Solid Forms of Dual RAF / MEK Inhibitors

Abstract

Solid forms of dual RAF / MEK inhibitors, pharmaceutical compositions thereof, oral dosage forms thereof, and methods of treating cancer are described herein. Also provided herein are processes for preparing solid forms of dual RAF / MEK inhibitors and pharmaceutical compositions and oral dosage forms thereof. In one aspect, a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of crystalline form 1 of a compound of formula II described herein, or a pharmaceutical composition or oral dosage form described herein, is provided herein.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 349,815, filed on June 7, 2022, and U.S. Non - Provisional Patent Application No. 18 / 147,921, filed on December 29, 2022, the entire contents of which are incorporated herein by reference.

Background Art

[0002] Background Components of the RAS / RAF / MEK / ERK (MAPK) signaling pathway present opportunities to treat abnormal cell growth, such as cancer. For example, mutations in RAS / RAF / MEK / ERK are found frequently in human cancers. These mutants result in constitutively active MAPK kinase cascades, leading to tumor cell proliferation, differentiation, survival, and migration. Selective inhibitors of certain components of the RAS / RAF / MEK / ERK signaling pathway, such as RAS, RAF, MEK, and ERK, are useful in treating abnormal cell growth in mammals, particularly cancer.

[0003] Due to the severity and breadth of diseases and disorders associated with abnormal cell growth (e.g., cancer), effective treatment means and methods of treatment are needed. The present disclosure relates to compounds of formula I, or solid forms of pharmaceutically acceptable salts thereof (e.g., compounds of formula II), their pharmaceutical compositions and oral dosage forms, processes for preparing them, and methods for using them, thereby addressing the need and providing exemplary advantages.

Summary of the Invention

Means for Solving the Problems

[0004] Summary This specification describes, in part, solid forms of dual RAF / MEK inhibitors (e.g., compounds of Formula II), pharmaceutical compositions and oral dosage forms thereof, methods of treating cancer, and processes for preparing solid forms of dual RAF / MEK inhibitors (e.g., compounds of Formula II), as well as pharmaceutical compositions and oral dosage forms thereof.

[0005] In one aspect, Formula II:

Chemical formula

[0006] In another aspect, Formula II:

Chemical formula

[0007] In another aspect, Formula II:

Chemical formula

[0008] In another aspect, Formula II:

Chemical formula

[0009] In another aspect, Formula II:

Chem.

[0010] In one aspect, Formula II:

Chem.

Chem.

[0011] In one aspect, there is provided herein a pharmaceutical composition comprising crystalline form 1 of a compound of Formula II described herein and a pharmaceutically acceptable carrier.

[0012] In one aspect, there is provided herein a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of crystalline form 1 of a compound of Formula II described herein, or a pharmaceutical composition or oral dosage form described herein. BRIEF DESCRIPTION OF THE DRAWINGS

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[0045] Detailed Description The present disclosure provides, in part, solid forms of dual RAF / MEK inhibitors (e.g., compounds of Formula II), pharmaceutical compositions and oral dosage forms thereof, methods of treating cancer, and processes for preparing solid forms of dual RAF / MEK inhibitors (e.g., compounds of Formula II), and pharmaceutical compositions and oral dosage forms thereof. Definitions

[0046] "About" and "approximately" generally mean the degree of error tolerated for a measured quantity, taking into account the nature or precision of the measurement. Exemplary degrees of error are within 20 percent (%), typically within 10%, more typically within 5% of a given value or range of values.

[0047] As used herein, "pharmaceutically acceptable salts" refer to salts that, within the scope of sound medical judgment, are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, etc., and that have a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1-19. The pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts of amino groups formed using inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, laurylsulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. Pharmaceutically acceptable salts derived from appropriate bases include alkali metals, alkaline earth metals, ammonium, and N + (C 1~4The (alkyl)4 salt is included. Representative alkali metal salts or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, where appropriate, non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0048] As used herein, "pharmaceutically acceptable carrier" refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound being formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that can be used in the compositions described herein include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffering substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol, and lanolin.

[0049] As used herein, "subject" to which administration is contemplated includes, but is not limited to, humans (i.e., males or females of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults or elderly adults)) or non-human animals such as mammals including primates (e.g., cynomolgus monkeys, rhesus monkeys), cows, pigs, horses, sheep, goats, rodents, cats, or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human", "patient", and "subject" are used interchangeably herein.

[0050] Diseases, disorders, and conditions are used interchangeably herein.

[0051] As used herein, unless otherwise specified, the terms "treating," "treatment," and "treat" are intended to mean an action taken while a patient is suffering from a particular disease, disorder, or condition that reduces the severity of, or delays or slows the progression of, the disease, disorder, or condition (also referred to as "therapeutic treatment").

[0052] Generally, an "effective amount" of a compound refers to an amount sufficient to elicit a desired biological response. As will be recognized by those of skill in the art, the effective amount of a compound of the present invention can vary depending on the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and factors such as the age, weight, health, and condition of the subject.

[0053] As used herein, unless otherwise specified, a "therapeutically effective amount" of a compound is an amount sufficient to provide a therapeutic benefit in the treatment of a disease, disorder, or condition, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition. A therapeutically effective amount of a compound means the amount of a therapeutic agent that provides a therapeutic benefit in the treatment of a disease, disorder, or condition, either alone or in combination with other treatments. The term "therapeutically effective amount" can include an amount that improves the overall treatment, reduces or avoids the symptoms or causes of a disease or condition, or enhances the therapeutic effectiveness of another therapeutic agent.

[0054] As used herein, "preventive treatment" is intended to mean an action taken before a subject begins to suffer from a particular disease, disorder, or condition.

[0055] As used herein, unless otherwise specified, a "prophylactically effective amount" of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or to prevent its recurrence. A prophylactically effective amount of a compound means the amount of a therapeutic agent, alone or in combination with other agents, that provides a prophylactic benefit in preventing a disease, disorder or condition. The term "prophylactically effective amount" can include an amount that improves prophylaxis overall or enhances the prophylactic effectiveness of another prophylactic agent.

[0056] The term "oral dosage form", as used herein, refers to a composition or medium used for administering an agent to a subject. Typically, an oral dosage form is administered via the mouth, but the term "oral dosage form" is intended to encompass any substance that is administered to a subject and absorbed across a membrane of the gastrointestinal tract, such as the mucosa, including the mouth, esophagus, stomach, small intestine, large intestine, and colon. For example, an "oral dosage form" encompasses a solution administered via a feeding tube to the stomach.

[0057] As used herein in the context of a cycle of drug administration, a "cycle" refers to the period during which a drug is administered to a patient. In some embodiments, one cycle is four weeks.

[0058] As used herein, the term "isolated" or "isolating" includes, but is not limited to, the act of obtaining one or more compounds by collecting them during or after the process steps disclosed herein, and the act of obtaining one or more compounds by separating them from one or more other chemical entities during or after the process steps disclosed herein.

[0059] The term "collection" or "collecting" refers to any act(s) known in the art for this purpose, including, but not limited to, decanting a mother liquor from a solid to obtain one or more compounds, and evaporating a liquid medium in a solution or other mixture to obtain a solid, oil, or other residue containing one or more compounds. The solid can be crystalline, semi-crystalline, amorphous, containing one or more solid forms, and among other characteristics known in the art, can be of various particle sizes, various surface areas, powders or granules of uniform particle size. The oil can, among other characteristics known in the art, have different colors and viscosities and can contain one or more solid forms as a non-uniform mixture.

[0060] The term "separation" or "separating" refers to any act(s) known in the art for this purpose, including, but not limited to, crystallization or other precipitation techniques (e.g., adding a poor solvent to a solution to induce precipitation of a compound; heating and then cooling a solution to induce precipitation of a compound; scratching the surface of a solution with an instrument to induce precipitation of a compound), with or without seed crystals, and distillation techniques, to isolate one or more compounds from a solution or mixture.

[0061] Isolating one or more compounds can include preparing salts, solvates, or hydrates of those compounds, mixtures thereof, and then collecting or separating as described above.

[0062] As used herein, unless otherwise specified, "polymorph" describes a crystalline substance of a compound that can exist in two or more crystal structures, e.g., crystal forms.

[0063] The compounds of the present disclosure include crystalline and amorphous forms of the compounds, including, for example, solvates, hydrates, co-crystals, non-solvated forms (including anhydrates), conformational forms, tautomeric forms, or their disordered crystal forms, and mixtures thereof.

[0064] As used herein, unless otherwise specified, a particular form of a compound of Formula II described herein means, inter alia, a solid form of a compound of Formula II, or a salt, solvate or hydrate thereof.

[0065] As used herein, unless otherwise specified, the term "crystalline" when used to describe a substance, component, or product means that the substance, component, or product is substantially crystalline as determined, for example, by X-ray diffraction. See, e.g., Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, 21 st ed. (2005). Crystalline substances, components, or products have a very regular chemical structure. Molecules are arranged in a regular periodic manner in the three-dimensional space of the crystal lattice.

[0066] As used herein, unless otherwise specified, the terms "crystalline form", "crystal form", and related terms herein refer to various crystalline substances including a given substance, which include crystalline forms of single components and crystalline forms of multiple components, and include, but are not limited to, polymorphs, solvates, hydrates, co-crystals and other molecular complexes, as well as salts, solvate salts, hydrate salts, other molecular complexes of salts, and their polymorphs. In some embodiments, the crystalline form of a substance may be substantially free of an amorphous form or other crystalline forms. In other embodiments, the crystalline form of a substance may contain, on a weight or molar basis, about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45% or about 50% of one or more amorphous forms or other crystalline forms.

[0067] Certain crystalline forms of a substance can be obtained by several methods including, but not limited to, melt recrystallization, melt cooling, solvent recrystallization, recrystallization in confined spaces such as nanopores or capillaries, recrystallization on surfaces or templates such as polymers, recrystallization in the presence of additives such as cocrystallizing molecules, desolvation, dehydration, rapid evaporation, rapid cooling, slow cooling, vapor diffusion, sublimation, grinding, solvent-drop grinding, microwave-induced precipitation, ultrasonic-induced precipitation, laser-induced precipitation, or precipitation from supercritical fluids, or combinations thereof. In some embodiments, the term "isolating" also encompasses purification.

[0068] As used herein, "XRPD" refers to X-ray powder diffraction.

[0069] Techniques for characterizing crystalline and amorphous forms can include, but are not limited to, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), single-crystal X-ray diffraction, vibrational spectroscopy such as infrared (IR) and Raman spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, optical microscopy, hot-stage optical microscopy, scanning electron microscopy (SEM), electron crystallographic structure analysis and quantitative analysis, particle size analysis (PSA), surface area analysis, solubility studies, and dissolution studies.

[0070] As used herein, unless otherwise specified, the term "peak" when used in connection with a spectrum or data presented in graphical form (e.g., XRPD, IR, Raman, and NMR spectra) refers to a peak or other distinctive feature that one of ordinary skill in the art would recognize as not being due to background noise. The term "significant peak" refers to a peak that is at least the median size (e.g., height) of other peaks in the spectrum or data, or at least 1.5, 2, or 2.5 times the background level in the spectrum or data.

[0071] As used herein, unless otherwise specified, the terms "amorphous" and "amorphous form", and related terms herein mean that the substance, component, or product is substantially non-crystalline when determined, for example, by X-ray diffraction. In some embodiments, the amorphous form of a substance may be substantially free of other amorphous or crystalline forms. In some embodiments, the amorphous form of a substance can include one or more disordered crystalline forms. In other embodiments, the amorphous form of a substance can contain, on a weight or molar basis, about 1%, about 2%, about 3%, about 4%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% of one or more other amorphous or crystalline forms.

[0072] The amorphous form of a substance can be obtained by several methods known in the art. Such methods include, but are not limited to, heating, melt quenching, rapid melt quenching, solvent evaporation, rapid solvent evaporation, desolvation, sublimation, grinding, cryogenic grinding, spray drying, and freeze drying.

[0073] As used herein, polymorphs, crystalline forms, or solid forms of the compounds described herein can be described by reference to patterns, spectra, or other graphic data that are “substantially” shown or illustrated in the figures, or by one or more data points. It will be understood that patterns, spectra, and other graphic data may have their positions, relative intensities, or other values shifted by several factors known to those of ordinary skill in the art. For example, in the techniques of crystallography and powder X-ray diffraction, shifts in the peak position or relative intensity of one or more peaks of a pattern can occur due to, but are not limited to, the apparatus used, sample preparation protocols, preferred packing and orientation, radiation source, operator error, method and length of data collection, etc. However, one of ordinary skill in the art can compare the figures herein with, for example, patterns generated for unknown forms of the compound of Formula II, and confirm identity with the forms disclosed herein. The same applies to other techniques that may be reported herein.

[0074] As used herein, unless otherwise specified, a solid form or composition “substantially free” of a compound (e.g., other forms or patterns or impurities) means that the solid form or composition contains less than about 20 weight percent, less than about 10 weight percent, less than about 5 weight percent, less than about 4 weight percent, less than about 3 weight percent, less than about 2 weight percent, less than about 1 weight percent, less than about 0.5 weight percent, or less than about 0.1 weight percent of the compound (e.g., other forms or patterns or impurities).

[0075] As used herein, unless otherwise specified, the term "substantially pure," when used to describe a polymorph, crystalline form, or solid form of a compound described herein, means a solid form of the compound that includes a particular solid form and substantially excludes other solid forms of the compound or other compounds. Representative substantially pure solid forms include one solid form of the compound that is greater than about 80% by weight and less than about 20% by weight of other solid forms of the compound or other compounds, one solid form of the compound that is greater than about 90% by weight and less than about 10% by weight of other solid forms of the compound or other compounds, one solid form of the compound that is greater than about 95% by weight and less than about 5% by weight of other solid forms of the compound or other compounds, one solid form of the compound that is greater than about 97% by weight and less than about 3% by weight of other solid forms of the compound or other compounds, or one solid form of the compound that is greater than about 99% by weight and less than about 1% by weight of other solid forms of the compound or other compounds.

[0076] As used herein, unless otherwise specified, a crystalline form that is "essentially free" of water or solvent in the crystal lattice has, when measured using conventional solid analysis techniques, such as those described herein, in some embodiments, an amount of water or solvent in the crystal lattice that is near the detection limit, in other embodiments, an amount of water or solvent that is approximately at the detection limit, and in other embodiments, an amount of water or solvent that is less than approximately the detection limit. In some embodiments, the solid analysis technique used to determine the amount of water or solvent in the crystal lattice is thermogravimetric analysis. In other embodiments, the solid analysis technique used to determine the amount of water or solvent in the crystal lattice is Karl Fischer analysis. In other embodiments, a crystalline form that is "essentially free" of water or solvent in the crystal lattice has less than about 5%, less than about 4%, less than about 3%, less than about 2%, less than about 1%, less than about 0.9%, less than about 0.8%, less than about 0.7%, less than about 0.6%, less than about 0.5%, less than about 0.4%, less than about 0.3%, less than about 0.2%, less than about 0.1%, less than about 0.05%, or less than about 0.01% by weight of water or solvent based on the total weight of the crystalline form.

