Synthesis of alkynyl derivatives of substituted 4-anilinoquinazolines as coupling partners for the Huisgen [3+2] cycloaddition reaction with novel azides

CHED 275

Robert N. Hanson, r.hanson@neu.edu, Kristen Bailey, Adam Visentin, Anton Kozhushynan, and Helen Trinh Pham. Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115
In our Merck Scholars and student coop programs, undergraduates in the chemistry department have the opportunity to undertake significant research projects. As part of our program to develop targeting agents for nanoparticle based drug delivery systems using a module assembly approach, we selected the 6,7-dialkoxy-4-anilinoquinazolines as the scaffold for one of the targeting modules. This class of compounds possesses potent activity against growth factor receptor tyrosine kinases, thereby serving as a targeting mechanism. Structure activity relationships indicate that significant substituent tolerance is present at the 3-position of the aniline group as well as at the 6- and 7-alkoxy positions. In this presentation, we will describe the synthesis of new alkynylated derivatives of the 4-anilinoquinazolines and their coupling to a variety of azide-containing reagents.