Solid Forms and Methods of Use

Abstract

Provided herein are crystalline forms of the compound of formula (I) and compositions thereof. [Formula 1] TIFF2026501784000073.tif33168

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 437,527, filed January 6, 2023, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Deuterium-enriched enantiomers of drug compounds are believed to be useful in the treatment of a wide range of human diseases, including, but not limited to, cancer, inflammatory diseases, and immune-mediated disorders. However, developing solid forms of these deuterium-enriched enantiomers with the physicochemical properties necessary to produce commercially available pharmaceuticals with the required efficacy remains a major challenge. This is because the results of solid form screening for any compound are unpredictable, and the physicochemical properties of the resulting solid forms are also unpredictable. Summary of the Invention [Problem to be solved by the invention]

[0003] Thus, there is an unmet need for new solid forms of deuterium-enriched compounds that possess the necessary physicochemical properties to provide superior therapeutic properties over non-deuterated compounds. [Means for solving the problem]

[0004] (overview) In one aspect, provided herein is a crystalline form of the compound of Formula (I). [ka]

[0005] In another aspect, provided herein is an anhydrous crystalline form of the compound of formula (I). [ka]

[0006] In various embodiments, provided herein is Form I of the compound of Formula (I). [ka]

[0007] In various embodiments, provided herein is Form III of the compound of Formula (I). [ka]

[0008] In various embodiments, provided herein is Form X of the compound of Formula (I). [ka]

[0009] In another aspect, provided herein is a crystalline hydrate of the compound of formula (I). [ka]

[0010] In various embodiments, provided herein is Form II of the compound of Formula (I). [ka]

[0011] In another aspect, pharmaceutical compositions are provided that generally contain a crystalline form of a compound of Formula (I) described herein and a pharmaceutically acceptable excipient.

[0012] In various embodiments, provided herein are pharmaceutical compositions containing an anhydrous crystalline form of the compound of Formula (I) described herein and a pharmaceutically acceptable excipient. In various embodiments, provided herein are pharmaceutical compositions containing Form I of the compound of Formula (I) described herein and a pharmaceutically acceptable excipient. In various embodiments, provided herein are pharmaceutical compositions containing Form II of the compound of Formula (I) described herein and a pharmaceutically acceptable excipient. In various embodiments, provided herein are pharmaceutical compositions containing Form III of the compound of Formula (I) described herein and a pharmaceutically acceptable excipient. In various embodiments, provided herein are pharmaceutical compositions containing Form X of the compound of Formula (I) described herein and a pharmaceutically acceptable excipient. [Brief explanation of the drawings]

[0013] [Figure 1A] 1 is an X-ray powder diffraction (XRPD) pattern of Form I of compound of formula (I) calculated from single crystal X-ray diffraction (XRD) data, as further described in Example 2. [Figure 1B] 1 is a superposition of an exemplary experimental XRPD pattern of Form I of compound of formula (I) with an XRPD pattern of Form I of compound of formula (I) calculated from single crystal XRD data. [Figure 1C] 1 is an illustrative XRPD pattern of Form I of compound of formula (I). [Figure 2] 1 is an XRPD pattern of Form II of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 3] 1 is an XRPD pattern of Form III of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 4] 1 is an XRPD pattern of Form IV of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 5]1 is an XRPD pattern of Form V of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 6] 1 is an XRPD pattern of Form VI of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 7] 1 is an XRPD pattern of Form VII of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 8] 1 is an XRPD pattern of Form VIII of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 9] 1 is an XRPD pattern of Form IX of compound of formula (I) calculated from single crystal XRD data, as further described in Example 2. [Figure 10] 1 is an illustrative XRPD pattern of Form X of compound of formula (I). [Figure 11] FIG. 1 is an Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagram of Form I of the compound of formula (I). [Figure 12] FIG. 1 is an ORTEP diagram of Form II of compound of formula (I). [Figure 13] FIG. 1 is an ORTEP diagram of Form III of compound of formula (I). [Figure 14] FIG. 1 is an ORTEP diagram of Form IV of compound of formula (I). [Figure 15] FIG. 1 is an ORTEP diagram of Form V of compound of formula (I). [Figure 16] FIG. 1 is an ORTEP representation of Form VI of compound of formula (I). [Figure 17] FIG. 1 is an ORTEP representation of Form VII of compound of formula (I). [Figure 18] FIG. 1 is an ORTEP representation of Form VIII of the compound of formula (I). [Figure 19] FIG. 1 is an ORTEP diagram of Form IX of compound of formula (I). [Figure 20] 1 is an overlay of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) thermograms for Form I of the compound of formula (I). [Figure 21] 1 is an exemplary moisture sorption isotherm recorded at 25° C. for Form I of the compound of formula (I). [Figure 22] 1 is an overlay of the DSC and TGA thermograms for Form X of the compound of formula (I). [Figure 23] 1 is an exemplary moisture sorption isotherm recorded at 25° C. for Form X of the compound of Formula (I). [Figure 24] 1 is an illustrative XRPD pattern of the crystalline material prepared as described in Example 1, showing a mixture of Form I and Form II of the compound of Formula (I). [Figure 25] 1 is an illustrative DSC thermogram of the crystalline material of the compound of Formula (I) prepared as described in Example 1. [Figure 26] 1 is an illustrative TGA thermogram of the crystalline material of the compound of Formula (I) prepared as described in Example 1. [Figure 27] Figure 1 shows plasma pharmacokinetic (PK) profiles (concentration versus time) of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione in mice after single oral administration of equal doses of the compound of Formula (I) (15 mg / kg, top panel) or the corresponding protonated racemic mixture, avadomide (30 mg / kg, bottom panel), where hR is the protonated (R)-enantiomer, hS is the protonated (S)-enantiomer, dR is the deuterated (R)-enantiomer, dS is the deuterated (S)-enantiomer, po is oral administration, and C is concentration. [Figure 28]Figure 1 shows plasma PK profiles (concentration versus time) of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione in rats after single oral administration of equivalent doses of the compound of Formula (I) (150 mg / kg, top panel) or the corresponding protonated racemic mixture, avadomide (300 mg / kg, bottom panel), where hS is the protonated (S)-enantiomer, hR is the protonated (R)-enantiomer, dS is the deuterated (S)-enantiomer, po is oral administration, and C is concentration. [Figure 29] Figure 1 shows the plasma PK profiles (concentration versus time) of the protonated and deuterated (R)- and (S)-enantiomers of 3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione in cynomolgus monkeys after a single oral dose of the compound of Formula (I) (0.25 mg / kg, top row; 0.75 mg / kg, middle row) or the corresponding protonated racemic mixture, avadomide (1.5 mg / kg, bottom row), as applicable, where hS is the protonated (S)-enantiomer, hR is the protonated (R)-enantiomer, dS is the deuterated (S)-enantiomer, po is oral dose, and C is concentration. DETAILED DESCRIPTION OF THE INVENTION

[0014] Detailed Description

[0015] As outlined herein, the present disclosure provides pharmaceutically acceptable forms of deuterium-enriched (S)-avadomide, also referred to herein as the compound of Formula (I), (e.g., crystalline forms of deuterium-enriched (S)-avadomide, and pharmaceutical compositions comprising same. In particular, the present invention provides crystalline forms of deuterium-enriched (S)-avadomide that have unexpectedly improved solubility at physiologically relevant pH and in vivo bioavailability compared to avadomide (racemate).

[0016] definition

[0017] To facilitate the understanding of the present invention, several terms and phrases are defined below.

[0018] Unless otherwise defined, all technical and scientific terms used herein have the meanings commonly understood by those of ordinary skill in the art to which this invention belongs. Abbreviations used herein have their conventional meanings in the chemical and biological arts. The chemical structures and formulas described herein are constructed according to the standard rules of chemical valence known in the chemical arts.

[0019] Throughout this specification, when compositions and kits are described as having, including, or comprising particular components, or when processes and methods are described as having, including, or comprising particular steps, it is further contemplated that there are compositions and kits of the invention that consist essentially of, or consist of, the recited components, and that there are processes and methods of the invention that consist essentially of, or consist of, the recited processing steps.

[0020] In this application, when an element or component is described as being included in and / or selected from a list of recited elements or components, it is to be understood that the element or component can be any one of the recited elements or components, or can be selected from a group consisting of two or more of the recited elements or components.

[0021] Furthermore, it should be understood that elements and / or features of the compositions or methods described herein, whether expressly or implicitly stated herein, can be combined in various ways without departing from the spirit and scope of the invention. For example, when a particular compound is referenced, that compound can be used in various embodiments of the compositions of the invention and / or methods of the invention, unless the context dictates otherwise. In other words, although embodiments have been described and illustrated in this application to enable clear and concise application writing and drawing, it is intended and understood that the embodiments can be combined or separated in various ways without departing from the present teachings and invention. For example, it will be understood that all features described and illustrated herein are applicable to all aspects of the invention described and illustrated herein.

[0022] In this disclosure, the articles "a" and "an" are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article, unless the context indicates otherwise. For example, "an element" means one element or two or more elements.

[0023] In this disclosure, the term "and / or" is used to mean either "and" or "or," unless otherwise stated.

[0024] The phrase "at least one" should be understood to include each of the listed objects following that phrase individually, unless context and usage dictate otherwise, and also to include two or more of the listed objects in combination, unless context and usage dictate otherwise. The phrase "and / or" in connection with more than two objects should be understood to have the same meaning, unless context dictates otherwise.

[0025] Use of the terms "include," "includes," "including," "have," "has," "having," "contain," "contains," or "containing," including grammatical equivalents thereof, is to be generally understood as open-ended and non-limiting, e.g., not excluding additional elements or steps, unless otherwise stated or understood from the context.

[0026] When the term "about" is used before a quantitative value, the present invention also includes the specific quantitative value itself unless otherwise specified. As used herein, the term "about" refers to a variation of ±10%, ±5%, ±3%, ±2%, or ±1% from the nominal value, unless otherwise specified or inferred from the context.

[0027] Due to factors of experimental variation well known to those skilled in the art, the value of each XRPD peak is typically preceded by the word "about" or followed by an appropriate range defining the experimental variation. For data reported herein, unless otherwise specified, values ​​are ±0.3°2θ. XRPD peaks cited herein are generally reported within this ±0.3°2θ range unless otherwise specified, and are intended to be reported within such ranges whenever disclosed herein, regardless of the presence or absence of the word "about," unless the context dictates otherwise.

[0028] Due to experimental variation factors well known to those skilled in the art, differential scanning calorimetry (DSC) endothermic or exothermic values ​​are typically preceded by the term "about" or followed by an appropriate range to define the experimental variation. For data reported herein, the values ​​are ±10°C unless otherwise specified. DSC endothermic / exothermic values ​​cited herein are generally reported within this ±10°C range unless otherwise specified, and are intended to be reported within such range whenever disclosed herein, regardless of the presence or absence of the term "about," unless the context dictates otherwise.

[0029] At various places in this specification, variables or parameters are disclosed in groups or ranges. This specification specifically includes all individual subcombinations of the members of such groups and ranges. For example, an integer in the range of 0 to 40 is specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and an integer in the range of 1 to 20 is specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20.

