反应详情

温度

50 °C

A mixture of 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (240 mg), iron(III) acetylacetonate (12 mg) in tetrahydrofuran (5 mL) was degassed by bubbling nitrogen through for 10 minutes. The cyclopropyl magnesium bromide in tetrahydrofuran solution prepared in step 1 was then added to the reaction mixture and stirred at 50° C. for 18 hours. The mixture was allowed to cool to rt then acidified to pH 1 via the addition of 1N hydrochloric acid (20 mL). The tetrahydrofuran was removed in vacuo and the aqueous neutralized via the addition of aqueous NaHCO3 and then extracted with ethyl acetate (×3), dried (Na2SO4) and concentrated to dryness. The residue was taken up in piperidine (1 mL) and heated in a microwave at 12° C. for 25 min to consume the remaining 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline. The title compound was then purified via preparatory HPLC to return the title compound (4 mg, 10%). Analytical data presented in Table 1.

1. customwas degassed
2. customby bubbling nitrogen through for 10 minutes
3. additionThe cyclopropyl magnesium bromide in tetrahydrofuran solution prepared in step 1 was then added to the reaction mixture
4. temperatureto cool to rt
5. additionthen acidified to pH 1 via the addition of 1N hydrochloric acid (20 mL)
6. customThe tetrahydrofuran was removed in vacuo
7. additionthe aqueous neutralized via the addition of aqueous NaHCO3
8. extractionextracted with ethyl acetate (×3)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated to dryness
11. temperatureheated in a microwave at 12° C. for 25 min
12. customto consume the remaining 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline
13. customThe title compound was then purified via preparatory HPLC