Butylamine → 1-{[6-(Butylamino)-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluorovinyl)pyrrolidin-2-one

HRID 1896412Notes

Reaction equation

HRID 1896412 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.[CH2:26]([NH2:30])[CH2:27][CH2:28][CH3:29].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:26]([NH:30][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)[CH2:27][CH2:28][CH3:29]

Participants

5

Reactant 3

HCID 8007ButylamineHCID 11430Potassium CarbonateHCID 15952753{[6-Chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one

Product 1

HCID 159519741-{[6-(Butylamino)-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluorovinyl)pyrrolidin-2-oneYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-{[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluorovinyl)pyrrolidin-2-one 33 (200 mg, 0.48 mmol, 1 eq) and n-butylamine (0.14 g, 0.96 mmol, 2 eq) in acetonitrile (2 ml) is heated in microwave apparatus (300 W, Tmax 150° C.) until complete conversion (2 h). After cooling to room temperature, a potassium carbonate aqueous saturated solution (10 ml) is added and the crude reaction mixture is extracted with dichloromethane (3×20 ml). Subsequent drying of cumulated organic layers over MgSO4, filtration and solvent evaporation under reduced pressure furnished the crude reaction mixture which is purified by preparative chromatography over silicagel (CH2Cl2/MeOH/NH4OH: 95/5/0.5) to afford 1-{[6-(butylamino)-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-(2,2-difluorovinyl)pyrrolidin-2-one 73.

Workup

  1. customthe crude reaction mixture
  2. extractionis extracted with dichloromethane (3×20 ml)
  3. dry with materialSubsequent drying of cumulated organic layers over MgSO4, filtration and solvent evaporation under reduced pressure
  4. customfurnished the crude
  5. customreaction mixture which
  6. customis purified by preparative chromatography over silicagel (CH2Cl2/MeOH/NH4OH: 95/5/0.5)

Sources & evidence

ORD record
ord-4b7c4473c781440c93132cc990ef7905
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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