A new
and efficient synthetic process for the synthesis of an endothelin
receptor antagonist, bosentan monohydrate, involves the coupling of p-tert-butyl-N-(6-chloro-5-(2-methoxy
phenoxy)-2,2′-bipyrimidin-4-yl)benzenesulfonamide (7) with (2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol (14) as a key step. This new process provides desired bosentan monohydrate
(1) with better quality and yields. Our new methodology
consists of technical innovations/improvements which totally eliminate
the probability for the formation of critical impurities such as pyrimidinone 8, dimer impurity 9, and N-alkylated impurity 13 in the final drug substance.
An efficient and improved synthesis of a novel anti‐inflammatory drug, Lifitegrast 1 is described from Benzofuran‐6‐carboxylicacid. This synthetic approach avoided the racemization, formation of dimer impurities and furnished higher overall yield (79 %) with high purity. The key step of the synthesis involves tertiary butylester protection of the aminoacid fragment, which was hydrolyzed in further stages under mild acidic conditions. The critical process parameters were thoroughly studied for protection and deprotection of the tertiary butyl functional group. The attractive features of synthesis are the usage of commercially cheaper and eco‐friendly reagents suitable for multi kilo scale synthesis of Lifitegrast 1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.