反应详情

To a suspension of 2.80 g (6.40 mmol) of 2-(4-fluorophenyl)-3-iodo-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine in 200 mL of a mixture of dimethoxyethane and water (9:1), are added 1.36 g (12.8 mmol) of sodium bicarbonate and 0.95 g (7.7 mmol) of (pyrid-4-yl)boronic acid. After sparging with a stream of argon for a few moments, 0.21 g (0.26 mmol) of a complex of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and dichloromethane (PdCl2(dppf).CH2Cl2) is added and the reaction mixture is refluxed under argon for 18 hours. A further 0.95 g (7.7 mmol) of (pyrid-4-yl)boronic acid, 0.21 g (0.26 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane and 10 mL of water are then added. Heating is continued for 24 hours. The solvent is then evaporated off under reduced pressure and the brown residue is triturated with aqueous 3N hydrochloric acid and then filtered on a Büchner funnel. The aqueous phase is washed twice with diethyl ether and then cautiously neutralized, using aqueous ammonia diluted with ice, to basic pH. The product is extracted with chloroform, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated off to give 2.5 g of a yellowish powder.

1. additionis added
2. temperaturethe reaction mixture is refluxed under argon for 18 hours
3. temperatureHeating
4. customThe solvent is then evaporated off under reduced pressure
5. customthe brown residue is triturated with aqueous 3N hydrochloric acid
6. filtrationfiltered on a Büchner funnel
7. washThe aqueous phase is washed twice with diethyl ether
8. additiondiluted with ice, to basic pH
9. extractionThe product is extracted with chloroform
10. dry with materialthe organic phase is dried over sodium sulfate
11. filtrationfiltered
12. customthe solvent is evaporated off