WO2014110259A1 - Solid forms of a jak inhibitor - Google Patents

Abstract

The present invention relates to solid state forms of JAK inhibitor (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide (Compound 1) including solvates, salts, co-crystals, and an amorphous form thereof. The present invention also provides pharmaceutical compositions comprising these solid forms of Compound 1 and methods of treating a JAK mediated disease therewith.

Description

SOLID FORMS OF A JAK INHIBITOR

CROSS REFERENCE TO RELATED APPLICATION

[0001] The present PCT Application claims the benefit of U.S. Application Serial No.

61/750,433, filed on January 9, 2013. This application is hereby incorporated by reference in its entirety.

TECHNICAL FIELD OF THE INVENTION

[0002] The present invention relates to solid state forms of JAK inhibitor (R)-2-(2-(lH- pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2- trifluoroethyl)butanamide, pharmaceutical compositions thereof, and methods therewith.

BACKGROUND OF THE INVENTION

[0003] The Janus kinases (JAK) are a family of tyrosine kinases consisting of JAK1, JAK2, JAK3 and TYK2. The JAKs play a critical role in cytokine signaling. The down-stream substrates of the JAK family of kinases include the signal transducer and activator of transcription (STAT) proteins. JAK/STAT signaling has been implicated in the mediation of many abnormal immune responses such as allergies, asthma, autoimmune diseases such as transplant rejection, rheumatoid arthritis, amyotrophic lateral sclerosis and multiple sclerosis as well as in solid and hematologic malignancies such as leukemias and lymphomas. JAK2 has also been implicated in myeloproliferative disorders, which include polycythemia vera, essential thrombocythemia, chronic idiopathic myelofibrosis, myeloid metaplasia with myelofibrosis, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome and systematic mast cell disease.

[0004] Compounds described as kinase inhibitors, particularly the JAK family kinases, are disclosed in WO 2005/095400 and WO 2007/084557 the entire contents of each of which are incorporated herein by reference. Also disclosed in these publications are processes and intermediates for the preparation of these compounds.

[0005] (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2- trifluoroethyl)butanamide (Compound 1) is a potent and selective JAK inhibitor. Compound 1 is useful for treating or reducing the severity of symptoms of one or more JAK mediated diseases (e.g., rheumatoid arthritis, psoriasis, vasculitis, uveitis, myositis, Sjogren's disease, scleroderma lung disease, bronchiolitis, idiopathic pulmonary fibrosis, Guillain-Barre' syndrome (GBS), chronic inflammatory demyelinating polyradiculopathy (CIDP), multifocal motor neuropathy (MMN), Lewis-Sumner syndrome, sarcoidosis, celiac disease, monoclonal gammopathy, amyloidosis, cryoglobulinemia, ulcerative colitis, systemic lupus erythematosis, and the like, or any combination thereof) in a patient.

[0006] Accordingly, there is a need for stable solid forms of JAK inhibitors, such as

Compound 1.

[0007] There is a need for methods of treating JAK-mediated diseases using such JAK inhibitors.

[0008] There also remains a need for economical processes for the preparation of these solid forms.

SUMMARY OF THE INVENTION

[0009] The present invention relates to solid forms of (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3- yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide ("Compound 1 ") having the structure below:

Compound 1

[0010] The solid forms of Compound 1 and pharmaceutically acceptable compositions thereof are useful for treating or lessening the severity of a variety of JAK mediated diseases.

[0011] In one aspect, the invention also provides a method of treating or lessening the severity of a JAK-mediated disease (e.g., rheumatoid arthritis (RA), psoriasis, ulcerative colitis (UC), systemic lupus erythematosis (SLE), or the like, or any combination thereof) in a patient comprising administering to the patient one of the compositions (e.g., solid forms) as defined herein.

[0012] In certain embodiments, the disease is RA or psoriasis.

[0013] Another aspect of the present invention provides a pharmaceutical composition comprising a solid form of Compound 1 (as described herein) and a chemotherapy agent (e.g., methotrexate or the like, or any combination thereof).

[0014] In one aspect the present invention provides a solid form of a solvate of Compound 1, wherein the solvate comprises Compound 1 and a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran (THF), 2-methyl tetrahydrofuran, or 1,4-dioxane. [0015] In some embodiments, the present invention provides a solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI . In some embodiments, solid Form XI is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 13.3 ± 0.2, 14.1 ± 0.2, 15.4 ± 0.2, 19.3 ± 0.2, and 25.0 ± 0.2 in an X-ray powder diffraction pattern. In other embodiments, solid Form XI is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.6 ± 0.2, 23.4 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern.

[0016] In some embodiments, the present invention provides a solid form of an ethyl acetate solvate of Compound 1 designated as Form X2. In some embodiments, the solid Form X2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ± 0.2, 1 1.9 ± 0.2, and 24.0 ± 0.2 in an X-ray powder diffraction pattern. In other embodiments, the solid Form X2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 18.5 ± 0.2 and 28.1 ± 0.2 in an X-ray powder diffraction pattern.

[0017] In some embodiments, the present invention provides a solid form of a methyl acetate solvate of Compound 1 designated as Form X3. In some embodiments, the solid Form X3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 11.1 ± 0.2, 12.0 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X3 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.1 ± 0.2 and 29.5 ± 0.2 in an X-ray powder diffraction pattern.

[0018] In some embodiments, the present invention provides a solid form of an N-methyl pyrrolidone solvate of Compound 1 designated as Form X4. In some embodiments, the solid Form X4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.9 ± 0.2, 17.4 ± 0.2, 19.1 ± 0.2, and 24.4 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.9 ± 0.2 and 27.0 ± 0.2 in an X-ray powder diffraction pattern.

[0019] In some embodiments, the present invention provides a solid form of a

tetrahydrofuran solvate of Compound 1 designated as Form X5. In some embodiments, the solid Form X5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.9 ± 0.2, 16.1 ± 0.2, 18.7 ± 0.2, 22.3 ± 0.2, and 23.7 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ± 0.2 and 24.5 ± 0.2 in an X-ray powder diffraction pattern.

[0020] In some embodiments, the present invention provides a solid form of a

2-methyltetrahydrofuran solvate of Compound 1 designated as Form X6. In some embodiments, the solid Form X6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.2 ± 0.2, 15.2 ± 0.2, 22.6 ± 0.2, and 23.0 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1 ± 0.2, 11.8 ± 0.2, 16.0 ± 0.2, 17.8 ± 0.2, 18.6 ± 0.2, 19.4 ± 0.2, 20.0 ± 0.2, and 20.7 ± 0.2 in an X-ray powder diffraction pattern.

[0021] In some embodiments, the present invention provides a solid form of a 1,4-dioxane solvate of Compound 1 designated as Form X7. In some embodiments, the solid Form X7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.5 ± 0.2, 15.7 ± 0.2, 21.7 ± 0.2, 22.9 ± 0.2, and 23.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 11.8 ± 0.2,

12.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

[0022] In another aspect, the present invention provides a solid form of a salt of Compound

I, wherein the salt comprises a hydrochloride, hydrobromide, sulfate, nitrate, mesylate, esylate, besylate, tosylate, naphthalate, naphthalene disulfonate, phosphate, edysilate, or camphor- 10-sulfonate salt of Compound 1.

[0023] In some embodiments, the present invention provides a solid form of a hydrobromide salt of Compound 1 designated as Form X8. In some embodiments, the solid Form X8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of

I I .5 ± 0.2, 15.6 ± 0.2, 19.5 ± 0.2, 21.7 ± 0.2, 23.9 ± 0.2, and 29.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X8 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.2 ± 0.2, 18.0 ± 0.2, and 30.1 ± 0.2 in an X-ray powder diffraction pattern.

[0024] In some embodiments, the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9a. In some embodiments, the solid Form X9a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.5 ± 0.2, 15.5 ± 0.2, 19.4 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X9a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.6 ± 0.2 and 29.0 ± 0.2 in an X-ray powder diffraction pattern.

[0025] In some embodiments, the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9b. In some embodiments, the solid Form X9b of claim 28, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 16.1 ± 0.2, 18.6 ± 0.2, 20.6 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X9b of claim 29, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.1 ± 0.2, 17.9 ± 0.2, 22.1 ± 0.2, 25.6 ± 0.2, and 26.5 ± 0.2 in an X-ray powder diffraction pattern.

