Sodium Bicarbonate → Ethyl 2-[6-[3-[4-[bis(4-fluorophenyl)methoxy) piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarate

HRID 1067522Notes

Reaction equation

HRID 1067522 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][NH2:19])[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.Cl[C:28]1[CH:29]=[CH:30][C:31]2[N:32]([CH:34]=[C:35]([C:37]([CH3:44])([CH3:43])[C:38]([O:40][CH2:41][CH3:42])=[O:39])[N:36]=2)[N:33]=1.[C:45](=[O:48])([OH:47])[O-].[Na+]>>[C:38]([OH:40])(=[O:39])/[CH:37]=[CH:35]/[C:45]([OH:47])=[O:48].[C:38]([OH:40])(=[O:39])/[CH:37]=[CH:35]/[C:45]([OH:47])=[O:48].[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[O:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][NH:19][C:28]3[CH:29]=[CH:30][C:31]4[N:32]([CH:34]=[C:35]([C:37]([CH3:43])([CH3:44])[C:38]([O:40][CH2:41][CH3:42])=[O:39])[N:36]=4)[N:33]=3)[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 109920244-[Bis(4-fluorophenyl)methoxy]-1-piperidinepropanamineHCID 11043751Ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropanoate

Product 1

HCID 70102551Ethyl 2-[6-[3-[4-[bis(4-fluorophenyl)methoxy) piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarate

Procedure

1.62 g of 4-[bis(4-fluorophenyl)methoxy]-1-piperidinepropanamine and 0.803 g of ethyl 2-[6chloroimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate were stirred at 190-200° C. for 3 hours. After cooling, aqueous sodium bicarbonate and saline were 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:triethylamine (90:10:1). The desired fraction was collected, dissolved in 20 ml of ethyl acetate; a solution of 301 mg of fumaric acid in 10 ml of methanol was added, followed by concentration. Acetone was added to the residue; the crystal precipitate was collected by filtration, washed with acetone and dried to yield 0.966 g 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:triethylamine (90:10:1)
  7. customThe desired fraction was collected
  8. dissolutiondissolved in 20 ml of ethyl acetate
  9. additiona solution of 301 mg of fumaric acid in 10 ml of methanol was added
  10. concentrationfollowed by concentration
  11. additionAcetone was added to the residue
  12. filtrationthe crystal precipitate was collected by filtration
  13. washwashed with acetone
  14. customdried

Sources & evidence

ORD record
ord-06f79b7573814df683db5b6243ab5efb
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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