Solid forms, pharmaceutical compositions, and preparations of heteroaromatic macrocyclic ether compounds

Abstract

Provided herein are solid forms comprising the compounds of formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharma- ceutically acceptable salt thereof.Also provided herein are methods of synthesizing the compounds of formula (I), pharmaceutical compositions comprising same, and methods of treating, preventing, and managing various disorders using the compositions provided herein.

Description

[Technical Field]

[0001] This application claims the benefit of priority to U.S. Patent Application No. 63 / 328,609, filed April 7, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] 1. Background technology Receptor tyrosine kinases (RTKs) are cell surface enzymes that receive external signals, such as those related to growth and division, and transmit these signals through kinase activity within the cell. Many RTKs are proto-oncogenes, and aberrant RTK activity can drive cell survival, growth, and proliferation, leading to cancer and related disorders. This aberrant kinase activity can be caused by mutations, such as activating mutations in the kinase domain, gene rearrangements that result in fusion proteins containing an intact kinase domain, amplification, and other means. RTK proto-oncogenes include ROS1, anaplastic lymphoma kinase (ALK), NTRK1 (encoding TRKA), NTRK2 (encoding TRKB), and NTRK3 (encoding TRKC).

[0003] ROS1 is a RTK proto-oncogene with ROS1 rearrangements detected in non-small cell lung cancer (NSCLC), glioblastoma, inflammatory myofibroblastic tumor (IMT), cholangiocarcinoma, ovarian cancer, gastric cancer, colorectal cancer, angiosarcoma, and spitzoid melanoma. Oncogenic ROS1 gene fusions contain the kinase domain (3' region) of ROS1 fused to the 5' region of various partner genes. Examples of ROS1 fusion partner genes observed in NSCLC include SLC34A2, CD74, TPM3, SDC4, EZR, LRIG3, KDELR2, CEP72, CLTL, CTNND2, GOPC, GPRC6A, LIMA1, LRIG3, MSN, MYO5C, OPRM1, SLC6A17 (putative), SLMAP, SRSF6, TFG, TMEM106B, TPD52L1, ZCCHC8, and CCDC6. Other fusion partners include CAPRIN1, CEP85L, CHCHD3, CLIP1 (putative), EEF1G, KIF21A (putative), KLC1, SART3, ST13 (putative), TRIM24 (putative), ERC1, FIP1L1, HLAA, KIAA1598, MYO5A, PPFIBP1, PWWP2A, FN1, YWHAE, CCDC30, NCOR2, NFKB2, APOB, PLG, RBP4, and GOLGB1.

[0004] ALK is a RTK proto-oncogene with ALK rearrangements detected in many cancers, including NSCLC, anaplastic large cell lymphoma (ALCL), IMT, diffuse large B-cell lymphoma (DLBCL), esophageal squamous cell carcinoma (ESCC), renal medullary carcinoma, renal cell carcinoma, breast cancer, colon cancer, serous ovarian cancer, papillary thyroid carcinoma, and spitzoid tumors, as well as ALK-activating mutations detected in neuroblastoma. Oncogenic ALK gene fusions contain the kinase domain (3' region) of ALK fused to the 5' region of more than 20 different partner genes, the most common partner genes being EML4 in NSCLC and NPM in ALCL. Other partner genes include TMP1, WDCP, GTF2IRD1, TPM3, TPM4, CLTC, LMNA, PRKAR1A, RANBP2, TFG, FN1, KLC1, VCL, STRN, HIP1, DCTN1, SQSTM1, TPR, CRIM1, PTPN3, FBXO36, ATIC, and KIF5B.

[0005] NTRK1, NTRK2, and NTRK3 are RTK proto-oncogenes that encode TRK family kinases, and RTK proto-oncogenes with NTRK1, NTRK2, and NTRK3 chromosomal rearrangements are detected at low frequencies in many cancers. However, TRK inhibition, particularly in the central nervous system (CNS), for the treatment of ROS1-positive or ALK-positive patients is associated with adverse reactions, including dizziness / ataxia / gait disturbance, paresthesia, weight gain, and cognitive changes.

[0006] Prior art drugs used to treat oncogenic ROS1 and ALK have significant deficiencies. These deficiencies may manifest as one or more of the following: associated TRK inhibition, limited CNS activity, and inadequate activity against resistance mutations. Treatment of ROS1- or ALK-positive patients with TRK inhibition is associated with adverse reactions, particularly in the CNS, including dizziness / ataxia / gait disturbances, paresthesia, weight gain, and cognitive changes. Additionally, there is a need for CNS-penetrant, TRK-sparing inhibitors of wild-type ROS1 kinase domain and ROS1 with acquired resistance mutations, occurring either individually or in combination, including G2032R, D2033N, S1986F, S1986Y, L2026M, L1951R, E1935G, L1947R, G1971E, E1974K, L1982F, F2004C, F2004V, E2020K, C2060G, F2075V, V2089M, V2098I, G2101A, D2113N, D2113G, L2155S, L2032K, and L2086F. Similarly, there is a need for CNS-penetrant, TRK-sparing inhibitors of ALK with acquired resistance mutations. A variety of ALK drug resistance mutations occurring either individually or in combination have been reported, including G1202R, L1196M, G1269A, C1156Y, I1171T, I1171N, I1171S, F1174L, F1174S, V1180L, S1206Y, E1210K, I1151Tins, T1151M, F1174C, G1202del, D1203N, S1206Y, S1206C, L1152R, L1196Q, L1198P, L1198F, R1275Q, L1152P, C1156T, and F1245V.

[0007] Additionally, for the manufacture of drug substances intended for human use, procedures must be in place that can control the levels of impurities and ensure that API products that consistently meet predetermined specifications are produced. Thus, a need exists for processes for preparing ROS1 and ALK inhibitors suitable for human use, particularly on a commercial scale, i.e., processes that are, among other things, safe, scalable, efficient, economically viable, and / or have other desirable properties. Disclosed herein are crystalline forms and pharmaceutical compositions comprising such crystalline forms to address these needs and provide exemplary advantages, among other entities. Summary of the Invention

[0008] 2. Summary of the invention Provided herein are solid forms comprising a compound of Formula (I) (also referred to as Compound 1), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof. [ka] In some embodiments, the solid form is a crystalline form. In other embodiments, the solid form is an amorphous form. In some embodiments, the solid form is a solid form of the compound of Formula (I). In some embodiments, the solid form is a solid form of the free base of the compound of Formula (I). In some embodiments, the solid form is a crystalline form of the free base of the compound of Formula (I).

[0009] Also provided herein are methods of preparing the solid forms. In some embodiments, provided herein are methods of preparing the solid form of the free base of the compound of Formula (I).

[0010] Also provided herein is a method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a solid form of a compound of Formula (I) provided herein.

[0011] Also provided herein are pharmaceutical compositions comprising a solid form of the compound of Formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises a solid form of the free base of the compound of Formula (I). In some embodiments, the pharmaceutical composition comprises a solid form of a pharmaceutically acceptable salt of the compound of Formula (I).

[0012] Also, the compound of formula (II): [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, comprising: (Step 2.0) a compound of formula (III), [ka] or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, with a brominating reagent.

[0013] Also, the compound of formula (II): [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, comprising: (Step 2a.1) a compound of formula (XXIX), [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, with a compound of formula (XXX): [ka] or a pharmaceutically acceptable salt thereof.

[0014] In some embodiments, the process comprises: (Step 1.0) Cyclizing a compound of formula (II), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, to give a compound of formula (I): [ka] or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof.

[0015] Also provided herein is a method of treating cancer, comprising administering a therapeutically effective amount of a solid form provided herein.

[0016] Also, Compound 1, [ka] Provided herein is a pharmaceutical composition comprising: or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof; a diluent; a disintegrant; a glidant; a binder; and a lubricant.

[0017] Also provided herein is a method of treating cancer, comprising administering a therapeutically effective amount of a pharmaceutical composition provided herein.

[0018] Also, the compound of formula (II): [ka] Salts of the formula:

[0019] Also, the compound of formula (II): [ka] Provided herein are solid forms comprising salts of

[0020] 3. Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawings]

[0021] 4. Brief description of the drawings [Figure 1] A is a representative X-ray powder diffraction (XRPD) pattern of Form 1 of the free base of Compound 1 (2-THF methyl solvate), and B is a representative XRPD pattern of Form 1 of the free base of Compound 1 (isopropyl acetate solvate).

[0022] [Figure 2] 1 is a representative integrated thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) thermogram for Form 1 of the free base of Compound 1 (2-THF methyl solvate).

[0023] [Figure 3] 1 is a representative integrated thermal TGA and DSC thermogram for Form 1 of the free base of Compound 1 (isopropyl acetate solvate).

[0024] [Figure 4] 1 is a representative XRPD pattern of Form 2 of the free base of Compound 1.

[0025] [Figure 5] 1 is a representative DSC thermogram of Form 2 of the free base of Compound 1.

[0026] [Figure 6] 1 is a representative DVS isotherm for Form 2 of the free base of Compound 1.

[0027] [Figure 7] FIG. 1 is a representative diagram of the unit cell a-axis of a single crystal X-ray diffraction study of Form 2 of the free base of Compound 1.

[0028] [Figure 8] 1 is a representative XRPD pattern of Form 3 of the free base of Compound 1.

[0029] [Figure 9] 1 is a representative integrated TGA and DSC thermogram for Form 3 of the free base of Compound 1.

[0030] [Figure 10] 1 is a representative XRPD pattern of Form 4 of the free base of Compound 1.

[0031] [Figure 11] 1 is a representative integrated TGA and DSC thermogram for Form 4 of the free base of Compound 1.

[0032] [Figure 12] A is a representative XRPD pattern of Form 5 of the free base of Compound 1 (mixed t-butanol and isopropanol solvate), B is a representative XRPD pattern of Form 5 of the free base of Compound 1 (mixed t-butanol and acetone solvate), and C is a representative XRPD pattern of Form 5 of the free base of Compound 1 (mixed t-butanol and THF solvate).

[0033] [Figure 13] 1 is a representative integrated TGA and DSC thermogram for Form 5 of the free base of Compound 1 (mixed t-butanol and isopropanol solvate).

[0034] [Figure 14] 1 is a representative integrated TGA and DSC thermogram for Form 5 of the free base of Compound 1 (mixed t-butanol and acetone solvate).

[0035] [Figure 15] 1 is a representative integrated TGA and DSC thermogram for the free base form 5 of Compound 1 (t-butanol and THF mixed solvate).

[0036] [Figure 16] 1 is a representative XRPD pattern of Form 6 of the free base of Compound 1.

[0037] [Figure 17] 1 is a representative XRPD pattern of Form 7 of the free base of Compound 1.

[0038] [Figure 18] 1 is a representative integrated TGA and DSC thermogram for Compound 1 free base form 7.

[0039] [Figure 19] 1 is a representative XRPD pattern of Form 8 of the free base of Compound 1.

[0040] [Figure 20] 1 is a representative integrated TGA and DSC thermogram for the free base form 8 of Compound 1.

[0041] [Figure 21] 1 is a representative XRPD pattern of Form 9 of the free base of Compound 1.

[0042] [Figure 22] 1 is a representative integrated TGA and DSC thermogram for the free base form 9 of Compound 1.

[0043] [Figure 23] 1 is a representative XRPD pattern of the free base form 10 of Compound 1.

[0044] [Figure 24] 1 is a representative integrated TGA and DSC thermogram for the free base form 10 of Compound 1.

[0045] [Figure 25] 1 is a representative XRPD pattern of the free base form 11 of Compound 1.

[0046] [Figure 26] 1 is a representative integrated TGA and DSC thermogram for the free base form 11 of Compound 1.

[0047] [Figure 27] 1 is a representative XRPD pattern of the free base form 12 of Compound 1.

[0048] [Figure 28] 1 is a representative integrated TGA and DSC thermogram for the free base form 12 of Compound 1.

[0049] [Figure 29] 1 is a representative XRPD pattern of the free base form 13 of Compound 1.

[0050] [Figure 30] 1 is a representative integrated TGA and DSC thermogram for the free base form 13 of Compound 1.

[0051] [Figure 31] 1 is a representative XRPD pattern of the free base form 14 of Compound 1.

[0052] [Figure 32] 1 is a representative integrated TGA and DSC thermogram for the free base form 14 of Compound 1.

[0053] [Figure 33] 1 is a representative XRPD pattern of the free base form 15 of Compound 1.

[0054] [Figure 34] 1 is a representative integrated TGA and DSC thermogram for the free base form 15 of Compound 1.

[0055] [Figure 35]1 is a representative XRPD pattern of Form A of the mesylate salt of Compound 2.

[0056] [Figure 36] 1 is a representative DSC thermogram of Form A of the mesylate salt of Compound 2.

[0057] [Figure 37] 1 is a representative TGA thermogram of Form A of the mesylate salt of Compound 2.

[0058] [Figure 38] 1 is a representative XRPD pattern of Form A of the camsylate salt of Compound 2.

[0059] [Figure 39] 1 is a representative DSC thermogram for Form A of the camsylate salt of Compound 2.

[0060] [Figure 40] 1 is a representative TGA thermogram of Form A of the camsylate salt of Compound 2.

[0061] [Figure 41] 1 is a representative DVS isotherm of Form A of the camsylate salt of Compound 2.

[0062] [Figure 42] 1 is a representative XRPD pattern of Form A of the esylate salt of Compound 2.

[0063] [Figure 43] 1 is a representative DSC thermogram for Form A of the esylate salt of Compound 2.

[0064] [Figure 44] 1 is a representative TGA thermogram of Form A of the esylate salt of Compound 2.

[0065] [Figure 45]1 is a representative DVS isotherm of Form A of the esylate salt of Compound 2.

[0066] [Figure 46] 1 is a representative XRPD pattern of Form A of the sulfate salt of Compound 2.

[0067] [Figure 47] 1 is a representative DSC thermogram of Form A of the sulfate salt of Compound 2.

[0068] [Figure 48] 1 is a representative TGA thermogram of Form A of the sulfate salt of Compound 2.

[0069] [Figure 49] 1 is a representative DVS isotherm of Form A of the sulfate salt of Compound 2.

[0070] [Figure 50] 1 is a representative XRPD pattern of Form A of the tosylate salt of Compound 2.

[0071] [Figure 51] 1 is a representative DSC thermogram for Form A of the tosylate salt of Compound 2.

[0072] [Figure 52] 1 is a representative XRPD pattern of Form A of the besylate salt of Compound 2.

[0073] [Figure 53] 1 is a representative DSC thermogram for Form A of the besylate salt of Compound 2.

[0074] [Figure 54] 1 is a representative XRPD pattern of Form B of the besylate salt of Compound 2.

[0075] [Figure 55] 1 is a representative XRPD pattern of Form A of the 2-naphthalenesulfonate salt of Compound 2.

[0076] [Figure 56] 1 is a representative DSC thermogram of Form A of the 2-naphthalenesulfonate salt of Compound 2.

[0077] [Figure 57] 1 shows the dissolution profile of Compound 1 tablets.

[0078] [Figure 58] 1 is a representative XRPD pattern of Form A of the salicylate salt of Compound 1.

[0079] [Figure 59] 1 is a representative XRPD pattern of Form A of the maleate salt of Compound 1. DETAILED DESCRIPTION OF THE INVENTION

[0080] 5. MODE FOR CARRYING OUT THE INVENTION 5.1 Definition Unless otherwise defined, all technical and scientific terms used herein have the meanings commonly understood by those of ordinary skill in the art to which this disclosure pertains. The following references provide those of ordinary skill in the art with general definitions of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the following meanings ascribed to them unless otherwise specified.

[0081] In some embodiments, chemical structures are disclosed with their corresponding chemical names. In case of conflict, the chemical structure, not the name, defines the meaning.

[0082] As used herein, the terms "comprising" and "including" may be used interchangeably. The terms "comprising" and "including" are interpreted as specifying the presence of a described feature or referenced component, but do not exclude the presence or addition of one or more features or components, or groups thereof. In addition, the terms "comprising" and "including" are intended to include examples encompassed by the term "consisting of." Thus, the term "consisting of" may be used in place of the terms "comprising" and "including" to provide more specific embodiments of the present invention.

[0083] The term "consisting of" means that the object has at least 90%, 95%, 97%, 98%, or 99% of the recited features or components it comprises. In another embodiment, the term "consisting of" excludes any other features or components from the scope of any succeeding recitation, except those that are not essential to the technical effect being achieved.

[0084] As used herein, the term "or" is understood to be inclusive unless specifically stated otherwise or clear from context. As used herein, the terms "a," "an," and "the" are understood to be singular or plural unless specifically stated otherwise or clear from context. For example, when a compound provided herein is administered to "a patient," this includes administering the compound to an individual patient or to a population of patients.

[0085] As used herein, unless otherwise specified, "stereoisomer" refers to various stereoisomeric forms of a compound containing one or more asymmetric centers or steric hindrance in its structure. In some embodiments, a stereoisomer is an enantiomer, a mixture of enantiomers, an atropisomer, or a tautomer thereof. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers, or geometric isomers (e.g., atropisomers), or in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. In some embodiments, the compounds provided herein may be atropisomers. In certain embodiments, atropisomers are stereoisomers resulting from hindrance of rotation about a single bond, where the energy difference due to steric strain or other contributors results in a sufficiently high hindrance of rotation to allow for the isolation of individual conformers. Stereoisomers may be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts, or preferred isomers may be prepared by asymmetric synthesis. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, ELS Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, SH Tables of Resolving Agents and Optical Resolution sp. 268 (E.L. Eliel, Ed., University of Notre Dame Press, Notre Dame, IN 1972). The present invention additionally encompasses compounds as individual isomers substantially free of other isomers, or alternatively, as mixtures of various isomers.

[0086] In certain embodiments, the compounds provided herein may be racemic. In certain embodiments, the compounds provided herein may be enriched in one enantiomer. For example, the compounds provided herein may have an ee of more than about 30%, more than about 40%, more than about 50%, more than about 60%, more than about 70%, more than about 80%, more than about 90%, or even more than about 95%. In certain embodiments, the compounds provided herein may have two or more stereocenters. In certain such embodiments, the compounds provided herein may be enriched in one or more diastereomers. For example, the compounds provided herein may have an ee of more than about 30%, more than about 40%, more than about 50%, more than about 60%, more than about 70%, more than about 80%, more than about 90%, or even more than about 95%.

[0087] In certain embodiments, therapeutic preparations can be enriched to provide predominantly one enantiomer of a compound. An enantiomerically enriched mixture can contain, for example, at least about 60 mole percent of one enantiomer, or more particularly, at least about 75, about 90, about 95, or even about 99 mole percent. In certain embodiments, a compound enriched in one enantiomer is substantially free of the other enantiomer, where substantially free means that the substance comprises, for example, less than about 10%, or less than about 5%, or less than about 4%, or less than about 3%, or less than about 2%, or less than about 1% of the amount of the other enantiomer in a composition or compound mixture. For example, if a composition or compound mixture contains about 98 grams of a first enantiomer and about 2 grams of a second enantiomer, the composition or compound mixture is said to contain about 98 mole percent of the first enantiomer and only about 2% of the second enantiomer.

[0088] In certain embodiments, therapeutic preparations can be enriched to provide predominantly one diastereomer of a compound. A diastereomerically enriched mixture can contain, for example, at least about 60 mole percent of one diastereomer, or more particularly, at least about 75, about 90, about 95, or even about 99 mole percent.

[0089] In some embodiments, moieties in a compound exist as a mixture of tautomers. A "tautomer" is a structural isomer of a moiety or compound that readily interconverts with another structural isomer. For example, a pyrazole ring has two tautomers: [ka] The two tautomers differ in the location of the pi bond and the hydrogen atoms. Unless otherwise specified, a representation of one tautomer of a moiety or compound encompasses all possible tautomers.

[0090] The term "subject" to which administration is contemplated includes, but is not limited to, humans (i.e., male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or an adult subject (e.g., a young adult, middle-aged adult, or elderly adult)) and / or other primates (e.g., cynomolgus monkeys, rhesus monkeys); mammals, including commercially relevant mammals, e.g., cows, pigs, horses, sheep, goats, cats, and / or dogs; and / or birds, including commercially relevant birds, e.g., chickens, ducks, geese, quail, and / or turkeys. In certain embodiments, the subject is a human adult at least 40 years of age. In certain embodiments, the subject is a human adult at least 50 years of age. In certain embodiments, the subject is a human adult at least 60 years of age. In certain embodiments, the subject is a human adult at least 70 years of age. In certain embodiments, the subject is a human adult at least 18 years of age or at least 12 years of age. As used herein, unless otherwise specified, a human subject to whom administration of a therapeutic agent (e.g., a compound described herein) is contemplated to treat, prevent, or manage a disease, disorder, or condition, or a symptom thereof, is also referred to as a "patient."

