Реакция #11322

Уравнение реакции

3,6-dichloro-4-cyclobutylpyridazine

benzoic hydrazide

triethylamine hydrochloride

→

title compound

Выход 34.0%

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

Выход 34.0%

Растворители

p-xylene

Условия реакции

Обработка

1. 1
   Температураheated
2. 2
   Температураat reflux under a stream of nitrogen for 24 hours
3. 3
   ТемператураUpon cooling the volatiles
4. 4
   Другоеwere removed in vacuo
5. 5
   ДругоеThe residue was partitioned between dichloromethane and water
6. 6
   workup.ADDITIONThe aqueous was basified by the addition of solid potassium carbonate
7. 7
   ДругоеSome dark insoluble material was removed by filtration at this stage
8. 8
   ЭкстракцияThe aqueous phase was further extracted with dichloromethane (×2)
9. 9
   СушкаThe combined extracts were dried (MgSO4)
10. 10
    Фильтрацияfiltered
11. 11
    Другоеevaporated
12. 12
    ДругоеThe residue was purified by chromatography on silica gel eluting with 5%→10%→25% ethyl acetate/dichloromethane

Методика

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]+.

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