[0030] The use of any and all examples herein, or exemplary language such as "such as" or "including," is intended only to better describe the invention and does not limit the scope of the invention unless otherwise stated in the claims. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0031] Deuterium is used herein as 2 Sometimes referred to as H and / or D, it is a stable, non-radioactive isotope of hydrogen with an atomic mass of 2.014. 1 H Hydrogen (i.e., protium), deuterium ( 2 H), and tritium ( 3 It exists in nature as a mixture of isotopes, deuterium (H). The natural abundance of deuterium is about 0.015%. Those skilled in the art will recognize that in all chemical compounds containing H atoms, the H atoms are actually 1 H Hydrogen, Deuterium ( 2 H), and tritium ( 3H), of which about 0.015% is deuterium. In various embodiments, compounds enriched to deuterium levels greater than about 0.015% of their natural abundance are considered unnatural compounds and, as a result, novel compared to their non-enriched counterparts. In certain embodiments, compounds enriched in deuterium content greater than about 0.015% of their natural abundance are deuterium-enriched compounds.

[0032] As used herein, "total deuterium content" or "total deuterium abundance" refers to the number of deuterium atoms present in a molecule. 2 The deuterium content at the chiral center of a molecule (e.g., a deuterium-enriched compound of formula (I)) can be measured, for example, by H-NMR. 1 It can be measured using H-NMR.

[0033] Generally, compositions expressed as percentages are by weight unless otherwise specified. Furthermore, if a variable is not accompanied by a definition, the previous definition of that variable applies.

[0034] As used herein, "pharmaceutical composition" or "pharmaceutical formulation" refers to a combination of an active substance with an inert or active carrier, and means a composition particularly suitable for in vivo or ex vivo diagnostic or therapeutic use.

[0035] "Pharmaceutically acceptable" means approved or approvable by a regulatory agency of the Federal or State government or a corresponding agency in a country other than the United States, or listed in the United States Pharmacopeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.

[0036] As used herein, "pharmaceutically acceptable excipient" refers to a substance that aids in the administration and / or absorption of an active agent by a subject and can be included in the compositions of the present invention without causing significant toxic effects to the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline such as phosphate-buffered saline, emulsions (e.g., oil / water or water / oil emulsions), lactated Ringer's solution, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coating agents, sweeteners, flavorings, salt solutions (such as Ringer's solution), alcohol, oils, gelatin, carbohydrates such as lactose, amylose, or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, and coloring agents. Such formulations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts that affect osmotic pressure, buffers, coloring agents, and / or flavoring agents that do not adversely react with the compounds of the present invention. For examples of excipients, see Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA (1975).

[0037] As used herein, "solid dosage form" means a solid pharmaceutical administration form such as tablets, capsules, granules, powders, sachets, reconstitutable powders, dry powder inhalants and chewables.

[0038] As used herein, "administration" refers to oral administration, administration as a suppository, topical contact, intravenous administration, parenteral administration, intraperitoneal administration, intramuscular administration, intralesional administration, intrathecal administration, intracranial administration, intranasal administration, or subcutaneous administration, or implantation of a sustained-release device, such as a mini-osmotic pump, into a subject. Administration can be by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, and the like. "Concurrent administration" refers to administration of a composition described herein simultaneously with, immediately before, or immediately after the administration of one or more additional therapies (e.g., anti-cancer agents, chemotherapeutic agents, or treatments for neurodegenerative diseases). The compound of the present disclosure or its pharmaceutically acceptable salt can be administered to a patient alone or simultaneously. Simultaneous administration means that the compound is administered alone or in combination with multiple compounds or drugs, simultaneously or sequentially.Therefore, these preparations can also be combined with other active substances if desired (for example, to reduce metabolic degradation).

[0039] As used herein, the terms "disease," "disorder," and "condition" are used interchangeably.

[0040] As used herein, and unless otherwise specified, the terms "treat," "treating," and "treatment" contemplate an action taken while a subject is afflicted with a particular disease, disorder, or condition that reduces the severity of the disease, disorder, or condition or slows or inhibits the progression of the disease, disorder, or condition (e.g., "therapeutic treatment").

[0041] In general, an "effective amount" of a compound refers to an amount sufficient to elicit a desired biological response, e.g., an amount sufficient to treat a condition, disease, or disorder described herein. As will be understood by those skilled in the art, an effective amount of a compound of the present disclosure may vary depending on factors such as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject.

[0042] Deuterium-enriched compounds

[0043] The deuterium-enriched compounds of the present disclosure have the formula (I): [ka] It is expressed as:

[0044] The compound of formula (I) is referred to herein as (S)-3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2 It may also be referred to as [H]-2,6-piperidinedione or deuterium-enriched (S)-avadomide.

[0045] As noted above, the deuterium-enriched compounds described herein include deuterium enrichment at the chiral center. Without wishing to be bound by theory, it is believed that deuterium enrichment at the chiral center may slow or inhibit the rate of interconversion of the two enantiomers.

[0046] Methods for chemically synthesizing compounds of formula (I) and preparing the crystalline forms described herein are provided in Examples 1-3.

[0047] In certain embodiments, the abundance of deuterium at the chiral center is about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100%, about 30% to about 95% , about 30% to about 90%, about 30% to about 85%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 60%, about 30% to about 50%, about 30% to about 40%, about 40% to about 95%, about 40% to about 90%, about 40% to about 85%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to about 60 %, about 40% to about 50%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 60%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 70% to about 9 5%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%.

[0048] In certain embodiments, the abundance of deuterium at the chiral centers is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

[0049] In certain embodiments, the abundance of deuterium at the chiral center is about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 101%, about 102%, about 103%, about 104%, about 105%, about 106%, about 107%, about 108%, about 109%, about 110%, about 111%, about 112%, about 113%, about 114%, about 115%, about 116%, about 117%, about 118%, about 119%, about 120%, about 121%, about 122%, about 123%, 3%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100%.

[0050] In certain embodiments, the deuterium-enriched compounds of Formula (I) described herein are from about 70% to about 100%, from about 75% to about 100%, from about 80% to about 100%, from about 85% to about 100%, from about 90% to about 100%, from about 95% to about 100%, from about 70% to about 95%, from about 70% to about 90%, from about 70% to about 85%, from about 70% to about 80%, from about 70% to about 75%, from about 75% to about 95%, from about 75% to about 90%, having an enantiomeric excess (enantiomeric excess (ee%) is defined as the difference in mole percent of each enantiomer in both mixtures; e.g., if %S > %R, then ee = %S - %R) of 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%.

[0051] In certain embodiments, the deuterium-enriched compounds of Formula (I) described herein have an enantiomeric excess of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

[0052] In certain embodiments, the deuterium-enriched compounds of Formula (I) described herein have an enantiomeric excess of about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100%. In certain embodiments, the deuterium-enriched compounds of Formula (I) described herein are enantiopure.

[0053] In various embodiments, provided herein are crystalline forms of the compound of Formula (I).

[0054] Crystalline forms of deuterium-enriched compounds of formula (I)

[0055] In one aspect, provided herein is a crystalline form of the compound of Formula (I). [ka]

[0056] In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.0° 2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.1° 2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, and about 14.1° 2θ.

[0057] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, and about 24.7° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ.

[0058] In certain embodiments, said crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, about 14.1°, about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, about 24.7°, about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ.

[0059] In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.3°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.3°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.3°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.3°, 11.9°±0.3°, and 14.1°±0.3°2θ.

[0060] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 19.7°±0.3°, 21.1°±0.3°, 21.5°±0.3°, 23.5°±0.3°, 24.0°±0.3°, and 24.7°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4°±0.3°, 27.1°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 31.1°±0.3°, 32.5°±0.3°, 33.7°±0.3°, and 34.5°±0.3°2θ.

[0061] In certain embodiments, said crystalline form of compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.3°, 11.9°±0.3°, 14.1°±0.3°, 15.3°±0.3°, 19.7°±0.3°, 21.1°±0.3°, 21.5°±0.3°, 23.5°±0.3°, 24.0°±0.3°, 24.7°±0.3°, 26.4°±0.3°, 27.1°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 31.1°±0.3°, 32.5°±0.3°, 33.7°±0.3°, and 34.5°±0.3° 2θ.

[0062] In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.2°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.2°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.2°2θ. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.2°, 11.9°±0.2°, and 14.1°±0.2°2θ.

[0063] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 19.7°±0.2°, 21.1°±0.2°, 21.5°±0.2°, 23.5°±0.2°, 24.0°±0.2°, and 24.7°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4°±0.2°, 27.1°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 31.1°±0.2°, 32.5°±0.2°, 33.7°±0.2°, and 34.5°±0.2° 2θ.

[0064] In certain embodiments, said crystalline form of compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.2°, 11.9°±0.2°, 14.1°±0.2°, 15.3°±0.2°, 19.7°±0.2°, 21.1°±0.2°, 21.5°±0.2°, 23.5°±0.2°, 24.0°±0.2°, 24.7°±0.2°, 26.4°±0.2°, 27.1°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 31.1°±0.2°, 32.5°±0.2°, 33.7°±0.2°, and 34.5°±0.2° 2θ.

[0065] In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 12. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 14. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 15. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 16. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 17. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 18. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 19. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20.

[0066] In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 1A. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 2. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 3. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 4. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 5. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 6. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 7. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 8. In certain embodiments, the crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG. 9. In certain embodiments, said crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0067] In certain embodiments, the crystalline form of the compound of Formula (I) exists in the orthorhombic crystal system. In certain embodiments, the crystalline form of the compound of Formula (I) exists in the orthorhombic crystal system and has a P212121 space group. In certain embodiments, the crystalline form of the compound of Formula (I) exists in the orthorhombic crystal system and has a C2221 space group.

[0068] In certain embodiments, the crystalline form of the compound of Formula (I) exists in the monoclinic crystal system. In certain embodiments, the crystalline form of the compound of Formula (I) exists in the monoclinic crystal system and has a P121 / n1 space group. In certain embodiments, the crystalline form of the compound of Formula (I) exists in the monoclinic crystal system and has a P1211 space group.

[0069] In certain embodiments, the crystalline form of the compound of Formula (I) is an anhydrous crystalline form. In certain embodiments, the crystalline form of the compound of Formula (I) is a crystalline hydrate. In certain embodiments, the crystalline form of the compound of Formula (I) is a crystalline solvate.

[0070] (1) Anhydrous crystalline form of the compound of formula (I)

[0071] In one embodiment, an anhydrous crystalline form of the compound of formula (I) is provided.

[0072] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.9°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.9°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.1°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, and about 14.1°2θ.

[0073] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, and about 24.6° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ.

[0074] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, about 14.1°, about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, about 24.6°, about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ.

[0075] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.3°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.3°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.3°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at 10.9°±0.3°, 11.9°±0.3°, and 14.1°±0.3°2θ.

[0076] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 18.7°±0.3°, 19.7°±0.3°, 21.2°±0.3°, 21.6°±0.3°, 23.3°±0.3°, 24.1°±0.3°, and 24.6°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4°±0.3°, 27.1°±0.3°, 28.8°±0.3°, 29.2°±0.3°, 30.6°±0.3°, 31.1°±0.3°, 32.4°±0.3°, 33.0°±0.3°, 33.8°±0.3°, and 34.7°±0.3°2θ.