[0091] As used herein, a therapeutic agent that "prevents" a disorder or condition refers to a compound that, in a statistical sample, reduces or delays the occurrence of the disorder or condition in a treated sample relative to an untreated control sample, or reduces the severity of one or more symptoms of the disorder or condition relative to an untreated control sample. These effects are also referred to as "prophylactic" effects. Thus, as used herein, unless otherwise specified, the terms "prevention" and "preventing" refer to an approach for obtaining a beneficial or desired result, which beneficial or desired result includes, but is not limited to, a prophylactic benefit. For a prophylactic benefit, a therapeutic agent may be administered to a patient at risk of developing a particular disease or who reports one or more physiological symptoms of a disease, even if the disease may not have been diagnosed. In one embodiment, a therapeutic agent is administered prior to clinical signs of an unwanted condition (e.g., the disease of interest or other unwanted condition) for a prophylactic benefit (e.g., the therapeutic agent protects the subject from developing the unwanted condition).

[0092] As used herein, unless otherwise specified, the terms "treatment" and "treating" refer to curative or palliative treatment. Beneficial or desired clinical results include, but are not limited to, the total or partial alleviation of symptoms associated with a disease or disorder or condition, whether detectable or undetectable, attenuation of the extent of the disease, a stabilized (i.e., not worsening) state of the disease, delay or slowing of disease progression, remission or alleviation of the disease state (e.g., one or more symptoms of the disease), and remission (whether partial or complete). "Treatment" can also mean prolonging survival compared to expected survival if not receiving treatment. In one embodiment, "treatment" includes administration of a therapeutic agent after the onset of an undesired condition (i.e., intended to attenuate, ameliorate, or stabilize an existing undesired condition or its side effects).

[0093] As used herein, unless otherwise specified, "cancer" refers to any malignant and / or invasive growth or tumor caused by abnormal cell growth, including solid tumors named for the type of cell that forms them, cancers of the blood, bone marrow, or lymphatic system. Examples of solid tumors include, but are not limited to, sarcomas and carcinomas. Examples of blood cancers include, but are not limited to, leukemia, lymphoma, and myeloma. Cancer includes, but is not limited to, primary cancers that originate in a particular part of the body, metastatic cancers that have spread to other parts of the body from where they began, recurrences from the original primary cancer after remission, and second primary cancers, which are new primary cancers in people with a history of a previous cancer of a different type than the latter.

[0094] As used herein, unless otherwise specified, "abnormal cell growth" refers to cell growth that is independent of normal regulatory mechanisms (e.g., contact loss inhibition). Abnormal cell growth can be benign (not cancerous) or malignant (cancerous). In some embodiments of the methods provided herein, the abnormal cell growth is cancer.

[0095] In some embodiments, the abnormal cell growth is cancer mediated by anaplastic lymphoma kinase (ALK). In some such embodiments, the ALK is genetically modified ALK. In other embodiments, the abnormal cell growth is cancer mediated by ROS1 kinase. In some such embodiments, the ROS1 kinase is genetically modified ROS1 kinase. In some embodiments, the abnormal cell growth is cancer, particularly NSCLC. In some such embodiments, the NSCLC is mediated by ALK or ROS1. In certain embodiments, the cancer is NSCLC mediated by genetically modified ALK or genetically modified ROS1.

[0096] As used herein, unless otherwise indicated, the term "managing" includes preventing the recurrence of a particular disease or disorder in a patient who has had it, extending the time that a patient who has had a disease or disorder remains in remission, reducing patient mortality, and / or maintaining a reduction in the severity or avoidance of symptoms associated with the disease or condition being managed.

[0097] As used herein, "effective amount" refers to an amount that is sufficient to achieve a desired biological effect.As used herein, "therapeutically effective amount" refers to an amount that is sufficient to achieve a desired therapeutic effect.For example, a therapeutically effective amount can refer to an amount that is sufficient to improve at least one sign or symptom of cancer.

[0098] A "response" to a treatment method can include, among other things, a decrease in or amelioration of negative symptoms, a decrease in the progression of the disease or its symptoms, an increase in beneficial symptoms or clinical outcomes, a reduction in side effects, stabilization of the disease, or a partial or complete cure of the disease.

[0099] As used herein, unless otherwise indicated, the term "recurrent" refers to a disorder, disease, or condition that responded (e.g., achieved a complete response) to previous treatment and then had progression. The previous treatment may include one or more lines of therapy.

[0100] As used herein, unless otherwise indicated, the term "resistant" refers to a disorder, disease or condition that has not responded to previous treatment, which may include one or more lines of therapy.

[0101] As used herein, "crystalline" refers to a homogeneous solid formed by a repeating three-dimensional pattern of atoms, ions, or molecules with a fixed distance between the constituent parts. A unit cell is the simplest repeating unit in this pattern. Despite the homogeneous nature of an ideal crystal, perfect crystals rarely, if ever, exist. As used herein, "crystalline" encompasses crystalline forms containing crystalline defects, such as those typically formed by manipulating (e.g., preparing, purifying) the crystalline forms described herein. One of skill in the art can determine whether a sample of a compound is crystalline despite the presence of such defects. Crystalline forms may be characterized by analytical methods, such as X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR), single crystal X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and / or any other suitable analytical technique.

[0102] As used herein, "solvate" refers to a crystalline form of a molecule, atom, and / or ion that further comprises one or more molecules of a solvent incorporated within the crystalline lattice structure. The solvent molecules in a solvate may exist in an ordered and / or disordered arrangement. A solvate may contain either a stoichiometric or non-stoichiometric amount of solvent molecules. For example, a solvate with a non-stoichiometric amount of solvent molecules may result from partial loss of solvent from the solvate. A solvate may occur as a dimer or oligomer comprising two or more molecules or compounds ABC within the crystalline lattice structure.

[0103] As used herein, "amorphous" refers to a solid form of molecules, atoms, and / or ions that are not crystalline. In particular, the term "amorphous form" describes a disordered solid form, i.e., a solid form that lacks long-range crystalline order. Amorphous solids do not exhibit definitive X-ray diffraction patterns. In certain embodiments, an amorphous form of a substance can be substantially pure from other amorphous and / or crystalline forms.

[0104] As used herein, unless otherwise specified, the term "solid form" and related terms refer to a physical form that is not primarily in a liquid or gaseous state. A solid form may be crystalline, amorphous, or a mixture thereof. As used herein, unless otherwise specified, the term "crystalline form" and related terms refer to a solid form that is crystalline. Crystalline forms include, but are not limited to, unsolvated forms, unhydrated forms, solvates, hydrates, and other molecular complexes thereof, as well as salts, solvates of salts, hydrates of salts, and other molecular complexes of salts. In certain embodiments, a solid or crystalline form of a substance may be substantially free of amorphous forms and / or other solid and / or crystalline forms. In certain embodiments, a solid and / or crystalline form of a substance may contain less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of one or more amorphous and / or other solid and / or crystalline forms. In certain embodiments, a solid or crystalline form of a substance may be physically and / or chemically pure. In certain embodiments, a solid or crystalline form of a substance may be about 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or 90% physically and / or chemically pure. In certain embodiments, a solid or crystalline form may be substantially chemically pure and / or substantially physically pure.

[0105] "Substantially pure," when used without further qualification, means that the compound has a purity of greater than about 90 weight percent, e.g., greater than about 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 weight percent, based on the weight of the compound, and includes a purity equal to about 100 weight percent. The remaining material may include other forms(s) of the compound and / or reaction and / or processing impurities resulting from its preparation. Purity may be assessed using techniques known in the art, e.g., HPLC assay.

[0106] The term "substantially pure" may also be used. When a compound is "substantially pure" with respect to the presence of chemical impurities (e.g., reaction and / or processing impurities resulting from its preparation), it may be referred to as "substantially chemically pure." When a compound is "substantially pure" with respect to the presence of the other enantiomer, it may be referred to as "substantially enantiomerically pure." In some embodiments, a compound (e.g., Compound 1) is substantially enantiomerically pure, with the other enantiomer (e.g., the S enantiomer) being present at less than about 10% by weight, less than about 5% by weight, less than about 3% by weight, less than about 1% by weight, less than about 0.5% by weight, or less than about 0.1% by weight. When a compound is "substantially pure" with respect to the presence of other physical forms of the compound having the structure shown, it may be referred to as "substantially physically pure." When qualified, "substantially pure" means that the indicated compound contains less than about 10%, less than about 5%, less than about 3%, less than about 1%, less than about 0.5%, or less than about 0.1% by weight of the indicated impurity. In certain embodiments, a solid form of Compound 1 is substantially pure (e.g., has a purity of at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% by weight). In certain embodiments, a solid form of Compound 1 has a purity of at least about 95% by weight. In certain embodiments, a solid form of Compound 1 is substantially enantiomerically pure (e.g., has an enantiomeric purity of at least about 98.0%, at least about 99.0%, at least about 99.5%, or at least about 99.9% by weight). In certain embodiments, a solid form of Compound 1 has an enantiomeric purity of at least about 99.5% by weight. In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 95% by weight. In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 96% by weight. In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 97% by weight.In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 98% by weight. In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 99% by weight. In certain embodiments, a pharmaceutical composition comprising Compound 1 has a purity of at least about 95% by weight for a period of 12 months.

[0107] A solid form may exhibit distinct physical characterization data that is specific to a particular solid form, such as the crystalline forms described herein. These characterization data may be obtained by various techniques known to those skilled in the art. The data provided by these techniques may be used to identify a particular solid form. For example, an XRPD pattern, DSC thermogram, or TGA thermogram that "matches" or, interchangeably, "substantially conforms" to one or more figures herein showing an XRPD pattern, DSC thermogram, or TGA thermogram, respectively, would be considered by those skilled in the art to represent a single crystalline form of a compound that is the same as the sample of the compound providing the pattern, thermogram, or thermogram of one or more figures provided herein. Thus, an XRPD pattern, DSC thermogram, or TGA thermogram that matches or substantially conforms to one of the figures may be identical to one of the figures, or perhaps may differ to some extent from one or more of the figures. For example, an XRPD pattern that differs to some extent from one or more of the figures may not necessarily exhibit every line of the diffraction pattern presented herein and / or may exhibit slight changes in the appearance or intensity of the lines, or shifts in the position of the lines. These differences typically result from differences in the conditions involved in obtaining the data or differences in the purity of the sample used to obtain the data. One skilled in the art can determine whether a sample of a crystalline compound is of the same or a different form than those disclosed herein by comparing the XRPD pattern or DSC thermogram or TGA thermogram of the sample with the corresponding XRPD pattern or DSC thermogram or TGA thermogram disclosed herein.

[0108] As used herein, unless otherwise specified, the terms "about" and "approximately," when used in connection with a dose, amount, or weight percent of a component of a composition or dosage form, refer to a dose, amount, or weight percent that would be recognized by one of ordinary skill in the art as providing an equivalent pharmacological effect to that obtained from the specified dose, amount, or weight percent. In certain embodiments, when used in this context, the terms "about" and "approximately" contemplate a dose, amount, or weight percent that is within 30%, within 20%, within 15%, within 10%, or within 5% of the specified dose, amount, or weight percent.

[0109] As used herein, unless otherwise specified, when used in reference to a numerical value or range of values ​​provided to characterize a particular solid form, such as a specific temperature or temperature range, e.g., describing a melting, dehydration, desolvation, or glass transition temperature; mass change, e.g., mass change as a function of temperature or humidity; solvent or water content, e.g., solvent or water content in terms of mass or percentage; or peak position, e.g., peak position in an analysis by IR or Raman spectroscopy or XRPD, the terms "about" and "approximately" indicate that the value or range of values ​​may deviate to an extent that would be considered reasonable by one skilled in the art, but still describe the particular solid form. For example, in certain embodiments, when used in this context, the terms "about" and "approximately" indicate that the numerical value or range of values ​​may vary within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0.5%, or 0.25% of the recited value or range of values. For example, in some embodiments, XRPD peak position values ​​may vary by up to ±0.2 degrees 2θ and still describe a particular XRPD peak. In one embodiment, XRPD peak position values ​​may vary by up to ±0.1 degrees 2θ. In one embodiment, XRPD peak position values ​​may vary by up to ±0.05 degrees 2θ.

[0110] The term "between" includes the endpoint numbers at both ends of a range. For example, a range described by "3 to 5" includes the numbers "3" and "5."

[0111] As used herein, unless otherwise specified, the term "pharmaceutically acceptable salt" refers to a salt that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of a subject without undue toxicity, irritation, allergic response, and the like, and that is commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1-19. In certain embodiments, pharmaceutically acceptable salts include, but are not limited to, alkyl, dialkyl, trialkyl, or tetraalkyl ammonium salts. In certain embodiments, pharmaceutically acceptable salts include, but are not limited to, L-arginine, benentamine, benzathine, betaine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, ethylenediamine, N-methylglucamine, hydrabamine, 1H-imidazole, lithium, L-lysine, magnesium, 4-(2-hydroxyethyl)morpholine, piperazine, potassium, 1-(2-hydroxyethyl)pyrrolidine, sodium, triethanolamine, tromethamine, and zinc salts. In certain embodiments, pharmaceutically acceptable salts include, but are not limited to, Na, Ca, K, Mg, Zn, or other metal salts.

[0112] Pharmaceutically acceptable acid addition salts may also exist as various solvates, for example with water, methanol, ethanol, dimethylformamide, etc. Also, mixtures of such solvates may be prepared. The source of such solvates may be from the solvent of crystallization, may be inherent in the solvent of preparation or crystallization, or may be exogenous to such solvent.

[0113] Pharmaceutically acceptable anionic salts include, but are not limited to, acetate, aspartate, benzenesulfonate, benzoate, besylate, bicarbonate, bitartrate, bromide, camsylate, carbonate, chloride, citrate, decanoate, edetate, esylate, fumarate, gluceptate, gluconate, glutamate, glycolate, hexanoate, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methyl sulfate, mucate, napsylate, nitrate, octanoate, oleate, pamoate, pantothenate, phosphate, polygalacturonate, propionate, salicylate, stearate, acetate, succinate, sulfate, tartrate, teoclate, and tosylate salts.

[0114] As used herein, unless otherwise specified, the term "enantiomerically pure" refers to a composition comprising one enantiomer of a compound having one or more chiral centers in an enantiomeric excess of at least about 50%, at least about 75%, at least about 90%, at least about 95%, or at least about 99%. In some embodiments, a composition can be "substantially enantiomerically pure," which refers to a preparation of a composition having at least about 85% by weight, e.g., at least about 90% by weight, or even, e.g., at least 95% by weight, of one enantiomer relative to the other enantiomer of the compound. In certain embodiments, the compositions provided herein comprise one enantiomer of the compound in an enantiomeric excess of at least about 90% by weight. In other embodiments, the compositions comprise one enantiomer of the compound in an enantiomeric excess of at least about 95% by weight, at least about 98% by weight, or at least about 99% by weight.

[0115] As used herein, unless otherwise indicated, the term "process(es)" provided herein refers to the methods provided herein that are useful for preparing the compounds described herein or the solid forms thereof (e.g., crystalline, partially crystalline, or amorphous forms) provided herein. Also provided herein are modifications of the methods provided herein (e.g., starting materials, reagents, protecting groups, solvents, temperatures, reaction times, purification). Generally, the technical teachings of one embodiment provided herein can be combined with those disclosed in any other embodiment provided herein.

[0116] As used herein, unless otherwise indicated, the terms "adding," "reacting," or "treating" and the like refer to contacting one reactant, reagent, solvent, catalyst, or reactive group, etc., with another reactant, reagent, solvent, catalyst, or reactive group, etc. The reactants, reagents, solvents, catalysts, or reactive groups, etc., can be added individually, simultaneously, or separately, and can be added in any order. The reactants, reagents, solvents, catalysts, or reactive groups, etc., can each be added in one portion, which may be delivered all at once or over a period of time, or in separate portions, which may also be delivered all at once or over a period of time. They can be added in the presence or absence of heat, and can optionally be added under an inert atmosphere. "Reacting" can refer to in situ formation or intramolecular reactions, where the reactive groups are within the same molecule.

[0117] As used herein, the term "combining" refers to the association of one or more chemical entities with one or more other chemical entities. Combining includes the process of adding one or more compounds to a solid, liquid, or gas mixture of one or more compounds (the same or other chemical entities), or to a liquid solution or multiphase liquid mixture. The act of combining includes one or more processes in which one or more compounds react with one or more compounds (the same or other chemical entities) (e.g., bond formation or cleavage, salt formation, solvate formation, chelation, or other non-bond associated modifications). The act of combining can include modification of one or more compounds, for example, modification of one or more compounds by isomerization (e.g., tautomerization, resolution of one isomer from another, or racemization).

[0118] As used herein, unless otherwise indicated, the term "converting" refers to subjecting an existing compound to reaction conditions suitable to result in the formation of an existing desired compound.

[0119] As used herein, the term "recovering" includes, but is not limited to, obtaining one or more compounds by collecting them during and / or after a process step disclosed herein, as well as obtaining one or more compounds by separating them from one or more other chemical entities during and / or after a process step disclosed herein. The term "collecting" refers to any process(es) known in the art for this purpose, including, but not limited to, filtering; decanting a mother liquor from a solid to obtain one or more compounds; and evaporating a liquid medium in a solution or other mixture to obtain a solid, oil, or other residue containing one or more compounds. Solids can be crystalline, non-crystalline, partially crystalline, or amorphous, of various particle sizes, powders of uniform particle size, or granules, among other characteristics known in the art. Oils can vary in color and viscosity and can include one or more solid forms as heterogeneous mixtures, among other characteristics known in the art. The term "separation" refers to any action(s) known in the art for this purpose, including, but not limited to, isolating one or more compounds from a solution or mixture by using, for example, seeded or unseeded crystallization or other precipitation techniques (e.g., adding an antisolvent to a solution to induce compound precipitation; heating the solution and then cooling to induce compound precipitation; scratching the surface of the solution with an instrument to induce compound precipitation), and distillation techniques. Recovering one or more compounds can include preparing a salt, solvate, hydrate, chelate, or other complex thereof, followed by collection or separation as described above.

[0120] As used herein, the term "catalyst precursor" refers to a chemical composition in which one or more components of an active catalyst (e.g., a metal center and a supporting ligand) are added to a reaction mixture, whereby the formation of the active catalyst occurs in situ. For example, a cataCXium A-linked palladium catalyst can be formed in situ by adding a catalyst precursor that includes a palladium source (e.g., Pd(OAc)2) and a source of cataCXium A (e.g., cataCXium A). Those skilled in the art will recognize that even when the metal source and supporting ligand are added to the reaction mixture in the form of a single chemical entity (e.g., Pd(dppf)Cl2), further activation and / or reaction in situ may be required to produce the active catalyst. However, as used herein, the term "catalyst" includes, but is not limited to, chemical compositions in which two or more components of an active catalyst (e.g., a metal center and a supporting ligand) are added to a reaction mixture in the form of a single chemical entity (e.g., Pd(dppf)Cl), even if further activation and / or reaction in situ is required to produce the active catalyst.

[0121] While most of the embodiments and examples provided herein are directed to one enantiomer of a compound, it is understood that the opposite enantiomer of a compound may be prepared by the provided processes when the stereochemistry of a chiral reactant, reagent, solvent, catalyst, or ligand, etc., is inverted.

[0122] As used herein, unless otherwise specified, the terms "solvent," "organic solvent," or "inert solvent" each mean a solvent that is inert under the conditions of the reaction being described. Unless specified to the contrary, for each gram of limiting reagent, 1 cc (or mL) of solvent constitutes a volumetric equivalent (or "volume").

[0123] The present disclosure can be more fully understood by reference to the following detailed description and illustrative examples, which are intended to exemplify non-limiting embodiments.

[0124] 5.2 Solid form Potential pharmaceutical solids include crystalline solids and amorphous solids. Amorphous solids are characterized by a lack of long-range structural order, while crystalline solids are characterized by structural periodicity. The desired class of pharmaceutical solid depends on the specific application; amorphous solids are often selected, for example, based on enhanced dissolution profiles, while crystalline solids may be desirable for properties such as physical or chemical stability (see, e.g., S.R. Vippagunta et al., Adv. Drug. Deliv. Rev., (2001) 48:3-26; L. Yu, Adv. Drug. Deliv. Rev., (2001) 48:27-42). Changes in solid form can affect various physical and chemical properties, which can provide advantages or disadvantages in processing, formulation, stability, and bioavailability, among other important pharmaceutical characteristics.

[0125] Whether crystalline or amorphous, potential solid forms of a pharmaceutical compound can include single-component and multi-component solids. Single-component solids consist essentially of the pharmaceutical compound in the absence of other compounds. Variability among single-component crystalline materials can potentially arise from the phenomenon of polymorphism, where multiple three-dimensional configurations exist for a particular pharmaceutical compound (see, e.g., S.R. Byrn et al., Solid State Chemistry of Drugs, (1999) SSCI, West Lafayette).

