Identification of new process-related impurity in the key intermediate in the synthesis of TCV-116 was written by Testen, Ana;Plevnik, Miha;Stefane, Bogdan;Cigic, Irena Kralj. And the article was included in Acta Pharmaceutica (Warsaw, Poland) in 2019.Synthetic Route of C33H34N6O6 This article mentions the following:
Development of safe and effective drugs requires complete impurity evaluation and, therefore, knowledge about the formation and elimination of impurities is necessary. During impurity profiling of a key intermediate during synthesis of candesartan cilexetil (1-(((cyclohexyloxy)carbonyl) oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl) methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, TCV-116), a novel compound, which had not been reported previously, was observed Structural elucidation of impurity was achieved by liquid chromatog. hyphenated to different high resolution mass analyzers. Based on exact mass measurements and fragmentation pattern, a chloro alkyl carbonate ester analog of the intermediate was identified. Structure of the impurity was confirmed by mass spectro-metric and NMR analyses of the target substance. Identified impurity could represent a hazard if it is transferred to the final API stage and its presence should be kept below allowed limits. Further investigation could reveal whether bis(1-chloroethyl) carbonate is a precursor to impurity formation. Therefore, synthesis should be regulated so as to minimize impurity production Anal. of the final product indicated that the amount of impurity did not exceed 50 mg L-1, which represents the detection limit, determined according to the signal/noise ratio. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Synthetic Route of C33H34N6O6).
1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Synthetic Route of C33H34N6O6
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem