Sodium Bicarbonate → Ethyl 2-[3-chloro-6-[3-[4-(diphenylmethyl)piperazino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate trihydrochloride

HRID 1169073Notes

Reaction equation

HRID 1169073 reaction equation
[C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:24][C:25]1[N:29]2[N:30]=[C:31](Cl)[CH:32]=[CH:33][C:28]2=[N:27][C:26]=1[C:35]([CH3:42])([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37].C(=O)(O)[O-].[Na+]>>[ClH:24].[ClH:24].[ClH:24].[Cl:24][C:25]1[N:29]2[N:30]=[C:31]([NH:17][CH2:16][CH2:15][CH2:14][N:11]3[CH2:10][CH2:9][N:8]([CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:13][CH2:12]3)[CH:32]=[CH:33][C:28]2=[N:27][C:26]=1[C:35]([CH3:41])([CH3:42])[C:36]([O:38][CH2:39][CH3:40])=[O:37]

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 137677783-(4-Benzhydryl-1-piperazinyl)-1-propanamineHCID 22989216Ethyl 2-(3,6-dichloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate

Product 1

HCID 22989265Ethyl 2-[3-chloro-6-[3-[4-(diphenylmethyl)piperazino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate trihydrochlorideYield 129.8%

Procedure

1.75 g of 4-(diphenylmethyl)-1-piperazinepropanamine and 854 mg of ethyl 2-[3,6-dichloroimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate were stirred at 160° C. for 4 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; 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 (30:1). The desired fraction was collected, concentrated under reduced pressure and dissolved in 5 ml of ethyl acetate; 1.55 ml of a 4 N solution of hydrogen chloride in ethyl acetate was added, followed by concentration again. The crystal precipitated was washed by the addition of ethanol-ethyl acetate (1:3), collected by filtration and dried to yield 628 mg of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  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 (30:1)
  7. customThe desired fraction was collected
  8. concentrationconcentrated under reduced pressure
  9. dissolutiondissolved in 5 ml of ethyl acetate
  10. addition1.55 ml of a 4 N solution of hydrogen chloride in ethyl acetate was added
  11. concentrationfollowed by concentration again
  12. customThe crystal precipitated
  13. washwas washed by the addition of ethanol-ethyl acetate (1:3)
  14. filtrationcollected by filtration
  15. customdried

Sources & evidence

ORD record
ord-3530c8ae41594ab68fbbf9a764e12453
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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