Dimethylformamide dimethyl acetal → (E)-3-(2-(Dimethylamino)vinyl)isonicotinonitrile

To a solution of 3-methylisonicotinonitrile (10 g, 85 mmol) in DMF (100 mL) was added 1,1-dimethoxy-N,N-dimethylmethanamine (18.05 mL, 135 mmol). The mixture was heated to reflux overnight. The mixture was cooled to rt and an additional 3.0 mL of 1,1-dimethoxy-N,N-dimethylmethanamine was added to the mixture, and it was again heated to reflux. After heating the mixture overnight, it was cooled to rt and an additional 3.0 mL of 1,1-dimethoxy-N,N-dimethylmethanamine was added to the mixture. The mixture was heated overnight at reflux. The mixture was cooled to rt and an additional 3.0 mL of 1,1-dimethoxy-N,N-dimethylmethanamine were added. The mixture was again heated to reflux. After heating the mixture overnight, it was cooled to rt. To the mixture was added 3.0 mL of 1,1-dimethoxy-N,N-dimethylmethanamine. The mixture was heated to reflux overnight. The mixture was cooled to rt and was concentrated under reduced pressure. The residue was dissolved in dichloromethane and was loaded onto a BIOTAGE® 65+M cartridge and was purified using a 10-70% EtOAc in hexanes gradient. The expected product, (E)-3-(2-(dimethylamino)vinyl)isonicotinonitrile (7.97 g, 46.0 mmol, 54.4% yield), was isolated as a bright-yellow solid. LC/MS: m/z 174.11 (M+H)+, 1.690 min (method 1). 1H NMR (500 MHz, chloroform-d) δ ppm 1H NMR (500 MHz, chloroform-d) δ ppm 8.69 (s, 1H) 8.14 (d, J=5.19 Hz, 1H) 7.23 (d, J=4.88 Hz, 1H) 7.15 (d, J=13.43 Hz, 1H) 5.21 (d, J=13.73 Hz, 1H) 2.95 (s, 6H)