Water → 4-(2,2-Difluorovinyl)-1-{[6-methoxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}pyrrolidin-2-one

HRID 1896411Notes

Reaction equation

HRID 1896411 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:15][N:16]3[CH2:20][CH:19]([CH:21]=[C:22]([F:24])[F:23])[CH2:18][C:17]3=[O:25])=[C:9]([C:11]([F:14])([F:13])[F:12])[N:10]=2)[N:7]=1.[CH3:26][O-:27].[Na+].O>CO.CCOC(C)=O.O(C(C)C)C(C)C>[F:23][C:22]([F:24])=[CH:21][CH:19]1[CH2:20][N:16]([CH2:15][C:8]2[N:6]3[N:7]=[C:2]([O:27][CH3:26])[CH:3]=[CH:4][C:5]3=[N:10][C:9]=2[C:11]([F:14])([F:13])[F:12])[C:17](=[O:25])[CH2:18]1

Participants

6

Reactant 3

HCID 962WaterHCID 10942334Sodium MethoxideHCID 15952753{[6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one

Product 1

HCID 159528514-(2,2-Difluorovinyl)-1-{[6-methoxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}pyrrolidin-2-oneYield 93.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 22281796Diisopropylether ethyl acetateSolvent

Procedure

A solution of {[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one 33 (500 mg, 1.31 mmol, 1 eq) and sodium methoxide (142 mg, 2.63 mmol, 2 eq) in methanol (5 ml) is heated in microwave apparatus (300 W, T 150° C.) until complete conversion (0.5 h). After cooling to room temperature, water (10 ml) is added and the methanol is removed under reduced pressure. Subsequent extraction with dichloromethane (2×20 ml), drying of cumulated organic layers over MgSO4, filtration and solvent evaporation under reduced pressure affords the crude reaction mixture which is recristallized in AcOEt/iPr2O to yield 0.46 g of 4-(2,2-difluorovinyl)-1-{[6-methoxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}pyrrolidin-2-one 42.

Workup

  1. customthe methanol is removed under reduced pressure
  2. extractionSubsequent extraction with dichloromethane (2×20 ml)
  3. dry with materialdrying of cumulated organic layers over MgSO4, filtration and solvent evaporation under reduced pressure
  4. customaffords the crude
  5. customreaction mixture which

Sources & evidence

ORD record
ord-d8f0724f5e83491bb08ccfa1d357b99e
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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