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

HRID 1067534Notes

Reaction equation

HRID 1067534 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-methylpropionateYield 27.7%

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 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. 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 with 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 with magnesium sulfate
  5. concentrationThe dry product was concentrated 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 with 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-2afb2a828c614c558545d2038558413d
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

Loading…