Gilead Sciences, Inc.

Detian Gao

Lars V Heumann

Tiago Vieira

Robert Ronald Milburn

Andrew C Stevens

Pavel Robertovich Badalov

Sean Timothy Neville

Dustin S Siegel

Bing Shi

Xianghong Wang

Edward Doerffler

Robert William Scott

Bruce Ross

Chiajen Lai

Willard Lew

Andrew W Waltman

Katrien Brak

Stacy Bremner

Nolan Griggs

Andrei Chtchemelinine

Mark Charles Whitcomb

Todd A Wenderski

Morin Mae Frick

Sankar Mohan

Silvio Campagna

Brittanie Hoang

Clarissa Tadeus

Lydia Wolfe

Chia-Yun Yu

Erik Rueden

Steven Donald Axt

Matthew R Chin

Nicholas A J Uhlig

The present disclosure generally describes methods of preparing 1'-cyano nucleosides, such as a compound of Formula (I). For example, the compound of Formula (I) can be prepared from a compound of Formula (II-a) in a flow reactor.

Methods of preparing 1'-cyano nucleosides

Provided are methods of preparing compounds and pharmaceutical compositions comprising a compound Formula VIII for treating Filoviridae virus infections. In one aspect, the compound of Formula VIII is formed from a reaction mixture comprising the compound of Formula IX, the compound of Formula X, a coupling agent such as magnesium chloride and a non-nucleophilic base such as diisopropylethylamine. The compound of Formula IX can be formed from a compound of Formula V and a cyanating agent. The compound of Formula V can be synthesized from a reaction mixture comprising a deprotonating agent such as phenylmagnesium chloride; a silylating agent such as chlorotrimethylsilane; a coupling agent such as isopropylmagnesium chloride, an additive such as LaCl-2LiCl, LaCl, CeCl, NdCl, or YCl; a compound of Formula VI; and 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine. The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Methods for the preparation of ribosides

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Edmonton, Canada

Detian Gao