反应详情

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(3-fluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (EXAMPLE 1, 0.2 g, 0.323 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.0717 g, 0.323 mmol), potassium phosphate (0.103 g, 0.484 mmol), (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) chloride (XPHOS Biphenyl Precatalyst) (0.0254 g, 0.032 mmol), THF (2.40 mL), and H2O (0.80 mL) were sealed in a microwave vessel and subject to microwave irradiation at 120 C for 1.5 hours. The resulting reaction mixture was worked up with brine/ethyl acetate. The combined extracts were dried over Na2SO4, filtered and evaporated to afford a dark mixture. This dark mixture was purified by flash chromatography (SiO2, ISCO, RediSep 12 g Cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 50% ethyl acetate). Related fractions were pooled and evaporated under reduced pressure to afford an off-white solid of 113 mg as the titled compound. LCMS (M+H)+: 680.4. 1H NMR (CDCl3, 500 MHz): δ 8.19-8.11 (m, 2H), 7.85 (s, 1H), 7.73 (s, 2H), 7.42-7.36 (m, 1H), 5.72-5.66 (d, J=8.5 Hz, 1H), 5.53 (s, 1H), 5.41 (s, 1H), 4.72-4.66 (m, 1H), 4.54-4.40 (m, 2H), 4.38-4.26 (m, 3H), 4.00 (s, 3H), 2.51 (m, 1H), 2.42 (s, 3H), 2.30-2.10 (m, 4H), 0.52 (d, J=6.5 Hz, 3H). RTA IC50: 5 nM.

1. customsubject to microwave irradiation at 120 C for 1.5 hours
2. customThe resulting reaction mixture
3. dry with materialThe combined extracts were dried over Na2SO4
4. filtrationfiltered
5. customevaporated
6. customto afford a dark mixture
7. customThis dark mixture was purified by flash chromatography (SiO2, ISCO, RediSep 12 g Cartridge)
8. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 50% ethyl acetate)
9. customevaporated under reduced pressure