[0126] Additional diversity among the potential solid forms of pharmaceutical compounds can arise from the possibility of multi-component solids. Crystalline solids containing two or more ionic species are called salts (see, e.g., Handbook of Pharmaceutical Salts: Properties, Selection and Use, P.H. Stahl and C.G. Wermuth, Eds., (2002), Wiley, Weinheim). Additional types of multi-component solids that could potentially provide other property improvements for pharmaceutical compounds or their salts include, for example, hydrates, solvates, cocrystals, and clathrates, among others (see, e.g., S.R. Byrn et al., Solid State Chemistry of Drugs, (1999) SSCI, West Lafayette). Multi-component crystalline forms can potentially be susceptible to polymorphism, meaning that a given multi-component composition can exist in two or more three-dimensional crystalline configurations. Solid form discovery is crucial in the development of safe, effective, stable, and marketable pharmaceutical compounds.

[0127] The solid forms provided herein are useful as active pharmaceutical ingredients for the preparation of formulations for animal or human use. Accordingly, embodiments herein encompass the use of these solid forms as final pharmaceutical products. Certain embodiments provide solid forms that are useful for creating final dosage forms with improved properties required for the manufacture, processing, formulation, and / or storage of final pharmaceutical products, such as, among others, powder flow properties, compression properties, tableting properties, stability properties, and excipient compatibility properties. Certain embodiments herein provide pharmaceutical compositions comprising single-component and / or multi-component crystalline forms comprising a compound of Formula (I) and a pharmaceutically acceptable excipient.

[0128] Solid form and related terms refer to physical forms that are not primarily liquid or gaseous. Solid forms can be crystalline or mixtures of crystalline and amorphous forms. A "single-component" solid form containing a particular compound consists essentially of that compound. A "multi-component" solid form containing a particular compound contains that compound and a significant amount of one or more additional species, e.g., ions and / or molecules, within the solid form. The solid forms provided herein can be crystalline or mesomorphic (e.g., mixtures of crystalline and amorphous forms). Thus, the crystalline forms described herein can have various degrees of crystallinity or lattice order. The solid forms described herein are not limited to any particular degree of crystallinity or lattice order and can be 0-100% crystalline. Methods for determining crystallinity are known to those skilled in the art, such as those described in Suryanarayanan, R., X-Ray Powder Diffractometry, Physical Characterization of Pharmaceutical Solids, HGBrittain, Editor, Marcel Dekker, Murray Hill, NJ, 1995, pp. 187-199, which is incorporated herein by reference in its entirety. In some embodiments, the solid forms described herein are about 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% crystalline.

[0129] A solid form may exhibit distinct physical characterization data that are specific to a particular solid form, such as the crystalline forms described herein. These characterization data may be obtained by a variety of techniques known to those skilled in the art, including, for example, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance spectroscopy. The data provided by these techniques may be used to identify a particular solid form. One skilled in the art can determine whether a solid form is one of the forms described herein by performing one of these characterization techniques and determining whether the obtained data is "substantially similar" to reference data provided herein that are identified as being characteristic of a particular solid form. One skilled in the art will understand that characterization data that is "substantially similar" to that of a reference solid form corresponds to the same solid form as the reference solid form. In analyzing whether data are "substantially similar," one skilled in the art will understand that a particular characterization data point may vary to a reasonable extent, for example, due to experimental error and routine sample-to-sample analysis, but still describe a given solid form.

[0130] In some embodiments, provided herein are solid forms comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof. [ka]

[0131] In one embodiment, the solid form comprising the compound of Formula (I) can be a crystalline form, a partially crystalline form, or a mixture of crystalline form(s) or amorphous form(s). In one embodiment, a solid form comprising a crystalline form of the compound of Formula (I) is provided herein. In one embodiment, the solid form comprises a salt, a solvate (e.g., a hydrate), or a solvate of a salt thereof, or a mixture thereof. In another embodiment, the solid form is an amorphous form. In one embodiment, the solid form is substantially pure. In one embodiment, the solid form is substantially chemically pure. In one embodiment, the solid form is substantially physically pure. In one embodiment, the solid form is substantially enantiomerically pure. In one embodiment, the solid form (e.g., Form 2) has an enantiomeric purity of at least about 98% (e.g., about 99% or about 99.5%). Compounds of formula (I) are described in International Patent Application No. PCT / US2021 / 030940, the entire contents of which are incorporated herein by reference.

[0132] 5.2.1. Solid Form of the Free Base of Compound 1 Provided herein are solid forms comprising the compound of formula (I). [ka]

[0133] In one embodiment, provided herein is a solid form comprising the free base of Compound 1. In one embodiment, provided herein is a solid form comprising an anhydrous free base of Compound 1. In one embodiment, provided herein is a solid form comprising a solvate of the free base of Compound 1. In one embodiment, provided herein is a solid form comprising a hydrate of the free base of Compound 1. In one embodiment, provided herein is a solid form comprising a 2-MeTHF, isopropyl acetate, 1,4-dioxane, 2-propanol, acetone, THF, t-butanol, MIBK, cyclohexanone, MEK, methylcyclohexane, or cyclohexane solvate of the free base of Compound 1.

[0134] As used herein, "Compound 1," "Compound 1 free base," "the free base of the compound of Formula (I)," and "Compound 1 free base" are used interchangeably.

[0135] It is contemplated that Compound 1, or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, can exist in various solid forms. Such solid forms include crystalline solids (e.g., crystalline forms of anhydrous Compound 1, crystalline forms of hydrates of Compound 1, and crystalline forms of solvates of Compound 1), amorphous solids, or mixtures of crystalline and amorphous solids. In one embodiment, the solid form is substantially crystalline. In one embodiment, the solid form is crystalline.

[0136] In some embodiments, the molar ratio of Compound 1 to solvent (e.g., water) in the solid form ranges from about 10:1 to about 1:10. In some embodiments, the molar ratio of Compound 1 to solvent (e.g., water) in the solid form ranges from about 5:1 to about 1:5. In some embodiments, the molar ratio of Compound 1 to solvent (e.g., water) in the solid form ranges from about 3:1 to about 1:3. In some embodiments, the molar ratio of Compound 1 to solvent (e.g., water) in the solid form ranges from about 2:1 to about 1:2. In one embodiment, the molar ratio is about 1:2 (i.e., a bis-solvate or dihydrate). In another embodiment, the molar ratio is about 1:1 (i.e., a mono-solvate or monohydrate). In yet another embodiment, the molar ratio is about 2:1 (i.e., a hemi-solvate or hemihydrate).

[0137] 5.2.1.1 Compound 1 Form 1 In one embodiment, Form 1 of Compound 1 is provided herein.

[0138] A representative XRPD pattern of Form 1 of Compound 1 is provided in Figure 1A.

[0139] In one embodiment, a solid form comprising the free base of Compound 1, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Kα radiation: 6.0, 8.9, 9.2, 10.3, 11.1, 12.2, 12.8, 15.8, 17.1, 17.3, 18.1, 18.5, 19.3, 19.5, 20.6, 21.4, 22.2, 22.5, 23.4, 24.5, 25.3, 25.7, 26.2, and 28.2 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0140] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 8.9, 9.2, 11.1, 12.2, 12.8, 17.1, 18.1, 18.5, 20.6, and 22.5 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 8.9, 9.2, 11.1, 12.2, 12.8, 17.1, 18.1, 18.5, 20.6, and 22.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 8.9, 9.2, 11.1, 12.2, 12.8, 17.1, 18.1, 18.5, 20.6, and 22.5°2θ.

[0141] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.0, 18.5, and 20.6 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 12.8 and 17.1 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 9.2 and 22.5 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.0, 8.9, 9.2, 11.1, 12.8, 17.1, 18.5, 20.6, and 22.5 °2θ.

[0142] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern consistent with the XRPD pattern shown in Figure 1A. In one embodiment, Form 1, provided in Figure 1A, is a 2-MeTHF solvate.

[0143] Another representative XRPD pattern of Form 1 of Compound 1 is provided in Figure 1B.

[0144] In one embodiment, a solid form comprising the free base of Compound 1, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 5.8, 6.0, 8.7, 8.8, 9.1, 10.8, 10.9, 12.0, 12.1, 12.7, 14.4, 15.7, 17.0, 18.0, 18.3, 19.3, 20.3, 20.4, 21.3, 22.2, 22.4, 25.0, 25.7, 26.0, 28.3, and 31.7 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0145] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.8, 12.7, 14.4, 17.0, 18.0, 18.3, 19.3, and 20.4 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.8, 12.7, 14.4, 17.0, 18.0, 18.3, 19.3, and 20.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.8, 12.7, 14.4, 17.0, 18.0, 18.3, 19.3, and 20.4 degrees 2θ.

[0146] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.0, 10.8, and 20.4 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 12.7 and 18.3 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 14.4 and 17.0 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.0, 10.8, 12.7, 14.4, 17.0, 18.0, 18.3, 19.3, and 20.4 °2θ.

[0147] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern consistent with the XRPD pattern shown in Figure 1B. In one embodiment, Form 1, provided in Figure 1B, is an isopropyl acetate solvate.

[0148] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0149] A representative overlay of TGA / DSC thermograms for Form 1 is provided in Figure 2. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 79°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 90°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 2. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which exhibits a weight loss of about 15.8% upon heating from about 60°C to about 110°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 2. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form 1 provided in FIG. 2 is a 2-MeTHF solvate.

[0150] Another representative overlay of TGA / DSC thermograms for Form 1 is provided in Figure 3. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal (endothermic) event having a peak temperature of about 117°C (e.g., ±2°). In one embodiment, the thermal event also has an onset temperature of about 110°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 3. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which exhibits a weight loss of about 13.0% upon heating from about 25°C to about 150°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 3. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form 1, provided in FIG. 3, is an isopropyl acetate solvate.

[0151] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0152] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is an isostructural solvate. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent ranges from about 1:0.5 to about 1:1. In one embodiment, the solid form is a 2-MeTHF solvate of the free base of Compound 1. In another embodiment, the solid form is an isopropyl acetate solvate of the free base of Compound 1.

[0153] In one embodiment, provided herein is a solid form comprising Form 1 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 1 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0154] All combinations of the above embodiments are encompassed by the present application.

[0155] 5.2.1.2 Form 2 of Compound 1 In one embodiment, provided herein is Form 2 of Compound 1. A representative XRPD pattern of Form 2 of Compound 1 is provided in FIG.

[0156] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 7.6, 9.4, 11.2, 12.4, 13.2, 14.3, 15.4, 15.6, 16.2, 16.9, 17.9, 18.9, 21.1, 21.6, 21.8, 22.5, 22.7, 23.0, 24.5, 24.9, 27.0, and 28.8 degrees 2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0157] In one embodiment, provided herein is a solid form (e.g., a crystalline or substantially crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.2, 12.4, 13.2, 14.3, 18.9, 21.1, 21.6, 21.8, 22.5, 22.7, 23.0, and 27.0 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.2, 12.4, 13.2, 14.3, 18.9, 21.1, 21.6, 21.8, 22.5, 22.7, 23.0, and 27.0 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.2, 12.4, 13.2, 14.3, 18.9, 21.1, 21.6, 21.8, 22.5, 22.7, 23.0, and 27.0 °2θ.

[0158] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 12.4, 18.9, and 21.1 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 13.2 and 22.5 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 11.2 and 22.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 11.2, 12.4, 13.2, 14.3, 18.9, 21.1, 21.8, 22.5, 22.7, 23.0, and 27.0 °2θ.

[0159] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0160] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0161] A representative DSC thermogram of Form 2 is provided in Figure 5. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 260°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 261°C (e.g., ±2°). In one embodiment, without being bound by a particular theory, the thermal event corresponds to melting. In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 5. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min.

[0162] A representative DVS isotherm for Form 2 is provided in Figure 6. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight gain of about 0.3% (e.g., ±0.05%) when subjected to an increase in relative humidity from about 0% relative humidity to about 90% relative humidity. In one embodiment, the solid form is characterized by a DVS isotherm consistent with the DVS isotherm shown in Figure 6. In one embodiment, the DVS isotherm is as measured at about 25°C.

[0163] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, having unit cell dimensions of approximately a=8.2 Å, b=14.8 Å, c=18.7 Å, α=90°, β=90°, and γ=90°. In one embodiment, Form 2 has unit cell dimensions of approximately a=8.17 Å, b=14.75 Å, c=18.69 Å, α=90°, β=90°, and γ=90°. In one embodiment, Form 2 has unit cell dimensions of approximately a=8.169 Å, b=14.750 Å, c=18.694 Å, α=90°, β=90°, and γ=90°. In one embodiment, Form 2 has a unit cell of the space group P212121. In one embodiment, Form 2 has a unit cell of approximately 2252.4 Å. 3 In one embodiment, Form 2 has a Z value of 4. In one embodiment, Form 2 has a volume of about 1.336 g / cm 3 It has a density of

[0164] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is anhydrous. In one embodiment, the solid form is a crystalline anhydrous free base of Compound 1. In one embodiment, the solid form is substantially free of amorphous Compound 1. In one embodiment, the solid form is substantially free of other crystalline forms of Compound 1. In one embodiment, the solid form is substantially free of salts of Compound 1. In one embodiment, the solid form is unsolvated. In one embodiment, one or more residual solvents may be present in the solid form, but the residual solvents do not form solvates of Compound 1. In one embodiment, the solid form is substantially pure. In one embodiment, the solid form is substantially chemically pure. In one embodiment, the solid form is greater than about 95% chemically pure by weight. In one embodiment, the solid form is greater than about 96% chemically pure by weight. In one embodiment, the solid form is greater than about 97% chemically pure by weight. In one embodiment, the solid form is greater than about 98% chemically pure by weight. In one embodiment, the solid form is greater than about 99% chemically pure by weight. In one embodiment, the solid form is substantially enantiomerically pure. In one embodiment, the solid form is at least about 98% enantiomerically pure. In one embodiment, the solid form is at least about 99% enantiomerically pure. In one embodiment, the solid form is at least about 99.5% enantiomerically pure. In one embodiment, the solid form is substantially physically pure.

[0165] In one embodiment, Form 2 is substantially non-hygroscopic. In one embodiment, Form 2 is non-hygroscopic. In one embodiment, Form 2 is stable after storage at 30°C ± 2°C / 65% ± 5% RH for at least 12 months. In one embodiment, Form 2 is stable after storage at 40°C ± 2°C / 75% ± 5% RH for at least 6 months. In one embodiment, Form 2 stored at 30°C ± 2°C / 65% ± 5% RH for at least 12 months, or at 40°C ± 2°C / 75% ± 5% RH for at least 6 months, is at least 97% chemically pure by weight. In one embodiment, Form 2 stored at 30°C ± 2°C / 65% ± 5% RH for at least 12 months, or at 40°C ± 2°C / 75% ± 5% RH for at least 6 months, is at least 99% enantiomerically pure by weight. In one embodiment, Form 2 stored at 30°C ± 2°C / 65% ± 5% RH for at least 12 months or at 40°C ± 2°C / 75% ± 5% RH for at least 6 months is at least 99% by weight physically pure (e.g., substantially free of amorphous Compound 1 or other solid forms of Compound 1).

[0166] In one embodiment, provided herein is a solid form comprising Form 2 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 2 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0167] All combinations of the above embodiments are encompassed by the present application.

[0168] 5.2.1.3 Form 3 of Compound 1 In one embodiment, provided herein is Form 3 of Compound 1. A representative XRPD pattern of Form 3 of Compound 1 is provided in FIG.

[0169] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by one, two, three, four, five, six, seven, eight, or all of the XRPD peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 9.0, 9.4, 10.4, 12.8, 15.3, 16.4, 16.6, 18.2, and 20.6 degrees 2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0170] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 9.0, 9.4, 10.4, 12.8, 15.3, 16.4, 16.6, 18.2, and 20.6 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 9.0, 9.4, 10.4, 12.8, 15.3, 16.4, 16.6, 18.2, and 20.6 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 9.0, 9.4, 10.4, 12.8, 15.3, 16.4, 16.6, 18.2, and 20.6°2θ.

[0171] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 9.4, 12.8, and 15.3 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 16.6 and 20.6 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 9.0 and 16.4 °2θ. In one embodiment, the XRPD pattern further comprises a peak at approximately (e.g., ±0.2°) 10.4 °2θ. In one embodiment, the XRPD pattern further comprises a peak at approximately (e.g., ±0.2°) 18.2 °2θ.

[0172] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0173] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0174] A representative overlay of TGA / DSC thermograms for Form 3 is provided in Figure 9. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 100°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 108°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 9. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 3 provided in Figure 9 is a 2-MeTHF solvate.

[0175] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 13.3% upon heating from about 50° C. to about 200° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 9. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0176] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0177] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent(s) ranges from about 1:1 to about 1:8. In one embodiment, the molar ratio of Compound 1 to solvent(s) ranges from about 1:4 to about 1:5. In one embodiment, the molar ratio of Compound 1 to water ranges from about 1:1 to about 1:6. In one embodiment, the molar ratio of Compound 1 to water ranges from about 1:3 to about 1:5. In one embodiment, the molar ratio of Compound 1 to organic solvent ranges from about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to organic solvent ranges from about 1:0.8 to about 1:1.1. In one embodiment, the solid form is a 2-MeTHF solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to 2-MeTHF is about 1:0.7. In one embodiment, the molar ratio of compound 1 to 2-MeTHF is about 1:0.8. In one embodiment, the molar ratio of compound 1 to 2-MeTHF is about 1:1.

[0178] In one embodiment, provided herein is a solid form comprising Form 3 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 3 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0179] All combinations of the above embodiments are encompassed by the present application.

[0180] 5.2.1.4 Form 4 of Compound 1 In one embodiment, provided herein is Form 4 of Compound 1. A representative XRPD pattern of Form 4 of Compound 1 is provided in Figure 10.

[0181] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.0, 6.1, 9.0, 9.2, 11.0, 12.2, 12.7, 17.2, 18.2, 18.4, 19.4, 20.5, 21.5, and 22.5 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least 11 of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0182] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 6.1, 9.2, 11.0, 12.2, 12.7, 17.2, 18.2, 20.5, and 21.5 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 6.1, 9.2, 11.0, 12.2, 12.7, 17.2, 18.2, 20.5, and 21.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.1, 9.2, 11.0, 12.2, 12.7, 17.2, 18.2, 20.5, and 21.5° 2θ.

[0183] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.1, 17.2, and 18.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 12.7 and 20.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 12.2 and 21.5 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.1, 9.2, 11.0, 12.2, 12.7, 17.2, 18.2, 20.5, and 21.5 °2θ.

[0184] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0185] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0186] A representative overlay of TGA / DSC thermograms for Form 4 is provided in Figure 11. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 64°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 67°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 11. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 4 provided in Figure 11 is a 1,4-dioxane solvate.

[0187] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 17.1% upon heating from about 75° C. to about 165° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 11. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0188] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0189] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.6 to about 1:2. In one embodiment, the solid form is a 1,4-dioxane solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to 1,4-dioxane is about 1:0.8. In one embodiment, the molar ratio of Compound 1 to 1,4-dioxane is about 1:1.1.

[0190] In one embodiment, provided herein is a solid form comprising Form 4 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 4 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0191] All combinations of the above embodiments are encompassed by the present application.

[0192] 5.2.1.5 Form 5 of Compound 1 In one embodiment, Form 5 of Compound 1 is provided herein.

[0193] A representative XRPD pattern of Form 5 of Compound 1 is provided in Figure 12A.

[0194] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, or all of the following XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.8, 7.0, 10.0, 10.3, 11.0, 17.2, 17.7, 18.9, 19.4, 20.0, 21.1, 21.3, 21.8, 22.2, 22.8, 23.2, and 23.5 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks, hi one embodiment, the solid form is characterized by at least 11 of the peaks, hi one embodiment, the solid form is characterized by all of the peaks.

[0195] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.0, 10.0, 17.2, 18.9, 19.4, 21.1, 22.2, and 22.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.0, 10.0, 17.2, 18.9, 19.4, 21.1, 22.2, and 22.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.0, 10.0, 17.2, 18.9, 19.4, 21.1, 22.2, and 22.8° 2θ.

[0196] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.8, 10.0, and 18.9 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 19.4 and 22.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 7.0 and 22.2 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.8, 7.0, 10.0, 17.2, 18.9, 19.4, 21.1, 22.2, and 22.8 °2θ.

[0197] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern that matches the XRPD pattern shown in Figure 12A. In one embodiment, Form 5, provided in Figure 12A, is a mixed solvate of 2-propanol and t-butanol.

[0198] Another representative XRPD pattern of Form 5 of Compound 1 is provided in Figure 12B.

[0199] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or all of the XRPD peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.9, 9.1, 9.9, 10.2, 11.9, 12.6, 17.2, 18.6, 19.1, 19.7, 20.8, 21.5, and 22.4 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0200] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 6.9, 9.9, 10.2, 12.6, 18.6, 19.1, 20.8, 21.5, and 22.4 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 6.9, 9.9, 10.2, 12.6, 18.6, 19.1, 20.8, 21.5, and 22.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.9, 9.9, 10.2, 12.6, 18.6, 19.1, 20.8, 21.5, and 22.4 degrees 2θ.