[0077] As used herein, unless otherwise specified, the term "stable" refers to a compound or composition that does not readily decompose and whose chemical composition or physical state does not change. The stable compounds or compositions provided herein do not significantly decompose under normal manufacturing or storage conditions. In some embodiments, when the term "stable" is used in relation to a formulation or dosage form, the active ingredient of the formulation or dosage form remains unchanged in chemical composition or physical state over a specified period of time, does not significantly decompose or aggregate, and is not otherwise altered (e.g., as determined by HPLC, FTIR, or XRPD). In some embodiments, after a specific period, about 70 percent or more, about 80 percent or more, about 90 percent or more, about 95 percent or more, about 98 percent or more, or about 99 percent or more of the compound remains unchanged. In one embodiment, the solid forms provided herein are stable upon long-term storage (e.g., no significant change in the solid form occurs after about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 30, 36, 42, 48, 54, 60, or more than about 60 months).

[0078] As used herein, the term "pattern" with respect to a compound of Formula II refers to a metastable form of the compound of Formula II.

[0079] As used herein, "filler" refers to an additive / carrier in a pharmaceutical composition that lacks pharmacological activity but may be pharmaceutically necessary or desirable, for example, to enhance or improve the properties of a pharmaceutical blend for manufacturing or physiological purposes. For example, fillers can be used to increase the bulk of a potent drug that is too small in mass to be manufactured or administered.

[0080] As used herein, "lubricant" refers to an additive / carrier that, for example, prevents components and additives from agglomerating together and / or from adhering to the capsule filling machine. The lubricant may also ensure that capsule formation, filling, and ejection can be carried out, for example, by reducing friction. Examples of lubricants are talc, silicon dioxide (silica), fatty acids or fatty acid salts, such as magnesium stearate, sodium fumarate stearate, stearic acid, and the like.

[0081] As used herein, the term "screening" refers to passing or causing to pass particulate solids (e.g., a compound of Formula II or a pharmaceutically acceptable carrier) through an instrument having a plurality of meshed or perforated openings, slits, or holes, for example, to separate particulate matter of the lost substance from the coarse particles.

[0082] The term "blending" refers to mixing pharmaceutical ingredients using various devices, such as, but not limited to, "V" blenders, bin blenders, cone blenders, etc., to form a mixture of ingredients defined by the pharmaceutical specifications of a pharmaceutical specification, such as a pharmaceutical active ingredient (API) and a pharmaceutically acceptable carrier(s).

[0083] As used herein, the term "high shear" may be related to various factors within the process and is not simply a function of tip speed and / or revolutions per minute, but those values may be referenced when describing the high shear and speed of the blades within a blender / mixer.

[0084] The term "encapsulation" refers to various techniques used to encapsulate a drug in a shell, such as, for example, a two-piece capsule, such as a two-piece hard shell capsule. The capsules referred to herein can be orally ingested. The capsule can be designed using nested caps and bodies made, for example, of gelatin or cellulose. Compound

[0085] In some embodiments, compounds that are dual RAF / MEK inhibitors are provided herein. Exemplary dual RAF / MEK inhibitors have the following structure: [Chemical Formula] a compound of Formula I having the following or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0086] In some embodiments, the compound of Formula I is [Chemical Formula] which is also referred to herein as the free form of VS-6766.

[0087] The compounds of Formula I can be synthesized according to the synthetic methods described in WO2007091736 and WO2013035754, which are hereby incorporated by reference in their entirety.

[0088] In some embodiments, the dual RAF / MEK inhibitor is a pharmaceutically acceptable salt of the compound of Formula I. In some embodiments, the dual RAF / MEK inhibitor is the potassium salt of the compound of Formula I, which is also referred to herein as VS-6766 or Compound 1.

[0089] For example, Compound 1 as referred to herein corresponds to a compound having the following structure. [Chemical Formula]

[0090] Compound 1 is also disclosed herein as a compound of Formula II.

[0091] Different solid forms of a pharmaceutical active ingredient can have different physicochemical properties and can result in solid forms of the active pharmaceutical ingredient having desirable processing characteristics such as ease of handling, ease of processing, storage stability, and ease of purification, improved dissolution profiles, dissolution rates, chemical stability, physical stability, bioavailability, storage conditions, shelf life, purity, process reproducibility, or formulation.

[0092] In some embodiments, solid forms of the compound of Formula II that are substantially free of other forms or patterns or impurities of the compound of Formula II are disclosed herein. Solid form Form 1

[0093] In one aspect, Formula II:

Chemical formula

[0094] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, and 14.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.

[0095] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.2, 10.7 ± 0.2, 13.5 ± 0.2, 16.6 ± 0.2, 17.1 ± 0.2, 17.7 ± 0.2, and 19.4 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.2, 23.1 ± 0.2, 25.1 ± 0.2, 27.0 ± 0.2, 32.3 ± 0.2, and 39.4 ± 0.2.

[0096] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2.

[0097] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, and 14.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.

[0098] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.3, 10.7 ± 0.3, 13.5 ± 0.3, 16.6 ± 0.3, 17.1 ± 0.3, 17.7 ± 0.3, and 19.4 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.3, 23.1 ± 0.3, 25.1 ± 0.3, 27.0 ± 0.3, 32.3 ± 0.3, and 39.4 ± 0.3.

[0099] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3.

[0100] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, and 14.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.

[0101] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.5, 10.7 ± 0.5, 13.5 ± 0.5, 16.6 ± 0.5, 17.1 ± 0.5, 17.7 ± 0.5, and 19.4 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.5, 23.1 ± 0.5, 25.1 ± 0.5, 27.0 ± 0.5, 32.3 ± 0.5, and 39.4 ± 0.5.

[0102] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5.

[0103] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0104] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2 and 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, and 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, 22.5 ± 0.2, 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, and 32.2 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2, 10.5 ± 0.2, 13.3 ± 0.2, 14.5 ± 0.2, 16.9 ± 0.2, 17.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 22.5 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, 32.2 ± 0.2, and 39.3 ± 0.2.

[0105] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3 and 8.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, and 14.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, and 19.2 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3.

[0106] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, and 32.2 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 14.5 ± 0.3, 16.9 ± 0.3, 17.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 22.5 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, 32.2 ± 0.3, and 39.3 ± 0.3.

[0107] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5 and 8.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, and 14.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, and 19.2 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5.

[0108] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, and 32.2 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 14.5 ± 0.5, 16.9 ± 0.5, 17.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 22.5 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, 32.2 ± 0.5, and 39.3 ± 0.5.

[0109] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1B.

[0110] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255 °C based on differential scanning calorimetry.

[0111] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0112] In some embodiments, Form 1 is an anhydride.

[0113] In some embodiments, Form 1 contains less than about 3.0% water. In some embodiments, Form 1 contains less than about 2.0% water. In some embodiments, Form 1 contains less than about 1.0% water. In some embodiments, Form 1 contains less than about 0.5% water.

[0114] In one aspect, Formula II:

Chemical Formula

[0115] In some embodiments, Form 1 contains less than about 10% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 9% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 8% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 7% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 6% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 5% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 4% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 3% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 2% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 1% area percentage of impurities as determined by HPLC.

[0116] In some embodiments, the impurity is Compound B, Compound C, or Compound D, or a combination thereof.

Chemical formula

[0117] In some embodiments, Form 1 contains less than about 5.0% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.8% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.6% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.5% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.4% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.2% Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.1% Compound B as determined by HPLC.

[0118] In some embodiments, Form 1 contains less than about 5.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.8% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.6% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.5% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.4% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.2% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.1% Compound C as determined by HPLC.

[0119] In some embodiments, Form 1 contains less than about 5.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.75% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.50% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.25% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.20% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.15% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.10% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.05% of Compound D as determined by HPLC.

[0120] In some embodiments, Form 1 contains less than about 5.0% water. In some embodiments, Form 1 contains less than about 4.0% water. In some embodiments, Form 1 contains less than about 3.0% water. In some embodiments, Form 1 contains less than about 2.0% water. In some embodiments, Form 1 contains less than about 1.0% water. In some embodiments, Form 1 contains less than about 0.5% water.

[0121] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, and 14.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.

[0122] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern including at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.2, 10.7 ± 0.2, 13.5 ± 0.2, 16.6 ± 0.2, 17.1 ± 0.2, 17.7 ± 0.2, and 19.4 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern including at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.2, 23.1 ± 0.2, 25.1 ± 0.2, 27.0 ± 0.2, 32.3 ± 0.2, and 39.4 ± 0.2.

[0123] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2.

[0124] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, and 14.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.

[0125] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.3, 10.7 ± 0.3, 13.5 ± 0.3, 16.6 ± 0.3, 17.1 ± 0.3, 17.7 ± 0.3, and 19.4 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.3, 23.1 ± 0.3, 25.1 ± 0.3, 27.0 ± 0.3, 32.3 ± 0.3, and 39.4 ± 0.3.

[0126] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3.

[0127] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, and 14.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.

[0128] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.5, 10.7 ± 0.5, 13.5 ± 0.5, 16.6 ± 0.5, 17.1 ± 0.5, 17.7 ± 0.5, and 19.4 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.5, 23.1 ± 0.5, 25.1 ± 0.5, 27.0 ± 0.5, 32.3 ± 0.5, and 39.4 ± 0.5.

[0129] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5.

[0130] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0131] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2 and 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, and 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, 22.5 ± 0.2, 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, and 32.2 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2, 10.5 ± 0.2, 13.3 ± 0.2, 14.5 ± 0.2, 16.9 ± 0.2, 17.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 22.5 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, 32.2 ± 0.2, and 39.3 ± 0.2.

[0132] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3 and 8.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, and 14.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern further comprising at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, and 19.2 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern further comprising at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3.

[0133] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, and 32.2 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 14.5 ± 0.3, 16.9 ± 0.3, 17.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 22.5 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, 32.2 ± 0.3, and 39.3 ± 0.3.

[0134] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5 and 8.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, and 14.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, and 19.2 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5.

[0135] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, and 32.2 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 14.5 ± 0.5, 16.9 ± 0.5, 17.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 22.5 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, 32.2 ± 0.5, and 39.3 ± 0.5.

[0136] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in Figure 1B.

[0137] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in Figure 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255 °C based on differential scanning calorimetry.

[0138] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in Figure 3.

[0139] In one embodiment, Form 1 is an anhydride.

[0140] In one aspect, Formula II:

Chemical formula

[0141] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.2, 10.7 ± 0.2, 13.5 ± 0.2, 16.6 ± 0.2, 17.1 ± 0.2, 17.7 ± 0.2, and 19.4 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.2, 23.1 ± 0.2, 25.1 ± 0.2, 27.0 ± 0.2, 32.3 ± 0.2, and 39.4 ± 0.2.

[0142] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2.

[0143] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0144] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255 °C based on differential scanning calorimetry.

[0145] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0146] In some embodiments, Form 1 is an anhydrate.

[0147] In one aspect, Formula II:

Chemical formula

[0148] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.3, 10.7 ± 0.3, 13.5 ± 0.3, 16.6 ± 0.3, 17.1 ± 0.3, 17.7 ± 0.3, and 19.4 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.3, 23.1 ± 0.3, 25.1 ± 0.3, 27.0 ± 0.3, 32.3 ± 0.3, and 39.4 ± 0.3.

[0149] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3.

[0150] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0151] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255 °C based on differential scanning calorimetry.

[0152] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0153] In some embodiments, Form 1 is an anhydrate.

[0154] In one aspect, Formula II:

Chemical formula

[0155] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.5, 10.7 ± 0.5, 13.5 ± 0.5, 16.6 ± 0.5, 17.1 ± 0.5, 17.7 ± 0.5, and 19.4 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.5, 23.1 ± 0.5, 25.1 ± 0.5, 27.0 ± 0.5, 32.3 ± 0.5, and 39.4 ± 0.5.

[0156] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5.

[0157] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0158] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255° C. based on differential scanning calorimetry.

[0159] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0160] In some embodiments, Form 1 is an anhydrate.

[0161] In some embodiments, Form 1 is substantially free of other forms or patterns of the compound of Formula II. In some embodiments, the other forms or patterns are selected from the group consisting of Form 8, Form 10, Pattern 2, Pattern 3, Pattern 5, Pattern 6, Pattern 7, Pattern 11, and Pattern 12, and combinations thereof.

[0162] In some embodiments, Form 1 is substantially free of impurities.

[0163] In some embodiments, Form 1 contains less than about 10% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 9% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 8% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 7% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 6% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 5% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 4% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 3% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 2% area percentage of impurities as determined by HPLC. In some embodiments, Form 1 contains less than about 1% area percentage of impurities as determined by HPLC.

[0164] In some embodiments, the impurities are Compound B, Compound C, or Compound D, or combinations thereof.

Chemical formula

[0165] In some embodiments, Form 1 contains less than about 5.0% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.8% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.6% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.5% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.4% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.2% of Compound B as determined by HPLC. In some embodiments, Form 1 contains less than about 0.1% of Compound B as determined by HPLC.

[0166] In some embodiments, Form 1 contains less than about 5.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.8% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.6% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.5% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.4% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.2% Compound C as determined by HPLC. In some embodiments, Form 1 contains less than about 0.1% Compound C as determined by HPLC.

[0167] In some embodiments, Form 1 contains less than about 5.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 4.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 3.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 2.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 1.5% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 1.0% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.75% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.50% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.25% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.20% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.15% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.10% of Compound D as determined by HPLC. In some embodiments, Form 1 contains less than about 0.05% of Compound D as determined by HPLC.

[0168] In some embodiments, Form 1 is characterized by unit cell dimensions of a = 19.5 ± 1.0 Å, b = 15.1 ± 1.0 Å, and c = 6.9 ± 1.0 Å. In some embodiments, Form 1 is characterized by unit cell dimensions of a = 19.5 ± 0.5 Å, b = 15.1 ± 0.5 Å, and c = 6.9 ± 0.5 Å. In some embodiments, Form 1 is characterized by unit cell dimensions of a = 19.5 ± 0.2 Å, b = 15.1 ± 0.2 Å, and c = 6.9 ± 0.2 Å. In some embodiments, Form 1 is characterized by having a monoclinic crystal system.

[0169] In one aspect, Formula II:

Chemical formula

[0170] In some embodiments, the solvent is a mixture of THF and water. In some embodiments, THF and water are present in a ratio of about 50:50 v / v. In some embodiments, THF and water are present in a ratio of about 60:40 v / v. In some embodiments, THF and water are present in a ratio of about 70:30 v / v. In some embodiments, THF and water are present in a ratio of about 80:20 v / v. In some embodiments, THF and water are present in a ratio of about 90:10 v / v. In some embodiments, THF and water are present in a ratio of about 95:5 v / v.

