Acetic Acid → 2-(4-Chlorophenyl)-6-(difluoromethyl)-4-(6-fluoro-3-methyl-1H-indazol-5-yl)-1,4-dihydropyridine-3,5-dicarbonitrile

Participants

Reaction Steps

A mixture of 200 mg (0.542 mmol) (2E)-2-(4-chlorobenzoyl)-3-(6-fluoro-3-methyl-1H-indazol-5-yl)prop-2-enenitrile (Example 6A) and 66 mg (0.542 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 31, 1 (1984)] in 2-propanol (1 ml) was stirred at reflux for 12 h. Then, acetic acid (1.5 ml) was added, and stirring at reflux was continued for 6 h. Upon cooling, the mixture was concentrated under reduced pressure, and the residue was directly purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 80:20 v/v) to yield 33 mg (14% of th.) of the racemic title compound.

Provenance & Evidence