Sodium hydride → 2-(2-Bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-2,4-dihydro-5-ethyl-3H-1,2,4-triazol-3-one

HRID 1648346Notes

Reaction equation

HRID 1648346 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[NH:14][C:13]([CH2:17][CH3:18])=[N:12]1.[H-].[Na+].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[C:30]([S:35]([NH:38][C:39]([CH3:42])([CH3:41])[CH3:40])(=[O:37])=[O:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:25][C:24]=1[F:43]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[S:35](=[O:36])(=[O:37])[NH:38][C:39]([CH3:42])([CH3:40])[CH3:41])=[CH:25][C:24]=2[F:43])[C:13]([CH2:17][CH3:18])=[N:12]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 100465214'-(Bromomethyl)-N-t-butyl-3'-fluoro-2-biphenylsulfonamideHCID 1355036252-(2-Bromo-5-nitrophenyl)-2,4-dihydro-5-ethyl-3H-1,2,4-triazol-3-one

Product 1

HCID 100777672-(2-Bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-2,4-dihydro-5-ethyl-3H-1,2,4-triazol-3-oneYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 2.00 g (6.39 mmol) of 2-(2-bromo-5-nitrophenyl)-2,4-dihydro -5-ethyl-3H-1,2,4-triazol-3-one (from Step B) and 184 mg (7.67 mmol) of sodium hydride in 7 mL of DMF was stirred at 50° C. for 3 hours. A solution of 4'-(bromomethyl)-N-t-butyl-3'-fluoro -2-biphenylsulfonamide (from Step F dissolved in 6 ml of DMF was then added and the resulting mixture was stirred at 50° C. for another 3 hours. The reaction mixture was quenched by addition of water followed by extractions with EtOAc, CH2Cl2, and MeOH. Water was removed and the organic layers were washed with brine, and dried over anhydrous Na2SO4. The entire crude product mixture thus obtained was flash chromatographed over silica gel (gradient elution using 0.5-2.0% MeOH in CH2Cl2) to afford 3.54 g (88%) of the title compound as a yellow solid (contaminated with some upper and lower Rf impurities by TLC but suitable for use in the next step without further purification), mp 223°-225° C.; mass spectrum (FAB) m/e 631, 633 (M+1)+.

Workup

  1. additionwas then added
  2. stirringthe resulting mixture was stirred at 50° C. for another 3 hours
  3. customThe reaction mixture was quenched by addition of water
  4. extractionfollowed by extractions with EtOAc, CH2Cl2, and MeOH
  5. customWater was removed
  6. washthe organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe entire crude product mixture thus obtained
  9. customchromatographed over silica gel (gradient elution using 0.5-2.0% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-0738fe7d8b8141bb99396d26718be0ee
Source dataset
uspto-grants-1995_07
Patent number
US05436259

Reaction notes

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