4-(Diphenylmethoxy)piperidinepropanol → 3-Tert-butyl-6-[3-[4-(diphenylmethoxy)piperidino]propoxy][1,2,4]triazolo[4,3-b]pyridazine

HRID 397560Notes

Reaction equation

HRID 397560 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.CC(C)([O-])C.[Na+].[C:31]([C:35]1[N:39]2[N:40]=[C:41](Cl)[CH:42]=[CH:43][C:38]2=[N:37][N:36]=1)([CH3:34])([CH3:33])[CH3:32]>O1CCCC1>[C:31]([C:35]1[N:39]2[N:40]=[C:41]([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:42]=[CH:43][C:38]2=[N:37][N:36]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 229892644-(Diphenylmethoxy)piperidinepropanolHCID 230003263-Tert-butyl-6-chloro-(1,2,4)triazolo(4,3-b)pyridazineHCID 23676156Sodium t-butoxide

Product 1

HCID 230002943-Tert-butyl-6-[3-[4-(diphenylmethoxy)piperidino]propoxy][1,2,4]triazolo[4,3-b]pyridazineYield 32.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

991 mg of 4-(diphenylmethoxy)-1-piperidinepropanol was dissolved in 20 ml of tetrahydrofuran; 322 mg of sodium tert-butoxide was added, followed by stirring at an external temperature of 60° C. for 2 hours. After cooling, 642 mg of 3-tert-butyl-6-chloro[1,2,4]triazolo[4,3-b]pyridazine was added, followed by refluxing under heating for 2 hours. After cooling, saline was added; the reaction mixture was extracted with ethyl acetate and dried over magnesium sulfate. After concentration 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 concentrated under reduced pressure; 1.26 g of the residue was dissolved in 3 ml of pyridine; 1.5 ml of acetic anhydride was added, followed by stirring at room temperature for 6 hours. After the reaction mixture 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 concentrated under reduced pressure; the residue crystallized from ethyl acetate-diethyl ether (1:1), washed with diethyl ether, and dried, to yield 500 mg of the title compound.

Workup

  1. temperatureAfter cooling
  2. temperatureby refluxing
  3. temperatureunder heating for 2 hours
  4. temperatureAfter cooling
  5. additionsaline was added
  6. extractionthe reaction mixture was extracted with ethyl acetate
  7. dry with materialdried over magnesium sulfate
  8. concentrationAfter concentration under reduced pressure
  9. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
  10. customThe desired fraction was collected
  11. concentrationconcentrated under reduced pressure
  12. dissolution1.26 g of the residue was dissolved in 3 ml of pyridine
  13. addition1.5 ml of acetic anhydride was added
  14. stirringby stirring at room temperature for 6 hours
  15. concentrationAfter the reaction mixture was concentrated under reduced pressure
  16. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
  17. customThe desired fraction was collected
  18. concentrationconcentrated under reduced pressure
  19. customthe residue crystallized from ethyl acetate-diethyl ether (1:1)
  20. washwashed with diethyl ether
  21. customdried

Sources & evidence

ORD record
ord-8a0f8287676b4a76a47ecf441700a154
Source dataset
uspto-grants-2003_08
Patent number
US06610694B1

Reaction notes

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