Crystalline forms of substituted benzimidazoles acting as CDK9 inhibitors and their uses

Abstract

The present disclosure provides novel crystalline forms of compounds that act as CDK9 modulators, methods for preparing novel crystalline forms of compounds that act as CDK9 modulators, and uses thereof.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 255,562, filed October 14, 2021, which is incorporated by reference herein in its entirety.

[0002] The present disclosure provides novel crystalline forms of compounds that act as CDK9 modulators, methods for preparing novel crystalline forms of compounds that act as CDK9 modulators, and uses thereof. [Background technology]

[0003] U.S. Provisional Patent Application No. 17 / 018005, filed September 11, 2020, and published March 11, 2021 as US20210070761, discloses compounds that act as regulators of cyclin-dependent kinases (CDKs), including CDK9, a family of serine / threonine kinases whose activity depends on association and activation by cyclins and plays a key role in controlling cell cycle and gene transcription (Malumbres, M. (2014). “Cyclin-dependent kinases.” Genome Biol 15(6):122). “CDK9: A key player in cancer and other diseases.” J Cell Biochem 119(2):1273-1284; Soutourina, J. (2018). CDK9 plays a pivotal role in promoting gene expression as a master regulator that controls the release of dormant Pol II from promoters.Consistently, inhibition of CDK9 induces a global downregulation of gene expression (Olson,CM,et al.(2018).“Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation.”Nat Chem Biol 14(2):163-170), including short-lived transcripts such as oncogenes, c-Myc, and Mcl-1, a member of the pro-survival Bcl-2 protein family that promotes cancer cell survival (Chen,R.,et al.(2005).“Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death.”Blood 106(7):2513-2519;Youle,RJand A.Strasser (2008).“The BCL-2 protein family:opposing activities that mediate cell death.”Nat Rev Mol Cell Biol 9(1):47-59), an indirect approach of targeting Mcl-1 to treat cancer has been suggested (Krystof,V.,et al.(2012).“Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target.”Curr Pharm Des 18(20):2883-2890). In fact, several CDK9 inhibitors have been developed, shown promising anticancer activity in preclinical models, and introduced into the clinic (Boffo,S.,et al.(2018).“CDK9 inhibitors in acute myeloid leukemia.”J Exp Clin Cancer Res 37(1):36).Interestingly, a recent study found that CDK9 inhibition also reactivates epigenetically silenced tumor suppressor genes, adding to the body of evidence supporting targeting CDK9 for cancer therapy (Zhang, H., et al., (2018). "Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer." Cell 175(5):1244-1258.e1226). For example, compounds that modulate the activity of CDK9, such as CDK9 inhibitors, may be beneficial in treating diseases or disorders associated with abnormal CDK activity, such as cancer and tumor cells. One particular compound has formula I. [ka] It is a compound having the formula:

[0004] The compounds of formula I described or provided herein, the ability of the compounds to affect CDK9 activity or the absence of such activity, methods for the preparation of the compounds of formula I described or provided herein, and other related compounds are disclosed in U.S. Provisional Patent Application No. 17 / 018005, published as US20210070761 on March 11, 2021, the contents of which are incorporated herein by reference in their entirety.

[0005] There remains a need in the art for improved forms of the compounds of formula I described or provided herein, having improved properties. There also remains a need in the art for improved methods for preparing compounds of formula I. The present embodiments described herein meet these and other needs. Summary of the Invention

[0006] The present disclosure provides novel crystalline forms of the compounds of formula I provided herein, methods for preparing the crystalline forms of the compounds, and optionally methods for isolating such crystalline forms.

[0007] The compound of formula I can be crystallized with or without a coformer and has excellent properties. In some embodiments, the crystalline form of the compound of formula I without a coformer is distinguished from the prior art by improved stability, processability, and can be used in pharmaceutical formulations. In some embodiments, the crystalline form of the compound of formula I with a coformer is distinguished from the prior art by improved stability, processability, and can be used in pharmaceutical formulations.

[0008] In some embodiments, a crystalline form of the compound of formula I described herein is provided.

[0009] In some embodiments, the compound of formula I provided herein can be crystallized without a coformer. In some embodiments, a crystalline form of the compound of formula I without a coformer is provided. In some embodiments, a crystalline form I and a form II of the compound of formula I without a coformer are provided.

[0010] In some embodiments, provided is crystalline Form I of the compound of Formula I. In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern including one or more peaks at about 7.2±0.5 degrees 2θ, about 8.0±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 13.0±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 15.3±0.5 degrees 2θ, about 16.8±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ. In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.3±0.5 degrees Angstroms, about 11.0±0.5 degrees Angstroms, about 8.7±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.8±0.5 degrees Angstroms, about 5.3±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms.

[0011] In some embodiments, provided is a crystalline Form II of the compound of Formula I. In some embodiments, the crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.3±0.5 degrees 2θ, about 8.1±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 11.5±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 15.4±0.5 degrees 2θ, about 16.1±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18.3±0.5 degrees 2θ, about 19.2±0.5 degrees 2θ, about 21.0±0.5 degrees 2θ, about 21.7±0.5 degrees 2θ, about 22.3±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ. In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.1±0.5 degrees Angstroms, about 10.9±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.7±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms.

[0012] In some embodiments, the compound of formula I provided herein can be crystallized with a coformer. In some embodiments, a crystalline form of the compound of formula I with a coformer is provided. In some embodiments, crystalline form III, form IV, form V, form VI, form VII, form VIII, form IX, form X, form XI, form XII, and form XIII of the compound of formula I with a coformer are provided. In some embodiments, the coformer is a coformer provided and described herein. In some embodiments, the coformer is succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, or D-(-)-tartaric acid.

[0013] In some embodiments, crystalline Form III is provided that comprises the compound of formula I and succinic acid in about a 1:1 molar ratio. In some embodiments, crystalline Form III is at about 5.8±0.5 degrees 2θ, about 8.8±0.5 degrees 2θ, about 10.5±0.5 degrees 2θ, about 12.4±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 17.9±0.5 degrees 2θ, about 18.5±0.5 degrees 2θ, about 19.5±0.5 degrees 2θ, about 20.0±0.5 degrees 2θ, about 20.7±0.5 degrees 2θ, about 21.4±0.5 degrees 2θ, about 22.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.5±0.5 degrees 2θ, about 25.5±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, about 27.5±0.5 degrees 2θ, about 28.5±0.5 degrees 2θ, about 29.5±0.5 degrees 2θ, about 30.5±0.5 degrees 2θ, about 31.5±0.5 degrees 2θ, about 32.5±0.5 degrees 2θ, about 33.5±0.5 degrees 2θ, about 34.5±0.5 degrees 2θ, about 35.5±0.5 degrees 2θ, about 36.5±0.5 degrees 2θ, about 37.5±0.5 degrees 2θ, about 38.5±0.5 degrees 2θ, about 39.5±0.5 degrees 2θ, about 40.5±0.5 degrees 2θ, about 41. 0.4±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.9±0.5 degrees 2θ, about 26.4±0.5 degrees 2θ, about 27.6±0.5 degrees 2θ, about 29.0±0.5 degrees 2θ, about 31.6±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ. In some embodiments, the crystalline Form III has a molecular weight of about 15.1±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.1±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.4±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.0±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.8±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0014] In some embodiments, crystalline Form IV is provided that comprises the compound of formula I and glutaric acid in a molar ratio of about 2:1. In some embodiments, crystalline Form IV is about 4.5±0.5 degrees 2θ, about 6.0±0.5 degrees 2θ, about 8.9±0.5 degrees 2θ, about 11.1±0.5 degrees 2θ, about 11.7±0.5 degrees 2θ, about 13.2±0.5 degrees 2θ, about 16.3±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 17.6±0.5 degrees 2θ, about 18.4±0.5 degrees 2θ, about 19. 7±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, about 21.0±0.5 degrees 2θ, about 21.9±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.0±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 29.2±0.5 degrees 2θ. In some embodiments, crystalline Form IV has a molecular weight of about 19.4±0.5 degrees Angstroms, about 14.7±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 6.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 5.0±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.5±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.1±0.5 degrees Angstroms.

[0015] In some embodiments, crystalline form V is provided that comprises the compound of formula I and adipic acid in about a 1:1 molar ratio. In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern that includes one or more peaks at about 4.7±0.5 degrees 2θ, about 7.4±0.5 degrees 2θ, about 9.2±0.5 degrees 2θ, about 11.2±0.5 degrees 2θ, about 13.8±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.1±0.5 degrees 2θ, about 18.9±0.5 degrees 2θ, about 25.1±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ. In some embodiments, crystalline Form V is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 18.8±0.5 degrees Angstroms, about 11.9±0.5 degrees Angstroms, about 9.6±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 6.4±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, and about 3.4±0.5 degrees Angstroms.

[0016] In some embodiments, crystalline Form VI is provided, comprising the compound of formula I and fumaric acid in a molar ratio of about 2:1. In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.4±0.5 degrees 2θ, about 9.5±0.5 degrees 2θ, about 13.6±0.5 degrees 2θ, about 14.7±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 16.4±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 19.4±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, about 21.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.8±0.5 degrees 2θ, about 25.7±0.5 degrees 2θ, about 26.9±0.5 degrees 2θ, about 29.4±0.5 degrees 2θ, and about 30.7±0.5 degrees 2θ. In some embodiments, crystalline Form VI has a crystallinity of about 12.0±0.5 degrees Angstroms, about 9.3±0.5 degrees Angstroms, about 6.5±0.5 degrees Angstroms, about 6.0±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.3±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.5±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, and about 2.9±0.5 degrees Angstroms.

[0017] In some embodiments, crystalline Form VII is provided that comprises the compound of formula I and fumaric acid in a molar ratio of about 2:1. In some embodiments, crystalline Form VII is about 4.7±0.5 degrees 2θ, about 5.8±0.5 degrees 2θ, about 10.6±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 11.8±0.5 degrees 2θ, about 12.6±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 14.0±0.5 degrees 2θ, about 16.0±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18 ... The compound is characterized by an X-ray powder diffraction pattern including one or more peaks at about 0.5±0.5 degrees 2θ, about 18.7±0.5 degrees 2θ, about 19.3±0.5 degrees 2θ, about 21.2±0.5 degrees 2θ, about 22.1±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 27.4±0.5 degrees 2θ. In some embodiments, crystalline Form VII has a molecular weight of about 18.9±0.5 degrees Angstroms, about 15.2±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 7.0±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 5.1±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.2±0.5 degrees Angstroms.

[0018] In some embodiments, crystalline Form VIII is provided that comprises the compound of formula I and fumaric acid in a molar ratio of about 1:1. In some embodiments, crystalline Form VIII is about 3.9±0.5 degrees 2θ, about 5.7±0.5 degrees 2θ, about 7.1±0.5 degrees 2θ, about 8.6±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 12.1±0.5 degrees 2θ, about 14.1±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 19.1±0.5 degrees 2θ, about 20.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, ... 2θ, about 23.0±0.5 degrees 2θ, about 24.3±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, about 28.5±0.5 degrees 2θ, about 34.6±0.5 degrees 2θ, about 35.4±0.5 degrees 2θ, about 36.8±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ. In some embodiments, crystalline Form VIII has a molecular weight of about 22.5±0.5 degrees Angstroms, about 15.5±0.5 degrees Angstroms, about 12.5±0.5 degrees Angstroms, about 10.3±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.3±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 5 ... 5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.4±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0019] In some embodiments, crystalline Form IX is provided that comprises the compound of formula I and D-(-)-tartaric acid. In some embodiments, crystalline Form IX is about 5.3±0.5 degrees 2θ, about 6.8±0.5 degrees 2θ, about 9.0±0.5 degrees 2θ, about 10.0±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 17.3±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 18.8±0.5 degrees 2θ, about 19.9±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.3±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, about 24. 3±0.5 degrees 2θ, about 25.5±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 27.1±0.5 degrees 2θ, about 28.0±0.5 degrees 2θ, about 28.8±0.5 degrees 2θ, about 29.8±0.5 degrees 2θ, about 33.4±0.5 degrees 2θ, about 34.2±0.5 degrees 2θ, about 36.3±0.5 degrees 2θ, about 38.6±0.5 degrees 2θ, and about 39.1±0.5 degrees 2θ. In some embodiments, crystalline Form IX has a molecular weight of about 16.7±0.5 degrees Angstroms, about 12.9±0.5 degrees Angstroms, about 9.8±0.5 degrees Angstroms, about 8.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.5±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 3.7±0.5 degrees Angstroms, about 3.5±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, about 2.7±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.3±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0020] In some embodiments, crystalline form X is provided that comprises the compound of formula I and hydrochloric acid. In some embodiments, crystalline form X is characterized by an X-ray powder diffraction pattern that includes one or more peaks as shown in Figure 50.

[0021] In some embodiments, crystalline form XI is provided that comprises the compound of formula I and salicylic acid in a molar ratio of about 2:1. In some embodiments, crystalline form XI is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG.

[0022] In some embodiments, crystalline Form XII is provided that comprises the compound of formula I and oxalic acid in a molar ratio of about 1:1. In some embodiments, crystalline Form XII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in Figure 54.

[0023] In some embodiments, there is provided a crystalline form XIII of the compound of formula I and 1-hydroxy-2-naphthoic acid. In some embodiments, the crystalline form XIII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in Figure 59.

[0024] In some embodiments, a pharmaceutical composition is provided that comprises a crystalline form of the compound of formula I, as described or provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form I, form II, form III, form IV, form V, form VI, form VII, form VIII, form IX, form X, form XI, form XII, or form XIII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form I, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form II, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form III, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VI, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form V, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VIII, comprising the compound of formula I. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form IX, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form X, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XI, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XIII, as described and provided herein.

[0025] In some embodiments, the pharmaceutical compositions comprising crystalline forms I-XIII described or provided herein further comprise a pharma- ceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises crystalline form I. In some embodiments, the pharmaceutical composition comprises crystalline form II. In some embodiments, the pharmaceutical composition comprises crystalline form III. In some embodiments, the pharmaceutical composition comprises crystalline form VI. In some embodiments, the pharmaceutical composition comprises crystalline form V. In some embodiments, the pharmaceutical composition comprises crystalline form VI. In some embodiments, the pharmaceutical composition comprises crystalline form VII. In some embodiments, the pharmaceutical composition comprises crystalline form VIII. In some embodiments, the pharmaceutical composition comprises crystalline form IX. In some embodiments, the pharmaceutical composition comprises crystalline form X. In some embodiments, the pharmaceutical composition comprises crystalline form XI. In some embodiments, the pharmaceutical composition comprises crystalline form XII. In some embodiments, the pharmaceutical composition comprises crystalline form XIII.

[0026] In some embodiments, there is provided a method for preparing a crystalline form of a compound of formula I, with or without a coformer, as described or provided herein, comprising crystallizing the compound to form a crystalline form and optionally isolating the crystalline form.

[0027] In some embodiments, a method of inhibiting a CDK enzyme is provided, the method comprising contacting the CDK enzyme with an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising same.

[0028] In some embodiments, there is provided a method of treating a disease or disorder associated with aberrant CDK activity in a subject or in a subject in need thereof, the method comprising administering to the subject a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising same.

[0029] In some embodiments, there is provided a method of treating cancer in a subject or in a subject in need thereof, the method comprising administering to the subject a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising same.

[0030] In some embodiments, there is provided a method of inducing apoptosis in cancer or tumor cells in a subject or a subject in need thereof, the method comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition provided herein.

[0031] In some embodiments, a method is provided for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells in a subject or a subject in need thereof, the method comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition provided herein.

[0032] In some embodiments, there is provided a method of reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, the method comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition provided herein.

[0033] In some embodiments, a method is provided for reducing the level of MYC protein in cancer or tumor cells in a subject or a subject in need thereof, the method comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition provided herein.

[0034] In some embodiments, a method of inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof is provided, the method comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition provided herein.

[0035] In some embodiments, pharmaceutical compositions are provided that include one or more of the crystalline forms provided herein, or a pharma- ceutically acceptable salt or solvate thereof.

[0036] The details of one or more embodiments are set forth in the description below. Other features, objects, and advantages of the present teachings will be apparent from the description of the embodiments, and from the appended claims. [Brief description of the drawings]

[0037] [Figure 1] FIG. 1 shows the X-ray powder diffraction pattern of the amorphous form of the compound of formula I.

[0038] [Diagram 2] FIG. 2 shows the X-ray powder diffraction pattern of crystalline Form I of the compound of formula I.

[0039] [Diagram 3] FIG. 3 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form I.

[0040] [Figure 4] FIG. 4 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form I.

[0041] [Diagram 5] FIG. 5 shows a proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form I.

[0042] [Figure 6]FIG. 6 shows the X-ray powder diffraction pattern of crystalline Form II of the compound of formula I.

[0043] [Figure 7] FIG. 7 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form II.

[0044] [Figure 8] FIG. 8 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form II.

[0045] [Figure 9] FIG. 9 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form II.

[0046] [Figure 10] FIG. 10 shows the extensive proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form I.

[0047] [Figure 11] FIG. 11 shows the large scale X-ray powder diffraction pattern of crystalline Form I of the compound of formula I.

[0048] [Figure 12] FIG. 12 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form III of succinic acid.

[0049] [Figure 13] FIG. 13 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form III.

[0050] [Figure 14] FIG. 14 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form III.

[0051] [Figure 15] FIG. 15 shows the high performance liquid chromatography analysis (HPLC) of crystalline Form III.

[0052] [Figure 16] FIG. 16 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form III.

[0053] [Figure 17] FIG. 17 shows a proton nuclear magnetic resonance spectroscopy ( 1 H NMR) comparison of the compound of formula I with crystalline Form III.

[0054] [Figure 18] FIG. 18 shows the X-ray powder diffraction patterns of crystalline Form IV of the compound of formula I and glutaric acid.

[0055] [Figure 19] FIG. 19 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form IV.

[0056] [Figure 20] FIG. 20 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form IV.

[0057] [Figure 21] FIG. 21 shows the high performance liquid chromatography analysis (HPLC) of crystalline Form IV.

[0058] [Figure 22] FIG. 22 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form IV.

[0059] [Diagram 23] FIG. 23 shows a proton nuclear magnetic resonance spectroscopy (.sup.1H NMR) comparison of the compound of formula I with crystalline Form IV.

[0060] [Figure 24] FIG. 24 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline form V of adipic acid.

[0061] [Diagram 25] FIG. 25 shows a differential scanning calorimetry (DSC) thermogram of crystalline form V.

[0062] [Figure 26] FIG. 26 shows a thermogravimetric analysis (TGA) thermogram of crystalline form V.

[0063] [Figure 27] FIG. 27 shows the high performance liquid chromatography analysis (HPLC) of crystalline form V.

[0064] [Figure 28] FIG. 28 shows a proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline form V.

[0065] [Figure 29] FIG. 29 shows a proton nuclear magnetic resonance spectroscopy ( 1 H NMR) comparison of the compound of formula I with crystalline form V.

[0066] [Diagram 30] FIG. 30 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form VI of gentisic acid.

[0067] [Diagram 31] FIG. 31 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form VI.

[0068] [Diagram 32] FIG. 32 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form VI.

[0069] [Diagram 33] FIG. 33 shows the high performance liquid chromatography analysis (HPLC) of crystalline Form VI.

[0070] [Diagram 34] FIG. 34 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form VI.

[0071] [Diagram 35]FIG. 35 shows a proton nuclear magnetic resonance spectroscopy (.sup.1H NMR) comparison of the compound of formula I with crystalline Form VI.

[0072] [Diagram 36] FIG. 36 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form VII of fumaric acid.

[0073] [Figure 37] FIG. 37 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form VII.

[0074] [Figure 38] FIG. 38 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form VII.

[0075] [Figure 39] FIG. 39 shows the high performance liquid chromatography analysis (HPLC) of crystalline Form VII.

[0076] [Diagram 40] FIG. 40 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form VII.

[0077] [Diagram 41] FIG. 41 shows a proton nuclear magnetic resonance spectroscopy (.sup.1H NMR) comparison of the compound of formula I with crystalline Form VII.

[0078] [Diagram 42] FIG. 42 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form VIII of fumaric acid.

[0079] [Diagram 43] FIG. 43 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form VIII.

[0080] [Diagram 44] FIG. 44 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form VIII.

[0081] [Diagram 45] FIG. 45 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form VIII.

[0082] [Diagram 46] FIG. 46 shows the X-ray powder diffraction patterns of crystalline Form IX of the compound of formula I and D-(−)-tartaric acid.

[0083] [Figure 47] FIG. 47 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form IX.

[0084] [Figure 48] FIG. 48 shows a thermogravimetric analysis (TGA) thermogram of crystalline Form IX.

[0085] [Figure 49] FIG. 49 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form IX.

[0086] [Figure 50] FIG. 50 shows the X-ray powder diffraction pattern overlay of crystalline form X of the compound of formula I with hydrochloric acid prepared from methyl ethyl ketone (MEK), n-butanol (n-BuOH), and n-propanol.

[0087] [Figure 51] FIG. 51 shows a differential scanning calorimetry (DSC) thermogram of crystalline form X.

[0088] [Figure 52] FIG. 52 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline form XI of salicylic acid.

[0089] [Diagram 53] FIG. 53 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline form XI.

[0090] [Figure 54] FIG. 54 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form XII of oxalic acid.

[0091] [Figure 55] FIG. 55 shows a differential scanning calorimetry (DSC) thermogram of crystalline Form XII.

[0092] [Figure 56] FIG. 56 shows the high performance liquid chromatography analysis (HPLC) of crystalline Form XII.

[0093] [Figure 57] FIG. 57 shows the proton nuclear magnetic resonance spectroscopy ( 1 H NMR) analysis of crystalline Form XII.

[0094] [Figure 58] FIG. 58 shows the carbon-13 nuclear magnetic resonance spectroscopy (C NMR) analysis of crystalline Form XII.

[0095] [Figure 59] FIG. 59 shows the X-ray powder diffraction patterns of the compound of formula I and crystalline Form XIII of 1-hydroxy-2-naphthoic acid. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0096] The term "salt" or "salts" may refer to any acid addition salt, including addition salts of free acids or addition salts of free bases. All of these salts (or other similar salts) may be prepared by conventional means. All such salts are acceptable provided they are non-toxic and do not substantially interfere with the desired pharmacological activity.

[0097] The term "therapeutically effective amount" means an amount of the crystalline form that is sufficient to effect Treatment (defined below) when administered to a mammal for treating a disease state, disorder, or condition. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, physical condition and responsiveness of the mammal being treated.

