HCID 17948959, compound → HCID 15953078, compound

HRID 1926784Notes

Reaction equation

HRID 1926784 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:14]O)=[C:9]([CH:11]3[CH2:13][CH2:12]3)[N:10]=2)[N:7]=1.[F:16][C:17]([F:25])=[CH:18][CH:19]1[CH2:23][NH:22][C:21](=[O:24])[CH2:20]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:14][N:22]3[CH2:23][CH:19]([CH:18]=[C:17]([F:25])[F:16])[CH2:20][C:21]3=[O:24])=[C:9]([CH:11]3[CH2:12][CH2:13]3)[N:10]=2)[N:7]=1

Participants

4

Reactant 2

HCID 17948959HCID 17948959, compoundHCID 58009731(6-Chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methanol

Product 1

HCID 15953078HCID 15953078, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (6-chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methanol x115 (889 mg, 3.97 mmol), 4-(2,2-difluorovinyl)pyrrolidin-2-one (643 mg, 4.37 mmol, 1.1 eq) and paratoluenesulfonic acid (76 mg, 0.40 mmol, 0.1 eq) in toluene (20 ml) is heated under reflux for 16 h. After cooling, the solvent is removed under reduced pressure, the crude product is dissolved in dichloromethane (100 ml). The organic layer is washed by water (150 ml). The aqueous layer is extracted by dichloromethane (100 ml). The cumulated organic layers are dried over MgSO4, filtered and evaporated under reduced pressure. The residue is purified by preparative chromatography over silicagel (benzine/AcOEt:60/40) to afford 1-[(6-chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one 62 after recrystallization in diisopropylether.

Workup

  1. temperatureunder reflux for 16 h
  2. temperatureAfter cooling
  3. customthe solvent is removed under reduced pressure
  4. dissolutionthe crude product is dissolved in dichloromethane (100 ml)
  5. washThe organic layer is washed by water (150 ml)
  6. extractionThe aqueous layer is extracted by dichloromethane (100 ml)
  7. dry with materialThe cumulated organic layers are dried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue is purified by preparative chromatography over silicagel (benzine/AcOEt:60/40)

Sources & evidence

ORD record
ord-749837b28f95444d84a79f48ba877876
Source dataset
uspto-grants-2012_05
Patent number
US08183241B2

Reaction notes

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