Synthetic Of Factor Xa Inhibitor Betrixaban And The Key Intermediate Of EGFR Inhibitor Erlotinib

This thesis contains two Parts:the synthesis of Betrixaban and the synthesis of the key intermediate of Erlotinib.Part Ⅰ:The synthesis of Betrixaban. This part analyzing the synthetic methods of Betrixaban reported previously, we designed a new route, starting from 5-methoxy-2-nitrobenzoic acid, followed by reduction with Pd/C and reaction with triphosgene, giving 5-methoxyisatoic anhydride, which was then subjected to the nucleophilic addition and acylation, finally affording Betrixaban in an overall yield of 55%. The synthetic route reported in this thesis is easy to perform and can be scaled up from commercially available materials in good yields with the benefit of reduced production cost and equipment requirements, which could be potentially used in industry.Part Ⅱ:The synthesis of the key intermediate of Erlotinib. This part summarized the synthetic routes of m-aminophenyl acetylene. m-Aminophenyl acetylene, the key intermediate of Erlotinib, was synthesized from m-nitrobenzaldehyde and CBr4 through Wittig reaction, debromination and reduction by zinc power, giving m-nitrophenyl acetylene in an overall yield of 69%.The structures of compounds were characterized by 1H NMR and 13C NMR.