反应详情

温度

65 °C

Potassium hydroxide (156 mg, 2.79 mmol) was added to 1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-one (200 mg, 0.70 mmol) and 1H-indole (90 mg, 0.77 mmol) in MeOH (3 mL). The resulting mixture was stirred at 65° C. for 20 hours. The reaction mixture was evaporated to dryness then quenched with saturated aqueous ammonium chloride (0.5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated brine (25 mL), dried over MgSO4, filtered and 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 6-[4-(1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine (107 mg, 40%) as a solid.

1. customThe reaction mixture was evaporated to dryness
2. customthen quenched with saturated aqueous ammonium chloride (0.5 mL)
3. additiondiluted with water (50 mL)
4. extractionextracted with ethyl acetate (2×50 mL)
5. washThe combined organic layers were washed with saturated brine (25 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customto afford crude product
10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM
11. customPure fractions were evaporated to dryness