Crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]methanone
AssigneeExelixis, Inc.
InventorAdrian St. Clair Brown
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Abstract
This disclosure relates to the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to pharmaceutical compositions comprising the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to methods of treating cancers comprising administering to a patient in need thereof the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone.
Claims9
A crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone having the formula:
- wherein the crystalline fumarate salt is designated as Form A.
A crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone, designated as Form A, wherein said salt is characterized by a solid state 13C NMR spectrum having three or more peaks selected from 175.3, 173.6, 117.5, 155.5, and 153.5, ±0.2 ppm.
A crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone, designated as Form A, wherein said salt is characterized by a powder x-ray diffraction pattern (CuKαλ=1.5418 Å) comprising three or more 2θ values selected from 4.6, 12.1, 13.2, 13.6 and 14.5±0.2°2θ, wherein measurement of the crystalline fumarate salt is at room temperature.
A crystalline fumarate salt of (S)[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-l-yl]-methanone of, wherein said salt is at least 90 weight % Form A.
A pharmaceutical composition comprising a crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-l-yl]-methanone, designated as Form A;
- and a pharmaceutically acceptable excipient.
A method of treating BRAF V600 mutant melanoma in a subject, the method comprising administering to the subject in need of the treatment a therapeutically effective amount of a crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone alone or in combination with vemurafenib.
A process for preparing a crystalline fumarate salt of Compound I designated as Form A, comprising:
- adding fumaric acid dissolved in a solvent to a mixture of Compound I dissolved in a solvent to form the crystalline fumarate salt of Compound I designated as Form A;
- and
- collecting the resulting crystals of the crystalline fumarate salt of Compound I designated as Form A;
- wherein Compund I is (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl]-methanone.
Dependencies are inferred from the claim text.