p-Toluenesulfonic acid → 6-Chloro-3-phenyl-7-(4-pyridinyl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 1383820Notes

Reaction equation

HRID 1383820 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.[C:15]([NH:23][NH2:24])(=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)=[CH:6][C:5]2[N:4]([C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:23][N:24]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 11955BenzoylhydrazineHCID 211875033,6-Dichloro-4-(pyridin-4-yl)pyridazine

Product 1

HCID 211875086-Chloro-3-phenyl-7-(4-pyridinyl)-1,2,4-triazolo[4,3-b]pyridazineYield 42%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A mixture of 3,6-dichloro-4-(pyridin-4-yl)pyridazine (390 mg, 1.7 mmol), benzoyl hydrazine (260 mg, 1.9 mmol), triethylamine (270 ml, 1.9 mmol) and p-toluenesulphonic acid (32 mg, 0.2 mmol) in xylene (mixture of isomers) (5 ml) was stirred and heated at reflux under nitrogen for 20 hours. The mixture was partitioned between dichloromethane and saturated aqueous potassium carbonate. The aqueous was further extracted with dichloromethane (×3). The combined extracts were dried (sodium sulphate), filtered and evaporated. The residue was purified by chromatography on silica gel eluting with 3% methanol/dichloromethane to afford the title compound (218 mg, 42%) as a pale yellow solid. 1H NMR (360 MHz, d6-DMSO) δ 7.60-7.69 (5H, m), 8.36-8.38 (2H, m), 8.72 (1H, s), 8.78-8.80 (2H, m). MS (ES+) m/e 308 [MH]+, 310 [MH]+.

Workup

  1. temperatureheated
  2. temperatureat reflux under nitrogen for 20 hours
  3. customThe mixture was partitioned between dichloromethane and saturated aqueous potassium carbonate
  4. extractionThe aqueous was further extracted with dichloromethane (×3)
  5. dry with materialThe combined extracts were dried (sodium sulphate)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel eluting with 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-677841504dc54c50ac44e91ea8455321
Source dataset
uspto-grants-2001_07
Patent number
US06255305B1

Reaction notes

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