[0077] In certain embodiments, the crystalline form of the compound of Formula (I) has the following crystal structures: 10.9°±0.3°, 11.9°±0.3°, 14.1°±0.3°, 15.3°±0.3°, 18.7°±0.3°, 19.7°±0.3°, 21.2°±0.3°, 21.6°±0.3°, 23.3°±0.3°, 24.1°±0.3°, 24.6°±0.3°, 25.6°±0.3°, 26.6°±0.3°, 27.6°±0.3°, 28.6°±0.3°, 29.6°±0.3°, 30.6°±0.3°, 31.6°±0.3°, 32.6°±0.3°, 33.6°±0.3°, 34.6°±0.3°, 35.6°±0.3°, 36.6°±0.3°, 37.6°±0.3°, 38.6°±0.3°, 39.6°±0.3°, 40.6°±0.3°, 41.6°±0.3°, 42.6°±0.3°, 43.6°±0.3°, 44.6°±0.3°, 45.6°±0.3°, 46.6°±0.3°, 47.6°±0.3°, 48.6°±0.3°, 49.6°±0.3°, 50.6°±0.3°, 51.6°±0.3°, 52.6°±0.3°, 53.6°±0.3°, 54.6°±0. 2θ, 26.4°±0.3°, 27.1°±0.3°, 28.8°±0.3°, 29.2°±0.3°, 30.6°±0.3°, 31.1°±0.3°, 32.4°±0.3°, 33.0°±0.3°, 33.8°±0.3°, and 34.7°±0.3° 2θ.

[0078] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.2°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.2°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.2°2θ. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising peaks at 10.9°±0.2°, 11.9°±0.2°, and 14.1°±0.2°2θ.

[0079] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.2°, 18.7°±0.2°, 19.7°±0.2°, 21.2°±0.2°, 21.6°±0.2°, 23.3°±0.2°, 24.1°±0.2°, and 24.6°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.4°±0.2°, 27.1°±0.2°, 28.8°±0.2°, 29.2°±0.2°, 30.6°±0.2°, 31.1°±0.2°, 32.4°±0.2°, 33.0°±0.2°, 33.8°±0.2°, and 34.7°±0.2° 2θ.

[0080] In certain embodiments, said anhydrous crystalline form of the compound of formula (I) has the following peaks: 10.9°±0.2°, 11.9°±0.2°, 14.1°±0.2°, 15.3°±0.2°, 18.7°±0.2°, 19.7°±0.2°, 21.2°±0.2°, 21.6°±0.2°, 23.3°±0.2°, 24.1°±0.2°, 24. It has an XRPD pattern containing peaks at 6°±0.2°, 26.4°±0.2°, 27.1°±0.2°, 28.8°±0.2°, 29.2°±0.2°, 30.6°±0.2°, 31.1°±0.2°, 32.4°±0.2°, 33.0°±0.2°, 33.8°±0.2°, and 34.7°±0.2° 2θ.

[0081] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20.

[0082] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in Figure 1A. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in Figure 3. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in Figure 10.

[0083] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) exists in the orthorhombic crystal system. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) exists in the orthorhombic crystal system and has the P212121 space group.

[0084] In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) exists in the monoclinic crystal system. In certain embodiments, the anhydrous crystalline form of the compound of Formula (I) exists in the monoclinic crystal system and has the P121 / n1 space group.

[0085] (A) Form I

[0086] In one aspect, provided herein is Form I of the compound of Formula (I).

[0087] In certain embodiments, Form I of the compound of formula (I) is an anhydrous crystalline form.

[0088] In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.3 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.0 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.9 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.7 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.0 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.8 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising peaks at about 11.0° and about 14.0 °2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising one or more peaks selected from about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, and about 14.8° 2θ.

[0089] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 17.4°, about 20.6°, about 21.1°, about 23.2°, and about 24.1° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.6°, about 18.7°, about 19.7°, about 21.6°, about 23.0°, about 23.7°, and about 24.6° 2θ.

[0090] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.8°, about 28.2°, about 30.3°, about 30.5°, and about 33.0° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 27.1°, about 28.9°, about 29.2°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ.

[0091] In certain embodiments, Form I of the compound of Formula (I) has an average molecular weight of about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, about 14.8°, about 15.3°, about 17.4°, 17.6°, about 18.7°, about 19.7°, about 20.6°, about 21.1°, about 21.6°, about 23.0°, about 23.2°, about 23.7°, about 24.1°, about 24.6°, about It has an XRPD pattern including peaks at 25.6°, about 26.1°, about 26.4°, about 26.8°, about 27.1°, about 28.2°, about 28.9°, about 29.2°, about 30.3°, about 30.5°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.0°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ.

[0092] In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.3°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.7°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.0°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.8°±0.3°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.3° and 14.0°±0.3° 2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising one or more peaks selected from 10.3°±0.3°, 11.0°±0.3°, 11.9°±0.3°, 13.7°±0.3°, 14.0°±0.3°, and 14.8°±0.3° 2θ.

[0093] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 17.4°±0.3°, 20.6°±0.3°, 21.1°±0.3°, 23.2°±0.3°, and 24.1°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.6°±0.3°, 18.7°±0.3°, 19.7°±0.3°, 21.6°±0.3°, 23.0°±0.3°, 23.7°±0.3°, and 24.6°±0.3°2θ.

[0094] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1°±0.3°, 26.4°±0.3°, 26.8°±0.3°, 28.2°±0.3°, 30.3°±0.3°, 30.5°±0.3°, and 33.0°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6°±0.3°, 27.1°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 30.9°±0.3°, 31.1°±0.3°, 32.1°±0.3°, 32.4°±0.3°, 33.8°±0.3°, 34.0°±0.3°, 34.5°±0.3°, and 34.7°±0.3°2θ.

[0095] In certain embodiments, Form I of the compound of Formula (I) may have any of the following temperatures: 10.3°±0.3°, 11.0°±0.3°, 11.9°±0.3°, 13.7°±0.3°, 14.0°±0.3°, 14.8°±0.3°, 15.3°±0.3°, 17.4°±0.3°, 17.6°±0.3°, 18.7°±0.3°, 19.7°±0.3°, 20.6°±0.3°, 21.1°±0.3°, 21.6°±0.3°, 23.0°±0.3°, 23.2°±0.3°, 23.7°±0.3°, 24.1°±0.3°, 24.6°±0.3°, having an XRPD pattern comprising peaks at 25.6°±0.3°, 26.1°±0.3°, 26.4°±0.3°, 26.8°±0.3°, 27.1°±0.3°, 28.2°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 30.3°±0.3°, 30.5°±0.3°, 30.9°±0.3°, 31.1°±0.3°, 32.1°±0.3°, 32.4°±0.3°, 33.0°±0.3°, 33.8°±0.3°, 34.0°±0.3°, 34.5°±0.3°, and 34.7°±0.3° 2θ.

[0096] In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.3°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.7°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.0°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.8°±0.2°2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising peaks at 11.0°±0.2° and 14.0°±0.2° 2θ. In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising one or more peaks selected from 10.3°±0.2°, 11.0°±0.2°, 11.9°±0.2°, 13.7°±0.2°, 14.0°±0.2°, and 14.8°±0.2° 2θ.

[0097] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.2°, 17.4°±0.2°, 20.6°±0.2°, 21.1°±0.2°, 23.2°±0.2°, and 24.1°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.6°±0.2°, 18.7°±0.2°, 19.7°±0.2°, 21.6°±0.2°, 23.0°±0.2°, 23.7°±0.2°, and 24.6°±0.2° 2θ.

[0098] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1°±0.2°, 26.4°±0.2°, 26.8°±0.2°, 28.2°±0.2°, 30.3°±0.2°, 30.5°±0.2°, and 33.0°±0.2°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6°±0.2°, 27.1°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 30.9°±0.2°, 31.1°±0.2°, 32.1°±0.2°, 32.4°±0.2°, 33.8°±0.2°, 34.0°±0.2°, 34.5°±0.2°, and 34.7°±0.2°2θ.

[0099] In certain embodiments, Form I of the compound of Formula (I) has the following chromatic aberrations: 10.3°±0.2°, 11.0°±0.2°, 11.9°±0.2°, 13.7°±0.2°, 14.0°±0.2°, 14.8°±0.2°, 15.3°±0.2°, 17.4°±0.2°, 17.6°±0.2°, 18.7°±0.2°, 19.7°±0.2°, 20.6°±0.2°, 21.1°±0.2°, 21.6°±0.2°, 23.0°±0.2°, 23.2°±0.2°, 23.7°±0.2°, 24.1°±0.2°, 24.6°±0.2°, having an XRPD pattern comprising peaks at 25.6°±0.2°, 26.1°±0.2°, 26.4°±0.2°, 26.8°±0.2°, 27.1°±0.2°, 28.2°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 30.3°±0.2°, 30.5°±0.2°, 30.9°±0.2°, 31.1°±0.2°, 32.1°±0.2°, 32.4°±0.2°, 33.0°±0.2°, 33.8°±0.2°, 34.0°±0.2°, 34.5°±0.2° and 34.7°±0.2° 2θ.

[0100] In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 11.

[0101] In certain embodiments, Form I of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in Figure 1A.

[0102] In certain embodiments, Form I of the compound of Formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form I of the compound of Formula (I) exists in an orthorhombic crystal system and has the P212121 space group. In certain embodiments, Form I of the compound of Formula (I) is characterized by the crystallographic unit cell parameters set forth in Table 1.

[0103] [Table 1]

[0104] In certain embodiments, Form I of the compound of Formula (I) has a differential scanning calorimetry (DSC) thermogram comprising an endotherm with a peak onset temperature at about 238° C. In certain embodiments, Form I of the compound of Formula (I) has a DSC thermogram comprising an endotherm with a peak onset temperature at about 273.9° C. In certain embodiments, Form I of the compound of Formula (I) has a DSC thermogram comprising one or more endotherms with peak onset temperatures at about 238° C. and about 273.9° C. In certain embodiments, Form I of the compound of Formula (I) has a DSC thermogram substantially identical to that shown in FIG.

[0105] In certain embodiments, Form I of the compound of Formula (I) exhibits a mass change of about 3% by weight or less when the relative humidity is varied between 0% and about 80% when measured at 25° C. The mass change of Form I of the compound of Formula (I) as a function of humidity can be determined, for example, using dynamic vapor sorption (DVS). In certain embodiments, Form I of the compound of Formula (I) has a moisture sorption isotherm when measured at 25° C. substantially identical to that shown in FIG. 21.

[0106] In certain embodiments, Form I of the compound of Formula (I) does not undergo detectable weight loss when heated from room temperature to about 150° C. The weight loss exhibited by Form I of the compound of Formula (I) upon heating can be measured, for example, using thermogravimetric analysis (TGA). In certain embodiments, Form I of the compound of Formula (I) has a TGA thermogram substantially identical to that shown in FIG.

[0107] (B) Form III

[0108] In one aspect, provided herein is Form III of the compound of Formula (I).

[0109] In certain embodiments, Form III of the compound of Formula (I) is an anhydrous crystalline form.

[0110] In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.7 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.9 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.9 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 12.2 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.3 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.3 °2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, and about 14.3° 2θ.

[0111] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.1°, about 19.0°, about 19.3°, about 21.8°, and about 24.9° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, and about 24.7° 2θ.

[0112] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 29.1°, about 32.3°, about 32.5°, about 33.1°, and about 34.1°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.8°, about 33.6°, about 33.8°, about 34.3°, and about 34.5°2θ.

