at 85° C. for 16 hours and concentrated under reduced pressure. The residue was dissolved in 5 ml of methanol, and 66 mg of sodium cyanotrihydroborate and 0.085 ml of acetic acid were added thereto. The mixture was stirred at room temperature for 15 hours. To this reaction mixture, 50 ml of ethyl acetate and 20 ml of water were added. The organic layer was washed with 20 ml of water and then with 20 ml of saturated brine and dried over anhydrous magnesium sulfate. The desiccating agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (55 mg).

Workup

  1. additionwere added
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in 5 ml of methanol
  4. addition66 mg of sodium cyanotrihydroborate and 0.085 ml of acetic acid were added
  5. stirringThe mixture was stirred at room temperature for 15 hours
  6. additionTo this reaction mixture, 50 ml of ethyl acetate and 20 ml of water were added
  7. washThe organic layer was washed with 20 ml of water
  8. dry with materialwith 20 ml of saturated brine and dried over anhydrous magnesium sulfate
  9. customThe desiccating agent was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-a7a4e8256eb64b0bb7053ec64a22e8ce
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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