[0026] In some embodiments, the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI 0a. In some embodiments, the solid Form X 10a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.5 ± 0.2, 19.4 ± 0.2, 21.6 ± 0.2, 23.6 ± 0.2, 25.4 ± 0.2, and 27.2 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form XlOa is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of

17.8 ± 0.2 and 24.8 ± 0.2 in an X-ray powder diffraction pattern.

[0027] In some embodiments, the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI 0b. In some embodiments, the solid Form XI 0b is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.6 ± 0.2, 17.9 ± 0.2, 20.1 ± 0.2, 22.0 ± 0.2, 24.3 ± 0.2, 25.0 ± 0.2, and 27.5 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form XI 0b is further characterized by a peak corresponding to a 2-theta value measured in degrees of 13.2 ± 0.2 in an X-ray powder diffraction pattern.

[0028] In some embodiments, the present invention provides a solid form of a nitrate salt of Compound 1 designated as Form XI 1. In some embodiments, the solid Form XI 1 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of

21.9 ± 0.2, 25.4 ± 0.2, and 33.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 1 is further characterized by one or more peaks

corresponding to 2-theta values measured in degrees of 1 1.5 ± 0.2, 13.2 ± 0.2, 14.7 ± 0.2, 15.6 ± 0.2, 19.0 ± 0.2, 22.5 ± 0.2, and 23.9 ± 0.2 in an X-ray powder diffraction pattern.

[0029] In some embodiments, the present invention provides a solid form of a mesylate salt of Compound 1 designated as Form X12. In some embodiments, the solid Form X12 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.8 ± 0.2, 20.1 ± 0.2, 20.6 ± 0.2, 21.4 ± 0.2, 22.5 ± 0.2, 23.2 ± 0.2, and 26.7 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form XI 2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of

8.5 ± 0.2, 18.0 ± 0.2, and 20.1 ± 0.2 in an X-ray powder diffraction pattern.

[0030] In some embodiments, the present invention provides a solid form of an esylate salt of Compound 1 designated as Form XI 3. In some embodiments, the solid Form XI 3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.3 ± 0.2, 12.6 ± 0.2, 13.8 ± 0.2, 23.7 ± 0.2, 25.2 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 3 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.8 ± 0.2 in an X-ray powder diffraction pattern.

[0031] In some embodiments, the present invention provides a solid form of a besylate salt of Compound 1 designated as Form X14. In some embodiments, the solid Form X14 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.6 ± 0.2, 21.8 ± 0.2, 24.0 ± 0.2, and 29.2 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.6 ± 0.2, 15.7 ± 0.2, 22.3 ± 0.2,

24.9 ± 0.2, and 30.2 ± 0.2 in an X-ray powder diffraction pattern.

[0032] In some embodiments, the present invention provides a solid form of a tosylate salt of Compound 1 designated as Form XI 5. In some embodiments, the solid Form XI 5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 12.1 ± 0.2, 15.7 ± 0.2, and 21.9 ± 0.2 in an X-ray powder diffraction pattern.

[0033] In some embodiments, the present invention provides a solid form of a naphthalate salt of Compound 1 designated as Form XI 6. In some embodiments, the solid Form XI 6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 14.0 ± 0.2, 16.6 ± 0.2, 19.1 ± 0.2, 21.7 ± 0.2, 24.6 ± 0.2, and 26.1 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form XI 6 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of

6.6 ± 0.2 and 23.5 ± 0.2 in an X-ray powder diffraction pattern.

[0034] In some embodiments, the present invention provides a solid form of a naphthalene disulfonate salt of Compound 1 designated as Form XI 7. In some embodiments, the solid Form XI 7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 22.9 ± 0.2, 26.1 ± 0.2, and 27.2 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.9 ± 0.2, 17.7 ± 0.2, 19.6 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern.

[0035] In some embodiments, the present invention provides a solid form of a phosphate salt of Compound 1 designated as Form XI 8. In some embodiments, the solid Form XI 8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.1 ± 0.2, 17.5 ± 0.2, 19.8 ± 0.2, 26.0 ± 0.2, and 27.1 ± 0.2 in an X-ray powder diffraction pattern.

[0036] In some embodiments, the present invention provides a solid form of an edysilate salt of Compound 1 designated as Form X19. In some embodiments, the solid Form X19 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.2 ± 0.2, 23.7 ± 0.2, and 28.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 9 is further characterized by one or more peaks

corresponding to 2-theta values measured in degrees of 22.6 ± 0.2 and 25.5 ± 0.2 in an X-ray powder diffraction pattern.

[0037] In some embodiments, the present invention provides a solid form of a

camphor- 10-sulfonate salt of Compound 1 designated as Form X20. In some embodiments, the solid Form X20 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.4 ± 0.2, 17.0 ± 0.2, 17.8 ± 0.2, 23.5 ± 0.2, 24.9 ± 0.2, and

27.5 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X20 of claim 63, further characterized by a peak corresponding to a 2-theta value measured in degrees of 16.7 ± 0.2 in an X-ray powder diffraction pattern.

[0038] In some embodiments, the present invention provides a solid form of a co-crystal comprising Compound 1 and an acid selected from malonic acid, succinic acid, glutaric acid, fumaric acid, maleic acid, acetylsalicylic acid, 2-oxoglutaric acid, oxalic acid, or glycolic acid.

[0039] In some embodiments, the present invention provides a solid form of a co-crystal comprising malonic acid and Compound 1 designated as Form X21. In some embodiments, the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ± 0.2, 14.7 ± 0.2, 16.1 ± 0.2, 18.2 ± 0.2, 25.0 ± 0.2, 25.7 ± 0.2, and 26.4 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X21 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.0 ± 0.2 and 19.7 ± 0.2 in an X-ray powder diffraction pattern.

[0040] In some embodiments, the present invention provides a solid form of a co-crystal comprising succinic acid and Compound 1 designated as Form X22. In some embodiments, the solid Form X22 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 11.3 ± 0.2, 15.4 ± 0.2, 17.2 ± 0.2, 19.2 ± 0.2, and 23.5 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X22 of claim 69, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.7 ± 0.2, 13.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

[0041] In some embodiments, the present invention provides a solid form of a co-crystal comprising glutaric acid and Compound 1 designated as Form X23. In some embodiments, the solid Form X23 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.3 ± 0.2, 19.0 ± 0.2, 24.1 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X23 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.6 ± 0.2 in an X-ray powder diffraction pattern.

[0042] In some embodiments, the present invention provides a solid form of a co-crystal comprising fumaric acid and Compound 1 designated as Form X24. In some embodiments, the solid Form X24 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 5.5 ± 0.2, 8.5 ± 0.2, 14.1 ± 0.2, 19.4 ± 0.2, 21.1 ± 0.2, 23.8 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X24 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 12.0 ± 0.2 in an X-ray powder diffraction pattern.

[0043] In some embodiments, the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X25. In some embodiments, the solid Form X25 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 3.9 ± 0.2, 5.3 ± 0.2, 16.7 ± 0.2, 19.3 ± 0.2, and 28.0 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X25 is further

characterized by a peak corresponding to a 2-theta value measured in degrees of 7.8 ± 0.2 and 11.0 ± 0.2 in an X-ray powder diffraction pattern.

[0044] In some embodiments, the present invention provides a solid form of a co-crystal comprising malic acid and Compound 1 designated as Form X26. In some embodiments, the solid Form X26 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.1 ± 0.2, 19.5 ± 0.2, 21.6 ± 0.2, 23.8 ± 0.2, and 26.0 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X25 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 15.5 ± 0.2 in an X-ray powder diffraction pattern. [0045] In some embodiments, the present invention provides a solid form of a co-crystal comprising acetylsalicylic acid and Compound 1 designated as Form X27. In some embodiments, the solid Form X27 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.0 ± 0.2, 19.9 ± 0.2, and 24.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X27 is further

characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 15.1 ± 0.2, and 28.0 ± 0.2 in an X-ray powder diffraction pattern.

[0046] In some embodiments, the present invention provides a solid form of a co-crystal comprising 2-oxoglutaric acid and Compound 1 designated as Form X28. In some embodiments, the solid Form X28 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 15.8 ± 0.2, 17.1 ± 0.2, 18.2 ± 0.2, and

23.6 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X28 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.9 ± 0.2 and 20.3 ± 0.2 in an X-ray powder diffraction pattern.

