Potassium Iodide → HCID 59233213, compound

HRID 1925147Notes

Reaction equation

HRID 1925147 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:20])([F:19])[C:12]3[N:17]=[N:16][C:15]([NH2:18])=[CH:14][CH:13]=3)=[N:9][N:10]=2)[CH:7]=1.P([O-])([O-])(O)=O.[Na+].[Na+].Br[CH2:29][C:30]([NH:32][C:33]([CH:35]1[CH2:37][CH2:36]1)=[O:34])=O.[I-].[K+]>CN(C)C(=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:20])([F:19])[C:12]3[CH:13]=[CH:14][C:15]4[N:16]([CH:29]=[C:30]([NH:32][C:33]([CH:35]5[CH2:37][CH2:36]5)=[O:34])[N:18]=4)[N:17]=3)=[N:9][N:10]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 24203Sodium Phosphate, DibasicHCID 59233013N-(2-bromoacetyl)cyclopropanecarboxamideHCID 592332076-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)pyridazin-3-amine

Product 1

HCID 59233213HCID 59233213, compoundYield 48.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)pyridazin-3-amine (21.8 g, 63.9 mmol) and sodium hydrogenphosphate (27.2 g, 192 mmol) in N,N-Dimethylacetamide (250 ml) were added N-(2-bromoacetyl)cyclopropanecarboxamide (19.75 g, 96 mmol) and potassium iodide (10.61 g, 63.9 mmol) at room temperature. The reaction mixture was stirred for 5 h at 100° C. Reaction mixture cooled to room temperature, diluted with EtOAc (1000 ml) and washed with brine solution (5×), dried over Na2SO4, volatiles evaporated and the residue was purified by combiflash (2 to 30% MeOH in dichloromethane over 120 min). Product containing fractions were combined and concentrated to get N-(6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (13.9 g, 31.0 mmol, 48.5% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.92 (s, 1H), 8.18-8.35 (m, 2H), 7.92-8.06 (m, 1H), 7.61-7.80 (m, 2H), 1.91-2.02 (m, 1H), 0.78-0.89 (m, 4H). ESI-MS:m/z 450.0 (M+2H)+.

Workup

  1. customReaction mixture
  2. temperaturecooled to room temperature
  3. washwashed with brine solution (5×)
  4. dry with materialdried over Na2SO4, volatiles
  5. customevaporated
  6. customthe residue was purified by combiflash (2 to 30% MeOH in dichloromethane over 120 min)
  7. additionProduct containing fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e894492aa39e4257b160e6c78ba0288a
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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