反应详情

温度

100 °C

To a mixture of 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyrazin-2-ylamide (Example 6 step 4; 100 mg, 0.285 mmol), 2-fluorophenylboronic acid (Aldrich, 60 mg, 0.428 mmol), potassium carbonate (118 mg, 0.86 mmol) and 1,1-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (23 mg, 10 mole %) in a microwave vial was added THF/H2O (10:1, 3 mL). Nitrogen gas was bubbled through the mixture for 5 mins and the vial sealed and heated at 100° C. in microwave synthesizer for 20 min. The cooled reaction mixture was diluted with ethyl acetate (20 mL) and filtered through celite (2.5 g IST cartridge). A further 10 mL of ethyl acetate was washed through the celite pad and combined filtrate was washed sequentially with water (25 mL) then sat. sodium chloride solution (25 mL). Mixture was dried over sodium sulphate and filtered. Filtrate solvents were removed in vacuo to afford a crude product, which was purified by flash chromatography, eluting with a gradient of 50 to 100% ethyl acetate in hexane to a afford a gummy solid. which was triturated with diethyl ether, filtered and dried to afford the title compound as colourless solid (67 mg, 64%)

1. customNitrogen gas was bubbled through the mixture for 5 mins
2. customthe vial sealed
3. customThe cooled reaction mixture
4. filtrationfiltered through celite (2.5 g IST cartridge)
5. washA further 10 mL of ethyl acetate was washed through the celite pad
6. washwas washed sequentially with water (25 mL)
7. dry with materialMixture was dried over sodium sulphate
8. filtrationfiltered
9. customFiltrate solvents were removed in vacuo
10. customto afford a crude product, which
11. customwas purified by flash chromatography
12. washeluting with a gradient of 50 to 100% ethyl acetate in hexane to
13. customa afford a gummy solid
14. customwhich was triturated with diethyl ether
15. filtrationfiltered
16. customdried