Tetrahydrofuran → Methyl 3-{3-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-methoxyphenyl}propanoate

Participants

Reaction Steps

[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]boronic acid (INTERMEDIATE 57) (200 mg, 0.404 mmol), ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Step C, INTERMEDIATE 56) (185 mg, 0.404 mmol), potassium carbonate (0.404 ml, 0.808 mmol), 1,1bis(di-tert-butylphosphino)ferrocene palladium dichloride (27.5 mg, 0.040 mmol) and THF (5 mL) were sealed in a microwave vessel and subject to microwave irradiation at 120° C. for 30 min. Volatiles were removed under reduced pressure. The resulting pot residue was purified by preparative HPLC (reverse phase, Waters SunFire PrepC18 OBD 5 um 19×150 mm) eluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min, then to 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford a dark solid. This dark solid was further purified by preparative TLC (silica gel) developed with EtOAc/hexanes (30% ethyl acetate v/v) to give the title compound as a colorless solid foam. LCMS calc.=781.14. found=782.25 (M+H)+.

Provenance & Evidence