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

HRID 885072Notes

Reaction equation

HRID 885072 reaction equation
[CH3:1][C:2]1[CH:9]=[N:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].CO[CH:12](OC)[N:13]([CH3:15])[CH3:14]>CN(C=O)C>[CH3:12][N:13]([CH3:15])/[CH:14]=[CH:1]/[C:2]1[CH:9]=[N:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetal5×HCID 820633-Methylisonicotinonitrile

Product 1

HCID 12884773(E)-3-(2-(Dimethylamino)vinyl)isonicotinonitrileYield 54.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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)

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperaturewas again heated to reflux
  4. temperatureAfter heating the mixture overnight, it
  5. temperaturewas cooled to rt
  6. temperatureThe mixture was heated overnight
  7. temperatureat reflux
  8. temperatureThe mixture was cooled to rt
  9. temperatureThe mixture was again heated to reflux
  10. temperatureAfter heating the mixture overnight, it
  11. temperaturewas cooled to rt
  12. temperatureThe mixture was heated
  13. temperatureto reflux overnight
  14. temperatureThe mixture was cooled to rt
  15. concentrationwas concentrated under reduced pressure
  16. dissolutionThe residue was dissolved in dichloromethane
  17. customwas purified

Sources & evidence

ORD record
ord-bf04a91ee4e4434e9e8bd7dc4a70152f
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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