反应详情

温度

130 °C

To a microwave vial was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (100 mg, 0.28 mmol, 1 equiv), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole (113 mg, 0.35 mmol, 1.25 equiv), K2CO3 (78 mg, 0.566 mmol, 2.0 equiv) followed by 1,4-dioxane (3 mL) and water (1.5 mL). [0542] The solution was degassed with nitrogen for 10 min and then dichloro [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (10 mg, 0.014 mmol, 0.05 equiv) was added. The microwave vessel was capped and heated in a microwave reactor at 130° C. for 30 min. The mixture was cooled and portioned between dichloromethane and water. The organic phase was absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) to give 6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-quinoline (106 mg, 80% yield). The solid was then added to a 20% solution of ethylene diamine in dimethylformamide and stirred for 3 hours. The solvent was removed and the residue triterated with ethanol to afford the title compound (65 mg, 85% yield). Analytical data presented in Table 2.

1. custom[0542] The solution was degassed with nitrogen for 10 min
2. customThe microwave vessel was capped
3. temperatureThe mixture was cooled
4. customThe organic phase was absorbed onto silica gel
5. custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20)