反应详情

温度

50 °C

A solution of (S)-2,2-dimethylcyclopropanecarboxylic acid (194 mg, 1.70 mmol), and carbonyldiimidazole (275 mg, 1.70 mmol) in THF was stirred at 50° C. for 3 hrs. To this was added dropwise a solution of DBU (258 mg, 1.7 mmol) and 5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one (300 mg, 0.57 mmol) (from Example 16, Step C) in THF. After stirring at 50° C. overnight, the reaction mixture was quenched by addition of 5% citric acid and extracted with EtOAc. The organic layers were combined and washed with water, 5% NaHCO3, and brine, and dried over anhydrous Na2SO4. The crude material obtained after filtration and evaporation of volatiles was flash chromatographed over 60 mL silica gel (gradient elution using 0.5-5.0% MeOH/CH2Cl2) to afford the title compound in 74% yield (263 mg) as a white solid, homogeneous by TLC in 5% MeOH/CH2Cl2 ; mass spectrum (FAB) m/e 627 (M+1)+, 649 (M+Na)+ ; mp 93°-95° C.

1. customthe reaction mixture was quenched by addition of 5% citric acid
2. extractionextracted with EtOAc
3. washwashed with water, 5% NaHCO3, and brine
4. dry with materialdried over anhydrous Na2SO4
5. customThe crude material obtained
6. filtrationafter filtration and evaporation of volatiles
7. customchromatographed over 60 mL silica gel (gradient elution using 0.5-5.0% MeOH/CH2Cl2)