[0113] In certain embodiments, Form III of the compound of Formula (I) is at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, about 14.3°, about 15.1°, about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.0°, about 19.3°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 21.8°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, about 24.7°, about 24.8°, about 24.9°, about 25.0°, about 25.1°, about 25.2°, about 25.3°, about 25.4°, about 25.5°, about 25.6°, about 25.7°, about 25.8°, about 25.9°, about 26.0°, about 26.1°, about 26.2°, about 26.3°, about 26.4°, about 26.5°, about 26.6°, about 26.7°, about 26.8°, about 27.0°, about 27.1°, about 27.2°, about 27.3°, about 27.4°, about 27.5°, about 27.6°, about 27.8°, about 27.9°, about 28.0°, about 28.1°, about 28.1°, about 28.2°, about 28.3°, about 28.4°, about 28.5°, about 28.6°, about 28.7° 0.9°, about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.1°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.3°, about 32.5°, about 32.8°, about 33.1°, about 33.6°, about 33.8°, about 34.1°, about 34.3°, and about 34.5° 2θ.

[0114] In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.7°±0.3°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.3°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.3°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.2°±0.3°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.3°±0.3°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.3°2θ. In certain embodiments, Form III of the compound of formula (I) has an XRPD pattern comprising peaks at 10.7°±0.3°, 10.9°±0.3°, 11.9°±0.3°, 12.2°±0.3°, 13.3°±0.3°, and 14.3°±0.3° 2θ.

[0115] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.1°±0.3°, 19.0°±0.3°, 19.3°±0.3°, 21.8°±0.3°, and 24.9°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0°±0.3°, 16.2°±0.3°, 16.8°±0.3°, 18.7°±0.3°, 19.9°±0.3°, 20.2°±0.3°, 21.2°±0.3°, 21.5°±0.3°, 22.7°±0.3°, 23.5°±0.3°, 24.0°±0.3°, 24.5°±0.3°, and 24.7°±0.3° 2θ.

[0116] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1°±0.3°, 26.4°±0.3°, 26.7°±0.3°, 26.9°±0.3°, 29.1°±0.3°, 32.3°±0.3°, 32.5°±0.3°, 33.1°±0.3°, and 34.1°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 27.7°±0.3°, 28.3°±0.3°, 28.6°±0.3°, 28.8°±0.3°, 29.6°±0.3°, 30.3°±0.3°, 30.6°±0.3°, 31.0°±0.3°, 31.4°±0.3°, 32.8°±0.3°, 33.6°±0.3°, 33.8°±0.3°, 34.3°±0.3°, and 34.5°±0.3°2θ.

[0117] In certain embodiments, Form III of the compound of Formula (I) is at 10.7°±0.3°, 10.9°±0.3°, 11.9°±0.3°, 12.2°±0.3°, 13.3°±0.3°, 14.3°±0.3°, 15.1°±0.3°, 16.0°±0.3°, 16.2°±0.3°, 16.8°±0.3°, 18.7°± 0.3°, 19.0°±0.3°, 19.3°±0.3°, 19.9°±0.3°, 20.2°±0.3°, 21.2°±0.3°, 21.5°±0.3°, 21.8°±0.3°, 22.7°±0.3°, 23.5°±0.3°, 24.0°±0.3°, 24.5°±0.3°, 24.7°±0.3°, 24.9° ±0.3°, 26.1°±0.3°, 26.4°±0.3°, 26.7°±0.3°, 26.9°±0.3°, 27.7°±0.3°, 28.3°±0.3°, 28.6°±0.3°, 28.8°±0.3°, 29.1°±0.3°, 29.6°±0.3°, 30.3°±0.3°, 30.6°±0.3°, 31.0 3°±0.3°, 31.4°±0.3°, 32.3°±0.3°, 32.5°±0.3°, 32.8°±0.3°, 33.1°±0.3°, 33.6°±0.3°, 33.8°±0.3°, 34.1°±0.3°, 34.3°±0.3°, and 34.5°±0.3° 2θ.

[0118] In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.7°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.9°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.2°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.3°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.2°2θ. In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising peaks at 10.7°±0.2°, 10.9°±0.2°, 11.9°±0.2°, 12.2°±0.2°, 13.3°±0.2°, and 14.3°±0.2° 2θ.

[0119] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.1°±0.2°, 19.0°±0.2°, 19.3°±0.2°, 21.8°±0.2°, and 24.9°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0°±0.2°, 16.2°±0.2°, 16.8°±0.2°, 18.7°±0.2°, 19.9°±0.2°, 20.2°±0.2°, 21.2°±0.2°, 21.5°±0.2°, 22.7°±0.2°, 23.5°±0.2°, 24.0°±0.2°, 24.5°±0.2°, and 24.7°±0.2° 2θ.

[0120] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.1°±0.2°, 26.4°±0.2°, 26.7°±0.2°, 26.9°±0.2°, 29.1°±0.2°, 32.3°±0.2°, 32.5°±0.2°, 33.1°±0.2°, and 34.1°±0.2°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 27.7°±0.2°, 28.3°±0.2°, 28.6°±0.2°, 28.8°±0.2°, 29.6°±0.2°, 30.3°±0.2°, 30.6°±0.2°, 31.0°±0.2°, 31.4°±0.2°, 32.8°±0.2°, 33.6°±0.2°, 33.8°±0.2°, 34.3°±0.2°, and 34.5°±0.2°2θ.

[0121] In certain embodiments, Form III of the compound of Formula (I) is at 10.7°±0.2°, 10.9°±0.2°, 11.9°±0.2°, 12.2°±0.2°, 13.3°±0.2°, 14.3°±0.2°, 15.1°±0.2°, 16.0°±0.2°, 16.2°±0.2°, 16.8°±0.2°, 18.7°± 0.2°, 19.0°±0.2°, 19.3°±0.2°, 19.9°±0.2°, 20.2°±0.2°, 21.2°±0.2°, 21.5°±0.2°, 21.8°±0.2°, 22.7°±0.2°, 23.5°±0.2°, 24.0°±0.2°, 24.5°±0.2°, 24.7°±0.2°, 24.9° ±0.2°, 26.1°±0.2°, 26.4°±0.2°, 26.7°±0.2°, 26.9°±0.2°, 27.7°±0.2°, 28.3°±0.2°, 28.6°±0.2°, 28.8°±0.2°, 29.1°±0.2°, 29.6°±0.2°, 30.3°±0.2°, 30.6°±0.2°, 31.0 and 34.5°±0.2° 2θ.

[0122] In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 13.

[0123] In certain embodiments, Form III of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0124] In certain embodiments, Form III of the compound of Formula (I) exists in a monoclinic crystal system. In certain embodiments, Form III of the compound of Formula (I) exists in a monoclinic crystal system and has a P121 / n1 space group. In certain embodiments, Form III of the compound of Formula (I) is characterized by the crystallographic unit cell parameters set forth in Table 2.

[0125] [Table 2]

[0126] (C)Form X

[0127] In one embodiment, Form X of the compound of Formula (I) is provided.

[0128] In certain embodiments, Form X of the compound of Formula (I) is an anhydrous crystalline form.

[0129] In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.6 °2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.9 °2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at about 12.0 °2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.1 °2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.5 °2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising peaks at about 10.6 °, about 10.9 °, about 12.0 °, about 14.1 °, and about 14.5 °2θ.

[0130] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.1°, about 21.9°, and about 24.1° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.5°, about 18.0°, about 18.8°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 22.3°, about 23.3°, and about 24.6° 2θ.

[0131] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 27.3°, about 29.0°, about 29.2°, about 30.8°, and about 31.1° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.8°, about 26.4°, about 28.7°, about 30.6°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ.

[0132] In certain embodiments, Form X of the compound of Formula (I) has an angle of about 10.6°, about 10.9°, about 12.0°, about 14.1°, about 14.5°, about 15.3°, about 17.5°, about 18.0°, about 18.8°, about 19.1°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 21.9°, about 22.3°, about 23.3°, It has an XRPD pattern including peaks at about 24.1°, about 24.6°, about 25.2°, about 25.8°, about 26.4°, about 27.3°, about 28.7°, about 29.0°, about 29.2°, about 30.6°, about 30.8°, about 31.1°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ.

[0133] In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.6°±0.3°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.3°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.0°±0.3°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.3°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.5°±0.3°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising peaks at 10.6°±0.3°, 10.9°±0.3°, 12.0°±0.3°, 14.1°±0.3°, and 14.5°±0.3° 2θ.

[0134] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 19.1°±0.3°, 21.9°±0.3°, and 24.1°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.5°±0.3°, 18.0°±0.3°, 18.8°±0.3°, 19.7°±0.3°, 20.7°±0.3°, 21.2°±0.3°, 21.6°±0.3°, 22.3°±0.3°, 23.3°±0.3°, and 24.6°±0.3°2θ.

[0135] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2°±0.3°, 27.3°±0.3°, 29.0°±0.3°, 29.2°±0.3°, 30.8°±0.3°, and 31.1°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.8°±0.3°, 26.4°±0.3°, 28.7°±0.3°, 30.6°±0.3°, 32.4°±0.3°, 33.0°±0.3°, 33.5°±0.3°, 33.9°±0.3°, and 34.7°±0.3°2θ.

[0136] In certain embodiments, Form X of the compound of Formula (I) may have any of the following angular trajectories: 10.6°±0.3°, 10.9°±0.3°, 12.0°±0.3°, 14.1°±0.3°, 14.5°±0.3°, 15.3°±0.3°, 17.5°±0.3°, 18.0°±0.3°, 18.8°±0.3°, 19.1°±0.3°, 19.7°±0.3°, 20.7°±0.3°, 21.2°±0.3°, 21.6°±0.3°, 21.9°±0.3°, 22.3°±0.3°, 23.3°±0.3°, It has an XRPD pattern containing peaks at 24.1°±0.3°, 24.6°±0.3°, 25.2°±0.3°, 25.8°±0.3°, 26.4°±0.3°, 27.3°±0.3°, 28.7°±0.3°, 29.0°±0.3°, 29.2°±0.3°, 30.6°±0.3°, 30.8°±0.3°, 31.1°±0.3°, 32.4°±0.3°, 33.0°±0.3°, 33.5°±0.3°, 33.9°±0.3°, and 34.7°±0.3° 2θ.

[0137] In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.6°±0.2°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.9°±0.2°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.0°±0.2°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.2°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.5°±0.2°2θ. In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising peaks at 10.6°±0.2°, 10.9°±0.2°, 12.0°±0.2°, 14.1°±0.2°, and 14.5°±0.2° 2θ.

[0138] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.2°, 19.1°±0.2°, 21.9°±0.2°, and 24.1°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.5°±0.2°, 18.0°±0.2°, 18.8°±0.2°, 19.7°±0.2°, 20.7°±0.2°, 21.2°±0.2°, 21.6°±0.2°, 22.3°±0.2°, 23.3°±0.2°, and 24.6°±0.2° 2θ.

[0139] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2°±0.2°, 27.3°±0.2°, 29.0°±0.2°, 29.2°±0.2°, 30.8°±0.2°, and 31.1°±0.2°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.8°±0.2°, 26.4°±0.2°, 28.7°±0.2°, 30.6°±0.2°, 32.4°±0.2°, 33.0°±0.2°, 33.5°±0.2°, 33.9°±0.2°, and 34.7°±0.2°2θ.

[0140] In certain embodiments, Form X of the compound of Formula (I) may have any of the following angles: 10.6°±0.2°, 10.9°±0.2°, 12.0°±0.2°, 14.1°±0.2°, 14.5°±0.2°, 15.3°±0.2°, 17.5°±0.2°, 18.0°±0.2°, 18.8°±0.2°, 19.1°±0.2°, 19.7°±0.2°, 20.7°±0.2°, 21.2°±0.2°, 21.6°±0.2°, 21.9°±0.2°, 22.3°±0.2°, 23.3°±0.2°, It has an XRPD pattern comprising peaks at 24.1°±0.2°, 24.6°±0.2°, 25.2°±0.2°, 25.8°±0.2°, 26.4°±0.2°, 27.3°±0.2°, 28.7°±0.2°, 29.0°±0.2°, 29.2°±0.2°, 30.6°±0.2°, 30.8°±0.2°, 31.1°±0.2°, 32.4°±0.2°, 33.0°±0.2°, 33.5°±0.2°, 33.9°±0.2°, and 34.7°±0.2° 2θ.

