5-aminoisoquinolin-1(2H)-one → 5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}isoquinolin-1(2H)-one

Participants

Reaction Steps

In the same way as in Example 130, 200 mg (0.62 mmol) of (2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 100 mg (0.62 mmol) of 5-aminoisoquinolin-1(2H)-one and 0.39 ml (1.25 mmol) of titanium tert-butoxide are reacted to give 5-{[(2R,4R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}isoquinolin-1 (2H)-one. 460 mg of crude imine are cyclized in the same way as in Example 130 at −30° C. with 7.9 ml (7.9 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 50-100%) yields 223 mg of desired product.

Provenance & Evidence