1355049-92-1Relevant articles and documents
Practical Remdesivir Synthesis through One-Pot Organocatalyzed Asymmetric (S)-P-Phosphoramidation
Gannedi, Veeranjaneyulu,Villuri, Bharath Kumar,Reddy, Sivakumar N.,Ku, Chiao-Chu,Wong, Chi-Huey,Hung, Shang-Cheng
, p. 4977 - 4985 (2021)
Remdesivir, an inhibitor of RNA-dependent RNA polymerase developed by Gilead Sciences, has been used for the treatment of COVID-19. The synthesis of remdesivir is, however, challenging, and the overall cost is relatively high. Particularly, the stereoselective assembly of the P-chirogenic center requires recrystallization of a 1:1 isomeric p-nitrophenylphosphoramidate mixture several times to obtain the desired diastereoisomer (39%) for further coupling with the d-ribose-derived 5-alcohol. To address this problem, a variety of chiral bicyclic imidazoles were synthesized as organocatalysts for stereoselective (S)-P-phosphoramidation employing a 1:1 diastereomeric mixture of phosphoramidoyl chloridates as the coupling reagent to avoid a waste of the other diastereomer. Through a systematic study of different catalysts at different temperatures and concentrations, a mixture of the (S)- and (R)-P-phosphoramidates was obtained in 97% yield with a 96.1/3.9 ratio when 20 mol % of the chiral imidazole-cinnamaldehyde-derived carbamate was utilized in the reaction at -20 °C. A 10-g scale one-pot synthesis via a combination of (S)-P-phosphoramidation and protecting group removal followed by one-step recrystallization gave remdesivir in 70% yield and 99.3/0.7 d.r. The organocatalyst was recovered in 83% yield for reuse, and similar results were obtained. This one-pot process offers an excellent opportunity for industrial production of remdesivir.
ISOMORPHS OF REMDESIVIR AND METHODS FOR SYNTHESIS OF SAME
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Paragraph 0082, (2021/06/04)
A new isoform of 2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3/4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate (Remdesivir) having increased water solubility is disclosed, along with methods
Compound containing guanidyl group, and preparation method and application thereof
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Paragraph 0122-0129, (2021/08/07)
The invention provides a preparation containing a guanidino compound and used for treating pneumoviridae virus infection, a method, a compound of a formula I, and a method and an intermediate for synthesizing the compound of the formula I.