[0098] The term "pharmaceutical acceptable" means biologically or pharmacologically compatible for in vivo use in animals or humans, and preferably means approved by a federal or state regulatory agency or listed in the United States Pharmacopeia or other generally recognized pharmacopoeias for use in animals, and more specifically, in humans.

[0099] As used herein, the terms "treat", "treated" or "treating" refer to both therapeutic and prophylactic treatments, the purpose of which is to delay (reduce) an undesirable physiological condition, disorder, or disease, or to obtain a beneficial or desired clinical outcome. For purposes of the present invention, beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms; reduction in the extent of a condition, disorder, or disease; stabilized (i.e., not worsening) pathology of a condition, disorder, or disease; delayed onset or progression of a condition, disorder, or disease; improvement or remission (whether partial or total) of a condition, disorder, or disease pathology, whether detectable or undetectable; improvement in at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or amelioration of a condition, disorder, or disease. Treatment includes eliciting a clinically significant response without excessive levels of side effects. Treatment also includes prolonging survival compared to expected survival in the absence of treatment. Thus, "treatment of pain" or "treating pain" refers to activities that reduce or ameliorate any of the primary phenomena or secondary symptoms associated with pain or other conditions described herein.

[0100] The term "additive" is defined as the interaction of two or more drugs whose combined effect is the same as the sum of their individual effects. For example, the effect of drug A alone on treatment is 25% and the effect of drug B alone on treatment is 25%, but when the two drugs are combined, the effect on treatment is 50%, and the effects of A and B are additive.

[0101] The term "pharmaceutical acceptable" or "therapeutically acceptable" refers to molecular entities and compositions that are physiologically acceptable and preferably do not normally produce allergic or similar adverse reactions, such as upset stomach, dizziness, etc., when administered to humans.Preferably, as used herein, the term "pharmaceutical acceptable" means approved by a federal or state government regulatory agency or listed in the United States Pharmacopeia or other generally recognized pharmacopoeias for use in animals, more specifically in humans (e.g., Remington's Pharmaceutical Sciences, Mack Publishing Co. (AR Gennaro edit. 1985)).

[0102] The terms "about," "ca.," or "approximately" mean plus or minus 5%. In some embodiments, the terms "about," "ca.," or "approximately" mean plus or minus 10%.

[0103] The present embodiments provide methods of crystallizing compound of formula I, with or without a coformer, as described or provided herein.

[0104] In some embodiments, a method for preparing a crystalline form of a compound having a formula of Formula I with or without a coformer, as described or provided herein. In some embodiments, a method for preparing a crystalline form of a compound of Formula I without a coformer, as described or provided herein. In some embodiments, a method for preparing a crystalline form of a compound of Formula I with a coformer, as described or provided herein. In some embodiments, the method includes co-crystallizing a compound of Formula I and a coformer to form a crystalline form of the compound and the coformer, and optionally isolating the crystalline form of the compound and the coformer. In some embodiments, the method includes slurrying the compound and the coformer in an organic solvent to form a crystalline form therefrom. In some embodiments, the method further includes washing the slurry with an organic solvent.

[0105] In some embodiments, a crystalline form of the compound of formula I with a coformer is provided. In some embodiments, the coformer is an acid. In some embodiments, the acid is a pharmaceutically acceptable acid. In some embodiments, the pharmaceutically acceptable acid is selected from succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, and D-(-)-tartaric acid. In some embodiments, the pharmaceutically acceptable acid is succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, or D-(-)-tartaric acid, or any combination thereof. In some embodiments, the pharmaceutically acceptable acid is succinic acid. In some embodiments, the pharmaceutically acceptable acid is adipic acid. In some embodiments, the pharmaceutically acceptable acid is fumaric acid. In some embodiments, the pharma- ceutically acceptable acid is glutaric acid. In some embodiments, the pharma- ceutically acceptable acid is gentisic acid. In some embodiments, the pharma- ceutically acceptable acid is hydrochloric acid. In some embodiments, the pharma- ceutically acceptable acid is 1-hydroxy-2-naphthoic acid. In some embodiments, the pharma- ceutically acceptable acid is salicylic acid. In some embodiments, the pharma- ceutically acceptable acid is oxalic acid. In some embodiments, the pharma- ceutically acceptable acid is D-(-)-tartaric acid.

[0106] The compounds of formula I, or pharma- ceutically acceptable salts thereof, described or provided herein, can be prepared according to the synthesis described in U.S. Provisional Patent Application No. 17 / 018005, published as US20210070761 on March 11, 2021, which is incorporated herein by reference in its entirety, or according to the synthesis described or provided herein. For example, in some embodiments, the compounds of formula I, or pharma- ceutically acceptable salts thereof, can be prepared according to the synthesis described in U.S. Provisional Patent Application No. 17 / 018005, which is incorporated herein by reference in its entirety.

[0107] The amorphous form of the compound of formula I, or a pharma- ceutically acceptable salt thereof, can be prepared according to the synthesis described in U.S. Provisional Patent Application No. 17 / 018005, published as US20210070761 on March 11, 2021, which is incorporated herein by reference in its entirety. The amorphous form of the compound of formula I, or a pharma- ceutically acceptable salt thereof, can then be isolated using silica gel chromatography. Silica gel chromatography may not be suitable for large-scale production of compounds for commercial production. Thus, there is a need for a crystalline form that can be better used in the manufacture and use of pharmaceutical compositions. In some cases, it may be straightforward to prepare a crystalline form of a compound, but this has not been the case for the compound of formula I. The present embodiments provide surprising and unexpected results of a crystalline form of formula I. In some embodiments, the crystalline form is Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, Form X, Form XI, Form XII, or Form XIII as provided herein. In some embodiments, the crystalline form is Form I as provided herein. In some embodiments, the crystalline form is Form II as provided herein. In some embodiments, the crystalline form is Form III as provided herein. In some embodiments, the crystalline form is Form VI as provided herein. In some embodiments, the crystalline form is Form V as provided herein. In some embodiments, the crystalline form is Form VI as provided herein. In some embodiments, the crystalline form is Form VII as provided herein. In some embodiments, the crystalline form is Form VIII as provided herein. In some embodiments, the crystalline form is Form IX as provided herein. In some embodiments, the crystalline form is Form X as provided herein. In some embodiments, the crystalline form is Form XI as provided herein. In some embodiments, the crystalline form is Form XII as provided herein. In some embodiments, the crystalline form is Form XIII as provided herein.

[0108] In some embodiments, the crystalline form of the compound having the formula of Formula I without a coformer, as described or provided herein. In some embodiments, the crystalline form is Form I or Form II. In some embodiments, the crystalline form is Form I. In some embodiments, the crystalline form is Form II.

[0109] In some embodiments, crystalline Form I of the compound of formula I is provided. In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 2. In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern that includes one or more peaks as provided in Table 2. In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern that includes substantially all, or all, of the peaks provided in Table 2.

[0110] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 7.2±0.5 degrees 2θ.

[0111] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 8.0±0.5 degrees 2θ.

[0112] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.1±0.5 degrees 2θ.

[0113] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.3±0.5 degrees 2θ.

[0114] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.0±0.5 degrees 2θ.

[0115] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 14.4±0.5 degrees 2θ.

[0116] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 15.3±0.5 degrees 2θ.

[0117] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 16.8±0.5 degrees 2θ.

[0118] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.2±0.5 degrees 2θ.

[0119] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.9±0.5 degrees 2θ.

[0120] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.6±0.5 degrees 2θ.

[0121] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.2±0.5 degrees 2θ.

[0122] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.1±0.5 degrees 2θ.

[0123] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, and about 10.1±0.5 degrees 2θ.

[0124] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, and about 18.2±0.5 degrees 2θ.

[0125] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, and about 20.9±0.5 degrees 2θ.

[0126] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, and about 21.6±0.5 degrees 2θ.

[0127] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ.

[0128] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, and about 18.2±0.5 degrees 2θ.

[0129] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.6±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ.

[0130] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.2±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.6±0.5 degrees 2θ, about 23.1±0.5 degrees 2θ.

[0131] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.2±0.5 degrees 2θ, about 8.0±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 13.0±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 15.3±0.5 degrees 2θ, about 16.8±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ.

[0132] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 6. In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern that includes one or more peaks as provided in Table 2. In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern that includes substantially all, or all, of the peaks provided in Table 2.

[0133] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 7.3±0.5 degrees 2θ.

[0134] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 8.1±0.5 degrees 2θ.

[0135] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.3±0.5 degrees 2θ.

[0136] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.5±0.5 degrees 2θ.

[0137] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.1±0.5 degrees 2θ.

[0138] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 15.4±0.5 degrees 2θ.

[0139] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 16.1±0.5 degrees 2θ.

[0140] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.0±0.5 degrees 2θ.

[0141] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.3±0.5 degrees 2θ.

[0142] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.2±0.5 degrees 2θ.

[0143] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.0±0.5 degrees 2θ.

[0144] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.7±0.5 degrees 2θ.

[0145] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.3±0.5 degrees 2θ.

[0146] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.1±0.5 degrees 2θ.

[0147] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 10.3±0.5 degrees 2θ.

[0148] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 11.5±0.5 degrees 2θ.

[0149] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 15.4±0.5 degrees 2θ.

[0150] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 17.0±0.5 degrees 2θ.

[0151] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 18.3±0.5 degrees 2θ.

[0152] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ and about 21.0±0.5 degrees 2θ.

[0153] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.3±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 11.5±0.5 degrees 2θ, about 15.4±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18.3±0.5 degrees 2θ, and about 21.0±0.5 degrees 2θ.

[0154] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.3±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 11.5±0.5 degrees 2θ, about 15.4±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18.3±0.5 degrees 2θ, and about 21.0±0.5 degrees 2θ.

[0155] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.3±0.5 degrees 2θ, about 8.1±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 11.5±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 15.4±0.5 degrees 2θ, about 16.1±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18.3±0.5 degrees 2θ, about 19.2±0.5 degrees 2θ, about 21.0±0.5 degrees 2θ, about 21.7±0.5 degrees 2θ, about 22.3±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ.

[0156] In some embodiments, a crystalline form of a compound having the formula of Formula I with a coformer, as described or provided herein. In some embodiments, the coformer is succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, or D-(-)-tartaric acid, or any combination thereof. In some embodiments, the coformer is succinic acid. In some embodiments, the coformer is adipic acid. In some embodiments, the coformer is fumaric acid. In some embodiments, the coformer is glutaric acid. In some embodiments, the coformer is gentisic acid. In some embodiments, the coformer is hydrochloric acid. In some embodiments, the coformer is 1-hydroxy-2-naphthoic acid. In some embodiments, the coformer is salicylic acid. In some embodiments, the coformer is oxalic acid. In some embodiments, the coformer is D-(-)-tartaric acid. In some embodiments, the crystalline form is any of Forms III-XIII. In some embodiments, the crystalline form is Form III. In some embodiments, the crystalline form is Form IV. In some embodiments, the crystalline form is Form V. In some embodiments, the crystalline form is Form VI. In some embodiments, the crystalline form is Form VII. In some embodiments, the crystalline form is Form VIII. In some embodiments, the crystalline form is Form IX. In some embodiments, the crystalline form is Form X. In some embodiments, the crystalline form is Form XI. In some embodiments, the crystalline form is Form XII. In some embodiments, the crystalline form is Form XIII.

[0157] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 12. In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern that includes one or more peaks as provided in Table 5. In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern that includes substantially all, or all, of the peaks provided in Table 5.

[0158] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 5.8±0.5 degrees 2θ.

[0159] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 8.8±0.5 degrees 2θ.

[0160] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.5±0.5 degrees 2θ.

[0161] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 12.4±0.5 degrees 2θ.

[0162] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 14.4±0.5 degrees 2θ.

[0163] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.5±0.5 degrees 2θ.

[0164] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.9±0.5 degrees 2θ.

[0165] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.5±0.5 degrees 2θ.

[0166] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.5±0.5 degrees 2θ.

[0167] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.0±0.5 degrees 2θ.

[0168] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.7±0.5 degrees 2θ.

[0169] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.4±0.5 degrees 2θ.

[0170] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.4±0.5 degrees 2θ.

[0171] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.7±0.5 degrees 2θ.

[0172] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.6±0.5 degrees 2θ.

[0173] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.0±0.5 degrees 2θ.

[0174] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.7±0.5 degrees 2θ.

[0175] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.9±0.5 degrees 2θ.

[0176] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.4±0.5 degrees 2θ.

[0177] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 27.6±0.5 degrees 2θ.

[0178] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 29.0±0.5 degrees 2θ.

[0179] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 31.6±0.5 degrees 2θ.

[0180] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising a peak at about 39.5±0.5 degrees 2θ.

[0181] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ and about 10.5±0.5 degrees 2θ.

[0182] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ and about 17.5±0.5 degrees 2θ.

[0183] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ and about 21.4±0.5 degrees 2θ.

[0184] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ and about 22.7±0.5 degrees 2θ.

[0185] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ and about 25.9±0.5 degrees 2θ.

[0186] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising peaks at about 8.8±0.5 degrees 2θ, about 10.5±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 21.4±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ.

[0187] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 8.8±0.5 degrees 2θ, about 10.5±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 21.4±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ.

[0188] In some embodiments, the crystalline Form III has a crystallinity of about 5.8±0.5 degrees 2θ, about 8.8±0.5 degrees 2θ, about 10.5±0.5 degrees 2θ, about 12.4±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 17.9±0.5 degrees 2θ, about 18.5±0.5 degrees 2θ, about 19.5±0.5 degrees 2θ, about 20.0±0.5 degrees 2θ, about 20.7±0.5 degrees 2θ, about 21.4±0.5 degrees 2θ, about 22.0±0.5 degrees 2θ, about 23.0±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 25.0±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 27.0±0.5 degrees 2θ, about 28.0±0.5 degrees 2θ, about 29.0±0.5 degrees 2θ, about 30.0±0.5 degrees 2θ, about 31.0±0.5 degrees 2θ, about 32.0±0.5 degrees 2θ, about 33.0±0.5 degrees 2θ, about 34.0±0.5 degrees 2θ, about 35.0±0.5 degrees 2θ, about 36.0±0.5 degrees 2θ, about 37.0±0.5 degrees 2θ, about 38.0±0.5 degrees 2θ, about 39.0±0.5 degrees 2θ, about 40.0±0.5 degrees 2θ, about 41.0±0.5 degrees 2θ, about 42.0±0.5 degrees 2θ, about 4 0.4±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.9±0.5 degrees 2θ, about 26.4±0.5 degrees 2θ, about 27.6±0.5 degrees 2θ, about 29.0±0.5 degrees 2θ, about 31.6±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ.

[0189] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 18. In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern that includes one or more peaks as provided in Table 6. In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern that includes substantially all, or all, of the peaks provided in Table 6.

[0190] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 4.5±0.5 degrees 2θ.

[0191] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 6.0±0.5 degrees 2θ.

[0192] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 8.9±0.5 degrees 2θ.

[0193] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.1±0.5 degrees 2θ.

[0194] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.7±0.5 degrees 2θ.

[0195] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.2±0.5 degrees 2θ.

[0196] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 16.3±0.5 degrees 2θ.

[0197] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.1±0.5 degrees 2θ.

[0198] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.6±0.5 degrees 2θ.

[0199] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.4±0.5 degrees 2θ.

[0200] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.7±0.5 degrees 2θ.

[0201] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.5±0.5 degrees 2θ.

[0202] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.0±0.5 degrees 2θ.

[0203] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.9±0.5 degrees 2θ.

[0204] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.0±0.5 degrees 2θ.

[0205] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.7±0.5 degrees 2θ.

[0206] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.0±0.5 degrees 2θ.

[0207] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.2±0.5 degrees 2θ.

[0208] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising a peak at about 29.2±0.5 degrees 2θ.

[0209] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 6.0±0.5 degrees 2θ.

[0210] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 8.9±0.5 degrees 2θ.

[0211] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 11.1±0.5 degrees 2θ.

[0212] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 11.7±0.5 degrees 2θ.

[0213] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 17.1±0.5 degrees 2θ.

[0214] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 17.6±0.5 degrees 2θ.

[0215] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 20.5±0.5 degrees 2θ.

[0216] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ and about 21.0±0.5 degrees 2θ.

[0217] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at about 4.5±0.5 degrees 2θ, about 6.0±0.5 degrees 2θ, about 8.9±0.5 degrees 2θ, about 11.1±0.5 degrees 2θ, about 11.7±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 17.6±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, and about 21.0±0.5 degrees 2θ.

[0218] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern including one or more peaks at about 4.5±0.5 degrees 2θ, about 6.0±0.5 degrees 2θ, about 8.9±0.5 degrees 2θ, about 11.1±0.5 degrees 2θ, about 11.7±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 17.6±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, and about 21.0±0.5 degrees 2θ.

[0219] In some embodiments, crystalline Form IV has a crystallinity of about 4.5±0.5 degrees 2θ, about 6.0±0.5 degrees 2θ, about 8.9±0.5 degrees 2θ, about 11.1±0.5 degrees 2θ, about 11.7±0.5 degrees 2θ, about 13.2±0.5 degrees 2θ, about 16.3±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 17.6±0.5 degrees 2θ, about 18.4±0.5 degrees 2θ, about 19. 7±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, about 21.0±0.5 degrees 2θ, about 21.9±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.0±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 29.2±0.5 degrees 2θ.

[0220] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 24. In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern that includes one or more peaks as provided in Table 7. In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern that includes substantially all, or all, of the peaks provided in Table 7.

[0221] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 4.7±0.5 degrees 2θ.

[0222] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 7.4±0.5 degrees 2θ.

[0223] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 9.2±0.5 degrees 2θ.

[0224] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.2±0.5 degrees 2θ.

[0225] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.8±0.5 degrees 2θ.

[0226] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.2±0.5 degrees 2θ.

[0227] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.1±0.5 degrees 2θ.

[0228] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.9±0.5 degrees 2θ.

[0229] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.1±0.5 degrees 2θ.

[0230] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.9±0.5 degrees 2θ.

[0231] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising peaks at about 9.2±0.5 degrees 2θ and about 18.1±0.5 degrees 2θ.

[0232] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising peaks at about 9.2±0.5 degrees 2θ and about 25.1±0.5 degrees 2θ.

[0233] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising peaks at about 9.2±0.5 degrees 2θ and about 25.9±0.5 degrees 2θ.

[0234] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 9.2±0.5 degrees 2θ, about 18.1±0.5 degrees 2θ, about 25.1±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ.

[0235] In some embodiments, crystalline form V is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 4.7±0.5 degrees 2θ, about 7.4±0.5 degrees 2θ, about 9.2±0.5 degrees 2θ, about 11.2±0.5 degrees 2θ, about 13.8±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.1±0.5 degrees 2θ, about 18.9±0.5 degrees 2θ, about 25.1±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ.

[0236] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 30. In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern including one or more peaks as provided in Table 8. In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern including substantially all, or all, of the peaks provided in Table 8.

[0237] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 7.4±0.5 degrees 2θ.

[0238] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 9.5±0.5 degrees 2θ.

[0239] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.6±0.5 degrees 2θ.

[0240] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 14.7±0.5 degrees 2θ.

[0241] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 15.5±0.5 degrees 2θ.

[0242] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 16.4±0.5 degrees 2θ.

[0243] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.2±0.5 degrees 2θ.

[0244] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.2±0.5 degrees 2θ.

[0245] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.4±0.5 degrees 2θ.

[0246] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.5±0.5 degrees 2θ.

[0247] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.5±0.5 degrees 2θ.

[0248] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.5±0.5 degrees 2θ.

[0249] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.8±0.5 degrees 2θ.

[0250] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.7±0.5 degrees 2θ.

[0251] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.9±0.5 degrees 2θ.

[0252] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 29.4±0.5 degrees 2θ.

[0253] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising a peak at about 30.7±0.5 degrees 2θ.

[0254] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 9.5±0.5 degrees 2θ.

[0255] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 14.7±0.5 degrees 2θ.

[0256] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 15.5±0.5 degrees 2θ.

[0257] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 21.5±0.5 degrees 2θ.

[0258] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 23.5±0.5 degrees 2θ.

[0259] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 24.8±0.5 degrees 2θ.

[0260] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 25.7±0.5 degrees 2θ.

[0261] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ and about 26.9±0.5 degrees 2θ.

[0262] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising peaks at about 7.4±0.5 degrees 2θ, about 9.5±0.5 degrees 2θ, about 14.7±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 21.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.8±0.5 degrees 2θ, about 25.7±0.5 degrees 2θ, and about 26.9±0.5 degrees 2θ.

[0263] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.4±0.5 degrees 2θ, about 9.5±0.5 degrees 2θ, about 14.7±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 21.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.8±0.5 degrees 2θ, about 25.7±0.5 degrees 2θ, and about 26.9±0.5 degrees 2θ.

[0264] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.4±0.5 degrees 2θ, about 9.5±0.5 degrees 2θ, about 13.6±0.5 degrees 2θ, about 14.7±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 16.4±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 19.4±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, about 21.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.8±0.5 degrees 2θ, about 25.7±0.5 degrees 2θ, about 26.9±0.5 degrees 2θ, about 29.4±0.5 degrees 2θ, and about 30.7±0.5 degrees 2θ.

[0265] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 36. In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern including one or more peaks as provided in Table 9. In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern including substantially all, or all, of the peaks provided in Table 9.

[0266] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 4.7±0.5 degrees 2θ.

[0267] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 5.8±0.5 degrees 2θ.

[0268] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.6±0.5 degrees 2θ.

[0269] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.3±0.5 degrees 2θ.

[0270] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 11.8±0.5 degrees 2θ.

[0271] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 12.6±0.5 degrees 2θ.

[0272] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 13.1±0.5 degrees 2θ.

[0273] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 14.0±0.5 degrees 2θ.

[0274] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 16.0±0.5 degrees 2θ.

[0275] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.0±0.5 degrees 2θ.

[0276] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.5±0.5 degrees 2θ.

[0277] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.7±0.5 degrees 2θ.

[0278] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.3±0.5 degrees 2θ.

[0279] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.2±0.5 degrees 2θ.

[0280] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.1±0.5 degrees 2θ.

[0281] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.2±0.5 degrees 2θ.

[0282] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.7±0.5 degrees 2θ.

[0283] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.2±0.5 degrees 2θ.

[0284] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising a peak at about 27.4±0.5 degrees 2θ.

