p-Toluenesulfonic acid → 6-(4-{4-[2-(4-Acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro [1,2,4]triazolo[4,3-b]pyridazine di-tosylate

HRID 2381105Notes

Reaction equation

HRID 2381105 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([OH:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:12]([N:15]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]4[CH2:37][CH2:38][C:39]5[N:40]([C:42]([C:45]([F:48])([F:47])[F:46])=[N:43][N:44]=5)[N:41]=4)[CH2:32][CH2:31]3)=[CH:26][CH:25]=2)[CH2:17][CH2:16]1)(=[O:14])[CH3:13].C(OC(=O)C)C>CO>[S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)([OH:10])(=[O:9])=[O:8].[S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)([OH:10])(=[O:9])=[O:8].[C:12]([N:15]1[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][O:23][C:24]2[CH:25]=[CH:26][C:27]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]4[CH2:37][CH2:38][C:39]5[N:40]([C:42]([C:45]([F:46])([F:47])[F:48])=[N:43][N:44]=5)[N:41]=4)[CH2:34][CH2:35]3)=[CH:28][CH:29]=2)[CH2:19][CH2:20]1)(=[O:14])[CH3:13]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 8857Ethyl AcetateHCID 46893585Azd 3514

Product 1

HCID 866466956-(4-{4-[2-(4-Acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro [1,2,4]triazolo[4,3-b]pyridazine di-tosylateYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
23.5 °C

Procedure

A clear solution of toluene-4-sulfonic acid (2.884 g, 15.0 m mol) in methanol (5.0 mL) was added to a clear solution of 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine, obtained as described in Example 5.5, (3.9 g, 7.5 m mol) in methanol (8.0 mL) at 22-25° C. Ethylacetate (20.0 mL) was added drop wise to the resulting clear solution at 22-25° C. The reaction mass was then stirred for 60 min at 22-25° C. The resulting white color material was collected by filtration and washed with methanol (105.0 mL). The material was dried under reduced pressure with nitrogen gas bleed at 50° C. to afford the desired product 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine di-tosylate (4.31 g, 67.0%) as free flowing white color material.

Workup

  1. customobtained
  2. filtrationThe resulting white color material was collected by filtration
  3. washwashed with methanol (105.0 mL)
  4. customThe material was dried under reduced pressure with nitrogen gas
  5. custombleed at 50° C.

Sources & evidence

ORD record
ord-d39ca5ef4200402eb3269e3cffd0cc57
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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