Lithium Hydroxide → 6-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylic acid

HRID 1925141Notes

Reaction equation

HRID 1925141 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:26])([F:25])[C:12]3[CH:13]=[CH:14][C:15]4[N:16]([CH:18]=[C:19]([C:21]([O:23]C)=[O:22])[N:20]=4)[N:17]=3)=[N:9][N:10]=2)[CH:7]=1.[Li+].[OH-]>O.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:26])([F:25])[C:12]3[CH:13]=[CH:14][C:15]4[N:16]([CH:18]=[C:19]([C:21]([OH:23])=[O:22])[N:20]=4)[N:17]=3)=[N:9][N:10]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 59233216Methyl 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylate

Product 1

HCID 592331396-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylic acidYield 90.5%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of 3.methyl 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylate (4.0 g, 9.45 mmol) and LiOH (0.340 g, 14.18 mmol) in 10% H2O/MeOH (150 mL) was stirred at ambient temperature for 4 hrs. Solvent was removed via rotary evaporation, and the resulting residue was diluted with H2O (100 mL). The aqueous phase was adjusted to pH=5 with concentrated HCl. The resulting precipitate was collected, rinsed with water, rinsed with EtOAc, and dried under vacuum over P2O5 for 18 hrs to provide the title compound, 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylic acid 45J (3.5 g, 8.55 mmol, 90%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.76 (dd, J=9.85, 1.77 Hz, 1 H) 7.82 (d, J=9.60 Hz, 1H) 8.02 (d, J=9.60 Hz, 1 H) 8.51 (d, J=9.85 Hz, 1 H) 8.90 (s, 1 H) 8.97 (s,1 H). ESI-MS:m/z 4.09 (M+H)+.

Workup

  1. customSolvent was removed via rotary evaporation
  2. additionthe resulting residue was diluted with H2O (100 mL)
  3. customThe resulting precipitate was collected
  4. washrinsed with water
  5. washrinsed with EtOAc
  6. dry with materialdried under vacuum over P2O5 for 18 hrs

Sources & evidence

ORD record
ord-1a062acf46a0439791ab1141eda99464
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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