稳定同位素标记氯丙那林-D6的合成

Synthesis of stable isotope labeled clorprenaline-D6

氯丙那林-D6的合成是以邻氯苯乙酮和氘代丙酮为起始原料,邻氯苯乙酮与溴化铜通过溴化反应得到α-溴代邻氯苯乙酮,氘代丙酮经过还原、溴化、胺化、肼解、碱解得到异丙胺-D6,α-溴代邻氯苯乙酮和异丙胺-D6通过胺化、还原"一步法"合成得到稳定同位素标记的氯丙那林-D6,以投入的异丙胺-D6的物质的量计算,氯丙那林-D6产率为26.2%。目标产物结构经NMR、MS、HPLC和X-ray单晶衍射等表征确认,液相色谱纯度大于98%,氘同位素丰度为99.7%atom D,可作为内标试剂用于氯丙那林残留的检测。

Clorprenaline-D6 was synthesized with 2’-chloroacetophenone and acetone-D6(99.9%atom D)as starting materials.Firstly,2-bromo-2’-chloroacetophenone was obtained by a bromination reaction of 2’-chloroacetophenone with copper bromide.Isopropyl-D6-amine was synthesized by reduction,bromination,amination,hydrazinolysis and alkali hydrolysis reaction from acetone-D6.Then,stable isotope labeled clorprenaline-D6 was synthesized by a one-pot method of amination and reduction with2-bromo-2’-chloroacetophenone and isopropyl-D6-amine.The yield of targeted product based on the amount of substance of isopropyl-D6-amine was 26.2%.The targeted product was characterized by NMR,MS,HPLC and single-crystal X-ray diffraction analysis.Its chemical purity was above 98%,and isotopic abundance was 99.7%(atom D).The prepared clorprenaline-D6 can be used as an internal standard reagent for the determination of residual clorprenaline.