Sodium Chloride → Ethyl 6-[3-[4-(Diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazine-2-carboxylate Difumarate

HRID 1169059Notes

Reaction equation

HRID 1169059 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]([O:37][CH2:38][CH3:39])=[O:36])[N:34]=2)[N:31]=1.C(N(C(C)C)C(C)C)C.[Cl-].[Na+].CN(C)[CH:53]=[O:54]>>[C:9]([OH:8])(=[O:54])/[CH:32]=[CH:33]/[C:35]([OH:37])=[O:36].[C:53]([OH:54])(=[O:8])/[CH:32]=[CH:33]/[C:35]([OH:37])=[O:36].[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]([O:37][CH2:38][CH3:39])=[O:36])[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 5

HCID 5234Sodium ChlorideHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2779714ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamine

Product 1

HCID 69843796Ethyl 6-[3-[4-(Diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazine-2-carboxylate Difumarate

Conditions

Temperature
80 °C

Procedure

686 mg of 4-(diphenylmethoxy)-1-piperidinepropanamine and 477 mg of ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylate were dissolved in 7 ml of N,N-dimethylformamide; 0.73 ml of N-ethyldiisopropylamine was added, followed by stirring in an oil bath (80° C.) for 18.5 hours. After cooling, ice water and sodium chloride were added, followed by extraction with ethyl acetate-tetrahydrofuran (1:1); the extract was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (50:5:1). The desired fraction was collected, dissolved in 5 ml of ethyl acetate; a solution of 95 mg of fumaric acid in 5 ml of ethanol was added, followed by concentration. Acetone-ethyl ether (1:2) was added to the residue to cause recrystallization; the crystal precipitate was collected by filtration and washed with ethyl ether to yield 211 mg of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate-tetrahydrofuran (1:1)
  3. washthe extract was washed with saturated saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washeluted with ethyl acetate:methanol:triethylamine (50:5:1)
  7. customThe desired fraction was collected
  8. dissolutiondissolved in 5 ml of ethyl acetate
  9. additiona solution of 95 mg of fumaric acid in 5 ml of ethanol was added
  10. concentrationfollowed by concentration
  11. additionAcetone-ethyl ether (1:2) was added to the residue
  12. customrecrystallization
  13. filtrationthe crystal precipitate was collected by filtration
  14. washwashed with ethyl ether

Sources & evidence

ORD record
ord-4d197d4113a54b1cbfc0d2fd556b5c2d
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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