2,5-Difluorobenzaldehyde → 7-tert-Butyl-6-chloro-3-(2,5-difluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 2301335Notes

Reaction equation

HRID 2301335 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:12][NH2:13])=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9].[F:14][C:15]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:16]=1[CH:17]=O>Cl.C(O)C.O.O.O.O.O.O.[Fe](Cl)(Cl)Cl>[Cl:1][C:2]1[C:7]([C:8]([CH3:9])([CH3:10])[CH3:11])=[CH:6][C:5]2[N:4]([C:17]([C:16]3[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:15]=3[F:14])=[N:13][N:12]=2)[N:3]=1

Participants

6

Reactant 2

HCID 1376632,5-DifluorobenzaldehydeHCID 229878864-(tert-Butyl)-3-chloro-6-hydrazinylpyridazine

Product 1

HCID 112557487-tert-Butyl-6-chloro-3-(2,5-difluorophenyl)-1,2,4-triazolo[4,3-b]pyridazineYield 35.8%

Reagents, catalysts & solvents 3

HCID 16211236Trichloroiron;hexahydrateCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

To a slurry of 3-chloro-4-(1,1-dimethylethyl)-6-hydrazinylpyridazine (1.3 g, 6.5 mmol) in 0.1N hydrochloric acid (60 ml) was added 2,5-difluorobenzaldehyde (0.70 ml, 6.5 mmol) and the reaction mixture was stirred at room temperature for 30 minutes and then heated to 60° C. for 40 minutes. The reaction mixture was allowed to cool and the resultant solid was collected by filtration, dried and dissolved in ethanol (60 ml). To this solution was added iron(III) chloride hexahydrate (5.4 g, 32.5 mmol) in ethanol (15 ml) dropwise over 10 minutes at 80° C. The reaction mixture was stirred at 80° C. for 2 h, allowed to cool and the solvent removed by evaporation under vacuum. The residue was dissolved in dichloromethane (100 ml) and washed with water (3×100 ml), brine, dried (MgSO4), filtered and concentrated under vacuum to yield the title compound (0.75 g). Data for the title compound: 1H NMR (250 MHz, CDCl3) δ1.57 (9H, s), 7.22-7.29 (2H, m), 7.65-7.71 (1H, m), 8.19 (1H, s); MS (ES+) m/e 323 [MH]+.

Workup

  1. temperatureheated to 60° C. for 40 minutes
  2. temperatureto cool
  3. filtrationthe resultant solid was collected by filtration
  4. customdried
  5. dissolutiondissolved in ethanol (60 ml)
  6. stirringThe reaction mixture was stirred at 80° C. for 2 h
  7. temperatureto cool
  8. customthe solvent removed by evaporation under vacuum
  9. dissolutionThe residue was dissolved in dichloromethane (100 ml)
  10. washwashed with water (3×100 ml), brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-084b0bba01fc42d286291012c2f08901
Source dataset
uspto-grants-2002_12
Patent number
US06500828B1

Reaction notes

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