[0141] In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 20.

[0142] In certain embodiments, Form X of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0143] In certain embodiments, Form X of the compound of Formula (I) has a DSC thermogram comprising an endotherm with a peak onset temperature at about 235.8° C. In certain embodiments, Form X of the compound of Formula (I) has a DSC thermogram comprising an endotherm with a peak onset temperature at about 281.9° C. In certain embodiments, Form X of the compound of Formula (I) has a DSC thermogram comprising one or more endotherms with peak onset temperatures at about 235.8° C. and about 281.9° C. In certain embodiments, Form X of the compound of Formula (I) has a DSC thermogram substantially identical to that shown in FIG.

[0144] In certain embodiments, Form X of the compound of Formula (I) exhibits a mass change of about 3% by weight or less when the relative humidity is varied between 0% and about 80% when measured at 25° C. The mass change of Form X of the compound of Formula (I) as a function of humidity can be determined, for example, using DVS. In certain embodiments, Form X of the compound of Formula (I) has a moisture sorption isotherm when measured at 25° C. substantially identical to that shown in Figure 23.

[0145] In certain embodiments, Form X of the compound of Formula (I) does not undergo detectable weight loss when heated from room temperature to about 150° C. The weight loss of Form X of the compound of Formula (I) upon heating can be measured, for example, using TGA. In certain embodiments, Form X of the compound of Formula (I) has a TGA thermogram substantially identical to that shown in FIG.

[0146] (2) Crystalline hydrate of the compound of formula (I)

[0147] In one aspect, provided herein is a crystalline hydrate of the compound of Formula (I). In certain embodiments, the crystalline hydrate of the compound of Formula (I) is a crystalline monohydrate.

[0148] (A) Form II

[0149] In one embodiment, there is provided Form II of the compound of Formula (I).

[0150] In certain embodiments, Form II of the compound of Formula (I) is a crystalline hydrate. In certain embodiments, Form II of the compound of Formula (I) is a crystalline monohydrate.

[0151] In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at about 6.9°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.7°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.9°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.3°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, and about 14.3°2θ.

[0152] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 15.5°, about 17.4°, about 20.9°, about 22.3°, and about 23.6° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 17.9°, about 19.7°, about 21.4°, about 22.8°, about 23.8°, and about 24.9° 2θ.

[0153] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, and about 28.8° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 28.6°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ.

[0154] In certain embodiments, Form II of the compound of Formula (I) has a β-glucan content of about 6.9°, about 11.2°, about 11.7°, about 13.9°, about 14.3°, about 15.3°, about 15.5°, about 17.4°, about 17.9°, about 19.7°, about 20.9°, about 21.4°, about 22.3°, about 22.8°, about 23.6°, about 23.8°, about 24.9°, about 25. 2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, about 28.6°, about 28.8°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ.

[0155] In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 6.9°±0.3°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.2°±0.3°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.7°±0.3°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.3°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.3°2θ. In certain embodiments, Form II of the compound of formula (I) has an XRPD pattern comprising peaks at 6.9°±0.3°, 11.2°±0.3°, 11.7°±0.3°, 13.9°±0.3°, and 14.3°±0.3° 2θ.

[0156] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.3°, 15.5°±0.3°, 17.4°±0.3°, 20.9°±0.3°, 22.3°±0.3°, and 23.6°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.9°±0.3°, 19.7°±0.3°, 21.4°±0.3°, 22.8°±0.3°, 23.8°±0.3°, and 24.9°±0.3° 2θ.

[0157] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2°±0.3°, 25.5°±0.3°, 25.7°±0.3°, 26.4°±0.3°, 27.0°±0.3°, 27.5°±0.3°, 28.1°±0.3°, 28.2°±0.3°, and 28.8°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 28.6°±0.3°, 29.2°±0.3°, 29.9°±0.3°, 31.3°±0.3°, 31.4°±0.3°, 31.9°±0.3°, 32.6°±0.3°, 33.7°±0.3°, and 34.3°±0.3°2θ.

[0158] In certain embodiments, Form II of the compound of Formula (I) is at 6.9°±0.3°, 11.2°±0.3°, 11.7°±0.3°, 13.9°±0.3°, 14.3°±0.3°, 15.3°±0.3°, 15.5°±0.3°, 17.4°±0.3°, 17.9°±0.3°, 19.7°±0.3°, 20.9°±0.3°, 21.4°±0.3°, 22.3°±0.3°, 22.8°±0.3°, 23.6°±0.3°, 23.8°±0.3°, 24.9°±0.3°, 25.2°± 0.3°, 25.5°±0.3°, 25.7°±0.3°, 26.4°±0.3°, 27.0°±0.3°, 27.5°±0.3°, 28.1°±0.3°, 28.2°±0.3°, 28.6°±0.3°, 28.8°±0.3°, 29.2°±0.3°, 29.9°±0.3°, 31.3°±0.3°, 31.4°±0.3°, 31.9°±0.3°, 32.6°±0.3°, 33.7°±0.3°, and 34.3°±0.3° 2θ.

[0159] In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 6.9°±0.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.2°±0.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.7°±0.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.2°2θ. In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising peaks at 6.9°±0.2°, 11.2°±0.2°, 11.7°±0.2°, 13.9°±0.2°, and 14.3°±0.2° 2θ.

[0160] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.3°±0.2°, 15.5°±0.2°, 17.4°±0.2°, 20.9°±0.2°, 22.3°±0.2°, and 23.6°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 17.9°±0.2°, 19.7°±0.2°, 21.4°±0.2°, 22.8°±0.2°, 23.8°±0.2°, and 24.9°±0.2° 2θ.

[0161] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.2°±0.2°, 25.5°±0.2°, 25.7°±0.2°, 26.4°±0.2°, 27.0°±0.2°, 27.5°±0.2°, 28.1°±0.2°, 28.2°±0.2°, and 28.8°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 28.6°±0.2°, 29.2°±0.2°, 29.9°±0.2°, 31.3°±0.2°, 31.4°±0.2°, 31.9°±0.2°, 32.6°±0.2°, 33.7°±0.2°, and 34.3°±0.2° 2θ.

[0162] In certain embodiments, Form II of the compound of Formula (I) is at 6.9°±0.2°, 11.2°±0.2°, 11.7°±0.2°, 13.9°±0.2°, 14.3°±0.2°, 15.3°±0.2°, 15.5°±0.2°, 17.4°±0.2°, 17.9°±0.2°, 19.7°±0.2°, 20.9°±0.2°, 21.4°±0.2°, 22.3°±0.2°, 22.8°±0.2°, 23.6°±0.2°, 23.8°±0.2°, 24.9°±0.2, 25.2°± having an XRPD pattern containing peaks at 0.2°, 25.5°±0.2°, 25.7°±0.2°, 26.4°±0.2°, 27.0°±0.2°, 27.5°±0.2°, 28.1°±0.2°, 28.2°±0.2°, 28.6°±0.2°, 28.8°±0.2°, 29.2°±0.2°, 29.9°±0.2°, 31.3°±0.2°, 31.4°±0.2°, 31.9±0.2°, 32.6°±0.2°, 33.7°±0.2°, and 34.3°±0.2° 2θ.

[0163] In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 12.

[0164] In certain embodiments, Form II of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0165] In certain embodiments, Form II of the compound of Formula (I) exists in an orthorhombic crystal system. In certain embodiments, Form II of the compound of Formula (I) exists in an orthorhombic crystal system and has the C2221 space group. In certain embodiments, Form II of the compound of Formula (I) is characterized by the crystallographic unit cell parameters set forth in Table 3.

[0166] [Table 3]

[0167] (3) Crystalline solvates of the compound of formula (I)

[0168] In one aspect, a crystalline solvate of the compound of formula (I) is provided. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetonitrile solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetic acid solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an ethanol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is a methanol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an ethylene glycol solvate. In certain embodiments, the crystalline solvate of the compound of formula (I) is an acetone solvate.

[0169] In certain embodiments, the crystalline solvate of the compound of Formula (I) exists in the orthorhombic crystal system. In certain embodiments, the crystalline solvate of the compound of Formula (I) exists in the orthorhombic crystal system and has the P212121 space group.

[0170] In certain embodiments, the crystalline solvate of the compound of Formula (I) exists in the monoclinic crystal system. In certain embodiments, the crystalline solvate of the compound of Formula (I) exists in the monoclinic crystal system and has the P1211 space group.

[0171] (A) Form IV

[0172] In one embodiment, there is provided Form IV of the compound of Formula (I).

[0173] In certain embodiments, Form IV of the compound of Formula (I) is a crystalline acetonitrile solvate. In certain embodiments, Form IV of the compound of Formula (I) is a crystalline monoacetonitrile solvate.

[0174] In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at about 7.2°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at about 9.6°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.8°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.1°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.5°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising peaks at about 7.2°, about 9.6°, about 10.8°, about 13.1°, and about 14.5°2θ.

[0175] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.8°, about 16.6°, about 18.2°, about 19.2°, and about 21.6° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 20.1°, about 21.9°, about 22.8°, and about 23.0° 2θ.

[0176] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.1°, about 25.3°, about 26.0°, about 26.3°, about 27.1°, about 27.6°, about 28.6°, about 31.8°, about 32.7°, and about 33.7° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 29.0°, about 29.2°, about 29.9°, about 31.2°, about 32.0°, about 32.4°, about 33.5°, and about 34.1° 2θ.

[0177] In certain embodiments, Form IV of the compound of Formula (I) has an azimuthal angle of about 7.2°, about 9.6°, about 10.8°, about 13.1°, about 14.5°, about 15.8°, about 16.6°, about 18.2°, about 19.2°, about 20.1°, about 21.6°, about 21.9°, about 22.8°, about 23.0°, about 25.1°, about 25.3°, about It has an XRPD pattern including peaks at 26.0°, about 26.3°, about 27.1°, about 27.6°, about 28.6°, about 29.0°, about 29.2°, about 29.9°, about 31.2°, about 31.8°, about 32.0°, about 32.4°, about 32.7°, about 33.5°, about 33.7°, and about 34.1° 2θ.

[0178] In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at 7.2°±0.3°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.6°±0.3°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at 10.8°±0.3°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.1°±0.3°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.5°±0.3°2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2°±0.3°, 9.6°±0.3°, 10.8°±0.3°, 13.1°±0.3°, and 14.5°±0.3° 2θ.

[0179] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.8°±0.3°, 16.6°±0.3°, 18.2°±0.3°, 19.2°±0.3°, and 21.6°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 20.1°±0.3°, 21.9°±0.3°, 22.8°±0.3°, and 23.0°±0.3° 2θ.

[0180] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1°±0.3°, 25.3°±0.3°, 26.0°±0.3°, 26.3°±0.3°, 27.1°±0.3°, 27.6°±0.3°, 28.6°±0.3°, 31.8°±0.3°, 32.7°±0.3°, and 33.7°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 29.0°±0.3°, 29.2°±0.3°, 29.9°±0.3°, 31.2°±0.3°, 32.0°±0.3°, 32.4°±0.3°, 33.5°±0.3°, and 34.1°±0.3°2θ.

