Reaction #64481

Reaction equation

4-morpholinecarbonyl chloride

5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]- 2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

5-n-Butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

sodium hydride

→

title compound

Yield 25.9%

5-n-Butyl-2,4-dihydro-4-[[2'-[N-(4-morpholinecarbonyl)sulfamoyl]biphenyl-4-yl]methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

Yield 25.9%

Solvents

THF

Conditions

Workup

1. 1
   workup.STIRRINGthe solution was stirred under N2 at room temperature overnight
2. 2
   OtherThe reaction was quenched by addition of 2 ml of H2O
3. 3
   Extractionfollowed by extraction with 3×5 ml of ethyl acetate
4. 4
   WashThe combined organic extracts were washed with 2×5 ml of H2O
5. 5
   Otherchromatographed on silica gel (gradient elution with 0.3-10% MeOH in CH2Cl2)

Procedure

To a solution of 51.1 mg (0.0964 mmole) of 5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]- 2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one (from Example 16, Step C) in 0.2 ml of dry THF was added 4.6 mg (0.116 mmole) of sodium hydride (60% in oil), and the mixture was allowed to stir at room temperature under N2 for 4 hours. Next, 17 μl (21.6 mg, 0.145 mmole) of 4-morpholinecarbonyl chloride was added, and the solution was stirred under N2 at room temperature overnight. The reaction was quenched by addition of 2 ml of H2O followed by extraction with 3×5 ml of ethyl acetate. The combined organic extracts were washed with 2×5 ml of H2O and then with 5 ml of brine. After co-evaporation twice from toluene, the crude product was flash chromatographed on silica gel (gradient elution with 0.3-10% MeOH in CH2Cl2) to give 16.1 mg of the title compound as a whitish glass; satisfactory purity by TLC in 19:1 and 9:1 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 682 (M+K)+.

Source