反应详情

温度

85 °C

A resealable vial was charged with (S)-2-amino-4′-fluoro-2′-morpholino-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (130 mg, 0.258 mmol; prepared as described in Method BB40), tetrakis(triphenylphosphine)palladium(0) (29.8 mg, 0.026 mmol), 2-fluoro-5-methylpyridin-3-ylboronic acid (64.0 mg, 0.413 mmol), DMF (1.3 mL) and 2 M aqueous sodium carbonate (387 μL, 0.775 mmol). The vial was sealed and the mixture stirred for 2 hr at 85° C. The mixture was cooled and diluted with EtOac (6 mL) and water (2 ml). The organic layer was filtered through celite, concentrated, and purified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA). The fractions containing product were concentrated in vacuo, neutralized with saturated sodium bicarbonage and extracted with ethyl acetate. Organic layer was washed with brine, and concentrated. The residue was redissoved in ˜1 mL 1:1 MeCN/water and liophilized to afford (S)-4′-fluoro-7′-(2-fluoro-5-methylpyridin-3-yl)-2′-morpholino-5H-spiro[oxazole-4,9′-xanthen]-2-amine.

1. customThe vial was sealed
2. temperatureThe mixture was cooled
3. filtrationThe organic layer was filtered through celite,
4. concentrationconcentrated
5. custompurified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA)
6. additionThe fractions containing product
7. concentrationwere concentrated in vacuo
8. extractionextracted with ethyl acetate
9. washOrganic layer was washed with brine
10. concentrationconcentrated