Sodium hydride → 6-[3-[4-(diphenylmethoxy)piperidino]propoxy]-2-triphenylmethyl[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 397577Notes

Reaction equation

HRID 397577 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[C:28]1[CH:29]=[CH:30][C:31]2[N:32]([C:34](=[O:56])[N:35]([C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:36]=2)[N:33]=1>CN(C)C=O>[C:19]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:28]3[CH:29]=[CH:30][C:31]4[N:32]([C:34](=[O:56])[N:35]([C:37]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)([C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=5)[C:50]5[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=5)[N:36]=4)[N:33]=3)[CH2:11][CH2:10]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 229892644-(Diphenylmethoxy)piperidinepropanolHCID 230003076-Chloro-2-triphenylmethyl[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 230003096-[3-[4-(diphenylmethoxy)piperidino]propoxy]-2-triphenylmethyl[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 104.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.326 g of 4-(diphenylmethoxy)-1-piperidinepropanol was dissolved in 3 ml of N,N-dimethylformamide; 0.044 g of 60% oily sodium hydride was added, followed by stirring at room temperature for 1 hour. 0.326 g of 6-chloro-2-triphenylmethyl[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one was added, followed by stirring at room temperature for 14 hours. After ice water was added, the reaction mixture was extracted with ethyl acetate; the extract was washed with saturated saline 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 (95:5). The desired fraction was collected and concentrated to yield 0.58 g of 6-[3-[4-(diphenylmethoxy)piperidino]propoxy]-2-triphenylmethyl[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one as an oily substance. 0.58 g of the oily substance obtained was dissolved in 10 ml of acetone; 467 mg of p-toluenesulfonic acid hydrate was added, followed by refluxing under heating in an oil bath for 5 hours. After cooling, the acetone was mostly distilled off under reduced pressure; to the residue, an aqueous solution of sodium hydrogen carbonate was added; the reaction mixture was extracted with ethyl acetate-tetrahydrofuran (2:1); the extract was washed with saturated saline 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 (85:15:1). The desired fraction was collected and concentrated; the crystal obtained was filtered, washed with ethyl acetate, and dried, to yield 0.137 g of the title compound.

Workup

  1. stirringby stirring at room temperature for 14 hours
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washthe extract was washed with saturated saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. washeluted with ethyl acetate-methanol (95:5)
  7. customThe desired fraction was collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4a7e11365f7b407dbf78eecc7fc9b8a1
Source dataset
uspto-grants-2003_08
Patent number
US06610694B1

Reaction notes

Loading…