Synthetic Study Of Anti-aids Drug Abacavir Sulfate And Its Synthesis Technics Research

Abacavir,(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1-cyclopent-2-enyl]me thanol,was developed by Glaxo Smith Kline company as a Human Immunodeficiency Virus(HIV)Nucleoside Reverse Transcriptase inhibitors and now is primarily used to treat Acquired Immunodeficiency Syndrome(AIDS).In this paper,HIV Nucleoside Reverse Transcriptase Inhibitors were reviewed many reported literatures,and then the synthetic route of Abacavir was carried out detailedly.Firstly,(1S,4R)-4-amino-2-cyclohexene-1-methanol was synthesized from 2-Azabicyclo [2.2.1] hept-5-en-3-one,through four steps including amino-protection,reduction,amino-deprotection and chiral separation,giving total yield 42.32% and ee value 99.43%.Secondly,N-(2-amino-4,6-dichloro-5-pyrimidiyl)formamide was synthesized from dietylaminomalonate hydrochloride and guanidine carbonate,through two steps including cyclization and Vilmeier reaction,giving total yield 82.62% and purity 99.62%.Thirdly,Abacavir sulfate was synthesized from(1S,4R)-4-amino-2-cyclohexene-1-methanol and N-(2-amino-4,6-dichloro-5-pyrimidiyl)formamide,through four steps including condensation,cyclization,and salt formation,giving total yield about 90% and purity above 99%.Finally,the optimized conditions of this synthetic route were obtained,through observing and studying on reaction time,temperature,material ratio and screen of the solvent.The structures of part intermediates and final product were confimed by NMR and MS spectra.This method was suitable for industrial process,due to simple operation,easy-obtaining raw materia.