Crystalline forms of 2-(tert-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol fumarate salt
AssigneeCognition Therapeutics, Inc.
InventorSteven A. Weissman
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Abstract
The present disclosure describes crystalline forms of 2-(tert-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol fumarate salts and pharmaceutical compositions of same. Also described are methods of using the crystalline forms treating Alzheimer's Disease, Dementia with Lewy Bodies and Dry age-related macular degeneration in a subject in need thereof, comprising administering the crystalline form to the subject. Methods of making the solid forms are also described.
Claims30
2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E characterized by an X-ray powder diffraction pattern (XRPD) comprising characteristic 2θ peaks at 9.69, 16.51, 17.23, 19.02, 25.10, and 26.49° (±0.2°).
A method of treating a disease selected from the group consisting of Alzheimer's Disease, Dementia with Lewy Bodies and Dry age-related macular degeneration in a subject in need thereof, comprising treating the subject with 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E characterized by an X-ray powder diffraction pattern (XRPD) comprising characteristic 2θ peaks at 9.69, 16.51, 17.23, 19.02, 25.10, and 26.49° (±0.2°).
A process for preparing 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E characterized by an X-ray powder diffraction pattern (XRPD) comprising characteristic 2θ peaks at 9.69, 16.51, 17.23, 19.02, 25.10, and 26.49° (±0.2°), comprising:
- a) heating 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol, and fumaric acid in ethanol to form a solution;
- b) slowly adding water to the solution of step a) to form a slurry;
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- c) slowly cooling the slurry to obtain the 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E.
A process for preparing 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E characterized by an X-ray powder diffraction pattern (XRPD) comprising characteristic 2θ peaks at 9.69, 16.51, 17.23, 19.02, 25.10, and 26.49° (±0.2°), comprising:
- a) heating 1 equivalent (moles) of 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol, and 0.5 equivalents (moles) of fumaric acid in ethanol at about 55° C. to form a solution;
- b) clarifying the solution through a cartridge, collecting the solution and readjusting the temperature of the solution to about 50° C.;
- c) adding water to the solution in step b) over a period of about 1 hour, followed by the addition of about 1% of seed crystals to form a slurry, wherein the amount of water added achieves about a 90/10 v/v ethanol to water mixture;
- d) aging the slurry of step c) for about 90 minutes at about 50° C.;
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- e) cooling the slurry of step d) to 20° C. over about 11 hours;
- to obtain the 2-(t-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol hemi-fumarate dihydrate salt crystal form E.
Dependencies are inferred from the claim text.