Amenamevir by Ugi-4CR

We report a concise, convenient and sustainable synthesis of the approved anti-herpes zoster drug, Amenamevir. Based on the Ugi-4CR, our approach can access Amenamevir by a simple, rapid and one-pot synthesis. Compared to other reported syntheses, ours is more sustainable, shorter, and higher yielding. The X-ray crystal structures of key intermediate 3-(4-isocyanophenyl)-1,2,4-oxadiazole 4 and Amenamevir are reported for the first time. Computational retrosynthesis of Amenamevir using four popular freeware could recapitulate the described multi-step approaches but disappointingly did not propose our one-pot synthesis.