[0171] In some embodiments, the mixture is heated to about 30 - 40 °C in step (ii). In some embodiments, the mixture is heated to about 30 - 60 °C in step (ii). In some embodiments, the mixture is heated to about 30 - 50 °C in step (ii). In some embodiments, the mixture is heated to about 40 - 60 °C in step (ii). In some embodiments, the mixture is heated to about 40 - 50 °C in step (ii). In some embodiments, the mixture is heated to about 50 - 60 °C in step (ii). In some embodiments, the mixture is heated to about 35 °C in step (ii). In some embodiments, the mixture is heated to about 35 °C in step (ii). In some embodiments, the mixture is heated to about 40 °C in step (ii). In some embodiments, the mixture is heated to about 45 °C in step (ii). In some embodiments, the mixture is heated to about 50 °C in step (ii). In some embodiments, the mixture is heated to about 55 °C in step (ii). In some embodiments, the mixture is heated to about 60 °C in step (ii).

[0172] In some embodiments, the heated mixture of step (ii) is cooled to about -20 to 15 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -15 to 15 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -10 to 15 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -5 to 15 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -20 to 10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -15 to 10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -10 to 10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -5 to 10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -20 to 5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -15 to 5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -10 to 5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -5 to 5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -20 to 0 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -15 to 0 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -10 to 0 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -5 to 0 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -20 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -15 °C in step (iii).In some embodiments, the heated mixture of step (ii) is cooled to about -10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about -5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about 0 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about 5 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about 10 °C in step (iii). In some embodiments, the heated mixture of step (ii) is cooled to about 15 °C in step (iii).

[0173] In some embodiments, the drying in step (iv) is carried out at a high temperature. In some embodiments, the drying in step (iv) is carried out at a temperature of about 20 °C to about 40 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 20 °C to about 50 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 20 °C to about 60 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 30 °C to about 40 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 30 °C to about 50 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 30 °C to about 60 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 40 °C to about 50 °C. In some embodiments, the drying in step (iv) is carried out at a temperature of about 40 °C to about 60 °C.

[0174] In some embodiments, the drying in step (iv) is carried out under reduced pressure. In some embodiments, the drying in step (iv) is carried out under reduced pressure and at a high temperature. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 20°C to about 40°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 20°C to about 50°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 20°C to about 60°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 30°C to about 40°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 30°C to about 50°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 30°C to about 60°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 40°C to about 50°C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 40°C to about 60°C.

[0175] In some embodiments, crystalline form 1 of the compound of formula II prepared according to the above method [Chemical formula] is provided.

[0176] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, and 14.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 18.1 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 18.1 ± 0.5, and 22.7 ± 0.5.

[0177] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern including at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.5, 10.7 ± 0.5, 13.5 ± 0.5, 16.6 ± 0.5, 17.1 ± 0.5, 17.7 ± 0.5, and 19.4 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern including at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.5, 23.1 ± 0.5, 25.1 ± 0.5, 27.0 ± 0.5, 32.3 ± 0.5, and 39.4 ± 0.5.

[0178] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern including at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 7.7 ± 0.5, 9.0 ± 0.5, 14.7 ± 0.5, 17.1 ± 0.5, 18.1 ± 0.5, 19.4 ± 0.5, and 22.7 ± 0.5.

[0179] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, and 14.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 18.1 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 18.1 ± 0.3, and 22.7 ± 0.3.

[0180] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.3, 10.7 ± 0.3, 13.5 ± 0.3, 16.6 ± 0.3, 17.1 ± 0.3, 17.7 ± 0.3, and 19.4 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.3, 23.1 ± 0.3, 25.1 ± 0.3, 27.0 ± 0.3, 32.3 ± 0.3, and 39.4 ± 0.3.

[0181] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 7.7 ± 0.3, 9.0 ± 0.3, 14.7 ± 0.3, 17.1 ± 0.3, 18.1 ± 0.3, 19.4 ± 0.3, and 22.7 ± 0.3.

[0182] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 14.7 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 18.1 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, and 14.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 18.1 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.2.

[0183] In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.2, 10.7 ± 0.2, 13.5 ± 0.2, 16.6 ± 0.2, 17.1 ± 0.2, 17.7 ± 0.2, and 19.4 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 21.9 ± 0.2, 23.1 ± 0.2, 25.1 ± 0.2, 27.0 ± 0.2, 32.3 ± 0.2, and 39.4 ± 0.2.

[0184] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least two peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least three peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising at least four peaks selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 7.7 ± 0.2, 9.0 ± 0.2, 14.7 ± 0.2, 17.1 ± 0.2, 18.1 ± 0.2, 19.4 ± 0.2, and 22.7 ± 0.2.

[0185] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1C.

[0186] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2 and 8.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, and 22.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, 22.5 ± 0.2, and 14.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, and 19.2 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, and 27.8 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, 22.5 ± 0.2, 14.5 ± 0.2, 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, and 27.8 ± 0.2.

[0187] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, and 22.5 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.2, 8.8 ± 0.2, 22.5 ± 0.2, 14.5 ± 0.2, 39.3 ± 0.2, and 10.5 ± 0.2. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.2, 13.3 ± 0.2, 16.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, and 32.2 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.2, 10.5 ± 0.2, 13.3 ± 0.2, 14.5 ± 0.2, 16.9 ± 0.2, 17.9 ± 0.2, 19.2 ± 0.2, 21.3 ± 0.2, 21.8 ± 0.2, 22.5 ± 0.2, 24.9 ± 0.2, 27.1 ± 0.2, 27.8 ± 0.2, 32.2 ± 0.2, and 39.3 ± 0.2.

[0188] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3 and 8.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, and 14.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, and 19.2 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, and 27.8 ± 0.3.

[0189] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, and 22.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.3, 8.8 ± 0.3, 22.5 ± 0.3, 14.5 ± 0.3, 39.3 ± 0.3, and 10.5 ± 0.3. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.3, 13.3 ± 0.3, 16.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, and 32.2 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.3, 10.5 ± 0.3, 13.3 ± 0.3, 14.5 ± 0.3, 16.9 ± 0.3, 17.9 ± 0.3, 19.2 ± 0.3, 21.3 ± 0.3, 21.8 ± 0.3, 22.5 ± 0.3, 24.9 ± 0.3, 27.1 ± 0.3, 27.8 ± 0.3, 32.2 ± 0.3, and 39.3 ± 0.3.

[0190] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5 and 8.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, and 14.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, and 19.2 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, and 27.8 ± 0.5.

[0191] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, and 22.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 17.9 ± 0.5, 8.8 ± 0.5, 22.5 ± 0.5, 14.5 ± 0.5, 39.3 ± 0.5, and 10.5 ± 0.5. In some embodiments, Form 1 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 10.5 ± 0.5, 13.3 ± 0.5, 16.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, and 32.2 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 8.8 ± 0.5, 10.5 ± 0.5, 13.3 ± 0.5, 14.5 ± 0.5, 16.9 ± 0.5, 17.9 ± 0.5, 19.2 ± 0.5, 21.3 ± 0.5, 21.8 ± 0.5, 22.5 ± 0.5, 24.9 ± 0.5, 27.1 ± 0.5, 27.8 ± 0.5, 32.2 ± 0.5, and 39.3 ± 0.5.

[0192] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1B.

[0193] In some embodiments, Form 1 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 2. In some embodiments, Form 1 exhibits an endotherm starting at about 255 °C based on differential scanning calorimetry.

[0194] In some embodiments, Form 1 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0195] In some embodiments, Form 1 is an anhydride.

[0196] In some embodiments, Form 1 contains less than about 3.0% water. In some embodiments, Form 1 contains less than about 2.0% water. In some embodiments, Form 1 contains less than about 1.0% water. In some embodiments, Form 1 contains less than about 0.5% water. Form 8

[0197] In another aspect, Formula II:

Chemical formula

[0198] In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.2 and 16.8 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.2, 16.8 ± 0.2, and 20.2 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.2, 14.8 ± 0.2, 16.8 ± 0.2, and 20.2 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.2, 13.3 ± 0.2, 14.8 ± 0.2, 16.8 ± 0.2, and 20.2 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 6.9 ± 0.2, 9.0 ± 0.2, 17.5 ± 0.2, 17.9 ± 0.2, 21.2 ± 0.2, 23.7 ± 0.2, 24.5 ± 0.2, 25.3 ± 0.2, 26.2 ± 0.2, and 27.1 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 4.6 ± 0.2, 5.2 ± 0.2, 7.7 ± 0.2, 8.5 ± 0.2, 10.3 ± 0.2, 11.7 ± 0.2, 12.4 ± 0.2, 12.9 ± 0.2, 13.3 ± 0.2, 14.2 ± 0.2, and 14.8 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 23.1 ± 0.2, 25.8 ± 0.2, and 28.2 ± 0.2. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 31.2 ± 0.2 and 37.8 ± 0.2.In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 6.9 ± 0.2, 9.0 ± 0.2, 9.9 ± 0.2, 13.3 ± 0.2, 14.8 ± 0.2, 16.8 ± 0.2, 17.5 ± 0.2, 17.9 ± 0.2, 20.2 ± 0.2, 21.2 ± 0.2, 23.7 ± 0.2, 24.5 ± 0.2, 25.3 ± 0.2, 26.2 ± 0.2, and 27.1 ± 0.2.

[0199] In some embodiments, also, Formula II:

Chemical Formula

[0200] In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.3 and 16.8 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.3, 16.8 ± 0.3, and 20.3 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.3, 14.8 ± 0.3, 16.8 ± 0.3, and 20.3 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.3, 13.3 ± 0.3, 14.8 ± 0.3, 16.8 ± 0.3, and 20.3 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)): 6.9 ± 0.3, 9.0 ± 0.3, 17.5 ± 0.3, 17.9 ± 0.3, 21.2 ± 0.3, 23.7 ± 0.3, 24.5 ± 0.3, 25.3 ± 0.3, 26.2 ± 0.3, and 27.1 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)): 4.6 ± 0.3, 5.2 ± 0.3, 7.7 ± 0.3, 8.5 ± 0.3, 10.3 ± 0.3, 11.7 ± 0.3, 12.4 ± 0.3, 12.9 ± 0.3, 13.3 ± 0.3, 14.2 ± 0.3, and 14.8 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)): 23.1 ± 0.3, 25.8 ± 0.3, and 28.2 ± 0.3. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)): 31.2 ± 0.3 and 37.8 ± 0.3.In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 6.9 ± 0.3, 9.0 ± 0.3, 9.9 ± 0.3, 13.3 ± 0.3, 14.8 ± 0.3, 16.8 ± 0.3, 17.5 ± 0.3, 17.9 ± 0.3, 20.3 ± 0.3, 21.2 ± 0.3, 23.7 ± 0.3, 24.5 ± 0.3, 25.3 ± 0.3, 26.2 ± 0.3, and 27.1 ± 0.3.

[0201] In some embodiments, also, Formula II:

Chemical Formula

[0202] In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.5 and 16.8 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)): 9.9 ± 0.5, 16.8 ± 0.5, and 20.3 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.5, 14.8 ± 0.5, 16.8 ± 0.5, and 20.3 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 9.9 ± 0.5, 13.3 ± 0.5, 14.8 ± 0.5, 16.8 ± 0.5, and 20.3 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 6.9 ± 0.5, 9.0 ± 0.5, 17.5 ± 0.5, 17.9 ± 0.5, 21.2 ± 0.5, 23.7 ± 0.5, 24.5 ± 0.5, 25.3 ± 0.5, 26.2 ± 0.5, and 27.1 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 4.6 ± 0.5, 5.2 ± 0.5, 7.7 ± 0.5, 8.5 ± 0.5, 10.3 ± 0.5, 11.7 ± 0.5, 12.4 ± 0.5, 12.9 ± 0.5, 13.3 ± 0.5, 14.2 ± 0.5, and 14.8 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 23.1 ± 0.5, 25.8 ± 0.5, and 28.2 ± 0.5. In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 31.2 ± 0.5 and 37.8 ± 0.5.In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 6.9 ± 0.5, 9.0 ± 0.5, 9.9 ± 0.5, 13.3 ± 0.5, 14.8 ± 0.5, 16.8 ± 0.5, 17.5 ± 0.5, 17.9 ± 0.5, 20.3 ± 0.5, 21.2 ± 0.5, 23.7 ± 0.5, 24.5 ± 0.5, 25.3 ± 0.5, 26.2 ± 0.5, and 27.1 ± 0.5.

[0203] In some embodiments, Form 8 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 13 (top).

[0204] In some embodiments, Form 8 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 14. In some embodiments, Form 8 exhibits an exotherm starting at approximately 252 °C based on differential scanning calorimetry.

[0205] In some embodiments, Form 8 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 3.

[0206] In some embodiments, Form 8 is an anhydrate.

[0207] In some embodiments, Form 8 contains less than about 3.0% water. In some embodiments, Form 1 contains less than about 2.0% water. In some embodiments, Form 1 contains less than about 1.0% water. In some embodiments, Form 1 contains less than about 0.5% water.

[0208] Also, Formula II:

Chemical Formula

[0209] In some embodiments, the drying in step (iv) is carried out under reduced pressure. In some embodiments, the drying in step (iv) is carried out at a temperature of about 30 to about 50 °C. In some embodiments, the drying in step (iv) is carried out under reduced pressure at a temperature of about 30 to about 50 °C.

[0210] In some embodiments, the isolation in step (iii) is carried out by filtration or centrifugation. Form 10

[0211] In another aspect, formula II:

Chemical formula

[0212] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2 and 25.5 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2 and 12.5 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2, 12.5 ± 0.2, and 25.5 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2, 12.5 ± 0.2, 24.4 ± 0.2, and 25.5 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2, 12.5 ± 0.2, 23.8 ± 0.2, 24.4 ± 0.2, and 25.5 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.2, 16.7 ± 0.2, 17.0 ± 0.2, 17.3 ± 0.2, 17.9 ± 0.2, 19.0 ± 0.2, 19.4 ± 0.2, and 20.7 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.2, 10.4 ± 0.2, 12.0 ± 0.2, 13.7 ± 0.2, 14.4 ± 0.2, 15.3 ± 0.2, 16.7 ± 0.2, 17.0 ± 0.2, 17.3 ± 0.2, 17.9 ± 0.2, 18.4 ± 0.2, 19.0 ± 0.2, 19.4 ± 0.2, 20.7 ± 0.2, 22.5 ± 0.2, and 27.2 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that further includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.2, 16.7 ± 0.2, 17.0 ± 0.2, 17.3 ± 0.2, 17.9 ± 0.2, 19.0 ± 0.2, 19.4 ± 0.2, 20.7 ± 0.2, 30.0 ± 0.2, and 38.8 ± 0.2.In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern further comprising at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.2, 10.4 ± 0.2, 12.0 ± 0.2, 13.7 ± 0.2, 14.4 ± 0.2, 15.3 ± 0.2, 16.7 ± 0.2, 17.0 ± 0.2, 17.3 ± 0.2, 17.9 ± 0.2, 18.4 ± 0.2, 19.0 ± 0.2, 19.4 ± 0.2, 20.7 ± 0.2, 22.5 ± 0.2, 27.2 ± 0.2, 30.0 ± 0.2, 32.6 ± 0.2, 38.2 ± 0.2, and 38.8 ± 0.2. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.2, 12.0 ± 0.2, 12.5 ± 0.2, 16.7 ± 0.2, 17.0 ± 0.2, 17.3 ± 0.2, 17.9 ± 0.2, 19.0 ± 0.2, 19.4 ± 0.2, 20.7 ± 0.2, 23.8 ± 0.2, 24.4 ± 0.2, 25.5 ± 0.2, 30.0 ± 0.2, and 38.8 ± 0.2.

