Patent number: 11344565
Abstract: 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 LaCl3-2LiCl, LaCl3, CeCl3, NdCl3, or YCl3; 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.
Type:
Grant
Filed:
October 29, 2015
Date of Patent:
May 31, 2022
Assignee:
Gilead Sciences, Inc.
Inventors:
Steven Donald Axt, Pavel Robertovich Badalov, Katrien Brak, Silvio Campagna, Andrei Chtchemelinine, Edward Doerffler, Morin Mae Frick, Detian Gao, Lars V. Heumann, Brittanie Hoang, Willard Lew, Robert Ronald Milburn, Sean Timothy Neville, Bruce Ross, Erik Rueden, Robert William Scott, Dustin Siegel, Andrew C. Stevens, Clarissa Tadeus, Tiago Vieira, Andrew W. Waltman, Xianghong Wang, Mark Charles Whitcomb, Lydia Wolfe, Chia-Yun Yu