[0201] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.9, 9.9, and 19.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.2 and 18.6 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 20.8 and 22.4 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.9, 9.9, 10.2, 12.6, 18.6, 19.1, 20.8, 21.5, and 22.4 °2θ.

[0202] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern consistent with the XRPD pattern shown in Figure 12B. In one embodiment, Form 5, provided in Figure 12B, is a mixed solvate of t-butanol and acetone.

[0203] Another representative XRPD pattern of Form 5 of Compound 1 is provided in Figure 12C.

[0204] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, or all of the following XRPD peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 3.2, 6.0, 6.9, 9.8, 12.7, 17.2, 19.2, 19.7, 20.9, 22.2, 25.6, and 28.8 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0205] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 6.0, 6.9, 9.8, 12.7, 17.2, 19.2, 19.7, 20.9, and 22.2 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 6.0, 6.9, 9.8, 12.7, 17.2, 19.2, 19.7, 20.9, and 22.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 6.9, 9.8, 12.7, 17.2, 19.2, 19.7, 20.9, and 22.2° 2θ.

[0206] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.9, 17.2, and 19.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 6.0 and 22.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 9.8 and 19.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.0, 6.9, 9.8, 12.7, 17.2, 19.2, 19.7, 20.9, and 22.2 °2θ.

[0207] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern consistent with the XRPD pattern shown in Figure 12C. In one embodiment, Form 5, provided in Figure 12C, is a mixed solvate of t-butanol and THF.

[0208] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0209] A representative overlay of TGA / DSC thermograms for Form 5 is provided in Figure 13. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 68°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 72°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 13. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which exhibits a weight loss of about 15.7% upon heating from about 25°C to about 170°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 13. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form 5, provided in FIG. 13, is a mixed 2-propanol and t-butanol solvate.

[0210] A representative overlay of TGA / DSC thermograms for Form 5 is provided in Figure 14. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 67°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 71°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 14. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which exhibits a weight loss of about 12.9% upon heating from about 25°C to about 170°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 14. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form 5, provided in FIG. 14, is a mixed acetone and t-butanol solvate.

[0211] A representative overlay of TGA / DSC thermograms for Form 5 is provided in Figure 15. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 59°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 62°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 15. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which exhibits a weight loss of about 19.1% upon heating from about 25°C to about 170°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 15. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form 5, provided in FIG. 15, is a mixed solvate of THF and t-butanol.

[0212] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0213] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is an isostructural solvate. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a mixed solvate. In one embodiment, the solid form is a 2-propanol and t-butanol mixed solvate. In another embodiment, the solid form is an acetone and t-butanol mixed solvate. In another embodiment, the solid form is a THF and t-butanol mixed solvate. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent ranges from about 1:0.1 to about 1:1.1. In one embodiment, the molar ratio of Compound 1 to solvent (e.g., acetone) is about 1:0.1. In one embodiment, the molar ratio of Compound 1 to solvent (e.g., 2-propanol) is about 1:0.4. In one embodiment, the molar ratio of Compound 1 to solvent (e.g., t-butanol) is about 1:0.6. In one embodiment, the molar ratio of compound 1 to a solvent (e.g., THF) is about 1:0.7. In one embodiment, the molar ratio of compound 1 to a solvent is about 1:0.7. In one embodiment, the molar ratio of compound 1 to a mixture of two solvents is about 1:0.5 to 1:1.9. In one embodiment, the molar ratio of compound 1 to a mixture of two solvents (e.g., 2-propanol and t-butanol) is about 1:1.0. In one embodiment, the molar ratio of compound 1 to a mixture of two solvents (e.g., acetone and t-butanol) is about 1:0.8. In one embodiment, the molar ratio of compound 1 to a mixture of two solvents (e.g., THF and t-butanol) is about 1:1.3.

[0214] In one embodiment, provided herein is a solid form comprising Form 5 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 5 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0215] All combinations of the above embodiments are encompassed by the present application.

[0216] 5.2.1.6 Form 6 of Compound 1 In one embodiment, provided herein is Form 6 of Compound 1. A representative XRPD pattern of Form 6 of Compound 1 is provided in Figure 16.

[0217] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or all of the XRPD peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.8, 6.0, 9.0, 10.0, 11.5, 12.0, 17.3, 18.0, 19.0, 20.1, 21.5, 22.4, and 24.1 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0218] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 5.8, 6.0, 10.0, 18.1, 20.1, 22.4, and 24.1 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 5.8, 6.0, 10.0, 18.1, 20.1, 22.4, and 24.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of about (e.g., ±0.2°) 5.8, 6.0, 10.0, 18.1, 20.1, 22.4, and 24.1 °2θ.

[0219] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.8, 10.0, and 18.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 6.0 and 22.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 20.1 and 24.1 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 11.5 and 12.0 °2θ.

[0220] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0221] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0222] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0223] In one embodiment, provided herein is a solid form comprising Form 6 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 6 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0224] All combinations of the above embodiments are encompassed by the present application.

[0225] 5.2.1.7 Form 7 of Compound 1 In one embodiment, provided herein is Form 7 of Compound 1. A representative XRPD pattern of Form 7 of Compound 1 is provided in Figure 17.

[0226] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, or all of the following XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.9, 8.6, 9.1, 10.6, 12.0, 12.1, 16.7, 17.8, 19.6, 20.7, 21.0, 21.2, 21.4, and 23.4 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least 11 of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0227] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.6, 12.0, 16.7, 17.8, 19.6, 21.2, and 23.4 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.6, 12.0, 16.7, 17.8, 19.6, 21.2, and 23.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.6, 12.0, 16.7, 17.8, 19.6, 21.2, and 23.4° 2θ.

[0228] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.9, 9.1, and 19.6 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 12.0 and 23.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.6 and 21.2 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.9, 9.1, 10.6, 12.0, 16.7, 17.8, 19.6, 21.2, and 23.4 °2θ.

[0229] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0230] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0231] A representative overlay of TGA / DSC thermograms for Form 7 is provided in Figure 18. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 83°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 89°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 18. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 7 provided in Figure 18 is an MIBK solvate.

[0232] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 15.5% upon heating from about 85° C. to about 135° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 18. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0233] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0234] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.6 to about 1:1.1. In one embodiment, the solid form is an MIBK solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to MIBK is about 1:0.7. In one embodiment, the molar ratio of Compound 1 to MIBK is about 1:0.8.

[0235] In one embodiment, provided herein is a solid form comprising Form 7 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 7 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0236] All combinations of the above embodiments are encompassed by the present application.

[0237] 5.2.1.8 Form 8 of Compound 1 In one embodiment, provided herein is Form 8 of Compound 1. A representative XRPD pattern of Form 8 of Compound 1 is provided in Figure 19.

[0238] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 6.0, 6.1, 8.8, 9.2, 9.8, 10.8, 11.9, 12.1, 17.0, 18.0, 18.9, 19.7, 20.1, 20.3, 20.9, 21.3, 21.5, 21.6, 23.6, 24.0, and 25.6 degrees 2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0239] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 9.2, 10.8, 11.9, 12.1, 17.0, 18.0, 19.7, and 21.5 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 9.2, 10.8, 11.9, 12.1, 17.0, 18.0, 19.7, and 21.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 9.2, 10.8, 11.9, 12.1, 17.0, 18.0, 19.7, and 21.5°2θ.

[0240] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.0, 17.0, and 19.7 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 9.2 and 21.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.8 and 18.0 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.0, 9.2, 10.8, 11.9, 12.1, 17.0, 18.0, 19.7, and 21.5 °2θ.

[0241] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0242] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0243] A representative overlay of TGA / DSC thermograms for Form 8 is provided in Figure 20. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 74°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 77°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 20. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 8 provided in Figure 20 is a THF solvate.

[0244] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 15.5% upon heating from about 70° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 20. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0245] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0246] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent ranges from about 1:0.5 to about 1:2. In one embodiment, the molar ratio of Compound 1 to solvent ranges from about 1:1 to about 1:1.7. In one embodiment, the solid form is a THF solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to THF is about 1:1.1. In one embodiment, the molar ratio of Compound 1 to THF is about 1:1.6.

[0247] In one embodiment, provided herein is a solid form comprising Form 8 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 8 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0248] All combinations of the above embodiments are encompassed by the present application.

[0249] 5.2.1.9 Form 9 of Compound 1 In one embodiment, provided herein is Form 9 of Compound 1. A representative XRPD pattern of Form 9 of Compound 1 is provided in Figure 21.

[0250] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.9, 8.7, 8.8, 9.2, 9.7, 10.5, 11.9, 12.0, 14.1, 17.2, 17.7, 18.0, 19.1, 19.4, 19.6, 21.1, 21.4, 23.3, 23.7, and 25.5 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0251] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 10.5, 11.9, 12.0, 17.2, 17.7, 19.4, 19.6, 21.4, and 23.3 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 10.5, 11.9, 12.0, 17.2, 17.7, 19.4, 19.6, 21.4, and 23.3 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 10.5, 11.9, 12.0, 17.2, 17.7, 19.4, 19.6, 21.4, and 23.3° 2θ.

[0252] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.9, 17.2, and 19.4 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 17.7 and 19.6 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 11.9 and 23.3 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.9, 10.5, 11.9, 12.0, 17.2, 17.7, 19.4, 19.6, 21.4, and 23.3 °2θ.

[0253] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0254] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0255] A representative overlay of TGA / DSC thermograms for Form 9 is provided in Figure 22. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 112°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 117°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 22. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 9 provided in Figure 22 is a cyclohexanone solvate.

[0256] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 17.9% upon heating from about 110° C. to about 180° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 22. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0257] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0258] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.8 to about 1:1.2. In one embodiment, the solid form is a cyclohexanone solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to cyclohexanone is about 1:1.

[0259] In one embodiment, provided herein is a solid form comprising Form 9 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 9 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0260] All combinations of the above embodiments are encompassed by the present application.

[0261] 5.2.1.10 Form 10 of Compound 1 In one embodiment, provided herein is Form 10 of Compound 1. A representative XRPD pattern of Form 10 of Compound 1 is provided in Figure 23.

[0262] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.7, 5.8, 5.9, 8.2, 8.4, 8.6, 10.6, 11.2, 12.9, 16.1, 17.7, 19.2, 19.3, 20.2, 21.0, 21.1, 21.3, 22.5, 22.7, and 22.9 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0263] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 5.9, 8.4, 8.6, 10.6, 11.2, 12.9, 16.1, 19.3, and 21.1 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 5.9, 8.4, 8.6, 10.6, 11.2, 12.9, 16.1, 19.3, and 21.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 8.4, 8.6, 10.6, 11.2, 12.9, 16.1, 19.3, and 21.1 degrees 2θ.

[0264] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.9, 8.4, and 8.6 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.6 and 16.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 11.2 and 19.3 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.9, 8.4, 8.6, 10.6, 11.2, 12.9, 16.1, 19.3, and 21.1 °2θ.

[0265] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern shown in FIG.

[0266] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0267] A representative overlay of TGA / DSC thermograms for Form 10 is provided in Figure 24. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 85°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 91°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 24. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 10 provided in Figure 24 is an MIBK solvate.

[0268] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 17.6% upon heating from about 85° C. to about 120° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 24. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0269] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0270] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent ranges from about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent ranges from about 1:0.8 to about 1:1.2. In one embodiment, the solid form is an MIBK solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to MIBK is about 1:1.

[0271] In one embodiment, provided herein is a solid form comprising Form 10 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 10 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0272] All combinations of the above embodiments are encompassed by the present application.

[0273] 5.2.1.11 Form 11 of Compound 1 In one embodiment, provided herein is Form 11 of Compound 1. A representative XRPD pattern of Form 11 of Compound 1 is provided in Figure 25.

[0274] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or all of the following XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.9, 8.6, 9.1, 10.0, 10.7, 10.9, 11.7, 12.0, 12.2, 14.4, 14.8, 16.7, 17.8, 19.3, 20.1, 20.7, 21.3, and 24.7 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least 7 of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks. In one embodiment, the solid form is characterized by at least 11 of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0275] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.7, 12.0, 12.2, 16.7, 17.8, 20.1, and 21.3 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.7, 12.0, 12.2, 16.7, 17.8, 20.1, and 21.3 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 9.1, 10.7, 12.0, 12.2, 16.7, 17.8, 20.1, and 21.3° 2θ.

[0276] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.9, 10.7, and 20.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 12.0 and 23.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 9.1 and 16.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.9, 9.1, 10.7, 12.0, 12.2, 16.7, 17.8, 20.1, and 21.3 °2θ.

[0277] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0278] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0279] A representative overlay of TGA / DSC thermograms for Form 11 is provided in Figure 26. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 92°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 97°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 26. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 11 provided in Figure 26 is a MEK solvate.

[0280] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 14.4% upon heating from about 90° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 26. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0281] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0282] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.7 to about 1:1.2. In one embodiment, the solid form is a MEK solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to MEK is about 1:0.8. In one embodiment, the molar ratio of Compound 1 to MEK is about 1:1.

[0283] In one embodiment, provided herein is a solid form comprising Form 11 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 11 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0284] All combinations of the above embodiments are encompassed by the present application.

[0285] 5.2.1.12 Form 12 of Compound 1 In one embodiment, provided herein is Form 12 of Compound 1. A representative XRPD pattern of Form 12 of Compound 1 is provided in Figure 27.

[0286] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, or all of the following XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.8, 5.9, 8.7, 9.1, 10.5, 11.8, 11.9, 14.0, 16.9, 17.7, 18.8, 19.2, 19.9, 20.4, 20.8, 21.1, 21.7, 22.1, and 23.0 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least 7 of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks. In one embodiment, the solid form is characterized by at least 11 of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0287] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 5.8, 5.9, 8.7, 9.1, 17.7, 18.8, 19.2, 21.1, and 22.1 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 5.8, 5.9, 8.7, 9.1, 17.7, 18.8, 19.2, 21.1, and 22.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.8, 5.9, 8.7, 9.1, 17.7, 18.8, 19.2, 21.1, and 22.1 degrees 2θ.

[0288] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.8, 19.2, and 22.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 5.9 and 17.7 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 8.7 and 18.8 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.8, 5.9, 8.7, 9.1, 17.7, 18.8, 19.2, 21.1, and 22.1 °2θ.

[0289] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0290] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0291] A representative overlay of TGA / DSC thermograms for Form 12 is provided in Figure 28. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 95°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 102°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 28. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 12 provided in Figure 28 is a methylcyclohexane solvate.

[0292] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 16.1% upon heating from about 95° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 28. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0293] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0294] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.7 to about 1:1.1. In one embodiment, the solid form is a methylcyclohexane solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to methylcyclohexane is about 1:0.8. In one embodiment, the molar ratio of Compound 1 to methylcyclohexane is about 1:0.9.

[0295] In one embodiment, provided herein is a solid form comprising Form 12 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 12 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0296] All combinations of the above embodiments are encompassed by the present application.

[0297] 5.2.1.13 Form 13 of Compound 1 In one embodiment, provided herein is Form 13 of Compound 1. A representative XRPD pattern of Form 13 of Compound 1 is provided in Figure 29.

[0298] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 5.9, 8.9, 9.2, 9.5, 10.4, 11.6, 11.9, 12.1, 13.9, 15.6, 17.2, 17.8, 18.5, 19.2, 19.9, 20.3, 20.8, 21.4, 22.2, 22.9, 23.1, and 24.0 degrees 2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0299] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 5.9, 8.9, 9.2, 10.4, 11.9, 17.2, 17.8, 19.2, 21.4, and 23.1 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 5.9, 8.9, 9.2, 10.4, 11.9, 17.2, 17.8, 19.2, 21.4, and 23.1 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 5.9, 8.9, 9.2, 10.4, 11.9, 17.2, 17.8, 19.2, 21.4, and 23.1 degrees 2θ.

[0300] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 5.9, 9.2, and 19.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 11.9 and 17.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.4, 21.4, and 23.1 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 5.9, 8.9, 9.2, 10.4, 11.9, 17.2, 17.8, 19.2, 21.4, and 23.1 °2θ.

[0301] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0302] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0303] A representative overlay of TGA / DSC thermograms for Form 13 is provided in Figure 30. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 123°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 129°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 30. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 13 provided in Figure 30 is a cyclohexane solvate.

[0304] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 14.5% upon heating from about 120° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 30. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0305] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0306] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent is in the range of about 1:0.5 to about 1:1.5. In one embodiment, the molar ratio of Compound 1 to solvent is in the range of about 1:0.6 to about 1:1.1. In one embodiment, the solid form is a cyclohexane solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to cyclohexane is about 1:0.7. In one embodiment, the molar ratio of Compound 1 to cyclohexane is about 1:0.9.

[0307] In one embodiment, provided herein is a solid form comprising Form 13 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 13 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0308] All combinations of the above embodiments are encompassed by the present application.

[0309] 5.2.1.14 Form 14 of Compound 1 In one embodiment, provided herein is Form 14 of Compound 1. A representative XRPD pattern of Form 14 of Compound 1 is provided in Figure 31.

[0310] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.7, 6.8, 9.7, 10.1, 12.5, 16.6, 16.9, 17.1, 18.2, 18.9, 19.4, 20.6, 21.2, 21.8, 22.2, 22.6, 23.5, 24.5, and 25.2 °2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0311] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 6.7, 6.8, 9.7, 12.5, 16.9, 17.1, 18.9, 21.2, and 22.2 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 6.7, 6.8, 9.7, 12.5, 16.9, 17.1, 18.9, 21.2, and 22.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.7, 6.8, 9.7, 12.5, 16.9, 17.1, 18.9, 21.2, and 22.2° 2θ.

[0312] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.7, 16.9, and 18.9 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 6.8 and 22.2 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 9.7 and 21.2 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.7, 6.8, 9.7, 12.5, 16.9, 17.1, 18.9, 21.2, and 22.2 °2θ.

[0313] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0314] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0315] A representative overlay of TGA / DSC thermograms for Form 14 is provided in Figure 32. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (endotherm) having an onset temperature of about 75°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 80°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 32. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 14 provided in Figure 32 is a mixed solvate of cyclohexanone and t-butanol.

[0316] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 27.9% upon heating from about 75° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 32. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0317] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0318] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which is a mixed solvate. In one embodiment, the solid form is a mixed solvate of cyclohexanone and t-butanol. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which has a molar ratio of Compound 1 to solvent ranging from about 1:0.9 to about 1:2. In one embodiment, the molar ratio of Compound 1 to solvent is about 1:1.4.

[0319] In one embodiment, provided herein is a solid form comprising Form 14 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 14 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0320] All combinations of the above embodiments are encompassed by the present application.

[0321] 5.2.1.15 Form 15 of Compound 1 In one embodiment, provided herein is Form 15 of Compound 1. A representative XRPD pattern of Form 15 of Compound 1 is provided in Figure 33.

[0322] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, or all of the following XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 5.7, 6.1, 6.7, 7.1, 7.7, 9.1, 10.0, 10.6, 12.8, 16.7, 17.5, 18.8, 19.3, 20.0, 20.5, 22.0, 22.8, 23.4, and 24.8 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least 7 of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks. In one embodiment, the solid form is characterized by at least 11 of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0323] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about (e.g., ±0.2°) 6.7, 7.1, 10.0, 10.6, 18.8, 20.0, 20.5, 22.0, and 22.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about (e.g., ±0.2°) 6.7, 7.1, 10.0, 10.6, 18.8, 20.0, 20.5, 22.0, and 22.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.7, 7.1, 10.0, 10.6, 18.8, 20.0, 20.5, 22.0, and 22.8° 2θ.

[0324] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.7, 22.0, and 22.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 18.8 and 20.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern further comprising peaks at approximately (e.g., ±0.2°) 10.6 and 20.0 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.7, 7.1, 10.0, 10.6, 18.8, 20.0, 20.5, 22.0, and 22.8 °2θ.

[0325] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0326] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0327] A representative overlay of TGA / DSC thermograms for Form 15 is provided in Figure 34. In one embodiment, provided herein is a solid form comprising the free base of Compound 1, which, as characterized by DSC, exhibits a thermal event (exotherm) having an onset temperature of about 173°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 179°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 34. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form 15 provided in Figure 34 is an acetone solvate.

[0328] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form exhibits a weight loss of about 8.5% upon heating from about 25° C. to about 150° C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 34. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min.

[0329] In some embodiments, provided herein is a solid form comprising the free base of Compound 1, wherein the solid form is a crystalline solvate of the free base of Compound 1. In some embodiments, the solid form is substantially free of amorphous Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of Compound 1. In some embodiments, the solid form is substantially free of salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0330] In one embodiment, provided herein is a solid form comprising the free base of Compound 1, wherein the molar ratio of Compound 1 to solvent ranges from about 1:0.5 to about 1:1.2. In one embodiment, the molar ratio of Compound 1 to solvent ranges from about 1:0.6 to about 1:1.1. In one embodiment, the solid form is an acetone solvate of the free base of Compound 1. In one embodiment, the molar ratio of Compound 1 to acetone is about 1:0.7. In one embodiment, the molar ratio of Compound 1 to acetone is about 1:1.

