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

HRID 1926786Notes

Reaction equation

HRID 1926786 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-72c16316fdec465aa53e19a1a9e647ca
Source dataset
uspto-grants-2012_05
Patent number
US08183241B2

Reaction notes

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