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

HRID 35649Notes

Reaction equation

HRID 35649 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 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3.0 g N-methyl-N-[3-(6-chloro-3-pyridazinyl)phenyl]acetamide and 2.0 g thiosemicarbazide in 100 ml ethanol was heated at reflux for 5.5 hours. The ethanol was removed in vacuo, 100 ml glacial acetic acid added and the mixture was refluxed for 18 hours. The acetic acid was removed in vacuo and the yellow residue added to 300 ml water. This mixture was brought to pH~7 with aqueous sodium bicarbonate and extracted with 100 ml portions of dichloromethane and dichloromethane-ethyl acetate. The combined extracts were dried, the solvent removed in vacuo, and the product mixture chromatographed on silica gel using dichloromethane-methanol (95.5) as solvent. Recombining the pure fractions and recrystalizing from ether-methanol-hexane afforded 1.10 g yellow crystals, mp 206°-207° C.

Workup

  1. temperatureat reflux for 5.5 hours
  2. customThe ethanol was removed in vacuo, 100 ml glacial acetic acid
  3. additionadded
  4. temperaturethe mixture was refluxed for 18 hours
  5. customThe acetic acid was removed in vacuo
  6. additionthe yellow residue added to 300 ml water
  7. extractionextracted with 100 ml portions of dichloromethane and dichloromethane-ethyl acetate
  8. customThe combined extracts were dried
  9. customthe solvent removed in vacuo
  10. customthe product mixture chromatographed on silica gel
  11. customrecrystalizing from ether-methanol-hexane

Sources & evidence

ORD record
ord-7291627e99ea49eab7bcb16d2ca2b69a
Source dataset
uspto-grants-1988_08
Patent number
US04767765

Reaction notes

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