Synthesis Of New Anti-obesity Drug Rimonabant

Obesity is rapidly becoming one of the major health threats facing our people,it is estimated to be associated with over 2,500,000 excess deaths every year. Obesity treatment demands combined measures, in which drug is a significant therapeutic tool of the total . Rimonabant,a selective CB1 antagonist,has been in phaseâ…¢clinical trials for treatment of obesity and can decrease appetite and weight in humans.No serious side effect of rimonabant has been reported yet.Rimonabant is also being developed for the treatment of other multiple cardiometabolic risk factors, including smoking and drug dependence.The synthesis routes of Rimonabant were researched in this thesis. Chlorobenzene was selected as the raw material, through acylation, bromination, substitution, condensation, cyclization, hydrolization, amidation,then the target product Rimonabant was prepared in total yield 15.4%. During the synthesis of Rimonabant, the key intermediates,1-aminopiperidine, 2,4-dichlorophenylhydrazine and 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid were synthesized in higher yield, shorter period and higher economic returns because of the improvement that made to the routes.We also did some studies about the condensation between 4-chloropropiophenone and diethyl oxylate with sodium hydride and sodium ethylate. This is very useful for sodium hydride to replace LiHMDS and LDA in later experiments.The structures of key intermediates and target product Rimonabant were confirmed by the analysis of 1H-NMR data.