[0285] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 10.6±0.5 degrees 2θ.

[0286] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 19.3±0.5 degrees 2θ.

[0287] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 21.2±0.5 degrees 2θ.

[0288] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 22.1±0.5 degrees 2θ.

[0289] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 24.2±0.5 degrees 2θ.

[0290] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ and about 26.2±0.5 degrees 2θ.

[0291] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.8±0.5 degrees 2θ, about 10.6±0.5 degrees 2θ, about 19.3±0.5 degrees 2θ, about 21.2±0.5 degrees 2θ, about 22.1±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, and about 26.2±0.5 degrees 2θ.

[0292] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 5.8±0.5 degrees 2θ, about 10.6±0.5 degrees 2θ, about 19.3±0.5 degrees 2θ, about 21.2±0.5 degrees 2θ, about 22.1±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, and about 26.2±0.5 degrees 2θ.

[0293] In some embodiments, crystalline Form VII has a crystallinity of about 4.7±0.5 degrees 2θ, about 5.8±0.5 degrees 2θ, about 10.6±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 11.8±0.5 degrees 2θ, about 12.6±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 14.0±0.5 degrees 2θ, about 16.0±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 18.5±0.5 degrees 2θ, about 19. The compound is characterized by an X-ray powder diffraction pattern including one or more peaks at about 0.5±0.5 degrees 2θ, about 18.7±0.5 degrees 2θ, about 19.3±0.5 degrees 2θ, about 21.2±0.5 degrees 2θ, about 22.1±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 27.4±0.5 degrees 2θ.

[0294] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 42. In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern including one or more peaks as provided in Table 10. In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern including substantially all, or all, of the peaks provided in Table 10.

[0295] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 3.9±0.5 degrees 2θ.

[0296] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 5.7±0.5 degrees 2θ.

[0297] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 7.1±0.5 degrees 2θ.

[0298] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 8.6±0.5 degrees 2θ.

[0299] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.3±0.5 degrees 2θ.

[0300] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 12.1±0.5 degrees 2θ.

[0301] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 14.1±0.5 degrees 2θ.

[0302] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.1±0.5 degrees 2θ.

[0303] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.1±0.5 degrees 2θ.

[0304] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.6±0.5 degrees 2θ.

[0305] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.2±0.5 degrees 2θ.

[0306] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.0±0.5 degrees 2θ.

[0307] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.3±0.5 degrees 2θ.

[0308] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.0±0.5 degrees 2θ.

[0309] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.5±0.5 degrees 2θ.

[0310] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 28.5±0.5 degrees 2θ.

[0311] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 34.6±0.5 degrees 2θ.

[0312] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 35.4±0.5 degrees 2θ.

[0313] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 36.8±0.5 degrees 2θ.

[0314] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising a peak at about 39.5±0.5 degrees 2θ.

[0315] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 5.7±0.5 degrees 2θ.

[0316] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 8.6±0.5 degrees 2θ.

[0317] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 10.3±0.5 degrees 2θ.

[0318] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 12.1±0.5 degrees 2θ.

[0319] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 14.1±0.5 degrees 2θ.

[0320] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 17.1±0.5 degrees 2θ.

[0321] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 19.1±0.5 degrees 2θ.

[0322] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 20.6±0.5 degrees 2θ.

[0323] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 23.0±0.5 degrees 2θ.

[0324] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 24.3±0.5 degrees 2θ.

[0325] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 26.5±0.5 degrees 2θ.

[0326] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ and about 28.5±0.5 degrees 2θ.

[0327] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising peaks at about 3.9±0.5 degrees 2θ, about 5.7±0.5 degrees 2θ, about 8.6±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 12.1±0.5 degrees 2θ, about 14.1±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 19.1±0.5 degrees 2θ, about 20.6±0.5 degrees 2θ, about 23.0±0.5 degrees 2θ, about 24.3±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, and about 28.5±0.5 degrees 2θ.

[0328] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 3.9±0.5 degrees 2θ, about 5.7±0.5 degrees 2θ, about 8.6±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 12.1±0.5 degrees 2θ, about 14.1±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 19.1±0.5 degrees 2θ, about 20.6±0.5 degrees 2θ, about 23.0±0.5 degrees 2θ, about 24.3±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, and about 28.5±0.5 degrees 2θ.

[0329] In some embodiments, crystalline Form VIII has a viscosity of about 3.9±0.5 degrees 2θ, about 5.7±0.5 degrees 2θ, about 7.1±0.5 degrees 2θ, about 8.6±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 12.1±0.5 degrees 2θ, about 14.1±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 19.1±0.5 degrees 2θ, about 20.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, about 23.2±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, about 25.2±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, about 27.2±0.5 degrees 2θ, about 28.2±0.5 degrees 2θ, about 29.2±0.5 degrees 2θ, about 30.2±0.5 degrees 2θ, about 31.2±0.5 degrees 2θ, about 32.2±0.5 degrees 2θ, about 33.2±0.5 degrees 2θ, about 34.2±0.5 degrees 2θ, about 35.2±0.5 degrees 2θ, about 36.2±0.5 degrees 2θ, about 37.2±0.5 degrees 2θ, about 38.2±0.5 degrees 2θ, about 39.2±0.5 degrees 2θ, about 40.2±0.5 degrees 2θ, about 41.2±0.5 degrees 2θ, about 42.2±0.5 degrees 2θ, about 43.2±0.5 degrees 2θ, about 44.2±0.5 degrees 2θ, about 45.2± 2θ, about 23.0±0.5 degrees 2θ, about 24.3±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, about 28.5±0.5 degrees 2θ, about 34.6±0.5 degrees 2θ, about 35.4±0.5 degrees 2θ, about 36.8±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ.

[0330] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern substantially as shown in Figure 46. In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern including one or more peaks as provided in Table 11. In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern including substantially all, or all, of the peaks provided in Table 11.

[0331] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 5.3±0.5 degrees 2θ.

[0332] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 6.8±0.5 degrees 2θ.

[0333] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 9.0±0.5 degrees 2θ.

[0334] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 10.0±0.5 degrees 2θ.

[0335] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 15.5±0.5 degrees 2θ.

[0336] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 17.3±0.5 degrees 2θ.

[0337] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.2±0.5 degrees 2θ.

[0338] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 18.8±0.5 degrees 2θ.

[0339] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 19.9±0.5 degrees 2θ.

[0340] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 20.9±0.5 degrees 2θ.

[0341] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 21.3±0.5 degrees 2θ.

[0342] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 22.7±0.5 degrees 2θ.

[0343] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 23.6±0.5 degrees 2θ.

[0344] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 24.3±0.5 degrees 2θ.

[0345] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 25.5±0.5 degrees 2θ.

[0346] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 26.0±0.5 degrees 2θ.

[0347] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 27.1±0.5 degrees 2θ.

[0348] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 28.0±0.5 degrees 2θ.

[0349] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 28.8±0.5 degrees 2θ.

[0350] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 29.8±0.5 degrees 2θ.

[0351] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 33.4±0.5 degrees 2θ.

[0352] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 34.2±0.5 degrees 2θ.

[0353] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 36.3±0.5 degrees 2θ.

[0354] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 38.6±0.5 degrees 2θ.

[0355] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising a peak at about 39.1±0.5 degrees 2θ.

[0356] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 9.0±0.5 degrees 2θ.

[0357] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 10.0±0.5 degrees 2θ.

[0358] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 17.3±0.5 degrees 2θ.

[0359] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 18.8±0.5 degrees 2θ.

[0360] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 19.9±0.5 degrees 2θ.

[0361] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 20.9±0.5 degrees 2θ.

[0362] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 21.3±0.5 degrees 2θ.

[0363] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 22.7±0.5 degrees 2θ.

[0364] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 23.6±0.5 degrees 2θ.

[0365] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ and about 26.0±0.5 degrees 2θ.

[0366] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising peaks at about 5.3±0.5 degrees 2θ, about 9.0±0.5 degrees 2θ, about 10.0±0.5 degrees 2θ, about 17.3±0.5 degrees 2θ, about 18.8±0.5 degrees 2θ, about 19.9±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.3±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, and about 26.0±0.5 degrees 2θ.

[0367] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern including one or more peaks at about 5.3±0.5 degrees 2θ, about 9.0±0.5 degrees 2θ, about 10.0±0.5 degrees 2θ, about 17.3±0.5 degrees 2θ, about 18.8±0.5 degrees 2θ, about 19.9±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.3±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, and about 26.0±0.5 degrees 2θ.

[0368] In some embodiments, crystalline Form IX has a crystallinity of about 5.3±0.5 degrees 2θ, about 6.8±0.5 degrees 2θ, about 9.0±0.5 degrees 2θ, about 10.0±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 17.3±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 18.8±0.5 degrees 2θ, about 19.9±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.3±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, about 24. 3±0.5 degrees 2θ, about 25.5±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 27.1±0.5 degrees 2θ, about 28.0±0.5 degrees 2θ, about 28.8±0.5 degrees 2θ, about 29.8±0.5 degrees 2θ, about 33.4±0.5 degrees 2θ, about 34.2±0.5 degrees 2θ, about 36.3±0.5 degrees 2θ, about 38.6±0.5 degrees 2θ, and about 39.1±0.5 degrees 2θ.

[0369] In some embodiments, crystalline form X is characterized by an X-ray powder diffraction pattern substantially as shown in FIG.

[0370] In some embodiments, crystalline form XI is characterized by an X-ray powder diffraction pattern substantially as shown in FIG.

[0371] In some embodiments, crystalline Form XII is characterized by an X-ray powder diffraction pattern substantially as shown in FIG.

[0372] In some embodiments, crystalline Form XIII is characterized by an X-ray powder diffraction pattern substantially as shown in FIG.

[0373] In some embodiments, crystalline forms I-XIII are characterized by DSC thermograms, e.g., crystalline forms I-X are characterized by the DSC thermograms shown in Figures 3, 7, 13, 19, 25, 31, 37, 43, 47, and 51, respectively.

[0374] In some embodiments, crystalline Forms I-XIII are characterized by any combination of the above data.

[0375] In some embodiments, the X-ray powder diffraction peaks listed herein for particular embodiments may vary by ±0.4 degrees 2θ, ±0.3 degrees 2θ, ±0.2 degrees 2θ, or ±0.1 degrees 2θ.

[0376] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 1.

[0377] In some embodiments, crystalline Form I is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.3±0.5 degrees Angstroms, about 11.0±0.5 degrees Angstroms, about 8.7±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.8±0.5 degrees Angstroms, about 5.3±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms.

[0378] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 2.

[0379] In some embodiments, crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.1±0.5 degrees Angstroms, about 10.9±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.7±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms.

[0380] In some embodiments, crystalline Form III is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 5.

[0381] In some embodiments, the crystalline Form III has a molecular weight of about 15.1±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.1±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.4±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.0±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.8±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0382] In some embodiments, crystalline Form IV is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 6.

[0383] In some embodiments, crystalline Form IV has a molecular weight of about 19.4±0.5 degrees Angstroms, about 14.7±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 6.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 5.0±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.5±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.1±0.5 degrees Angstroms.

[0384] In some embodiments, crystalline Form V is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 7.

[0385] In some embodiments, crystalline Form V is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 18.8±0.5 degrees Angstroms, about 11.9±0.5 degrees Angstroms, about 9.6±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 6.4±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, and about 3.4±0.5 degrees Angstroms.

[0386] In some embodiments, crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 8.

[0387] In some embodiments, crystalline Form VI has a crystallinity of about 12.0±0.5 degrees Angstroms, about 9.3±0.5 degrees Angstroms, about 6.5±0.5 degrees Angstroms, about 6.0±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.3±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.5±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, and about 2.9±0.5 degrees Angstroms.

[0388] In some embodiments, crystalline Form VII is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 9.

[0389] In some embodiments, crystalline Form VII has a molecular weight of about 18.9±0.5 degrees Angstroms, about 15.2±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 7.0±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, The compound is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 5.1±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.2±0.5 degrees Angstroms.

[0390] In some embodiments, crystalline Form VIII is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 10.

[0391] In some embodiments, crystalline Form VIII has a molecular weight of about 22.5±0.5 degrees Angstroms, about 15.5±0.5 degrees Angstroms, about 12.5±0.5 degrees Angstroms, about 10.3±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.3±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4. and is characterized by an X-ray powder diffraction pattern including d-spacing values ​​of about 0±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.4±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0392] In some embodiments, crystalline Form IX is characterized by an X-ray powder diffraction pattern comprising d-spacing values ​​substantially as shown in Table 11.

[0393] In some embodiments, crystalline Form IX is about 16.7±0.5 degrees Angstroms, about 12.9±0.5 degrees Angstroms, about 9.8±0.5 degrees Angstroms, about 8.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.5±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms. 3.7±0.5 degrees Angstroms, about 3.5±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, about 2.7±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.3±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms.

[0394] In some embodiments, X-ray powder diffraction peaks listed herein for particular embodiments having d-spacing values ​​may vary by ±4% nm, ±3% nm, ±2% nm, or ±1% nm, or ±4% Angstroms, ±3% Angstroms, ±2% Angstroms, or ±1% Angstroms.

[0395] One of ordinary skill in the art will appreciate that the relative intensities and positions of peaks obtained by X-ray powder diffraction may vary depending, among other things, on the sample preparation technique, sample mounting procedure, and the particular instrument used. For example, in some embodiments, the listed X-ray powder diffraction pattern peaks for any of crystalline Forms I-XIII are within about ±0.2 degrees 2θ.

[0396] In some embodiments, the crystalline forms I-XIII of the compound of formula I are identified by proton nuclear magnetic resonance spectroscopy ( 1For example, Figures 5, 9, 16, 22, 28, 34, 40, 45, and 49 show the proton nuclear magnetic resonance spectroscopy (H NMR) of crystalline forms I-IX. 1 H NMR analyses are shown, respectively. Other methods can also be used to characterize crystalline forms I-XIII.

[0397] Crystalline forms I-XIII can have any desired purity relative to other substances or components in the preparation. In some embodiments, any of crystalline forms I-XIII are provided to be substantially pure, such as having a purity of, for example, greater than 30%, greater than 40%, greater than 50%, greater than 60%, greater than 70%, greater than 80%, greater than 85%, greater than 90%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%, greater than 99.2%, greater than 99.4%, greater than 99.5%, greater than 99.6%, greater than 99.7%, or greater than 99.9%, relative to other substances or components in the preparation.

[0398] In exemplary embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, is about 45%-95% pure, e.g., about 50%-95% pure, about 55%-90% pure, about 60%-95% pure, or about 70%-99% pure, relative to other substances or components in the preparation. In some embodiments, the crystalline form of any one of Forms I-XIII is about 95%-99% pure. In some embodiments, the crystalline form is about 90%-95% pure. In some embodiments, the crystalline form is about 85%-90% pure. In some embodiments, the crystalline form is about 80%-85% pure. In some embodiments, the crystalline form is about 75%-80% pure. In some embodiments, crystalline form I is about 70%-75% pure. In certain embodiments, the crystalline form is about 65%-70% pure. In some embodiments, the crystalline form is about 60%-65% pure. In other embodiments, the crystalline form is about 55%-60% pure. In still other embodiments, crystalline Form I is about 50%-55% pure. In some embodiments, the crystalline form is about 45%-50% pure.

[0399] In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may contain one or more impurities and / or decomposition products, such as hydrolysis products, acetylation products, formylation products, oxidation products, water-mediated decomposition products, and / or deamidation products. In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may contain one or more impurities and / or decomposition products, such as hydrolysis products, acetylation products, formylation products, oxidation products, water-mediated decomposition products, and / or deamidation products. In some embodiments, the one or more impurities may be biologically active.

[0400] In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may comprise any desired purity with respect to hydrolysis products. In some embodiments, the composition comprises less than about 10% by weight of hydrolysis products, e.g., less than about 7.5% by weight, less than about 5% by weight, or less than about 2% by weight of hydrolysis products, based on the total weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof comprises from about 0.05% by weight to about 5% by weight of hydrolysis products. In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof comprises from about 0.05% by weight to about 2% by weight of hydrolysis products. In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions thereof, comprises from about 0.1% to about 2% by weight of the hydrolysis products. In some embodiments, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions thereof, comprises from about 0.01% to about 2% by weight of the hydrolysis products.

[0401] Alternatively or additionally, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may comprise any desired purity relative to the acetylation product. In some embodiments, the acetylation product may comprise less than 10% by weight of any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof. In some embodiments, the acetylation product may comprise less than 7.5% by weight of any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof. In some embodiments, the acetylation product may comprise less than 5% by weight of any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof. In some embodiments, the acetylation product may comprise less than 2% by weight of any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof. In some embodiments, the acetylated product may comprise less than 1% by weight of any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and / or compositions thereof. In some embodiments, the acetylated product may comprise less than 0.5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the acetylated product may comprise from about 0.05% to about 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the acetylated product may comprise from about 0.05% to about 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the acetylated product may comprise from about 0.1% to about 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof.In some embodiments, the acetylation product may comprise from about 0.01% to about 2% by weight of the composition.

[0402] Alternatively or additionally, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, may comprise any desired purity relative to the formylation product. In some embodiments, the formylation product may comprise less than 10% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the formylation product may comprise less than 7.5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the formylation product may comprise less than 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the formylation product may comprise less than 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the formylation product may comprise from about 0.05% to about 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the formylation product may comprise from about 0.05% to about 2% by weight of any one of the crystalline forms described or provided herein, and / or of the composition. In some embodiments, the formylation product may comprise from about 0.1% to about 2% by weight of any one of the crystalline forms described or provided herein, and / or of the composition.

[0403] Alternatively or additionally, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, may comprise any desired purity with respect to the oxidation product. In some embodiments, the oxidation product may comprise less than 10% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the oxidation product may comprise less than 7.5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the oxidation product may comprise less than 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the oxidation product may comprise less than 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the oxidation product may comprise about 0.05% to about 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the oxidation product may comprise from about 0.05% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof. In some embodiments, the oxidation product may comprise from about 0.1% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof. In some embodiments, the oxidation product may comprise from about 0.01% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof.

[0404] Alternatively or additionally, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions thereof comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, may comprise any desired purity with respect to water-mediated decomposition products. In some embodiments, the water-mediated decomposition products may comprise less than 10% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the water-mediated decomposition products may comprise less than 7.5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the water-mediated decomposition products may comprise less than 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In other embodiments, the water-mediated decomposition products may comprise less than 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In some embodiments, the water-mediated decomposition products may comprise about 0.05% to about 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions thereof. In exemplary embodiments, the water-mediated degradation products may comprise from about 0.05% to about 2% by weight of any one of the crystalline forms described or provided herein and / or the composition. In some embodiments, the water-mediated degradation products may comprise from about 0.1% to about 2% by weight of any one of the crystalline forms described or provided herein and / or the composition. In some embodiments, the water-mediated degradation products may comprise from about 0.01% to about 2% by weight of any one of the crystalline forms described or provided herein and / or the composition.

[0405] Alternatively or additionally, any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and / or compositions comprising any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, may comprise any desired purity with respect to the deamidation product. In some embodiments, the deamidation product may comprise less than 10% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the deamidation product may comprise less than 7.5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the deamidation product may comprise less than 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In other embodiments, the deamidation product may comprise less than 2% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the deamidation product may comprise about 0.05% to about 5% by weight of any one of the crystalline forms described or provided herein, and / or compositions. In some embodiments, the deamidation product may comprise from about 0.05% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof. In some embodiments, the deamidation product may comprise from about 0.1% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof. In some embodiments, the deamidation product may comprise from about 0.01% to about 2% by weight of any one of the crystalline forms described or provided herein and / or compositions thereof.

[0406] In some embodiments, a composition is provided that comprises any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and less than 10% by weight, e.g., less than 8%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.25% by weight of the sum of degradation products, such as hydrolysis products, formylation products, oxidation products, water-mediated degradation products, and / or deamidation products.

[0407] In some embodiments, a composition is provided that comprises any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and less than 20% by weight, e.g., less than 18% by weight, less than 16% by weight, less than 14% by weight, less than 12% by weight, less than 10% by weight, less than 8% by weight, less than 6% by weight, less than 5% by weight, less than 4% by weight, less than 3% by weight, less than 2% by weight, less than 1% by weight, less than 0.5% by weight, or less than 0.25% by weight of the sum of degradation products, such as hydrolysis products, acetylation products, formylation products, oxidation products, water-mediated degradation products, and / or deamidation products.

[0408] In some embodiments, a composition is provided that comprises any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and less than 10% by weight, e.g., less than 8%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.25% by weight of the sum of one or more impurities and / or decomposition products, such as hydrolysis products, formylation products, oxidation products, water-mediated decomposition products, and / or deamidation products.

[0409] In some embodiments, a composition is provided that comprises any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, and less than 20% by weight, e.g., less than 18% by weight, less than 16% by weight, less than 14% by weight, less than 12% by weight, less than 10% by weight, less than 8% by weight, less than 6% by weight, less than 5% by weight, less than 4% by weight, less than 3% by weight, less than 2% by weight, less than 1% by weight, less than 0.5% by weight, or less than 0.25% by weight of the sum of one or more impurities and / or degradation products, such as hydrolysis products, acetylation products, formylation products, oxidation products, water-mediated degradation products, and / or deamidation products.

[0410] In some embodiments, a composition is provided that comprises any one of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, and less than about 40% by weight, e.g., less than about 30% by weight, less than about 20% by weight, less than about 15% by weight, less than about 10% by weight, less than about 8% by weight, less than about 6% by weight, less than about 5% by weight, less than about 4% by weight, less than about 3% by weight, less than about 2% by weight, less than about 1% by weight, less than about 0.5% by weight, less than about 0.1% by weight, or less than about 0.01% by weight of an amorphous form of the compound of formula I.

[0411] In some embodiments, a method for preparing a crystalline form of a compound of formula I is provided. In some embodiments, a crystal of any one of the crystalline forms described or provided herein is produced by precipitating and crystallizing a compound of formula I with or without a coformer, and optionally isolating a crystal of any one of the crystalline forms described or provided herein. In some embodiments, a crystal of any one of the crystalline forms described or provided herein is prepared by slurrying a compound of formula I with or without a coformer in an organic solvent, and optionally isolating a crystal of any one of the crystalline forms described or provided herein. In some embodiments, a crystal of any one of the crystalline forms described or provided herein is prepared by slurrying and crystallizing a compound of formula I with or without a coformer in a supersaturated organic solvent, and optionally isolating a crystal of any one of the crystalline forms described or provided herein.

