Dabco → (Z)-3-(3-(2,6-bis(trifluoromethyl)pyridin-4-yl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one

HRID 1486972Notes

Reaction equation

HRID 1486972 reaction equation
[NH:1]1[CH:5]=[N:4][C:3]([C:6]2[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[N:9]=[C:8]([C:16]([F:19])([F:18])[F:17])[CH:7]=2)=[N:2]1.[F:20][C:21]1([F:30])[CH2:24][N:23]([C:25](=[O:29])/[CH:26]=[CH:27]\I)[CH2:22]1.C1N2CCN(CC2)C1.CO.ClCCl>CN(C=O)C>[F:18][C:16]([F:19])([F:17])[C:8]1[CH:7]=[C:6]([C:3]2[N:4]=[CH:5][N:1](/[CH:27]=[CH:26]\[C:25]([N:23]3[CH2:24][C:21]([F:30])([F:20])[CH2:22]3)=[O:29])[N:2]=2)[CH:11]=[C:10]([C:12]([F:13])([F:14])[F:15])[N:9]=1

Participants

6

Reactant 4

HCID 9237DabcoHCID 21226129Dichloromethane methanolHCID 86730374(Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-oneHCID 178506085HCID 178506085, compound

Product 1

HCID 71493651(Z)-3-(3-(2,6-bis(trifluoromethyl)pyridin-4-yl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-oneYield 12.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 3-neck 50 mL round-bottomed flask, 4-(1H-1,2,4-triazol-3-yl)-2,6-bis(trifluoromethyl)pyridine (3) (0.060 g, 1 eq.) and (Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-one (0.064 g, 1.1 eq) was dissolved in DMF (2 mL). DABCO (0.047 g, 2 eq.) was added at RT. Reaction mixture was stirred for 1 h at RT. Reaction completion was monitored on TLC using MeOH:dichloromethane (0.25:9.75) as mobile phase. The reaction mixture was quenched into the ice-water slurry (50 mL) and was extracted with ethyl acetate (3×25 mL). Organic layer was washed with brine solution (3×25 mL). The organic layer was dried using anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide the 0.70 g crude compound which was purified by preparative TLC using 2.5% methanol in dichloromethane as mobile phase to afford 0.011 g (12%) title compound.

Workup

  1. customReaction mixture
  2. customReaction completion
  3. customThe reaction mixture was quenched into the ice-water slurry (50 mL)
  4. extractionwas extracted with ethyl acetate (3×25 mL)
  5. washOrganic layer was washed with brine solution (3×25 mL)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide the 0.70 g crude compound which
  10. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-353e302fa10a4ccb866a6fd322b00c6f
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

Loading…