[0047] In some embodiments, the present invention provides a solid form of a co-crystal comprising oxalic acid and Compound 1 designated as Form X29. In some embodiments, the solid Form X29 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 15.8 ± 0.2, 17.1 ± 0.2, 18.2 ± 0.2, and 23.6 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X29 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of

19.7 ± 0.2, 25.4 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern.

[0048] In some embodiments, the present invention provides a solid form of a co-crystal comprising glycolic acid and Compound 1 designated as Form X30. In some embodiments, the solid Form X30 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 15.6 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X30 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.5 ± 0.2, 18.4 ± 0.2,

18.5 ± 0.2, 19.7 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern.

[0049] In some embodiments, the present invention provides an amorphous form of

Compound 1 designated as Form X31.

BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The Figures are provided by way of example and are not intended to limit the scope of the claims.

[0051] Figure 1 is an exemplary X-Ray powder diffraction pattern of Form XI . [0052] Figure 2 is an exemplary X-Ray powder diffraction pattern of Form X2.

[0053] Figure 3 is an exemplary X-Ray powder diffraction pattern of Form X3.

[0054] Figure 4 is an exemplary X-Ray powder diffraction pattern of Form X4.

[0055] Figure 5 is an exemplary X-Ray powder diffraction pattern of Form X5.

[0056] Figure 6 is an exemplary X-Ray powder diffraction pattern of Form X6.

[0057] Figure 7 is an exemplary X-Ray powder diffraction pattern of Form X7.

[0058] Figure 8 is an exemplary X-Ray powder diffraction pattern of Form X8.

[0059] Figure 9 is an exemplary X-Ray powder diffraction pattern of Form X9a.

[0060] Figure 10 is an exemplary X-Ray powder diffraction pattern of Form X9b.

[0061] Figure 1 1 is an exemplary X-Ray powder diffraction pattern of Form XlOa.

[0062] Figure 12 is an exemplary X-Ray powder diffraction pattern of Form XI 0b.

[0063] Figure 13 is an exemplary X-Ray powder diffraction pattern of Form XI 1.

[0064] Figure 14 is an exemplary X-Ray powder diffraction pattern of Form XI 2.

[0065] Figure 15 is an exemplary X-Ray powder diffraction pattern of Form XI 3.

[0066] Figure 16 is an exemplary X-Ray powder diffraction pattern of Form X14.

[0067] Figure 17 is an exemplary X-Ray powder diffraction pattern of Form XI 5.

[0068] Figure 18 is an exemplary X-Ray powder diffraction pattern of Form XI 6.

[0069] Figure 19 is an exemplary X-Ray powder diffraction pattern of Form XI 7.

[0070] Figure 20 is an exemplary X-Ray powder diffraction pattern of Form XI 8.

[0071] Figure 21 is an exemplary X-Ray powder diffraction pattern of Form X19.

[0072] Figure 22 is an exemplary X-Ray powder diffraction pattern of Form X20.

[0073] Figure 23 is an exemplary X-Ray powder diffraction pattern of Form X21.

[0074] Figure 24 is an exemplary X-Ray powder diffraction pattern of Form X22.

[0075] Figure 25 is an exemplary X-Ray powder diffraction pattern of Form X23.

[0076] Figure 26 is an exemplary X-Ray powder diffraction pattern of Form X24.

[0077] Figure 27 is an exemplary X-Ray powder diffraction pattern of Form X25.

[0078] Figure 28 is an exemplary X-Ray powder diffraction pattern of Form X26.

[0079] Figure 29 is an exemplary X-Ray powder diffraction pattern of Form X27.

[0080] Figure 30 is an exemplary X-Ray powder diffraction pattern of Form X28.

[0081] Figure 31 is an exemplary X-Ray powder diffraction pattern of Form X29.

[0082] Figure 32 is an exemplary X-Ray powder diffraction pattern of Form X30.

[0083] Figure 33 is an exemplary X-Ray powder diffraction pattern of Form X31. DETAILED DESCRIPTION

[0084] The present invention provides solid forms of Compound 1 , methods of preparing solid forms of Compound 1, and methods of treating JAK-mediated diseases (e.g., RA, psoriasis, UC, SLE, or the like, or any combination thereof) using a solid form of Compound 1.

[0085] I. DEFINITIONS

[0086] As used herein, "Compound 1 " is (R)-2-(2-(lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin- 4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide ("Compound 1") having the structure below:

Compound 1

[0087] As used herein, "solid form" refers to a compound or composition (e.g., salts, solvates, or co-crystals of compounds) in a solid physical state. Solid forms includes crystalline, semi-crystalline, and amorphous compounds and compositions. Crystalline solid forms of compounds or compositions possess structural units that are arranged in fixed geometric patterns or lattices, so that crystalline solids have rigid long range order. The structural units that constitute the crystal structure can be atoms, molecules, or ions.

Crystalline solids may possess physical properties that may include a definite melting point.

[0088] As used herein, an "ion" refers to an atom or polyatomic species wherein the total number of electrons is not equal to the total number of protons, giving the atom a net positive or negative electrical charge.

[0089] As used herein, a "salt" refers to an ionic compound that results from the

neutralization reaction of an acid (e.g., salt coformer) and a base (e.g., Compound No. 1). Salts are composed of cations (positively charged ions) and anions (negative ions) so that the product is electrically neutral (without a net charge).

[0090] As used herein, a "co-crystal" consists of two or more components that form a unique crystalline structure having unique properties. In some instances, a co-crystal comprises a crystalline structure composed of at least two components, where the components may be atoms, ions or molecules. In some embodiments, the components of the co-crystal are solid in their pure forms at ambient conditions. [0091] As used herein, a "solvate" refers to a crystal form of a compound with either stoichiometric or non-stoichiometric amount of solvent.

[0092] As used herein, "X-ray powder diffraction" and "XRPD" are used interchangeable.

[0093] II. COMMONLY USED ABREVIATIONS

[0094] The following abbreviations are used:

XRPD X-ray powder diffraction

PG protecting group

LG leaving group

DCM dichloromethane

Ac acetyl

THF tetrohydrofuran

2-Me-THF 2-methyl-tetrahydrofuran

TMS trimethylsilyl

TBS tert-butyldimethylsilyl

TIPS tri-wo-propylsilyl

TBDPS tert-butyldiphenylsilyl

TOM tri-z^'so-propylsilyloxymethyl

DMP Dess-Martin periodinane

IBX 2-iodoxybenzoic acid

DMF dimethylformamide

MTBE methyl-tert-butylether

TBAF tetra-H-butylammonium fluoride

d.e. diastereomeric excess

e.e. enantiomeric excess

EtOAc ethyl acetate

DMSO dimethyl sulfoxide

MeCN acetonitrile

TCA trichloroacetic acid

ATP adenosine triphosphate

EtOH ethanol

Ph phenyl

Me methyl

Et ethyl

Bu butyl DEAD diethylazodicarboxylate

HEPES 4-(2-hydroxyethyl)- 1 -piperazineethanesulfonic acid

DTT dithiothreitol

MOPS 4-morpholinepropanesulfonic acid

NMR nuclear magnetic resonance

HPLC high performance liquid chromatography

LCMS liquid chromatography-mass spectrometry

TLC thin layer chromatography

Rt retention time

HOBt hydroxybenzotriazole

Ms mesyl

Es esyl

Ts tosyl

Tf triflyl

Bs besyl

Ns nosyl

Cbz carboxybenzyl

Moz -methoxybenzyl carbonyl

Boc ter/-butyloxycarbonyl

Fmoc 9-fluorenylmethyloxycarbonyl

Bz benzoly

Bn benzyl

PMB -methoxybenzyl

DMPM 3 ,4-dimethoxybenzyl

PMP >-methoxyphenyl

ACN acetonitrile

[0095] III. SOLID FORMS OF COMPOUND 1

[0096] A. Analytical Methods

[0097] Method 1 : XRPD patterns were acquired at room temperature in reflection mode using a Bruker D8 Discover diffractometer equipped with a sealed tube Cu source and a Hi- Star area detector (Bruker AXS, Madison, WI). The X-Ray generator was operating at a voltage of 40 kV and a current of 35 mA. The powder sample was placed in a nickel holder. Two frames were registered with an exposure time of 120 s each. The data frames were subsequently integrated over the range of 4.5° - 22.4° and 21.0° - 39.0° 2q merged into one continuous pattern. [0098] Method 2: XRPD patterns were recorded at room temperature in reflection mode using a Bruker D8 Advance diffractometer equipped with a sealed tube Cu source and a Vantec PSD detector (Bruker AXS, Madison, WI). The X-ray generator was operating at a voltage of 40 kV and a current of 40 mA. The powder sample was placed in a silicon or PMM holder. The data were recorded in a q-q scanning mode over the range of 4°-45° 2q with a step size of 0.014° and a dwell time of Is per step.

