Dimethylformamide → HCID 136136825, compound

HRID 1930056Notes

Reaction equation

HRID 1930056 reaction equation
C[N:2]([CH:4]=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+].[NH2:42][NH2:43]>C(Cl)(Cl)Cl.C(Cl)Cl>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:19]1[NH:43][N:42]=[C:4]([NH2:2])[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 9321HydrazineHCID 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 136136825HCID 136136825, compoundYield 91.4%

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 1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.500 mg, 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, 4.7 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 then filtered and concentrated under reduced pressure. The resulting oil was dissolved in EtOH (4 mL) then hydrazine (0.15 mL, 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 (0.513 g, 91%): LC/MS (Table 1, Method a) Rt=2.38 min; MS m/z: 356.3 (M+H)+.

Workup

  1. temperaturethe mixture was cooled to about 5° C.
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationthen filtered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting 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-f97bc1e731fc47138e2d70c712eca18b
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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