In recent years Mercachem worked with FORUM Pharmaceuticals on several discovery programs in the area of neurodegenerative diseases. Very challenging molecules were designed and synthesized in the course of this exciting collaboration.
Finding new, widely applicable methodology was a prerequisite for the success of discovery chemistry in these projects, in order to be able to probe the SAR around several structure classes.
Scientists from Mercachem and FORUM Pharmaceuticals now publish in Heterocycles on “Strategic and tactical approaches to the synthesis of 5,6-Dihydro-[1,2,4]oxadiazines”.
"In our project we needed an approach where the substituent on the 5-position could be selectively introduced and easily modified. Even though several synthetic methods have been described, the overall scope of those approaches was limited", says Johan Veerman, Group Leader at Mercachem.
Yorik Bruseker, explains: "Three methods were developed for the synthesis of substituted 5,6-dihydro-4H-[1,2,4]oxadiazines. For all methods the scope with respect to the substituents that could be introduced was explored. The condensation of a diamine with an imidate was the most versatile route and led to isolated yields up to 91%. This route is also suitable for the introduction of chirality on the C5 and C6 position of the oxadiazine rings and also allowed variation on the 3 and 4 position."