[0099] B. Solid Form Solvates of Compound 1

[0100] One aspect the present invention provides a solid form of a solvate of Compound 1, wherein the solvate comprises Compound 1 and a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran (THF), 2-methyl tetrahydrofuran, or 1,4-dioxane.

[0101] 1. Dimethyl Formamide Solvate of Compound 1

[0102] In some embodiments, the present invention provides a solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI . In some embodiments, solid

Form XI is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 13.3 ± 0.2, 14.1 ± 0.2, 15.4 ± 0.2, 19.3 ± 0.2, and 25.0 ± 0.2 in an X-ray powder diffraction pattern. In other embodiments, solid Form XI is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.6 ± 0.2,

23.4 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern.

[0103] Referring to Figure 1, in one embodiment, Form XI is characterized by an XRPD

Pattern, obtained using Method 1, having the following peaks:

Table 1 : XRPD pattern for Form XI .

[0104] 2. Ethyl Acetate Solvate of Compound 1

[0105] In some embodiments, the present invention provides a solid form of an ethyl acetate solvate of Compound 1 designated as Form X2. In some embodiments, the solid Form X2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ± 0.2, 11.9 ± 0.2, and 24.0 ± 0.2 in an X-ray powder diffraction pattern. In other embodiments, the solid Form X2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 18.5 ± 0.2 and 28.1 ± 0.2 in an X-ray powder diffraction pattern.

[0106] Referring to Figure 2, in one embodiment, Form X2 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 2: XRPD pattern for Form X2.

[0107] 3. Methyl Acetate Solvate of Compound 1.

[0108] In some embodiments, the present invention provides a solid form of a methyl acetate solvate of Compound 1 designated as Form X3. In some embodiments, the solid Form X3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 1 1.1 ± 0.2, 12.0 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X3 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.1 ± 0.2 and 29.5 ± 0.2 in an X-ray powder diffraction pattern.

[0109] Referring to Figure 3, in one embodiment, Form X3 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 3: XRPD pattern for Form X3.

[0110] 4. N-methyl pyrrolidone Solvate of Compound 1 [0111] In some embodiments, the present invention provides a solid form of an N-methyl pyrrolidone solvate of Compound 1 designated as Form X4. In some embodiments, the solid Form X4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.9 ± 0.2, 17.4 ± 0.2, 19.1 ± 0.2, and 24.4 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.9 ± 0.2 and 27.0 ± 0.2 in an X-ray powder diffraction pattern.

[0112] Referring to Figure 4, in one embodiment, Form X4 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 4: XRPD pattern for Form X4.

[0113] 5. THF Solvate of Compound 1

[0114] In some embodiments, the present invention provides a solid form of a

tetrahydrofuran solvate of Compound 1 designated as Form X5. In some embodiments, the solid Form X5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.9 ± 0.2, 16.1 ± 0.2, 18.7 ± 0.2, 22.3 ± 0.2, and 23.7 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of

19.7 ± 0.2 and 24.5 ± 0.2 in an X-ray powder diffraction pattern.

[0115] Referring to Figure 5, in one embodiment, Form X5 is characterized by an XRPD

Pattern, obtained using Method 1, having the following peaks:

Table 5: XRPD pattern for Form X5.

[0116] 6. 2-Me-THF Solvate of Compound 1

[0117] In some embodiments, the present invention provides a solid form of a

2-methyltetrahydrofuran solvate of Compound 1 designated as Form X6. In some embodiments, the solid Form X6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.2 ± 0.2, 15.2 ± 0.2, 22.6 ± 0.2, and 23.0 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X5 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1 ± 0.2, 11.8 ± 0.2, 16.0 ± 0.2, 17.8 ± 0.2, 18.6 ± 0.2, 19.4 ± 0.2, 20.0 ± 0.2, and 20.7 ± 0.2, in an X-ray powder diffraction pattern.

[0118] Referring to Figure 6, in one embodiment, Form X6 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 6: XRPD pattern for Form X6.

[0119] 7. 1,4-Dioxane Solvate of Compound 1

[0120] In some embodiments, the present invention provides a solid form of a 1,4-dioxane solvate of Compound 1 designated as Form X7. In some embodiments, the solid Form X7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of

10.5 ± 0.2, 15.7 ± 0.2, 21.7 ± 0.2, 22.9 ± 0.2, and 23.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 1 1.8 ± 0.2,

12.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

[0121] Referring to Figure 7, in one embodiment, Form X7 is characterized by an XRPD

Pattern, obtained using Method 1, having the following peaks: Table 7: XRPD pattern for Form X7.

[0122] C. Salts of Compound 1

[0123] In another aspect, the present invention provides a salt of Compound 1. In some embodiments, the salt of Compound 1 comprises a solid form of a salt of Compound 1 , wherein the salt comprises a hydrochloride, hydrobromide, sulfate, nitrate, mesylate, esylate, besylate, tosylate, naphthalate, naphthalene disulfonate, phosphate, edysilate, or

camphor- 10-sulfonate salt of Compound 1.

[0124] 1. Hydrobromide Salt of Compound 1

[0125] In some embodiments, the present invention provides a hydrobromide salt of

Compound 1 : Compound 1 · HBr. In some embodiments, the present invention provides a solid form of a hydrobromide salt of Compound 1 designated as Form X8. In some embodiments, the solid Form X8 is characterized by one or more peaks corresponding to

2-theta values measured in degrees of 11.5 ± 0.2, 15.6 ± 0.2, 19.5 ± 0.2, 21.7 ± 0.2,

23.9 ± 0.2, and 29.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X8 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.2 ± 0.2, 18.0 ± 0.2, and 30.1 ± 0.2 in an X-ray powder diffraction pattern.

[0126] Referring to Figure 8, in one embodiment, Form X8 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 8: XRPD pattern for Form X8.

2-Theta Relative Intensity (%)

23.9 >10

29.1 >10

30.1 >10

[0127] 2. Hydrochloride Salts of Compound 1

[0128] In some embodiments, the present invention provides a hydrochloride salt of Compound 1 : Compound 1 · HC1. In some embodiments, the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9a. In some embodiments, the solid Form X9a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.5 ± 0.2, 15.5 ± 0.2, 19.4 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X9a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.6 ± 0.2 and 29.0 ± 0.2 in an X-ray powder diffraction pattern.

[0129] Referring to Figure 9, in one embodiment, Form X9a is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 9: XRPD pattern for Form X9a.

[0130] In some embodiments, the present invention provides a hydrochloride salt of Compound 1 : Compound 1· HC1. In some embodiments, the present invention provides a solid form of a hydrochloride salt of Compound 1 designated as Form X9b. In some embodiments, the solid Form X9b of claim 28, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 16.1 ± 0.2, 18.6 ± 0.2, 20.6 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X9b of claim 29, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.1 ± 0.2, 17.9 ± 0.2, 22.1 ± 0.2, 25.6 ± 0.2, and 26.5 ± 0.2 in an X-ray powder diffraction pattern. [0131] Referring to Figure 10, in one embodiment, Form X9b is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 10: XRPD pattern for Form X9b.

[0132] 3. Sulfate Salts of Compound 1

[0133] In some embodiments, the present invention provides a sulfate salt of Compound 1 : Compound 1 · H₂S0₄. In some embodiments, the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XlOa. In some embodiments, the solid Form X 10a is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.5 ± 0.2, 19.4 ± 0.2, 21.6 ± 0.2, 23.6 ± 0.2, 25.4 ± 0.2, and 27.2 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 0a is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.8 ± 0.2 and 24.8 ± 0.2 in an X-ray powder diffraction pattern.

[0134] Referring to Figure 11, in one embodiment, Form XI 0a is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 11 : XRPD pattern for Form XI 0a.

