反应详情

A mixture of 1,1-dimethylethyl (3S)-3-{[(7-chloro-1,6-naphthyridin-5-yl)oxy]methyl}-3-fluoro-1-piperidinecarboxylate (1.1 g, 2.78 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.679 g, 3.06 mmol) and caesium carbonate (2.263 g, 6.95 mmol) in 1,4-dioxane (16 ml) and water (3 ml) was degassed with nitrogen before adding tetrakis(triphenylphosphine)palladium (0) (0.096 g, 0.083 mmol). This was heated under reflux for 18 h. The reaction was partitioned between ethyl acetate and aqueous ammonium chloride. The aqueous was re-extracted with ethyl acetate and the combined organics were washed with brine, passed through a hydrophobic frit and concentrated in vacuo to give crude product. This was dissolved in DCM and purified through silica (20 g) eluting with a gradient of ethyl acetate in DCM. The product eluted in neat ethyl acetate. Appropriate fractions were combined and concentrated in vacuo to yield the title compound as a pinkish cream foam (1.10 g).

1. customwas degassed with nitrogen
2. temperatureThis was heated
3. temperatureunder reflux for 18 h
4. customThe reaction was partitioned between ethyl acetate and aqueous ammonium chloride
5. extractionThe aqueous was re-extracted with ethyl acetate
6. washthe combined organics were washed with brine
7. concentrationconcentrated in vacuo
8. customto give crude product
9. custompurified through silica (20 g)
10. washeluting with a gradient of ethyl acetate in DCM
11. washThe product eluted in neat ethyl acetate
12. concentrationconcentrated in vacuo