Dichloromethane → 4''-[3-Butyl-1-(2-chloro-phenyl)-5-oxo-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid tert-butylamide

HRID 36192Notes

Reaction equation

HRID 36192 reaction equation
[CH2:1]([C:5]1[NH:6][C:7](=[O:17])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:9]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[C:20]([NH:24][S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]1[CH:39]=[CH:38][C:37]([CH2:40]Br)=[CH:36][CH:35]=1)(=[O:27])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(Cl)Cl>CN(C=O)C.CO>[CH2:1]([C:5]1[N:6]([CH2:40][C:37]2[CH:38]=[CH:39][C:34]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[S:25](=[O:27])(=[O:26])[NH:24][C:20]([CH3:21])([CH3:23])[CH3:22])=[CH:35][CH:36]=2)[C:7](=[O:17])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 15282100[2'-(N-t-Butylsulfamoyl)biphenyl-4-yl]methyl bromideHCID 1355359253H-1,2,4-Triazol-3-one, 5-butyl-2-(2-chlorophenyl)-2,4-dihydro-

Product 1

HCID 117573574''-[3-Butyl-1-(2-chloro-phenyl)-5-oxo-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid tert-butylamideYield 76%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 78 mg (0.310 mmole) of 5-n-butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (from Example 5, Step A) in 620 μL of dry DMF was added 14.9 mg (0.372 mmole) of sodium hydride (60% in oil), and the mixture was stirred under N2 at 50° C. for 1 hour, until gas evolution was complete. The resulting solution was cooled to room temperature and treated dropwise with a solution of 178 mg (0.465 mmole) of [2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl bromide (from Example 12, Step D) in DMF. The mixture was stirred at 50° C. for 1.5 hours, by which time TLC (98:2 CH2Cl2 --MeOH) indicated complete reaction. The mixture was quenched by addition of approximately 6 ml of H2O followed by extraction with 3×10 ml of EtOAc. The combined EtOAc extracts were washed with 2×15ml of H2O followed by 15 ml of brine. The organic phase was dried over Na2SO4, filtered, and concentrated. Column chromatography of the residue on silica gel (elution with 0.5% MeOH in CH2Cl2) yielded 130 mg (76%) of the title compound as a white, stiff foam, homogeneous by TLC in 98:2 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 553 (M+1)+.

Workup

  1. temperatureThe resulting solution was cooled to room temperature
  2. customreaction
  3. customThe mixture was quenched by addition of approximately 6 ml of H2O
  4. extractionfollowed by extraction with 3×10 ml of EtOAc
  5. washThe combined EtOAc extracts were washed with 2×15ml of H2O
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b673eafd96e94cb58237e1154b4043e8
Source dataset
uspto-grants-1995_05
Patent number
US05411980

Reaction notes

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