反应详情

Add 2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (500 mg, 2.07 mmol), toluene (10 mL), tris(dibenzylideneacetone)dipalladium(0) (95 mg, 0.104 mmol), 2-(di-tert-butylphosphino)biphenyl (62 mg, 0.207 mmol), and methanesulfonamide sodium salt (363 mg, 3.11 mmol) to a sealed flask flushed with nitrogen. (Prepare methanesulfonamide sodium salt by adding sodium hydride (2.0 g, 50.0 mmol, 60% dispersion in mineral oil) slowly to a solution of methanesulfonamide (5.0 g, 52.6 mmol) and THF (80 mL) at 0° C.) Stir the mixture at room temperature overnight. Concentrate and dry the residue under vacuum. Heat and stir the sealed flask at 100° C. for 18 h. Cool to room temperature, filter through a pad of filtering agent, wash with dichloromethane, concentrate the filtrate and purify (silica gel chromatography, eluting with 20:80 to 25:75 ethyl acetate:hexanes) to give the title compound (475 mg, 76%).

1. customflushed with nitrogen
2. custom(Prepare methanesulfonamide sodium salt
3. concentrationConcentrate
4. customdry the residue under vacuum
5. temperatureHeat
6. stirringstir the sealed flask at 100° C. for 18 h
7. temperatureCool to room temperature
8. filtrationfilter through a pad
9. filtrationof filtering agent
10. washwash with dichloromethane
11. concentrationconcentrate the filtrate
12. custompurify
13. wash(silica gel chromatography, eluting with 20:80 to 25:75 ethyl acetate:hexanes)