Trifluoroacetic acid → 6-Chloro-2-cyclopropylimidazo[1,2-b]pyridazine-3-carbaldehyde

HRID 1924271Notes

Reaction equation

HRID 1924271 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH:11]3[CH2:13][CH2:12]3)[N:10]=2)[N:7]=1.FC(F)(F)[C:16](O)=[O:17]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:16]=[O:17])=[C:9]([CH:11]3[CH2:13][CH2:12]3)[N:10]=2)[N:7]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 536291716-Chloro-2-cyclopropylimidazo[1,2-b]pyridazine

Product 1

HCID 577430506-Chloro-2-cyclopropylimidazo[1,2-b]pyridazine-3-carbaldehydeYield 45%

Procedure

6-chloro-2-cyclopropylimidazo[1,2-b]pyridazine x105 (1.88 g, 9.71 mmol) and hexamethyltetramine (HMTE, 13.61 g, 97.09 mmol, 10 eq) in trifluoroacetic acid (75 ml) are heated at 60° C. during 6 days. After cooling and solvent evaporation under reduced pressure, the crude product is dissolved in dichloromethane (150 ml). The organic layer is washed with water (150 ml) and the resulting aqueous layer is extracted with dichloromethane (150 ml). The cumulated organic layers are dried over MgSO4, filtered and the solvent is removed by evaporation under reduced pressure. The resulting crude compound is purified by preparative chromatography (benzine/AcOEt:80/20) affording 0.82 g of 6-chloro-2-cyclopropylimidazo[1,2-b]pyridazine-3-carbaldehyde x110.

Workup

  1. temperatureAfter cooling
  2. customsolvent evaporation under reduced pressure
  3. dissolutionthe crude product is dissolved in dichloromethane (150 ml)
  4. washThe organic layer is washed with water (150 ml)
  5. extractionthe resulting aqueous layer is extracted with dichloromethane (150 ml)
  6. dry with materialThe cumulated organic layers are dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent is removed by evaporation under reduced pressure
  9. customThe resulting crude compound is purified by preparative chromatography (benzine/AcOEt:80/20)

Sources & evidence

ORD record
ord-a4453eccd2bb421e9ecd10d0ea870499
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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