Réaction #11322

Équation de réaction

3,6-dichloro-4-cyclobutylpyridazine

benzoic hydrazide

triethylamine hydrochloride

→

title compound

Rendement 34.0%

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

Rendement 34.0%

Solvants

p-xylene

Conditions de réaction

Traitement

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

Mode opératoire

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