[0213] In another aspect, Formula II:

Chemical formula

[0214] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3 and 25.5 ± 0.3. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3 and 12.5 ± 0.3. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3, 12.5 ± 0.3, and 25.5 ± 0.3. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3, 12.5 ± 0.3, 24.4 ± 0.3, and 25.5 ± 0.3.

[0215] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3, 12.5 ± 0.3, 23.8 ± 0.3, 24.4 ± 0.3, and 25.5 ± 0.3. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.3, 16.7 ± 0.3, 17.0 ± 0.3, 17.3 ± 0.3, 17.9 ± 0.3, 19.0 ± 0.3, 19.4 ± 0.3, and 20.7 ± 0.3. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.3, 10.4 ± 0.3, 12.0 ± 0.3, 13.7 ± 0.3, 14.4 ± 0.3, 15.3 ± 0.3, 16.7 ± 0.3, 17.0 ± 0.3, 17.3 ± 0.3, 17.9 ± 0.3, 18.4 ± 0.3, 19.0 ± 0.3, 19.4 ± 0.3, 20.7 ± 0.3, 22.5 ± 0.3, and 27.2 ± 0.3. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.3, 16.7 ± 0.3, 17.0 ± 0.3, 17.3 ± 0.3, 17.9 ± 0.3, 19.0 ± 0.3, 19.4 ± 0.3, 20.7 ± 0.3, 30.0 ± 0.3, and 38.8 ± 0.3. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.3, 10.4 ± 0.3, 12.0 ± 0.3, 13.7 ± 0.3, 14.4 ± 0.3, 15.3 ± 0.3, 16.7 ± 0.3, 17.0 ± 0.3, 17.3 ± 0.3, 17.9 ± 0.3, 18.4 ± 0.3, 19.0 ± 0.3, 19.4 ± 0.3, 20.7 ± 0.3, 22.5 ± 0.3, 27.2 ± 0.3, 30.0 ± 0.3, 32.6 ± 0.3, 38.2 ± 0.3, and 38.8 ± 0.3.In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.3, 12.0 ± 0.3, 12.5 ± 0.3, 16.7 ± 0.3, 17.0 ± 0.3, 17.3 ± 0.3, 17.9 ± 0.3, 19.0 ± 0.3, 19.4 ± 0.3, 20.7 ± 0.3, 23.8 ± 0.3, 24.4 ± 0.3, 25.5 ± 0.3, 30.0 ± 0.3, and 38.8 ± 0.3.

[0216] In some embodiments, also, Formula II: [Chemical Formula] Form 10 of the compound of is provided herein, which exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angle (2θ (degrees)) = 11.7 ± 0.5, and the compound is a hydrate.

[0217] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5 and 25.5 ± 0.5. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5 and 12.5 ± 0.5. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5, 12.5 ± 0.5, and 25.5 ± 0.5. In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5, 12.5 ± 0.5, 24.4 ± 0.5, and 25.5 ± 0.5.

[0218] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5, 12.5 ± 0.5, 23.8 ± 0.5, 24.4 ± 0.5, and 25.5 ± 0.5. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.5, 16.7 ± 0.5, 17.0 ± 0.5, 17.3 ± 0.5, 17.9 ± 0.5, 19.0 ± 0.5, 19.4 ± 0.5, and 20.7 ± 0.5. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.5, 10.4 ± 0.5, 12.0 ± 0.5, 13.7 ± 0.5, 14.4 ± 0.5, 15.3 ± 0.5, 16.7 ± 0.5, 17.0 ± 0.5, 17.3 ± 0.5, 17.9 ± 0.5, 18.4 ± 0.5, 19.0 ± 0.5, 19.4 ± 0.5, 20.7 ± 0.5, 22.5 ± 0.5, and 27.2 ± 0.5. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 12.0 ± 0.5, 16.7 ± 0.5, 17.0 ± 0.5, 17.3 ± 0.5, 17.9 ± 0.5, 19.0 ± 0.5, 19.4 ± 0.5, 20.7 ± 0.5, 30.0 ± 0.5, and 38.8 ± 0.5. In some embodiments, Form 10 further exhibits an X-ray powder diffraction pattern that includes at least one characteristic XRPD peak selected from diffraction angles (2θ (degrees)) = 5.1 ± 0.5, 10.4 ± 0.5, 12.0 ± 0.5, 13.7 ± 0.5, 14.4 ± 0.5, 15.3 ± 0.5, 16.7 ± 0.5, 17.0 ± 0.5, 17.3 ± 0.5, 17.9 ± 0.5, 18.4 ± 0.5, 19.0 ± 0.5, 19.4 ± 0.5, 20.7 ± 0.5, 22.5 ± 0.5, 27.2 ± 0.5, 30.0 ± 0.5, 32.6 ± 0.5, 38.2 ± 0.5, and 38.8 ± 0.5.In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that includes peaks at the following diffraction angles (2θ (degrees)) = 11.7 ± 0.5, 12.0 ± 0.5, 12.5 ± 0.5, 16.7 ± 0.5, 17.0 ± 0.5, 17.3 ± 0.5, 17.9 ± 0.5, 19.0 ± 0.5, 19.4 ± 0.5, 20.7 ± 0.5, 23.8 ± 0.5, 24.4 ± 0.5, 25.5 ± 0.5, 30.0 ± 0.5, and 38.8 ± 0.5.

[0219] In some embodiments, Form 10 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 7 (top).

[0220] In some embodiments, Form 10 has a differential scanning calorimetry curve that is substantially the same as that shown in FIG. 8. In some embodiments, Form 10 exhibits endotherms starting at approximately 39 °C and approximately 243 °C based on differential scanning calorimetry.

[0221] In some embodiments, Form 10 has a dynamic vapor sorption plot that is substantially the same as that shown in FIG. 10.

[0222] Also provided herein is a method for preparing crystalline Form 10 of the hydrate of the compound of formula II:

Chemical formula

[0223] In some embodiments, the drying of step (iii) is performed under reduced pressure.

[0224] In some embodiments, the drying of step (iii) is performed at ambient temperature.

[0225] In some embodiments, the isolation of step (ii) is performed by filtration or centrifugation. Pattern 2

[0226] In another aspect, Formula II: [Chemical Formula] The crystal pattern 2 of the compound of is provided herein.

[0227] In some embodiments, pattern 2 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 7 (bottom). Pattern 3

[0228] In another aspect, Formula II: [Chemical Formula] The crystal pattern 3 of the compound of is provided herein.

[0229] In some embodiments, pattern 3 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 12B. Pattern 5

[0230] In another aspect, Formula II: [Chemical Formula] The crystal pattern 5 of the compound of is provided herein.

[0231] In some embodiments, pattern 5 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 13 (bottom). Pattern 6

[0232] In another aspect, Formula II: [Chemical Formula] The crystal pattern 6 of the compound of is provided herein.

[0233] In some embodiments, Pattern 6 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 19. Pattern 7

[0234] In another aspect, Formula II:

Chemical formula

[0235] In some embodiments, Pattern 7 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 20. Pattern 9

[0236] In another aspect, Formula II:

Chemical formula

[0237] In some embodiments, Pattern 9 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 21. Pattern 11

[0238] In another aspect, Formula II:

Chemical formula

[0239] In some embodiments, Pattern 11 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 23. Pattern 12

[0240] In another aspect, Formula II:

Chemical formula

[0241] In some embodiments, Pattern 12 exhibits an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 24. Administration and Dosage

[0242] In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered at least once a week (e.g., once a week, twice a week, three times a week, four times a week, five times a week, or six times a week). In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered once a week. In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered twice a week. In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered three times a week.

[0243] In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 0.1 mg to about 100 mg (based on the free form), for example, about 0.1 mg to about 50 mg, about 0.1 mg to about 10 mg, about 0.1 mg to about 5 mg, about 0.1 mg to about 4 mg, about 0.1 mg to about 3 mg, about 0.1 mg to about 2 mg, about 0.1 mg to about 1 mg, about 1 mg to about 5 mg, about 1 mg to about 10 mg, about 1 mg to about 20 mg, about 1 mg to about 40 mg, about 1 mg to about 60 mg, about 1 mg to about 80 mg, about 1 mg to about 100 mg, about 10 mg to about 100 mg, about 20 mg to about 100 mg, about 40 mg to about 100 mg, about 60 mg to about 100 mg, or about 80 mg to about 100 mg. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 0.5 mg to about 10 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 0.8 mg to about 10 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 1 mg to about 5 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 2 mg to about 4 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 0.1 mg, 0.2 mg, 0.5 mg, 1 mg, 1.5 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, or 100 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II is administered at about 4 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 3.2 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered orally.

[0244] In some embodiments, the solid form of the compound of Formula II disclosed herein is administered as a cycle. In some embodiments, a cycle comprises administering the solid form of the compound of Formula II disclosed herein for 3 weeks and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered once a week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 0.8 mg to about 10 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 1 mg to about 5 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 2 mg to about 4 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II is administered at about 4 mg (based on the free form) per administration. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered at about 3.2 mg (based on the free form) per administration.

[0245] In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 0.8 mg to about 10 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 1 mg to about 5 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 2 mg to about 4 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of 3.2 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered twice a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of 4 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the cycle is repeated at least once.

[0246] In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 0.8 mg to about 10 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 1 mg to about 5 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of about 2 mg to about 4 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of 3.2 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the solid form of the compound of Formula II disclosed herein is administered three times a week as a cycle, and the cycle comprises administering the solid form of the compound of Formula II disclosed herein at a dose of 4 mg (based on the free form) per administration for 3 weeks, and then not administering the solid form of the compound of Formula II disclosed herein for 1 week. In some embodiments, the cycle is repeated at least once.

[0247] In some embodiments, Form 1 is administered at about 0.1 mg to about 100 mg per administration, such as about 0.1 mg to about 50 mg, about 0.1 mg to about 10 mg, about 0.1 mg to about 5 mg, about 0.1 mg to about 4 mg, about 0.1 mg to about 3 mg, about 0.1 mg to about 2 mg, about 0.1 mg to about 1 mg, about 1 mg to about 5 mg, about 1 mg to about 10 mg, about 1 mg to about 20 mg, about 1 mg to about 40 mg, about 1 mg to about 60 mg, about 1 mg to about 80 mg, about 1 mg to about 100 mg, about 10 mg to about 100 mg, about 20 mg to about 100 mg, about 40 mg to about 100 mg, about 60 mg to about 100 mg, or about 80 mg to about 100 mg. In some embodiments, Form 1 is administered at about 0.5 mg to about 10 mg per administration. In some embodiments, Form 1 is administered at about 0.8 mg to about 10 mg per administration. In some embodiments, Form 1 is administered at about 1 mg to about 5 mg per administration. In some embodiments, Form 1 is administered at about 2 mg to about 4 mg per administration. In some embodiments, Form 1 is administered at about 0.1 mg, 0.2 mg, 0.5 mg, 1 mg, 1.5 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, or 100 mg per administration. In some embodiments, Form 1 is administered at about 4.3 mg per administration. In some embodiments, Form 1 is administered at about 3.5 mg per administration. In some embodiments, Form 1 is administered orally.

[0248] In some embodiments, Form 8 is administered at about 0.1 mg to about 100 mg per administration, such as about 0.1 mg to about 50 mg, about 0.1 mg to about 10 mg, about 0.1 mg to about 5 mg, about 0.1 mg to about 4 mg, about 0.1 mg to about 3 mg, about 0.1 mg to about 2 mg, about 0.1 mg to about 1 mg, about 1 mg to about 5 mg, about 1 mg to about 10 mg, about 1 mg to about 20 mg, about 1 mg to about 40 mg, about 1 mg to about 60 mg, about 1 mg to about 80 mg, about 1 mg to about 100 mg, about 10 mg to about 100 mg, about 20 mg to about 100 mg, about 40 mg to about 100 mg, about 60 mg to about 100 mg, or about 80 mg to about 100 mg. In some embodiments, Form 8 is administered at about 0.5 mg to about 10 mg per administration. In some embodiments, Form 8 is administered at about 0.8 mg to about 10 mg per administration. In some embodiments, Form 8 is administered at about 1 mg to about 5 mg per administration. In some embodiments, Form 8 is administered at about 2 mg to about 4 mg per administration. In some embodiments, Form 8 is administered at about 0.1 mg, 0.2 mg, 0.5 mg, 1 mg, 1.5 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, or 100 mg per administration. In some embodiments, Form 8 is administered at about 4.3 mg per administration. In some embodiments, Form 8 is administered at about 3.5 mg per administration. In some embodiments, Form 8 is administered orally.

[0249] In alternative embodiments, the solid forms of the compounds of Formula II disclosed herein are administered continuously (i.e., without a period of, for example, one week during which the solid forms of the compounds of Formula II disclosed herein are not administered). In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered once a week. In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered twice a week. In some embodiments, the solid forms of the compounds of Formula II disclosed herein are administered three times a week. Pharmaceutical Compositions and Dosage Forms

[0250] In one aspect, there is provided herein a pharmaceutical composition comprising a solid form of a compound of Formula II disclosed herein and a pharmaceutically acceptable carrier.

[0251] In some embodiments, the pharmaceutical composition is suitable for oral administration. In some embodiments, the pharmaceutical composition is orally administered in any orally acceptable dosage form including, but not limited to, liqui - gel tablets or capsules, syrups, emulsions, and aqueous suspensions. The liqui - gel may include gelatin, plasticizers or opacifiers, or combinations thereof, if necessary to achieve a suitable consistency, and may be coated with an enteric coating approved for use, such as shellac. When used as an oral dosage form, additional thickening agents, such as gums, such as xanthan gum, starches, such as corn starch, or gluten, may be added to achieve the desired consistency of the pharmaceutical composition. If desired, certain sweetening agents, flavoring or coloring agents, or combinations thereof may be added.

[0252] In some embodiments, a pharmaceutical composition in a form suitable for oral administration, such as tablets, capsules, pills, powders, sustained - release formulations, extended - release formulations, delayed - release formulations, solutions, and suspensions, is administered to a subject. The pharmaceutical composition can be in unit dosage form suitable for a single administration of an exact dosage.

[0253] For oral administration, the solid forms of the active ingredient, e.g., the compounds of Formula II disclosed herein, can be readily formulated by combining the active ingredient with pharmaceutically acceptable carriers well known in the art. Such carriers enable the active ingredient of the present invention to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, powders or granules, suspensions or solutions in aqueous or non-aqueous media, etc. for oral ingestion by a subject. Pharmacological preparations for oral use can be manufactured using solid additives, pulverizing the resulting mixture if necessary, and treating the mixture of granules after adding auxiliaries suitable for obtaining, for example, tablets. Suitable additives such as diluents, binders or disintegrants would be desirable.

