反应详情

A solution of 2-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-ethanone (300 mg, 0.99 mmol) in dichloroethane (3 mL) is stirred at room temperature while TiCl4 (311 mg, 1.64 mmol) is added dropwise. After the addition, the mixture is stirred at room temperature for 5 minutes and a solution of 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile (150 mg, 0.815 mmol) in dichloroethane (3 mL) is added dropwise. After the addition, the mixture is heated to 125° C. for 5 hours. After cooling, the mixture is poured into a mixture of ice cold saturated aqueous NaHCOs solution (30 mL) and EtOAc (30 mL). The resultant precipitate is filtered through celite and washed with EtOAc (2×10 mL). The filtrate is extracted by EtOAc (3×15 mL). The organic layers are combined and washed with brine and dried (MgSO4). After filtering off the drying agent, the filtrate is concentrated and purified by column chromatography (silica gel, 0%˜40% EtOAc/hexane) to provide the titled compound 5-(4-chloro-phenyl)-6-(2,4-dichloro-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridin-4-ylamine as light yellow solid:

1. additionis added dropwise
2. additionAfter the addition
3. additionAfter the addition
4. temperaturethe mixture is heated to 125° C. for 5 hours
5. temperatureAfter cooling
6. filtrationThe resultant precipitate is filtered through celite
7. washwashed with EtOAc (2×10 mL)
8. extractionThe filtrate is extracted by EtOAc (3×15 mL)
9. washwashed with brine
10. dry with materialdried (MgSO4)
11. filtrationAfter filtering off the drying agent
12. concentrationthe filtrate is concentrated
13. custompurified by column chromatography (silica gel, 0%˜40% EtOAc/hexane)