[0135] In some embodiments, the present invention provides a sulfate salt of Compound 1 : Compound 1· H₂S0₄. In some embodiments, the present invention provides a solid form of a sulfate salt of Compound 1 designated as Form XI Ob. In some embodiments, the solid Form XI Ob is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.6 ± 0.2, 17.9 ± 0.2, 20.1 ± 0.2, 22.0 ± 0.2, 24.3 ± 0.2, 25.0 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 0b is further characterized by a peak corresponding to a 2-theta value measured in degrees of 13.2 ± 0.2 in an X-ray powder diffraction pattern.

[0136] Referring to Figure 12, in one embodiment, Form XI 0b is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 12: XRPD pattern for Form XlOb.

[0137] 4. Nitrate Salt of Compound 1

[0138] In some embodiments, the present invention provides a nitrate salt of Compound 1 : Compound 1· HNO3. In some embodiments, the present invention provides a solid form of a nitrate salt of Compound 1 designated as Form XI 1. In some embodiments, the solid Form XI 1 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.9 ± 0.2, 25.4 ± 0.2, and 33.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 1 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.5 ± 0.2, 13.2 ± 0.2, 14.7 ± 0.2, 15.6 ± 0.2, 19.0 ± 0.2, 22.5 ± 0.2, and 23.9 ± 0.2 in an X-ray powder diffraction pattern.

[0139] Referring to Figure 13, in one embodiment, Form XI 1 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 13 : XRPD pattern for Form X 1 1.

2-Theta Relative Intensity (%)

11.5 >10

13.2 >10

14.7 >10

15.6 >10

19.0 >10

21.9 >10 2-Theta Relative Intensity (%)

22.5 >10

23.9 >10

25.4 >10

33.1 >10

[0140] 5. Mesylate Salt of Compound 1

[0141] In some embodiments, the present invention provides a mesylate salt of Compound 1 : Compound 1 · CH3SO3H. In some embodiments, the present invention provides a solid form of a mesylate salt of Compound 1 designated as Form XI 2. In some embodiments, the solid Form XI 2 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.8 ± 0.2, 20.1 ± 0.2, 20.6 ± 0.2, 21.4 ± 0.2, 22.5 ± 0.2, 23.2 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 2 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.5 ± 0.2, and 18.0 ± 0.2 in an X-ray powder diffraction pattern.

[0142] Referring to Figure 14, in one embodiment, Form X12 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 14: XRPD pattern for Form X12.

[0143] 6. Esylate Salt of Compound 1

[0144] In some embodiments, the present invention provides an esylate salt of Compound 1 : Compound 1 · CH3CH2SO3H. In some embodiments, the present invention provides a solid form of an esylate salt of Compound 1 designated as Form XI 3. In some embodiments, the solid Form XI 3 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.3 ± 0.2, 12.6 ± 0.2, 13.8 ± 0.2, 23.7 ± 0.2, 25.2 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 3 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.8 ± 0.2 in an X-ray powder diffraction pattern. [0145] Referring to Figure 15, in one embodiment, Form XI 3 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 15: XRPD pattern for Form X13.

[0146] 7. Besylate Salt of Compound 1

[0147] In some embodiments, the present invention provides a besylate salt of Compound 1 : Compound 1 · benzenesulfonic acid. In some embodiments, the present invention provides a solid form of a besylate salt of Compound 1 designated as Form XI 4. In some embodiments, the solid Form XI 4 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.6 ± 0.2, 21.8 ± 0.2, 24.0 ± 0.2, and 29.2 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 4 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.6 ± 0.2, 15.7 ± 0.2, 22.3 ± 0.2, 24.9 ± 0.2, and 30.2 ± 0.2 in an X-ray powder diffraction pattern.

[0148] Referring to Figure 16, in one embodiment, Form X14 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 16: XRPD pattern for Form X14.

[0149] 8. Tosylate Salt of Compound 1 [0150] In some embodiments, the present invention provides a tosylate salt of Compound 1 : Compound 1 · p-toluenesulfonic acid. In some embodiments, the present invention provides a solid form of a tosylate salt of Compound 1 designated as Form XI 5. In some

embodiments, the solid Form XI 5 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 12.1 ± 0.2, 15.7 ± 0.2, and 21.9 ± 0.2 in an X-ray powder diffraction pattern.

[0151] Referring to Figure 17, in one embodiment, Form XI 5 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 17: XRPD pattern for Form XI 5.

[0152] 9. Naphthalate Salt of Compound 1

[0153] In some embodiments, the present invention provides a naphthalate salt of Compound 1 : Compound 1 · naphthalic acid. In some embodiments, the present invention provides a solid form of a naphthalate salt of Compound 1 designated as Form XI 6. In some embodiments, the solid Form XI 6 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 14.0 ± 0.2, 16.6 ± 0.2, 19.1 ± 0.2,

21.7 ± 0.2, 24.6 ± 0.2, and 26.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 6 is further characterized by one or more peaks

corresponding to 2-theta values measured in degrees of 6.6 ± 0.2 and 23.5 ± 0.2 in an X-ray powder diffraction pattern.

[0154] Referring to Figure 18, in one embodiment, Form XI 6 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 18: XRPD pattern for Form XI 6.

2-Theta Relative Intensity (%)

21.7 >20

23.5 >20

24.6 >20

26.1 >20

[0155] 10. Naphthalene Disulfate Salt of Compound 1

[0156] In some embodiments, the present invention provides a naphthalene disulfonate salt of Compound 1 : Compound 1 · naphthalene- 1,2-disulfonic acid. In some embodiments, the present invention provides a solid form of a naphthalene disulfonate salt of Compound 1 designated as Form XI 7. In some embodiments, the solid Form XI 7 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 22.9 ± 0.2, 26.1 ± 0.2, and 27.2 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 7 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.9 ± 0.2, 17.7 ± 0.2, 19.6 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern.

[0157] Referring to Figure 19, in one embodiment, Form XI 7 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 19: XRPD pattern for Form XI 7.

[0158] 1 1. Phosphate Salt of Compound 1

[0159] In some embodiments, the present invention provides a phosphate salt of Compound 1 : Compound 1 · phosphoric acid. In some embodiments, the present invention provides a solid form of a phosphate salt of Compound 1 designated as Form XI 8. In some

embodiments, the solid Form XI 8 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.1 ± 0.2, 17.5 ± 0.2, 19.8 ± 0.2,

26.0 ± 0.2, and 27.1 ± 0.2 in an X-ray powder diffraction pattern.

[0160] Referring to Figure 20, in one embodiment, Form XI 8 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks: Table 20: XRPD pattern for Form XI 8.

[0161] 12. Edisilate Salt of Compound 1

[0162] In some embodiments, the present invention provides an edisilate salt of Compound 1 : Compound 1 · ethane- 1 ,2-disulfonic acid. In some embodiments, the present invention provides a solid form of an edysilate salt of Compound 1 designated as Form XI 9. In some embodiments, the solid Form XI 9 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.2 ± 0.2, 23.7 ± 0.2, and 28.1 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form XI 9 is further

characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.6 ± 0.2 and 25.5 ± 0.2 in an X-ray powder diffraction pattern.

[0163] Referring to Figure 21, in one embodiment, Form X19 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 21 : XRPD pattern for Form XI 9.

[0164] 13. Camphor- 10-sulfonate Salt of Compound 1

[0165] In some embodiments, the present invention provides a camphor- 10-sulfonate salt of Compound 1 : Compound 1 · camphor- 10-sulfonic acid. In some embodiments, the present invention provides a solid form of a camphor- 10-sulfonate salt of Compound 1 designated as Form X20. In some embodiments, the solid Form X20 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.4 ± 0.2, 17.0 ± 0.2, 17.8 ± 0.2, 23.5 ± 0.2, 24.9 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X20 of claim 63, further characterized by a peak corresponding to a 2-theta value measured in degrees of 16.7 ± 0.2 in an X-ray powder diffraction pattern.

[0166] Referring to Figure 22, in one embodiment, Form X20 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 22: XRPD pattern for Form X20.

[0167] D. Solid Form Co-crystals of Compound 1

[0168] In some embodiments, the present invention provides a solid form of a co-crystal comprising Compound 1 and malonic acid, succinic acid, glutaric acid, fumaric acid, maleic acid, or 2-oxoglutaric acid.