[0254] Oral dosage forms can, if desired, be presented in a pack or dispenser device, such as an FDA-approved kit, which may contain one or more unit dosage forms containing the active ingredient. A pack, such as a blister pack, may include, for example, a metal or plastic foil. Instructions for administration may be attached to the pack or dispenser device. A notice associated with the form of the container as defined by a government agency regulating the manufacture, use or sale of pharmaceuticals, reflecting the approval of the form of the composition or the agency of human or veterinary administration, may also be attached to the pack or dispenser. Such notice may be, for example, that of a label approved by the U.S. Food and Drug Administration for prescription drugs or an approved product insert.

[0255] In one aspect, provided herein is an oral dosage form comprising (a) a crystalline form 1 of an effective amount of a compound of formula II that exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2, and (b) at least one pharmaceutically acceptable carrier. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.2, and 9.0 ± 0.2. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.2, 9.0 ± 0.2, and 18.1 ± 0.2.

[0256] In some embodiments, provided herein is an oral dosage form comprising (a) a crystalline form 1 of an effective amount of a compound of formula II that exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3, and (b) at least one pharmaceutically acceptable carrier. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.3, and 9.0 ± 0.3. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.3, 9.0 ± 0.3, and 18.1 ± 0.3.

[0257] In some embodiments, provided herein is an oral dosage form comprising (a) a crystalline form 1 of an effective amount of a compound of formula II that exhibits an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.5, and (b) at least one pharmaceutically acceptable carrier. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.5, and 9.0 ± 0.5. In some embodiments, form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.5, 9.0 ± 0.5, and 18.1 ± 0.5.

[0258] In some embodiments, the oral dosage form is a solid oral dosage form contained in a capsule.

[0259] In some embodiments, the oral dosage form comprises a solid form of the compound of Formula II at about 0.8 mg (based on the free form; 0.864 mg based on Form 1). In some embodiments, the oral dosage form comprises a solid form of the compound of Formula II at about 0.8% w / w (based on the free form; 0.864% w / w based on Form 1).

[0260] In some embodiments, the pharmaceutically acceptable carrier is a filler. In some embodiments, the filler is mannitol. In some embodiments, the mannitol is a mixture of fine mannitol and granular mannitol.

[0261] In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 90% w / w to about 99% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 95% w / w to about 99% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 97% w / w to about 99% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 97% w / w to about 98% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 90% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 95% w / w. In some embodiments, the filler (e.g., mannitol) is present in the oral dosage form in an amount of about 97% w / w.

[0262] In some embodiments, the oral dosage form further comprises a lubricant. In some embodiments, the lubricant is magnesium stearate.

[0263] In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.05% w / w to about 3% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.1% w / w to about 3% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.5% w / w to about 3% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 1% w / w to about 3% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 1% w / w to about 2% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.05% w / w to about 2% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.1% w / w to about 2% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.5% w / w to about 2% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.1% w / w to about 3% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 0.5% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 1% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 1.5% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 2% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 2.5% w / w. In some embodiments, a lubricant (e.g., magnesium stearate) is present in the oral dosage form in an amount of about 3% w / w.

[0264] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.2, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0265] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 9.0 ± 0.2, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0266] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 9.0 ± 0.2, and 18.1 ± 0.2, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0267] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising characteristic XRPD peaks at the following diffraction angles (2θ (degrees)) = 9.0 ± 0.3, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0268] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 9.0 ± 0.3, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0269] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3, 9.0 ± 0.3, and 18.1 ± 0.3, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0270] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising a characteristic XRPD peak at the following diffraction angle (2θ (degrees)) = 9.0 ± 0.5, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0271] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5 and 9.0 ± 0.5, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0272] In some embodiments, an oral dosage form is provided herein that comprises (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) exhibiting an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, 9.0 ± 0.5, and 18.1 ± 0.5, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%.

[0273] In one aspect, a method of manufacturing an oral dosage form comprising (a) Form 1 of the compound of Formula II at about 0.8% w / w (based on the free form) exhibiting an X-ray powder diffraction pattern comprising a characteristic XRPD peak at the following diffraction angle (2θ (degrees)) = 9.0 ± 0.2, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2% comprises: (i) sieving a first portion of the filler through a screen and blending the sieved first portion of the filler; (ii) sieving Form 1 of the compound of Formula II through a screen and blending the sieved Form 1 with the sieved and blended first portion of the filler from step (i) to form a pre-blend 1; (iii) sieving a second portion of the filler through a screen and blending the sieved second portion of the filler; (iv) contacting and blending pre-blend 1 with the sieved and blended second portion of the filler from step (iii) to form a pre-blend 2; (v) sieving a third portion of the filler through a screen and blending the sieved third portion of the filler; (vi) contacting and blending pre-blend 2 with the sieved and blended third portion of the filler from step (v) to form a blend; (vii) sieving the lubricant through a screen and blending with the blend from step (vi) to form a final blend. (viii) encapsulating the final blend into a capsule shell, thereby forming an oral dosage form; A method comprising the above is provided herein.

[0274] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2 and 9.0 ± 0.2. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.2, 9.0 ± 0.2, and 18.1 ± 0.2.

[0275] In one aspect, a method for manufacturing an oral dosage form comprising (a) Form 1 of a compound of Formula II at about 0.8% w / w (based on the free form) showing an X-ray powder diffraction pattern comprising a characteristic XRPD peak at the following diffraction angle (2θ (degrees)) = 9.0 ± 0.3, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%, comprising: (i) sieving a first portion of the filler through a screen and blending the sieved first portion of the filler; (ii) sieving Form 1 of the compound of Formula II through a screen and blending the sieved Form 1 with the sieved and blended first portion of the filler from step (i) to form a pre-blend 1; (iii) sieving a second portion of the filler through a screen and blending the sieved second portion of the filler; (iv) contacting and blending pre-blend 1 with the sieved and blended second portion of the filler from step (iii) to form a pre-blend 2; (v) sieving a third portion of the filler through a screen and blending the sieved third portion of the filler; (vi) contacting and blending pre-blend 2 with the sieved and blended third portion of the filler from step (v) to form a blend; (vii) Sieving the lubricant through a screen and blending it with the blend of step (vi) to form a final blend; (viii) Encapsulating the final blend in a capsule shell, thereby forming an oral dosage form; A method comprising the above is provided herein.

[0276] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.3 and 9.0 ± 0.3. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.3, 9.0 ± 0.3, and 18.1 ± 0.3.

[0277] In one aspect, a method for manufacturing an oral dosage form comprising (a) Form 1 of a compound of Formula II at about 0.8% w / w (based on the free form) exhibiting an X-ray powder diffraction pattern comprising a characteristic XRPD peak at the following diffraction angle (2θ (degrees)) = 9.0 ± 0.5, and (b) a pharmaceutically acceptable filler in an amount of about 95% w / w to about 98% w / w, and (c) a pharmaceutically acceptable lubricant in an amount of about 1% to about 2%, comprising: (i) Sieving a first portion of the filler through a screen and blending the sieved first portion of the filler; (ii) Sieving Form 1 of the compound of Formula II through a screen and blending the sieved Form 1 with the sieved and blended first portion of the filler of step (i) to form a pre-blend 1; (iii) Sieving a second portion of the filler through a screen and blending the sieved second portion of the filler; (iv) Contacting and blending pre-blend 1 with the sieved and blended second portion of the filler of step (iii) to form a pre-blend 2; (v) Sieving a third portion of the filler through a screen and blending the sieved third portion of the filler; (vi) sieving the pre-blend 2, contacting it with a third portion of the blended filler, and blending to form a blend; (vii) sieving the lubricant through a screen and blending it with the blend of step (vi) to form a final blend; (viii) encapsulating the final blend in a capsule shell, thereby forming an oral dosage form A method comprising is provided herein.

[0278] In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) = 4.5 ± 0.5, and 9.0 ± 0.5. In some embodiments, Form 1 exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ (degrees)) 4.5 ± 0.5, 9.0 ± 0.5, and 18.1 ± 0.5.

[0279] In some embodiments, blending is performed using high shear dry blending.

[0280] In some embodiments, the first portion of the filler is fine mannitol powder.

[0281] In some embodiments, the second portion of the filler is granular mannitol.

[0282] In some embodiments, the second portion of the filler is granular mannitol.

[0283] In some embodiments, the lubricant is magnesium stearate.

[0284] In some embodiments, the capsule shell is a hypromellose capsule shell. Treatment method

[0285] The methods described herein contemplate treating abnormal cell growth (e.g., cancer) in a subject in need of treatment thereof by administering to the subject a solid form of a compound of Formula II or a pharmaceutical composition in an effective amount as described herein. Abnormal cell growth

[0286] As used herein, abnormal cell growth, unless otherwise indicated, refers to cell growth independent of normal regulatory mechanisms (e.g., loss of contact inhibition). This includes (1) tumor cells (tumors) that grow, for example, by expressing a mutant tyrosine kinase or by overexpressing a receptor tyrosine kinase; (2) benign and malignant cells of other proliferative diseases in which, for example, abnormal tyrosine kinase activation occurs; (3) any tumor that grows by a receptor tyrosine kinase; (4) any tumor that may grow by abnormal serine / threonine kinase activation; and (5) abnormal growth of benign and malignant cells of other proliferative diseases in which, for example, abnormal serine / threonine kinase activation occurs. Abnormal cell growth can refer to cell growth in epithelial (e.g., carcinoma, adenocarcinoma); mesenchymal (e.g., sarcoma (e.g., leiomyosarcoma, Ewing's sarcoma)); hematopoietic; or other (e.g., melanoma, mesothelioma, and other tumors of unknown origin) cells. Neoplastic disorder

[0287] Abnormal cell growth can refer to a neoplastic disorder. A "neoplastic disorder" is a disease or disorder characterized by cells having the ability to grow or replicate autonomously, e.g., an abnormal condition or state characterized by proliferative cell growth. An abnormal mass of tissue, or "neoplasm," resulting from abnormal cell growth or division can be benign, pre-malignant (intraepithelial carcinoma) or malignant (cancer).

[0288] Exemplary neoplastic disorders include carcinomas, sarcomas, metastatic disorders (e.g., tumors arising from prostate, colon, lung, breast, and liver origin), hematopoietic neoplastic disorders, such as leukemia, metastatic tumors. Treatment with the solid forms of the compounds of Formula II disclosed herein can be in an amount effective to ameliorate at least one symptom of a neoplastic disorder, e.g., reduce cell proliferation, reduce tumor mass, etc. cancer

[0289] The inventive methods of the present invention can be useful in the prevention and treatment of cancers, including, for example, solid tumors, soft tissue tumors, and metastases thereof. The disclosed methods can also be useful in the treatment of non-solid cancers. Exemplary solid tumors include malignant diseases of various organ systems (e.g., sarcomas, adenocarcinomas, and carcinomas), such as those of the lung, breast, lymphatic system, gastrointestinal tract (e.g., colon), and genitourinary tract (e.g., kidney, urothelial, or testicular tumors), pharynx, prostate, and ovary. Exemplary adenocarcinomas include colorectal cancer, renal cell carcinoma, liver cancer (e.g., hepatocellular carcinoma), non-small cell lung cancer, pancreatic (e.g., metastatic pancreatic ductal adenocarcinoma), and small intestine cancers.

[0290] Cancers can include mesothelioma; neurofibromatosis, e.g., neurofibromatosis type 2, neurofibromatosis type 1; kidney cancer; lung cancer, e.g., non-small cell lung cancer, e.g., metastatic NSCLC; lung adenocarcinoma, e.g., NSCLC adenocarcinoma; liver cancer; thyroid cancer; ovarian cancer, e.g., low-grade serous ovarian cancer; breast cancer; pancreatic cancer, e.g., pancreatic adenocarcinoma; colorectal cancer, e.g., colorectal adenocarcinoma; endometrial cancer; gynecological cancers, e.g., cervical cancer, ovarian cancer, uterine cancer, vaginal cancer, endometrial cancer, or vulvar cancer; liver cancer; prostate cancer; mesothelioma; bladder cancer; melanoma, e.g., unresectable melanoma, metastatic melanoma; thyroid cancer, e.g., papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer; glioblastoma; kidney cancer; nervous system tumors; schwannoma; meningioma; neurofibromatosis; acoustic neuroma; adenoid cystic carcinoma; epithelioma; and epithelioma tumors.

[0291] In some embodiments, the cancer is lung cancer, such as non-small cell lung cancer. In some embodiments, the cancer is ovarian cancer, such as low-grade serous ovarian cancer.

[0292] The cancer can include cancers characterized as including cancer stem cells, cancer-associated mesenchymal cells, or tumor-initiating cancer cells. The cancer can include cancers characterized as being enriched in cancer stem cells, cancer-associated mesenchymal cells, or tumor-initiating cancer cells (e.g., tumors or metastatic tumors enriched in cells that have undergone epithelial-mesenchymal transition).

[0293] The cancer can be a primary tumor, i.e., can be located at the anatomical site where tumor growth begins. The cancer can also be metastatic, i.e., can appear at at least a second anatomical site other than the anatomical site where tumor growth begins. The cancer can be a recurrent cancer, i.e., a cancer that recurs after treatment and after a period during which the cancer was undetectable. The recurrent cancer can be anatomically local to the original tumor, e.g., anatomically near the original tumor; locally to the original tumor, e.g., in lymph nodes located near the original tumor; or distal to the original tumor, e.g., in regions anatomically distant from the original tumor.

[0294] The cancer can also include, for example, but not limited to, epithelial cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, prostate cancer, head and neck cancer, melanoma, acute myeloid leukemia, and glioblastoma. Exemplary breast cancers include triple-negative breast cancer, basal-like breast cancer, low-claudin breast cancer, invasive, inflammatory, dysplastic, and treatment-resistant advanced HER-2 positive or ER positive cancers.

[0295] Cancer may also include lung adenocarcinoma, colorectal cancer (CRC), uveal melanoma, ovarian cancer, endometrial cancer, bladder urothelial cancer, invasive lobular carcinoma of the breast, squamous cell carcinoma of the cervix, cutaneous melanoma, endocervical adenocarcinoma, hepatocellular carcinoma, pancreatic adenocarcinoma, biphasic type pleural mesothelioma, renal clear cell carcinoma, renal clear cell carcinoma, gastric adenocarcinoma, gastric tubular adenocarcinoma, carcinosarcoma of the uterus, or uterine malignant mixed Mullerian tumor.

[0296] In some embodiments, the cancer is unresectable or metastatic melanoma, melanoma with lymph node metastasis or metastatic disease following complete resection, metastatic non-small cell lung cancer and progression during or after platinum-based chemotherapy, metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy, progressive renal cell carcinoma previously treated with anti-angiogenic therapy, progressive renal cell carcinoma, classical Hodgkin lymphoma, recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression during or after platinum-based therapy, locally advanced or metastatic urothelial cancer, high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) metastatic colorectal cancer, or hepatocellular carcinoma.

[0297] In some embodiments, the cancer is melanoma, non-small cell lung cancer, small cell lung cancer, squamous cell carcinoma of the head and neck, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial cancer, high-frequency microsatellite instability cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, or endometrial cancer.

