Abstract The synthesizing route of Azelnidipine was studied and an appropriate synthesizing process was designed for industrialization.Azelnidipine was synthesized by Michael Reaction of(1-benzhydryl-3-azetidinyl)3,3-diaminoacrylate(Ⅲ) and isopropyl 2-(3-nitrobenzylidene) acetoacetate(Ⅳ).The yield of Azelnidipine was 86%,with purity of 99.5% by HPLC.Compound(Ⅳ) was synthesized by 3-Nitrobenzaldehyde and isopropyl acetoacetate,the yield was 76%.1-Benzhydryl-3-azetidinol(Ⅰ) was synthesized by benzhydrylamine and epichlorohydrin,the yield was 58%.(1-Benzhydryl-3-azetidinyl) cyanoacetate(Ⅱ) was synthesized by esterification of compound(Ⅰ) with cyanoacetic acid,the yield was 90%.Next,compound(Ⅲ) was prepared by alcoholysis and ammonolysis of compound(Ⅱ),the yield was 85%.The total yield of this route was 30%,higher than those of other synthesis routes reported.Azelnidipine was recrystallized from benzene and n-hexane to α-crystal form,and from chlorobenzene to β-crystal form.The intermediates and final products were characterized by HPLC and(()~1HNMR.)
CHEN Guo-bin~1,SONG Jian~1,YANG Xun~2,ZHANG Xiao-xing~1.Synthesis of Azelnidipine and Its Crystallization[J] Chemcial Industry and Engineering, 2009,V26(1): 15-18
2009, Vol. 26 
