Methanol → 6-(benzylthio)-1-(4'-chloro-2-fluoro-5-methoxy-3'-methyl-[1,1'-biphenyl]-4-yl)-3-methoxyquinolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 5-(benzylthio)-2-((4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)amino)benzaldehyde (0.809 g, 1.644 mmol) and a MeOH solution of sodium methoxide (16.44 ml, 8.22 mmol) was added. Then methyl methoxyacetate (0.489 ml, 4.93 mmol) followed by toluene (1.644 ml) were added. A reflux condenser was attached and the mixture was heated at 70° C. for 48 h. The resulting solution was concentrated for purification by MPLC (Biotage Isolera). The crude residue was taken up in minimal DCM and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® Gold pre-packed silica gel column (40 g) using 95:5 Heptane: EtOAc to 100% EtOAc gradient (with 1% DCM for solubility) to afford 6-(benzylthio)-1-(4′-chloro-2-fluoro-5-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)-3-methoxyquinolin-2(1H)-one (0.410 g, 0.751 mmol, 45.7% yield) as a off-white amorphous solid. (ESI) 546.0 (M+H)+.

Provenance & Evidence