[0412] In this regard, any suitable organic solvent can be used, such as, for example, acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, H2O, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane, and any combination thereof. Such solvents can include, but are not limited to, acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, H2O, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane, and any combination thereof. In some embodiments, the organic solvent comprises acetonitrile. In some embodiments, the organic solvent comprises n-butanol. In some embodiments, the organic solvent comprises methyl ethyl ketone. In some embodiments, the organic solvent comprises methanol. In some embodiments, the organic solvent comprises ethyl acetate. In some embodiments, the organic solvent comprises acetone. In some embodiments, the organic solvent comprises tetrahydrofuran. In some embodiments, the organic solvent comprises 2-propanol. In some embodiments, the organic solvent comprises ethanol. In some embodiments, the organic solvent comprises isopropyl acetate. In some embodiments, the organic solvent comprises toluene. In some embodiments, the organic solvent comprises cyclohexane. In some embodiments, the organic solvent comprises dichloromethane. In some embodiments, the organic solvent comprises chloroform. In some embodiments, the organic solvent comprises H2O. In some embodiments, the organic solvent comprises nitromethane. In some embodiments, the organic solvent comprises n-pentane. In some embodiments, the organic solvent comprises n-hexane. In some embodiments, the organic solvent comprises 1-propanol. In some embodiments, the organic solvent comprises methyl acetate.In some embodiments, the organic solvent comprises ethyl ether, hi some embodiments, the organic solvent comprises octane.

[0413] The crystals of any one of the crystalline forms described or provided herein of the compound of formula I can be identified, characterized, and distinguished from amorphous or oily forms using any suitable method. Those skilled in the art will know many different methods of identifying and characterizing the crystals of any one of the crystalline forms described or provided herein. For example, the crystals of any one of the crystalline forms described or provided herein of the compound of formula I can be identified and characterized based on the difference in the diffraction, thermal, intensity, and / or spectroscopic properties of the amorphous and crystalline forms. Suitable methods include X-ray diffraction, proton nuclear magnetic resonance spectroscopy ( 1 H NMR), carbon nuclear magnetic resonance spectroscopy ( 13 These include, but are not limited to, C NMR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC).

[0414] In some embodiments, Formula I [ka] A method for preparing a crystalline form of a compound having the formula of Formula I, comprising crystallizing the compound of formula I to form crystalline Form I, and optionally isolating Form I. In some embodiments, the crystallization comprises dissolving the compound in an organic solvent and crystallizing the compound to obtain Form I therefrom. In some embodiments, the organic solvent is selected from the group consisting of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane.

[0415] In some embodiments, Formula I [ka] A method for preparing a crystalline form of a compound having a formula of Formula II, comprising crystallizing the compound of Formula II to form a crystalline form, such as, for example, Form I and Form II, as described herein, and optionally isolating the crystalline form. In some embodiments, the crystallization comprises dissolving the compound in an organic solvent and crystallizing the compound to form a crystalline form therefrom. In some embodiments, the organic solvent is selected from the group consisting of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, and octane. In some embodiments, the organic solvent is selected from the group consisting of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane, and any combination thereof. In some embodiments, the organic solvent is acetonitrile. In some embodiments, the organic solvent is n-butanol. In some embodiments, the organic solvent is methyl ethyl ketone. In some embodiments, the organic solvent is methanol. In some embodiments, the organic solvent is ethyl acetate. In some embodiments, the organic solvent is acetone. In some embodiments, the organic solvent is tetrahydrofuran. In some embodiments, the organic solvent is 2-propanol. In some embodiments, the organic solvent is ethanol. In some embodiments, the organic solvent is isopropyl acetate. In some embodiments, the organic solvent is toluene. In some embodiments, the organic solvent is cyclohexane. In some embodiments, the organic solvent is dichloromethane. In some embodiments, the organic solvent is chloroform. In some embodiments, the organic solvent is HO.In some embodiments, the organic solvent is nitromethane. In some embodiments, the organic solvent is n-pentane. In some embodiments, the organic solvent is n-hexane. In some embodiments, the organic solvent is 1-propanol. In some embodiments, the organic solvent is methyl acetate. In some embodiments, the organic solvent is ethyl ether. In some embodiments, the organic solvent is octane. In some embodiments, the organic solvent is any combination of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, and octane.

[0416] In some embodiments, Formula I [ka] A method for preparing a crystalline form of the compound of formula I and a coformer as described or provided herein. In some embodiments, the method includes co-crystallizing the compound and the coformer to form a crystalline form of the compound of formula I and the coformer, such as crystalline forms III-XIII, and optionally isolating the crystalline form of the compound and the coformer. In some embodiments, the method includes slurrying the compound and the coformer in an organic solvent to form a crystalline form therefrom. In some embodiments, the method further includes washing the slurry with an organic solvent. In some embodiments, the organic solvent is selected from the group consisting of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, H2O, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane, and any combination thereof. In some embodiments, the organic solvent is acetonitrile. In some embodiments, the organic solvent is n-butanol. In some embodiments, the organic solvent is methyl ethyl ketone. In some embodiments, the organic solvent is methanol. In some embodiments, the organic solvent is ethyl acetate. In some embodiments, the organic solvent is acetone. In some embodiments, the organic solvent is tetrahydrofuran. In some embodiments, the organic solvent is 2-propanol. In some embodiments, the organic solvent is ethanol. In some embodiments, the organic solvent is isopropyl acetate. In some embodiments, the organic solvent is toluene. In some embodiments, the organic solvent is cyclohexane. In some embodiments, the organic solvent is dichloromethane. In some embodiments, the organic solvent is chloroform. In some embodiments, the organic solvent is HO. In some embodiments, the organic solvent is nitromethane. In some embodiments, the organic solvent is n-pentane. In some embodiments, the organic solvent is n-hexane.In some embodiments, the organic solvent is 1-propanol. In some embodiments, the organic solvent is methyl acetate. In some embodiments, the organic solvent is ethyl ether. In some embodiments, the organic solvent is octane. In some embodiments, the organic solvent is any combination of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, and octane.

[0417] In some embodiments, the coformer is the coformer provided and described herein.In some embodiments, the coformer is succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, or D-(-)-tartaric acid.In some embodiments, the coformer is succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, or D-(-)-tartaric acid.

[0418] In some embodiments, the coformer is succinic acid. In some embodiments, the compound of formula I and the crystalline form of succinic acid have a molar ratio of compound to succinic acid anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 1.9:1, about 0.2:1 to about 1.8:1, about 0.3:1 to about 1.7:1, about 0.4:1 to about 1.6:1, about 0.5:1 to about 1.5:1, about 0.6:1 to about 1.4:1, about 0.7:1 to about 1.3:1, about 0.8:1 to about 1.2:1, or about 0.9:1 to about 1.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the crystalline form is crystalline form III of the compound and succinic acid, and the molar ratio of the compound to succinic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline form III of the compound and succinic acid, and the molar ratio of the compound to succinic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline form III of the compound and succinic acid, and the molar ratio of the compound to succinic acid is about 1:1.

[0419] In some embodiments, the coformer is glutaric acid. In some embodiments, the compound of formula I and the crystalline form of glutaric acid have a molar ratio of compound to glutaric acid anywhere from about 0.1:1 to about 4:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 3.9:1, about 0.2:1 to about 3.8:1, about 0.3:1 to about 3.7:1, about 0.4:1 to about 3.6:1, about 0.5:1 to about 3.5:1, about 0.6:1 to about 3.4:1, about 0.7:1 to about 3.3:1, about 0.8:1 to about 3.2:1, about 0.9:1 to about 3.1:1, about ... The ratio is within the range of about 0.1:1 to about 3:1, about 1.1:1 to about 2.9:1, about 1.2:1 to about 2.8:1, about 1.3:1 to about 2.7:1, about 1.4:1 to about 2.6:1, about 1.5:1 to about 2.5:1, about 1.6:1 to about 2.4:1, about 1.7:1 to about 1.3:1, about 1.8:1 to about 2.2:1, or about 1.9:1 to about 2.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the ratio is about 2.1:1. In some embodiments, the ratio is about 2.2:1. In some embodiments, the ratio is about 2.3:1.In some embodiments, the ratio is about 2.4:1. In some embodiments, the ratio is about 2.5:1. In some embodiments, the ratio is about 2.6:1. In some embodiments, the ratio is about 2.7:1. In some embodiments, the ratio is about 2.8:1. In some embodiments, the ratio is about 2.9:1. In some embodiments, the ratio is about 3:1. In some embodiments, the ratio is about 3.1:1. In some embodiments, the ratio is about 3.2:1. In some embodiments, the ratio is about 3.3:1. In some embodiments, the ratio is about 3.4:1. In some embodiments, the ratio is about 3.5:1. In some embodiments, the ratio is about 3.6:1. In some embodiments, the ratio is about 3.7:1. In some embodiments, the ratio is about 3.8:1. In some embodiments, the ratio is about 3.9:1. In some embodiments, the ratio is about 4:1. In some embodiments, the crystalline form is crystalline Form IV of the compound and glutaric acid, and the molar ratio of the compound to glutaric acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form IV of the compound and glutaric acid, and the molar ratio of the compound to glutaric acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form IV of the compound and glutaric acid, and the molar ratio of the compound to glutaric acid is about 2:1.

[0420] In some embodiments, the coformer is adipic acid. In some embodiments, the crystalline form of the compound of formula I and adipic acid has a molar ratio of the compound to adipic acid anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 1.9:1, about 0.2:1 to about 1.8:1, about 0.3:1 to about 1.7:1, about 0.4:1 to about 1.6:1, about 0.5:1 to about 1.5:1, about 0.6:1 to about 1.4:1, about 0.7:1 to about 1.3:1, about 0.8:1 to about 1.2:1, or about 0.9:1 to about 1.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the crystalline form is crystalline form V of the compound and adipic acid, and the molar ratio of the compound to adipic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline form V of the compound and adipic acid, and the molar ratio of the compound to adipic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline form V of the compound and adipic acid, and the molar ratio of the compound to adipic acid is about 1:1.

[0421] In some embodiments, the coformer is gentisic acid. In some embodiments, the compound of formula I and the crystalline form of gentisic acid have a molar ratio of compound to gentisic acid anywhere from about 0.1:1 to about 4:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 4:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 3.9:1, about 0.2:1 to about 3.8:1, about 0.3:1 to about 3.7:1, about 0.4:1 to about 3.6:1, about 0.5:1 to about 3.5:1, about 0.6:1 to about 3.4:1, about 0.7:1 to about 3.3:1, about 0.8:1 to about 3.2:1, about 0.9:1 to about 3.1:1, about ... The ratio is within the range of about 0.1:1 to about 3:1, about 1.1:1 to about 2.9:1, about 1.2:1 to about 2.8:1, about 1.3:1 to about 2.7:1, about 1.4:1 to about 2.6:1, about 1.5:1 to about 2.5:1, about 1.6:1 to about 2.4:1, about 1.7:1 to about 1.3:1, about 1.8:1 to about 2.2:1, or about 1.9:1 to about 2.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the ratio is about 2.1:1. In some embodiments, the ratio is about 2.2:1. In some embodiments, the ratio is about 2.3:1.In some embodiments, the ratio is about 2.4:1. In some embodiments, the ratio is about 2.5:1. In some embodiments, the ratio is about 2.6:1. In some embodiments, the ratio is about 2.7:1. In some embodiments, the ratio is about 2.8:1. In some embodiments, the ratio is about 2.9:1. In some embodiments, the ratio is about 3:1. In some embodiments, the ratio is about 3.1:1. In some embodiments, the ratio is about 3.2:1. In some embodiments, the ratio is about 3.3:1. In some embodiments, the ratio is about 3.4:1. In some embodiments, the ratio is about 3.5:1. In some embodiments, the ratio is about 3.6:1. In some embodiments, the ratio is about 3.7:1. In some embodiments, the ratio is about 3.8:1. In some embodiments, the ratio is about 3.9:1. In some embodiments, the ratio is about 4:1. In some embodiments, the crystalline form is crystalline Form VI of the compound and gentisic acid, and the molar ratio of the compound to gentisic acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form VI of the compound and gentisic acid, and the molar ratio of the compound to gentisic acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form VI of the compound and gentisic acid, and the molar ratio of the compound to gentisic acid is about 2:1.

[0422] In some embodiments, the coformer is fumaric acid. In some embodiments, the compound of formula I and the crystalline form of fumaric acid have a molar ratio of compound to fumaric acid anywhere from about 0.1:1 to about 4:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 3.9:1, about 0.2:1 to about 3.8:1, about 0.3:1 to about 3.7:1, about 0.4:1 to about 3.6:1, about 0.5:1 to about 3.5:1, about 0.6:1 to about 3.4:1, about 0.7:1 to about 3.3:1, about 0.8:1 to about 3.2:1, about 0.9:1 to about 3.1:1, about ... The ratio is within the range of about 0.1:1 to about 3:1, about 1.1:1 to about 2.9:1, about 1.2:1 to about 2.8:1, about 1.3:1 to about 2.7:1, about 1.4:1 to about 2.6:1, about 1.5:1 to about 2.5:1, about 1.6:1 to about 2.4:1, about 1.7:1 to about 1.3:1, about 1.8:1 to about 2.2:1, or about 1.9:1 to about 2.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the ratio is about 2.1:1. In some embodiments, the ratio is about 2.2:1. In some embodiments, the ratio is about 2.3:1.In some embodiments, the ratio is about 2.4:1. In some embodiments, the ratio is about 2.5:1. In some embodiments, the ratio is about 2.6:1. In some embodiments, the ratio is about 2.7:1. In some embodiments, the ratio is about 2.8:1. In some embodiments, the ratio is about 2.9:1. In some embodiments, the ratio is about 3:1. In some embodiments, the ratio is about 3.1:1. In some embodiments, the ratio is about 3.2:1. In some embodiments, the ratio is about 3.3:1. In some embodiments, the ratio is about 3.4:1. In some embodiments, the ratio is about 3.5:1. In some embodiments, the ratio is about 3.6:1. In some embodiments, the ratio is about 3.7:1. In some embodiments, the ratio is about 3.8:1. In some embodiments, the ratio is about 3.9:1. In some embodiments, the ratio is about 4:1. In some embodiments, the crystalline form is crystalline Form VII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form VII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline Form VII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is about 2:1.

[0423] In some embodiments, the compound of formula I and the crystalline form of fumaric acid have a molar ratio of compound to fumaric acid anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 1.9:1, about 0.2:1 to about 1.8:1, about 0.3:1 to about 1.7:1, about 0.4:1 to about 1.6:1, about 0.5:1 to about 1.5:1, about 0.6:1 to about 1.4:1, about 0.7:1 to about 1.3:1, about 0.8:1 to about 1.2:1, or about 0.9:1 to about 1.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the crystalline form is crystalline Form VIII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form VIII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form VIII of the compound and fumaric acid, and the molar ratio of the compound to fumaric acid is about 1:1.

[0424] In some embodiments, the coformer is D-(-)-tartaric acid. In some embodiments, the compound of formula I and the crystalline form of D-(-)-tartaric acid have a molar ratio of compound to D-(-)-tartaric acid anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 1.9:1, about 0.2:1 to about 1.8:1, about 0.3:1 to about 1.7:1, about 0.4:1 to about 1.6:1, about 0.5:1 to about 1.5:1, about 0.6:1 to about 1.4:1, about 0.7:1 to about 1.3:1, about 0.8:1 to about 1.2:1, or about 0.9:1 to about 1.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the crystalline form is crystalline Form IX of the compound and D-(-)-tartaric acid, and the molar ratio of the compound to D-(-)-tartaric acid is anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is anywhere from about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form IX of the compound and D-(-)-tartaric acid, and the molar ratio of the compound to D-(-)-tartaric acid is anywhere from about 0.1:1 to about 2:1.In some embodiments, the crystalline form is crystalline Form IX of the compound and D-(-)-tartaric acid, and the molar ratio of the compound to D-(-)-tartaric acid is within any range from about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form IX of the compound and D-(-)-tartaric acid, and the molar ratio of the compound to D-(-)-tartaric acid is about 1:1.

[0425] In some embodiments, the coformer is hydrochloric acid. In some embodiments, the crystalline form is crystalline form X of the compound and hydrochloric acid.

[0426] In some embodiments, the coformer is salicylic acid. In some embodiments, the compound of formula I and the crystalline form of salicylic acid have a molar ratio of compound to salicylic acid ranging anywhere from about 0.1:1 to about 4:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 3.9:1, about 0.2:1 to about 3.8:1, about 0.3:1 to about 3.7:1, about 0.4:1 to about 3.6:1, about 0.5:1 to about 3.5:1, about 0.6:1 to about 3.4:1, about 0.7:1 to about 3.3:1, about 0.8:1 to about 3.2:1, about 0.9:1 to about 3.1:1, about ... The ratio is within the range of about 0.1:1 to about 3:1, about 1.1:1 to about 2.9:1, about 1.2:1 to about 2.8:1, about 1.3:1 to about 2.7:1, about 1.4:1 to about 2.6:1, about 1.5:1 to about 2.5:1, about 1.6:1 to about 2.4:1, about 1.7:1 to about 1.3:1, about 1.8:1 to about 2.2:1, or about 1.9:1 to about 2.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the ratio is about 2.1:1. In some embodiments, the ratio is about 2.2:1. In some embodiments, the ratio is about 2.3:1.In some embodiments, the ratio is about 2.4:1. In some embodiments, the ratio is about 2.5:1. In some embodiments, the ratio is about 2.6:1. In some embodiments, the ratio is about 2.7:1. In some embodiments, the ratio is about 2.8:1. In some embodiments, the ratio is about 2.9:1. In some embodiments, the ratio is about 3:1. In some embodiments, the ratio is about 3.1:1. In some embodiments, the ratio is about 3.2:1. In some embodiments, the ratio is about 3.3:1. In some embodiments, the ratio is about 3.4:1. In some embodiments, the ratio is about 3.5:1. In some embodiments, the ratio is about 3.6:1. In some embodiments, the ratio is about 3.7:1. In some embodiments, the ratio is about 3.8:1. In some embodiments, the ratio is about 3.9:1. In some embodiments, the ratio is about 4:1. In some embodiments, the crystalline form is crystalline form XI of the compound and salicylic acid, and the molar ratio of the compound to salicylic acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline form XI of the compound and salicylic acid, and the molar ratio of the compound to salicylic acid is within any range of about 0.1:1 to about 4:1. In some embodiments, the crystalline form is crystalline form XI of the compound and salicylic acid, and the molar ratio of the compound to salicylic acid is about 2:1.

[0427] In some embodiments, the coformer is oxalic acid. In some embodiments, the compound of formula I and the crystalline form of oxalic acid have a molar ratio of compound to oxalic acid anywhere from about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 2:1. In some embodiments, the ratio is within the range of about 0.1:1 to about 1.9:1, about 0.2:1 to about 1.8:1, about 0.3:1 to about 1.7:1, about 0.4:1 to about 1.6:1, about 0.5:1 to about 1.5:1, about 0.6:1 to about 1.4:1, about 0.7:1 to about 1.3:1, about 0.8:1 to about 1.2:1, or about 0.9:1 to about 1.1:1. In some embodiments, the ratio is about 0.1:1. In some embodiments, the ratio is about 0.2:1. In some embodiments, the ratio is about 0.3:1. In some embodiments, the ratio is about 0.4:1. In some embodiments, the ratio is about 0.5:1. In some embodiments, the ratio is about 0.6:1. In some embodiments, the ratio is about 0.7:1. In some embodiments, the ratio is about 0.8:1. In some embodiments, the ratio is about 0.9:1. In some embodiments, the ratio is about 1:1. In some embodiments, the ratio is about 1.1:1. In some embodiments, the ratio is about 1.2:1. In some embodiments, the ratio is about 1.3:1. In some embodiments, the ratio is about 1.4:1. In some embodiments, the ratio is about 1.5:1. In some embodiments, the ratio is about 1.6:1. In some embodiments, the ratio is about 1.7:1. In some embodiments, the ratio is about 1.8:1. In some embodiments, the ratio is about 1.9:1. In some embodiments, the ratio is about 2:1. In some embodiments, the crystalline form is crystalline Form XII of the compound and oxalic acid, and the molar ratio of the compound to oxalic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form XII of the compound and oxalic acid, and the molar ratio of the compound to oxalic acid is within any range of about 0.1:1 to about 2:1. In some embodiments, the crystalline form is crystalline Form XII of the compound and oxalic acid, and the molar ratio of the compound to oxalic acid is about 1:1.

[0428] In some embodiments, the coformer is 1-hydroxy-2-naphthoic acid. In some embodiments, the crystalline form is crystalline Form XIII of the compound and 1-hydroxy-2-naphthoic acid.

[0429] Pharmaceutical Compositions / Formulations The embodiments described herein can be used in pharmaceutical compositions, which can be formulated by standard techniques using one or more physiologically acceptable carriers or excipients. In some embodiments, the formulations may contain buffers and / or preservatives. Any of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, as well as physiologically acceptable salts, anhydrates, hydrates and / or solvates thereof, can be formulated for administration by any suitable route, including inhalation, topical, nasal, oral, parenteral (e.g., intravenous, intraperitoneal, intravesical, or intrathecal) or rectal, in a vehicle containing one or more pharma-ceutically acceptable carriers, the proportions being determined by the route of administration and standard biological practice. Other routes of administration are described herein and can be used as well.

[0430] In some embodiments, a pharmaceutical composition is provided that comprises a crystalline form of the compound of formula I, as described or provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form I, form II, form III, form IV, form V, form VI, form VII, form VIII, form IX, form X, form XI, form XII, or form XIII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form I, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form II, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form III, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VI, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form V, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form VIII, comprising the compound of formula I. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form IX, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form X, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XI, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XII, as described and provided herein. In some embodiments, a pharmaceutical composition is provided that comprises crystalline form XIII, as described and provided herein.

