Crystalline forms of spleen tyrosine kinase inhibitor ski-o-703
AssigneeOscotec Inc.
InventorsPingyun Chen, Min-Woo Kim, Song-Eun Park, Dong-Sik Jung, Yutae Kim, Young Chun Jung
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Abstract
Disclosed are crystalline forms of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (SKI-O-703, “Compound 1”), their process of manufacture, pharmaceutical compositions, and methods for using the inventive crystal forms for the treatment of diseases such as cancer, autoimmune diseases, neurodegenerative diseases, and disorders associated with the dysfunction of tyrosine kinase.
Claims25
A monohydrate crystalline Form J of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), characterized by an X-ray powder diffraction (XRPD) pattern, comprising signals at 14.1, 16.9, 18.1, 19.9, 15.3, and 26.5 2θ±0.2 °2θ as determined on a diffractometer using Cu-Kα radiation at a wavelength of 1.54 Å.
A monohydrate crystalline Form F of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), characterized by an X-ray powder diffraction (XRPD) pattern comprising signals at 5.6, 16.7, 18.9, 20.3, 24.0, and 29.3 °2θ±0.2 θ2θ as determined using a diffractometer using Cu-Kα radiation at a wavelength of 1.54 Å.
A partial hydrate crystalline Form N of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), characterized by an X-ray powder diffraction (XRPD) pattern comprising signals at 14.5, 16.7, 17.1, 19.4, 20.2, 24.1, and 25.7 °2θ±0.2 °2θ as determined using a diffractometer using Cu-Kα, radiation at a wavelength of 1.54 Å.
An anhydrate crystalline Form M of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), characterized by an X-ray powder diffraction (XRPD) pattern comprising signals at 16.3, 18.2, 19.9, 20.4, 23.5, and 26.0 °2θ±0.2 °2θ as determined using a diffractometer using Cu-Kα, radiation at a wavelength of 1.54 Å.
Crystalline Form E of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), characterized by an X-ray powder diffraction (XRPD) pattern substantially as shown in FIG. 7.
A method for synthesizing crystalline Form J of cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone bis-mesylate (“Compound 1”), comprising:
- (a) dissolving cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone in warm DMSO whereby a solution is formed;
- (b) contacting the solution from (a) with a DMSO solution of methanesulfonic acid whereby a second solution is formed;
- (c) adding water and then acetone to the second solution from (b) whereby a third solution is formed;
- and
- (d) cooling the third solution from (c) whereby Form J is formed.
Dependencies are inferred from the claim text.