反应详情

温度

70 °C

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.06 g, 0.19 mmol) and 4-(toluene-4-sulfonyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (0.08 g, 0.20 mmol) in DMF (3 mL) was added NaI (0.014 g, 0.009 mmol) and K2CO3 (0.08 g, 0.56 mmol). The reaction mixture was heated to 70° C. for 20 hours. The mixture was diluted with ether and water and the layers were separated. The aqueous layer was extracted with ether (2×) and the combined organic layers were washed with water and brine, and dried over Na2SO4. The crude mixture was concentrated under reduced pressure and purified by reverse phase HPLC. The desired fraction was concentrated to 0.037 g that was then treated with HCl (4N in dioxane) for 7 hours. The solvent was removed under reduced pressure and the final product was dried under high vacuum to obtain 0.031 g solid (37% yield). MS (APCI+) m/z 416 (M+1) detected.

1. customthe layers were separated
2. extractionThe aqueous layer was extracted with ether (2×)
3. washthe combined organic layers were washed with water and brine
4. dry with materialdried over Na2SO4
5. concentrationThe crude mixture was concentrated under reduced pressure
6. custompurified by reverse phase HPLC
7. concentrationThe desired fraction was concentrated to 0.037 g that
8. additionwas then treated with HCl (4N in dioxane) for 7 hours
9. customThe solvent was removed under reduced pressure
10. dry with materialthe final product was dried under high vacuum