反应详情

温度

130 °C

A mixture of (4S,5R)-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 18, 211 mg, 0.389 mmol), bis(pinacolato)diboron (296 mg, 1.17 mmol), and potassium acetate (114 mg, 1.17 mmol) in N,N-dimethylacetamide (2.0 mL) was degassed three times with nitrogen gas before the addition of (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) chloride (XPHOS Biphenyl Precatalyst) (15.5 mg, 0.019 mmol). The system was degassed three times and was then heated to 130° C. for 24 hours. LC/MS analysis indicated complete conversion to the product, but almost exclusively as the boronic acid. For this reason the crude reaction mixture was taken directly into the next step. Accordingly, methyl 4-bromo-3,5-dimethylbenzoate (142 mg, 0.584 mmol), (1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (24.5 mg, 0.039 mmol), and aqueous potassium carbonate (0.389 mL, 2.0 M) were added. The mixture was degassed, flushed with nitrogen and heated to 100° C. for 45 minutes. The reaction was diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography to afford methyl 4-{5-[4-({(4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzoate (158 mg, 0.236 mmol). LCMS (M+H)+: 671.1

1. customwas degassed three times with nitrogen gas
2. customThe system was degassed three times
3. customFor this reason the crude reaction mixture
4. customThe mixture was degassed
5. customflushed with nitrogen
6. temperatureheated to 100° C. for 45 minutes
7. additionThe reaction was diluted with ethyl acetate
8. washwashed with water, brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product was purified by column chromatography