Dimethylformamide dimethyl acetal → 6-((E)-3-Dimethylamino-acryloyl)-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile
Reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]#[N:11])[C:7]([N:12]2[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].CO[CH:20](OC)[N:21]([CH3:23])[CH3:22]>C1(C)C=CC=CC=1>[CH3:20][N:21]([CH3:23])/[CH:22]=[CH:2]/[C:1]([C:4]1[N:9]=[C:8]([C:10]#[N:11])[C:7]([N:12]2[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13]2)=[CH:6][CH:5]=1)=[O:3]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
6-Acetyl-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile (65) (1.32 g, 5.71 mmol) was dissolved in dry toluene (30 mL). N,N-dimethylformamide dimethyl acetal (2.3 mL, 17.3 mmol) was added and the mixture was stirred at reflux for 5 hours. N,N-Dimethylformamide dimethyl acetal (5.0 mL, 37.6 mmol) was added and the mixture was stirred at reflux for 4 hours. The solution was cooled to rt and the solution left to stand at rt for 16 hours. The solvent was carefully decanted and the remaining reside triturated with Et2O (50 mL) followed by EtOAc (50 mL). The residual solvent was evaporated in vacuo. The title compound 66 was afforded as an orange solid (1.11 g, 68%); LCMS, Rt=1.98 min (MeOH-FA method), m/z 287 (MH+).