Dimethylformamide → HCID 57929957, compound

HRID 1930058Notes

Reaction equation

HRID 1930058 reaction equation
[CH3:1][N:2](C=O)C.P(Cl)(Cl)(Cl)=O.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:19](=O)[CH2:20][C:21]1[CH:22]=[CH:23][C:24]2[N:25]([C:27]([CH:30]([CH3:32])[CH3:31])=[N:28][N:29]=2)[N:26]=1.Cl.NO.C([O-])(O)=O.[Na+].[NH:42]([CH2:44][CH2:45][OH:46])[NH2:43]>C(Cl)(Cl)Cl.C(Cl)Cl>[NH2:2][C:1]1[N:42]([CH2:44][CH2:45][OH:46])[N:43]=[C:19]([C:13]2[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=2[F:11])[C:20]=1[C:21]1[CH:22]=[CH:23][C:24]2[N:25]([C:27]([CH:30]([CH3:32])[CH3:31])=[N:28][N:29]=2)[N:26]=1

Participants

9

Reactant 6

HCID 6228Dimethylformamide2×HCID 80172-HydrazinoethanolHCID 24813Phosphorus oxychlorideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 579298581-(2,4-Difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Product 1

HCID 57929957HCID 57929957, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

DMF (1.00 mL, 12.6 mmol) was cooled to about 5° C. then phosphorus oxychloride (0.44 mL, 4.7 mmol) was added dropwise. After about 15 min the 1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.500 g, 1.58 mmol, Preparation #K.1) in chloroform (10 mL) was added dropwise. The solution was heated to about 80° C. for about 15 min and then the mixture was cooled to about 5° C. then hydroxylamine hydrochloride (0.330 g, 4.74 mmol) and DMF (0.979 mL, 12.7 mmol) were added. The mixture was stirred at ambient temperature for about 3 h then DCM and saturated aqueous NaHCO3 were added. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The oil was dissolved in EtOH (4 mL) then 2-hydrazinylethanol (0.36 g, 4.7 mmol) was added. The mixture was refluxed for about 1 h then cooled, diluted with DCM and filtered to give the title compound (0.250 g, 40%): LC/MS (Table 1, Method a) Rt=2.09 min; MS m/z: 400.3 (M+H)+.

Workup

  1. temperaturethe mixture was cooled to about 5° C.
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe oil was dissolved in EtOH (4 mL)
  6. temperatureThe mixture was refluxed for about 1 h
  7. temperaturethen cooled
  8. filtrationfiltered

Sources & evidence

ORD record
ord-3f285cb5eb554408ab4d1297e743ac23
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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