6-Amino-3-chloropyridazine → Methyl (6-chloroimidazo[1,2-b]pyridazin-2-yl)acetate

HRID 1067584Notes

Reaction equation

HRID 1067584 reaction equation
[NH2:1][C:2]1[N:3]=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.Cl[CH2:10][C:11](=O)[CH2:12][C:13]([O:15][CH3:16])=[O:14]>CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]2[N:3]([CH:10]=[C:11]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[N:1]=2)[N:4]=1

Participants

4

Reactant 2

HCID 216436-Amino-3-chloropyridazineHCID 36240Methyl 4-chloroacetoacetate

Product 1

HCID 11009644Methyl (6-chloroimidazo[1,2-b]pyridazin-2-yl)acetateYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

10.1 g of 3-amino-6-chloropyridazine was suspended in 120 ml of methanol; 23.5 g of methyl 4-chloroacetoacetate was added, followed by heating and refluxing for 20 hours. After cooling, the mixture was concentrated under reduced pressure; the residue was ajusted to pH 7 by the addition of an aqueous solution of sodium hydrogen carbonate, followed by extraction with ethyl ether; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with hexane:ethyl acetate (1:4). The desired fraction was collected to yield 9.15 g of methyl 6-chloroimidazo[1,2-b]pyridazin-2-acetate was dissolved in 10 ml of N,N-dimethylformamide; while the solution was stirred under ice water cooling conditions, 3.5 g of a 60% sodium hydride dispersion in mineral oil was add little by little, followed by stirring at room temperature for 30 minutes. Under ice water cooling conditions, 6.3 ml of methyl iodide was added, followed by stirring at room temperature for 5 hours. Ice water was poured, followed by extraction with ethyl acetate; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with hexane:ethyl acetate (1:1). The desired fraction was collected and concentrated to yield 14.1 g of the title compound.

Workup

  1. temperatureby heating
  2. temperaturerefluxing for 20 hours
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated under reduced pressure
  5. additionthe residue was ajusted to pH 7 by the addition of an aqueous solution of sodium hydrogen carbonate
  6. extractionfollowed by extraction with ethyl ether
  7. washthe extract was washed with saline
  8. dry with materialdried with magnesium sulfate
  9. concentrationThe dry product was concentrated under reduced pressure
  10. washeluted with hexane:ethyl acetate (1:4)
  11. customThe desired fraction was collected

Sources & evidence

ORD record
ord-5fac30cd9dbb4565abb4501996410fb8
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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