Sodium Bicarbonate → Ethyl 2-[3-chloro-6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate dihydrochloride

HRID 1067536Notes

Reaction equation

HRID 1067536 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:25][C:26]1[N:30]2[N:31]=[C:32](Cl)[CH:33]=[CH:34][C:29]2=[N:28][C:27]=1[C:36]([CH3:43])([CH3:42])[C:37]([O:39][CH2:40][CH3:41])=[O:38].C(=O)(O)[O-].[Na+]>>[ClH:25].[ClH:25].[Cl:25][C:26]1[N:30]2[N:31]=[C:32]([NH:18][CH2:17][CH2:16][CH2:15][N:12]3[CH2:13][CH2:14][CH:9]([O:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:10][CH2:11]3)[CH:33]=[CH:34][C:29]2=[N:28][C:27]=1[C:36]([CH3:42])([CH3:43])[C:37]([O:39][CH2:40][CH3:41])=[O:38]

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989216Ethyl 2-(3,6-dichloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate

Product 1

HCID 22989228Ethyl 2-[3-chloro-6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate dihydrochlorideYield 152.8%

Procedure

2.56 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.19 g of ethyl 2-[3,6-dichloroimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate were stirred at 160° C. for 3 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:triethylamine (50:5:1). The desired fraction was collected and dissolved in 5 ml of ethyl acetate; 0.80 ml of a 4 N hydrogen chloride solution in ethyl acetate was added, followed by concentration. The residue was powdered by the addition of ether and dried to yield 1.33 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 (50:5:1)
  7. customThe desired fraction was collected
  8. dissolutiondissolved in 5 ml of ethyl acetate
  9. addition0.80 ml of a 4 N hydrogen chloride solution in ethyl acetate was added
  10. concentrationfollowed by concentration
  11. additionThe residue was powdered by the addition of ether
  12. customdried

Sources & evidence

ORD record
ord-ca91ebbf4c65449c9c26082fb226da95
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

Loading…