Crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy) (phenoxy) phosphoryl)amino)propanoate
AssigneeGilead Sciences, Inc.
InventorsKatrien Brak, Ernest A. Carra, Lars V. Heumann, Nate Larson
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Abstract
The present invention relates to novel salts and crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate for use in treating viral infections. In some embodiments, the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.
Claims44
A crystalline form selected from the group consisting of:
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 5.3°, 20.6°, and 22.7°;
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 4.1°, 8.2°, 17.1°, and 23.8°;
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 22.6°, 19.9°, and 14.1°;
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 15.9°, 22.6°, and 14.1°;
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 16.1°, 22.4°, and 12.7°;
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3 S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 16.7°, 12.6°, and 17.2°;
- and
- (S)-2-Ethylbutyl 2-(((S)-(((2R,3 S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate maleate Form I characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 16.3°, 4.6°, and 9.0°.
A method of preparing a crystalline form of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate (Formula I) characterized by an X-ray powder diffraction (XRPD) pattern comprising degree 2θ-reflections (±0.2° 2θ) at 22.3°, 16.9°, and 16.2°, comprising
- Contacting the Formula I and a solvent mixture comprising isopropanol and water, wherein the Formula I remains substantially insoluble in the solvent mixture, thereby preparing the crystalline form.
Dependencies are inferred from the claim text.