A novel bi-pharmacophore contained by-product found in the synthesis of landiolol

Aim To separate and determine the less polar compound in the epoxide-opening reaction with the amine.Methods During the synthesis of some derivatives having ultra short β_2-blocking activity,one less polar compound was always formed during the last epoxide-opening reaction with the amines.To clarify this phenomena,the synthesis of landiolol was selected as a model,the less polar by-product(4)was purified and its structure was identified with SCI-MS,HR-MS and NMR.Result and conclusion The primary amine attacked the epoxide two times in the epoxide-opening reaction and thus the novel bi-pharmacophore contained compound named as N-[2-(morpholine-4-carboxamido)ethyl]-3,3′-iminobis｛3-[4-(2-hydroxypropoxy)phenyl]propionic acid(2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester｝was formed.This finding will be helpful for optimizing the synthetic process and for the quality control of landiolol.This will also attract the attention of some synthetic chemists or pharmacists.