[0169] 1. Malonic Acid Co-crystal of Compound 1

[0170] In some embodiments, the present invention provides a solid form of a co-crystal comprising malonic acid and Compound 1 designated as Form X21. In some embodiments, the solid Form X21 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ± 0.2, 14.7 ± 0.2, 16.1 ± 0.2, 18.2 ± 0.2, 25.0 ± 0.2, 25.7 ± 0.2, and 26.4 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form

X21 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.0 ± 0.2 and 19.7 ± 0.2 in an X-ray powder diffraction pattern.

[0171] Referring to Figure 23, in one embodiment, Form X21 is characterized by an XRPD

Pattern, obtained using Method 2, having the following peaks:

Table 23: XRPD pattern for Form X21.

2-Theta Relative Intensity (%)

25.0 >40

25.7 >40

26.4 >40

[0172] 2. Succinic Acid Co-crystal of Compound 1

[0173] In some embodiments, the present invention provides a solid form of a co-crystal comprising succinic acid and Compound 1 designated as Form X22. In some embodiments, the solid Form X22 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 11.3 ± 0.2, 15.4 ± 0.2, 17.2 ± 0.2, 19.2 ± 0.2, and 23.5 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X22 of claim 69, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.7 ± 0.2, 13.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

[0174] Referring to Figure 24, in one embodiment, Form X22 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 24: XRPD pattern for Form X22.

[0175] 3. Glutaric Acid Co-crystal of Compound 1

[0176] In some embodiments, the present invention provides a solid form of a co-crystal comprising glutaric acid and Compound 1 designated as Form X23. In some embodiments, the solid Form X23 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.3 ± 0.2, 19.0 ± 0.2, 24.1 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X23 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.6 ± 0.2 in an X-ray powder diffraction pattern.

[0177] Referring to Figure 25, in one embodiment, Form X23 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks: Table 25: XRPD pattern for Form X23.

[0178] 4. Fumaric Acid Co-crystal of Compound 1

[0179] In some embodiments, the present invention provides a solid form of a co-crystal comprising fumaric acid and Compound 1 designated as Form X24. In some embodiments, the solid Form X24 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 5.5 ± 0.2, 8.5 ± 0.2, 14.1 ± 0.2, 19.4 ± 0.2, 21.1 ± 0.2, 23.8 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X24 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 12.0 ± 0.2 in an X-ray powder diffraction pattern.

[0180] Referring to Figure 26, in one embodiment, Form X24 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 26: XRPD pattern for Form X24.

[0181] 5. Maleic Acid Co-crystals of Compound 1

[0182] In some embodiments, the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X25. In some embodiments, the solid Form X25 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 3.9 ± 0.2, 5.3 ± 0.2, 16.7 ± 0.2, 19.3 ± 0.2, and 28.0 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X25 is further

characterized by a peak corresponding to a 2-theta value measured in degrees of 7.8 ± 0.2 and 11.0 ± 0.2 in an X-ray powder diffraction pattern.

[0183] Referring to Figure 27, in one embodiment, Form X25 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 27: XRPD pattern for Form X25.

[0184] 6. Malic Acid Co-crystals of Compound 1

[0185] In some embodiments, the present invention provides a solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X26. In some embodiments, the solid Form X26 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.1 ± 0.2, 19.5 ± 0.2, 21.6 ± 0.2, 23.8 ± 0.2, and 26.0 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X26 is further characterized by a peak corresponding to a 2-theta value measured in degrees of 15.5 ± 0.2 in an X-ray powder diffraction pattern.

[0186] Referring to Figure 28, in one embodiment, Form X26 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 28: XRPD pattern for Form X26.

[0187] 7. Acetylsalicylic Acid Co-crystal of Compound 1

[0188] In some embodiments, the present invention provides a solid form of a co-crystal comprising acetylsalicylic acid and Compound 1 designated as Form X27. In some embodiments, the solid Form X27 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ± 0.2, 19.9 ± 0.2, and 24.7 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X27 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 15.1 ± 0.2, and 28.0 ± 0.2 in an X-ray powder diffraction pattern.

[0189] Referring to Figure 29, in one embodiment, Form X27 is characterized by an XRPD Pattern, obtained using Method 2, having the following peaks:

Table 29: XRPD pattern for Form X27.

[0190] 7. 2-Oxoglutaric Acid Co-crystal of Compound 1

[0191] In some embodiments, the present invention provides a solid form of a co-crystal comprising 2-oxoglutaric acid and Compound 1 designated as Form X28. In some embodiments, the solid Form X28 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 12.9 ± 0.2, 22.6 ± 0.2, 24.7 ± 0.2, and 25.3 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X28 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.9 ± 0.2 and 20.3 ± 0.2 in an X-ray powder diffraction pattern.

[0192] Referring to Figure 30, in one embodiment, Form X28 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 30: XRPD pattern for Form X28.

[0193] 8. Oxalic Acid Co-crystal of Compound 1 [0194] In some embodiments, the present invention provides a solid form of a co-crystal comprising oxalic acid and Compound 1 designated as Form X29. In some embodiments, the solid Form X29 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 15.8 ± 0.2, 17.1 ± 0.2, 18.2 ± 0.2, and 23.6 ± 0.2 in an X- ray powder diffraction pattern. In some embodiments, the solid Form X29 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ± 0.2, 25.4 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern.

[0195] Referring to Figure 31, in one embodiment, Form X29 is characterized by an XRPD Pattern, obtained using Method 1, having the following peaks:

Table 31 : XRPD pattern for Form X29.

[0196] 9. Glycolic Acid Co-crystal of Compound 1

[0197] In some embodiments, the present invention provides a solid form of a co-crystal comprising glycolic acid and Compound 1 designated as Form X30. In some embodiments, the solid Form X30 is characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 15.6 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern. In some embodiments, the solid Form X30 is further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.5 ± 0.2, 18.4 ± 0.2,

18.5 ± 0.2, 19.7 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern.

[0198] Referring to Figure 32, in one embodiment, Form X30 is characterized by an XRPD

Pattern, obtained using Method 1, having the following peaks:

Table 32: XRPD pattern for Form X30.

2-Theta Relative Intensity (%)

7.8 >35

14.5 >35

15.6 >35

17.0 >35

18.4 >35 2-Theta Relative Intensity (%)

18.5 >35

19.7 >35

23.8 >35

26.7 >35

[0199] E. Amorphous Solid Form of Compound 1

[0200] Referring to Figure 33, generated using Method 1, some embodiments of the present invention provide an amorphous form of Compound 1 designated as Form X31.

[0201] IV. EXAMPLES

[0202] Example 1: Solvates of Compound 1.

[0203] Solvates of Compound 1, described in section B, were generated by suspending 500 mg of Compound 1 in 0.5 to 2 ml of the relevant solvent overnight, i.e., from 12 to 72 hrs. The solvent was evaporated to dryness to generate the resulting solvates of Compound 1 . identified as solid forms XI -X7. The dried solvates were tested without further purification.

[0204] Example 2: Salts of Compound 1.

[0205] Salts of Compound 1, as described in section C, were generated at a scale of 250 mg by mixing Compound 1 and the salt coformer as described by Table 31.

Table 31 : Solutions for generating salts of Compound 1.

Salt Coformer Ratio Solvent Solid Form

(Compound 1: No. Coformer)

Edisilate ethane- 1,2- 1 :1 :1 ACN (3 ml) X19 disulfonic acid

Camphor- 10- Camphor- 10- 1 :1 :1 ACN (3 ml) X20 sulfonate sulfonic acid

[0206] The mixtures described in Table 31 were, in some instances, sonicated for 30 min and stirred overnight, i.e., from 12 to 72 hrs. The solvent was evaporated to dryness to generate the resulting salts of Compound 1 identified as solid forms X8-X20. The dried salts were tested without further purification.

[0207] Example 3: Co-crystals of Compound 1.

[0208] All co-crystals, as described in section D, were prepared by slurry conversion in dichloromethane or dichloromethane, acetonitrile mixtures. The mixtures contained a 1 :1 ratio of Compound 1 and the co-crystal coformer. Crystallization of solid forms X21-X30 was promoted by sonication over 30 min before stirring for 12-72 hours. Solvent was evaporated to dryness and the resulting co-crystals were tested without further purification.

[0209] Example 4: Form X31

[0210] Amorphous Compound 1 was generated by spray drying a mixture of Compound 1 in a 1 :2 methanol: dichloromethane solution using a Buchi Mini Spray Dryer B-290.

