Trifluoroacetic acid → 6-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1674981Notes

Reaction equation

HRID 1674981 reaction equation
[CH3:1][C@@H:2]1[CH2:7][N:6]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([C:17]([F:20])([F:19])[F:18])=[N:15][N:16]=3)[N:13]=2)[C@@H:5]([CH3:21])[CH2:4][N:3]1C(OC(C)(C)C)=O.C(O)(C(F)(F)F)=O>>[CH3:21][C@H:5]1[CH2:4][NH:3][C@H:2]([CH3:1])[CH2:7][N:6]1[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

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67340727HCID 67340727, compound

Product 1

HCID 673408626-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazineYield 78.1%

Procedure

(2R,5S)-tert-Butyl 2,5-dimethyl-4-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carboxylate (6.01 g, 15 mmol) was added in portions to stirred TFA (25 mL) over 5 minutes. There was a moderate exotherm and the reaction mixture was allowed to stir for a further 15 minutes. The bulk of the TFA was evaporated and the residue was basified with 1M aqueous K2CO3. It was extracted thoroughly with DCM (4×200 mL) and the combined organic phase was dried over MgSO4 and evaporated to give an oil which rapidly crystallised. The solid was collected by filtration and dried under vacuum to give 6-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (3.52 g, 78%) as a white crystalline solid.

Workup

  1. customThe bulk of the TFA was evaporated
  2. extractionIt was extracted thoroughly with DCM (4×200 mL)
  3. dry with materialthe combined organic phase was dried over MgSO4
  4. customevaporated
  5. customto give an oil which
  6. customrapidly crystallised
  7. filtrationThe solid was collected by filtration
  8. customdried under vacuum

Sources & evidence

ORD record
ord-a9bfd3b7036e4cafb836cbe200a1ceef
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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