[0331] In one embodiment, provided herein is a solid form comprising Form 15 of the free base of Compound 1 and an amorphous free base of Compound 1. In one embodiment, provided herein is a solid form comprising Form 15 of the free base of Compound 1 and one or more other crystalline forms of the free base of Compound 1 provided herein.

[0332] All combinations of the above embodiments are encompassed by the present application.

[0333] 5.2.2. Process for Preparing Solid Forms of Compound 1 As used herein, all solvent ratios are by volume unless otherwise specified.

[0334] In one embodiment, there is provided a process for preparing Form 1 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 1 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 1 solid form(s) to Form 1; (ii) recovering said Form 1.

[0335] In one embodiment, the non-Form 1 solid form is exposed to one solvent. In one embodiment, the non-Form 1 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 1 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-MeTHF, isopropyl acetate, heptane, or a mixture thereof. In one embodiment, the solvent is 2-MeTHF. In one embodiment, the solvent is isopropyl acetate. In one embodiment, the solvent is a mixture of 2-MeTHF and heptane. In one embodiment, the ratio of 2-MeTHF to heptane is about 1:2 to about 1:6. In one embodiment, the solvent is a mixture of isopropyl acetate and heptane. In one embodiment, the ratio of isopropyl acetate to heptane is about 1:2 to about 1:6. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is 2-MeTHF and the anti-solvent is heptane. In one embodiment, the solvent is isopropyl acetate and the anti-solvent is heptane. In one embodiment, the final ratio of solvent to anti-solvent is about 1:2 to about 1:6. In one embodiment, the Non-Form 1 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the Non-Form 1 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the Non-Form 1 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0336] In one embodiment, the Non-Form 1 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 1 solid form is any one of Forms 2 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 1 solid form to Form 1 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0337] Form 1 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0338] In one embodiment, Form 1 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-MeTHF. In one embodiment, the solvent is isopropyl acetate.

[0339] In one embodiment, Form 1 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of 2-MeTHF and heptane. In one embodiment, the volume ratio of 2-MeTHF to heptane is about 1:10 to about 1:2. In one embodiment, the mixture of two solvents is a mixture of isopropyl acetate and heptane. In one embodiment, the volume ratio of isopropyl acetate to heptane is about 1:10 to about 1:2. In one embodiment, the volume ratio of isopropyl acetate to heptane is about 1:1.

[0340] In one embodiment, Form 1 of the compound of Formula (I) is prepared by evaporating a solution of the compound in 2-MeTHF. In one embodiment, the evaporation is carried out at about 20° C. In one embodiment, the evaporation is slow evaporation (e.g., for about 7 days).

[0341] In one embodiment, Form 1 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0342] In one embodiment, there is provided a process for preparing Form 2 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 2 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 2 solid form(s) to Form 2; (ii) recovering said Form 2.

[0343] In one embodiment, the non-Form 2 solid form is exposed to one solvent. In one embodiment, the non-Form 2 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 2 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is ethanol, acetonitrile, t-butyl methyl ether, isobutyl acetate, cyclopentyl methyl ether, isopropyl acetate, ethyl acetate, 1-butanol, 2-butanol, cyclohexane, THF, cyclopentyl methyl ether (CPME), diisopropyl ether (DIIPE), methyl ether ketone (MEK), methyl isobutyl ketone (MIBK), 1-propanol, 2-propanol, t-amyl alcohol, n-butyl acetate, methanol, toluene, dichloromethane, ethyl tert-butyl ether (tBME), cyclopentyl methyl ether, methylcyclohexane, acetone, 2-methyl THF, 2-ethoxyethanol, anisole, DMSO, 1,4-dioxane, heptane, or a mixture thereof. In one embodiment, the solvent is ethanol. In one embodiment, the solvent is a mixture of ethanol and heptane. In one embodiment, the volume ratio of ethanol to heptane is about 1:2 to about 1:15. In one embodiment, the volume ratio of ethanol to heptane is about 1:6 to about 1:10. In one embodiment, the solvent is ethyl acetate. In one embodiment, the solvent is a mixture of ethyl acetate and heptane. In one embodiment, the volume ratio of ethyl acetate to heptane is about 1:2 to about 1:15. In one embodiment, the volume ratio of ethyl acetate to heptane is about 1:6 to about 1:10. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the final volume ratio of solvent to anti-solvent is about 1:1 to about 1:15. In one embodiment, the final volume ratio of solvent to anti-solvent is about 1:6 to about 1:10. In one embodiment, the non-Form 2 solid form is exposed to the solvent and / or anti-solvent at room temperature.In one embodiment, the Non-Form 2 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the Non-Form 2 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25° C. to about 60° C. In one embodiment, the Non-Form 2 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 35° C. to about 55° C.

[0344] In one embodiment, the Non-Form 2 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 2 solid form is Form 1 or any one of Forms 3 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 2 solid form to Form 2 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0345] Form 2 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0346] In one embodiment, Form 2 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is ethanol. In one embodiment, the solvent is ethyl acetate.

[0347] In one embodiment, Form 2 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of ethanol and heptane. In one embodiment, the volume ratio of ethanol to heptane is about 1:15 to about 1:2. In one embodiment, the mixture of two solvents is a mixture of ethyl acetate and heptane. In one embodiment, the volume ratio of ethyl acetate to heptane is about 1:15 to about 1:2. In one embodiment, the volume ratio of ethyl acetate to heptane is about 1:8. In one embodiment, the weight ratio of EtOAc to heptane is about 1:3 to about 1:10. In one embodiment, the weight ratio of EtOAc to heptane is about 1:6.2.

[0348] In one embodiment, Form 2 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0349] In one embodiment, there is provided a process for preparing Form 2 of the compound of Formula (I), comprising: (i) dissolving a compound of formula (I) in a solvent; (ii) adding an anti-solvent; (iii) recovering said Form 2.

[0350] In one embodiment, the solvent is ethanol. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is ethanol and the anti-solvent is heptane.

[0351] In another embodiment, the solvent is ethyl acetate. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is ethyl acetate and the anti-solvent is heptane.

[0352] In one embodiment, there is provided a process for preparing Form 2 of the compound of Formula (I), comprising: (i) desolvating at least one non-Form 2 solid form of the compound of Formula (I) for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 2 solid form(s) to Form 2; (ii) recovering said Form 2.

[0353] In one embodiment, at least one Non-Form 2 solid form is desolvated at a temperature above room temperature. In one embodiment, the temperature is about 30 to about 60°C. In one embodiment, the temperature is about 40 to 60°C. In one embodiment, the temperature is about 50 to 60°C. In one embodiment, the temperature is about 100 to about 200°C. In one embodiment, at least one Non-Form 2 solid form is desolvated under vacuum. In one embodiment, at least one Non-Form 2 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, at least one Non-Form 2 solid form is Form 1 or any one of Forms 3 to 15 of the compound of Formula (I). In one embodiment, at least one Non-Form 2 solid form is Form 1 of the compound of Formula (I). In one embodiment, at least one Non-Form 2 solid form is Form 3 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of non-Form 2 solid form to Form 2 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours or more than 121 hours.

[0354] In one embodiment, Form 2 of compound of Formula (I) is prepared by a process comprising: (i) concentrating a solution comprising Compound 1 in a mixture of EtOH and heptane (volume ratio of EtOH:heptane of about 1:0.2 to about 1:0.7); (ii) adding about 3 to about 15 times the solution volume of heptane (e.g., 6 to 8 times); and (iii) heating the solution to about 45 to about 55° C. In one embodiment, the process further comprises, after step (iii), stirring the solution at about 10 to 15° C.

[0355] In one embodiment, Form 2 of the compound of Formula (I) is prepared by a process comprising: (i) concentrating a solution comprising the compound of Formula (I) in EtOAc; (ii) adding heptane to form a solution; and (iii) heating the solution to about 45 to about 55°C. In one embodiment, the concentration is performed at less than about 50°C. In one embodiment, the process further comprises adding a seeding amount of Form 2 after step (ii). In certain embodiments, the seeding amount is about 0.5% to about 15% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 1% to about 10% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 5% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 4% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 3% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 2% by weight of the compound of Formula (I). In certain embodiments, the seeding amount is about 1% by weight of the compound of Formula (I).

[0356] In one embodiment, there is provided a process for preparing Form 3 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 3 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 3 solid form(s) to Form 3; (ii) recovering said Form 3.

[0357] In one embodiment, the non-Form 3 solid form is exposed to one solvent. In one embodiment, the non-Form 3 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 3 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-MeTHF. In one embodiment, the non-Form 3 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 3 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 3 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0358] In one embodiment, the non-Form 3 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 3 solid form is any one of Forms 1-2 or Forms 4-15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 3 solid form to Form 3 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0359] Form 3 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0360] In one embodiment, Form 3 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-MeTHF.

[0361] In one embodiment, Form 3 of the compound of Formula (I) is prepared by a process comprising evaporating a solution of the compound in 2-MeTHF. In one embodiment, the evaporation is carried out at about 20° C. In one embodiment, the evaporation is carried out at about 50° C. In one embodiment, the evaporation is slow evaporation (e.g., for about 3 days or about 7 days).

[0362] In one embodiment, Form 3 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0363] In one embodiment, there is provided a process for preparing Form 4 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 4 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 4 solid form(s) to Form 4; (ii) recovering said Form 4.

[0364] In one embodiment, the non-Form 4 solid form is exposed to one solvent. In one embodiment, the non-Form 4 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 4 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 1,4-dioxane, water, heptane, or a mixture thereof. In one embodiment, the solvent is 1,4-dioxane. In one embodiment, the solvent is a mixture of 1,4-dioxane and heptane. In one embodiment, the volume ratio of 1,4-dioxane to heptane is about 1:2 to about 1:6. In one embodiment, the solvent is a mixture of 1,4-dioxane and water. In one embodiment, the volume ratio of 1,4-dioxane to water is about 1:2 to about 10:1. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the anti-solvent is water. In one embodiment, the solvent is 1,4-dioxane and the anti-solvent is heptane. In one embodiment, the solvent is 1,4-dioxane and the anti-solvent is water. In one embodiment, the final ratio of solvent to anti-solvent is about 1:2. In one embodiment, the final ratio of solvent to anti-solvent is about 1:1 to about 10:1. In one embodiment, the final ratio of solvent to anti-solvent is about 8:1. In one embodiment, the Non-Form 4 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the Non-Form 4 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the Non-Form 4 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0365] In one embodiment, the Non-Form 4 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 4 solid form is any one of Forms 1 through 3 or Forms 5 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 4 solid form to Form 4 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0366] Form 4 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0367] In one embodiment, Form 4 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 1,4-dioxane.

[0368] In one embodiment, Form 4 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of 1,4-dioxane and heptane. In one embodiment, the volume ratio of 1,4-dioxane to heptane is about 1:10 to about 1:1. In one embodiment, the mixture of two solvents is a mixture of 1,4-dioxane and water. In one embodiment, the volume ratio of 1,4-dioxane to water is about 1:10 to about 10:1. In one embodiment, the volume ratio of 1,4-dioxane to water is about 1:1. In one embodiment, the volume ratio of 1,4-dioxane to water is about 8:1.

[0369] In one embodiment, Form 4 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in a mixture of 1,4-dioxane and water. In one embodiment, the mixture has a volume ratio of 1,4-dioxane to water of about 1:2. In one embodiment, the mixture has a volume ratio of 1,4-dioxane to water of about 8:1. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 12 hours.

[0370] In one embodiment, Form 4 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0371] In one embodiment, there is provided a process for preparing Form 5 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 5 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 5 solid form(s) to Form 5; (ii) recovering said Form 5.

[0372] In one embodiment, the non-Form 5 solid form is exposed to one solvent. In one embodiment, the non-Form 5 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 5 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-propanol, t-butanol, THF, acetone, heptane, or a mixture thereof. In one embodiment, the solvent is 2-propanol. In one embodiment, the solvent is t-butanol. In one embodiment, the solvent is THF. In one embodiment, the solvent is acetone. In one embodiment, the solvent is a mixture of 2-propanol and t-butanol. In one embodiment, the solvent is a mixture of acetone and t-butanol. In one embodiment, the solvent is a mixture of THF and t-butanol. In one embodiment, the non-Form 5 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 5 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 5 solid form is exposed to the solvent at a temperature of about 25°C to about 60°C.

[0373] In one embodiment, the Non-Form 5 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 5 solid form is any one of Forms 1 through 4 or Forms 6 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 5 solid form to Form 5 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0374] Form 5 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0375] In one embodiment, Form 5 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is 2-propanol, t-butanol, THF, acetone, heptane, or a mixture thereof. In one embodiment, the solvent is 2-propanol. In one embodiment, the solvent is t-butanol. In one embodiment, the solvent is THF. In one embodiment, the solvent is acetone.

[0376] In one embodiment, Form 5 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the solvent is a mixture of 2-propanol and t-butanol. In one embodiment, the solvent is a mixture of acetone and t-butanol. In one embodiment, the solvent is a mixture of THF and t-butanol.

[0377] In one embodiment, Form 5 of the compound of Formula (I) is prepared by a process comprising milling the compound in t-butanol (e.g., with steel beads). In one embodiment, the compound is milled with the beads at 6000 RPM. In one embodiment, milling is performed in cycles, for example, 90-second cycles with a 10-second pause per cycle. In one embodiment, 40 cycles are performed.

[0378] In one embodiment, Form 5 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0379] In one embodiment, there is provided a process for preparing Form 6 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 6 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 6 solid form(s) to Form 6; (ii) recovering said Form 6.

[0380] In one embodiment, the non-Form 6 solid form is exposed to one solvent. In one embodiment, the non-Form 6 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 6 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is acetone. In one embodiment, the non-Form 6 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 6 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 6 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0381] In one embodiment, the Non-Form 6 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 6 solid form is any one of Forms 1 through 5 or Forms 7 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 6 solid form to Form 6 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0382] Form 6 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0383] In one embodiment, Form 6 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is acetone.

[0384] In one embodiment, Form 6 of the compound of Formula (I) is prepared by a process comprising milling the compound in acetone (e.g., with steel beads). In one embodiment, the compound is milled with the beads at 6000 RPM. In one embodiment, milling is performed in cycles, for example, 90-second cycles with a 10-second pause per cycle. In one embodiment, 40 cycles are performed.

[0385] In one embodiment, Form 6 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0386] In one embodiment, there is provided a process for preparing Form 7 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 7 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 7 solid form(s) to Form 7; (ii) recovering said Form 7.

[0387] In one embodiment, the non-Form 7 solid form is exposed to one solvent. In one embodiment, the non-Form 7 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 7 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MIBK, heptane, or a mixture thereof. In one embodiment, the solvent is MIBK. In one embodiment, the solvent is a mixture of MIBK and heptane. In one embodiment, the ratio of MIBK to heptane is about 1:1 to about 1:6. In one embodiment, the ratio of MIBK to heptane is about 1:2. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is MIBK and the anti-solvent is heptane. In one embodiment, the final ratio of solvent to anti-solvent is about 1:1 to about 1:6. In one embodiment, the final ratio of solvent to anti-solvent is about 1:2. In one embodiment, the non-Form 7 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the non-Form 7 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the non-Form 7 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0388] In one embodiment, the Non-Form 7 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 7 solid form is any one of Forms 1 through 6 or Forms 8 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 7 solid form to Form 7 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0389] Form 7 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0390] In one embodiment, Form 7 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MIBK.

[0391] In one embodiment, Form 7 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of MIBK and heptane. In one embodiment, the volume ratio of MIBK to heptane is about 1:10 to about 1:1. In one embodiment, the volume ratio of MIBK to heptane is about 1:2.

[0392] In one embodiment, Form 7 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in a mixture of MIBK and heptane. In one embodiment, the mixture has a volume ratio of MIBK to heptane of about 1:2. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 12 hours.

[0393] In one embodiment, Form 7 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0394] In one embodiment, there is provided a process for preparing Form 8 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 8 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 8 solid form(s) to Form 8; (ii) recovering said Form 8.

[0395] In one embodiment, the non-Form 8 solid form is exposed to one solvent. In one embodiment, the non-Form 8 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 8 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is THF, heptane, or a mixture thereof. In one embodiment, the solvent is THF. In one embodiment, the solvent is a mixture of THF and heptane. In one embodiment, the volume ratio of THF to heptane is about 1:1 to about 1:6. In one embodiment, the volume ratio of THF to heptane is about 1:1. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is THF and the anti-solvent is heptane. In one embodiment, the final volume ratio of solvent to anti-solvent is about 1:1 to about 1:6. In one embodiment, the final volume ratio of solvent to anti-solvent is about 1:1. In one embodiment, the non-Form 8 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the non-Form 8 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the non-Form 8 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0396] In one embodiment, the Non-Form 8 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 8 solid form is any one of Forms 1 through 7 or Forms 9 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 8 solid form to Form 8 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0397] Form 8 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0398] In one embodiment, Form 8 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is THF.

[0399] In one embodiment, Form 8 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of THF and heptane. In one embodiment, the volume ratio of THF to heptane is about 1:10 to about 1:1. In one embodiment, the volume ratio of THF to heptane is about 1:1.

[0400] In one embodiment, Form 8 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in a mixture of THF and heptane. In one embodiment, the mixture has a volume ratio of THF to heptane of about 1:2. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 24 hours.

[0401] In one embodiment, Form 8 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0402] In one embodiment, there is provided a process for preparing Form 9 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 9 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 9 solid form(s) to Form 9; (ii) recovering said Form 9.

[0403] In one embodiment, the non-Form 9 solid form is exposed to one solvent. In one embodiment, the non-Form 9 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 9 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexanone, heptane, or a mixture thereof. In one embodiment, the solvent is cyclohexanone. In one embodiment, the solvent is cyclohexanone. In one embodiment, the ratio of cyclohexanone to heptane is from about 1:1 to about 1:6. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is cyclohexanone and the anti-solvent is heptane. In one embodiment, the final ratio of solvent to anti-solvent is from about 1:1 to about 1:6. In one embodiment, the Non-Form 9 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the Non-Form 9 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the Non-Form 9 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0404] In one embodiment, the Non-Form 9 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 9 solid form is any one of Forms 1 through 8 or Forms 10 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 9 solid form to Form 9 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0405] Form 9 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0406] In one embodiment, Form 9 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexanone.

[0407] In one embodiment, Form 9 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of cyclohexanone and heptane. In one embodiment, the volume ratio of cyclohexanone to heptane is from about 1:10 to about 1:1.

[0408] In one embodiment, Form 9 of the compound of Formula (I) is prepared by evaporating a solution of the compound in cyclohexanone. In one embodiment, the evaporation is carried out at about 20° C. In one embodiment, the evaporation is slow evaporation (e.g., for about 7 days).

[0409] In one embodiment, Form 9 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0410] In one embodiment, there is provided a process for preparing Form 10 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 10 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 10 solid form(s) to Form 10; (ii) recovering said Form 10.

[0411] In one embodiment, the non-Form 10 solid form is exposed to one solvent. In one embodiment, the non-Form 10 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 10 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MIBK. In one embodiment, the non-Form 10 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 10 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 10 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0412] In one embodiment, the Non-Form 10 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the Non-Form 10 solid form is any one of Forms 1 through 9 or Forms 11 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the Non-Form 10 solid form to Form 10 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0413] Form 10 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0414] In one embodiment, Form 10 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MIBK. In one embodiment, the solvent mixture is MIBK and water. In one embodiment, the solvent mixture is MIBK and water in a volume ratio of about 1:3 to 3:1. In one embodiment, the solvent mixture is MIBK and water in a volume ratio of about 1:1.

[0415] In one embodiment, Form 10 of the compound of Formula (I) is prepared by evaporating a solution of the compound in MIBK. In one embodiment, the evaporation is carried out at about 20° C. In one embodiment, the evaporation is slow evaporation (e.g., for about 7 days).

[0416] In one embodiment, Form 10 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0417] In one embodiment, there is provided a process for preparing Form 11 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 11 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 11 solid form(s) to Form 11; (ii) recovering said Form 11.

[0418] In one embodiment, the non-Form 11 solid form is exposed to one solvent. In one embodiment, the non-Form 11 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 11 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MEK, heptane, or a mixture thereof. In one embodiment, the solvent is MEK. In one embodiment, the solvent is a mixture of MEK and heptane. In one embodiment, the volume ratio of MEK to heptane is about 1:1 to about 1:6. In one embodiment, the volume ratio of MEK to heptane is about 1:1. In one embodiment, the solvent is a mixture of MEK and water. In one embodiment, the solvent is a mixture of MEK and water having a volume ratio of about 10:1 to 1:1. In one embodiment, the solvent is a mixture of MEK and water in a volume ratio of about 5:1. In one embodiment, an anti-solvent is added to the solvent. In one embodiment, the anti-solvent is a non-polar organic solvent. In one embodiment, the non-polar organic solvent is a hydrocarbon solvent. In one embodiment, the anti-solvent is heptane. In one embodiment, the solvent is MEK and the anti-solvent is heptane. In one embodiment, the final volume ratio of solvent to anti-solvent is about 1:1 to about 1:6. In one embodiment, the Non-Form 11 solid form is exposed to the solvent and / or anti-solvent at room temperature. In one embodiment, the Non-Form 11 solid form is exposed to the solvent and / or anti-solvent at a temperature above room temperature. In one embodiment, the Non-Form 11 solid form is exposed to the solvent and / or anti-solvent at a temperature of about 25°C to about 60°C.

