3-Amino-4,4-difluorobut-2-enenitrile → N-{2-[3,5-Dicyano-2,6-bis(difluoromethyl)-1,4-dihydropyridin-4-yl]furo[3,2-c]pyridin-4-yl}benzamide

Participants

Reaction Steps

A solution of 200 mg (0.75 mmol) N-(2-formylfuro[3,2-c]pyridin-4-yl)benzamide (Example 3A) in acetic acid (1.3 ml) was treated with a solution of 200 mg (1.69 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 1-butanol (1.0 ml). The mixture was heated to reflux temperature for 2 h. Upon cooling, the reaction mixture was concentrated under reduced pressure, and the residue was treated with ethyl acetate and saturated aq. sodium bicarbonate solution. The organic layer was separated, washed with brine and with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 100% methanol) yielding 28 mg (8% of th.) of the title compound.

Provenance & Evidence