HCID 17948959, compound → HCID 15953078, compound

HRID 2043633Notes

Reaction equation

HRID 2043633 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 recristallization 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-82e7c0178cf04555b57121fa369c9d8c
Source dataset
uspto-grants-2013_11
Patent number
US08586623B2

Reaction notes

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