反应详情

温度

40 °C

To an ice cold solution of the sulfonamide (1-36, 6.82 g, 10.61 mmol) in anhydrous DMF (100 ml) under argon was added NaH (95.0%, 697 mg, 27.58 mmol). The solution was stirred for 5 min, and then 3-chloro-N,N-dimethylpropan-1-amine hydrochloride (2.18 g, 13.8 mmol) was added. After 10 min, the reaction mixture was transferred to a pre heated oil bath at 40° C. and stirred for 3 days. LCMS showed the presence of monoalkylated and bisalkylated products (ratio, 65:25) together with unreacted starting material. After cooling, 1N NaOH was added to the reaction mixture and extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and the filtrate was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography. The unreacted starting material was recovered when the column was eluted with 40° A) EtOAc in hexane. Pure monoalkylated product (13-1, LCMS, MS 728.0 (MH+)) was obtained when eluted using EtOAc alone and the bisalkylated product (1-70, LCMS, MS 813.2 (MH+)) was isolated with 5% triethylamine in EtOAc as the eluent. The fractions collected were evaporated under reduced pressure to dryness to get 13-1 (3.02 g, 53%) and 1-70 (1.10 g, 17%).

1. waitAfter 10 min
2. stirringstirred for 3 days
3. temperatureAfter cooling
4. extractionextracted with ethyl acetate
5. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
6. customthe filtrate was evaporated under reduced pressure
7. customThe crude mixture was purified by silica gel column chromatography
8. customwas recovered when the column
9. washwas eluted with 40° A) EtOAc in hexane
10. customPure monoalkylated product (13-1, LCMS, MS 728.0 (MH+)) was obtained when
11. washeluted
12. customthe bisalkylated product (1-70, LCMS, MS 813.2 (MH+)) was isolated with 5% triethylamine in EtOAc as the eluent
13. customThe fractions collected
14. customwere evaporated under reduced pressure to dryness