反应详情

A mixture of 0.330 g (0.58 mmol) of 6-chloro-2(4-fluorophenyl)-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine, 0.116 g (1.16 mmol) of (2R)-2-methylpiperazine and 0.08 ml (0.6 mmol) of triethylamine in 5 ml of pentanol is heated under reflux for 24 hours. The reaction medium is diluted with 100 ml of an aqueous solution of hydrochloric acid and the solution is washed with ethyl acetate. The aqueous phase is then basified by addition of aqueous ammonia and the product is extracted with dichloromethane. The organic phase is separated, dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The chestnut brown solid obtained is then purified by chromatography on a silica gel column (35 g) by eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order to give 0.232 g of 2-(4-fluorophenyl)-6-[(3R)-3-methylpiperazin-1-yl]-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine in the form of a yellow powder after drying.

1. temperatureis heated
2. temperatureunder reflux for 24 hours
3. washthe solution is washed with ethyl acetate
4. additionThe aqueous phase is then basified by addition of aqueous ammonia
5. extractionthe product is extracted with dichloromethane
6. customThe organic phase is separated
7. dry with materialdried over sodium sulphate
8. customthe solvent is removed by evaporation under reduced pressure
9. customThe chestnut brown solid obtained
10. customis then purified by chromatography on a silica gel column (35 g)
11. washby eluting with a mixture of dichloromethane, methanol and aqueous ammonia (95/5/0.5) in order