Reaction #11322

Reaction equation

3,6-dichloro-4-cyclobutylpyridazine

benzoic hydrazide

triethylamine hydrochloride

→

title compound

Yield 34.0%

6-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine

Yield 34.0%

Solvents

p-xylene

Conditions

Workup

1. 1
   Temperatureheated
2. 2
   Temperatureat reflux under a stream of nitrogen for 24 hours
3. 3
   TemperatureUpon cooling the volatiles
4. 4
   Otherwere removed in vacuo
5. 5
   OtherThe residue was partitioned between dichloromethane and water
6. 6
   workup.ADDITIONThe aqueous was basified by the addition of solid potassium carbonate
7. 7
   OtherSome dark insoluble material was removed by filtration at this stage
8. 8
   ExtractionThe aqueous phase was further extracted with dichloromethane (×2)
9. 9
   DryingThe combined extracts were dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Otherevaporated
12. 12
    OtherThe residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane

Procedure

A mixture of 3,6-dichloro-4-cyclobutylpyridazine from above (55.7 g, 0.27 mol), benzoic hydrazide (41.1 g, 0.30 mol) and triethylamine hydrochloride (41.5 g, 0.30 mol) in p-xylene (0.4 l) was stirred and heated at reflux under a stream of nitrogen for 24 hours. Upon cooling the volatiles were removed in vacuo. The residue was partitioned between dichloromethane and water. The aqueous was basified by the addition of solid potassium carbonate. Some dark insoluble material was removed by filtration at this stage. The aqueous phase was further extracted with dichloromethane (×2). The combined extracts were dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane to give the title compound, (26.4 g, 34%) as an off-white solid. Data for the title compound: 1H NMR (360 MHz, CDCl3) δ 1.90–2.00 (1H, m), 2.12–2.28 (3H, m), 2.48–2.57 (2H, m), 3.69–3.78 (1H,m), 7.49–7.59 (3H, m), 7.97 (1H, s), 8.45–8.48 (2H, m); MS (ES+) m/e 285 [MH]+, 287 [MH]+.

Source