[0181] In certain embodiments, Form IV of the compound of Formula (I) is at 7.2°±0.3°, 9.6°±0.3°, 10.8°±0.3°, 13.1°±0.3°, 14.5°±0.3°, 15.8°±0.3°, 16.6°±0.3°, 18.2°±0.3°, 19.2°±0.3°, 20.1°±0.3°, 21.6°±0.3°, 21.9°±0.3°, 22.8°±0.3°, 23.0°±0.3°, 25.1°±0.3°, 25.3°±0.3°, 26.0°±0.3°, 27.0°±0.3°, 28.0°±0.3°, 29.0°±0.3°, 30.0°±0.3°, 31.0°±0.3°, 32.0°±0.3°, 33.0°±0.3°, 34.0°±0.3°, 35.0°±0.3°, 36.0°±0.3°, 37.0°±0.3°, 38.0°±0.3°, 39.0°±0.3°, 40.0°±0.3°, 41.0°±0.3°, 42.0°±0.3°, 43.0°±0.3°, 44.0°±0.3°, 45.0°±0.3°, 46.0°±0.3°, 47.0°±0.3°, 48.0°±0.3°, 49.0°±0.3°, 50.0°±0.3°, 51. having an XRPD pattern containing peaks at 6.0°±0.3°, 26.3°±0.3°, 27.1°±0.3°, 27.6°±0.3°, 28.6°±0.3°, 29.0°±0.3°, 29.2°±0.3°, 29.9°±0.3°, 31.2°±0.3°, 31.8°±0.3°, 32.0°±0.3°, 32.4°±0.3°, 32.7°±0.3°, 33.5°±0.3°, 33.7°±0.3°, and 34.1°±0.3° 2θ.

[0182] In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern including a peak at 7.2°±0.2°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern including a peak at 9.6°±0.2°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern including a peak at 10.8°±0.2°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern including a peak at 13.1°±0.2°2θ. In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern including a peak at 14.5°±0.2°2θ. In certain embodiments, Form IV of the compound of formula (I) has an XRPD pattern comprising peaks at 7.2°±0.2°, 9.6°±0.2°, 10.8°±0.2°, 13.1°±0.2°, and 14.5°±0.2° 2θ.

[0183] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.8°±0.2°, 16.6°±0.2°, 18.2°±0.2°, 19.2°±0.2°, and 21.6°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 20.1°±0.2°, 21.9°±0.2°, 22.8°±0.2°, and 23.0°±0.2° 2θ.

[0184] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1°±0.2°, 25.3°±0.2°, 26.0°±0.2°, 26.3°±0.2°, 27.1°±0.2°, 27.6°±0.2°, 28.6°±0.2°, 31.8°±0.2°, 32.7°±0.2°, and 33.7°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 29.0°±0.2°, 29.2°±0.2°, 29.9°±0.2°, 31.2°±0.2°, 32.0°±0.2°, 32.4°±0.2°, 33.5°±0.2°, and 34.1°±0.2° 2θ.

[0185] In certain embodiments, Form IV of the compound of Formula (I) is at 7.2°±0.2°, 9.6°±0.2°, 10.8°±0.2°, 13.1°±0.2°, 14.5°±0.2°, 15.8°±0.2°, 16.6°±0.2°, 18.2°±0.2°, 19.2°±0.2°, 20.1°±0.2°, 21.6°±0.2°, 21.9°±0.2°, 22.8°±0.2°, 23.0°±0.2°, 25.1°±0.2°, 25.3°±0.2°, 26.0°±0.2°, 27.0°±0.2°, 28.0°±0.2°, 29.0°±0.2°, 30.0°±0.2°, 31.0°±0.2°, 32.0°±0.2°, 33.0°±0.2°, 34.0°±0.2°, 35.0°±0.2°, 36.0°±0.2°, 37.0°±0.2°, 38.0°±0.2°, 39.0°±0.2°, 40.0°±0.2°, 41.0°±0.2°, 42.0°±0.2°, 43.0°±0.2°, 44.0°±0.2°, 45.0°±0.2°, 46.0°±0.2°, 47.0°±0.2°, 48.0°±0.2°, 49.0°±0.2°, 50.0°±0.2°, 51. It has an XRPD pattern containing peaks at 6.0°±0.2°, 26.3°±0.2°, 27.1°±0.2°, 27.6°±0.2°, 28.6°±0.2°, 29.0°±0.2°, 29.2°±0.2°, 29.9°±0.2°, 31.2°±0.2°, 31.8°±0.2°, 32.0°±0.2°, 32.4°±0.2°, 32.7°±0.2°, 33.5°±0.2°, 33.7°±0.2°, and 34.1°±0.2° 2θ.

[0186] In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 14.

[0187] In certain embodiments, Form IV of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0188] In certain embodiments, Form IV of the compound of Formula (I) exists in a monoclinic crystal system. In certain embodiments, Form IV of the compound of Formula (I) exists in a monoclinic crystal system and has the P1211 space group. In certain embodiments, Form IV of the compound of Formula (I) is characterized by the crystallographic unit cell parameters shown in Table 4.

[0189] [Table 4]

[0190] (B) Form V

[0191] In one aspect, provided herein is Form V of the compound of Formula (I).

[0192] In certain embodiments, Form V of the compound of Formula (I) is a crystalline acetic acid solvate. In certain embodiments, Form V of the compound of Formula (I) is a crystalline bis-acetic acid solvate.

[0193] In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 7.6 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 8.0 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 8.4 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.3 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.9 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at about 15.0 °2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising peaks at about 7.6°, about 8.0°, about 8.4°, about 13.3°, about 13.9°, and about 15.0° 2θ.

[0194] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.2°, about 19.0°, about 19.5°, about 20.2°, about 20.7°, and about 24.0° 2θ, hi certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.4°, about 16.1°, about 22.1°, about 22.5°, about 23.1°, about 24.4°, and about 24.7° 2θ.

[0195] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.4°, about 25.9°, about 26.5°, about 27.1°, about 27.3°, about 29.6°, about 29.9°, about 30.1°, about 30.6°, and about 30.7°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 26.7°, about 27.6°, about 28.5°, about 29.4°, about 30.3°, about 31.1°, about 31.4°, about 32.2°, about 32.8°, about 33.1°, about 33.4°, about 33.6°, about 34.1°, about 34.3°, about 34.6°, and about 35.0°2θ.

[0196] In certain embodiments, Form V of the compound of Formula (I) has an average molecular weight of about 7.6°, about 8.0°, about 8.4°, about 13.3°, about 13.9°, about 15.0°, about 15.2°, about 15.4°, about 16.1°, about 19.0°, about 19.5°, about 20.2°, about 20.7°, about 22.1°, about 22.5°, about 23.1°, about 24.0°, about 24.4°, and about 24.7°, about 25.4°, about 25.6°, about 25.9°, about 26.5°, It has an XRPD pattern including peaks at about 26.7°, about 27.1°, about 27.3°, about 27.6°, about 28.5°, about 29.4°, about 29.6°, about 29.9°, about 30.1°, about 30.3°, about 30.6°, about 30.7°, about 31.1°, about 31.4°, about 32.2°, about 32.8°, about 33.1°, about 33.4°, about 33.6°, about 34.1°, about 34.3°, about 34.6°, and about 35.0° 2θ.

[0197] In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 7.6°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.0°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.4°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.3°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 15.0°±0.3°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising peaks at 7.6°±0.3°, 8.0°±0.3°, 8.4°±0.3°, 13.3°±0.3°, 13.9°±0.3°, and 15.0°±0.3° 2θ.

[0198] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2°±0.3°, 19.0°±0.3°, 19.5°±0.3°, 20.2°±0.3°, 20.7°±0.3°, and 24.0°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.4°±0.3°, 16.1°±0.3°, 22.1°±0.3°, 22.5°±0.3°, 23.1°±0.3°, 24.4°±0.3°, and 24.7°±0.3°2θ.

[0199] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.4°±0.3°, 25.9°±0.3°, 26.5°±0.3°, 27.1°±0.3°, 27.3°±0.3°, 29.6°±0.3°, 29.9°±0.3°, 30.1°±0.3°, 30.6°±0.3°, and 30.7°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6°±0.3°, 26.7°±0.3°, 27.6°±0.3°, 28.5°±0.3°, 29.4°±0.3°, 30.3°±0.3°, 31.1°±0.3°, 31.4°±0.3°, 32.2°±0.3°, 32.8°±0.3°, 33.1°±0.3°, 33.4°±0.3°, 33.6°±0.3°, 34.1°±0.3°, 34.3°±0.3°, 34.6°±0.3°, and 35.0°±0.3°2θ.

[0200] In certain embodiments, Form V of the compound of Formula (I) is 7.6°±0.3°, 8.0°±0.3°, 8.4°±0.3°, 13.3°±0.3°, 13.9°±0.3°, 15.0°±0.3°, 15.2°±0.3°, 15.4°±0.3°, 16.1°±0.3°, 19.0°±0.3°, 19.5°±0.3°, 19.6°±0.3°, 19.7°±0.3°, 19.8°±0.3°, 19.9°±0.3°, 20.0°±0.3°, 20.1°±0.3°, 20.2°±0.3°, 20.3°±0.3°, 20.4°±0.3°, 20.5°±0.3°, 20.6°±0.3°, 20.8°±0.3°, 20.9°±0.3°, 21.0°±0.3°, 21.1°±0.3°, 21.2°±0.3°, 21.4°±0.3°, 21.6°±0.3°, 21.8 ... .3°, 20.2°±0.3°, 20.7°±0.3°, 22.1°±0.3°, 22.5°±0.3°, 23.1°±0.3°, 24.0°±0.3°, 24.4°±0.3°, 24.7°±0.3°, 25.4°±0.3°, 25.6°±0.3°, 25.9°±0.3°, 26.5°±0.3°, 26 .7°±0.3°, 27.1°±0.3°, 27.3°±0.3°, 27.6°±0.3°, 28.5°±0.3°, 29.4°±0.3°, 29.6°±0.3°, 29.9°±0.3°, 30.1°±0.3°, 30.3°±0.3°, 30.6°±0.3°, 30.7°±0.3°, 31.1°±0. and 35.0°±0.3° 2θ.

[0201] In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 7.6°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.0°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.4°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.3°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising a peak at 15.0°±0.2°2θ. In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising peaks at 7.6°±0.2°, 8.0°±0.2°, 8.4°±0.2°, 13.3°±0.2°, 13.9°±0.2°, and 15.0°±0.2° 2θ.

[0202] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2°±0.2°, 19.0°±0.2°, 19.5°±0.2°, 20.2°±0.2°, 20.7°±0.2°, and 24.0°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.4°±0.2°, 16.1°±0.2°, 22.1°±0.2°, 22.5°±0.2°, 23.1°±0.2°, 24.4°±0.2°, and 24.7°±0.2° 2θ.

[0203] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.4°±0.2°, 25.9°±0.2°, 26.5°±0.2°, 27.1°±0.2°, 27.3°±0.2°, 29.6°±0.2°, 29.9°±0.2°, 30.1°±0.2°, 30.6°±0.2°, and 30.7°±0.2°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.6°±0.2°, 26.7°±0.2°, 27.6°±0.2°, 28.5°±0.2°, 29.4°±0.2°, 30.3°±0.2°, 31.1°±0.2°, 31.4°±0.2°, 32.2°±0.2°, 32.8°±0.2°, 33.1°±0.2°, 33.4°±0.2°, 33.6°±0.2°, 34.1°±0.2°, 34.3°±0.2°, 34.6°±0.2°, and 35.0°±0.2°2θ.

