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+).
Workup
- temperatureat reflux for 5 hours
- stirringthe mixture was stirred
- temperatureat reflux for 4 hours
- waitthe solution left
- customThe solvent was carefully decanted
- customthe remaining reside triturated with Et2O (50 mL)
- customThe residual solvent was evaporated in vacuo
Sources & evidence
- ORD record
- ord-62540e0adf9345dd9ad6b8f56e6b5e4f
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09433622B2
Reaction notes
Loading…