反应详情

温度

76 °C

10% Palladium on carbon (0.276 g, 0.26 mmol) was added to 6-[4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (13.80 g, 25.96 mmol) and ammonium formate (16.37 g, 259.61 mmol) in ethanol (300 mL) at 20° C. The resulting slurry was stirred at 76° C. for 32 hours, regularly adding more ammonium formate and catalyst to force the reaction to completion. The cooled reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under vacuum to give a colourless gum which was dissolved in DCM (1 L) and the solution washed with water (1 L). The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 8% MeOH in DCM. Pure fractions were evaporated to dryness and the resulting oil was triturated with ether to give 6-[4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (9.90 g, 71.4%) as a white solid.

1. customthe reaction to completion
2. customThe cooled reaction mixture
3. filtrationwas filtered through diatomaceous earth
4. concentrationthe filtrate was concentrated under vacuum
5. customto give a colourless gum which
6. washthe solution washed with water (1 L)
7. washThe organic layer was washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated to dryness
11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 8% MeOH in DCM
12. customPure fractions were evaporated to dryness
13. customthe resulting oil was triturated with ether