A Concise Route to MK-4482 (EIDD-2801)

• DOI: 10.26434/chemrxiv.12818327.v1
• Publication Date: 2020-08-19T05:13:19Z
• Authors: Natarajan Vasudevan; Grace P. Ahlqvist; Catherine P. McGe...; Dinesh J. Paymode; Flavio S. P. Cardoso; Tobias Lucas; Jule-Phillip Dietz; Till Opatz; Timothy F. Jamison; B. Frank Gupton; David Snead
• Keywords: Cytidine; Transamination; Hydroxylamine; Nucleobase

A two-step route to MK-4482 (EIDD-2801, 1 ) was developed consisting of an esterification and hydroxamination cytidine. The reactions can be conducted in either order with overall yields 67% (first step—esterification) 37% step—hydroxamination). Selective the nucleoside’s primary alcohol by enzymatic means eliminated need for diol protection/deprotection, direct transamination hydroxylamine precluded necessity activating nucleobase amine coupling. This results a significant advancement over reported synthesis which is formed at best 17% yield. step count reduced from five transformation two, more expensive uridine replaced available