[0204] In certain embodiments, Form V of the compound of Formula (I) is at 7.6°±0.2°, 8.0°±0.2°, 8.4°±0.2°, 13.3°±0.2°, 13.9°±0.2°, 15.0°±0.2°, 15.2°±0.2°, 15.4°±0.2°, 16.1°±0.2°, 19.0°±0.2°, 19.5°±0.2°, 19.6°±0.2°, 19.7°±0.2°, 19.8°±0.2°, 20.4°±0.2°, 20.6°±0.2°, 20.8 ... .2°, 20.2°±0.2°, 20.7°±0.2°, 22.1°±0.2°, 22.5°±0.2°, 23.1°±0.2°, 24.0°±0.2°, 24.4°±0.2°, 24.7°±0.2°, 25.4°±0.2°, 25.6°±0.2°, 25.9°±0.2°, 26.5°±0.2°, 26 .7°±0.2°, 27.1°±0.2°, 27.3°±0.2°, 27.6°±0.2°, 28.5°±0.2°, 29.4°±0.2°, 29.6°±0.2°, 29.9°±0.2°, 30.1°±0.2°, 30.3°±0.2°, 30.6°±0.2°, 30.7°±0.2°, 31.1°±0. 2°, 31.4°±0.2°, 32.2°±0.2°, 32.8°±0.2°, 33.1°±0.2°, 33.4°±0.2°, 33.6°±0.2°, 34.1°±0.2°, 34.3°±0.2°, 34.6°±0.2°, and 35.0°±0.2° 2θ.

[0205] In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 15.

[0206] In certain embodiments, Form V of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0207] In certain embodiments, Form V of the compound of Formula (I) exists in a monoclinic crystal system. In certain embodiments, Form V of the compound of Formula (I) exists in a monoclinic crystal system and has the P1211 space group. In certain embodiments, Form V of the compound of Formula (I) is characterized by the crystallographic unit cell parameters set forth in Table 5.

[0208] [Table 5]

[0209] (C) Form VI

[0210] In one embodiment, there is provided Form VI of the compound of Formula (I).

[0211] In certain embodiments, Form VI of the compound of Formula (I) is a crystalline ethanol solvate. In certain embodiments, Form VI of the compound of Formula (I) is a crystalline monoethanol solvate.

[0212] In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at about 8.5°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at about 9.0°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.5°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.1°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.4°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising peaks at about 8.5°, about 9.0°, about 11.5°, about 14.1°, and about 14.4°2θ.

[0213] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.1°, about 17.4°, about 16.1°, about 18.8°, about 21.3°, about 22.0°, about 22.7°, and about 24.4° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 18.0°, about 20.3°, about 20.4°, about 23.3°, about 23.8°, and about 24.2° 2θ.

[0214] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.5°, about 25.7°, about 26.3°, about 28.4°, about 29.5°, about 29.6°, about 30.5°, and about 31.1°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.5°, about 27.3°, about 28.0°, about 28.9°, about 29.2°, about 30.1°, about 31.5°, about 31.7°, about 32.2°, about 32.6°, about 33.4°, about 34.3°, about 34.4°, and about 34.7°2θ.

[0215] In certain embodiments, Form VI of compound of Formula (I) is at about 8.5°, about 9.0°, about 11.5°, about 14.1°, about 14.4°, about 16.1°, about 17.4°, about 16.1°, about 18.0°, about 18.8°, about 20.3°, about 20.4°, about 21.3°, about 22.0°, about 22.7°, 23.3°, about 23.8°, about 24.2°, about 24.4°, about 25.5°, about 25.7°, about 26.7°, about 27.7°, about 28.7°, about 29.7°, about 30.7°, about 31.7°, about 32.7°, about 33.7°, about 34.7°, about 35.7°, about 36.7°, about 37.7°, about 38.7°, about 39.7°, about 40.7°, about 41.7°, about 42.7°, about 43.7°, about 44.7°, about 45.7°, about 46.7°, about 47.7°, about 48.7°, about 49.7°, about 50.7°, about 51.7°, about 52.7°, about 53.7°, about 54.7°, about 55.7°, about 56.7°, about 57.7°, about 58.7°, about 59.7°, about 60.7°, about 61.7°, about 62.7°, about 63.7°, about 64.7°, about 65.7°, about 66.7°, about 2θ, about 26.3°, about 26.5°, about 27.3°, about 28.0°, about 28.4°, about 28.9°, about 29.2°, about 29.5°, about 29.6°, about 30.1°, about 30.5°, about 31.1°, about 31.5°, about 31.7°, about 32.2°, about 32.6°, about 33.4°, about 34.3°, about 34.4°, and about 34.7° 2θ.

[0216] In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.5°±0.3°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.0°±0.3°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.5°±0.3°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.3°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.4°±0.3°2θ. In certain embodiments, Form VI of compound of formula (I) has an XRPD pattern comprising peaks at 8.5°±0.3°, 9.0°±0.3°, 11.5°±0.3°, 14.1°±0.3°, and 14.4°±0.3° 2θ.

[0217] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.1°±0.3°, 17.4°±0.3°, 16.1°±0.3°, 18.8°±0.3°, 21.3°±0.3°, 22.0°±0.3°, 22.7°±0.3°, and 24.4°±0.3°. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 18.0°±0.3°, 20.3°±0.3°, 20.4°±0.3°, 23.3°±0.3°, 23.8°±0.3°, and 24.2°±0.3°2θ.

[0218] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.5°±0.3°, 25.7°±0.3°, 26.3°±0.3°, 28.4°±0.3°, 29.5°±0.3°, 29.6°±0.3°, 30.5°±0.3°, and 31.1°±0.3°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.5°±0.3°, 27.3°±0.3°, 28.0°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 30.1°±0.3°, 31.5°±0.3°, 31.7°±0.3°, 32.2°±0.3°, 32.6°±0.3°, 33.4°±0.3°, 34.3°±0.3°, 34.4°±0.3°, and 34.7°±0.3°2θ.

[0219] In certain embodiments, Form VI of the compound of Formula (I) is at 8.5°±0.3°, 9.0°±0.3°, 11.5°±0.3°, 14.1°±0.3°, 14.4°±0.3°, 16.1°±0.3°, 17.4°±0.3°, 16.1°±0.3°, 18.0°±0.3°, 18.8°±0.3°, 20.3°±0.3°, 20.4°±0.3°, 21.3°±0.3°, 22.0°±0.3°, 22.7°±0.3°, 23.3°±0.3°, 23.8°±0.3°, 24.2°±0.3°, 24.4°±0.3°, 25.5°±0.3°, 25.7°± 0.3°, 26.3°±0.3°, 26.5°±0.3°, 27.3°±0.3°, 28.0°±0.3°, 28.4°±0.3°, 28.9°±0.3°, 29.2°±0.3°, 29.5°±0.3°, 29.6°±0.3°, 30.1°±0.3°, 30.5°±0.3°, 31.1°±0.3°, 31.5°±0.3°, 31.7°±0.3°, 32.2°±0.3°, 32.6°±0.3°, 33.4°±0.3°, 34.3°±0.3°, 34.4°±0.3°, and 34.7°±0.3° 2θ.

[0220] In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.5°±0.2°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.0°±0.2°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.5°±0.2°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.1°±0.2°2θ. In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.4°±0.2°2θ. In certain embodiments, Form VI of compound of formula (I) has an XRPD pattern comprising peaks at 8.5°±0.2°, 9.0°±0.2°, 11.5°±0.2°, 14.1°±0.2°, and 14.4°±0.2° 2θ.

[0221] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.1°±0.2°, 17.4°±0.2°, 16.1°±0.2°, 18.8°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 22.7°±0.2°, and 24.4°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 18.0°±0.2°, 20.3°±0.2°, 20.4°±0.2°, 23.3°±0.2°, 23.8°±0.2°, and 24.2°±0.2° 2θ.

[0222] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.5°±0.2°, 25.7°±0.2°, 26.3°±0.2°, 28.4°±0.2°, 29.5°±0.2°, 29.6°±0.2°, 30.5°±0.2°, and 31.1°±0.2°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 26.5°±0.2°, 27.3°±0.2°, 28.0°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 30.1°±0.2°, 31.5°±0.2°, 31.7°±0.2°, 32.2°±0.2°, 32.6°±0.2°, 33.4°±0.2°, 34.3°±0.2°, 34.4°±0.2°, and 34.7°±0.2°2θ.

[0223] In certain embodiments, Form VI of the compound of Formula (I) is at 8.5°±0.2°, 9.0°±0.2°, 11.5°±0.2°, 14.1°±0.2°, 14.4°±0.2°, 16.1°±0.2°, 17.4°±0.2°, 16.1°±0.2°, 18.0°±0.2°, 18.8°±0.2°, 20.3°±0.2°, 20.4°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 22.7°±0.2°, 23.3°±0.2°, 23.8°±0.2°, 24.2°±0.2°, 24.4°±0.2°, 25.5°±0.2°, 25.7°± 0.2°, 26.3°±0.2°, 26.5°±0.2°, 27.3°±0.2°, 28.0°±0.2°, 28.4°±0.2°, 28.9°±0.2°, 29.2°±0.2°, 29.5°±0.2°, 29.6°±0.2°, 30.1°±0.2°, 30.5°±0.2°, 31.1°±0.2°, 31.5°±0.2°, 31.7°±0.2°, 32.2°±0.2°, 32.6°±0.2°, 33.4°±0.2°, 34.3°±0.2°, 34.4°±0.2°, and 34.7°±0.2° 2θ.

[0224] In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 16.

[0225] In certain embodiments, Form VI of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0226] In certain embodiments, Form VI of the compound of Formula (I) exists in a monoclinic crystal system. In certain embodiments, Form VI of the compound of Formula (I) exists in a monoclinic crystal system and has the P1211 space group. In certain embodiments, Form VI of the compound of Formula (I) is characterized by the crystallographic unit cell parameters shown in Table 6.

[0227] [Table 6]

[0228] (D) Form VII

[0229] In one aspect, provided herein is Form VII of the compound of Formula (I).

[0230] In certain embodiments, Form VII of the compound of formula (I) is a crystalline methanol solvate. In certain embodiments, Form VII of the compound of formula (I) is a crystalline hemi-methanol solvate.

[0231] In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 4.9 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 8.5 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 9.5 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 9.8 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.0 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 12.1 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 12.8 °2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.9°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.4°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.6°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.8°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising peaks at about 4.9°, about 8.5°, about 9.5°, about 9.8°, about 11.0°, about 12.1°, about 12.8°, about 13.9°, about 14.4°, and about 14.8°2θ.

[0232] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.2°, about 16.3°, about 16.5°, about 17.5°, about 18.0°, about 19.0°, about 19.1°, about 20.2°, about 20.4°, about 21.0°, about 21.6°, about 22.5°, about 23.7°, about 24.5°, and about 24.9°2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.2°, about 16.9°, about 17.1°, about 19.8°, about 20.7°, about 21.4°, about 22.1°, about 23.1°, about 23.9°, and about 24.3°2θ.

