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

HRID 1067537Notes

Reaction equation

HRID 1067537 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 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 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 with magnesium sulfate
  5. concentrationThe dry product was concentrated 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-3d7e3c66ad804420becb19ac405715d8
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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