[0431] In some embodiments, the pharmaceutical compositions comprising crystalline forms I-XIII described or provided herein further comprise a pharma- ceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises crystalline form I. In some embodiments, the pharmaceutical composition comprises crystalline form II. In some embodiments, the pharmaceutical composition comprises crystalline form III. In some embodiments, the pharmaceutical composition comprises crystalline form VI. In some embodiments, the pharmaceutical composition comprises crystalline form V. In some embodiments, the pharmaceutical composition comprises crystalline form VI. In some embodiments, the pharmaceutical composition comprises crystalline form VII. In some embodiments, the pharmaceutical composition comprises crystalline form VIII. In some embodiments, the pharmaceutical composition comprises crystalline form IX. In some embodiments, the pharmaceutical composition comprises crystalline form X. In some embodiments, the pharmaceutical composition comprises crystalline form XI. In some embodiments, the pharmaceutical composition comprises crystalline form XII. In some embodiments, the pharmaceutical composition comprises crystalline form XIII.

[0432] In some embodiments, pharmaceutical compositions are provided that include an effective amount of any of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of Formula I, together with, for example, pharma- ceutically acceptable diluents, preservatives, solubilizers, emulsifiers, adjuvants, and / or other carriers. Such compositions are known to those of skill in the art, and the compositions can be formulated using standard techniques. For example, diluents of various buffer contents can be used, including, but not limited to, TRIS or other amines, carbonates, phosphates, amino acids, such as glycinamide hydrochloride (especially in the physiological pH range), N-glycylglycine, sodium or potassium phosphates (dibasic, tribasic, or TRIS-HCl or acetate), pH and ionic strength; additives such as surfactants and solubilizers (e.g., surfactants such as Pluronic, Tween 20, Tween 80 (polysorbate 80), Cremophor, polyols such as polyethylene glycol, propylene glycol, etc.), antioxidants (e.g., ascorbic acid, sodium metabisulfite), preservatives (e.g., thimerosol, benzyl alcohol, parabens, etc.) and bulking agents (e.g., sugars such as sucrose, lactose, mannitol, polymers such as polyvinylpyrrolidone or dextran, etc.); and / or particulate preparations of polymeric compounds such as polylactic acid, polyglycolic acid, or incorporation of the material into liposomes. Hyaluronic acid can also be used. Such compositions can be used to affect the physical state, stability, in vivo release rate, and in vivo clearance rate of any one of the crystalline forms I-XIII described herein, or a composition containing crystalline form VIII. See, for example, pages 1435-1712 of Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack Publishing Co., Easton, Pa. 18042), which is incorporated herein by reference.When a buffer is included in the formulation, the buffer can be, for example, but not limited to, sodium acetate, sodium carbonate, citrate, glycylglycine, histidine, glycine, lysine, arginine, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, and tris(hydroxymethyl)-aminomethane, or mixtures thereof.Each buffer can be used independently or in combination with another buffer.In some embodiments, the buffer is glycylglycine, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, or mixtures thereof.

[0433] When a pharma- ceutically acceptable preservative is included in the formulation, the preservative may be, but is not limited to, phenol, m-cresol, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, 2-phenoxyethanol, butyl p-hydroxybenzoate, 2-phenylethanol, benzyl alcohol, chlorobutanol, and thiomerosal, or mixtures thereof. In some embodiments, the preservative is phenol and / or m-cresol.

[0434] In some embodiments, the preservative is present in a concentration of about 0.1 mg / ml to about 100 mg / ml, more preferably about 0.1 mg / ml to about 50 mg / ml, more preferably about 0.1 mg / ml to about 25 mg / ml, In some embodiments, the preservative is present in a concentration of about 0.1 mg / ml to about 10 mg / ml.

[0435] The use of preservatives in pharmaceutical compositions is well known to those of skill in the art. See, for convenience, Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0436] In some embodiments, the formulation may further comprise a chelating agent, which may be a salt of ethylenediaminetetraacetic acid (EDTA), citric acid, and aspartic acid, and mixtures thereof.

[0437] In some embodiments, the chelating agent is present in a concentration of 0.1 mg / ml to 10 mg / ml, particularly 0.1 mg / ml to 5 mg / ml. In some embodiments, the chelating agent is present in a concentration of 0.1 mg / ml to 2 mg / ml. In some embodiments, the chelating agent is present in a concentration of 2 mg / ml to 5 mg / ml.

[0438] The use of chelating agents in pharmaceutical compositions is well known to those of skill in the art. See, for convenience, Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0439] In some embodiments, the formulation may further comprise a stabilizer selected from the group of high molecular weight polymers or low molecular weight compounds, including but not limited to polyethylene glycol (e.g., PEG 3350), polyvinyl alcohol (PVA), polyvinylpyrrolidone, carboxymethylcellulose, different salts (e.g., sodium chloride), L-glycine, L-histidine, imidazole, arginine, lysine, isoleucine, aspartic acid, tryptophan, threonine, and mixtures thereof. In some embodiments, the stabilizer is L-histidine, imidazole, arginine, or any combination thereof.

[0440] In some embodiments, the high molecular weight polymer is present in a concentration of 0.1 mg / ml to 100 mg / ml, such as from 0.1 mg / ml to 50 mg / ml. In some embodiments, the high molecular weight polymer is present in a concentration of 0.1 mg / ml to 5 mg / ml. In some embodiments, the high molecular weight polymer is present in a concentration of 5 mg / ml to 10 mg / ml. In some embodiments, the high molecular weight polymer is present in a concentration of 10 mg / ml to 20 mg / ml. In some embodiments, the high molecular weight polymer is present in a concentration of 20 mg / ml to 30 mg / ml. In some embodiments, the high molecular weight polymer is present in a concentration of 30 mg / ml to 50 mg / ml.

[0441] In some embodiments, the low molecular weight polymer is present at a concentration of 0.1 mg / ml to 100 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 0.1 mg / ml to 50 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 0.1 mg / ml to 5 mg / ml. In some embodiments, the low molecular weight polymer compound is present at a concentration of 5 mg / ml to 10 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 10 mg / ml to 20 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 20 mg / ml to 30 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 30 mg / ml to 50 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 50 mg / ml to 60 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 60 mg / ml to 80 mg / ml. In some embodiments, the low molecular weight polymer is present at a concentration of 80 mg / ml to 100 mg / ml.

[0442] The use of a stabilizer in pharmaceutical compositions is well known to the skilled artisan. See, for convenience, Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0443] In some embodiments, the formulation may include a surfactant, which may be a detergent, an ethoxylated castor oil, a polyglycolized glyceride, an acetylated monoglyceride, a sorbitan fatty acid ester, a poloxamer such as 188 and 407, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene derivative such as an alkylated and alkoxylated derivative (tween, e.g., Tween-20, or Tween-80), a monoglyceride or an ethoxylated derivative thereof, a diglyceride or a polyoxyethylene derivative thereof, glycerol, cobalt, glycerol ... oleic acid or its derivatives, lecithin, alcohol and phospholipids, glycerophospholipids (lecithin, cephalin, phosphatidylserine), glyceroglycolipids (galactopyranosides), sphingophospholipids (sphingomyelin), and sphingoglycolipids (ceramides, gangliosides), DSS (docusate sodium, docusate calcium, docusate potassium, SDS (sodium dodecyl sulfate or sodium lauryl sulfate), dipalmitoylphosphatidic acid, sodium caprylate, bile acids and their salts, and glycine or taurine. conjugates, ursodeoxycholic acid, sodium cholate, sodium deoxycholate, sodium taurocholate, sodium glycocholate, N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, anionic (alkyl-aryl-sulfonate) monovalent surfactants, palmitoyl lysophosphatidyl-L-serine, lysophospholipids (e.g., 1-acyl-sn-glycero-3-phosphate esters of ethanolamine, choline, serine, or threonine), lysophosphatidyl and phosphatidylcholine esters Alkyl, alkoxyl (alkyl ester), alkoxy (alkyl ether)-derivatives, e.g., lauroyl and myristoyl derivatives of lysophosphatidylcholine, dipalmitoylphosphatidylcholine, as well as modifications of the polar head group, i.e., choline, ethanolamine, phosphatidic acid, serine, threonine, glycerol, inositol, as well as the positively charged DODAC, DOTMA, DCP, BISHOP, lysophosphatidylserine, and lysophosphatidylthreonine, zwitterionic surfactants (e.g., N-alkyl-N,N-dimethylammonio-1-propanesulfonate, 3-cholamido-1-propyldimethylammonio-1-propanesulfonate, dodecylphosphocholine, myristoyl lysophosphatidylcholine, egg yolk lysolecithin), cationic surfactants (quaternary ammonium bases) (e.g., cetyl-trimethylammonium bromide, cetylpyridinium chloride), non-ionic surfactants, polyethylene oxide / polypropylene oxide block copolymers (Pluronics / Tetronics, Triton X-100, dodecyl β-D-glucopyranoside) or polymeric surfactants (Tween-40, Tween-80, Brij-35), fusidic acid derivatives - (e.g., sodium tauro-dihydrofusidate, etc.), long chain fatty acids and their salts C6-C12 (e.g., oleic acid and caprylic acid), acylcarnitines and derivatives, N-amino acids of lysine, arginine, or histidine, α -acylated derivatives, or side chain acylated derivatives of lysine or arginine, N-acylated derivatives of dipeptides containing lysine, arginine or histidine and any combination of neutral or acidic amino acids. α -acylated derivatives of tripeptides containing any combination of neutral and two charged amino acids α -acylated derivatives, imidazoline derivatives, or any mixture thereof.

[0444] The use of surfactants in pharmaceutical compositions is well known to the skilled artisan. See, for convenience, Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0445] The formulation may also include a pharma- ceutically acceptable sweetener. In some embodiments, the sweetener includes at least one intense sweetener, such as, but not limited to, saccharin, sodium or calcium saccharin, aspartame, potassium acesulfame, sodium cyclamate, alitame, dihydrochalcone sweetener, monellin, stevioside, or sucralose (4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose), preferably saccharin, sodium or calcium saccharin, and optionally a bulk sweetener, such as sorbitol, mannitol, fructose, sucrose, maltose, isomalt, glucose, hydrogenated glucose syrup, xylitol, caramel, or honey.

[0446] Intense sweeteners are conveniently used in low concentrations. For example, in the case of sodium saccharin, the concentration may range from 0.04% to 0.1% (w / v), based on the total volume of the final formulation, or about 0.06% for low-dose formulations and about 0.08% for high-dose formulations. Bulk sweeteners can be effectively used in larger amounts, ranging from about 10% to about 35%, or about 10% to 15% (w / v).

[0447] For formulations, see, e.g., Remington's Pharmaceutical Sciences, 1985 or Remington: The Science and Practice of Pharmacy, 19th edition, 1995. Such traditional techniques in the pharmaceutical industry involve dissolving and mixing the ingredients as necessary to obtain the desired final product.

[0448] The administration of the compound or formulation described herein may be carried out by any method known in the art.For example, administration may be by transdermal, parenteral, intravenous, intraarterial, subcutaneous, intramuscular, intracranial, intraorbital, intraocular, intraventricular, intraarticular, intraspinal, intracisternal, intraperitoneal, intraventricular, intrathecal, intranasal, aerosol, suppository, inhalation, or oral administration.In some embodiments, the compound or formulation is administered intravenously or by injection.

[0449] For oral administration, any one of crystalline forms I-XIII or a therapeutically acceptable salt thereof may be formulated in unit dosage form such as gelcaps, caplets, granules, lozenges, bulk powders, capsules, or tablets. Tablets or capsules may be prepared by conventional means using pharma- ceutically acceptable excipients, including binders such as pregelatinized corn starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose; fillers such as lactose, microcrystalline cellulose, or calcium hydrogen phosphate; lubricants such as magnesium stearate, talc, or silica; disintegrants such as potato starch or sodium starch glycolate; or wetting agents such as sodium lauryl sulfate. Tablets may be coated by methods well known in the art.

[0450] Liquid preparations for oral administration can take the form of, for example, solution, syrup, or suspension, or can be presented as a dry product for constitution with water or other suitable vehicle before use.These liquid preparations can be prepared by conventional means using pharmaceutically acceptable additives, such as suspending agents, such as sorbitol syrup, cellulose derivatives, or hydrogenated edible fats, emulsifying agents, such as lecithin or acacia, non-aqueous vehicles, such as almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils, and preservatives, such as methyl or propyl-p-hydroxybenzoates or sorbic acid.Preparations can also contain buffer salts, flavoring agents, coloring agents, and / or sweetening agents as necessary.Preparations for oral administration can be suitably formulated to control the release of active compounds as necessary.

[0451] For topical administration, any of the crystals or crystalline forms provided or described herein, such as crystalline forms I-XIII of the compound of Formula I, can be formulated in a pharma- ceutically acceptable vehicle containing 0.1 to 10 percent, preferably 0.5 to 5 percent, of the active compound. Such formulations may be in the form of creams, lotions, sublingual tablets, aerosols, and / or emulsions, and may be included in matrix or reservoir-type transdermal or buccal patches conventional in the art for this purpose.

[0452] For parenteral administration, any crystalline form described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may be administered in a composition with a pharma- ceutically acceptable vehicle or carrier, either by intravenous, subcutaneous, or intramuscular injection. The crystalline forms described and provided herein may be formulated for parenteral administration by injection, e.g., bolus injection or continuous infusion. Formulations for injection may be presented, e.g., in unit dosage form, e.g., in ampoules or multi-dose containers, with added preservatives. The compositions may take forms such as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents, e.g., suspending, stabilizing, and / or dispersing agents. Additionally, the compounds may be precipitated and stored in ampoules or other containers, and then dissolved in solution prior to administration to a subject.

[0453] For administration by injection, the compounds can be used in solution, for example, in a sterile aqueous vehicle, which may also contain other solutes, such as buffers or preservatives, as well as a sufficient amount of pharma- ceutically acceptable salts or glucose to make the solution isotonic. In some embodiments, the pharmaceutical composition may be formulated with a pharma- ceutically acceptable carrier to provide a sterile solution or suspension for injectable administration. In particular, injectables can be prepared in conventional forms, either as liquid solutions or suspensions, as solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Suitable excipients are, for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine ​​hydrochloride, and the like. In addition, if desired, injectable pharmaceutical compositions may contain small amounts of non-toxic auxiliary substances, such as wetting agents, pH buffering agents, and the like. Absorption enhancing preparations (e.g., liposomes) may be utilized if desired. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by EW Martin.

[0454] For administration by inhalation, the compound can be conveniently delivered in the form of aerosol spray presentation from pressurized pack or nebulizer by using suitable propellant, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas.In the case of pressurized aerosol, dosage unit can be determined by providing a valve to deliver a metered amount.For example, gelatin capsules and cartridges for use in inhaler or insufflator can be formulated to contain the powder mixture of the compound and suitable powder base, for example, lactose or starch.For intranasal administration, the compound can be used, for example, as liquid spray, as powder, or in the form of droplets.

[0455] The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, eg, containing conventional suppository bases such as cocoa butter or other glycerides.

[0456] In addition, compound can be formulated as depot preparation.This long-acting preparation can be administered by implantation (for example, subcutaneous or intramuscular) or intramuscular injection.Thus, for example, compound can be formulated with suitable polymer or hydrophobic material (for example, as emulsion in acceptable oil) or ion exchange resin, or as sparingly soluble derivative, for example, as sparingly soluble salt.

[0457] The composition may be presented in a pack or dispenser device that may contain one or more unit dosage forms containing the active ingredient, if desired. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack may also comprise individual vials or other containers. The pack or dispenser device may be accompanied by instructions for administration.

[0458] dose Any of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may be administered to a patient in a therapeutically effective dose to prevent, treat, or control diseases and disorders mediated in whole or in part by the GPCR-ligand interactions described herein. A pharmaceutical composition comprising any of the crystalline forms described or provided herein, such as crystalline forms I-XIII of the compound of formula I, may be administered to a patient in an amount sufficient to induce an effective protective or therapeutic response in the patient. The dose is determined by the efficacy of the particular compound used and the condition of the subject, as well as the weight or surface area of ​​the area to be treated. The size of the dose is also determined by the existence, nature, and extent of any adverse effects associated with the administration of a particular compound or vector in a particular subject.

[0459] The amount and frequency of administration of the compound, including any crystalline form described or provided herein, such as crystalline forms I-XIII of the compound of formula I prepared according to the methods described herein, and / or pharma- ceutically acceptable salts thereof, may be adjusted according to the judgment of the attending physician, taking into consideration factors such as the age, condition, and size of the patient, and the severity of the condition being treated. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the agent required to prevent, combat, or halt the progression of the condition. In general, an effective amount is contemplated to be 0.001 mg to 10 mg per kg of body weight, particularly 0.01 mg to 1 mg per kg of body weight. More specifically, an effective amount is contemplated to be 0.01 micrograms / kg body weight / min to 100 micrograms / kg body weight / min, continuously infused by intravenous administration for 12 hours to 14 days. It may be appropriate to administer the required dose as two, three, four, or more partial doses at appropriate intervals throughout the day. Sub-doses may be formulated as unit dosage forms, for example, containing 0.01 to 500 mg, particularly 0.1 mg to 200 mg, of active ingredient per unit dosage form.

[0460] In some embodiments, the pharmaceutical preparation is in unit dosage form. In such form, the preparation is subdivided into appropriately sized unit doses containing an appropriate amount of the active ingredient, e.g., an effective amount to achieve the desired purpose. The amount of active compound in a unit dose of the preparation can be varied or adjusted from about 0.01 mg to about 1000 mg, about 0.01 mg to about 750 mg, about 0.01 mg to about 500 mg, or about 0.01 mg to about 250 mg, according to the specific application. The actual dose used may vary depending on the needs of the patient and the severity of the condition being treated. The determination of the appropriate dosage regimen for a particular situation is within the skill of one of ordinary skill in the art. For convenience, the total dose may be administered in portions throughout the day as needed.

[0461] medical use In some embodiments, the method includes administering to a subject or a subject in need thereof an amount, such as a therapeutically effective amount, of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, or a pharma- ceutically acceptable salt or solvate thereof. The therapeutically effective amount of a crystalline form may vary depending on the intended application (in vitro or in vivo), or the subject and disease state to be treated, such as the subject's weight and age, the severity of the disease state, the mode of administration, etc., which can be readily determined by one of ordinary skill in the art. The term also applies to a dose that induces a particular response in a target cell, such as a reduction in proliferation or downregulation of the activity of a target protein. The specific dose will vary depending on the particular crystalline form provided herein selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, and the physical delivery system in which it is delivered.

[0462] As used herein, the term "IC50" refers to the half-maximal inhibitory concentration of an inhibitor in inhibiting a biological or biochemical function. This quantitative measure indicates how much of a particular inhibitor is needed to half-inhibit a given biological process (or a component of the process, i.e., an enzyme, a cell, a cellular receptor, or a microorganism). In other words, it is the half-maximal (50%) inhibitory concentration (IC) of a substance (50% IC, or IC50). EC50 refers to the plasma concentration required to obtain >50% of the maximum effect in vivo.

[0463] In some embodiments, the subject methods utilize CDK inhibitors that have IC50 values ​​at or below about a given value as determined in an in vitro assay. In some embodiments, the CDK inhibitor is at or below about 1 nM or less, 2 nM or less, 5 nM or less, 7 nM or less, 10 nM or less, 20 nM or less, 30 nM or less, 40 nM or less, 50 nM or less, 60 nM or less, 70 nM or less, 80 nM or less, 90 nM or less, 100 nM or less, 120 nM or less, 140 nM or less, 150 nM or less, 160 nM or less, 170nM or less, 180nM or less, 190nM or less, 200nM or less, 225nM or less, 250nM or less, 275nM or less, 300nM or less, 325nM or less, 35 0nM or less, 375nM or less, 400nM or less, 425nM or less, 450nM or less, 475nM or less, 500nM or less, 550nM or less, 600nM or less, 650nM Inhibits CDK with an IC50 value of 0.1 μM or less, 700 nM or less, 750 nM or less, 800 nM or less, 850 nM or less, 900 nM or less, 950 nM or less, 1 μM or less, 1.1 μM or less, 1.2 μM or less, 1.3 μM or less, 1.4 μM or less, 1.5 μM or less, 1.6 μM or less, 1.7 μM or less, 1.8 μM or less, 1.9 μM or less, 2 μM or less, 5 μM or less, 10 μM or less, 15 μM or less, 20 μM or less, 25 μM or less, 30 μM or less, 40 μM or less, 50 μM, 60 μM, 70 μM, 80 μM, 90 μM, 100 μM, 200 μM, 300 μM, 400 μM, or 500 μM, or less (or within a range defined by and inclusive of any two of the above numbers). In some embodiments, the CDK enzyme is CDK9.

[0464] In some embodiments, a subject method of inhibiting a CDK enzyme comprises contacting the CDK enzyme with an effective amount of a crystalline form described herein, or a pharma- ceutically acceptable salt thereof. In some embodiments, the CDK enzyme is CDK9.

[0465] In some embodiments, the CDK inhibitor selectively inhibits a CDK with an IC50 value that is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, or 1000 times lower (or within a range defined by and including any two numbers above) than its IC50 value for one, two, or three other CDKs. In some embodiments, the CDK inhibitor is a CDK9 inhibitor.

[0466] In some embodiments, the CDK inhibitor is at or near 1 nM, 2 nM, 5 nM, 7 nM, 10 nM, 20 nM, 30 nM, 40 nM, 50 nM, 60 nM, 70 nM, 80 nM, 90 nM, 100 nM, 120 nM, 140 nM, 150 nM, 160 nM, 170 nM, 180 nM, 190 nM, 200 nM, 225 nM, 250 nM, 27 5nM, 300nM, 325nM, 350nM, 375nM, 400nM, 425nM, 450nM, 475nM, 500nM, 550nM, 600nM, 650nM , 700nM, 750nM, 800nM, 850nM, 900nM, 950nM, 1μM, 1.1μM, 1.2μM, 1.3μM, 1.4μM, 1.5μM, 1.6μM , 1.7 μM, 1.8 μM, 1.9 μM, 2 μM, 5 μM, 10 μM, 15 μM, 20 μM, 25 μM, 30 μM, 40 μM, 50 μM, 60 μM, 70 μM, 80 μM, 90 μM, 100 μM, 200 μM, 300 μM, 400 μM, or 500 μM (or within a range defined by any two numbers above, inclusive) which is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, or 1000 fold (or within a range defined by any two numbers above, inclusive) less than its IC50 value against one, two or three other CDKs. In some embodiments, the CDK inhibitor is a CDK9 inhibitor.

[0467] In some embodiments, the compounds described herein are used to inhibit a CDK enzyme in a subject, the use comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline Forms I-XIII of the crystalline form of Formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0468] In some embodiments, provided herein is a pharmaceutical composition described herein for use in inhibiting a CDK enzyme in a subject, the use comprising administering to the subject an effective amount of one or more pharmaceutical compositions provided herein.

