Isomorphs of Remdesivir and methods for synthesis of same
AssigneeAnzalp Pharmasolutions Pvt. Ltd.
InventorsVinay Shankar Tripathi, Akshay Nikhil Patel
Life of this patent
Estimating the term…
Abstract
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 for making the same. Also disclosed are solid and liquid pharmaceutical compositions suitable for treating viral infections such as Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, or Paramyxoviridae viral infections which contain an effective amount of Remdesivir prepared according to the inventive method and the use of those compositions for treating such viral infections.
Claims4
A method for the synthesis of Remdesivir, which comprises:
- (a) reacting (3R,4R,5R)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)dihydrofuran-2(3H)-one with a halo-pyrazole in presence of boron trichloride in an organic solvent at room temperature;
- (b) cyanating (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol;
- (c) hydrolysing (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-carbonitrile in presence of boron trichloride;
- and (d) condensing (3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile with 2-ethylbutyl (chloro(phenoxy)phosphoryl)-L-alaninate.
The method according to claim I, wherein (d) is replaced by:
- (d1) reacting (3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile with 2,2 dimethoxy propane in presence of PTSA and isopropylacetate;
- and (d2) reacting (3aR,4R,6R,6aR)-4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[5 3,4-d][1,3]dioxole-4-carbonitrile with t-BuMgCl in presence of 2-ethylbutyl (chloro(phenoxy)phosphoryl)-L-alaninate.
Dependencies are inferred from the claim text.