反应详情

Methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (EXAMPLE 59 100 mg, 0.144 mmol), cyclopropylboronic acid (62.0 mg, 0.721 mmol), 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (19.62 mg, 0.029 mmol), aqueous K2CO3 (1M, 1.010 mL, 1.010 mmol) and THF (1.002 mL) were stirred at 80° C. for 3.5 h then slowly cooled to ambient overnight. Volatiles were removed under reduced pressure. The resulting pot residue was worked up with brine, extracted with EtOAc, dried (Na2SO4), filtered and evaporated to a dark mixture. The mixture was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The aqueous mixture was extracted with EtOAc, washed with aqueous NaHCO3, dried (Na2SO4), filtered and concentrated to afford the titled compound. LCMS calc.=698.22; found=699.30 (M+H)+.

1. customwere stirred at 80° C. for 3.5 h
2. temperaturethen slowly cooled to ambient overnight
3. customVolatiles were removed under reduced pressure
4. extractionextracted with EtOAc
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated to a dark mixture
8. customThe mixture was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
9. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min)
10. customevaporated in vacuo
11. customto afford an aqueous mixture
12. extractionThe aqueous mixture was extracted with EtOAc
13. washwashed with aqueous NaHCO3
14. dry with materialdried (Na2SO4)
15. filtrationfiltered
16. concentrationconcentrated