[0469] In some embodiments, provided herein is a use of crystalline Forms I-XIII of the compound of Formula I provided herein in the manufacture of a formulation for inhibiting a CDK enzyme in a subject, the use comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline Forms I-XIII of the compound of Formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0470] In some embodiments, provided herein is a use of a pharmaceutical composition described herein for inhibiting a CDK enzyme in a subject, the use comprising administering to the subject an effective amount of one or more pharmaceutical compositions described herein. In some embodiments, the CDK enzyme is CDK9.

[0471] The subject method is useful for treating a disease or disorder condition associated with CDK. Any disease or disorder condition resulting directly or indirectly from an abnormal activity or expression level of CDK may be a disease or disorder condition of interest. In some embodiments, the method for treating a disease or disorder condition associated with CDK in a subject or a subject in need thereof comprises administering to the subject a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I described herein, or a pharma- ceutically acceptable salt thereof.

[0472] Various diseases or disorders related to CDK have been reported.CDK is involved in, for example, autoimmune disease, neurodegeneration (e.g., Parkinson's disease, Alzheimer's disease and ischemia), inflammatory disease, viral infection and cancer (e.g., colon cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia or pancreatic cancer, etc.).

[0473] Non-limiting examples of such conditions include acanthoma, acinic cell carcinoma, acoustic neuroma, acral lentiginous melanoma, acrohidroma, acute eosinophilic leukemia, acute lymphoblastic leukemia, acute lymphocytic leukemia, acute megakaryoblastic leukemia, acute monocytic leukemia, acute myeloblastic leukemia with maturation, acute myeloid dendritic cell leukemia, acute myeloid leukemia, acute myelogenous ... leukemia), acute promyelocytic leukemia, adamantinoma, adenocarcinoma, adenoid cystic carcinoma, adenoma, adenoid odontogenic tumor, adrenal cortical carcinoma, adult T-cell leukemia, aggressive NK-cell leukemia, AIDS-related cancer, AIDS-related lymphoma, alveolar soft part sarcoma, ameloblastic fibroma, anal carcinoma, anaplastic large cell lymphoma, anaplastic thyroid carcinoma, angioimmunoblastic T-cell lymphoma, angiomyolipoma, angiosarcoma, appendix cancer, astrocytoma, atypical teratoid rhabdoid tumor, basal cell carcinoma, basal-like carcinoma, B-cell Leukemia, B-cell lymphoma, Bellini duct carcinoma, biliary tract cancer, bladder cancer, blastoma, bone cancer, bone tumor, brain stem glioma, brain tumor, breast cancer, Brenner tumor, bronchial tumor, bronchioloalveolar carcinoma, Brown tumor, Burkitt lymphoma, cancer of unknown primary site, carcinoid tumor, carcinoma, intraepithelial carcinoma, penile cancer, cancer of unknown primary site, carcinosarcoma, Castleman disease, central nervous system embryonal tumor, cerebellar astrocytoma, brain astrocytoma, cervical cancer, bile duct cancer, chondroma, chondrosarcoma, chordoma, choriocarcinoma, choroid plexus papilloma, chronic lymphocytic Leukemia, chronic monocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorder, chronic neutrophilic leukemia, clear cell tumor, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, Degos disease, dermatofibrosarcoma protozoa, dermoid cyst, decidual small round cell tumor, diffuse large B-cell lymphoma, decidual neuroepithelial tumor, germ cell carcinoma, endodermal sinus tumor, uterine cancer, endometrial cancer, endometrioid tumor, gut-associated T-cell lymphoma, ependymoblastoma, ependymoma, epidermoid carcinoma, parathyroid sarcoma, erythroblastic leukemia, phagocytosis ductal cancer, esthesioneublastoma, Ewing family tumors, Ewing family sarcoma, Ewing sarcoma, extracranial germ cell tumor, extracarinal germ cell tumor, extrahepatic bile duct carcinoma, extramammary Paget's disease, fallopian tube cancer, fetal, fibroma, fibrosarcoma, follicular lymphoma, follicular thyroid cancer, gallbladder cancer, gallbladder cancer, ganglioneuroma, radiculourinoma, gastric cancer, gastric lymphoma, gastrointestinal cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gastrointestinal stromal tumor, germ cell tumor, germinoma, gestational choriocarcinoma, gestational trophoblastic tumor, giant cell tumor of bone,Glioblastoma multiforme, glioma, gliomatosis cerebri, glomus tumor, glucagonoma, gonadoblastoma, granulosa cell tumor, hairy cell leukemia, head and neck cancer, head and neck cancer, cardiac cancer, hemoglobinopathies such as b-thalassemia and sickle cell disease (SCD), hemangioblastoma, hemangiopericytoma, hemangiosarcoma, hematologic malignancies, hepatocellular carcinoma, hepatosplenic T-cell lymphoma, hereditary breast and ovarian cancer syndrome, Hodgkin lymphoma, Hodgkin lymphoma, hypopharyngeal cancer, hypothalamic glioma, inflammatory breast cancer, intraocular melanoma, islet cell carcinoma, islet cell tumor, juvenile myelomonocytic leukemia, Kaposi's sarcoma, Kaposi's sarcoma, kidney cancer, Klatskin tumor, Krukenberg tumor, laryngeal cancer, lentigo maligna, leukemia, lip and oral cancer, liposarcoma, lung cancer, luteoma, lymphangioma, lymphangiosarcoma, lymphoma Paedicoma, lymphocytic leukemia, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, malignant fibrous histiocytoma of bone, malignant glioma, malignant mesothelioma, malignant peripheral nerve sheath tumor, malignant rhabdoid tumor, malignant triton tumor, MALT lymphoma, mantle cell lymphoma, mast cell leukemia, mastocytosis, breast germ cell tumor, breast tumor, medullary thyroid carcinoma, medulloblastoma, medulloepithelioma, melanoma, meningioma, Merkel cell carcinoma, mesothelioma, mesothelioma, occult squamous cell carcinoma, metastatic urothelial carcinoma, mixed Mullerian tumor, monocytic leukemia , oral cancer, mucinous tumors, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myeloid leukemia, myelosarcoma, myeloproliferative disorders, myxoma, nasal cancer, nasopharyngeal cancer, nasopharyngeal carcinoma, neoplasms, schwannoma, neuroblastoma, neurofibroma, neuroma, nodular melanoma, non-Hodgkin's lymphoma, non-melanoma skin cancer, non-small cell lung cancer, ophthalmic tumors, oligodendroglioma, oligodendroglioma, optic nerve sheath meningioma, oral cancer, oral cancer, oropharyngeal cancer, osteosarcoma, osteosarcoma ovarian cancer, ovarian epithelial cancer, ovarian germ cell tumor, ovarian low malignant grade tumor, breast Paget's disease of the pancreas, Pancoast tumor, Pancreatic cancer, Papillary thyroid carcinoma, Papillomatosis, Paraganglioma, Paranasal sinus cancer, Parathyroid carcinoma, Penile cancer, Hemangioperiepithelioma, Pharyngeal carcinoma, Pheochromocytoma, Intermediate differentiation pineal tumor, Pineoblastoma, Pituitary cell tumor, Pituitary adenoma, Pituitary tumor, Plasma cell neoplasm, Alveolar germinoma, Polygerminoma, Precursor T-lymphoblastic lymphoma, Primary central nervous system lymphoma, Primary pleural effusion lymphoma, Primary hepatocellular carcinoma, Primary liver cancer, Primary peritoneal carcinoma, Primitive neuroectodermal tumor, Prostate cancer, Peritoneal pseudomyxoma, Rectal cancer, Renal cell carcinoma,Respiratory tract cancer involving the NUT gene on chromosome 15, retinoblastoma, rhabdomyoma, rhabdomyosarcoma, Richter transformation, sacral teratoma, salivary gland carcinosarcoma, Schwannomatosis, sebaceous gland carcinoma, secondary neoplasms, seminoma, serous tumor, Sertoli-Leydig cell tumor, sex cord-stromal tumor, Sezary syndrome, signet ring cell tumor, skin cancer, small blue round cell tumor, small cell carcinoma, small cell lung cancer, small cell lymphoma, small intestine cancer, soft tissue sarcoma, somatostatinoma, soot warts, spinal cord tumor, spinal cord tumor, splenic marginal zone lymphoma, squamous cell carcinoma, gastric cancer, superficial spreading melanoma, superficial primitive neuroectoderm These include, but are not limited to, follicular tumors, superficial epithelial stromal tumors, synovial sarcoma, T-cell acute lymphoblastic leukemia, T-cell large granular lymphocytic leukemia, T-cell leukemia, T-cell lymphoma, T-cell prolymphocytic leukemia, teratoma, peripheral lymphatic duct carcinoma, testicular carcinoma, sarcoma, pharyngeal carcinoma, thymic carcinoma, thymoma, thyroid carcinoma, renal pelvis and ureter transitional cell carcinoma, transitional cell carcinoma, urethral carcinoma, urinary tract neoplasms, uterine sarcoma, uveal melanoma, vaginal carcinoma, Berner-Morrison syndrome, verrucous carcinoma, visual pathway glioma, vulvar carcinoma, Waldenstrom's macroglobulinemia, Warthin's tumor, Wilms' tumor, and combinations thereof.

[0474] In some embodiments, the method is for treating a disease selected from the group consisting of tumor angiogenesis, chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease, skin diseases such as psoriasis, eczema, and scleroderma, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma, and ovarian cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, colon cancer, and epidermoid cancer.

[0475] In other embodiments, the method is for treating a disease selected from breast cancer, lung cancer, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, uterine cancer, or cervical cancer. In some embodiments, the method comprises administering to a subject or a subject in need thereof a crystalline form provided herein or a pharma- ceutically acceptable salt thereof.

[0476] In other embodiments, the method is for treating a disease selected from acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, myelodysplasia, myeloproliferative disorders, leukemia, such as acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), mastocytosis, chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic syndrome (MDS) or epidermoid carcinoma.

[0477] In some embodiments, provided herein is a crystalline form provided herein, such as crystalline Forms I-XIII of the compound of Formula I, for use in treating a disease or disorder associated with aberrant CDK activity in a subject or in a subject in need thereof, the use comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline Forms I-XIII of the compound of Formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0478] In some embodiments, provided herein is a pharmaceutical composition described herein for use in treating a disease or disorder associated with aberrant CDK activity in a subject or in a subject in need thereof, the use comprising administering to the subject an effective amount of one or more pharmaceutical compositions described herein.

[0479] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline Forms I-XIII of the compound of Formula I, in the manufacture of a formulation for treating a disease or disorder associated with aberrant CDK activity in a subject or a subject in need thereof, comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline Forms I-XIII of the compound of Formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0480] In some embodiments, the use of a pharmaceutical composition described herein for treating a disease or disorder associated with abnormal CDK activity in a subject or a subject in need thereof, comprising administering to the subject an effective amount of one or more pharmaceutical compositions described herein. In some embodiments, the disease or disorder associated with abnormal CDK activity is colon cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer.

[0481] In some embodiments, provided herein is a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, for use in treating cancer in a subject or a subject in need thereof, the use comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0482] In some embodiments, provided herein is a pharmaceutical composition described herein for use in treating cancer in a subject or a subject in need thereof, the use comprising administering to the subject an effective amount of one or more pharmaceutical compositions described herein.

[0483] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, in the manufacture of a formulation for treating cancer in a subject or a subject in need thereof, comprising administering to the subject an effective amount of one or more crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, a pharma- ceutically acceptable salt, solvate, pharmaceutical composition, or prodrug thereof.

[0484] In some embodiments, provided herein is a use of a pharmaceutical composition described herein for treating cancer in a subject or a subject in need thereof, comprising administering to the subject an effective amount of one or more pharmaceutical compositions described herein. In some embodiments, the cancer is colon cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer.

[0485] In some embodiments, provided herein is a method of inducing apoptosis in cancer or tumor cells in a subject or a subject in need thereof. In some embodiments, the method comprises contacting a cancer or tumor cell with an effective amount of a crystalline form provided herein, such as crystalline Forms I-XIII of the compound of Formula I, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, or administering to the subject. In some embodiments, provided herein is a method of inducing apoptosis in cancer or tumor cells in a subject or a subject in need thereof. In some embodiments, the method comprises contacting a cancer or tumor cell with an effective amount of a crystalline form provided herein, such as crystalline Forms I-XIII of the compound of Formula I, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, provided herein is a method of inducing apoptosis in cancer or tumor cells in a subject or a subject in need thereof, the method comprises contacting a cancer or tumor cell with an effective amount of a pharmaceutical composition described herein, or administering to the subject. In some embodiments, the cancer or tumor has high levels of MYC amplification and overexpression. In some embodiments, the cancer cells or tumors are characterized as malignant. In some embodiments, the cancer cells or tumors are characterized as hematological cancer cells or tumors. In some embodiments, the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). In some embodiments, the tumor cells are of a solid tumor. In some embodiments, the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. In some embodiments, the methods described herein further comprise contacting the tumor cells with an additional therapeutic agent, such as a targeted therapy. In some embodiments, the targeted therapy is as described herein. In some embodiments, the targeted therapy is a BCL2 inhibitor.In some embodiments, the BCL2 inhibitor is venetoclax. In some embodiments, the method achieves a complete response, such as complete tumor regression.

[0486] In some embodiments, provided herein are crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, for use in inducing apoptosis in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with, or administering to the subject, an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof.

[0487] In some embodiments, provided herein is a use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, for inducing apoptosis in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with, or administering to the subject, an effective amount of the crystalline form, or a pharma-ceutically acceptable salt or solvate thereof.

[0488] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, in the manufacture of a formulation for inducing apoptosis in cancer or tumor cells, comprising contacting cancer or tumor cells in a subject or a subject in need thereof with, or administering to, an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof.

[0489] In some embodiments, provided herein is a pharmaceutical composition described herein in use for inducing apoptosis in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of a pharmaceutical composition described herein or administering to the subject.

[0490] In some embodiments, provided herein is a use of a pharmaceutical composition described herein for inducing apoptosis in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with or administering to the subject an effective amount of a pharmaceutical composition described herein.

[0491] In some embodiments, provided herein is a use of a pharmaceutical composition described herein in the manufacture of a formulation for inducing apoptosis in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with or administering to the subject an effective amount of a pharmaceutical composition described herein.

[0492] In some embodiments, provided herein is a method of inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, or administering to the subject. In some embodiments, provided herein is a method of inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, provided herein is a method of inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a pharmaceutical composition described herein, or administering to the subject. In some embodiments, phosphorylation is inhibited by at least or about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%. In some embodiments, the cancer or tumor has high levels of MYC amplification and overexpression. In some embodiments, the cancer cells are malignant. In some embodiments, the cancer cells are hematological cancer cells. In some embodiments, the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). In some embodiments, the tumor cells are of a solid tumor. In some embodiments, the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. In some embodiments, the methods described herein further comprise contacting the tumor cells with a targeted therapy. In some embodiments, the targeted therapy is as described herein.In some embodiments, the targeted therapy is a BCL2 inhibitor. In some embodiments, the BCL2 inhibitor is venetoclax. In some embodiments, the method achieves complete tumor regression.

[0493] In some embodiments, provided herein are crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, for use in a subject or a subject in need thereof to inhibit phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells with an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject.

[0494] In some embodiments, provided herein is a use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the crystalline form, or a pharma-ceutically acceptable salt or solvate thereof, or administering to the subject.

[0495] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, in the manufacture of a formulation for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject.

[0496] In some embodiments, provided herein is a pharmaceutical composition for use in inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the pharmaceutical composition or administering to the subject.

[0497] In some embodiments, provided herein is a use of a pharmaceutical composition for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the pharmaceutical composition or administering to the subject.

[0498] In some embodiments, provided herein is the use of a pharmaceutical composition in the manufacture of a formulation for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the pharmaceutical composition or administering to the subject.

[0499] In some embodiments, provided herein is a method of reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of formula I, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, or administering to the subject. In some embodiments, provided herein is a method of reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, provided herein is a method of reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a pharmaceutical composition described herein, or administering to the subject. In some embodiments, the cancer or tumor has high levels of MYC amplification and overexpression. In some embodiments, the cancer cells are malignant. In some embodiments, the cancer cells are hematological cancer cells. In some embodiments, the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). In some embodiments, the tumor cells are of a solid tumor. In some embodiments, the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. In some embodiments, the methods described herein further comprise contacting the tumor cells with a targeted therapy. In some embodiments, the targeted therapy is as described herein. In some embodiments, the targeted therapy is a BCL2 inhibitor. In some embodiments, the BCL2 inhibitor is venetoclax.In some embodiments, the method achieves complete tumor regression.

[0500] In some embodiments, provided herein are crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, for use in a subject or a subject in need thereof to reduce the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells, comprising contacting the cancer or tumor cells with an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) is reduced by at least or about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0501] In some embodiments, provided herein is a use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, for reducing levels of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the crystalline form or a pharma-ceutically acceptable salt or solvate thereof, or administering to the subject.

[0502] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, in the manufacture of a formulation for reducing levels of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the crystalline form or a pharma-ceutically acceptable salt or solvate thereof, or administering to the subject.

[0503] In some embodiments, provided herein is a pharmaceutical composition for use in reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the pharmaceutical composition or administering to the subject.

[0504] In some embodiments, provided herein is a use of a pharmaceutical composition for reducing the level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells, comprising contacting the cancer or tumor cells with an effective amount of the pharmaceutical composition in a subject or a subject in need thereof, or administering to the subject.

[0505] In some embodiments, provided herein is the use of a pharmaceutical composition in the manufacture of a formulation for reducing a level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in a cancer or tumor cell, comprising contacting the cancer or tumor cell in a subject or a subject in need thereof with an effective amount of the pharmaceutical composition or administering to the subject.

[0506] In some embodiments, provided herein is a method of reducing the level of MYC protein in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, or administering to the subject. In some embodiments, provided herein is a method of reducing the level of MYC protein in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, provided herein is a method of reducing the level of MYC protein in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of a pharmaceutical composition described herein, or administering to the subject. In some embodiments, the cancer or tumor has high levels of MYC amplification and overexpression. In some embodiments, the cancer cells are malignant. In some embodiments, the cancer cells are hematological cancer cells. In some embodiments, the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). In some embodiments, the tumor cells are of a solid tumor. In some embodiments, the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. In some embodiments, the method described herein further comprises contacting the tumor cells with a targeted therapy. In some embodiments, the targeted therapy is as described herein. In some embodiments, the targeted therapy is a BCL2 inhibitor. In some embodiments, the BCL2 inhibitor is venetoclax. In some embodiments, the method achieves complete tumor regression.In some embodiments, the tumor regresses by at least or about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0507] In some embodiments, provided herein are crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, for use in a subject or a subject in need thereof to reduce levels of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells with, or administering to the subject, an effective amount of the crystalline form, or a pharma-ceutically acceptable salt or solvate thereof.

[0508] In some embodiments, provided herein is a use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, for reducing levels of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with, or administering to the subject, an effective amount of the crystalline form, or a pharma-ceutically acceptable salt or solvate thereof.

[0509] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, in the manufacture of a formulation for reducing levels of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with, or administering to, an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof.

[0510] In some embodiments, provided herein is a pharmaceutical composition for use in reducing levels of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with or administering to the subject an effective amount of the pharmaceutical composition.

[0511] In some embodiments, provided herein is a use of a pharmaceutical composition for reducing the level of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with an effective amount of the pharmaceutical composition or administering to the subject.

[0512] In some embodiments, provided herein is the use of a pharmaceutical composition in the manufacture of a formulation for reducing levels of MYC protein in cancer or tumor cells, comprising contacting the cancer or tumor cells in a subject or a subject in need thereof with or administering to the subject an effective amount of the pharmaceutical composition.

[0513] In some embodiments, provided herein is a method of inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, or administering to the subject. In some embodiments, provided herein is a method of inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the crystalline form provided herein, or a pharma- ceutically acceptable salt or solvate thereof, or administering to the subject. In some embodiments, provided herein is a method of inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the pharmaceutical composition described herein, or administering to the subject. In some embodiments, the cancer or tumor has high levels of MYC amplification and overexpression. In some embodiments, the cancer cells are malignant. In some embodiments, the cancer cells are hematological cancer cells. In some embodiments, the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). In some embodiments, the tumor cells are of a solid tumor. In some embodiments, the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. In some embodiments, the method described herein further comprises contacting the tumor cells with a targeted therapy. In some embodiments, the targeted therapy is as described herein. In some embodiments, the targeted therapy is a BCL2 inhibitor. In some embodiments, the BCL2 inhibitor is venetoclax. In some embodiments, the method achieves complete tumor regression.

[0514] In some embodiments, provided herein are crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, for use in a subject or a subject in need thereof to inhibit the proliferation of cancer or tumor cells, comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof, in some embodiments, proliferation is inhibited by at least or about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0515] In some embodiments, provided herein is a use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, for inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with, or administering to the subject, an effective amount of the crystalline form, or a pharma-ceutically acceptable salt or solvate thereof.

[0516] In some embodiments, provided herein is the use of a crystalline form provided herein, such as crystalline forms I-XIII of the compound of Formula I, in the manufacture of a formulation for inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with, or administering to the subject, an effective amount of the crystalline form, or a pharma- ceutically acceptable salt or solvate thereof.

[0517] In some embodiments, provided herein is a pharmaceutical composition for use in inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the pharmaceutical composition or administering to the subject.

[0518] In some embodiments, provided herein is a use of a pharmaceutical composition for inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with an effective amount of the pharmaceutical composition or administering to the subject.

[0519] In some embodiments, provided herein is the use of a pharmaceutical composition in the manufacture of a formulation for inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of the pharmaceutical composition.

[0520] The crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I of the present disclosure, as well as pharmaceutical compositions comprising them, can be administered alone or in combination with medical therapy to treat any of the diseases described.Medical therapy includes, for example, surgery and radiation therapy (e.g., gamma radiation, neutron radiation therapy, electron beam radiation therapy, proton radiation therapy, brachytherapy, total body radioisotopes).

[0521] In other aspects, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I of the present disclosure, as well as pharmaceutical compositions comprising them, can be administered alone or in combination with one or more other agents to treat any of the diseases described.

[0522] In another method, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I of the present disclosure, as well as pharmaceutical compositions comprising them, can be administered in combination with an agonist of a nuclear receptor.

[0523] In another method, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I of the present disclosure, as well as pharmaceutical compositions comprising them, can be administered in combination with an antagonist of a nuclear receptor.

