Synthesis And Characterization Of Key Intermediates For Anticarcinogen: Levitinib And Carbotinib

Levitinib is a multi-target enzyme inhibitor for the treatment of thyroid cancer.Compared to previous treatments,Levitinib significantly improved survival.Carbotinib is an oral tyrosine kinase inhibitor that acts on both the vascular endothelin growth factor 2VEGF2 and MET and can be used to treat multiple solid tumors.However,only a few foreign research institutions are carrying out the synthesis of Levitinib and Carbotinib,while it is difficult to discover the report on the synthesis of Levitinib and Carbotinib in domestic.Based on the great medicinal value of Levitinib and Carbotinib,it is important to investigate the synthesis of Levitinib and Carbotinib.The key intermediates of Levitinib and Carbotinib are 4-chloro-7-methoxyquinoline-6-carboxamide and 4-[(6,7-dimethoxy-4-quinolinyl)oxy] aniline,which can be used to synthesize Levitinib and Carbotinib by a few steps.In this thesis,it was carried out that the synthesis and characterization of Levitinib and Carboti-ni b for cheap malonic acid as raw material.4-chloro-7-methoxyquinoline-6-carboxamide was successfully synthesized by condensation,methylation,chlorination with malonic acid as raw materials.To shortening the synthetic route and simplifying the operation,the idea of one-pot synthesis was used,and it was solved that the problem of technical steps such as cyclization.The total yield of 4-chloro-7-methoxyquinoline-6-carboxamide has improved nearly 21% and the final product has high purity.The obtained product was characterized by NMR,IR,MS and was confirmed to be 4-chloro-7-methoxyquinoline-6-carboxamide.The superior conditions obtained through the bench scale experiment was used to amplification experiment,which the yield of target product by six-steps reaction is 50.2% and the final product has high purity.4-[(6,7-dimethoxy-4-quinolinyl)oxy]aniline was successfully synthesized by condensation,cyclization,chlorination and substitution with malonic acid as raw materials.To shortening the synthetic route and simplifying the operation,the idea of one-pot synthesis was used,and it was resolved that the problem of technical steps such as cyclization?substitution.The total yield of 4-[(6,7-dimethoxy-4-quinolinyl)oxy]aniline has enhanced nearly 20% and the final product has high purity.The obtained product was characterized by NMR,IR,MS and was confirmed to be 4-[(6,7-dimethoxy-4-quinolinyl)oxy]aniline.The superior conditions obtained through the bench scale experiment was used to amplification experiment,which the yield of target product by five-steps reaction is 53.3% and the final product has high purity.