反应详情

温度

60 °C

A suspension of (2-amino-5-chlorophenyl) (pyridin-4-yl)methanone (156 g) in pyridine (2350 mL) was heated at 60° C. N,N-Dimethyl-4-aminopyridine (8.21 g) and 4-tert-butylbenzenesulfonyl chloride (180 g) were added, and the mixture was heated at 75° C. for 18 hr. 4-tert-Butylbenzenesulfonyl chloride (15.6 g) was further added, and the mixture was stirred for 1 hr, and this operation was repeated 6 times. The solvent was evaporated under reduced pressure, ethyl acetate was added, and the mixture was washed twice with water (500 mL), and twice with saturated aqueous sodium hydrogen carbonate solution (500 mL). The organic layer was washed twice with 2N hydrochloric acid (200 mL), once with saturated aqueous sodium hydrogen carbonate solution (500 mL), and once with saturated brine (500 mL). The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, 2-propanol was added to the residue and the mixture was stirred at 50° C. for 1 hr. After cooling, the solid was washed with cold 2-propanol (600 mL) and hexane, and dried. 2-Propanol/ethyl acetate (800 mL/80 mL) was added, and the mixture was stirred at 50° C. for 1 hr. After cooling, the solid was washed with cold 2-propanol and hexane, and dried to give the object 4-tert-butyl-N-(4-chloro-2-isonicotinoylphenyl)benzenesulfonamide (162 g, pale-yellow solid). The filtrate was purified by silica gel column chromatography (ethyl acetate/chloroform) to give the object 4-tert-butyl-N-(4-chloro-2-isonicotinoylphenyl)benzenesulfonamide (29 g, pale-yellow solid). A total of 191 g of the object product 4-tert-butyl-N-(4-chloro-2-isonicotinoylphenyl)benzenesulfonamide was obtained.

1. temperaturethe mixture was heated at 75° C. for 18 hr
2. customThe solvent was evaporated under reduced pressure, ethyl acetate
3. additionwas added
4. washthe mixture was washed twice with water (500 mL)
5. washThe organic layer was washed twice with 2N hydrochloric acid (200 mL), once with saturated aqueous sodium hydrogen carbonate solution (500 mL)
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. customThe solvent was evaporated under reduced pressure, 2-propanol
8. additionwas added to the residue
9. stirringthe mixture was stirred at 50° C. for 1 hr
10. temperatureAfter cooling
11. washthe solid was washed with cold 2-propanol (600 mL) and hexane
12. customdried
13. addition2-Propanol/ethyl acetate (800 mL/80 mL) was added
14. stirringthe mixture was stirred at 50° C. for 1 hr
15. temperatureAfter cooling
16. washthe solid was washed with cold 2-propanol and hexane
17. customdried