反应详情

To a microwave vessel was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (80 mg, 0.23 mmol, 1 equiv), bis(pinacol)borane (69 mg, 0.27 mmol, 1.2 equiv), potassium acetate (66 mg, 0.67 mmol, 3.0 equiv) followed by dimethylacetamide (0.8 mL). The solution was degassed for 10 min and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv added. The microwave vessel was capped and reacted in a microwave reactor at 120° C. for 1 hour. The microwave vessel was cooled and then 2-(4-bromo-pyrazol-1-yl)-ethanol (0.18 mmol, 0.8 equiv) dissolved in dimethylacetamide (0.6 mL) was added, followed by 2 M aqueous sodium carbonate (0.6 mL). The solution was degassed for 10 min and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv) added. The microwave vessel was capped and reacted in a microwave reactor at 120° C. for 2 hours. After cooling, Na2SO4 (3 g) was added and the mixture diluted with acetonitrile and filtered through a pad of celite. The filtrate was concentrated onto silica gel and purified by either flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) or preparative HPLC to return the title compound. Analytical data presented in Table 2.

1. customThe solution was degassed for 10 min
2. additiondichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv added
3. customThe microwave vessel was capped
4. customreacted in a microwave reactor at 120° C. for 1 hour
5. temperatureThe microwave vessel was cooled
6. additionwas added
7. customThe solution was degassed for 10 min
8. customThe microwave vessel was capped
9. customreacted in a microwave reactor at 120° C. for 2 hours
10. temperatureAfter cooling
11. filtrationfiltered through a pad of celite
12. concentrationThe filtrate was concentrated onto silica gel
13. custompurified by either flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) or preparative HPLC