反应详情

4-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide (Preparation 245, 70 mg, 0.21 mmol), 2-tert-butoxy-3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Preparation 118, 72.9 mg, 0.234 mmol), tetrakistriphenylphosphinepalladium (24.3 mg, 0.021 mmol), aqueous potassium carbonate solution (1.8 M, 0.35 mL, 0.639 mmol) and tetrahydrofuran (15 mL) were combined and stirred under nitrogen at reflux for 5 hours. After cooling, the mixture was filtered through Celite™ and the filtrate evaporated. The residue was dissolved in water (20 mL) and acidified with aqueous potassium hydrogen sulphate solution (0.5 M) to pH 2 and the mixture extracted with ethyl acetate (30 mL). The organic layer was separated and washed with brine (3×20 mL), dried over sodium sulphate, filtered and evaporated to give an oil. The oil was purified using silica gel column chromatography eluting with heptane to ethyl acetate:heptane 1:1 to give a solid. The solid was further purified by reverse phase HPLC to give the title compound (21 mg, 23%) as a white solid.

1. temperatureat reflux for 5 hours
2. temperatureAfter cooling
3. filtrationthe mixture was filtered through Celite™
4. customthe filtrate evaporated
5. dissolutionThe residue was dissolved in water (20 mL)
6. extractionthe mixture extracted with ethyl acetate (30 mL)
7. customThe organic layer was separated
8. washwashed with brine (3×20 mL)
9. dry with materialdried over sodium sulphate
10. filtrationfiltered
11. customevaporated
12. customto give an oil
13. customThe oil was purified
14. washeluting with heptane to ethyl acetate:heptane 1:1
15. customto give a solid
16. customThe solid was further purified by reverse phase HPLC