[0419] In one embodiment, the non-Form 11 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 11 solid form is any one of Forms 1 through 10 or Forms 12 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 11 solid form to Form 11 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0420] Form 11 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0421] In one embodiment, Form 11 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is MEK.

[0422] In one embodiment, Form 11 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I) from a solvent comprising a mixture of two solvents. In one embodiment, the mixture of two solvents is a mixture of MEK and heptane. In one embodiment, the volume ratio of MEK to heptane is about 1:10 to about 1:1.

[0423] In one embodiment, Form 11 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in a mixture of MEK and heptane. In one embodiment, the mixture has a volume ratio of MEK to heptane of about 1:1. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 12 hours.

[0424] In one embodiment, Form 11 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0425] In one embodiment, there is provided a process for preparing Form 12 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 12 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 12 solid form(s) to Form 12; (ii) recovering said Form 12.

[0426] In one embodiment, the non-Form 12 solid form is exposed to one solvent. In one embodiment, the non-Form 12 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 12 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is methylcyclohexane. In one embodiment, the non-Form 12 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 12 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 12 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0427] In one embodiment, the non-Form 12 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 12 solid form is any one of Forms 1 through 11 or Forms 13 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 12 solid form to Form 12 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0428] Form 12 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0429] In one embodiment, Form 12 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is methylcyclohexane.

[0430] In one embodiment, Form 12 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in methylcyclohexane. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 24 hours.

[0431] In one embodiment, Form 12 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0432] In one embodiment, there is provided a process for preparing Form 13 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 13 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 13 solid form(s) to Form 13; (ii) recovering said Form 13.

[0433] In one embodiment, the non-Form 13 solid form is exposed to one solvent. In one embodiment, the non-Form 13 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 13 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexane. In one embodiment, the non-Form 13 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 13 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 13 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0434] In one embodiment, the non-Form 13 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 13 solid form is any one of Forms 1 through 12 or Forms 14 through 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 13 solid form to Form 13 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0435] Form 13 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0436] In one embodiment, Form 13 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexane.

[0437] In one embodiment, Form 13 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring the compound in cyclohexane. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 24 hours.

[0438] In one embodiment, Form 13 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0439] In one embodiment, there is provided a process for preparing Form 14 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 14 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 14 solid form(s) to Form 14; (ii) recovering said Form 14.

[0440] In one embodiment, the non-Form 14 solid form is exposed to one solvent. In one embodiment, the non-Form 14 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 14 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexanone, t-butanol, or a mixture thereof. In one embodiment, the solvent is cyclohexanone. In one embodiment, the non-Form 14 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 14 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 14 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0441] In one embodiment, the non-Form 14 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 14 solid form is any one of Forms 1 through 13 or Form 15 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 14 solid form to Form 14 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0442] Form 14 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0443] In one embodiment, Form 14 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is cyclohexanone, t-butanol, or a mixture thereof.

[0444] In one embodiment, Form 14 of the compound of Formula (I) is prepared by a process comprising milling the compound in cyclohexanone (e.g., with steel beads). In one embodiment, the compound is milled with the beads at 6000 RPM. In one embodiment, milling is performed in cycles, for example, 90-second cycles with a 10-second pause per cycle. In one embodiment, 40 cycles are performed.

[0445] In one embodiment, Form 14 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0446] In one embodiment, there is provided a process for preparing Form 15 of the compound of Formula (I), comprising: (i) exposing a composition comprising at least one non-Form 15 solid form of the compound of Formula (I) to one or more solvents for a period of time sufficient to convert at least about 50% of the total amount of the non-Form 15 solid form(s) to Form 15; (ii) recovering said Form 15.

[0447] In one embodiment, the non-Form 15 solid form is exposed to one solvent. In one embodiment, the non-Form 15 solid form is exposed to a mixture of two solvents. In one embodiment, the non-Form 15 solid form is exposed to more than one solvent. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is acetone. In one embodiment, the non-Form 15 solid form is exposed to one solvent at room temperature. In one embodiment, the non-Form 15 solid form is exposed to a solvent at a temperature above room temperature. In one embodiment, the non-Form 15 solid form is exposed to a solvent at a temperature of about 25°C to about 60°C.

[0448] In one embodiment, the non-Form 15 solid form is an amorphous solid form of the compound of Formula (I). In one embodiment, the non-Form 15 solid form is any one of Forms 1 through 14 of the compound of Formula (I). In one embodiment, the period of time sufficient to convert at least about 50% of the total amount of the non-Form 15 solid form to Form 15 is about 1 hour, about 2 hours, about 5 hours, about 10 hours, about 12 hours, about 20 hours, about 24 hours, about 30 hours, about 40 hours, about 48 hours, about 72 hours, about 97 hours, about 121 hours, or more than 121 hours.

[0449] Form 15 of the compound of Formula (I) can be prepared by exposing a composition comprising the compound of Formula (I) to one or more solvents as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, impingement cooling, temperature cycling, slurrying, bead milling, or solvent drop milling.

[0450] In one embodiment, Form 15 of the compound of Formula (I) is prepared by crystallizing or recrystallizing the compound of Formula (I), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, from one or more solvents. In one embodiment, the solvent is an organic solvent. In one embodiment, the solvent is acetone.

[0451] In one embodiment, Form 15 of the compound of Formula (I) is prepared by a process comprising slurrying and / or stirring Form 2 of the compound in acetone. In one embodiment, the slurrying and / or stirring is performed at about 20° C. In one embodiment, the slurrying and / or stirring is performed for at least 36 hours.

[0452] In one embodiment, Form 15 of the compound of Formula (I) is prepared by crystallization or recrystallization as described in the experiments provided herein, including, but not limited to, evaporation, antisolvent addition, slow cooling, or impingement cooling.

[0453] 5.2.3. Salts of Compounds of Formula (I) In certain embodiments, provided herein are solid forms comprising salts of compounds of Formula (I). [ka]

[0454] In one embodiment, provided herein is a hydrochloride (HCl), methanesulfonate (mesylate), benzenesulfonate (besylate), maleate (maleate), phosphate (phosphate), citrate (citrate), L-tartrate (L-tartrate), fumarate (fumarate), toluenesulfonate (tosylate), or salicylate (salicylate) salt of Compound 1. In one embodiment, provided herein is a hydrochloride (HCl), methanesulfonate (mesylate), maleate (maleate), phosphate (phosphate), citrate (citrate), L-tartrate (L-tartrate), fumarate (fumarate), toluenesulfonate (tosylate), or salicylate (salicylate) salt of Compound 1.

[0455] The molar ratio of Compound 1 to the counterion of the salt of Compound 1 can be about 1:1, about 1:2, about 1:3, or about 1:4. In one embodiment, the molar ratio of Compound 1 to the counterion is about 1:1. In one embodiment, the molar ratio of Compound 1 to the counterion is about 1:2. In one embodiment, the molar ratio of Compound 1 to the counterion is about 1:3. In one embodiment, the molar ratio of Compound 1 to the counterion is about 1:4.

[0456] In one embodiment, the counterion is chloride, mesylate, besylate, maleate, phosphate, citrate, L-tartarate, fumarate, tosylate, or salicylate. In one embodiment, the salt of Compound 1 is the hydrochloride salt (HCl) of Compound 1. In one embodiment, the salt of Compound 1 is the methanesulfonate salt (mesylate) of Compound 1. In one embodiment, the salt of Compound 1 is the benzenesulfonate salt (besylate) of Compound 1. In one embodiment, the salt of Compound 1 is the maleate salt (Malate) of Compound 1. In one embodiment, the salt of Compound 1 is the phosphate salt (Phosphate) of Compound 1. In one embodiment, the salt of Compound 1 is the citrate salt (Citrate) of Compound 1. In one embodiment, the salt of Compound 1 is the L-tartrate salt (L-Tartrate). In one embodiment, the salt of Compound 1 is the fumarate salt (Fumarate). In one embodiment, the salt of Compound 1 is the toluenesulfonate (Tosylate). In one embodiment, the salt of Compound 1 is a salicylate salt (salicylate).

[0457] In one embodiment, provided herein is a solid form comprising a salt of Compound 1. In one embodiment, the salt of Compound 1 provided herein is amorphous.

[0458] 5.2.4. Solid Forms of Salts of Compounds of Formula (I) In certain embodiments, provided herein are solid forms comprising salts of compounds of Formula (I). [ka]

[0459] In one embodiment, provided herein is a solid form comprising a salt of Compound 1. In one embodiment, the solid form comprises a salicylate (salicylate) or maleate (maleate) salt of Compound 1. In one embodiment, provided herein is a solid form comprising the anhydrous free base of Compound 1.

[0460] It is contemplated that salts of Compound 1 can exist in various solid forms. Such solid forms include crystalline solids (e.g., crystalline forms of an anhydrous salt of Compound 1), amorphous solids, or mixtures of crystalline and amorphous solids. In one embodiment, the solid form is substantially crystalline. In one embodiment, the solid form is crystalline.

[0461] 5.2.4.1 Form A of the Salicylate Salt of Compound 1 In one embodiment, provided herein is Form A of the salicylate salt of Compound 1. In one embodiment, Form A is the monosalicylate salt of Compound 1.

[0462] A representative XRPD pattern of Form A of the salicylate salt of Compound 1 is provided in FIG.

[0463] In one embodiment, provided herein is a solid form comprising a salicylate salt of Compound 1, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.5, 8.5, 9.0, 9.7, 11.7, 12.9, 13.7, 14.7, 14.9, 17.7, 18.2, 18.8, 19.6, 20.0, 21.6, 22.0, 23.0, 24.6, 25.0, and 25.9 °2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0464] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a salicylate salt of Compound 1, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.5, 8.5, 9.7, 11.7, 14.7, 17.7, and 18.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.5, 8.5, 9.7, 11.7, 14.7, 17.7, and 18.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.5, 8.5, 9.7, 11.7, 14.7, 17.7, and 18.8 °2θ.

[0465] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a salicylate salt of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 9.7, 11.7, and 14.7 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 6.5 and 18.8 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 8.5 and 17.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.5, 8.5, 9.7, 11.7, 14.7, 17.7, 18.2, 18.8, and 19.6 °2θ.

[0466] In one embodiment, provided herein is a solid form comprising a salicylate salt of Compound 1, wherein the solid form is characterized by an XRPD pattern that corresponds to the XRPD pattern displayed in Figure 58. In one embodiment, Form A, provided in Figure 58, is anhydrous.

[0467] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0468] In some embodiments, provided herein is a solid form comprising a salicylate salt of Compound 1, wherein the solid form is a crystalline anhydrous salicylate salt of Compound 1. In some embodiments, the solid form is substantially free of amorphous salicylate salt of Compound 1. In some embodiments, the solid form is substantially free of a solid form (e.g., a crystalline form) of the salicylate salt of Compound 1. In some embodiments, the solid form is substantially free of the free base form of Compound 1. In some embodiments, the solid form is substantially free of other salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially enantiomerically pure. In some embodiments, the solid form is substantially physically pure.

[0469] Also provided herein, in some embodiments, is a process for preparing a salicylate salt of Compound 1, comprising exposing a composition comprising the free base of Compound 1 to salicylic acid. In one embodiment, the free base of Compound 1 is exposed to salicylic acid in an organic solvent, such as isopropyl acetate. In some embodiments, the organic solvent is isopropyl acetate. In some embodiments, the organic solvent is ethyl acetate.

[0470] All combinations of the above embodiments are encompassed by the present application.

[0471] 5.2.4.2 Form A of the Maleate Salt of Compound 1 In one embodiment, provided herein is Form A of the maleate salt of Compound 1. In one embodiment, Form A is the monomaleate salt of Compound 1.

[0472] A representative XRPD pattern of Form A of the maleate salt of Compound 1 is provided in FIG.

[0473] In one embodiment, a solid form comprising the maleate salt of Compound 1, wherein one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Kα radiation: 6.0, 10.5, 10.9, 11.3, 12.1, 13.8, 16.0, 17.4, 18.2, 19.7, 21.0, 21.3, 22.1, 22.3, 22.9, 23.9, 24.8, 25.3, 26.9, 27.5, 28.3, and 28.8 degrees 2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0474] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a maleate salt of Compound 1, wherein the solid form is characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.5, 10.9, 11.3, 12.1, 13.8, 16.0, 17.4, 18.2, 19.7, 21.0, 21.3, 22.1, 22.3, 22.9, 23.9, 24.8, 25.3, 26.9, 27.5, 28.3, and 28.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.5, 10.9, 11.3, 12.1, 13.8, 16.0, 17.4, 18.2, 19.7, 21.0, 21.3, 22.1, 22.3, 22.9, 23.9, 24.8, 25.3, 26.9, 27.5, 28.3, and 28.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.0, 10.5, 10.9, 11.3, 12.1, 13.8, 16.0, 17.4, 18.2, 19.7, 21.0, 21.3, 22.1, 22.3, 22.9, 23.9, 24.8, 25.3, 26.9, 27.5, 28.3, and 28.8 °2θ.

[0475] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a maleate salt of Compound 1, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.0, 13.8, and 21.3 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 16.0 and 17.4 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 18.2 and 22.9 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.0, 10.5, 10.9, 12.1, 13.8, 16.0, 17.4, 18.2, 21.3, and 22.9 °2θ.

[0476] In one embodiment, provided herein is a solid form comprising a maleate salt of Compound 1, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in Figure 59. In one embodiment, Form A, provided in Figure 59, is anhydrous.

[0477] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0478] In some embodiments, provided herein is a solid form comprising a maleate salt of Compound 1, wherein the solid form is a crystalline anhydrous maleate salt of Compound 1. In some embodiments, the solid form is substantially free of amorphous maleate salt of Compound 1. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the maleate salt of Compound 1. In some embodiments, the solid form is substantially free of the free base form of Compound 1. In some embodiments, the solid form is substantially free of other salts of Compound 1. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially enantiomerically pure. In some embodiments, the solid form is substantially physically pure.

[0479] Also provided herein, in some embodiments, is a process for preparing a maleate salt of Compound 1, comprising exposing a composition comprising the free base of Compound 1 to maleic acid. In one embodiment, the free base of Compound 1 is exposed to maleic acid in an organic solvent, such as isopropyl acetate. In some embodiments, the organic solvent is isopropyl acetate. In some embodiments, the organic solvent is ethyl acetate.

[0480] All combinations of the above embodiments are encompassed by the present application.

[0481] 5.2.5. Salts of the Compound of Formula (II) In certain embodiments, provided herein are salts of compounds of Formula (II). [ka]

[0482] In one embodiment, provided herein is a benzenesulfonic acid, ethanedisulfonic acid, citric acid, fumaric acid, hydrochloric acid, L-malic acid, maleic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, sulfuric acid, succinic acid, L-tartaric acid, phosphoric acid, toluenesulfonic acid, oxalic acid, camphorsulfonic acid, ethanesulfonic acid, 2-naphthalenesulfonic acid, 2-hydroxyethanesulfonic acid, trifluoroacetic acid, or hydrobromide salt of a compound of Formula (II). In one embodiment, provided herein is a methanesulfonic acid (mesylic acid), toluenesulfonic acid (tosylic acid), camphorsulfonic acid (camsylic acid), ethanesulfonic acid (esylic acid), benzenesulfonic acid (besylic acid), 2-naphthalenesulfonic acid (2-naphthalenesulfonic acid), or sulfuric acid (sulfate) salt of a compound of Formula (II).

[0483] The molar ratio of the compound of Formula (II) (also referred to herein as "Compound 2") to the counterion of the salt of Compound 2 can be about 1:1, about 1:2, about 1:3, or about 2:1. In one embodiment, the molar ratio of Compound 2 to the counterion is about 1:1. In one embodiment, the molar ratio of Compound 2 to the counterion is about 1:2.

[0484] In one embodiment, the counterion is besylate, mesylate, tosylate, camsylate, esylate, sulfate, or 2-naphthalenesulfonic acid. In one embodiment, the salt of Compound 2 is the benzenesulfonate (besylate) salt of Compound 2. In one embodiment, the salt of Compound 2 is the monobesylate salt of Compound 2. In one embodiment, the salt of Compound 2 is the methanesulfonate (mesylate) salt of Compound 2. In one embodiment, the salt of Compound 2 is the monomesylate salt of Compound 2. In one embodiment, the salt of Compound 2 is the toluenesulfonate (tosylate) salt of Compound 2. In one embodiment, the salt of Compound 2 is the monotosylate salt of Compound 2. In one embodiment, the salt of Compound 2 is the camphorsulfonate (camsylate) salt of Compound 2. In one embodiment, the salt of Compound 2 is the monocamsylate salt of Compound 2. In one embodiment, the salt of Compound 2 is the ethanesulfonate (esylate) salt of Compound 2. In one embodiment, the salt of Compound 2 is the monoesylate salt of Compound 2. In one embodiment, the salt of Compound 2 is the sulfate salt of Compound 2. In one embodiment, the salt of Compound 2 is the hemisulfate salt of Compound 2 (e.g., about 0.5 molar equivalent sulfate salt). In one embodiment, the salt of Compound 2 is the 2-naphthalenesulfonate salt of Compound 2 (2-naphthalenesulfonate). In one embodiment, the salt of Compound 2 is the mono 2-naphthalenesulfonate salt of Compound 2.

[0485] In one embodiment, provided herein is a solid form comprising a salt of Compound 2. In one embodiment, the salt of Compound 2 provided herein is amorphous. In one embodiment, the salt of Compound 2 provided herein is a crystalline solid form.

[0486] 5.2.6. Solid Forms of Salts of the Compound of Formula (II) In certain embodiments, provided herein are solid forms comprising a salt of a compound of Formula (II). [ka]

[0487] In one embodiment, provided herein is a solid form comprising a salt of Compound 2. In one embodiment, the solid form comprises the benzenesulfonic acid, ethanedisulfonic acid, citric acid, fumaric acid, hydrochloric acid, L-malic acid, maleic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, sulfuric acid, succinic acid, L-tartaric acid, phosphoric acid, toluenesulfonic acid, oxalic acid, camphorsulfonic acid, ethanesulfonic acid, 2-naphthalenesulfonic acid, 2-hydroxyethanesulfonic acid, trifluoroacetic acid, or hydrobromide salt of Compound 2. In one embodiment, the solid form comprises the methanesulfonic acid (mesylate), toluenesulfonic acid (tosylate), camphorsulfonic acid (camsylate), ethanesulfonic acid (esylate), benzenesulfonic acid (besylate), 2-naphthalenesulfonic acid (2-naphthalenesulfonic acid), or sulfuric acid (sulfate) salt of Compound 2. In one embodiment, a solid form comprising the anhydrous free base of Compound 2 is provided herein.

[0488] It is contemplated that the salt of Compound 2 can exist in various solid forms. Such solid forms include crystalline solids (e.g., crystalline forms of an anhydrous salt of Compound 2), amorphous solids, or mixtures of crystalline and amorphous solids. In one embodiment, the solid form is substantially crystalline. In one embodiment, the solid form is crystalline.

[0489] 5.2.6.1 Form A of the mesylate salt of compound 2 In one embodiment, provided herein is Form A of the mesylate salt of Compound 2. In one embodiment, Form A is the monomesylate salt of Compound 2.

[0490] A representative XRPD pattern of Form A of the mesylate salt of Compound 2 is provided in FIG.

[0491] In one embodiment, a solid form comprising the mesylate salt of Compound 2, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 7.7, 10.6, 11.7, 15.1, 15.9, 16.4, 17.1, 17.5, 17.9, 19.5, 19.7, 21.5, 22.7, 23.1, 23.4, 23.6, 23.9, 24.2, 25.5, 25.9, 27.0, 28.4, 28.5, 30.5, and 32.9 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0492] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a mesylate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 7.7, 10.6, 11.7, 15.1, 15.9, 17.1, 17.5, 19.5, 19.7, 21.5, 22.7, 23.4, 23.6, and 25.9 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 7.7, 10.6, 11.7, 15.1, 15.9, 17.1, 17.5, 19.5, 19.7, 21.5, 22.7, 23.4, 23.6, and 25.9 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 7.7, 10.6, 11.7, 15.1, 15.9, 17.1, 17.5, 19.5, 19.7, 21.5, 22.7, 23.4, 23.6, and 25.9 °2θ.

