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

HRID 1169071Notes

Reaction equation

HRID 1169071 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][OH:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:27][C:28]1[N:32]2[N:33]=[C:34](Cl)[CH:35]=[CH:36][C:31]2=[N:30][C:29]=1[C:38]([CH3:45])([CH3:44])[C:39]([O:41][CH2:42][CH3:43])=[O:40]>CN(C)C=O>[Cl:27][C:28]1[N:32]2[N:33]=[C:34]([O: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:35]=[CH:36][C:31]2=[N:30][C:29]=1[C:38]([CH3:44])([CH3:45])[C:39]([O:41][CH2:42][CH3:43])=[O:40]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 22989216Ethyl 2-(3,6-dichloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionateHCID 229892644-(Diphenylmethoxy)piperidinepropanol

Product 1

HCID 22989285Ethyl 2-[3-chloro-6-[3-[4-(diphenylmethoxy)piperidino]propoxy]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

334 mg of 4-(diphenylmethoxy)-1-piperidinepropanol was dissolved in 20 ml of N,N-dimethylformamide; 45 mg of a 60% dispersion of sodium hydride in mineral oil was added, followed by stirring at room temperature under reduced pressure for 35 minutes. 310:mg of ethyl 2-[3,6-dichloroimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate was then added, followed by stirring at 0° C. for 2 hours. Ice water 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. The desired fraction was collected; the crystal precipitated was dissolved in 5 ml of ethanol; 160 mg of fumaric acid was added, followed by concentration under reduced pressure. Ethyl acetate was added to the residue; the mixture was washed with aqueous sodium bicarbonate and saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. Ethyl acetate was added to the residue to cause crystallization; the crystal precipitated was collected by filtration, washed with ethyl ether and dried to yield 168 mg of the title compound.

Workup

  1. stirringby stirring at 0° C. for 2 hours
  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
  7. customThe desired fraction was collected
  8. customthe crystal precipitated
  9. dissolutionwas dissolved in 5 ml of ethanol
  10. addition160 mg of fumaric acid was added
  11. concentrationfollowed by concentration under reduced pressure
  12. additionEthyl acetate was added to the residue
  13. washthe mixture was washed with aqueous sodium bicarbonate and saturated saline
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. additionEthyl acetate was added to the residue
  17. customcrystallization
  18. customthe crystal precipitated
  19. filtrationwas collected by filtration
  20. washwashed with ethyl ether
  21. customdried

Sources & evidence

ORD record
ord-e9c30193268f4dab8c00944bfc879cfe
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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