[0298] Other cancers include, but are not limited to, uveal melanoma, brain cancer, abdominal cancer, esophageal cancer, gastrointestinal cancer, glioma, liver cancer, tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, retinoblastoma, Wilms tumor, multiple myeloma, skin cancer, lymphoma, blood cancer, and bone marrow cancer (e.g., advanced hematological malignancies, leukemia, e.g., acute myeloid leukemia (primary or secondary), acute lymphoblastic leukemia, acute lymphocytic leukemia, T-cell leukemia, hematological malignancies, advanced myeloproliferative disorders, myelodysplastic syndromes, relapsed or refractory multiple myeloma, advanced myeloproliferative disorders), retinal cancer, bladder cancer, cervical cancer, kidney cancer, endometrial cancer, meningioma, lymphoma, skin cancer, uterine cancer, lung cancer, non-small cell lung cancer, nasopharyngeal carcinoma, neuroblastoma, solid tumors, hematological malignancies, squamous cell carcinoma, testicular cancer, thyroid cancer, mesothelioma, brain cancer, vulvar cancer, sarcoma, intestinal cancer, oral cancer, endocrine cancer, salivary gland cancer, spermatocytic seminoma, sporadic medullary thyroid carcinoma, non-proliferating testicular cells, cancers associated with malignant mast cells, non-Hodgkin lymphoma, and diffuse large B-cell lymphoma.

[0299] In some embodiments, the tumor is a solid tumor. In some embodiments, the solid tumor is locally advanced or metastatic. In some embodiments, the solid tumor is refractory (e.g., resistant) after standard treatment.

[0300] The methods described herein can reduce, ameliorate, or completely eliminate a disorder or its associated symptoms, or combinations thereof, prevent them from worsening, slow their rate of progression, or minimize their recurrence rate (i.e., avoid relapse) once the disorder has been initially eliminated. Suitable dosages and treatment regimens can vary depending on the specific compound, combination, or pharmaceutical composition used, as well as the mode of delivery of the compound, combination, or pharmaceutical composition. In some embodiments, the method significantly increases the mean length of survival, increases the mean length of progression-free survival, or decreases the recurrence rate, or combinations thereof, of a subject treated with a solid form of a compound of Formula II described herein.

[0301] In some embodiments, the cancer is lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer (e.g., unresectable low-grade ovarian cancer, advanced or metastatic ovarian cancer), rectal cancer, anal cancer, gastric cancer, colon cancer, breast cancer (e.g., triple-negative breast cancer (e.g., breast cancer that does not express the estrogen receptor, progesterone receptor, and Her2 / neu genes)), uterine cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureteral cancer, renal cell carcinoma, renal pelvis carcinoma, central nervous system (CNS) neoplasm, primary CNS lymphoma, spinal axis tumor, brainstem glioma, pituitary adenoma, mesothelioma (e.g., malignant pleural mesothelioma, e.g., surgically resectable malignant pleural mesothelioma) or one or more combinations of the foregoing cancers. In some embodiments, the cancer is metastatic. In some embodiments, the abnormal cell growth is locally recurrent (e.g., the subject has a locally recurrent disease, e.g., cancer). Additional treatment

[0302] In some embodiments, the methods and compositions described herein are administered with an additional treatment or an additional agent. In one embodiment, a mixture of one or more compounds or pharmaceutical compositions can be administered to a subject in need thereof with an additional treatment or an additional agent. In yet another embodiment, one or more compounds or pharmaceutical compositions can be administered with an additional treatment or an additional agent for the treatment or avoidance of various diseases including, for example, cancer, diabetes, neurodegenerative diseases, cardiovascular diseases, blood clotting, inflammation, flushing, obesity, aging, stress, and the like. In various embodiments, the combination therapies comprising the compounds or pharmaceutical compositions described herein can refer to (1) a pharmaceutical composition comprising one or more compounds in combination with an additional treatment or an additional agent, and (2) the simultaneous administration of one or more compounds or pharmaceutical compositions described herein that are not formulated in the same composition with an additional treatment or an additional agent. In some embodiments, a solid form of a compound of Formula II described herein is administered with an additional treatment (e.g., an additional cancer treatment). In some embodiments, the additional treatment (e.g., an additional cancer treatment) can be administered simultaneously (e.g., at the same time) or sequentially with the same or a separate composition. Sequential administration refers to the administration of an additional treatment, e.g., a second treatment (e.g., a compound or treatment), before (e.g., immediately before, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, less than 60 minutes before; 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours, 72 hours, 96 hours or longer before; 4 days, 5 days, 6 days, 7 days, 8 days, 9 days or longer before; 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or longer before) the administration of a certain treatment. The order of administration of the first and second compounds or treatments can also be reversed.

[0303] In some embodiments, the additional treatment is a cancer treatment. Exemplary cancer treatments include, for example, chemotherapy, targeted chemotherapy, such as antibody therapy, immunotherapy, and hormone therapy. Examples of each of these treatments are provided below. Chemotherapy

[0304] In some embodiments, the solid forms of the compounds of Formula II described herein are administered with chemotherapy. Chemotherapy is the treatment of cancer with drugs that can destroy cancer cells. "Chemotherapy" generally refers to cytotoxic drugs that affect cells that are generally rapidly dividing, as opposed to targeted chemotherapy. Chemotherapy drugs interfere with cell division in various possible ways, such as the replication of DNA or the separation of newly formed chromosomes. Almost all forms of chemotherapy target rapidly dividing cells and are not specific to cancer cells, although some degree of specificity can arise from the fact that many cancer cells cannot repair DNA damage, while normal cells generally can.

[0305] In some embodiments, the solid forms of the compounds of Formula II described herein are administered with one or more chemotherapeutic agents. Examples of chemotherapeutic agents used in cancer treatment include, for example, antimetabolites (e.g., folic acid, purine, and pyrimidine derivatives) and alkylating agents (e.g., nitrogen mustard, nitrosourea, platinum, alkyl sulfonate, hydrazine, triazene, aziridine, spindle poison, cytotoxic agent, topoisomerase inhibitor, etc.). Exemplary agents include aclarubicin, actinomycin, alitretinon, altretamine, aminopterin, aminolevulinic acid, amrubicin, amsacrine, anagrelide, arsenic trioxide, asparaginase, atrasentan, belotecan, bexarotene, bendamustine, bleomycin, bortezomib, busulfan, camptotnecin, capecitabine, carboplatin, carboquone, carmofur, carmustine, celecoxib, chlorambucil, chloromethine, cisplatin, cladribine, clofarabine, chrysantasparase, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, decitabine, dexamethasone, docetaxel, doxorubicin, efaproxiral, elesclomol, elsamitrucin, enocitabine, epirubicin, estramustine, etoglucid, etoposide, floxuridine, fludarabine, fluorouracil (5FU), folfirinox, fotemustine, gemcitabine, gliadel implant, hydroxycarbamide, hydroxyurea, idarubicin, ifosfamide, irinotecan, irofulven, ixabepilone, larotaxel, leucovorin, liposomal doxorubicin, liposomal daunorubicin, lonidamine, lomustine, lucanthone, mannosulfan, masoprocol, melphalan, mercaptopurine, mesna, methotrexate, methyl aminolevulinate, mitobronitol, mitoguazone, mitotane, mitomycin, mitoxantrone, nedaplatin, nimustine, oblimersen, omacetaxine, ortataxel, oxaliplatin, paclitaxel, pegaspargase,Pemetrexed, pentostatin, pirarubicin, pixantrone, plicamycin, porfimer sodium, prednimustine, procarbazine, raltitrexed, ranimustine, rubitecan, sapacitabine, semustine, sitimagene ceradenovec, strataplatin, streptozocin, talaporfm, tegafur-uracil, temoporfin, temozolomide, teniposide, tesetaxel, testolactone, tetranitrate, thiotepa, thiazofurin, thioguanine, tipifarnib, topotecan, trabectedin, triaziquone, triethylenemelamine, triplatin, tretinoin, treosulfan, trofosfamide, uramustine, valrubicin, verteporfin, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vorinostat, zolbetuximab, and other cytostatic or cytotoxic agents described herein are included.,

[0306] Some drugs work better together than alone, so often two or more drugs are given at the same time or sequentially. Often, two or more chemotherapeutic agents are used as combination chemotherapy. In some embodiments, chemotherapeutic agents (including combination chemotherapy) can be used in combination with the solid form of the compound of Formula II described herein. Targeted chemotherapy

[0307] In some embodiments, a solid form of a compound of Formula II described herein is administered in a targeted therapy. Targeted therapy comprises the use of agents specific for deregulated proteins in cancer cells. Small molecule targeted therapy drugs are generally inhibitors of the enzymatic domains of proteins that are mutated, overexpressed, or otherwise critically important within cancer cells. Notable examples are tyrosine kinase inhibitors such as axitinib, bosutinib, cediranib, dasatinib, erolotinib, imatinib, gefitinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sorafenib, sunitinib, and vandetanib, and also cyclin-dependent kinase inhibitors such as alvocidib and seliciclib. Monoclonal antibody therapy is another strategy where the therapeutic agent is an antibody that specifically binds to a protein on the surface of cancer cells. Examples include the anti-HER2 / neu antibody trastuzumab (HERCEPTIN®), which is typically used in breast cancer, and the anti-CD20 antibodies rituximab and tositumomab, which are typically used in various B-cell malignancies. Other exemplary antibodies include cetuximab, panitumumab, trastuzumab, alemtuzumab, bevacizumab, edrecolomab, and gemtuzumab. Exemplary fusion proteins include aflibercept and denileukin diftitox. In some embodiments, the targeted therapy can be used in combination with a solid form of a compound of Formula II described herein.

[0308] Targeted therapy can also involve small molecule peptides as "homing devices" that can bind to cell surface receptors or the diseased extracellular matrix surrounding the tumor. Radionuclides (e.g., RGD) attached to these peptides will decay in the vicinity of the cells and ultimately kill the cancer cells. An example of such a therapy is BEXXAR®. Immunotherapy

[0309] In some embodiments, a solid form of a compound of Formula II described herein is administered with immunotherapy. Cancer immunotherapy refers to a diverse set of treatment strategies designed to induce the subject's own immune system to fight tumors.

[0310] Modern methods for generating an immune response against tumors include intravesical BCG immunotherapy for superficial bladder cancer, as well as the use of interferons and other cytokines to induce an immune response in subjects with renal cell carcinoma and melanoma. Allogeneic hematopoietic stem cell transplantation can be considered a form of immunotherapy since donor immune cells often attack tumors with a graft-versus-tumor effect. In some embodiments, an immunotherapeutic agent can be used in combination with a solid form of a compound of Formula II described herein. Hormone Therapy

[0311] In some embodiments, a solid form of a compound of Formula II described herein is administered with hormone therapy. The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast cancer and prostate cancer. Removing or blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of a hormone agonist such as a progestogen can be therapeutically beneficial. In some embodiments, a hormone therapy agent can be used in combination with a solid form of a compound of Formula II described herein.

[0312] In some embodiments, the additional agent is an agent that modifies ER, PR, or AR, or a combination thereof. For example, the additional agent is an AR antagonist, including but not limited to flutamide, bicalutamide, and nilutamide. In some embodiments, the additional agent is an agent that blocks estrogen or progesterone, including but not limited to aromatase inhibitors such as anastrozole, letrozole, and exemestane. In some embodiments, the additional agent is an estrogen receptor modulator, including but not limited to fulvestrant, tamoxifen, and raloxifene. Radiation therapy

[0313] The solid forms of the compounds of Formula II described herein can be used in combination with directed energy or particles, or radioisotope treatment, such as radiation therapy, such as radiation oncology, to treat proliferative diseases, such as cancer, such as cancer associated with cancer stem cells. The solid forms of the compounds of Formula II described herein can be administered to a subject simultaneously or sequentially with directed energy or particles, or radioisotope treatment. For example, the solid forms of the compounds of Formula II described herein can be administered before, during, or after directed energy or particles, or radioisotope treatment, or a combination thereof. Directed energy or particle therapy can include whole body irradiation, local irradiation, or point irradiation. Directed energy or particles can be derived from an accelerator, synchrotron, nuclear reaction, vacuum tube, laser, or radioisotope. This therapy can include external beam radiation therapy, teletherapy, brachytherapy, sealed source radiation therapy, systemic radioisotope therapy, or unsealed source radiotherapy. This therapy can include the uptake of a radioisotope, such as radioactive iodine, cobalt, cesium, potassium, bromine, fluorine, carbon, or placement in proximity thereto. External irradiation can include exposure to directed alpha particles, electrons (e.g., beta particles), protons, neutrons, positrons, or photons (e.g., radio waves, millimeter waves, microwaves, infrared light, visible light, ultraviolet light, X-rays, or gamma ray photons). Radiation can be directed to any part of the subject in need of treatment. Surgery

[0314] The solid forms of the compounds of formula II described herein can be used in combination with surgery, such as surgical examination, intervention, biopsy, for treating proliferative diseases, such as cancer, for example, cancer associated with cancer stem cells. The solid forms of the compounds of formula II described herein can be administered to a subject simultaneously or sequentially with surgery. For example, the solid forms of the compounds of formula II described herein can be administered before (pre-operative), during, or after (post-operative) surgery, or a combination thereof. Surgery can be a biopsy in which one or more cells are collected for further analysis. The biopsy can be achieved, for example, by a scalpel, needle, catheter, endoscope, spatula, or forceps. The biopsy can be an excisional biopsy, incisional biopsy, core biopsy, or needle biopsy, for example, a needle aspiration biopsy. Surgery can involve the removal of local tissue suspected or identified as being cancerous. For example, the procedure can involve the removal of a cancerous lesion, mass, polyp, or mole. The procedure can involve the removal of large amounts of tissue, such as breast, bone, skin, fat, or muscle. The procedure can involve the removal of an organ or node, such as part or all of the lung, throat, tongue, bladder, cervix, ovary, testis, lymph node, liver, pancreas, brain, eye, kidney, gallbladder, stomach, colon, rectum, or intestine. In one embodiment, the cancer is breast cancer, such as triple-negative breast cancer, and the surgery is a mastectomy or lumpectomy. Anti-inflammatory agent

[0315] The solid forms of the compounds of formula II described herein can be administered with an anti-inflammatory agent. The anti-inflammatory agents can include, but are not limited to, non-steroidal anti-inflammatory agents (e.g., salicylates (such as aspirin (acetylsalicylic acid), diflunisal, salsalate), propionic acid derivatives (ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, loxoprofen), acetic acid derivatives (indomethacin, sulindac, etodolac, ketorolac, diclofenac, nabumetone), enolic acid (oxicam) derivatives (piroxicam, meloxicam, tenoxicam, droxicam, lomoxicam, isoxicam), fenamic acid derivatives (fenamates) (mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid), selective COX-2 inhibitors (coxibs) (celecoxib), sulfonanilide (nimesulide), steroids (e.g., hydrocortisone (cortisol), cortisone acetate, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclomethasone, fludrocortisone acetate, deoxycorticosterone acetate, aldosterone). Analgesic

[0316] Analgesics may include, but are not limited to, opioids (e.g., morphine, codeine, oxycodone, hydrocodone, dihydromorphine, pethidine, buprenorphine, tramadol, venlafaxine), paracetamol, and non-steroidal anti-inflammatory drugs (e.g., salicylates (aspirin (acetylsalicylic acid), diflunisal, salsalate), propionic acid derivatives (ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, loxoprofen), acetic acid derivatives (indomethacin, sulindac, etodolac, ketorolac, diclofenac, nabumetone), enolic acid (oxicam) derivatives (piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam), fenamic acid derivatives (fenamate) (mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid), selective COX-2 inhibitors (coxib) (celecoxib), sulfonanilide (nimesulide). Antiemetics

[0317] The solid forms of the compounds of formula II described herein can be administered with an antiemetic. Antiemetics can include, but are not limited to, 5-HT3 receptor antagonists (dolasetron (Anzemet), granisetron (Kytril, Sancuso), ondansetron (Zofran), tropisetron (Navoban), palonosetron (Aloxi), mirtazapine (Remeron)), dopamine antagonists (domperidone, olanzapine, droperidol, haloperidol, chlorpromazine, promethazine, prochlorperazine, metoclopramide (Reglan), alizapride, prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil)), NK1 receptor antagonists (aprepitant (Emend), antihistamines (cyclizine, diphenhydramine (Benadryl), dimenhydrinate (Gravol, Dramamine), meclizine (Bonine, Antivert), promethazine (Pentazine, Phenergan, Promacot), hydroxyzine), benzodiazapines (lorazepam, midazolam), anticholinergics (hyoscyamine), steroids (dexamethasone). Combination

[0318] The phrase "in combination with" and the terms "co-administer", "co-administering" or "co-providing", as used herein in the context of the administration of the compounds described herein or the treatments described herein, mean that two (or more) different compounds or treatments are delivered to a subject during the course of the subject's affliction with a disease or disorder (e.g., a disease or disorder described herein, such as cancer), e.g., two (or more) different compounds or treatments are delivered to the subject after the subject has been diagnosed with a disease or disorder (e.g., a disease or disorder described herein, such as cancer) and before the disease or disorder is cured or eliminated, or the treatment is discontinued for some other reason.

