反应详情

温度

90 °C

100 mg (0.44 mmol) 6-Chloro-7-phenyl-imidazo[1,2-b]pyridazine (intermediate example Int-1-0) in 1.5 mL DME, 178.8 mg (0.48 mmol) {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, 0.85 mL aqueous sodium carbonate (10%) and 16 mg (0.02 mmol) 1,1 bis(diphenylphosphino)ferrocenedichloropalladium(II) were put in a microwave vial (no complete dissolution). The reaction mixture was degassed with argon, the vial closed with a cap and put in a heating block. The reaction mixture was stirred for 18 h at 90° C. (complete dissolution). Due to the still presence of starting material additional 86 mg boronic ester, 0.42 mL aqueous base and 8 mg palladium catalyst were added and stirring was continued for 6 hours at 90° C. 20 mL water and 100 mL dichloromethane were added and the reaction mixture was vigorously stirred for one hour. After separation of the organic phase the aqueous phase was extracted once more with dichloromethane. The combined organic extracts were washed with water and dried over sodium sulfate. After removal of the drying agent the solvent was evaporated and the residue was purified by chromatography on silicagel (eluents: dichloromethane/methanol) yielding 109 mg (56.8%) of the desired compound which was yet slightly contaminated.

1. dissolutionno complete dissolution)
2. customThe reaction mixture was degassed with argon
3. customthe vial closed with
4. customa cap
5. dissolution(complete dissolution)
6. additionDue to the still presence of starting material additional 86 mg boronic ester, 0.42 mL aqueous base and 8 mg palladium catalyst were added
7. stirringstirring
8. waitwas continued for 6 hours at 90° C
9. addition20 mL water and 100 mL dichloromethane were added
10. stirringthe reaction mixture was vigorously stirred for one hour
11. customAfter separation of the organic phase the aqueous phase
12. extractionwas extracted once more with dichloromethane
13. washThe combined organic extracts were washed with water
14. dry with materialdried over sodium sulfate
15. customAfter removal of the drying agent the solvent
16. customwas evaporated
17. customthe residue was purified by chromatography on silicagel (eluents: dichloromethane/methanol)