反应详情

A suspension containing 2-amino-5-(2,4-difluorophenyl)thiophene-3-carboxamide (60 mg, 0.24 mmol), (6-bromo-pyridin-2-yl)methanol (44.4 mg, 0.24 mmol), 2-dicylohexylphosphino-2′,4′,6′-triisopropyl-1,1-biphenyl (5.62 mg, 0.012 mmol), dibenyzlideneacetone bis(triphenylphosphine) (2.161 mg, 2.36 μmol) and potassium carbonate (35.9 mg, 0.26 mmol) in tert-butanol or tert-amyl alcohol (0.5 mL) was sealed in 5 mL microwave reaction vessel and was purged of oxygen by doing 5 vacuum/argon flush cycles. After heating the reaction at 100° C. for 2 hours, the mixture was cooled, diluted with ethyl acetate (10 mL), washed with saturated aqueous sodium bicarbonate (2×5 mL) and brine (2×5 mL), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by reverse phase HPLC (35-95% acetonitrile/water with 0.05% trifluoroacetic acid), and then the appropriate fractions were diluted with ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (15 mL). The layers were separated, and the organic layer was washed with saturated aqueous sodium bicarbonate (15 mL) and water (2×15 mL), dried over sodium sulfate, filtered and concentrated to yield the title compound as a light yellow solid.

1. customwas sealed in 5 mL microwave reaction vessel
2. customwas purged of oxygen
3. customflush cycles
4. temperatureAfter heating
5. customthe reaction at 100° C. for 2 hours
6. temperaturethe mixture was cooled
7. washwashed with saturated aqueous sodium bicarbonate (2×5 mL) and brine (2×5 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by reverse phase HPLC (35-95% acetonitrile/water with 0.05% trifluoroacetic acid)
12. additionthe appropriate fractions were diluted with ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (15 mL)
13. customThe layers were separated
14. washthe organic layer was washed with saturated aqueous sodium bicarbonate (15 mL) and water (2×15 mL)
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated