A concise route to MK-4482 (EIDD-2801) from cytidine
N. Vasudevan, Grace P. Ahlqvist, Catherine P. McGeough, Dinesh J. Paymode, Flávio S. P. Cardoso, Tobias Lucas, Jule-Phillip Dietz, Till Opatz, Timothy F. Jamison, Frank Gupton, David R. Snead
Abstract
A two-step route to MK-4482 (EIDD-2801, 1) was developed consisting of an esterification and hydroxamination of cytidine. The selective acylation and direct amination eliminate the need for protecting and activating groups and proceed in overall yield of 75%, a significant advancement over the reported yield of 17%. The step count is reduced from five transformations to two, and expensive uridine is replaced with the more available cytidine.
Topics & Concepts
CytidineChemistryCombinatorial chemistryBiochemistryEnzymeCancer therapeutics and mechanismsBiochemical and Molecular ResearchPharmacogenetics and Drug Metabolism