反应详情

Triphenylphosphine (1.29 g, 4.92 mmol) was dissolved in 21 mL anhydrous dichloromethane. Bromine (253 μl, 4.94 mmol) was added dropwise under argon atmosphere and the reaction was stirred at room temperature for 30 min. Triethylamine (1.96 mL, 4 mmol) and (S)-tert-butyl (4-(benzyloxy)-1-((3-bromo-2-((3,5-difluorophenyl)carbamoyl)-1H-pyrrol-1-yl)amino)-1-oxobutan-2-yl)carbamate (2.15 g, 3.52 mmol) were added and the reaction mixture was heated at 60° C. for 2 h. The mixture was poured into 75 mL 4% aqueous solution sodium bicarbonate and extracted with dichlorometane. The organics were dried over sodium sulphate, filtered and evaporated. The residue was re-dissolved in 19 mL tetrahydrofuran and 2 mL dichloromethane and, under argon conditions, sodium methanethiolate was added and the reaction was stirred at room temperature for 1 h. The mixture was poured into 4% aqueous solution sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulphate, filtered and concentrated. The residue was purified using Isolera® Purification System (0% to 20%, hexane-ethyl acetate) to obtain 1.66 g (74% yield) of the title compound as a white solid.

1. temperaturethe reaction mixture was heated at 60° C. for 2 h
2. extractionextracted with dichlorometane
3. dry with materialThe organics were dried over sodium sulphate
4. filtrationfiltered
5. customevaporated
6. dissolutionThe residue was re-dissolved in 19 mL tetrahydrofuran
7. addition2 mL dichloromethane and, under argon conditions, sodium methanethiolate was added
8. stirringthe reaction was stirred at room temperature for 1 h
9. additionThe mixture was poured into 4% aqueous solution sodium bicarbonate
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with water, brine
12. dry with materialdried over sodium sulphate
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue was purified
16. customIsolera® Purification System (0% to 20%, hexane-ethyl acetate)