Reacción #11322

Ecuación de reacción

3,6-dichloro-4-cyclobutylpyridazine

benzoic hydrazide

triethylamine hydrochloride

→

title compound

Rendimiento 34.0%

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

Rendimiento 34.0%

Disolventes

p-xylene

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheated
2. 2
   Temperaturaat reflux under a stream of nitrogen for 24 hours
3. 3
   TemperaturaUpon cooling the volatiles
4. 4
   Otrowere removed in vacuo
5. 5
   OtroThe residue was partitioned between dichloromethane and water
6. 6
   workup.ADDITIONThe aqueous was basified by the addition of solid potassium carbonate
7. 7
   OtroSome dark insoluble material was removed by filtration at this stage
8. 8
   ExtracciónThe aqueous phase was further extracted with dichloromethane (×2)
9. 9
   SecadoThe combined extracts were dried (MgSO4)
10. 10
    Filtraciónfiltered
11. 11
    Otroevaporated
12. 12
    OtroThe residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane

Procedimiento

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]+.

Fuente