反应详情

温度

85 °C

A solution of palladium(II) acetate (2.55 mg, 0.011 mmol) and butyldi-1-adamantyl phosphine (CataCXium A, 8.14 mg, 0.023 mmol) in THF (1.42 mL) was stirred for 10 min while nitrogen was bubbled through gently. Intermediate 13 (100 mg, 0.189 mmol), Intermediate 1 (51.0 mg, 0.218 mmol), potassium fluoride (33.0 mg, 0.568 mmol) and water (473 μl) were added. The tube was sealed (screw cap) and heated overnight at 85° C. The reaction was cooled to room temperature and diluted with ethyl acetate. After decanting the solids and extraction with ethyl acetate, the organic layer was washed with brine and dried over MgSO4. Filtration and subsequent solvent evaporation gave a residue which was purified by chromatography on silica gel (5-50% ethyl acetate in hexanes) to give 75 mg (86%) of 1-{5-[3-(trifluoromethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}cyclobutanol as a grey solid. MS ESI [M+H]+ 461.1. 1H NMR (400 MHz, DMSO-d6): δ 10.67 (s, 1H); 8.93 (d, J=4.9 Hz, 1H); 8.33 (s, 1H); 8.24 (s, 1H); 8.17 (s, 1H); 7.68 (s, 1H); 7.41 (d, J=4.9 Hz, 1H); 6.62 (s, 1H); 2.59-2.48 (m, 2H); 2.42-2.31 (m, 2H); 1.98-1.87 (m, 2H). rhSYK activity=++

1. customwas bubbled through gently
2. customThe tube was sealed
3. custom(screw cap)
4. temperatureThe reaction was cooled to room temperature
5. customAfter decanting
6. extractionthe solids and extraction with ethyl acetate
7. washthe organic layer was washed with brine
8. dry with materialdried over MgSO4
9. filtrationFiltration and subsequent solvent evaporation
10. customgave a residue which
11. customwas purified by chromatography on silica gel (5-50% ethyl acetate in hexanes)