[0211] The spray parameters were as follows:

OTHER EMBODIMENTS

[0212] All publications and patents referred to in this disclosure are incorporated herein by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Should the meaning of the terms in any of the patents or publications incorporated by reference conflict with the meaning of the terms used in this disclosure, the meaning of the terms in this disclosure are intended to be controlling. Furthermore, the foregoing discussion discloses and describes merely exemplary embodiments of the present invention. One skilled in the art will readily recognize from such discussion and from the accompanying drawings and claims, that various changes, modifications and variations can be made therein without departing from the spirit and scope of the invention as defined in the following claims.

Claims

WHAT IS CLAIMED IS

1. A solid form of a solvate of Compound 1, wherein the solvate comprises Compound 1 and a solvent selected from dimethyl formamide, ethyl acetate, methyl acetate, N-methyl pyrrolidone, tetrahydrofuran, 2-methyltetrahydrofuran, or 1,4-dioxane.

2. A solid form of a dimethyl formamide solvate of Compound 1 designated as Form XI.

3. The solid Form XI of claim 2, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 13.3 ± 0.2, 14.1 ± 0.2, 15.4 ± 0.2, 19.3 ± 0.2, and 25.0 ± 0.2 in an X-ray powder diffraction pattern.

4. The solid Form XI of claim 3, further characterized by one or more peaks

corresponding to 2-theta values measured in degrees of 17.6 ± 0.2, 23.4 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern.

5. A solid form of an ethyl acetate solvate of Compound 1 designated as Form X2.

6. The solid Form X2 of claim 5, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ± 0.2, 1 1.9 ± 0.2, and 24.0 ± 0.2 in an X-ray powder diffraction pattern.

7. The solid Form X2 of claim 6, further characterized by one or more peaks

corresponding to 2-theta values measured in degrees of 18.5 ± 0.2 and 28.1 ± 0.2 in an X-ray powder diffraction pattern.

8. A solid form of a methyl acetate solvate of Compound 1 designated as Form X3.

9. The solid Form X3 of claim 8, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 11.1 ± 0.2, 12.0 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern.

10. The solid Form X3 of claim 9, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.1 ± 0.2 and 29.5 ± 0.2 in an X-ray powder diffraction pattern.

11. A solid form of an N-methyl pyrrolidone solvate of Compound 1 designated as Form X4.

12. The solid Form X4 of claim 1 1 , characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.9 ± 0.2, 17.4 ± 0.2, 19.1 ± 0.2, and 24.4 ± 0.2 in an X-ray powder diffraction pattern.

13. The solid Form X4 of claim 12, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.9 ± 0.2 and 27.0 ± 0.2 in an X-ray powder diffraction pattern.

14. A solid form of a tetrahydrofuran solvate of Compound 1 designated as Form X5.

15. The solid Form X5 of claim 14, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.9 ± 0.2, 16.1 ± 0.2, 18.7 ± 0.2, 22.3 ± 0.2, and 23.7 ± 0.2 in an X-ray powder diffraction pattern.

16. The solid Form X5 of claim 15, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ± 0.2 and 24.5 ± 0.2 in an X-ray powder diffraction pattern.

17. A solid form of a 2-methyltetrahydrofuran solvate of Compound 1 designated as Form X6.

18. The solid Form X6 of claim 17, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.2 ± 0.2, 15.2 ± 0.2, 22.6 ± 0.2, and 23.0 ± 0.2 in an X-ray powder diffraction pattern.

19. The solid Form X5 of claim 18, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1 ± 0.2, 1 1.8 ± 0.2, 16.0 ± 0.2,

17.8 ± 0.2, 18.6 ± 0.2, 19.4 ± 0.2, 20.0 ± 0.2, and 20.7 ± 0.2, in an X-ray powder diffraction pattern.

20. A solid form of a 1,4-dioxane solvate of Compound 1 designated as Form X7.

21. The solid Form X7 of claim 20, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 10.5 ± 0.2, 15.7 ± 0.2, 21.7 ± 0.2, 22.9 ± 0.2, and 23.7 ± 0.2 in an X-ray powder diffraction pattern.

22. The solid Form X7 of claim 21 , further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 11.8 ± 0.2, 12.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

23. A solid form of a salt of Compound 1 , wherein the salt comprises a hydrochloride, hydrobromide, sulfate, nitrate, mesylate, esylate, besylate, tosylate, naphthalate, naphthalene disulfonate, phosphate, edysilate, or camphor- 10-sulfonate salt of Compound 1.

24. A hydrobromide salt of Compound 1.

25. A solid form of a hydrobromide salt of Compound 1 designated as Form X8.

26. The solid Form X8 of claim 25, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 1 1.5 ± 0.2, 15.6 ± 0.2, 19.5 ± 0.2, 21.7 ± 0.2,

23.9 ± 0.2, and 29.1 ± 0.2 in an X-ray powder diffraction pattern.

27. The solid Form X8 of claim 26, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.2 ± 0.2, 18.0 ± 0.2, and 30.1 ± 0.2 in an X-ray powder diffraction pattern.

28. A hydrochloride salt of Compound 1.

29. A solid form of a hydrochloride salt of Compound 1 designated as Form X9a.

30. The solid Form X9a of claim 29, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.5 ± 0.2, 15.5 ± 0.2, 19.4 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern.

31. The solid Form X9a of claim 30, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.6 ± 0.2 and 29.0 ± 0.2 in an X-ray powder diffraction pattern.

32. A solid form of a hydrochloride salt of Compound 1 designated as Form X9b.

33. The solid Form X9b of claim 32, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.2 ± 0.2, 16.1 ± 0.2, 18.6 ± 0.2, 20.6 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern.

34. The solid Form X9b of claim 33, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.1 ± 0.2, 17.9 ± 0.2, 22.1 ± 0.2, 25.6 ± 0.2, and 26.5 ± 0.2 in an X-ray powder diffraction pattern.

35. A sulfate salt of Compound 1.

36. A solid form of a sulfate salt of Compound 1 designated as Form XI 0a.

37. The solid Form XI 0a of claim 36, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.5 ± 0.2, 19.4 ± 0.2, 21.6 ± 0.2,

23.6 ± 0.2, 25.4 ± 0.2, and 27.2 ± 0.2 in an X-ray powder diffraction pattern.

38. The solid Form X 10a of claim 37, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.8 ± 0.2 and 24.8 ± 0.2 in an X-ray powder diffraction pattern.

A solid form of a sulfate salt of Compound 1 designated as Form XI 0b.

40. The solid Form XI Ob of claim 39, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.6 ± 0.2, 17.9 ± 0.2, 20.1 ± 0.2, 22.0 ± 0.2,

24.3 ± 0.2, 25.0 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern.

41. The solid Form XI 0b of claim 40, further characterized by a peak corresponding to a 2-theta value measured in degrees of 13.2 ± 0.2 in an X-ray powder diffraction pattern.

42. A nitrate salt of Compound 1.

43. A solid form of a nitrate salt of Compound 1 designated as Form XI 1.

44. The solid Form XI 1 of claim 43, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.9 ± 0.2, 25.4 ± 0.2, and 33.1 ± 0.2 in an X-ray powder diffraction pattern.

45. The solid Form XI 1 of claim 44, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.5 ± 0.2, 13.2 ± 0.2, 14.7 ± 0.2, 15.6 ± 0.2, 19.0 ± 0.2, 22.5 ± 0.2, and 23.9 ± 0.2 in an X-ray powder diffraction pattern.

46. A mesylate salt of Compound 1.

47. A solid form of a mesylate salt of Compound 1 designated as Form X12.

48. The solid Form XI 2 of claim 47, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 16.8 ± 0.2, 20.1 ± 0.2, 20.6 ± 0.2, 21.4 ± 0.2, 22.5 ± 0.2, 23.2 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern.

49. The solid Form XI 2 of claim 48, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.5 ± 0.2, 18.0 ± 0.2, and 20.1 ± 0.2 in an X-ray powder diffraction pattern.

50. An esylate salt of Compound 1.

A solid form of an esylate salt of Compound 1 designated as Form

52. The solid Form XI 3 of claim 51, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.3 ± 0.2, 12.6 ± 0.2, 13.8 ± 0.2, 23.7 ± 0.2,

25.2 ± 0.2, and 28.3 ± 0.2 in an X-ray powder diffraction pattern.

53. The solid Form XI 3 of claim 52, further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.8 ± 0.2 in an X-ray powder diffraction pattern.

