Fumaric Acid → Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino] propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarate

HRID 1169161Notes

Reaction equation

HRID 1169161 reaction equation
[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:26]1[CH:27]=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([C:35]([CH3:42])([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:34]=2)[N:31]=1.C(=O)(O)[O-].[Na+].[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52]>CO>[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].[C:19]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:26]3[CH:27]=[CH:28][C:29]4[N:30]([CH:32]=[C:33]([C:35]([CH3:41])([CH3:42])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:34]=4)[N:31]=3)[CH2:11][CH2:10]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 444972Fumaric AcidHCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 11043751Ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropanoate

Product 1

HCID 69842492Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino] propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarateYield 78.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4.2 g of 4-(diphenylmethoxy)-1-piperidinepropaneamine and 1.76 g of ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate were stirred at 192-200° C. for 3.5 hours. After cooling, an aqueous sodium bicarbonate solution was added thereto and extracted with ethyl acetate. The extract was washed with a brine solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography to be eluted with ethyl acetate:methanol:triethyl amine (100:5:1). The desired fraction was collected and dissolved in 16 mL of ethyl acetate, and a solution prepared by dissolving 867 mg of fumaric acid in 16 mL of methanol was added thereto, followed by concentration. To the residue was added acetone and the crystals formed were collected by filtration, washed with acetone and dried to provide 2.30 g of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with a brine solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washto be eluted with ethyl acetate:methanol:triethyl amine (100:5:1)
  7. customThe desired fraction was collected
  8. dissolutiondissolved in 16 mL of ethyl acetate
  9. customa solution prepared
  10. additionwas added
  11. concentrationfollowed by concentration
  12. additionTo the residue was added acetone
  13. customthe crystals formed
  14. filtrationwere collected by filtration
  15. washwashed with acetone
  16. customdried

Sources & evidence

ORD record
ord-5e9ee67e05ff44568d4c2222abdaa2da
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

Loading…