Water → 4''-[3-Butyl-5-oxo-1-(2-trifluoromethyl-phenyl)-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid (4-nitro-phenyl)-amide

HRID 36243Notes

Reaction equation

HRID 36243 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[S:34](=[O:37])(=[O:36])[NH2:35])=[CH:24][CH:23]=2)[C:7](=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].F[C:41]1[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=1.O>CN(C=O)C.CCOC(C)=O>[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[S:34](=[O:37])(=[O:36])[NH:35][C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=[CH:24][CH:23]=2)[C:7](=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 103469025-n-Butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

Product 1

HCID 104168364''-[3-Butyl-5-oxo-1-(2-trifluoromethyl-phenyl)-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid (4-nitro-phenyl)-amideYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-4-one (100 mg, 0.19 mmol) (from Example 16, Step C) and sodium hydride (4.5 mg, 0.19 mmol) in DMF, (0.5 mL) which had been stirring at room temperature for 2 h, was added dropwise a solution of 4-fluoro-nitrobenzene (27 mg, 0.19 mmol) dissolved in 0.3 mL DMF. The yellow reaction mixture was stirred at 60° C. for 29 hours. After cooling to room temperature, water and EtOAc were added and the phases were separated. After two more extractions with EtOAc, the organic layers were combined and washed twice with water, and brine, and then dried over Na2SO4. The crude product obtained after filtration and evaporation of volatiles was flash chromatographed over silica gel (gradient elution using 0.3-5.0% MeOH/CH2Cl2) to afford 53 mg (43%) of the title compound as an off-white solid, homogeneous by TLC in 5% MeOH/CH2Cl2 ; mass spectrum (FAB) m/e 652 (M+1)+ ; mp 186°-187° C.

Workup

  1. stirringThe yellow reaction mixture was stirred at 60° C. for 29 hours
  2. temperatureAfter cooling to room temperature
  3. customthe phases were separated
  4. extractionAfter two more extractions with EtOAc
  5. washwashed twice with water, and brine
  6. dry with materialdried over Na2SO4
  7. customThe crude product obtained
  8. filtrationafter filtration and evaporation of volatiles
  9. customchromatographed over silica gel (gradient elution using 0.3-5.0% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e3e7d199df7a4d569dc12e5a115a9241
Source dataset
uspto-grants-1995_05
Patent number
US05411980

Reaction notes

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