Water → (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one

HRID 1487009Notes

Reaction equation

HRID 1487009 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12]2[N:16]=[CH:15][NH:14][N:13]=2)=[CH:4][C:3]=1[C:17]([F:20])([F:19])[F:18].C1N2CCN(CC2)C1.[F:29][C:30]1([F:39])[CH2:33][N:32]([C:34](=[O:38])/[CH:35]=[CH:36]\I)[CH2:31]1.O>CN(C=O)C>[Cl:1][C:2]1[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][C:5]([C:12]2[N:16]=[CH:15][N:14](/[CH:36]=[CH:35]\[C:34]([N:32]3[CH2:33][C:30]([F:39])([F:29])[CH2:31]3)=[O:38])[N:13]=2)=[CH:4][C:3]=1[C:17]([F:18])([F:19])[F:20]

Participants

6

Reactant 4

HCID 962WaterHCID 9237DabcoHCID 86730374(Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-oneHCID 178506084HCID 178506084, compound

Product 1

HCID 71494280(Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-oneYield 3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-Chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole (0.1 g, 1.0 eq.) was dissolved in DMF (5 mL). DABCO (0.071 g, 2 eq.) was added and stirred for 30 min. (Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-one (0.095 g, 1.1 eq.) was then added. The reaction mixture was stirred at room temperature for 5 h and then poured into iced water (50 mL). Product was extracted with EtOAc (3×15 mL). The combined organic layers was washed with brine, (20 mL), dried over Na2SO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 0.150 g of crude product, which was purified by chromatography to obtain (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one (0.004 g, 3% yield). 1H NMR (400 MHz, DMSO) δ=9.32 (s, 1H), 8.46 (s, 1H), 8.32 (s, 1H), 7.47-7.49 (d, J=10.4 Hz, 1H), 6.00-5.04 (d, J=10.4 Hz, 1H), 4.55-4.58 (m, 2H), 4.33-4.36 (m, 2H) LCMS calcd for C16H10ClF8N4O [M+H]+: 461.7. Found: 461.14, at 2.99 min retention time.

Workup

  1. additionwas then added
  2. extractionProduct was extracted with EtOAc (3×15 mL)
  3. washThe combined organic layers was washed with brine, (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  7. customto afford 0.150 g of crude product, which
  8. customwas purified by chromatography

Sources & evidence

ORD record
ord-86275b3eebff4e56bc3b425c7917525d
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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