1,3-Dichloroacetone → 6-chloro-2-(chloromethyl)imidazo[1,2-b]pyridazine

HRID 1798699Notes

Reaction equation

HRID 1798699 reaction equation
[Cl:1][CH2:2][C:3]([CH2:5]Cl)=O.[Cl:7][C:8]1[N:13]=[N:12][C:11]([NH2:14])=[CH:10][CH:9]=1>C(#N)C>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH:5]=[C:3]([CH2:2][Cl:1])[N:14]=2)[N:13]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 216436-Amino-3-chloropyridazine

Product 1

HCID 109655626-chloro-2-(chloromethyl)imidazo[1,2-b]pyridazineYield 64.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,3-Dichloroacetone (21.4 g, 168.0 mmol) was added to a solution of 6-chloropyridazin-3-amine (10 g, 77.2 mmol) in acetonitrile (200 ml). The mixture was heated at reflux for 14 h (the reaction was monitored by TLC). The volatiles were removed under reduced pressure and the reaction mixture was diluted with water. The pH was adjusted to ˜7.5 with sodium bicarbonate solution and then extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 14% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 6-chloro-2-(chloromethyl) imidazo[1,2-b]pyridazine (6.0 g, 64.1%) as white solid. 1H NMR: 200 MHz, CDCl3: δ 8.0 (s, 1H), 7.9 (d, 1H), 7.1 (d, 1H), 4.75 (s, 2H). MS: [M+H]+: m/z=202.8.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 14 h (the reaction
  3. customThe volatiles were removed under reduced pressure
  4. additionthe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-3196673f190949a6a695068335cc3568
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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