[0319] In some embodiments, the delivery of a compound or treatment continues even when the delivery of a second compound or treatment begins such that there is an overlap with respect to administration. This is sometimes referred to herein as "simultaneous" or "co-delivery". In other embodiments, the delivery of a compound or treatment ends before the delivery of another compound or treatment begins. In some embodiments in either case, the treatment (e.g., administration of a compound, composition, or treatment) is more effective for combination administration. For example, the second compound or treatment is more effective than would be seen if the second compound or treatment were administered in the absence of the first compound or treatment, e.g., a second compound or treatment with fewer equivalent effects is seen, or the second compound or treatment reduces symptoms to a greater extent, or a similar situation is seen with the first compound or treatment. In some embodiments, the delivery is such that the reduction of symptoms, or other parameters associated with the disorder, is greater than that observed with one of the compounds or treatments delivered in the absence of the other. The effects of the two compounds or treatments can be partially additive, fully additive, or supra-additive (e.g., synergistic). The delivery can be such that the first compound or treatment delivered is still detectable when the second compound or treatment is delivered.

[0320] In some embodiments, the first compound or treatment and the second compound or treatment can be administered simultaneously (e.g., at the same time) or sequentially in the same or separate compositions. Sequential administration refers to the administration of a compound or treatment before the administration of an additional, e.g., secondary, compound or treatment (e.g., immediately before, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, less than 60 minutes before; 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours, 72 hours, 96 hours or longer before; 4 days, 5 days, 6 days, 7 days, 8 days, 9 days or longer before; 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or longer before). The order of administration of the first and second compounds or treatments can also be reversed.

[0321] The combinations described herein can be a first - line treatment for abnormal cell growth, e.g., cancer (i.e., used in subjects not previously administered another drug intended to treat cancer); a second - line treatment for cancer (i.e., used in subjects in need thereof who have been previously administered another drug intended to treat cancer); or a third or fourth treatment for cancer (i.e., used in subjects who have been previously administered two or three other drugs intended to treat cancer).

Examples

[0322] The following representative examples are intended to assist in explaining the present invention and are not intended, nor should they be construed, to limit the scope of the present invention.

Table 12 - 1

Table 12 - 2

[0323] Samples were analyzed using a TA Instruments Q2000. Samples of 2 - 8 mg were hermetically sealed in corresponding Tzero aluminum sample pans with lids. The samples were scanned from 25 °C to 300 °C at a rate of 10 °C / min under a nitrogen purge of 50 mL / min. Thermogravimetric analysis (TGA)

[0324] Thermal analysis of the samples was performed using a TA Instruments Q500 TGA equipped with a single - position sampler. Samples of 2 - 10 mg were loaded into pre - weighed, sealed aluminum DSC pans with pin - holes in the lids to allow gas escape. The samples were scanned from 25 °C to 350 °C at a rate of 10 °C / min in combination with a nitrogen purge of 60 mL / min. Dynamic vapor sorption (DVS)

[0325] The sample was analyzed using a TA Instruments Q5000SA gravimetric moisture sorption analyzer. The weight of the sample was continuously monitored and recorded with respect to relative humidity (RH) and time. A 5 - 10 mg sample was placed in a sealed aluminum DVS pan that had been tared under ambient conditions. After perforating the sample pan, it was placed in the humidity chamber. The moisture sorption isotherm was performed at 25 °C at 10% RH intervals over the range of 0 - 90% RH. Three cycles were performed. If the mass increase or decrease during the sorption step was less than 0.1% over 15 minutes, the next humidity interval could be started. If the weight continued to change after 120 minutes at a given step, the step timed out and could proceed to the next humidity interval. X - ray powder diffraction (XRPD)

[0326] The X - ray powder diffraction pattern was obtained using a Bruker D8 equipped with a Cu Kα radiation source (40 kV, 40 mA) (λ = 1.54 Å), a 9 - position sample holder, and a θ - 2θ goniometer with a Ge monochromator. The incident beam passed through a 2.0 mm divergence slit and then through a 0.2 mm anti - scatter slit. The diffracted beam passed through an 8.0 mm receiving slit with a 2.5° soller slit and then through a LYNXEYE ultra - fast detector. The sample was prepared on a polished zero - background silicon plate and run using a low - background airtight sample dome.

[0327] For the initial pattern screening, the Bruker D8 followed a 4 - minute method with an angular range of 3 - 40° and a step size of 0.014° 2θ at 0.1 second per step. For the final form collection, the Bruker D8 followed a 30 - minute method with an angular range of 3 - 40° and a step size of 0.018° 2θ at 0.85 second per step. The software used for data collection and analysis was Diffrac Plus XRD Commander and Diffrac Plus EVA, respectively.

[0328] Proton nuclear magnetic resonance (1H NMR)

[0329] The 1H NMR data were collected using a Bruker Ascend 600 MHz NMR equipped with TopSpin 4.0.8 software. The sample was prepared by dissolving the compound in deuterated dimethyl sulfoxide containing 0.05% (v / v) tetramethylsilane (TMS). The spectra were collected using 16 scans at 298K. Polarizing microscopy (PLM)

[0330] The sample was analyzed using an Olympus BX53 polarizing microscope. There are four magnifications for the lens options: 4x, 10x, 25x, and 50x.

[0331] To capture images, the Olympus BX53 is equipped with a PAXcam3 digital microscope camera. The camera has a resolution of 3.1 megapixels, 2048×1536 pixels, and is equipped with a camera adapter with a magnification of 0.5x. Karl Fischer titration (KF)

[0332] The apparent water content of the sample was determined using a Mettler Toledo DL39 Coulometric KF titrator. Approximately 90 - 100 mg of solid was used for the titration. To limit the exposure of the solution to air, the opening of the titrator was closed with a stopper immediately after adding the sample. HYDRANAL - Coulomat AD was used as the titrant and added at a rate of 40%. The mixing time used before analysis was 30 seconds. Ultra - performance liquid chromatography (UPLC)

[0333] The purity of the sample was determined using a method provided by JM's Analytical Development. Data were collected using an Agilent 12900 series UPLC system and analyzed using Chemstation software. (Example 1) Exemplary preparation of Form 1

[0334] Exemplary Form 1 of VS-6766 was prepared, for example, with Compound A having a batch size of about 3300 g, according to the following synthetic scheme and the flow diagram shown in Figure 1A. [Chemical formula]

[0335] In summary, a potassium hydroxide solution was added to a solution of Compound A in THF / water at about 15 ± 5 °C over about 15 minutes, heated to about 55 ± 5 °C, and stirred at about 55 ± 5 °C for about 1 hour. The mixture was then cooled to about 20 ± 5 °C and gradually filled with THF. The mixture was further cooled to -5 ± 5 °C and then stirred. The resulting precipitate was filtered. The reactor was rinsed with THF / water and the solid was filtered. The reactor was rinsed with THF and then the solid was filtered as the washing liquid. The filtered solid was dried at a high temperature (for example, about 35 °C in an oven) to produce Compound 1 as Form 1.

[0336] Exemplary Form 1 produced according to the above method contains, when determined by HPLC, 1.0% or less of Compound B: [Chemical formula] 0.8% or less of Compound C: [Chemical formula] 0.25% or less of Compound D: [Chemical formula] and contains.

[0337] Exemplary Form 1 produced according to the above method contains 3.0% or less of total impurities when determined by HPLC. Furthermore, the water content of Exemplary Form 1 was 1.0% or less when determined by Karl Fischer (KF) analysis.

[0338] Other exemplary batches of Form 1 prepared according to the above synthetic scheme to produce approximately 350 g, 450 g, or 1.3 g of Compound 1 each had a total impurity of 0.92% (of which 0.43% was Compound B, 0.42% was Compound C, and 0.07% was Compound D) as determined by HPLC and a water content of 0.17% as determined by Karl Fischer analysis, a total impurity of 0.94% (of which 0.36% was Compound B, 0.47% was Compound C, and 0.11% was Compound D) as determined by HPLC and a water content of 0.12% as determined by Karl Fischer analysis, and a total impurity of 1.2% (of which 0.47% was Compound B, 0.62% was Compound C, and 0.12% was Compound D) as determined by HPLC and a water content of 0.3% as determined by Karl Fischer analysis. (Example 2) Solid Forms of Compound 1

[0339] Polymorph screening was performed on Compound 1, including aging / slurrying at desired temperatures (e.g., RT (room temperature, about 20 - 25 °C) and 50 °C), heating / cooling cycles, cooling of saturated solutions, and addition of poor solvents. From the screening, 10 forms / patterns were observed, including two anhydrates (Form 1 and Form 8), one hydrate (Form 10), and seven metastable forms (Patterns 2, 3, 5, 6, 7, 11, and 12).

[0340] Figure 1B shows an exemplary XRPD pattern of Form 1 prepared according to Example 1. DSC and TGA were performed on Form 1. A weight loss of 0.4% was observed by TGA prior to melting (Figure 2). The DSC shown in Figure 2 exhibits an endotherm starting at 255 °C, which indicates the melting of Compound 1. The material is slightly hygroscopic and there was a weight change of approximately 1.8% at RH between 0 and 90% as shown in Figure 3. Above 80% RH, a significant weight gain was observed (an increase of more than 1% was observed at RH between 80 and 90%). The weight gain at 90% RH did not stabilize after 120 minutes. Figure 4 shows that there was no morphological change after DVS. The 1H NMR spectrum shown in Figure 5 was consistent with the structure. No impurities or residual solvents were observed in the sample. Table 1A shows the XRPD peaks of Form 1. Due to the preferred orientation of the crystals, there may be variations in the peak intensities. Table 1B shows the XRPD peaks of Form 1 corresponding to the XRPD pattern of Form 1 (Figure 1C). Peaks with relative intensities exceeding 3% were included.

Table 1-1

Table 1-2

[0341] Figure 6 shows the relationship between all the forms and patterns observed from the polymorph screening. Table 2 summarizes the patterns and forms observed in the polymorph screening.

Table 2-1

Table 2-2

[0342] Form 10 was generated by stirring Compound 1 (about 50 mg) in 0.5 mL of water at room temperature (RT) over the weekend. The solid was separated by centrifuge and analyzed by XRPD (Figure 7). Form 10 was converted to Form 1 by drying in vacuo at 40 °C for 4 h, while Form 10 was converted to Form 10 by air drying at RT for 2 days (in an isolator). Form 10 was further characterized. Figure 7 shows the XRPD of Form 10. In Figure 8, two endotherms with onset temperatures of 39.4 and 243.4 °C correspond to dehydration and melting of the API, respectively. The TGA thermogram showed a 8.5% weight loss due to moisture loss. The NMR spectrum of Form 10 (Figure 9) was consistent with that of the starting material. Furthermore, KF indicated that 3.0% moisture was present in the sample. Figure 10 shows that Form 10 is hygroscopic with a ~5.5% weight change at RH between 0% and 90%. After DVS, Form 10 was converted to Form 1 as shown in Figure 11. Table 3 shows the XRPD peaks of Form 10.

Table 3

[0343] Pattern 3 was generated by stirring Compound 1 (about 50 mg) in 0.5 mL of THF:water (95:5, v / v) at RT over the weekend. The solid was separated by centrifuge and analyzed by XRPD (Figure 12B). Furthermore, Pattern 3 was converted to Pattern 4 by drying in vacuo at 40 °C for 4 h. Considering the temperature, Pattern 4 is consistent with Form 1 (Figure 12A). Synthesis and Characterization of Pattern 5 and Form 8

[0344] Pattern 5 was generated by adding a poor solvent of acetone to a DMSO solution of Compound 1. 575 mg of Compound 1 was dissolved in 5 mL of DMSO at RT. 0.4 mL of the DMSO solution was taken, and 3.2 mL (8 volumes) of acetone was added dropwise to the DMSO solution. After adding acetone, precipitation was observed. The solid was isolated by vacuum filtration and analyzed by XRPD (Figure 13). Further, Pattern 5 was converted to Form 8 by vacuum drying at 40 °C for 4 hours. Form 8 was further characterized. The wet and dry samples from the addition of the poor solvent of acetone to DMSO showed different XRPD patterns as shown in Figure 13. In Figure 14, only one exotherm was observed at 252.7 °C (onset), and the TGA thermogram showed negligible weight loss. The NMR spectrum of Form 10 was consistent with the NMR spectrum of the starting material (Figure 15). Further, KF indicated that only 0.1% water was present in the sample. The results of DVS (Figures 16 and 17) showed that Form 8 was slightly hygroscopic, showing a maximum weight change of 0.44% at RH between 0 and 80%. Above 80% RH, at least a 1.12% weight increase was observed (an increase exceeding 0.27% was observed at RH between 80 and 90%). After DVS, Form 8 was converted to Form 1 as shown in Figure 18. Table 4 shows the XRPD peaks of Form 8.

