A Scalable Synthesis of MN-447, an Antagonist for Integrins α_vβ₃and α_IIbβ₃

(2S)-Benzenesulfonylamino-3-[3-methoxy-4-{4-(1,4,5,6-tetrahydro-pyrimidin-2-ylamino)piperidin-1-yl}benzoylamino]propionic acid, MN-447, is a potent antagonist of the integrins alpha(v)beta(3) and alpha(IIb)beta(3)-Herein, we report a novel synthetic protocol that produces MN-447 in an overall yield of 45%. This protocol, when compared with the original synthetic route for MN-447, is more cost-effective, requires fewer steps, does not require chromatographic purification of intermediates and MN-447, and increases the overall yield by 35%. This report focuses on the synthetic strategies that were developed for this protocol. Now, the large quantities of MN-447 that are needed for preclinical and toxicological studies can be readily obtained.