Thiosemicarbazide → N-Methyl-N-[3-(3-amino-1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamide

HRID 35629Notes

Reaction equation

HRID 35629 reaction equation
[CH3:1][N:2]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[N:13]=[N:14][C:15](Cl)=[CH:16][CH:17]=2)[CH:7]=1)[C:3](=[O:5])[CH3:4].[NH2:19][NH:20][C:21]([NH2:23])=S>C(O)C>[CH3:1][N:2]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]3[N:14]([C:21]([NH2:23])=[N:20][N:19]=3)[N:13]=2)[CH:7]=1)[C:3](=[O:5])[CH3:4]

Participants

4

Reactant 2

HCID 2723789ThiosemicarbazideHCID 15595702N-Methyl-N-[3-(6-chloro-3-pyridazinyl)phenyl]acetamide

Product 1

HCID 15595668N-Methyl-N-[3-(3-amino-1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamideYield 25.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2.2 g of N-methyl-N-[3-(6-chloro-3-pyridazinyl)phenyl]acetamide and 1.5 g of thiosemicarbazide in 100 ml of ethanol was refluxed for 5 hours, then the solvent was removed in vacuo. To the residue was added 100 ml of glacial acetic acid, this mixture was refluxed 18 hours, then the acetic acid was removed in vacuo. Saturated aqueous sodium bicarbonate was added to neutralize the mixture which was then extracted with dichloromethane:methanol (9:1). The extract was washed with water, dried and evaporated. The residue was chromatographed on a silica gel column, eluting with dichloromethane:methanol (9:1). The product was crystallized from dichloromethane-hexane, giving 0.6 g of the desired compound as yellow crystals mp 196°-197° C.

Workup

  1. customthe solvent was removed in vacuo
  2. additionTo the residue was added 100 ml of glacial acetic acid
  3. temperaturethis mixture was refluxed 18 hours
  4. customthe acetic acid was removed in vacuo
  5. additionSaturated aqueous sodium bicarbonate was added
  6. extractionwas then extracted with dichloromethane:methanol (9:1)
  7. washThe extract was washed with water
  8. customdried
  9. customevaporated
  10. customThe residue was chromatographed on a silica gel column
  11. washeluting with dichloromethane:methanol (9:1)
  12. customThe product was crystallized from dichloromethane-hexane

Sources & evidence

ORD record
ord-bd46bd1ec30842aa944c63a2f8420783
Source dataset
uspto-grants-1988_08
Patent number
US04767765

Reaction notes

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