反应详情

To 6-bromo-4-sulfanylisoquinolin-1(2H)-one (Example 58a, 0.62 g) was added tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (0.676 g) and potassium carbonate (0.769 g). After thoroughly flushing with nitrogen, DMF (6 mL) was added and the reaction stirred at room temperature for 30 min. Further DMF (9 mL) was added, and the reaction stirred at 40° C. for 1 h. Further DMF (10 mL) was added and the reaction stirred at 50° C. for 16 h. The reaction was partitioned between ethyl acetate and water. The aqueous was extracted with further ethyl acetate (3×) and the combined organics were washed with saturated brine (3×100 mL). The organics were dried (MgSO4), filtered and evaporated under reduced pressure. DCM was added, and the resulting suspension was filtered. The filtrate was concentrated under reduced pressure, dissolved in the minimum volume of DCM and purified (SiO2 chromatography, elution with 50%-100% diethyl ether/isohexane followed by ethyl acetate flush) to afford the subtitle compound (0.353 g).

1. customAfter thoroughly flushing with nitrogen, DMF (6 mL)
2. additionwas added
3. additionFurther DMF (9 mL) was added
4. stirringthe reaction stirred at 40° C. for 1 h
5. additionFurther DMF (10 mL) was added
6. stirringthe reaction stirred at 50° C. for 16 h
7. customThe reaction was partitioned between ethyl acetate and water
8. extractionThe aqueous was extracted with further ethyl acetate (3×)
9. washthe combined organics were washed with saturated brine (3×100 mL)
10. dry with materialThe organics were dried (MgSO4)
11. filtrationfiltered
12. customevaporated under reduced pressure
13. additionDCM was added
14. filtrationthe resulting suspension was filtered
15. concentrationThe filtrate was concentrated under reduced pressure
16. dissolutiondissolved in the minimum volume of DCM
17. custompurified
18. wash(SiO2 chromatography, elution with 50%-100% diethyl ether/isohexane followed by ethyl acetate flush)