5-aminoisoquinolin-1(2H)-one → (Rac.) 5-{[4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentylidene]amino}isoquinolin-1(2h)-one

Participants

Reaction Steps

560 mg of the mixture that consists of (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal and (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-hydroxy-pentanoic acid ethyl ester (since the aldehyde constitutes two thirds in the mixture, the 560.2 mg mixture corresponds to 336.1 mg (0.981 mmol) of aldehyde) is heated for two hours to 120° C. with 157.1 mg (0.981 mmol) of 5-amino-isoquinolin-1(2H)-one and 0.557 mg (1.962 mmol) of titanium tetraisopropylate in 6 ml of o-xylene. After cooling, the batch is diluted with ethyl acetate and mixed with brine. The organic phase is separated and worked up as usual. After chromatography on a Flashmaster, 144.7 mg (30.4%) of the desired compound is obtained (relative to the aldehyde portion in the mixture).

Provenance & Evidence