反应详情

To a suspension of 1.25 g (2.39 mmol) of tert-butyl 4-[2-(4-fluorophenyl)-3-iodoimidazo[1,2-b]pyridazin-6-yl]piperazine-1-carboxylate in a mixture of tetrahydrofuran and water are added 2.33 g (7.17 mmol) of cesium carbonate and 0.45 g (2.9 mmol) of 2-chloropyridine-4-boronic acid. After sparging with a stream of argon for a few moments, 0.18 g (0.21 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloro)palladium(II) (PdCl2(dppf)) is added and the reaction mixture is refluxed under argon for 18 hours. The solvent is then stripped off under reduced pressure, the residue is taken up in chloroform, the organic phase obtained is washed with water, dried over sodium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The brown solid obtained is purified by chromatography on silica gel (50 g), eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5). The product obtained is crystallized from 20 ml of refluxing acetonitrile to give 0.95 g of a white powder after cooling, filtering off and drying.

1. additionis added
2. temperaturethe reaction mixture is refluxed under argon for 18 hours
3. customthe organic phase obtained
4. washis washed with water
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationthe filtrate is concentrated under reduced pressure
8. customThe brown solid obtained
9. customis purified by chromatography on silica gel (50 g)
10. washeluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5)
11. customThe product obtained
12. customis crystallized from 20 ml of refluxing acetonitrile