反应详情

Acetic acid (0.081 mL, 1.41 mmol) was added to 1-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)propan-2-one (595 mg, 1.41 mmol), N-acetylpiperazine (199 mg, 1.55 mmol) and a catalytic amount of MgSO4 in THF (5 mL). The resulting mixture was stirred at ambient temperature for 1 hour, then sodium triacetoxyborohydride (359 mg, 1.69 mmol) was added and stirring was continued for a further 16 hours. The reaction mixture was concentrated, diluted with DCM (25 mL), washed with saturated NaHCO3 (25 mL) and then filtered through a PTFE cup. The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford racemic 6-(4-{4-[2-(4-acetylpiperazin-1-yl)propoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (199 mg, 26.4%) as a gum.

1. stirringstirring
2. waitwas continued for a further 16 hours
3. concentrationThe reaction mixture was concentrated
4. additiondiluted with DCM (25 mL)
5. washwashed with saturated NaHCO3 (25 mL)
6. filtrationfiltered through a PTFE cup
7. customThe organic layer was evaporated
8. customto afford crude product
9. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM
10. customPure fractions were evaporated to dryness