Synthetic Study Of Intermediates For Anti-Aids Drug-Ritonavir

Acquired immunodeficiency syndrome (AIDS) is a sort of contagious disease caused by human immunodeficiency virus (HIV). The common therapeutic drug can be classified into three categories, nucleotide reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor and proteinase inhibitor, among which ritonavir is one of quite effective proteinase inhibitor. After retrosynthetic analysis, comprehensive literature search and analysis, we divide ritonavir into three sections. This thesis focused on the synthesis of ((5-Thiazoyl)methyl)-(4-nitrophenyl)- carbonate and N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L- valine methyl ester as two intermediates .The effects of moisture, catalyst, reaction temperature and the mole ratio of materials on yield or purity to synthesis ((5-Thiazoyl)methyl)-(4-nitrophenyl)- carbonate were investigated in this thesis. The reaction mechanism has also been presented. This thesis brings out a new separation process, coupling of reaction and solvating-out crystallization, to purify ((5-Thiazoyl)methyl)-(4-nitrophenyl) carbonate, and make a further investigate to this new process. With the new process product purity could attain 99.81% from initial material whose purity is 93.42%and yield could reach 93.73 %. The process using column chromatography refered in references has been avoided.N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine meth- yl ester has been initiatively synthesized in this thesis. The synthesis involved five steps and the yield rate of each step has attained the level mentioned in references. The reaction mechanism was also investigated in detail. Part of synthesis processes and technology of after treatment were improved.The structure of intermediates and the target product were confirmed by analysis of 1H-NMR data.