[0493] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a mesylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 15.9, 17.5, and 19.5 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 10.6 and 11.7 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 21.5 and 22.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 7.7, 10.6, 11.7, 15.9, 17.5, 19.5, 21.5, and 22.7 °2θ.

[0494] In one embodiment, provided herein is a solid form comprising a mesylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern presented in Figure 35. In one embodiment, Form A, which provides Figure 35, is anhydrous.

[0495] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0496] Representative DSC and TGA thermograms of Form A of the mesylate salt of Compound 2 are provided in Figure 36 and Figure 37, respectively. In one embodiment, provided herein is a solid form comprising the mesylate salt of Compound 2, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 194°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 196°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 36. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the mesylate salt of Compound 2, which exhibits about 0% weight loss upon heating from about 30°C to about 210°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 37. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form A, provided in Figures 36 and 37, is the anhydrous mesylate salt of Compound 2.

[0497] In some embodiments, provided herein is a solid form comprising a mesylate salt of Compound 2, wherein the solid form is a crystalline anhydrous mesylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous mesylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the mesylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially enantiomerically pure. In some embodiments, the solid form is substantially physically pure.

[0498] Also provided herein, in some embodiments, is a process for preparing the mesylate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to methanesulfonic acid. In one embodiment, the free base of Compound 2 is exposed to methanesulfonic acid in an organic solvent such as acetonitrile, ethyl acetate, THF, isopropyl acetate, or a mixture of ethyl acetate and heptane. In some embodiments, the organic solvent is acetonitrile. In some embodiments, the organic solvent is ethyl acetate. In some embodiments, the organic solvent is isopropyl acetate. In some embodiments, the organic solvent is a mixture of ethyl acetate and heptane. In some embodiments, the organic solvent is a mixture of isopropyl acetate and heptane.

[0499] All combinations of the above embodiments are encompassed by the present application.

[0500] 5.2.6.2 Form A of the Camsylate Salt of Compound 2 In one embodiment, provided herein is Form A of the camsylate salt of Compound 2. In one embodiment, Form A is the monocamsylate salt of Compound 2.

[0501] A representative XRPD pattern of Form A of the camsylate salt of Compound 2 is provided in FIG.

[0502] In one embodiment, a solid form comprising the camsylate salt of Compound 2, wherein one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 6.7, 8.7, 10.1, 11.0, 13.3, 14.1, 15.7, 16.0, 17.4, 17.6, 18.0, 18.7, 18.8, 20.0, 20.2, 20.8, 21.9, 22.1, 22.5, 23.7, 24.1, 24.8, 25.7, 26.8, and 32.2 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0503] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a camsylate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.7, 8.7, 10.1, 11.0, 13.3, 16.0, 17.4, 18.0, 18.8, 20.2, 20.8, 22.5, 24.8, and 25.7 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.7, 8.7, 10.1, 11.0, 13.3, 16.0, 17.4, 18.0, 18.8, 20.2, 20.8, 22.5, 24.8, and 25.7 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.7, 8.7, 10.1, 11.0, 13.3, 16.0, 17.4, 18.0, 18.8, 20.2, 20.8, 22.5, 24.8, and 25.7 °2θ.

[0504] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a camsylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.7, 13.3, and 20.2 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 10.1 and 16.0 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 8.7 and 18.0 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.7, 8.7, 10.1, 11.0, 13.3, 14.1, 16.0, 18.0, and 20.2 °2θ.

[0505] In one embodiment, provided herein is a solid form comprising a camsylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in Figure 38. In one embodiment, Form A, provided in Figure 38, is anhydrous.

[0506] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0507] Representative DSC and TGA thermograms for Form A of the camsylate salt of Compound 2 are provided in Figure 39 and Figure 40, respectively. In one embodiment, provided herein is a solid form comprising the camsylate salt of Compound 2, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 201°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 204°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 39. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the camsylate salt of Compound 2, which exhibits a weight loss of about 0.2% upon heating from about 185°C to about 215°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 40. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form A, provided in Figures 39 and 40, is the anhydrous camsylate salt of Compound 2.

[0508] In some embodiments, provided herein is a solid form comprising a camsylate salt of Compound 2, wherein the solid form is a crystalline anhydrous camsylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous camsylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the camsylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially enantiomerically pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0509] Also provided herein, in some embodiments, is a process for preparing the camsylate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to camphorsulfonic acid. In one embodiment, the free base of Compound 2 is exposed to camphorsulfonic acid in an organic solvent, such as a mixture of methyl acetate and heptane, a mixture of ethyl acetate and heptane, or a mixture of isopropyl acetate and heptane. In certain embodiments, the organic solvent is about 1:1 methyl acetate and heptane. In certain embodiments, the organic solvent is about 1:1 ethyl acetate and heptane. In certain embodiments, the organic solvent is about 1:1 isopropyl acetate and heptane.

[0510] All combinations of the above embodiments are encompassed by the present application.

[0511] 5.2.6.3 Form A of the Esylate Salt of Compound 2 In one embodiment, provided herein is Form A of the esylate salt of Compound 2. In one embodiment, Form A is the monoesylate salt of Compound 2.

[0512] A representative XRPD pattern of Form A of the esylate salt of Compound 2 is provided in FIG.

[0513] In one embodiment, a solid form comprising an esylate salt of Compound 2, wherein one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 7.8, 10.5, 11.6, 12.6, 13.2, 14.4, 15.1, 15.7, 16.3, 17.0, 17.3, 17.7, 19.2, 19.6, 21.4, 22.6, 23.0, 23.2, 23.5, 24.0, 25.2, 25.5, 25.9, 26.6, 26.8, 27.8, 28.2, 28.4, 30.2, 30.9, 31.9, and 32.5 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks, hi one embodiment, the solid form is characterized by at least 11 of the peaks, hi one embodiment, the solid form is characterized by all of the peaks.

[0514] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising an esylate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 8.7, 10.5, 11.6, 12.6, 13.2, 14.4, 15.1, 15.7, 17.0, 17.3, 19.2, 19.6, 21.4, 22.6, 23.0, 23.2, 23.5, and 25.5 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 8.7, 10.5, 11.6, 12.6, 13.2, 14.4, 15.1, 15.7, 17.0, 17.3, 19.2, 19.6, 21.4, 22.6, 23.0, 23.2, 23.5, and 25.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 8.7, 10.5, 11.6, 12.6, 13.2, 14.4, 15.1, 15.7, 17.0, 17.3, 19.2, 19.6, 21.4, 22.6, 23.0, 23.2, 23.5, and 25.5 °2θ.

[0515] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising an esylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 11.6, 15.7, and 19.2 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 10.5 and 17.3 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 14.4 and 15.1 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 7.8, 10.5, 11.6, 12.6, 13.2, 14.4, 15.1, 15.7, 17.3, and 19.2 °2θ.

[0516] In one embodiment, provided herein is a solid form comprising an esylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern provided in Figure 42. In one embodiment, Form A, provided in Figure 42, is anhydrous.

[0517] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0518] Representative DSC and TGA thermograms for Form A of an esylate salt of Compound 2 are provided in Figure 43 and Figure 44, respectively. In one embodiment, provided herein is a solid form comprising an esylate salt of Compound 2, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 189°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 193°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 43. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising an esylate salt of Compound 2, which exhibits a weight loss of about 0.5% upon heating from about 170°C to about 235°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 44. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form A, which provides Figures 43 and 44, is the anhydrous esylate salt of Compound 2.

[0519] In some embodiments, provided herein is a solid form comprising an esylate salt of Compound 2, wherein the solid form is a crystalline anhydrous esylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous esylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the esylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0520] Also provided herein, in some embodiments, is a process for preparing an esylate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to ethanesulfonic acid. In one embodiment, the free base of Compound 2 is exposed to ethanesulfonic acid in an organic solvent, such as a 1:1 mixture of ethyl acetate and heptane.

[0521] All combinations of the above embodiments are encompassed by the present application.

[0522] 5.2.6.4 Form A of the sulfate salt of compound 2 In one embodiment, provided herein is Form A of the sulfate salt of Compound 2. In one embodiment, Form A is a hemisulfate salt of Compound 2 (e.g., about 0.5 molar equivalents of the sulfate salt).

[0523] A representative XRPD pattern of Form A of the sulfate salt of Compound 2 is provided in FIG.

[0524] In one embodiment, a solid form comprising the sulfate salt of Compound 2, wherein one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 10.8, 11.4, 12.3, 13.1, 14.9, 15.1, 15.5, 16.8, 17.2, 17.8, 18.3, 18.8, 19.9, 21.0, 21.5, 22.1, 22.5, 22.8, 23.4, 23.7, 24.0, 24.5, 24.8, 25.7, 26.0, 26.2, 27.0, 27.3, 28.0, 29.2, 30.0, and 34.6 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks, hi one embodiment, the solid form is characterized by at least 11 of the peaks, hi one embodiment, the solid form is characterized by all of the peaks.

[0525] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a sulfate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 10.8, 11.4, 12.3, 13.1, 15.1, 15.5, 17.2, 18.3, 19.9, 21.5, 22.1, 22.8, 24.0, and 24.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 10.8, 11.4, 12.3, 13.1, 15.1, 15.5, 17.2, 18.3, 19.9, 21.5, 22.1, 22.8, 24.0, and 24.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 10.8, 11.4, 12.3, 13.1, 15.1, 15.5, 17.2, 18.3, 19.9, 21.5, 22.1, 22.8, 24.0, and 24.8 °2θ.

[0526] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a sulfate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 13.1, 17.2, and 18.3 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 10.8 and 11.4 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 15.1 and 19.9 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 10.8, 11.4, 12.3, 13.1, 15.1, 15.5, 16.8, 17.2, 18.3, and 19.9 °2θ.

[0527] In one embodiment, provided herein is a solid form comprising a sulfate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern provided in Figure 46. In one embodiment, Form A, provided in Figure 46, is anhydrous.

[0528] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0529] Representative DSC and TGA thermograms for Form A of the sulfate salt of Compound 2 are provided in Figure 47 and Figure 48, respectively. In one embodiment, provided herein is a solid form comprising the sulfate salt of Compound 2, which, as characterized by DSC, exhibits a thermal (endothermic) event with an onset temperature of about 183°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 188°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 47. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, provided herein is a solid form comprising the sulfate salt of Compound 2, which exhibits a weight loss of about 0.6% upon heating from about 30°C to about 200°C. In one embodiment, the solid form is characterized by a TGA thermogram consistent with the TGA thermogram shown in Figure 48. In one embodiment, the TGA thermogram is as measured using a heating rate of about 10° C. / min. In one embodiment, Form A, which provides Figures 47 and 48, is the anhydrous sulfate salt of Compound 2.

[0530] In some embodiments, provided herein is a solid form comprising a sulfate salt of Compound 2, wherein the solid form is a crystalline anhydrous sulfate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous sulfate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the sulfate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0531] Also provided herein, in some embodiments, is a process for preparing the sulfate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to sulfuric acid. In one embodiment, the free base of Compound 2 is exposed to sulfuric acid in an organic solvent, such as a 1:1 mixture of ethanol and heptane.

[0532] All combinations of the above embodiments are encompassed by the present application.

[0533] 5.2.6.5 Form A of the Tosylate Salt of Compound 2 In one embodiment, provided herein is Form A of the tosylate salt of Compound 2. In one embodiment, Form A is the monotosylate salt of Compound 2.

[0534] A representative XRPD pattern of Form A of the tosylate salt of Compound 2 is provided in FIG.

[0535] In one embodiment, provided herein is a solid form comprising a tosylate salt of Compound 2, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, 12, 13, 14, 15, 16, 17, 18, 19, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 7.0, 12.2, 13.5, 14.2, 15.1, 17.0, 17.6, 18.8, 19.2, 19.4, 19.8, 20.6, 21.2, 21.3, 21.7, 23.4, 24.8, 25.1, 25.3, and 25.5 °2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0536] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a tosylate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 12.2, 13.5, 14.2, 15.1, 17.0, 17.6, 18.8, 19.2, 19.4, 19.8, 20.6, 21.2, 21.3, 21.7, 23.4, 24.8, 25.1, 25.3, and 25.5 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 12.2, 13.5, 14.2, 15.1, 17.0, 17.6, 18.8, 19.2, 19.4, 19.8, 20.6, 21.2, 21.3, 21.7, 23.4, 24.8, 25.1, 25.3, and 25.5 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 12.2, 13.5, 14.2, 15.1, 17.0, 17.6, 18.8, 19.2, 19.4, 19.8, 20.6, 21.2, 21.3, 21.7, 23.4, 24.8, 25.1, 25.3, and 25.5 °2θ.

[0537] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a tosylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 12.2, 14.2, and 17.6 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 19.2 and 20.6 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 19.8 and 21.2 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 7.0, 12.2, 13.5, 14.2, 15.1, 17.6, 19.2, 19.8, 20.6, and 21.2 °2θ.

[0538] In one embodiment, provided herein is a solid form comprising a tosylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in Figure 50. In one embodiment, Form A, provided in Figure 50, is anhydrous.

[0539] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0540] A representative DSC thermogram of Form A of the tosylate salt of Compound 2 is provided in Figure 51. In one embodiment, provided herein is a solid form comprising the tosylate salt of Compound 2, which, as characterized by DSC, exhibits a thermal (endothermic) event having an onset temperature of about 143°C (e.g., ±2°). In one embodiment, the thermal event also has a peak temperature of about 148°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 51. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form A provided in Figure 51 is an anhydrous tosylate salt of Compound 2.

[0541] In some embodiments, provided herein is a solid form comprising a tosylate salt of Compound 2, wherein the solid form is a crystalline anhydrous tosylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous tosylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the tosylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0542] Also provided herein, in some embodiments, is a process for preparing the tosylate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to toluenesulfonic acid. In one embodiment, the free base of Compound 2 is exposed to toluenesulfonic acid in an organic solvent, such as a 1:1 mixture of ethyl acetate and heptane.

[0543] All combinations of the above embodiments are encompassed by the present application.

[0544] 5.2.6.6 Form A of the Besylate Salt of Compound 2 In one embodiment, provided herein is Form A of the besylate salt of Compound 2. In one embodiment, Form A is the monobesylate salt of Compound 2.

[0545] A representative XRPD pattern of Form A of the besylate salt of Compound 2 is provided in FIG.

[0546] In one embodiment, a solid form comprising a besylate salt of Compound 2, wherein one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, or all of the XRPD peaks are selected from the group consisting of Cu, Provided herein are solid forms characterized by peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 6.8, 6.9, 9.2, 10.0, 10.9, 11.7, 12.7, 13.5, 13.8, 14.3, 14.5, 15.1, 16.8, 17.7, 18.1, 18.4, 19.0, 19.4, 19.7, 19.9, 20.1, 20.3, 20.8, 21.2, 21.5, 21.9, 22.3, 22.9, 23.6, 23.8, 24.3, and 25.4 degrees 2θ, as measured using Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least 9 of the peaks, hi one embodiment, the solid form is characterized by at least 11 of the peaks, hi one embodiment, the solid form is characterized by all of the peaks.

[0547] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a besylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.9, 9.2, 10.0, 10.9, 11.7, 12.7, 13.5, 13.8, 14.3, 14.5, 15.1, 16.8, 17.7, 18.1, 18.4, 19.0, 19.4, 19.7, 19.9, 20.1, 20.3, and 20.8 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.9, 9.2, 10.0, 10.9, 11.7, 12.7, 13.5, 13.8, 14.3, 14.5, 15.1, 16.8, 17.7, 18.1, 18.4, 19.0, 19.4, 19.7, 19.9, 20.1, 20.3, and 20.8 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.9, 9.2, 10.0, 10.9, 11.7, 12.7, 13.5, 13.8, 14.3, 14.5, 15.1, 16.8, 17.7, 18.1, 18.4, 19.0, 19.4, 19.7, 19.9, 20.1, 20.3, and 20.8 °2θ.

[0548] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a besylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.9, 10.9, and 16.8 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 13.8 and 15.1 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 11.7 and 12.7 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.9, 9.2, 10.0, 10.9, 11.7, 12.7, 13.5, 13.8, 15.1, 16.8, 19.4, and 20.8 °2θ.

[0549] In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in Figure 52. In one embodiment, Form A, provided in Figure 52, is anhydrous.

[0550] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0551] A representative DSC thermogram of Form A of a besylate salt of Compound 2 is provided in Figure 53. In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, which, as characterized by DSC, exhibits a first thermal (endothermic) event having an onset temperature of about 33°C (e.g., ±2°). In one embodiment, the first thermal event also has a peak temperature of about 42°C (e.g., ±2°). In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, which, as characterized by DSC, exhibits a second thermal (endothermic) event having an onset temperature of about 100°C (e.g., ±2°). In one embodiment, the second thermal event also has a peak temperature of about 103°C (e.g., ±2°). In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, which, as characterized by DSC, exhibits a third thermal (endothermic) event having an onset temperature of about 142°C (e.g., ±2°). In one embodiment, the third thermal event also has a peak temperature of about 152°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 53. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10°C / min. In one embodiment, Form A, provided in Figure 53, is the anhydrous besylate salt of Compound 2.

[0552] In some embodiments, provided herein is a solid form comprising a besylate salt of Compound 2, wherein the solid form is a crystalline anhydrous besylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous besylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the besylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0553] Also provided herein, in some embodiments, is a process for preparing Form A of the besylate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to benzenesulfonic acid. In one embodiment, the free base of Compound 2 is exposed to benzenesulfonic acid in an organic solvent, such as a 1:1 mixture of methyl acetate and heptane. In one embodiment, the process further comprises drying the besylate salt of Compound 2 under vacuum.

[0554] All combinations of the above embodiments are encompassed by the present application.

[0555] 5.2.6.7 Besylate Form B of Compound 2 In one embodiment, provided herein is Form B of the besylate salt of Compound 2. In one embodiment, Form B is a monobesylate salt of Compound 2.

[0556] A representative XRPD pattern of Form B of the besylate salt of Compound 2 is provided in FIG.

[0557] In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, wherein the solid form is characterized by having one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all of the XRPD peaks located at approximately (e.g., ±0.2 degrees 2θ) the following positions: 7.3, 9.8, 11.0, 11.7, 12.4, 13.4, 15.9, 16.9, 17.2, 19.2, 19.8, 20.8, 21.1, 21.6, 21.7, 22.1, 22.4, 23.0, 23.8, 24.6, 24.9, and 26.9 degrees 2θ, as measured using Cu Kα radiation. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0558] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a besylate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.0, 11.7, 12.4, 13.4, 15.9, 16.9, 17.2, 19.2, 19.8, 20.8, 21.1, 21.6, 21.7, 22.1, 22.4, 23.0, 23.8, 24.6, 24.9, and 26.9 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.0, 11.7, 12.4, 13.4, 15.9, 16.9, 17.2, 19.2, 19.8, 20.8, 21.1, 21.6, 21.7, 22.1, 22.4, 23.0, 23.8, 24.6, 24.9, and 26.9 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 11.0, 11.7, 12.4, 13.4, 15.9, 16.9, 17.2, 19.2, 19.8, 20.8, 21.1, 21.6, 21.7, 22.1, 22.4, 23.0, 23.8, 24.6, 24.9, and 26.9 °2θ.

[0559] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a besylate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 11.0, 12.4, and 13.4 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 17.2 and 20.7 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 15.9 and 19.2 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 7.3, 9.8, 11.0, 11.7, 12.4, 13.4, 15.9, 17.2, 19.2, and 20.7 °2θ.

[0560] In one embodiment, provided herein is a solid form comprising a besylate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in FIG.

[0561] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0562] In some embodiments, provided herein is a solid form comprising a besylate salt of Compound 2, wherein the solid form is a crystalline besylate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous besylate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of the besylate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0563] Also provided herein, in some embodiments, is a process for preparing Form B of a besylate salt of Compound 2, comprising exposing Form A of a besylate salt of Compound 2 to a humidified environment, such as 95% RH.

[0564] All combinations of the above embodiments are encompassed by the present application.

[0565] 5.2.6.8 Form A of the 2-naphthalenesulfonate salt of Compound 2 In one embodiment, provided herein is Form A of the 2-naphthalenesulfonate salt of Compound 2. In one embodiment, Form A is a mono-2-naphthalenesulfonate salt of Compound 2.

[0566] A representative XRPD pattern of Form A of the 2-naphthalenesulfonate salt of Compound 2 is provided in FIG.

[0567] In one embodiment, provided herein is a solid form comprising a 2-naphthalenesulfonate salt of Compound 2, characterized in that one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, or all of the XRPD peaks are located at approximately (e.g., ±0.2 degrees 2θ) the following positions when measured using Cu Kα radiation: 6.8, 7.9, 9.6, 10.6, 11.6, 13.7, 18.1, 18.6, 19.1, 19.8, 20.2, 20.9, 21.3, 21.9, 23.1, 23.7, 24.2, 25.7, and 26.3 °2θ. In one embodiment, the solid form is characterized by at least three of the peaks. In one embodiment, the solid form is characterized by at least five of the peaks. In one embodiment, the solid form is characterized by at least seven of the peaks. In one embodiment, the solid form is characterized by at least nine of the peaks. In one embodiment, the solid form is characterized by at least eleven of the peaks. In one embodiment, the solid form is characterized by all of the peaks.

