Hexane → {[6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one

HRID 1896403Notes

Reaction equation

HRID 1896403 reaction equation
[H-].[Na+].CCCCCC.[F:9][C:10]([F:18])=[CH:11][CH:12]1[CH2:16][NH:15][C:14](=[O:17])[CH2:13]1.Br[CH2:20][C:21]1[N:25]2[N:26]=[C:27]([Cl:30])[CH:28]=[CH:29][C:24]2=[N:23][C:22]=1[C:31]([F:34])([F:33])[F:32]>C1COCC1.O>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]2[N:25]([C:21]([CH2:20][N:15]3[CH2:16][CH:12]([CH:11]=[C:10]([F:18])[F:9])[CH2:13][C:14]3=[O:17])=[C:22]([C:31]([F:34])([F:33])[F:32])[N:23]=2)[N:26]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 24758Sodium hydride3×HCID 17948959HCID 17948959, compoundHCID 536291543-(Bromomethyl)-6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazine

Product 1

HCID 15952753{[6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-oneYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (60% wt mineral oil dispersion, 0.82 g, 1.3 eq, 20.5 mmol) is washed three times by hexane (15 ml). THF (15 ml) is added at room temperature to this clean sodium hydride, a solution of 4-(2,2-difluorovinyl)pyrrolidin-2-one x98 (3.42 g, 23 mmol, 1.4 eq) and 3-(bromomethyl)-6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazine x36 (4.97 mg, 15.8 mmol, 1 eq) in THF (15 ml). After 3 hours of stirring at room temperature, a small amount of sodium hydride is added in order to complete the reaction and stirring is pursue overnight. Water (25 ml) is then added to the mixture and THF is removed evaporation under reduced pressure. The aqueous layer is extracted by ethyl acetate (2×50 ml), the resulting organic layer is dried over MgSO4, filtered and concentrated to dryness. The residue is purified by preparative chromatography (benzine/AcOEt: 50/50) to afford 4.33 g of {[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one 33.

Workup

  1. customthe reaction
  2. stirringstirring
  3. waitis pursue overnight
  4. customis removed
  5. customevaporation under reduced pressure
  6. extractionThe aqueous layer is extracted by ethyl acetate (2×50 ml)
  7. dry with materialthe resulting organic layer is dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue is purified by preparative chromatography (benzine/AcOEt: 50/50)

Sources & evidence

ORD record
ord-efbd73c5c34046cab4d7b29c0947e931
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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