Table 4-1

Table 4-2

[0345] Pattern 6 was generated by adding a poor solvent of dioxane to a DMSO solution of Compound 1. 575 mg of Compound 1 was dissolved in 5 mL of DMSO at RT. 0.4 mL of the DMSO solution was taken, and 8.0 mL (20 volumes) of acetone was added dropwise to the DMSO solution. After stirring the sample at RT for about 20 minutes, precipitation was observed. The solid was separated by vacuum filtration and analyzed by XRPD (Figure 19). Further, Pattern 6 was converted to Form 1 by vacuum drying at 40 °C for 4 hours. Synthesis and Characterization of Pattern 7

[0346] Pattern 7 was generated by the addition of a poor solvent of DCM to a DMSO solution of Compound 1. 575 mg of Compound 1 was dissolved in 5 mL of DMSO at RT. 0.4 mL of the DMSO solution was taken, and 2.4 mL (6 volumes) of DCM was added dropwise to the DMSO solution. After the addition of DCM, precipitation was observed. The solid was separated by vacuum filtration and analyzed by XRPD (Figure 20). Furthermore, Pattern 7 was converted to Form 1 by vacuum drying at 40 °C for 4 hours. Synthesis and Characterization of Pattern 9

[0347] Pattern 9 was generated by the addition of a poor solvent of water to a DMF solution of Compound 1. 547 mg of Compound 1 was dissolved in 14 mL of DMF at RT. 1.0 mL of the DMF solution was taken, and 12 mL (12 volumes) of water was added dropwise to the DMF solution. After the sample was stirred at RT for 15 minutes, precipitation was observed. The solid was separated by vacuum filtration and analyzed by XRPD (Figure 21). Pattern 9 was obtained with both wet and dry samples, which was consistent with the XRPD pattern of VS-6766 (free form). The NMR spectrum of Pattern 9 (Figure 22) was consistent with the NMR spectrum of VS-6766 (free form). Synthesis and Characterization of Pattern 11

[0348] Pattern 11 was generated by the temperature cycle of a DMF:IPAc (1:2, v / v) sample. Approximately 50 mg of Compound 1 was charged into 0.3 mL of DMF:IPAc (1:2, v / v) to form a suspension. The suspension was heated to 50 °C at a heating rate of 5 °C / min, held for 30 minutes, then cooled to 5 °C at a rate of 0.1 °C / min and held for 30 minutes. The heating and cooling steps were repeated once. The solid was isolated by a centrifuge for XRPD analysis. The XRPD pattern is shown in Figure 23. Pattern 11 was converted to Form 1 by drying under vacuum for 4 hours. Synthesis and Characterization of Pattern 12

[0349] Pattern 12 was generated by cooling a DMSO:MeOH (1:1, v / v) solution of Compound 1. Approximately 50 mg of Compound 1 was suspended in 1 mL of DMSO:MeOH (1:1, v / v) at 50 °C and stirred for 2 hours. A transparent solution was obtained by filtering the suspension using a 0.45 μL PTFE filter. The solution was then cooled from 50 °C to 5 °C at a cooling rate of 0.1 °C / min. Precipitation was observed at 5 °C. The solid was isolated by a centrifuge and analyzed by XRPD (Figure 24). Pattern 12 was converted to Form 1 by drying under vacuum for 4 hours. (Example 3) Slurrying of Compound 1 at Different Temperatures

[0350] Approximately 50 mg of Compound 1 was dispersed in 0.5 mL of a given solvent and slurried at 20 °C for 2 days. The solid was obtained by a centrifuge and analyzed by XRPD. If no new XRPD pattern was observed, the remaining solid was slurried again at 50 °C for 2 days. As summarized in Table 5, Form 1, Pattern 2, Pattern 3 and Pattern 4 were observed from the slurrying experiments. [Table 5-1] [Table 5-2] (Example 4) Addition of Poor Solvent to Compound 1

[0351] DMSO, NMP and DMF were selected as solvents for preparing the solution of Compound 1. Solutions of Compound 1 in each solvent were prepared at RT (DMSO: solution concentration 115 mg / mL, NMP: solution concentration 59 mg / mL, DMF: solution concentration 46 mg / mL). The prepared solutions were dispensed into 10 vials for poor solvent addition. Details of the poor solvents and the corresponding XRPD results are summarized in Table 6 respectively. [Table 6-1] [Table 6-2] (Example 5) Temperature cycle of Form 1

[0352] Approximately 50 mg of Compound 1 was suspended in 0.3 mL of a selected solvent system. The sample was heated to 50 °C at a heating rate of 5 °C / min, held at 50 °C for 30 minutes, then cooled to 5 °C at a cooling rate of 0.1 °C / min and held at 5 °C for 30 minutes. The heating and cooling steps were repeated, and after holding the sample at 5 °C, it was isolated for XRPD analysis. Table 7 summarizes the results of the temperature cycle experiment. Form 1, Pattern 2, Pattern 5, Pattern 11, and low crystallinity were observed. [Table 7] (Example 6) Slow cooling of Form 1

[0353] A suspension of Compound 1 was prepared at 50 °C and stirred for 2 hours. The suspension was filtered through a 0.2 μm PTFE filter and then cooled from 50 °C to 5 °C at a cooling rate of 0.1 °C / min to obtain a clear solution. The results of the slow cooling are shown in Table 8. Form 1, Pattern 2, Form 8 excluding some peaks, Pattern 12, and low crystallinity were observed. [Table 8] (Example 7) Stability of Form 1 under stress conditions

[0354] Solids of Form 1 were stored under the conditions of 40 °C / 75% RH or 30 °C / 65% RH. XRPD and UPLC purity were measured at the 1st week and 4th week time points. The results are summarized in Table 9. The purity determined by UPLC remained statistically unchanged. Furthermore, the water content was measured by KF at the 5th week. The water content was consistent with the initial water content. [Table 9] (Example 8) Dosage form of VS-6766 Form 1 and exemplary manufacturing process

[0355] An exemplary method for manufacturing an oral dosage form of VS-6766 is described. For example, the composition of VS-6766 (0.8 mg based on the free form of VS-6766, 0.864 mg of VS-6766 corresponds to 0.8 mg of the free form of VS-6766) is presented in Table 10. [Table 10]

[0356] An exemplary manufacturing process for VS-6766 capsules involves performing a series of multiple blendings, followed by encapsulation of the final blend to produce the capsules. Mannitol (fine powder) is sieved through a 0.150 mm screen and blended. VS-6766 is sieved and added to a blender, and blended with the mannitol blend (fine) obtained from the previous step to produce "Pre-blend 1" when blended. Granular mannitol is sieved into two parts (Part 1 and Part 2) using a 0.315 mm screen. The sieved mannitol (Part 1) is added to the blender and blended. Pre-blend 1 is added to the blender and further blended with the blended mannitol (Part 1) to produce "Pre-blend 2" when blended together. The sieved mannitol (Part 2) is added to the blender and blended. Pre-blend 2 is added to the blender and further blended with the blended mannitol (Part 2). Magnesium stearate is sieved using a 0.200 mm screen and added to the blender together with the blend (VS-6766, fine mannitol, Part 1 and Part 2 of granular mannitol) to produce "Final Blend" when blended. The capsule agent is manufactured by encapsulating the final blend into size 4 HPMC capsule shells. Figure 25 shows a flow diagram of the manufacturing process. Since conventional blending could not provide a drug product with appropriate content uniformity, high shear blending was used to blend the materials.

[0357] In batch A of VS-6766 capsules using the conventional blending (free fall) method, the blending uniformity fluctuated during the dilution step, the blend became non-uniform after the final lubrication step, the API content of the final blend and capsules was low, and it became difficult to increase the API content during the encapsulation process. In another exemplary production batch (batch B) using the conventional blending method, 40,000 capsules were obtained based on 34.56 g of VS-6766. In batch B, to improve the blending uniformity compared to batch A and optimize the process, the API was sandwiched between fine mannitol powders, the screen used for pre-blend 1 was flushed with fine mannitol powder, and pre-blend 1 was sandwiched between granular mannitol to produce pre-blend 2. Further, the lubricant was not sieved over the complete blend in the blending bin. Instead, a fixed portion of the blend was removed from the bin. The lubricant was sieved over this fixed portion and then manually blended, and the pre-mixture was added to the remaining blend for lubrication to avoid the formation of agglomerates during lubrication. Further, after the powder sensor stopped the machine, the encapsulation was stopped. The powder was not manually transferred to the dosing plate to optimize the capsule yield and avoid separation of the blend during encapsulation. In batch B, pre-blend 1 showed a low API content and high RSD (average recovery 78.8% with RSD 8.8% at n = 6). Pre-blend 2 showed a low API content (average recovery 87.1% with RSD 5.5% at n = 18). In the final blend, wide variations in blending uniformity were observed among samples (average recovery 85.74%, RSD 22.4%). The average API content was below the target and the RSD exceeded 20% (target: 90 - 110% of the average assay as the target, RSD of individual values ≤ 5%).

[0358] Assay and Content Uniformity: The assay and content uniformity were determined by HPLC. The assays (%) of Batches C and D (manufactured using high shear blending instead of conventional direct blending) were 95.1 and 98.2%, respectively, while the assays (%) of Batches A and B were 79.7 and 80.2%, respectively. Content uniformity samples were taken, for example, every 10 minutes during the execution of encapsulation. The results of the content uniformity test confirmed that low API content was found during the assay tests of Batch A (content uniformity: average 86.70%, RSD 7.60%) and Batch B (content uniformity: average 80.48%, RSD 3.47%).

[0359] Dissolution: Relatively rapid dissolution was observed in Batches A and B compared to Batches C and D. For example, Figure 26 shows the dissolution profiles of Batches B, C, and D. (Example 9) Single Crystal of Form 1 Growth and Sample Preparation of Single Crystal

[0360] Form 1 was analyzed by single crystal X-ray diffraction. The crystals were obtained from a DMF solution of Form 1 and subsequently evaporated slowly. The crystal structure was determined at 100(2) K. Results

[0361] The crystals are in the monoclinic space group P21 / c, and the final R1 [I>2σ(I)] = 4.37%. The structure was specified as shown in Figure 27, and it was found that the asymmetric unit contains one molecule of Compound 1. The structure of Compound 1 is a coordination polymer in which the potassium cation is coordinated by four ligands (Figure 28). Table 11 summarizes the sample and crystal data of Form 1. The simulated XRPD pattern at 100 K is shown in Figure 29.

Table 11-1

Table 11-2

[0362] In the claims, articles such as "a", "an", and "the" may mean one or more than one, unless the contrary is indicated or is not apparent from the context. A claim or description that includes "or" between one or more members of a group is considered satisfied if, unless the contrary is indicated or is not apparent from the context, one, more than one, or all of the members of the group are present in, employed in, or relevant to a given product or process. The invention includes embodiments in which exactly one member of the group is present in, employed in, or relevant to a given product or process. The invention includes embodiments in which more than one, or all, of the members of the group are present in, employed in, or relevant to a given product or process.

[0363] Furthermore, the present invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms derived from one or more of the recited claims are introduced into another claim. For example, any claim that depends on another claim can be modified to include one or more limitations found in other claims that depend on the same basic claim. When elements are presented as a list, for example in Markush group form, each subgroup of the elements is also disclosed, and any element can be removed from the group. Generally, when the present invention, or an aspect of the present invention, is referred to as including a particular element or feature, it should be understood that some embodiments of the present invention or aspects thereof consist of, or consist essentially of, such elements or features. For the sake of brevity, these embodiments are not specifically shown herein in these exact words. It should also be noted that the terms "comprising" and "including" are intended to be open-ended and allow the inclusion of additional elements or steps. When ranges are given, the endpoints are included. Further, unless otherwise indicated, or unless it is obvious from the context and the understanding of one of ordinary skill in the art, values expressed as ranges are assumed to be any specific value or sub-range within the ranges explicitly stated in different embodiments of the present invention, down to one-tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0364] This application references various registered patents, published patent applications, journal articles, and other publications, all of which are hereby incorporated by reference into this specification. In the event of any conflict between any of the incorporated references and this specification, this specification shall prevail. Further, any embodiments of the present invention that fall within the prior art may be explicitly excluded from one or more of the claims. Such embodiments are considered to be known to one of ordinary skill in the art, and thus may be excluded even if the exclusion is not explicitly stated herein. Any embodiment of the present invention may be excluded from any claim for any reason, regardless of the existence of the prior art.

[0365] One of ordinary skill in the art will recognize, or be able to ascertain, many equivalents to the specific embodiments described herein using only routine experimentation. The scope of the embodiments described herein is not intended to be limited to the above description, but rather is as set forth in the appended claims. One of ordinary skill in the art will recognize that various changes and modifications can be made to this specification without departing from the spirit or scope of the invention as defined in the following claims.

Claims

1. (a) Equation II: 【Chemistry 41】 Crystal form 1 of the compound, which exhibits an X-ray powder diffraction pattern including a characteristic XRPD peak at the following diffraction angle (2θ (degrees)): 9.0 ± 0.2, and (b) Pharmacologically acceptable carriers A solid oral dosage form comprising a composition containing the following.

2. The oral dosage form according to claim 1, wherein the X-ray powder diffraction pattern of form 1 further includes a characteristic XRPD peak at the following diffraction angle (2θ (degrees)): 4.5 ± 0.

2.

3. The oral dosage form according to claim 1, wherein the X-ray powder diffraction pattern of form 1 further includes a characteristic XRPD peak at the following diffraction angle (2θ (degrees)): 18.1 ± 0.

2.

4. The oral dosage form according to claim 1, wherein form 1 exhibits an X-ray powder diffraction pattern further comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 4.5 ± 0.2, 14.7 ± 0.2, 18.1 ± 0.2, and 22.7 ± 0.

2.

5. The oral dosage form according to claim 4, wherein form 1 exhibits an X-ray powder diffraction pattern further comprising at least one characteristic XRPD peak selected from the following diffraction angles (2θ (degrees)) = 7.3 ± 0.2, 17.1 ± 0.2, and 19.4 ± 0.

2.

6. The oral dosage form according to claim 1, wherein form 1 exhibits substantially the same X-ray powder diffraction pattern as that shown in Figure 1C.

7. The oral dosage form according to claim 1, wherein form 1 exhibits endothermic activity starting at approximately 255°C based on differential scanning calorimetry.

8. Embodiment 1 is an oral dosage form according to claim 1, wherein the differential scanning calorimetry curve is substantially the same as that shown in Figure 2.

9. The oral dosage form according to claim 1, wherein form 1 exhibits substantially the same dynamic vapor sorption plot as that shown in Figure 3.

10. The oral dosage form according to claim 1, wherein form 1 is an anhydrous substance.

11. The oral dosage form according to claim 1, wherein the oral dosage form substantially does not include any other solid form or pattern of the compound of formula II.

12. When the oral dosage form is determined by HPLC, compound B, compound C, and compound D: 【Chemistry 42】 The oral dosage form according to claim 1, which is substantially free of impurities selected from the group consisting of the following.

13. A composition for treating cancers of a target requiring treatment, comprising the oral dosage form described in claim 1.

14. The composition according to claim 13, wherein the cancer is selected from the group consisting of melanoma, lung cancer, ovarian cancer, pancreatic cancer, and colorectal cancer.

15. The composition according to claim 14, wherein the ovarian cancer is low-grade serous ovarian cancer.

16. The composition according to claim 14, wherein the lung cancer is non-small cell lung cancer.

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