Y. Xinlin
2007
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Journal
Fine chemicals
Abstract
Synthesis of saquinavir,an HIV protease inhibitor,was researched via convergence method.In the process of synthesis of one intermediate(S)-4-amino-4-oxo-2-(quinoline-2-carboxamido)butanoic acid,quinaldine-2-carboxylic acid reacted with thionyl chloride under reflux for 8 h to give its acyl chloride as an activating reagent in 95.0% yield.The intermediate was prepared in the water with a yield of 82.0%.Benzyl(S)-1-((S)-oxiran-2-yl)-2-phenylethylcarbamate reacted with(3S,4aS,8aS)N-tert-butyl-decahydroisoquinoline-3-carboxamide in the presence of silica gel at room temperature for 72 h,giving benzyl(2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)-decahydroisoquinoline-2((1H)-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate,which,without purification,was mixed with Pd/C(w(Pd)=10%) and stirred in hydrogen atmosphere at room temperature for 12 h to remove the benzyloxycarbonyl group,and recrystallized in acetontrile to get(3S,4aS,8aS)-2-((2R,3S)-3amino-2-hydroxy-4-phenylbutyl)-N-tert-butyl-decahydroisoquinoline3-carboxamide,another intermediate,with a yield of 87.0%.N-Hydroxysuccinimide was applied to the reaction of two intermediates to get the target product in 82.0% yield.