反应详情

NaH (350 mg) was added to a solution of 3-difluoromethyl-6,6-dimethyl-1,5,6,7-tetrahydro-indazol-4-one (3.12 g) in DMSO (75 mL) at room temperature. After 20 minutes of stirring, 2-bromo-4-fluorobenzonitrile (4.67 g) was added and stirred at 45° C. overnight. The reaction was diluted with saturated aqueous NH4Cl (100 mL), H2O (100 mL). The mixture was extracted with ethyl acetate (4×150 mL), dried over Na2SO4, filtered, concentrated, purified by column chromatography eluting with a 1:2 mixture of ethyl acetate/hexanes. The concentrate of desired fractions was made into a slurry in ether, stirred for 2 h, filtered, washed by hexane to give pure solid 2-bromo-4-(6,6-dimethyl-4-oxo-3-difluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (2.82 g, 49.2%). LCMS m/z: (M+H)=395.65, (MW: 394).

1. stirringstirred at 45° C. overnight
2. extractionThe mixture was extracted with ethyl acetate (4×150 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified by column chromatography
7. washeluting with a 1:2 mixture of ethyl acetate/hexanes
8. concentrationThe concentrate of desired fractions
9. stirringstirred for 2 h
10. filtrationfiltered
11. washwashed by hexane