Studies On The Synthesis Of 1,3-Diaryl-pyrazole-4-carboxyaldehyde Derivatives And Heterocyclic Drugs Gefitinib,Lamivudine

The thesis is divided into two parts, Synthesis of a series 1,3-Diaryl-pyrazole-4-carboxyaldehyde derivatives which are of interest as building blocks toconstruct focused libraries in drug discovery, dealing with the process develop-ment of an industrially applicable route for the synthesis of Gefitinib, a recentlymarketed drug for the treatment of Non-small cell lung cancer. And synthesis of afunctionalised 1,3-Oxathiolane moeity,a key intermediate of Lamivudine to Anti-hepatitis B virus.In the first part, various alkyl substituted phenylhydrazone intermediateswere first constructed by reaction of 1-Aryl-ethanones and Aryl-hydraz-ines inthe presence of Acetic acid. Then applications of Vilsmeier-Haack Reaction ,Synthesis of some 1,3-Diaryl-pyrazole-4-carboxyaldehyde derivatives.and inaccordance with the LC/MS of intermediate,the pyrazole's Vilsmeier-HaackReaction mechanism was discussed。In the second part, Two routes were explored in the synthesis of Gefitinib,Then an eight-step synthetic route to Gefitinib was adopted .The synthesis startedfrom commercially available 2-Amino-4,5-dimethoxy-benzoic acid methyl esterand Formamide by a sequence of reactions including quinazoline Synthesis,Selectivity deprotection of methoxy group, protection of hydroxy group,nucleophilic replacement, Gefitinib was eventually obtained in more than 10%yield without any complicated purification methods, Which is more suitable forindustrial production.The final product was fully characterized by HPLC-MS, H 1NMR, (13)~CNMR and DTA.Lamivudine is one of the only two kinds of medicines that are sanctioned...