Triethylamine → 4-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol

HRID 2381103Notes

Reaction equation

HRID 2381103 reaction equation
CC(N(C)C)=O.Cl[C:8]1[CH:9]=[CH:10][C:11]2[N:12]([C:14]([C:17]([F:20])([F:19])[F:18])=[N:15][N:16]=2)[N:13]=1.[NH:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.C(N(CC)CC)C>O>[F:18][C:17]([F:20])([F:19])[C:14]1[N:12]2[N:13]=[C:8]([N:21]3[CH2:26][CH2:25][CH:24]([C:27]4[CH:28]=[CH:29][C:30]([OH:33])=[CH:31][CH:32]=4)[CH2:23][CH2:22]3)[CH:9]=[CH:10][C:11]2=[N:16][N:15]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31374DimethylacetamideHCID 6136576-Chloro-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-b)pyridazineHCID 105115114-Piperidin-4-ylphenol

Product 1

HCID 367300784-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenolYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

Dimethylacetamide (250.0 mL) was added to 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine [CAS: 40971-95-7] (50.0 g, 225 m mol) at 22-25° C. in a suitable round bottom flask followed by 4-(piperidin-4-yl)phenol [CAS: 62614-84-0] (60.9 g, 236 m mol) at 22-25° C. The reaction mass was stirred to obtain a clear solution. Triethylamine (79.1 mL, 561 m mol) was slowly added to the reaction mass by drop wise addition over a period of 60 min at 25-30° C. Temperature was raised to 40° C. and the reaction mass stirred for 1.0 h. After completion of reaction, water (500.0 mL) was added to the reaction mass by drop wise addition over a period of 30 min at 40-43° C. The slurry mass was stirred for 30 min at 40° C. and then filtered under reduced pressure. The wet material was slurry washed using water (500.0 mL) for 30 min at 40° C. The solid was collected by filtration and the material washed with water (125.0 mL). The material was dried under reduced pressure with nitrogen gas bleed at 50° C. to afford the desired product 4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (75.1 g, 89.9%) as a free flowing solid.

Workup

  1. customto obtain a clear solution
  2. stirringthe reaction mass stirred for 1.0 h
  3. additionwas added to the reaction mass by drop wise addition over a period of 30 min at 40-43° C
  4. stirringThe slurry mass was stirred for 30 min at 40° C.
  5. filtrationfiltered under reduced pressure
  6. washThe wet material was slurry washed
  7. customfor 30 min
  8. customat 40° C
  9. filtrationThe solid was collected by filtration
  10. washthe material washed with water (125.0 mL)
  11. customThe material was dried under reduced pressure with nitrogen gas
  12. custombleed at 50° C.

Sources & evidence

ORD record
ord-8423e449356a401e868c6bde5d5242a3
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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