Gilead Sciences, Inc.

Sean Timothy Neville

Nolan Griggs

Olga Viktorovna Lapina

Lars V Heumann

Peter C Fung

Jeffrey N Hemenway

Tiago Vieira

Robert Ronald Milburn

Anna Michelle Wagner

Andrew C Stevens

Pavel Robertovich Badalov

Derek M Dalton

Matthew M Logan

Hui-Wen Shih

Bryan J Reynolds

Detian Gao

Dustin S Siegel

Bing Shi

Xianghong Wang

Edward Doerffler

Robert William Scott

Bruce Ross

Chiajen Lai

Willard Lew

Andrew W Waltman

Katrien Brak

Silvio A Campagna

Stacy Bremner

Andrei Chtchemelinine

Sankar Mohan

Mark Charles Whitcomb

Todd A Wenderski

Morin Mae Frick

Clarissa Tadeus

Silvio Campagna

Brittanie Hoang

Matthew R Chin

Nicholas A J Uhlig

Lydia Wolfe

Chia-Yun Yu

Erik Rueden

Steven Donald Axt

Dustin Siegel

Erick Rueden

Tiago Viera

Disclosed herein are novel solid forms of FXR agonists. The disclosure also relates to pharmaceutical compositions containing one or more of the solid forms disclosed herein, as well as methods of using the solid forms in the treatment of conditions mediated by FXR. The disclosure also relates to methods for obtaining such solid forms.

Solid forms of FXR agonists

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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San Mateo, CA, United States of America

Sean Timothy Neville