Morphic forms of 4-amino-7-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide and uses thereof
The present disclosure relates to crystalline morphic forms of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. The morphic form can be a stable hemihydrate crystalline form.
1. Crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate.
2. A crystalline hemihydrate form (“Form A”) of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, wherein said Form has a powder X-ray diffraction pattern comprising a peak at a diffraction angle (20) of about 26.2°, wherein said powder X-ray diffraction pattern is obtained using Cu Kα1 X-rays at a wavelength of 1.5406 Å.
3. The crystalline hemihydrate of claim 2 , wherein the morphic form is further characterized by an endothermic peak at about 231° C. as measured by differential scanning calorimetry.
4. The crystalline hemihydrate form of claim 2 , further characterized by a mass loss of about 2.4% between a temperature of about 110° C. and 220° C. as measured by thermogravimetric analysis.
5. The crystalline hemihydrate form of claim 2 , further characterized by a PXRD pattern substantially similar to that set forth in FIG. 1A .
6. The crystalline hemihydrate form of claim 2 , further characterized by a PXRD pattern substantially similar to that set forth in FIG. 1B .
7. The crystalline hemihydrate form of claim 2 , further characterized by a TG-FTIR profile substantially similar to that set forth in FIG. 8 .
8. The crystalline hemihydrate form of claim 2 , further characterized by a DSC profile substantially similar to that set forth in FIG. 15 .
9. The crystalline hemihydrate form of claim 2 , further characterized by a DVS profile substantially similar to that set forth in FIG. 20A .
10. The crystalline hemihydrate form of claim 2 , further characterized by a DVS profile substantially similar to that set forth in FIG. 20B .
11. The crystalline hemihydrate form of claim 2 , wherein the morphic form is substantially non-hygroscopic.
12. A method of preparing a crystalline hemihydrate form of 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide comprising:
recrystallizing the 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide from a solvent having a water activity of at least about 0.18.
13. A pharmaceutical composition comprising the crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate of claim 1 , and a pharmaceutically acceptable carrier.
14. A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline 4-amino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide hemihydrate of claim 1 .
15. A pharmaceutical composition comprising the crystalline hemihydrate form of claim 2 , and a pharmaceutically acceptable carrier.
16. A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline hemihydrate form of claim 2 .