反应详情

The 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.276 g, 0.699 mmol, Preparation #A.2), 1-tert-butylpiperidine-4-carbothioamide (0.140 g, 0.699 mmol) and HOAc (0.080 mL, 1.40 mmol) were added to DMF (4 mL). The mixture was stirred at ambient temperature for about 1 h then at about 85° C. for about 1.5 h. The reaction was cooled to ambient temperature and then concentrated under reduced pressure. The residue was partitioned between EtOAc and 1 N aqueous NaOH. The organic solution was dried over MgSO4, filtered and concentrated under reduced pressure to an oil which was then purified by flash chromatography on silica gel using DCM/MeOH with 3% NH4OH (95:5) as an eluent to give the title compound: (0.077 g, 22%): LC/MS (Table 1, Method a) Rt=1.66 min; MS m/z: 497.2 (M+H)+.

1. waitat about 85° C. for about 1.5 h
2. temperatureThe reaction was cooled to ambient temperature
3. concentrationconcentrated under reduced pressure
4. customThe residue was partitioned between EtOAc and 1 N aqueous NaOH
5. dry with materialThe organic solution was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure to an oil which
8. customwas then purified by flash chromatography on silica gel