54. A besylate salt of Compound 1.

55. A solid form of a besylate salt of Compound 1 designated as Form X14.

56. The solid Form X14 of claim 55, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.6 ± 0.2, 21.8 ± 0.2, 24.0 ± 0.2, and 29.2 ± 0.2 in an X-ray powder diffraction pattern.

57. The solid Form X14 of claim 56, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.6 ± 0.2, 15.7 ± 0.2, 22.3 ± 0.2, 24.9 ± 0.2, and 30.2 ± 0.2 in an X-ray powder diffraction pattern.

58. A tosylate salt of Compound 1.

59. A solid form of a tosylate salt of Compound 1 designated as Form XI 5.

60. The solid Form XI 5 of claim 59, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 12.1 ± 0.2, 15.7 ± 0.2, and 21.9 ± 0.2 in an X-ray powder diffraction pattern.

61. A naphthalate salt of Compound 1.

A solid form of a naphthalate salt of Compound 1 designated as Form

63. The solid Form XI 6 of claim 62, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 14.0 ± 0.2, 16.6 ± 0.2, 19.1 ± 0.2, 21.7 ± 0.2, 24.6 ± 0.2, and 26.1 ± 0.2 in an X-ray powder diffraction pattern.

64. The solid Form XI 6 of claim 63, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2 and 23.5 ± 0.2 in an X-ray powder diffraction pattern.

65. A naphthalene disulfonate salt of Compound 1.

66. A solid form of a naphthalene disulfonate salt of Compound 1 designated as Form X17.

67. The solid Form XI 7 of claim 66, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 22.9 ± 0.2, 26.1 ± 0.2, and 27.2 ± 0.2 in an X-ray powder diffraction pattern.

68. The solid Form XI 7 of claim 67, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.9 ± 0.2, 17.7 ± 0.2, 19.6 ± 0.2, and 24.1 ± 0.2 in an X-ray powder diffraction pattern.

69. A phosphate salt of Compound 1.

70. A solid form of a phosphate salt of Compound 1 designated as Form XI 8.

71. The solid Form XI 8 of claim 70, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.0 ± 0.2, 16.1 ± 0.2, 17.5 ± 0.2, 19.8 ± 0.2, 26.0 ± 0.2, and 27.1 ± 0.2 in an X-ray powder diffraction pattern.

72. An edysilate salt of Compound 1.

73. A solid form of an edysilate salt of Compound 1 designated as Form XI 9.

74. The solid Form XI 9 of claim 73, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.2 ± 0.2, 23.7 ± 0.2, and 28.1 ± 0.2 in an X-ray powder diffraction pattern.

75. The solid Form XI 9 of claim 74, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 22.6 ± 0.2 and 25.5 ± 0.2 in an X-ray powder diffraction pattern.

76. A camphor- 10-sulfonate salt of Compound 1.

77. A solid form of a camphor- 10-sulfonate salt of Compound 1 designated as Form X20.

78. The solid Form X20 of claim 77, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 13.4 ± 0.2, 17.0 ± 0.2, 17.8 ± 0.2, 23.5 ± 0.2, 24.9 ± 0.2, and 27.5 ± 0.2 in an X-ray powder diffraction pattern.

79. The solid Form X20 of claim 78, further characterized by a peak corresponding to a 2-theta value measured in degrees of 16.7 ± 0.2 in an X-ray powder diffraction pattern.

80. A solid form of a co-crystal comprising Compound 1 and an acid selected from malonic acid, succinic acid, glutaric acid, fumaric acid, maleic acid, acetylsalicylic acid, glycolic acid, oxalic acid, or 2-oxoglutaric acid.

81. A solid form of a co-crystal comprising malonic acid and Compound 1 designated as Form X21.

82. The solid Form X21 of claim 81 , characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.4 ± 0.2, 14.7 ± 0.2, 16.1 ± 0.2, 18.2 ± 0.2, 25.0 ± 0.2, 25.7 ± 0.2, and 26.4 ± 0.2 in an X-ray powder diffraction pattern.

83. The solid Form X21 of claim 82, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.0 ± 0.2 and 19.7 ± 0.2 in an X-ray powder diffraction pattern.

84. A solid form of a co-crystal comprising succinic acid and Compound 1 designated as Form X22.

85. The solid Form X22 of claim 84, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 6.6 ± 0.2, 11.3 ± 0.2, 15.4 ± 0.2, 17.2 ± 0.2,

19.2 ± 0.2, and 23.5 ± 0.2 in an X-ray powder diffraction pattern.

86. The solid Form X22 of claim 85, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.7 ± 0.2, 13.9 ± 0.2, and 18.3 ± 0.2 in an X-ray powder diffraction pattern.

87. A solid form of a co-crystal comprising glutaric acid and Compound 1 designated as Form X23.

88. The solid Form X23 of claim 87, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 17.3 ± 0.2, 19.0 ± 0.2, 24.1 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern.

89. The solid Form X23 of claim 88, further characterized by a peak corresponding to a 2-theta value measured in degrees of 18.6 ± 0.2 in an X-ray powder diffraction pattern.

90. A solid form of a co-crystal comprising fumaric acid and Compound 1 designated as Form X24.

91. The solid Form X24 of claim 90, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 5.5 ± 0.2, 8.5 ± 0.2, 14.1 ± 0.2, 19.4 ± 0.2,

21.1 ± 0.2, 23.8 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern.

92. The solid Form X24 of claim 91, further characterized by a peak corresponding to a 2-theta value measured in degrees of 12.0 ± 0.2 in an X-ray powder diffraction pattern.

93. A solid form of a co-crystal comprising maleic acid and Compound 1 designated as Form X25.

94. The solid Form X25 of claim 93, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 3.9 ± 0.2, 5.3 ± 0.2, and 19.3 ± 0.2 in an X-ray powder diffraction pattern.

95. The solid Form X25 of claim 94, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2 and 16.7 ± 0.2 in an X-ray powder diffraction pattern.

96. A solid form of a co-crystal comprising malic acid and Compound 1 designated as Form X26.

97. The solid Form X26 of claim 96, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.1 ± 0.2, 19.5 ± 0.2, 21.6 ± 0.2, 23.8 ± 0.2, and 26.0 ± 0.2 in an X-ray powder diffraction pattern.

98. The solid Form X26 of claim 97, further characterized by a peak corresponding to a 2-theta value measured in degrees of 15.5 ± 0.2 in an X-ray powder diffraction pattern.

99. A solid form of a co-crystal comprising acetylsalicylic acid and Compound 1 designated as Form X27.

100. The solid Form X27 of claim 99, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 11.0 ± 0.2, 19.9 ± 0.2, and 24.7 ± 0.2 in an X-ray powder diffraction pattern.

101. The solid Form X27 of claim 100, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 8.1 ± 0.2, 15.1 ± 0.2, and 28.0 ± 0.2 in an X-ray powder diffraction pattern.

102. A solid form of a co-crystal comprising 2-oxoglutaric acid and Compound 1 designated as Form X28.

103. The solid Form X28 of claim 102, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 12.9 ± 0.2, 22.6 ± 0.2, 24.7 ± 0.2, and 25.3 ± 0.2 in an X-ray powder diffraction pattern.

104. The solid Form X28 of claim 103, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.9 ± 0.2 and 20.3 ± 0.2 in an X-ray powder diffraction pattern.

105. A solid form of a co-crystal comprising oxalic acid and Compound 1 designated as Form X29.

106. The solid Form X29 of claim 105, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.9 ± 0.2, 15.8 ± 0.2, 17.1 ± 0.2, 18.2 ± 0.2, and

23.6 ± 0.2 in an X-ray powder diffraction pattern.

107. The solid Form X29 of claim 106, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 19.7 ± 0.2, 25.4 ± 0.2, and 26.6 ± 0.2 in an X-ray powder diffraction pattern.

108. A solid form of a co-crystal comprising glycolic acid and Compound 1 designated as Form X30.

109. The solid Form X30 of claim 108, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.8 ± 0.2, 15.6 ± 0.2, and 23.8 ± 0.2 in an X-ray powder diffraction pattern.

110. The solid Form X30 of claim 109, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 14.5 ± 0.2, 18.4 ± 0.2, 18.5 ± 0.2,

19.7 ± 0.2, and 26.7 ± 0.2 in an X-ray powder diffraction pattern.

11 1. An amorphous form of Compound 1 designated as Form X31.