[0524] In another method, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I of the present disclosure, as well as pharmaceutical compositions comprising them, can be administered in combination with an antiproliferative agent.

[0525] Combination therapy To treat cancer and other proliferative diseases, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, can be used in combination with chemotherapeutic agents, nuclear receptor agonists or antagonists, or other antiproliferative agents. The compounds can also be used in combination with drug therapies, such as surgery or radiation therapy, e.g., gamma radiation, neutron radiation therapy, electron beam radiation therapy, proton radiation therapy, brachytherapy, and total body radioisotopes. Examples of suitable chemotherapeutic agents include abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, all-trans retinoic acid, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bendamustine, bevacizumab, bexarotene, bleomycin, bortezomib, bortezomib, busulfan intravenous, busulfan oral, castellon, capecitabine, carboplatin, carmustine, carbamazepine ... tin, cetuximab, chlorambucil, cisplatin, cladribine, clochalabin, cyclophosphamide, cicarabin, dacarbazine, dactinomycin, dalteparin sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanone propionate, eculizumab, epirubicin, erlotinib, estramustine, ethoxyquin, ethylhexyl phosphate Poside, Exemestane, Fentanyl citrate, Filgrastim, Floxuridine, Fludarabine, Fluorouracil, Fulvestrant, Gefitinib, Gemcitabine, Gemtuzumab ozogamicin, Goserelin acetate, Hisrelin acetate, Ibritumomab tiuxetan acetate, Idarubicin, Ifosfamide, Imatinib mesylate, Interferon alfa 2a, Irinotecan, Lapatinib ditosylate, Lenalidomide, Lebro zole, leucovorin, leuprolide acetate, levamisole, lomustine, mechlorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab, oxaliplatin, paclitaxel, pamidronate, panobinostat, panitumumab, pegaspagase, pegfilgrastim,Pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat and zoledronic acid.

[0526] In some embodiments, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, can be used in combination with therapeutic agents that target epigenetic regulators. Examples of epigenetic regulators include bromodomain inhibitors, histone lysine methyltransferase inhibitors, histone arginine methyltransferase inhibitors, histone demethylase inhibitors, histone deacetylase inhibitors, histone acetylase inhibitors, and DNA methyltransferase inhibitors. Histone deacetylase inhibitors include, for example, vorinostat. Histone arginine methyltransferase inhibitors include inhibitors of protein arginine methyltransferases (PRMTs), such as PRMT5, PRMT1, and PRMT4. DNA methyltransferase inhibitors include inhibitors of DNMT1 and DNMT3.

[0527] For the treatment of cancer and other proliferative diseases, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, can be used in combination with targeted therapies including JAK kinase inhibitors (e.g., ruxolitinib), PI3 kinase inhibitors, including PI3K-delta selective and broad-spectrum PI3K inhibitors, cyclin-dependent kinase inhibitors, including MEK inhibitors, CDK4 / 6 inhibitors and CDK9 inhibitors, BRAF inhibitors, mTOR inhibitors, proteasome inhibitors (e.g., bortezomib, carfilzomib), HDAC inhibitors (e.g., panobinostat, vorinostat), DNA methyltransferase inhibitors, dexamethasone, bromo- and extra terminal family member (BET) inhibitors, BTK inhibitors (e.g., ibrutinib, acalabrutinib), BCL2 inhibitors (e.g., venetoclax), dual BCL2 family inhibitors (e.g., BCL2 / BCLxL), PARP inhibitors, FLT3 inhibitors, or LSD1 inhibitors.

[0528] In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of PD-1, e.g., an anti-PD-1 monoclonal antibody. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab, pembrolizumab (also known as MK-3475), or PDR001. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab or pembrolizumab. In some embodiments, the anti-PD1 antibody is pembrolizumab. In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of PD-L1, e.g., an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab, durvalumab, or BMS-935559. In some embodiments, the inhibitor of the immune checkpoint molecule is an inhibitor of CTLA-4, e.g., an anti-CTLA-4 antibody. In some embodiments, the anti-CTLA-4 antibody is ipilimumab.

[0529] In some embodiments, the agent is an alkylating agent, a proteasome inhibitor, a corticosteroid, or an immunomodulator. Examples of alkylating agents include cyclophosphamide (CY), melphalan (MEL), and bendamustine. In some embodiments, the proteasome inhibitor is carfilzomib. In some embodiments, the corticosteroid is dexamethasone (DEX). In some embodiments, the immunomodulator is lenalidomide (LEN) or pomalidomide (POM).

[0530] To treat autoimmune or inflammatory conditions, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, can be administered in combination with a corticosteroid (e.g., triamcinolone, dexamethasone, fluocinolone, cortisone, prednisolone, or flumetholone).

[0531] To treat autoimmune or inflammatory conditions, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of Formula I, can be administered in combination with an immunosuppressant, such as fluocinolone acetonide (Retisert®), rimexolone (AL-2178, Vexol, Alcon), or cyclosporine (Restasis®).

[0532] In some embodiments, the crystalline forms provided herein, such as crystalline forms I-XIII of the compound of formula I, are used in the prevention (prophylaxis or prevention) or prophylaxis of a disease, disorder, or condition provided herein. In some embodiments, the crystalline forms are used to prevent the recurrence of a condition or disease provided herein.

[0533] The present disclosure is also directed to the following aspects: Aspect 1. Formula I [ka] A crystalline form of a compound having the formula: Aspect 2. Formula I [ka] A crystalline form of a compound having the formula: Aspect 3. 3. The crystalline form of embodiment 2, wherein crystalline Form I is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.2±0.5 degrees 2θ, about 8.0±0.5 degrees 2θ, about 10.1±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 13.0±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 15.3±0.5 degrees 2θ, about 16.8±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ. Aspect 4. The crystalline form of embodiment 2, wherein crystalline form I is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. Aspect 5. 3. The crystalline form of embodiment 2, wherein crystalline Form I is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.3±0.5 degrees Angstroms, about 11.0±0.5 degrees Angstroms, about 8.7±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.8±0.5 degrees Angstroms, about 5.3±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms. Aspect 6. Formula I [ka] A crystalline form of a compound having the formula: Aspect 7. 7. The crystalline form of embodiment 6, wherein crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.3±0.5 degrees 2θ, about 8.1±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 11.5±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 15.4±0.5 degrees 2θ, about 16.1±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 18.3±0.5 degrees 2θ, about 19.2±0.5 degrees 2θ, about 21.0±0.5 degrees 2θ, about 21.7±0.5 degrees 2θ, about 22.3±0.5 degrees 2θ, and about 23.1±0.5 degrees 2θ. Aspect 8. The crystalline form of embodiment 6, wherein crystalline form II is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. Aspect 9. 7. The crystalline form of embodiment 6, wherein crystalline Form II is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 12.1±0.5 degrees Angstroms, about 10.9±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.7±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, and about 3.8±0.5 degrees Angstroms. Aspect 10. Formula I [ka] and a coformer. Aspect 11. The crystalline form of embodiment 10, wherein the coformer is an acid. Aspect 12. The crystalline form of embodiment 11, wherein the acid is a pharma- ceutically acceptable acid. Aspect 13. The crystalline form of embodiment 12, wherein the pharma- ceutically acceptable acid is selected from succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, and D-(-)-tartaric acid. Aspect 14. Formula I [ka] and succinic acid. Aspect 15. The crystalline form of embodiment 14, wherein the molar ratio of the compound of formula I to succinic acid is about 1:1. Aspect 16. The crystalline form of embodiment 15, wherein the crystalline form is Form III. Aspect 17. Crystalline Form III is at about 5.8±0.5 degrees 2θ, about 8.8±0.5 degrees 2θ, about 10.5±0.5 degrees 2θ, about 12.4±0.5 degrees 2θ, about 14.4±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 17.9±0.5 degrees 2θ, about 18.5±0.5 degrees 2θ, about 19.5±0.5 degrees 2θ, about 20.0±0.5 degrees 2θ, about 20.7±0.5 degrees 2θ, about 21.4±0.5 degrees 2θ, about 22.4±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.5±0.5 degrees 2θ, about 25.5±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, about 27.5±0.5 degrees 2θ, about 28.5±0.5 degrees 2θ, about 29.5±0.5 degrees 2θ, about 30.5±0.5 degrees 2θ, about 31.5±0.5 degrees 2θ, about 32.5±0.5 degrees 2θ, about 33.5±0.5 degrees 2θ, about 34.5±0.5 degrees 2θ, about 35.5±0.5 degrees 2θ, about 36.5±0.5 degrees 2θ, about 37.5±0.5 degrees 2θ, about 38.5±0.5 degrees 2θ, about 39.5±0.5 degrees 2θ, about 40.5±0.5 degrees 2θ, about 41.5±0.5 degrees 2θ, about 42.5±0.5 degrees 2θ, about 43.5±0.5 degrees 17. The crystalline form of embodiment 16, characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 23.6±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.9±0.5 degrees 2θ, about 26.4±0.5 degrees 2θ, about 27.6±0.5 degrees 2θ, about 29.0±0.5 degrees 2θ, about 31.6±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ. Aspect 18. The crystalline form of embodiment 16, wherein crystalline form III is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 12. Aspect 19. Crystalline Form III is preferably from about 15.1±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.1±0.5 degrees Angstroms, about 6.2±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.4±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms 17. The crystalline form of embodiment 16, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.8±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms. Aspect 20. Formula I [ka] and glutaric acid. Aspect 21. 21. The crystalline form of embodiment 20, wherein the molar ratio of the compound of formula I to glutaric acid is about 2:1. Aspect 22. 22. The crystalline form of embodiment 21, wherein the crystalline form is Form IV. Aspect 23. Crystalline form IV has the following properties: about 4.5±0.5 degrees 2θ, about 6.0±0.5 degrees 2θ, about 8.9±0.5 degrees 2θ, about 11.1±0.5 degrees 2θ, about 11.7±0.5 degrees 2θ, about 13.2±0.5 degrees 2θ, about 16.3±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 17.6±0.5 degrees 2θ, about 18.4±0.5 degrees 2θ, about 19.7±0.5 degrees 2θ, and about 20. 23. The crystalline form of embodiment 22, characterized by an X-ray powder diffraction pattern comprising one or more peaks at: about 21.0±0.5 degrees 2θ, about 21.9±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 25.0±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 29.2±0.5 degrees 2θ. Aspect 24. 23. The crystalline form of embodiment 22, wherein crystalline form IV is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. Aspect 25. Crystalline Form IV is about 19.4±0.5 degrees Angstroms, about 14.7±0.5 degrees Angstroms, about 10.0±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 6.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 5.0±0.5 degrees Angstroms, about 4.8±0.5 degrees Angstroms, about 4.5±0.5 degrees Angstroms 23. The crystalline form of embodiment 22, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.1±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.1±0.5 degrees Angstroms. Aspect 26. Formula I [ka] and adipic acid. Aspect 27. 27. The crystalline form of embodiment 26, wherein the molar ratio of the compound of formula I to adipic acid is about 1:1. Aspect 28. 28. The crystalline form of embodiment 27, wherein the crystalline form is form V. Aspect 29. 30. The crystalline form of embodiment 28, wherein crystalline form V is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 4.7±0.5 degrees 2θ, about 7.4±0.5 degrees 2θ, about 9.2±0.5 degrees 2θ, about 11.2±0.5 degrees 2θ, about 13.8±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.1±0.5 degrees 2θ, about 18.9±0.5 degrees 2θ, about 25.1±0.5 degrees 2θ, and about 25.9±0.5 degrees 2θ. Aspect 30. The crystalline form of embodiment 28, wherein crystalline form V is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 24. Aspect 31. 29. The crystalline form of embodiment 28, wherein crystalline form V is characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 18.8±0.5 degrees Angstroms, about 11.9±0.5 degrees Angstroms, about 9.6±0.5 degrees Angstroms, about 7.9±0.5 degrees Angstroms, about 6.4±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, and about 3.4±0.5 degrees Angstroms. Aspect 32. Formula I [ka] and gentisic acid. Aspect 33. The crystalline form according to embodiment 32, wherein the molar ratio of the compound of formula I to gentisic acid is about 2:1. Aspect 34. The crystalline form of embodiment 33, wherein the crystalline form is Form VI. Aspect 35. 35. The crystalline form of embodiment 34, wherein crystalline Form VI is characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 7.4±0.5 degrees 2θ, about 9.5±0.5 degrees 2θ, about 13.6±0.5 degrees 2θ, about 14.7±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 16.4±0.5 degrees 2θ, about 17.2±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 19.4±0.5 degrees 2θ, about 20.5±0.5 degrees 2θ, about 21.5±0.5 degrees 2θ, about 23.5±0.5 degrees 2θ, about 24.8±0.5 degrees 2θ, about 25.7±0.5 degrees 2θ, about 26.9±0.5 degrees 2θ, about 29.4±0.5 degrees 2θ, and about 30.7±0.5 degrees 2θ. Aspect 36. The crystalline form of embodiment 34, wherein crystalline form VI is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 36. Aspect 37. Crystalline Form VI has an average crystallinity of about 12.0±0.5 degrees Angstroms, about 9.3±0.5 degrees Angstroms, about 6.5±0.5 degrees Angstroms, about 6.0±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms 35. The crystalline form of embodiment 34, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.1±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.5±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, and about 2.9±0.5 degrees Angstroms. Aspect 38. Formula I [ka] and fumaric acid. Aspect 39. The crystalline form of embodiment 38, wherein the molar ratio of the compound of formula I to fumaric acid is about 2:1. Aspect 40. The crystalline form of embodiment 39, wherein the crystalline form is a formic acid. Aspect 41. Crystalline Form VII is at about 4.7±0.5 degrees 2θ, about 5.8±0.5 degrees 2θ, about 10.6±0.5 degrees 2θ, about 11.3±0.5 degrees 2θ, about 11.8±0.5 degrees 2θ, about 12.6±0.5 degrees 2θ, about 13.1±0.5 degrees 2θ, about 14.0±0.5 degrees 2θ, about 16.0±0.5 degrees 2θ, about 17.0±0.5 degrees 2θ, about 17.5±0.5 degrees 2θ, about 18. 41. The crystalline form of embodiment 40, characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 0.7±0.5 degrees 2θ, about 19.3±0.5 degrees 2θ, about 21.2±0.5 degrees 2θ, about 22.1±0.5 degrees 2θ, about 24.2±0.5 degrees 2θ, about 24.7±0.5 degrees 2θ, about 26.2±0.5 degrees 2θ, and about 27.4±0.5 degrees 2θ. Aspect 42. The crystalline form according to embodiment 40, wherein crystalline form VII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 30. Aspect 43. Crystalline Form VII has an average molecular weight of about 18.9±0.5 degrees Angstroms, about 15.2±0.5 degrees Angstroms, about 8.4±0.5 degrees Angstroms, about 7.8±0.5 degrees Angstroms, about 7.5±0.5 degrees Angstroms, about 7.0±0.5 degrees Angstroms, about 6.8±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 5.3±0.5 degrees Angstroms, about 5.4±0.5 degrees Angstroms, about 5.5±0.5 degrees Angstroms, about 5.6±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.8±0.5 degrees Angstroms, about 5.9 ... 41. The crystalline form of embodiment 40, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 4.8±0.5 degrees Angstroms, about 4.6±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.6±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, and about 3.2±0.5 degrees Angstroms. Aspect 44. The crystalline form of embodiment 38, wherein the molar ratio of the compound of formula I to fumaric acid is about 1:1. Aspect 45. The crystalline form of embodiment 39, wherein the crystalline form is Form VIII. Aspect 46. Crystalline Form VIII is preferably crystalline or crystalline and has a molecular weight of about 3.9±0.5 degrees 2θ, about 5.7±0.5 degrees 2θ, about 7.1±0.5 degrees 2θ, about 8.6±0.5 degrees 2θ, about 10.3±0.5 degrees 2θ, about 12.1±0.5 degrees 2θ, about 14.1±0.5 degrees 2θ, about 17.1±0.5 degrees 2θ, about 19.1±0.5 degrees 2θ, about 20.6±0.5 degrees 2θ, about 22.2±0.5 degrees 2θ, about 23.0±0.5 degrees 2θ, about 24.0±0.5 degrees 2θ, about 25.0±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 27.0±0.5 degrees 2θ, about 28.0±0.5 degrees 2θ, about 29.0±0.5 degrees 2θ, about 30.0±0.5 degrees 2θ, about 31.0±0.5 degrees 2θ, about 32.0±0.5 degrees 2θ, about 33.0±0.5 degrees 2θ, about 34.0±0.5 degrees 2θ, about 35.0±0.5 degrees 2θ, about 36.0±0.5 degrees 2θ, about 37.0±0.5 degrees 2θ, about 38.0±0.5 degrees 2θ, about 39.0±0.5 degrees 2θ, about 40.0±0.5 degrees 2θ, about 41.0±0.5 degrees 2θ, about 42.0±0.5 degrees 2θ, about 43.0±0.5 degrees 2θ, about 44.0±0.5 degrees 2θ, about 46. ​​The crystalline form of embodiment 45, characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 24.3±0.5 degrees 2θ, about 26.0±0.5 degrees 2θ, about 26.5±0.5 degrees 2θ, about 28.5±0.5 degrees 2θ, about 34.6±0.5 degrees 2θ, about 35.4±0.5 degrees 2θ, about 36.8±0.5 degrees 2θ, and about 39.5±0.5 degrees 2θ. Aspect 47. The crystalline form of embodiment 45, wherein crystalline form VIII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 42. Aspect 48. Crystalline Form VIII is preferably from about 22.5±0.5 degrees Angstroms, about 15.5±0.5 degrees Angstroms, about 12.5±0.5 degrees Angstroms, about 10.3±0.5 degrees Angstroms, about 8.6±0.5 degrees Angstroms, about 7.3±0.5 degrees Angstroms, about 6.3±0.5 degrees Angstroms, about 5.2±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, about 4.0±0.5 degrees Angstroms, about 5 ... 46. ​​The crystalline form of embodiment 45, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 0.9±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.4±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms. Aspect 49. Formula I [ka] and D-(-)-tartaric acid. Aspect 50. The crystalline form of embodiment 49, wherein the molar ratio of the compound of formula I to D-(-)-tartaric acid is about 1:1. Aspect 51. The crystalline form of embodiment 50, wherein the crystalline form is Form IX. Aspect 52. Crystalline Form IX is at about 5.3±0.5 degrees 2θ, about 6.8±0.5 degrees 2θ, about 9.0±0.5 degrees 2θ, about 10.0±0.5 degrees 2θ, about 15.5±0.5 degrees 2θ, about 17.3±0.5 degrees 2θ, about 18.2±0.5 degrees 2θ, about 18.8±0.5 degrees 2θ, about 19.9±0.5 degrees 2θ, about 20.9±0.5 degrees 2θ, about 21.3±0.5 degrees 2θ, about 22.7±0.5 degrees 2θ, about 23.6±0.5 degrees 2θ, about 24.3±0.5 degrees 2θ, and about 25. 52. The crystalline form of embodiment 51, characterized by an X-ray powder diffraction pattern comprising one or more peaks at about 26.0±0.5 degrees 2θ, about 27.1±0.5 degrees 2θ, about 28.0±0.5 degrees 2θ, about 28.8±0.5 degrees 2θ, about 29.8±0.5 degrees 2θ, about 33.4±0.5 degrees 2θ, about 34.2±0.5 degrees 2θ, about 36.3±0.5 degrees 2θ, about 38.6±0.5 degrees 2θ, and about 39.1±0.5 degrees 2θ. Aspect 53. 52. The crystalline form of embodiment 51, wherein crystalline form IX is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 46. Aspect 54. Crystalline Form IX is preferably from about 16.7±0.5 degrees Angstroms, about 12.9±0.5 degrees Angstroms, about 9.8±0.5 degrees Angstroms, about 8.8±0.5 degrees Angstroms, about 5.7±0.5 degrees Angstroms, about 5.1±0.5 degrees Angstroms, about 4.9±0.5 degrees Angstroms, about 4.7±0.5 degrees Angstroms, about 4.5±0.5 degrees Angstroms, about 4.3±0.5 degrees Angstroms, about 4.2±0.5 degrees Angstroms, about 3.9±0.5 degrees Angstroms, about 3.8±0.5 degrees Angstroms, about 3.7±0.5 degrees Angstroms 52. The crystalline form of embodiment 51, characterized by an X-ray powder diffraction pattern comprising one or more d-spacing values ​​of about 3.5±0.5 degrees Angstroms, about 3.4±0.5 degrees Angstroms, about 3.3±0.5 degrees Angstroms, about 3.2±0.5 degrees Angstroms, about 3.1±0.5 degrees Angstroms, about 3.0±0.5 degrees Angstroms, about 2.7±0.5 degrees Angstroms, about 2.6±0.5 degrees Angstroms, about 2.5±0.5 degrees Angstroms, about 2.3±0.5 degrees Angstroms, and about 2.3±0.5 degrees Angstroms. Aspect 55. Formula I [ka] and hydrochloric acid. Aspect 56. 56. The crystalline form of embodiment 55, wherein the crystalline form is form X. Aspect 57. 57. The crystalline form of embodiment 56, wherein crystalline form X is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 50. Aspect 58. Formula I [ka] and salicylic acid. Aspect 59. 59. The crystalline form of embodiment 58, wherein the molar ratio of the compound of formula I to salicylic acid is about 2:1. Aspect 60. The crystalline form according to embodiment 59, wherein the crystalline form is form XI. Aspect 61. The crystalline form of embodiment 60, wherein crystalline form XI is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 52. Aspect 62. Formula I [ka] and oxalic acid. Aspect 63. The crystalline form of embodiment 62, wherein the molar ratio of the compound of formula I to oxalic acid is about 1:1. Aspect 64. The crystalline form according to embodiment 63, wherein the crystalline form is form XII. Aspect 65. The crystalline form of embodiment 64, wherein crystalline form XII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 54. Aspect 66. Formula I [ka] and 1-hydroxy-2-naphthoic acid. Aspect 67. The crystalline form of embodiment 66, wherein the crystalline form is Form XIII. Aspect 68. 68. The crystalline form of embodiment 67, wherein crystalline form XIII is characterized by an X-ray powder diffraction pattern comprising one or more peaks as shown in FIG. 59. Aspect 69. A pharmaceutical composition comprising a crystalline form according to any one of aspects 1 to 68. Aspect 70. A pharmaceutical composition comprising crystalline form I according to any one of aspects 2 to 5. Aspect 71. A pharmaceutical composition comprising crystalline form II according to any one of aspects 6 to 9. Aspect 72. 20. A pharmaceutical composition comprising crystalline form III according to any one of aspects 16 to 19. Aspect 73. 26. A pharmaceutical composition comprising crystalline form IV according to any one of aspects 22 to 25. Aspect 74. A pharmaceutical composition comprising crystalline form V according to any one of aspects 28 to 31. Aspect 75. 38. A pharmaceutical composition comprising crystalline form VI according to any one of aspects 34 to 37. Aspect 76. A pharmaceutical composition comprising crystalline form VII according to any one of aspects 40 to 43. Aspect 77. 49. A pharmaceutical composition comprising crystalline form VIII according to any one of aspects 45 to 48. Aspect 78. 55. A pharmaceutical composition comprising crystalline form IX according to any one of aspects 51 to 54. Aspect 79. 58. A pharmaceutical composition comprising crystalline form X according to any one of aspects 56 to 57. Aspect 80. 62. A pharmaceutical composition comprising crystalline form XI according to any one of aspects 60-61. Aspect 81. A pharmaceutical composition comprising crystalline form XII according to any one of aspects 64-65. Aspect 82. 69. A pharmaceutical composition comprising crystalline form XIII according to any one of aspects 67-68. Aspect 83. 83. The pharmaceutical composition according to any one of aspects 69 to 82, further comprising a pharma- ceutically acceptable excipient. Aspect 84. Formula I [ka] to form a crystalline form, and optionally isolating the crystalline form. Aspect 85. The method of embodiment 84, wherein the crystallizing comprises dissolving the compound of formula I in an organic solvent and crystallizing the compound of formula I to form crystalline Form I or Form II therefrom. Aspect 86. 85. The method of embodiment 84, wherein the crystallizing comprises dissolving the compound of formula I in an organic solvent with a pharma- ceutically acceptable acid, and crystallizing the compound of formula I to form any one of crystalline Forms III-XIII therefrom. Aspect 87. The method of embodiment 86, wherein the pharma- ceutically acceptable acid is selected from succinic acid, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, and D-(-)-tartaric acid. Aspect 88. 85. The method of embodiment 84, wherein the crystallizing comprises dissolving the compound of formula I in an organic solvent with succinic acid and crystallizing the compound of formula I to form crystalline Form III therefrom. Aspect 89. 89. The method of any one of aspects 85 to 88, wherein the organic solvent is selected from the group consisting of acetonitrile, n-butanol, methyl ethyl ketone, methanol, ethyl acetate, acetone, tetrahydrofuran, 2-propanol, ethanol, isopropyl acetate, toluene, cyclohexane, dichloromethane, chloroform, HO, nitromethane, n-pentane, n-hexane, 1-propanol, methyl acetate, ethyl ether, octane, and any combination thereof. Aspect 90. The method of embodiment 85, wherein the solvent is acetonitrile. Aspect 91. The method of embodiment 88, wherein the solvent is ethyl acetate. Aspect 92. A method for inhibiting a CDK enzyme, the method comprising contacting the CDK enzyme with an effective amount of a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 93. 93. The method of embodiment 92, wherein the CDK enzyme is CDK9. Aspect 94. A method for treating a disease or disorder associated with abnormal CDK activity in a subject or in a subject in need thereof, comprising administering to the subject a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 95. 95. The method of embodiment 94, wherein the disease or disorder associated with abnormal CDK activity is colon cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer. Aspect 96. A method of treating cancer in a subject or a subject in need thereof, comprising administering to the subject a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 97. 97. The method of embodiment 96, wherein the cancer is colon cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphocytic leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer. Aspect 98. A method for inducing apoptosis in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting said cancer or tumor cells with or administering to said subject an effective amount of a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 99. A method for inhibiting phosphorylation of Ser2RNAP2 in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form described in any one of aspects 1 to 68, a pharmaceutical composition described in any one of aspects 69 to 83, or a crystalline form prepared according to the method described in any one of aspects 84 to 91. Aspect 100. A method for reducing a level of induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 101. A method for reducing the level of MYC protein in cancer or tumor cells in a subject or a subject in need thereof, comprising contacting the cancer or tumor cells with or administering to the subject an effective amount of a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 102. A method for inhibiting the proliferation of cancer or tumor cells in a subject or a subject in need thereof, comprising contacting said cancer or tumor cells with, or administering to said subject, an effective amount of a crystalline form according to any one of aspects 1 to 68, a pharmaceutical composition according to any one of aspects 69 to 83, or a crystalline form prepared according to the method according to any one of aspects 84 to 91. Aspect 103. The method of any one of embodiments 98 to 102, wherein the cancer or tumor has high levels of MYC amplification and overexpression. Aspect 104. The method according to any one of aspects 98 to 103, wherein the cancer cells are malignant. Aspect 105. 104. The method according to any one of aspects 98 to 103, wherein the cancer cells are blood cancer cells. Aspect 106. The method of embodiment 105, wherein the hematological cancer is B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia (AML), non-Hodgkin's lymphoma, sarcoma, prostate, adenoid cystic carcinoma (ACC), or non-small cell lung cancer (NSCLC). Aspect 107. 103. The method according to any one of aspects 98 to 102, wherein the tumor cells are from a solid tumor. Aspect 108. The method of embodiment 106, wherein the solid tumor is pancreatic cancer, gastric and gastroesophageal cancer, NSCLC, or sarcoma. Aspect 109. 109. The method of embodiment 107 or 108, further comprising contacting the tumor cells with a targeted therapy. Aspect 110. The method of embodiment 109, wherein the targeted therapy is a BCL2 inhibitor. Aspect 111. The method of embodiment 110, wherein the BCL2 inhibitor is venetoclax. Aspect 112. 112. The method according to any one of aspects 109 to 111, wherein complete tumor regression is achieved.

