Ethyl Acetate → 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 fumarate

HRID 2381107Notes

Reaction equation

HRID 2381107 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[C:9]([N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH2:34][CH2:35][C:36]5[N:37]([C:39]([C:42]([F:45])([F:44])[F:43])=[N:40][N:41]=5)[N:38]=4)[CH2:29][CH2:28]3)=[CH:23][CH:22]=2)[CH2:14][CH2:13]1)(=[O:11])[CH3:10].C(OC(=O)C)C>CO>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[C:9]([N:12]1[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][O:20][C:21]2[CH:22]=[CH:23][C:24]([CH:27]3[CH2:28][CH2:29][N:30]([C:33]4[CH2:34][CH2:35][C:36]5[N:37]([C:39]([C:42]([F:43])([F:44])[F:45])=[N:40][N:41]=5)[N:38]=4)[CH2:31][CH2:32]3)=[CH:25][CH:26]=2)[CH2:16][CH2:17]1)(=[O:11])[CH3:10]

Participants

5

Reactant 3

HCID 8857Ethyl Acetate2×HCID 444972Fumaric AcidHCID 46893585Azd 3514

Product 1

HCID 684979466-(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 fumarateYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

A clear solution of fumaric acid (0.223 g, 1.92 m mol) in methanol (3.0 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, (1.0 g, 1.92 m mol) in methanol (2.0 mL) at 22-25° C. and the resulting clear solution heated to 50° C. for 30 min. The mixture was cooled to 22-25° C. and ethylacetate (8.0 mL) charged drop wise into the reaction mass at 22-25° C. The solvent was stripped off and the reaction mass charged with fresh ethylacetate (8.0 mL). The reaction mass was then stirred for 60 min at 22-25° C. The resulting white color material was collected by filtration. The material was then 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 fumarate (0.91 g, 74.0%) as free flowing white color material.

Workup

  1. customobtained
  2. temperatureThe mixture was cooled to 22-25° C.
  3. filtrationThe resulting white color material was collected by filtration
  4. customThe material was then dried under reduced pressure with nitrogen gas
  5. custombleed at 50° C.

Sources & evidence

ORD record
ord-a4d8eb473bae4094a93a7002c41182a2
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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