[0568] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising 2-naphthalenesulfonate salt of Compound 2, characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.9, 9.6, 10.6, 11.6, 13.7, 18.1, 18.6, 19.1, 19.8, 20.2, 20.9, 21.3, 21.9, 23.1, 23.7, 24.2, 25.7, and 26.3 °2θ, when measured using Cu Kα radiation. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.9, 9.6, 10.6, 11.6, 13.7, 18.1, 18.6, 19.1, 19.8, 20.2, 20.9, 21.3, 21.9, 23.1, 23.7, 24.2, 25.7, and 26.3 °2θ. In one embodiment, the solid form is characterized by an XRPD pattern comprising at least five peaks selected from the group consisting of approximately (e.g., ±0.2°) 6.8, 7.9, 9.6, 10.6, 11.6, 13.7, 18.1, 18.6, 19.1, 19.8, 20.2, 20.9, 21.3, 21.9, 23.1, 23.7, 24.2, 25.7, and 26.3 °2θ.

[0569] In one embodiment, provided herein is a solid form (e.g., a crystalline form) comprising a 2-naphthalenesulfonate salt of Compound 2, characterized by an XRPD pattern comprising peaks at approximately (e.g., ±0.2°) 6.8, 7.9, and 9.6 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 11.6 and 13.7 °2θ. In one embodiment, the XRPD pattern further comprises peaks at approximately (e.g., ±0.2°) 10.6 and 19.8 °2θ. In one embodiment, the XRPD pattern comprises peaks at approximately (e.g., ±0.2°) 6.8, 7.9, 9.6, 10.6, 11.6, 13.7, 18.1, 19.8, and 20.2 °2θ.

[0570] In one embodiment, provided herein is a solid form comprising a 2-naphthalenesulfonate salt of Compound 2, wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern displayed in Figure 55. In one embodiment, Form A, provided in Figure 55, is anhydrous.

[0571] In one embodiment, the XRPD patterns described herein are obtained using Cu Kα radiation. In one embodiment, the XRPD patterns are measured by XRPD using Cu Kα radiation, including Kα1 radiation having a wavelength of 1.5406 Å and Kα2 radiation having a wavelength of 1.5444 Å.

[0572] A representative DSC thermogram of Form A of the 2-naphthalenesulfonate salt of Compound 2 is provided in Figure 56. In one embodiment, provided herein is a solid form comprising the 2-naphthalenesulfonate salt of Compound 2, which, as characterized by DSC, exhibits a first thermal (endothermic) event having an onset temperature of about 36°C (e.g., ±2°). In one embodiment, the first thermal event also has a peak temperature of about 50°C (e.g., ±2°). In one embodiment, provided herein is a solid form comprising the 2-naphthalenesulfonate salt of Compound 2, which, as characterized by DSC, exhibits a second thermal (endothermic) event having an onset temperature of about 97°C (e.g., ±2°). In one embodiment, the second thermal event also has a peak temperature of about 109°C (e.g., ±2°). In one embodiment, the solid form is characterized by a DSC thermogram consistent with the DSC thermogram shown in Figure 56. In one embodiment, the DSC thermogram is as measured by DSC using a scan rate of about 10° C. / min. In one embodiment, Form A, provided in FIG. 56, is the anhydrous 2-naphthalenesulfonic acid salt of Compound 2.

[0573] In some embodiments, provided herein is a solid form comprising 2-naphthalenesulfonate salt of Compound 2, wherein the solid form is a crystalline anhydrous 2-naphthalenesulfonate salt of Compound 2. In some embodiments, the solid form is substantially free of amorphous 2-naphthalenesulfonate salt of Compound 2. In some embodiments, the solid form is substantially free of other solid forms (e.g., crystalline forms) of 2-naphthalenesulfonate salt of Compound 2. In some embodiments, the solid form is substantially free of the free base form of Compound 2. In some embodiments, the solid form is substantially free of other salts of Compound 2. In some embodiments, the solid form is provided as substantially pure. In some embodiments, the solid form is substantially chemically pure. In some embodiments, the solid form is substantially physically pure.

[0574] Also provided herein, in some embodiments, is a process for preparing the 2-naphthalenesulfonate salt of Compound 2, comprising exposing a composition comprising the free base of Compound 2 to 2-naphthalenesulfonic acid. In one embodiment, the free base of Compound 2 is exposed to 2-naphthalenesulfonic acid in an organic solvent such as 2-MeTHF.

[0575] All combinations of the above embodiments are encompassed by the present application.

[0576] 5.3 Process for the Preparation of Compound 1 In certain embodiments, a compound of formula (II): [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, comprising: (Step 2.0) a compound of formula (III), [ka] or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, with a brominating reagent.

[0577] In another embodiment, the compound of formula (II): [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, comprising: (Step 2a.1) a compound of formula (XXIX), [ka] or a stereoisomer or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, with a compound of formula (XXX): [ka] or a pharmaceutically acceptable salt thereof.

[0578] In some embodiments, the process comprises: (Step 1.0) Cyclizing a compound of formula (II), or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, to give a compound of formula (I): [ka] or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof.

[0579] In some embodiments, a salt of the compound of Formula (II) is cyclized in Step 1.0. In some embodiments, a solid form of a salt of the compound of Formula (II) is cyclized in Step 1.0. In one embodiment, a camsylate salt of the compound of Formula (II) is cyclized in Step 1.0. In one embodiment, a solid form of a camsylate salt of the compound of Formula (II) (e.g., Form A) is cyclized in Step 1.0. In another embodiment, Step 1.0 comprises: (Step 1.1) converting the camsylate salt of a compound of formula (II) into the free base of the compound under basic conditions; (Step 1.2) cyclizing the free base of the compound.

[0580] In some embodiments, step 1.0 is carried out in the presence of a base. In some embodiments, the base is an organic base. In some embodiments, the organic base is a carboxylic acid base. In some embodiments, the carboxylic acid base is lithium acetate, sodium acetate, potassium acetate, lithium pivalate, sodium pivalate, potassium pivalate, cesium acetate, or cesium pivalate. In one embodiment, the base is potassium pivalate.

[0581] In some embodiments, the molar ratio of the compound of Formula (II) to the base in Step 1.0 is from about 1:2 to about 1:6. In one embodiment, the molar ratio of the compound of Formula (II) to the base in Step 1.0 is about 1:3.

[0582] In some embodiments, step 1.0 is performed in the presence of a catalyst precursor. In some embodiments, the catalyst precursor comprises a palladium source. In some embodiments, the palladium source is Pd-G3, Pd2(dba)3, PdCl2(MeCN)2, Pd(OAc)2, Pd(PPh3)4, PdCl2(PPh3)2, PdCl2(Pcy3)2, PdCl2(dtbpf), PdCl2(dppf), PdCl2(Amphos), {Pd(μ-Br)[P(tBu)3]}2, PdCl2[P(Cy)3]2, Pd[P(tBu)3]2, PdCl2(dtbpf), Pd[P(Cy)3]2, or PdCl2[P(tBu)(Cy)2]2. In one embodiment, the palladium source is Pd(OAc)2. In one embodiment, the catalyst precursor comprises Pd(OAc)2. In some embodiments, the catalyst precursor comprises a ligand. In some embodiments, the ligand is a phosphine ligand or a bisphosphine ligand. In some embodiments, the ligand is a phosphine or bisphosphine ligand commonly used in the art. In one embodiment, the ligand is a cataCXium ligand. In one embodiment, the cataCXium ligand is cataCXium A, cataCXium Abn, cataCXium AHI, cataCXium PintB, cataCXium PICy, cataCXium PtB, cataCXium PomeB, or cataCXium C. In one embodiment, the cataCXium ligand is cataCXium A. In one embodiment, the catalyst precursor comprises cataCXium A. In some embodiments, the catalyst precursor comprises a palladium source and a ligand. In some embodiments, the catalyst precursor and the ligand are preformed palladium ligand complexes, such as cataCXium A Pd G2, cataCXium A Pd G3, or bis(butyldi-1-adamantylphosphine)palladium diacetate. In one embodiment, the catalyst precursor comprises Pd(OAc)2 and cataCXium A.

[0583] In some embodiments, the molar ratio of the compound of Formula (II) to the palladium source (e.g., Pd(OAc)) in Step 1.0 is about 1:0.02 (i.e., 2 mol%) to about 1:0.3 (i.e., 30 mol%). In some embodiments, the molar ratio of the compound of Formula (II) to the palladium source in Step 1.0 is about 1:0.02, about 1:0.03, about 1:0.04, about 1:0.05, about 1:0.06, about 1:0.07, about 1:0.08, about 1:0.09, about 1:0.10, about 1:0.11, about 1:0.12, about 1:0.13, about 1:0.14, about 1:0.15, about 1:0.16, about 1:0.17, about 1:0.18, about 1:0.19, or about 1:0.20. In one embodiment, the molar ratio of the compound of Formula (II) to the palladium source in Step 1.0 is about 1:0.05 (i.e., 5 mol%). In one embodiment, the molar ratio of the compound of Formula (II) to the palladium source in Step 1.0 is about 1:0.12 (i.e., 12 mol%). In one embodiment, a palladium loading of less than about 20 mol%, less than about 15 mol%, less than about 10 mol%, or less than about 5 mol% is used in Step 1.0.

[0584] In some embodiments, the molar ratio of the compound of Formula (II) to the ligand (e.g., cataCXium ligand) in Step 1.0 is about 1:0.05 (i.e., 5 mol%) to about 1:0.32 (i.e., 32 mol%). In some embodiments, the molar ratio of the compound of Formula (II) to the ligand in Step 1.0 is about 1:0.05, about 1:0.08, about 1:0.10, about 1:0.16, about 1:0.17, about 1:0.18, about 1:0.19, about 1:0.20, about 1:0.21, about 1:0.22, about 1:0.23, about 1:0.24, about 1:0.25, about 1:0.26, about 1:0.27, about 1:0.28, about 1:0.29, about 1:0.30, about 1:0.31, or about 1:0.32. In one embodiment, the molar ratio of the compound of Formula (II) to the ligand in Step 1.0 is about 1:0.10 (i.e., 10 mol%). In one embodiment, the molar ratio of the compound of Formula (II) to the ligand in Step 1.0 is about 1:0.24 (i.e., 24 mol%). In one embodiment, a ligand load of less than about 30 mol% is used in Step 1.0.

[0585] In one embodiment, the molar ratio of the ligand (e.g., cataCXium ligand) to the palladium source (e.g., Pd(OAc)2) in step 1.0 is about 5:1 to about 1:5. In one embodiment, the molar ratio of the ligand to the palladium source is about 2:1 to about 1:2. In one embodiment, the molar ratio of the ligand to the palladium source is about 2:1 to about 1:1. In one embodiment, the ligand is a monodentate ligand and the molar ratio of the ligand to the palladium source is about 2:1. In one embodiment, the ligand is a monodentate ligand and the molar ratio of the ligand to the palladium source is about 1:1. In one embodiment, the ligand is a bidentate ligand and the molar ratio of the ligand to the palladium source is about 1:1. In one embodiment, the ligand is a bidentate ligand and the molar ratio of the ligand to the palladium source is about 1:2.

[0586] Step 1.0 can be carried out in a solvent suitable for the reaction. In some embodiments, the solvent is an organic solvent or a mixture of organic solvents. In one embodiment, the solvent is a high boiling point solvent, and the high boiling point solvent is C 4~12 Examples of suitable solvents include, but are not limited to, aliphatic alcohols (branched or unbranched), anisole, 2-MeTHF, DMF, NMP, DMA, or tAmOH. In one embodiment, the solvent is an alcohol. In one embodiment, the solvent is t-amyl alcohol (tAmOH). In one embodiment, the solvent is n-BuOH, s-BuOH, or t-BuOH.

[0587] In some embodiments, the volume of solvent in Step 1.0 is from about 10 volumes to about 30 volumes. In one embodiment, the volume of solvent in Step 1.0 is about 20 volumes.

[0588] As used herein, volume refers to the volume of solvent (L or mL) relative to the weight of the limiting reagent (kg or g, respectively). In some embodiments, step 1.0 is performed in an inert atmosphere (i.e., under conditions that eliminate or substantially reduce the presence of atmospheric oxygen). In one embodiment, the solvent is sparged with an inert gas (e.g., dinitrogen or argon) in step 1.0.

[0589] In some embodiments, Step 1.0 is carried out at a reaction temperature of about 90°C to about 120°C. In one embodiment, the reaction temperature is the boiling temperature of the solvent. In one embodiment, the reaction temperature is about 100°C to about 110°C. In one embodiment, the reaction temperature is about 102°C.

[0590] In some embodiments, step 1.0 is carried out for a reaction time of about 16 hours to about 30 hours, hi one embodiment, the reaction time is about 16 hours to about 20 hours.

[0591] In one embodiment, Step 1.0 is carried out in the presence of potassium pivalate base and a catalyst precursor comprising Pd(OAc)2 and cataCXium A. In one embodiment, the molar ratios of the compound of Formula (II) to potassium pivalate, Pd(OAc)2, and cataCXium A are about 1:3, about 1:0.12, and about 1:0.24, respectively. In one e...

Claims

1. Solid forms comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 。

2. The solid form according to claim 1, which is crystalline.

3. The solid form according to claim 1, comprising a free base of the compound of formula (I), and characterized by an XRPD pattern including peaks at 12.4, 18.9 and 21.1°²θ (±0.2°) when measured using Cu Kα radiation.

4. The solid form according to claim 3, wherein the XRPD pattern further includes peaks at 13.2° and 22.5°²θ (±0.2°).

5. The solid form according to claim 4, wherein the XRPD pattern further includes peaks at 11.2 and 22.7°²θ (±0.2°).

6. The solid form according to claim 3, characterized by an XRPD pattern that matches the XRPD pattern shown in Figure 4.

7. It exhibits an endothermic event characterized by an onset temperature of 260°C (±2°) and / or a peak temperature of 261°C (±2°), as characterized by DSC; and / or It exhibits a weight increase of approximately 0.3% when subjected to an increase in relative humidity from approximately 0% relative humidity to approximately 90% relative humidity; and / or It has unit cell dimensions of approximately a = 8.2 Å, b = 14.8 Å, c = 18.7 Å, α = 90°, β = 90°, and γ = 90°; and / or It is anhydrous. The solid form according to any one of claims 3 to 6.

8. (a) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.0, 18.5 and 20.6°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 12.8 and 17.1°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 9.2 and 22.5°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 1A; (b) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 9.4, 12.8 and 15.3°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 16.6 and 20.6°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 9.0 and 16.4°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 8; (c) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.1, 17.2 and 18.2°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 12.7° and 20.5°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 12.2° and 21.5°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 10; (d) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.8, 10.0 and 18.9°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 19.4° and 22.8°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 7.0 and 22.2°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 12A; (e) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.8, 10.0 and 18.1°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 6.0 and 22.4°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 20.1 and 24.1°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 16; (f) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.9, 9.1 and 19.6°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 12.0 and 23.4°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 10.6 and 21.2°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 17; (g) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.0, 17.0 and 19.7°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 9.2 and 21.5°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 10.8 and 18.0°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 19; (h) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.9, 17.2 and 19.4°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 17.7° and 19.6°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 11.9° and 23.3°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 21; (i) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.9, 8.4 and 8.6°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 10.6 and 16.1°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 11.2 and 19.3°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 23; (j) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.9, 10.7 and 20.1°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 12.0 and 23.1°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 9.1 and 16.7°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 25; (k) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.8, 19.2 and 22.1°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 5.9 and 17.7°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 8.7° and 18.8°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 27; (l) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 5.9, 9.2 and 19.2°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 11.9 and 17.2°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 10.4° and 21.4°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 29; (m) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.7, 16.9 and 18.9°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 6.8 and 22.2°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 9.7 and 21.2°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 31; (n) The solid form contains the free base of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.7, 22.0 and 22.8°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 18.8° and 20.5°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 10.6 and 20.0°²θ (±0.2°); Optionally, the XRPD pattern matches the XRPD pattern shown in Figure 33; (o) The solid form comprises a salicylate of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 9.7, 11.7 and 14.7°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 6.5 and 18.8°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 8.5 and 17.7°²θ (±0.2°); or (p) The solid form comprises the maleate of the compound of formula (I) and is characterized by an XRPD pattern that includes peaks at 6.0, 13.8 and 21.3°²θ (±0.2°) when measured using Cu Kα radiation; Optionally, the XRPD pattern further includes peaks at 16.0 and 17.4°²θ (±0.2°); Optionally, the XRPD pattern further includes peaks at 18.2° and 22.9°²θ (±0.2°), The solid form according to claim 1.

9. Compound of formula (I): 【Chemistry 2】 Hydrochloride, methanesulfonate (mesylate), benzenesulfonate (besylate), maleate, phosphate, citrate, L-tartrate, fumarate, toluenesulfonate (tosylate), or salicylate.

10. Compound of formula (I): 【Transformation 3】 Solid forms containing hydrochloride, methanesulfonate (mesylate), benzenesulfonate (besylate), maleate, phosphate, citrate, L-tartrate, fumarate, toluenesulfonate (tosylate), or salicylate.

11. A pharmaceutical composition comprising a solid form according to any one of claims 1 to 6, 8, and 10, or a salt according to claim 9, and a pharmaceutically acceptable excipient.

12. A pharmaceutical composition for the treatment of cancer, comprising a solid form according to any one of claims 1 to 6, 8, and 10, or a salt according to claim 9.

13. Form 2 of the compound of formula (I): 【Chemistry 4】 A method for preparing, (i) Dissolve the compound of formula (I) in a solvent. (ii) Adding a poor solvent, and (ii) The method comprising recovering the second form.

14. The method according to claim 13, wherein the solvent is ethyl acetate or ethanol; and / or the poor solvent is heptane.

15. Salt of the compound of formula (II): 【Transformation 5】 And; The salt is optionally a salt of a compound of formula (II) of benzenesulfonic acid, ethanedisulfonic acid, citric acid, fumaric acid, hydrochloric acid, L-malic acid, maleic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, sulfuric acid, succinic acid, L-tartaric acid, phosphoric acid, toluenesulfonic acid, oxalic acid, camphorsulfonic acid, ethanesulfonic acid, 2-naphthalenesulfonic acid, 2-hydroxyethanesulfonic acid, trifluoroacetic acid, or hydrobromic acid.

16. Salt of the compound of formula (II): 【Transformation 6】 A solid form including; Optionally, the solid form comprises a salt of the compound of formula (II) of benzenesulfonic acid, ethanedisulfonic acid, citric acid, fumaric acid, hydrochloric acid, L-malic acid, maleic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, sulfuric acid, succinic acid, L-tartaric acid, phosphoric acid, toluenesulfonic acid, oxalic acid, camphorsulfonic acid, ethanesulfonic acid, 2-naphthalenesulfonic acid, 2-hydroxyethanesulfonic acid, trifluoroacetic acid, or hydrobromic acid.

17. Compound of formula (II): 【Transformation 7】 A method for preparing a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, (Step 2.0) Compound of formula (III): 【Transformation 8】 or reacting a stereoisomer thereof, a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof with a brominating agent; or (Step 2a.1) Compound of formula (XXIX): 【Chemistry 9】 or its stereoisomer or mixture of stereoisomers, or its pharmaceutically acceptable salt, a compound of formula (XXX): 【Chemistry 10】 or react with a pharmaceutically acceptable salt thereof. The method, including the method described above.

18. (Step 1.0) Cyclizing the compound of formula (II) or its stereoisomer or mixture of stereoisomers, or a pharmaceutically acceptable salt thereof, to obtain the compound of formula (I): 【Chemistry 11】 The method according to claim 17, further comprising providing a stereoisomer thereof, a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof.

19. Compound of formula (I): 【Chemistry 12】 A method for preparing a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, (Step 1.0) Compound of formula (II): 【Chemistry 13】 The present invention provides a compound of formula (I) or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, by cyclizing the stereoisomer or mixture of stereoisomers thereof, wherein The method wherein step 1.0 is carried out in the presence of a base, and the base is potassium pivalate.

20. A solid form of the compound of formula (I) or a stereoisomer or mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, prepared by the method described in claim 18 or 19.

21. Compounds of formulas (III), (IV), (SP-1), (SP-2), (SP-3), (SP-4), (SP-5), (SP-6), (SP-7), or (SP-8): 【Chemistry 14】 【Chemistry 15】 or its stereoisomers or mixtures thereof, or pharmaceutically acceptable salts thereof.

22. Compound 1: 【Chemistry 16】 A pharmaceutical composition comprising a stereoisomer thereof or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, a diluent, a disintegrant, a fluidizing agent, a binder, and a lubricant.

23. A pharmaceutical composition according to claim 22 for the treatment of cancer.

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