反应详情

温度

150 °C

A solution of N-t-butoxycarbonyl-N-{4-[2-(benzhydryl-amino)-5-chloro-phenyl]-but-3-ynyl}-C-(3,4-dichlorophenyl)-methanesulfonamide (400 g, 0.585 mol) and N,N-dimethylacetamide (800 mL) was added slowly over 1 h to a hot (150° C.), stirred mixture of copper (I) iodide (12.2 g, 0.064 mol) and N,N-dimethylacetamide (740 mL). The reaction mixture was stirred and maintained at 150° C. for an additional 2 h. The reaction mixture was cooled to 40° C. The mixture was filtered through a celite pad and the pad was washed with IPA (2×100 mL). An additional charge of IPA (1400 mL) was added to the filtrate. The mixture was stirred and warmed to 60° C. Water (2.2 L) was added to the mixture over 30 m, maintaining an internal temperature of 55-60° C. The mixture was held at 60° C. for 30 m, then it was cooled to 5° C. The solid product was collected by filtration and the cake was washed with cold IPA/water (3/2 v/v, 2×200 mL). The solid was vacuum dried at <50° C. to give N-[2-(1-benzhydryl-5-chloro-1 H-indol-2-yl)-ethyl]-C-(3,4-dichloro-phenyl)-methanesulfonamide (338 g, 99%) with 98% purity (as determined by HPLC).

1. stirringThe reaction mixture was stirred
2. temperatureThe reaction mixture was cooled to 40° C
3. filtrationThe mixture was filtered through a celite pad
4. washthe pad was washed with IPA (2×100 mL)
5. additionAn additional charge of IPA (1400 mL)
6. additionwas added to the filtrate
7. stirringThe mixture was stirred
8. temperaturewarmed to 60° C
9. additionWater (2.2 L) was added to the mixture over 30 m
10. temperaturemaintaining an internal temperature of 55-60° C
11. customwas held at 60° C. for 30 m
12. temperatureit was cooled to 5° C
13. filtrationThe solid product was collected by filtration
14. washthe cake was washed with cold IPA/water (3/2 v/v, 2×200 mL)
15. customdried at <50° C.