[0534] The following examples are illustrative, but not limiting, of the methods, crystalline forms, and pharmaceutical compositions described herein. Other suitable modifications and adaptations of the variety of conditions and parameters normally encountered in the therapeutic, synthetic, and other embodiments disclosed herein are within the spirit and scope of the embodiments. EXAMPLES

[0535] Example 1 Preparation of Crystalline Form I of the Compound of Formula I Crystalline Form I of the compound of formula I was prepared according to the procedures described herein. Single crystalline Form I of the compound of formula I was obtained by the following procedure. [Table 1]

[0536] DSC analysis of this sample shows melting beginning at about 165°C as shown in Figure 3. TGA analysis of crystalline form I shows decomposition occurring after 176°C as shown in Figure 4. TGA analysis shows decomposition begins between 100°C and 125°C. Figure 5 shows 1 H NMR analysis indicates that crystalline Form I contains only the compound of formula I, confirming that crystalline Form I is greater than 99% pure based on HPLC analysis. Figure 1 shows the amorphous X-ray powder diffraction pattern of the compound of formula I.

[0537] Example 2 Preparation of Crystalline Form I of the Compound of Formula I Crystalline Form I of the compound of formula I was also prepared according to the procedures described herein. Single crystalline Form I of the compound of formula I was obtained by the following procedure. [Table 2]

[0538] Figure 10 shows 1 H NMR analysis indicates that crystalline form I contains only the compound of formula I, confirming that crystalline form I is >99% pure based on HPLC analysis. Figure 11 shows the X-ray powder diffraction pattern of crystalline form I, which matches the diffraction pattern shown in Figure 2. Figure 11 shows the X-ray powder diffraction pattern of crystalline form I. Peak positions for crystalline form I are provided in Table 1. [Table 3]

[0539] Example 3 Preparation of Crystalline Form II of the Compound of Formula I Crystalline Form II of the compound of formula I was prepared according to the procedures described herein. Single crystalline Form II of the compound of formula I was obtained by the following procedure. [Table 4]

[0540] DSC analysis of this sample shows melting beginning at about 175° C. as shown in FIG. 7. TGA analysis of crystalline Form II shows decomposition occurring after 176° C. as shown in FIG. 8. TGA analysis shows decomposition begins between 120° C. and 140° C. FIG. 9 shows 1 H NMR analysis indicates that crystalline form II contains only the compound of formula I, confirming that crystalline form II is over 99% pure based on HPLC analysis. Figure 6 shows the X-ray powder diffraction pattern of crystalline form II. Peak positions for crystalline form II are provided in Table 2. [Table 5]

[0541] Example 4 Salt Screening of Compounds of Formula I Salt screening of the compound of formula I with coformers was performed through the procedure described herein. Pharmaceutically acceptable acids (including HCl, H2SO4, HBr, H3PO4) were used for salt screening, as shown in Table 3. As shown in Table 3, crystalline solids of the compound of formula I were obtained by mixing 0.05 mmol of the compound of formula I in the free base (23.8 mg) with 1.05 to 1.10 equivalents of the acid, respectively, succinate, adipic acid, fumaric acid, glutaric acid, gentisic acid, hydrochloric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, oxalic acid, and D-(-)-tartaric acid. [Table 6]

[0542] Example 5 Solvent Selection for Crystallizing Compounds of Formula I and Pharmaceutically Acceptable Salts Ten solvents were tested for salt formation of the compound of formula I with pharma- ceutically acceptable acids, as shown in Table 4. The compound of formula I and each acid mixture shown in Table 4 were individually screened against the list of solvents listed in Table 4, and the results are shown in Table 4. [Table 7]

[0543] Example 6 Preparation of Crystalline Form III of the Compound of Formula I and Succinic Acid The compound of formula I and crystalline form III of succinic acid were obtained according to the following procedure. [Table 8]

[0544] The crystallinity of crystalline Form III was confirmed by XPRD, as shown in Figure 12. Its DSC and TGA are shown in Figures 13 and 14, respectively. The HPLC purity of the salt was 99.2% (Figure 15). 1 H NMR spectrum (Figure 16) and the compound of formula I 1 This is supported by comparison with H NMR (Figure 17). The NMR of the compound of formula I (Figure 17) shows a clear peak for the NH attached to the pyridine ring at about 10.5 ppm. To determine the stoichiometry of succinic acid to the compound of formula I, the NMR signals at about 2.4 ppm (CH of succinic acid), about 12.1 ppm (COOH of succinic acid), and about 10.5 ppm (NH attached to the pyridine ring of the compound of formula I) are used. Quantitative determination of the salt 1 The H NMR spectrum (Figure 16) showed that the stoichiometry of the compound of formula I and succinic acid was 1:1. Figure 12 shows the X-ray powder diffraction pattern of crystalline Form III. The peak positions of crystalline Form III are provided in Table 5. [Table 9]

[0545] Example 7 Preparation of Crystalline Form IV of the Compound of Formula I and Glutaric Acid The crystalline form IV of the compound of formula I and glutaric acid was obtained according to the following procedure. [Table 10]

[0546] The crystallinity of crystalline Form IV was confirmed by XPRD, as shown in Figure 18. Its DSC and TGA are shown in Figures 19 and 20, respectively. The HPLC purity of the salt was 99.0% (Figure 21). 1 H NMR spectrum (Figure 22) and the compound of formula I 1 This is supported by comparison with H NMR (Figure 23). The NMR of the compound of formula I (Figure 23) shows a clear peak for the NH attached to the pyridine ring at about 10.5 ppm. To determine the stoichiometry of glutaric acid to the compound of formula I, the NMR signals at about 12.1 ppm (COOH of glutaric acid) and about 10.5 ppm (NH attached to the pyridine ring of the compound of formula I) are used. Quantitative analysis of the salts 1 The H NMR spectrum (Figure 22) showed that the stoichiometry of the compound of formula I and glutaric acid was 2:1. Figure 18 shows the X-ray powder diffraction pattern of crystalline form IV. The peak positions of crystalline form IV are provided in Table 6. [Table 11]

[0547] Example 8 Preparation of Crystalline Form V of the Compound of Formula I and Adipic Acid The compound of formula I and crystalline form V of adipic acid were obtained according to the following procedure. [Table 12]

[0548] The crystallinity of crystalline form V was confirmed by XPRD, as shown in Figure 24. Its DSC and TGA are shown in Figures 25 and 26, respectively. The HPLC purity of the salt was 99.2% (Figure 27). 1 H NMR spectrum (Figure 28) and the compound of formula I 1 This is supported by comparison with H NMR (Figure 29). The NMR of the compound of formula I (Figure 29) shows a clear peak for the NH attached to the pyridine ring at about 10.5 ppm. To determine the stoichiometry of adipic acid to the compound of formula I, the NMR signals at about 12.0 ppm (COOH of adipic acid) and about 10.5 ppm (NH attached to the pyridine ring of the compound of formula I) are used. Quantitative analysis of the salts 1 The H NMR spectrum (Figure 28) showed that the stoichiometry of the compound of formula I and adipic acid was 1:1. Figure 24 shows the X-ray powder diffraction pattern of crystalline form V. The peak positions of crystalline form V are provided in Table 7. [Table 13]

[0549] Example 9 Preparation of the compound of formula I and crystalline form VI of gentisic acid The compound of formula I and crystalline form VI of gentisic acid were obtained according to the following procedure. [Table 14]

[0550] The crystallinity of crystalline Form VI was confirmed by XPRD, as shown in Figure 30. Its DSC and TGA are shown in Figures 31 and 32, respectively. The HPLC purity of the salt was 99.4% (Figure 33). 1 H NMR spectrum (Figure 34) and the compound of formula I 1This is supported by comparison with H NMR (Figure 35). The NMR of the compound of formula I (Figure 34) shows a clear peak for the NH attached to the pyridine ring at about 10.5 ppm. To determine the stoichiometry of fumaric acid to the compound of formula I, the NMR signals at about 6.8, 6.9, 7.2 ppm (the three hydrogens on the phenyl ring of fumaric acid), and about 10.5 ppm (NH attached to the pyridine ring of the compound of formula I) are used. Quantitative analysis of the salts 1 The H NMR spectrum (Figure 34) showed that the stoichiometry of the compound of formula I and gentisic acid was 1:1. Figure 30 shows the X-ray powder diffraction pattern of crystalline Form VI. The peak positions of crystalline Form VI are provided in Table 8. [Table 15]

[0551] Example 10 Preparation of Crystalline Form VII from the Compound of Formula I and Fumaric Acid in a 2:1 Molar Ratio Crystalline Form VII of the compound of formula I and fumaric acid was obtained according to the following procedure. [Table 16]

[0552] The crystallinity of crystalline Form VII was confirmed by XPRD, as shown in Figure 36. Its DSC and TGA are shown in Figures 37 and 38, respectively. The HPLC purity of the salt was 98.6% (Figure 39). 1 H NMR spectrum (Figure 40) and the compound of formula I 1 This is supported by comparison with H NMR (Figure 41). The NMR of the compound of formula I (Figure 40) shows a clear peak for the NH attached to the pyridine ring at about 10.5 ppm. To determine the stoichiometry of fumaric acid to the compound of formula I, the NMR signals at about 13.1 ppm (COOH of fumaric acid) and about 10.5 ppm (NH attached to the pyridine ring of the compound of formula I) are used. Quantitative analysis of the salts 1The H NMR spectrum (Figure 40) showed a stoichiometry / molar ratio of the compound of formula I to fumaric acid of 2:1. Figure 36 shows the X-ray powder diffraction pattern of crystalline Form VII. The peak positions of crystalline Form VII are provided in Table 9. [Table 17]

[0553] Example 11 Preparation of Crystalline Form VIII with 1:1 Molar Ratio of Compound of Formula I and Fumaric Acid Crystalline Form VIII of the compound of formula I and fumaric acid was obtained according to the following procedure. [Table 18]

[0554] The crystallinity of crystalline Form VIII was confirmed by XPRD as shown in Figure 42 and further supported by DSC (Figure 43), which showed the salt with an onset temperature of 211.7°C and a peak at 215.8°C, and TGA (Figure 44). The stoichiometry / molar ratio of crystalline Form VIII between the compound of formula I in the free base and fumaric acid was calculated as: 1 The 1:1 ratio was determined by 1 H NMR (Figure 45). HPLC purity of the salt was 1 The stoichiometry of fumaric acid relative to the compound of formula I was 98.2%, as shown below (Figure 45), which is supported by the H NMR spectrum. The NMR signals at about 6.63 ppm (CH of fumaric acid) and about 10.5 ppm (NH, attached to the pyridine ring of the compound of formula I) are used to determine the stoichiometry of fumaric acid relative to the compound of formula I. [Table 19] Quantitative salt content 1 The H NMR spectrum (Figure 45) showed that the stoichiometry of the compound of formula I and fumaric acid was 1:1. Figure 42 shows the X-ray powder diffraction pattern of crystalline Form VIII. The peak positions of crystalline Form VIII are provided in Table 10. [Table 20]

[0555] Example 12 Preparation of Crystalline Form IX of the Compound of Formula I and D-(-)-Tartaric Acid The compound of formula I and crystalline form IX of D-(-)-tartaric acid were obtained according to the following procedure. [Table 21]

[0556] The crystallinity of crystalline Form IX was confirmed by XPRD as shown in Figure 46, and further supported by DSC (Figure 47), which showed the salt with an onset temperature of 133.3°C and a peak at 139.8°C, and TGA (Figure 48). [Table 22] The stoichiometric ratio of the compound of formula I in the free base and D-(-)-tartaric acid in crystalline form IX is 1 The 1:1 ratio was determined by 1 H NMR (Figure 49). HPLC purity of the salt was 1 The NMR signals at about 6.63 ppm (CH of fumaric acid) and about 10.5 ppm (NH, attached to the pyridine ring of the compound of Formula I) are used to determine the stoichiometry of the fumaric acid relative to the compound of Formula I. 1 The H NMR spectrum (Figure 49) showed that the stoichiometry of the compound of formula I and fumaric acid was 1:1. Figure 46 shows the X-ray powder diffraction pattern of crystalline Form IX. The peak positions of crystalline Form IX are provided in Table 11. [Table 23]

[0557] Example 13 Preparation of Crystalline Form X of the Compound of Formula I and Hydrochloric Acid The compound of formula I and crystalline form X of hydrochloric acid were obtained according to the procedures described herein. The compound of formula I was mixed with n-propanol, 2-butanone (MEK, methyl ethyl ketone), and hydrochloric acid in n-butanol, respectively, to obtain crystalline form X in about 30% yield. The crystallinity of crystalline form X was confirmed by XPRD as shown in Figure 50 and further supported by DSC (Figure 51) which showed the salt with an onset temperature of 160.57°C and a peak at 176.99°C. The HPLC purity of the salt was 98.2% as shown below. [Table 24]

[0558] Example 14 Preparation of the Compound of Formula I and Crystalline Form XI of Salicylic Acid [Table 25] The compound of formula I and crystalline form XI of salicylic acid were obtained according to the procedure described herein. The compound of formula I was reacted with salicylic acid in 2-propanol to obtain crystalline form XI. The crystallinity of crystalline form XI was confirmed by XPRD, as shown in Figure 52. To determine the stoichiometric ratio of fumaric acid to the compound of formula I, the NMR signal at about 7.8 ppm (CH on the phenyl ring of salicylic acid) is used, as shown in Figure 53. Quantitative analysis of the salts 1 The 1 H NMR spectrum (Figure 53) showed a 2:1 stoichiometry of the compound of formula I and salicylic acid.

[0559] Example 15 Preparation of Crystalline Form XII of the Compound of Formula I and Oxalic Acid Crystalline form XII of the compound of formula I and oxalic acid was obtained according to the procedures described herein. The compound of formula I was reacted with oxalic acid in 2-butanone (MEK) to obtain crystalline form XII in about 70% yield. The crystallinity of crystalline form XII was confirmed by XPRD as shown in Figure 54 and further supported by DSC (Figure 55) which showed the salt with an onset temperature of 144.6°C and a peak at 157.7°C. The structure is: 1 H NMR (Figure 57) and13 It was characterized by C NMR (Figure 58) and the purity was analyzed by HPLC (Figure 56). Elemental analysis was used to determine the stoichiometry of the compound of formula I to oxalic acid. The results of elemental analysis showed that crystalline form XII is a mono-oxalate hydrate: Elemental Analysis: C 28 H 31 Calculated for FN6O6.H2O: C, 57.53; H, 5.69; N, 14.38. Found: C, 57.32; H, 5.41; N, 13.77. The results indicated that the stoichiometry of the compound of formula I to oxalic acid in crystalline form XII was 1:1.

[0560] Example 16 Preparation of the compound of formula I and crystalline form XIII of 1-hydroxy-2-naphthoic acid The compound of formula I and crystalline form XIII of 1-hydroxy-2-naphthoic acid were obtained according to the procedure described herein. The compound of formula I was reacted with 1-hydroxy-2-naphthoic acid in methanol to obtain crystalline form XIII. The crystallinity of crystalline form XIII was confirmed by XPRD, as shown in Figure 59.

[0561] Example 17 XRPD analysis X-ray powder diffraction (XRPD) measurements were performed using a Rigaku MiniFlex X-ray powder diffractometer (XRPD) instrument. The general experimental procedure for XRPD was as follows: (1) 1.54056 Å X-rays were emitted from copper using a K filter, (2) X-rays were output at 30 KV and 15 mA, and (3) the sample powder was dispersed on a zero-background sample holder. The general measurement conditions for XRPD were as follows: start angle 3 degrees, stop angle 45 degrees, sampling 0.02 degrees, and scan speed 2 degrees / min.

[0562] Example 18 Differential Scanning Calorimetry (DSC) The crystalline form of the compound of formula I was analyzed using differential scanning calorimetry. DSC Measurements Differential scanning calorimetry (DSC) was performed on a TA Instruments Differential Scanning Calorimetry, Model Q200 equipped with an autosampler. DSC instrument conditions were as follows: 20-300°C at 10°C / min, Tzero aluminum sample pan and lid, and nitrogen gas flow at 50 mL / min.

[0563] Example 19 Thermogravimetric Analysis (TGA) Thermogram The crystalline form of the compound of formula I was analyzed using a TA Instruments thermogravimetric analyzer, TGA Q500, equipped with an autosampler. The general experimental conditions for the TGA were: 25°C to 600°C at 20°C / min, nitrogen purge, gas flow 25mL / min, platinum sample pan.

[0564] Example 20 High-performance liquid chromatography (HPLC) The crystalline forms of the compound of formula I were analyzed for their purity by high performance liquid chromatography. The general experimental conditions for HPLC are as follows: [Table 26] [Table 27]

Claims

[Claim 1] The invention as described herein or in the drawings.

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