| 54.4% |
In N,N-dimethyl-formamide;Reflux; |
Preparation of (E)-3-(2-(dimethylamino)vinyl)isonicotinonitrile; [00150] To a solution of <strong>[7584-05-6]3-methylisonicotinonitrile</strong> (10 g, 85 mmol) in DMF (100 mL) was added l,l-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 l,l-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 l,l-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 l,l-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-^) I ppm 1H NMR (500 MHz, chloroform-^ I ppm 8.69 (s, 1 H) 8.14 (d, J= 5.19 Hz, 1 H) 7.23 (d, J= 4.88 Hz, 1 H) 7.15 (d, J= 13.43 Hz, 1 H) 5.21 (d, J= 13.73 Hz, 1 H) 2.95 (s, 6 H) |
| 20% |
In N,N-dimethyl-formamide;Reflux; |
To a solution of <strong>[7584-05-6]3-methylisonicotinonitrile</strong> (26, 168 mg, 1.4 mmol)in DMF (3 mL) was added 1,1-dimethoxyl-N,N-dimethylmethanamine(400 muL, 2.8 mmol). The mixture was heated to reflux overnight. Thenthe mixture was cooled to RT and additional 200 muL of 1,1-dimethoxyl-N,N-dimethylmethanamine was added to the mixture. The mixture washeated to reflux overnight. Then repeated addition of 200 muL 1,1-dimethoxyl-N,N-dimethylmethanamine to the mixture. The mixture washeated to reflux overnight. After completion of the reaction, the mixturewas cooled to RT and concentrated in vacuo to give a brown oil,the residue was purified by flash column chromatography on silica(EtOAc/Petroleum ether 1:2) to yield the yellow solid (20%). 1H NMR(400 MHz, CDCl3) delta 8.69 (s, 1H), 8.14-8.11 (m, 1H), 7.25-7.23 (m,1H), 7.16 (d, J=13.6 Hz, 1H), 5.21 (d, J=13.6 Hz, 1H), 2.95 (s, 6H). |
|
In N,N-dimethyl-formamide; for 18h;Reflux; |
Step B: To a solution of <strong>[7584-05-6]4-cyano-3-methylpyridine</strong> 1 (123 g, 1.0 mol) inN,N-dimethylformamide (800 mL) is added N,N-dimethylformamide dimethyl acetal (800 mL). The mixture is heated at reflux for 18 h. After cooling and concentration in <n="31"/>vacuo, the residue is dissolved in dichloromethane (400 rnL) and precipitated with n- pentane. Filtration and washing with n-pentane, followed by drying under high vacuum, yielded 3-[(E)-2-(dimehtylamino)ethenyl]-4-cyanopyridine 2 as a light-green solid: 1H NMR (400 MHz, CDCl3) delta = 8.69 (s, IH), 8.13 (d, J = 6.8 Hz, IH), 7.23 (dd, J = 6.8, 1.0 Hz, IH), 7.16 (d, J = 17.6 Hz, IH), 5.21 (d, J = 17.6 Hz, IH), 2.96 (s, 6H). |
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