[0233] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.1°, about 25.3°, about 25.8°, about 27.1°, about 27.5°, about 27.7°, about 28.4°, about 29.5°, about 29.8°, about 31.0°, and about 34.9° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 26.3°, about 26.6°, about 26.7°, about 27.9°, about 28.1°, about 28.7°, about 28.9°, about 29.1°, about 30.2°, about 30.7°, about 31.3°, about 31.6°, about 31.8°, about 32.2°, about 32.6°, about 33.1°, about 33.4°, about 33.8°, about 34.0°, about 34.2°, and about 34.6° 2θ.

[0234] In certain embodiments, Form VII of the compound of Formula (I) is at about 4.9°, about 8.5°, about 9.5°, about 9.8°, about 11.0°, about 12.1°, about 12.8°, about 13.9°, about 14.4°, about 14.8°, about 15.2°, about 16.2°, about 16.3°, about 16.5°, about 16.9°, about 17.0°, about 18.0°, about 19.0°, about 20.0°, about 21.0°, about 22.0°, about 23.0°, about 24.0°, about 25.0°, about 26.0°, about 27.0°, about 28.0°, about 29.0°, about 30.0°, about 31.0°, about 32.0°, about 33.0°, about 34.0°, about 35.0°, about 36.0°, about 37.0°, about 38.0°, about 39.0°, about 40.0°, about 41.0°, about 42.0°, about 43.0°, about 44.0°, about 45.0°, about 46.0°, about 47.0°, about 48.0°, about 49.0°, about 50.0°, about 51.0°, about 52.0°, about 53.0°, about 54.0°, about 55.0°, about 56.0°, about 57.0°, about 58.0°, about 59.0°, about 60.0°, about 61.0°, about 62.0°, about 63.0°, about 7.1°, approximately 17.5°, approximately 18.0°, approximately 19.0°, approximately 19.1°, approximately 19.8°, approximately 20.2°, approximately 20.4°, approximately 20.7°, approximately 21.0°, approximately 21.4°, approximately 21.6°, approximately 22.1°, approximately 22.5°, approximately 23.1°, approximately 23.7°, approximately 23.9°, approximately 24.3°, approximately 24.5 2θ, about 24.9°, about 25.1°, about 25.3°, about 25.8°, about 26.3°, about 26.6°, about 26.7°, about 27.1°, about 27.5°, about 27.7°, about 27.9°, about 28.1°, about 28.4°, about 28.7°, about 28.9°, about 29.1°, about 29.5°, about 29.8°, about 30.2°, about 30.7°, about 31.0°, about 31.3°, about 31.6°, about 31.8°, about 32.2°, about 32.6°, about 33.1°, about 33.4°, about 33.8°, about 34.0°, about 34.2°, about 34.6°, and about 34.9° 2θ.

[0235] In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 4.9°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.5°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.5°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.8°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.1°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.8°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.4°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.6°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.8°±0.3°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising peaks at 4.9°±0.3°, 8.5°±0.3°, 9.5°±0.3°, 9.8°±0.3°, 11.0°±0.3°, 12.1°±0.3°, 12.8°±0.3°, 13.9°±0.3°, 14.4°±0.3°, and 14.8°±0.3° 2θ.

[0236] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2°±0.3°, 16.3°±0.3°, 16.5°±0.3°, 17.5°±0.3°, 18.0°±0.3°, 19.0°±0.3°, 19.1°±0.3°, 20.2°±0.3°, 20.4°±0.3°, 21.0°±0.3°, 21.6°±0.3°, 22.5°±0.3°, 23.7°±0.3°, 24.5°±0.3°, and 24.9°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.2°±0.3°, 16.9°±0.3°, 17.1°±0.3°, 19.8°±0.3°, 20.7°±0.3°, 21.4°±0.3°, 22.1°±0.3°, 23.1°±0.3°, 23.9°±0.3°, and 24.3°±0.3° 2θ.

[0237] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1°±0.3°, 25.3°±0.3°, 25.8°±0.3°, 27.1°±0.3°, 27.5°±0.3°, 27.7°±0.3°, 28.4°±0.3°, 29.5°±0.3°, 29.8°±0.3°, 31.0°±0.3°, and 34.9°±0.3°2θ. In certain embodiments, the XRPD patterns are 26.3°±0.3°, 26.6°±0.3°, 26.7°±0.3°, 27.9°±0.3°, 28.1°±0.3°, 28.7°±0.3°, 28.9°±0.3°, 29.1°±0.3°, 30.2°±0.3°, 30.7°±0.3°, 31.3°±0.3 31.6°±0.3°, 31.8°±0.3°, 32.2°±0.3°, 32.6°±0.3°, 33.1°±0.3°, 33.4°±0.3°, 33.8°±0.3°, 34.0°±0.3°, 34.2°±0.3°, and 34.6°±0.3°2θ.

[0238] In certain embodiments, Form VII of the compound of Formula (I) is at 4.9°±0.3°, 8.5°±0.3°, 9.5°±0.3°, 9.8°±0.3°, 11.0°±0.3°, 12.1°±0.3°, 12.8°±0.3°, 13.9°±0.3°, 14.4°±0.3°, 14.8°±0.3°, 15.2°±0.3°, 16.2°±0.3°, 16.3°±0.3°, 16.5°±0.3°, 16.9°±0.3°, 17.1°±0.3° °, 17.5°±0.3°, 18.0°±0.3°, 19.0°±0.3°, 19.1°±0.3°, 19.8°±0.3°, 20.2°±0.3°, 20.4°±0.3°, 20.7°±0.3°, 21.0°±0.3°, 21.4°±0.3°, 21.6°±0.3°, 22.1°±0.3°, 22.5°±0.3°, 23.1°±0.3°, 23.7°±0.3°, 23.9°±0.3°, 24.3°±0.3°, 24.5°±0.3° .3°, 24.9°±0.3°, 25.1°±0.3°, 25.3°±0.3°, 25.8°±0.3°, 26.3°±0.3°, 26.6°±0.3°, 26.7°±0.3°, 27.1°±0.3°, 27.5°±0.3°, 27.7°±0.3°, 27.9°±0.3°, 28.1°±0.3°, 28.4°±0.3°, 28.7°±0.3°, 28.9°±0.3°, 29.1°±0.3°, 29.5°±0.3°, 29.8° ±0.3°, 30.2°±0.3°, 30.7°±0.3°, 31.0°±0.3°, 31.3°±0.3°, 31.6°±0.3°, 31.8°±0.3°, 32.2°±0.3°, 32.6°±0.3°, 33.1°±0.3°, 33.4°±0.3°, 33.8°±0.3°, 34.0°±0.3°, 34.2°±0.3°, 34.6°±0.3°, and 34.9°±0.3° 2θ.

[0239] In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 4.9°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.5°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.5°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 9.8°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.0°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.1°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 12.8°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.9°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.4°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.6°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.8°±0.2°2θ. In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising peaks at 4.9°±0.2°, 8.5°±0.2°, 9.5°±0.2°, 9.8°±0.2°, 11.0°±0.2°, 12.1°±0.2°, 12.8°±0.2°, 13.9°±0.2°, 14.4°±0.2°, and 14.8°±0.2° 2θ.

[0240] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 15.2°±0.2°, 16.3°±0.2°, 16.5°±0.2°, 17.5°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 19.1°±0.2°, 20.2°±0.2°, 20.4°±0.2°, 21.0°±0.2°, 21.6°±0.2°, 22.5°±0.2°, 23.7°±0.2°, 24.5°±0.2°, and 24.9°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.2°±0.2°, 16.9°±0.2°, 17.1°±0.2°, 19.8°±0.2°, 20.7°±0.2°, 21.4°±0.2°, 22.1°±0.2°, 23.1°±0.2°, 23.9°±0.2°, and 24.3°±0.2°2θ.

[0241] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.1°±0.2°, 25.3°±0.2°, 25.8°±0.2°, 27.1°±0.2°, 27.5°±0.2°, 27.7°±0.2°, 28.4°±0.2°, 29.5°±0.2°, 29.8°±0.2°, 31.0°±0.2°, and 34.9°±0.2°2θ. In certain embodiments, the XRPD patterns are 26.3°±0.2°, 26.6°±0.2°, 26.7°±0.2°, 27.9°±0.2°, 28.1°±0.2°, 28.7°±0.2°, 28.9°±0.2°, 29.1°±0.2°, 30.2°±0.2°, 30.7°±0.2°, 31.3°±0.2°, 31.6°±0.2°, 31.8°±0.2°, 32.2°±0.2°, 32.6°±0.2°, 33.1°±0.2°, 33.4°±0.2°, 33.8°±0.2°, 34.0°±0.2°, 34.2°±0.2°, and 34.6°±0.2° 2θ.

[0242] In certain embodiments, Form VII of the compound of Formula (I) is at 4.9°±0.2°, 8.5°±0.2°, 9.5°±0.2°, 9.8°±0.2°, 11.0°±0.2°, 12.1°±0.2°, 12.8°±0.2°, 13.9°±0.2°, 14.4°±0.2°, 14.8°±0.2°, 15.2°±0.2°, 16.2°±0.2°, 16.3°±0.2°, 16.5°±0.2°, 16.9°±0.2°, 17.1°±0.2° °, 17.5°±0.2°, 18.0°±0.2°, 19.0°±0.2°, 19.1°±0.2°, 19.8°±0.2°, 20.2°±0.2°, 20.4°±0.2°, 20.7°±0.2°, 21.0°±0.2°, 21.4°±0.2°, 21.6°±0.2°, 22.1°±0.2°, 22.5°±0.2°, 23.1°±0.2°, 23.7°±0.2°, 23.9°±0.2°, 24.3°±0.2°, 24.5°±0.2° .2°, 24.9°±0.2°, 25.1°±0.2°, 25.3°±0.2°, 25.8°±0.2°, 26.3°±0.2°, 26.6°±0.2°, 26.7°±0.2°, 27.1°±0.2°, 27.5°±0.2°, 27.7°±0.2°, 27.9°±0.2°, 28.1°±0.2°, 28.4°±0.2°, 28.7°±0.2°, 28.9°±0.2°, 29.1°±0.2°, 29.5°±0.2°, 29.8° ±0.2°, 30.2°±0.2°, 30.7°±0.2°, 31.0°±0.2°, 31.3°±0.2°, 31.6°±0.2°, 31.8°±0.2°, 32.2°±0.2°, 32.6°±0.2°, 33.1°±0.2°, 33.4°±0.2°, 33.8°±0.2°, 34.0°±0.2°, 34.2°±0.2°, 34.6°±0.2°, and 34.9°±0.2° 2θ.

[0243] In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 17.

[0244] In certain embodiments, Form VII of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0245] In certain embodiments, Form VII of the compound of Formula (I) exists in an orthorhombic crystalline system. In certain embodiments, Form VII of the compound of Formula (I) exists in an orthorhombic crystalline system and has the P212121 space group. In certain embodiments, Form VII of the compound of Formula (I) is characterized by the crystallographic unit cell parameters shown in Table 7.

[0246] [Table 7]

[0247] In certain embodiments, Form VII of the compound of Formula (I) further comprises water. In certain embodiments, the molar ratio of methanol to water in Form VII of the compound of Formula (I) is about 1:1.

[0248] (E) Form VIII

[0249] In one embodiment, Form VIII of the compound of Formula (I) is provided.

[0250] In certain embodiments, Form VIII of the compound of Formula (I) is a crystalline ethylene glycol solvate. In certain embodiments, Form VIII of the compound of Formula (I) is a crystalline monoethylene glycol solvate.

[0251] In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 8.9°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 11.4°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.1°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.0°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising peaks at about 8.9°, about 11.4°, about 13.1°, about 14.0°, and about 14.3°2θ.

[0252] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 17.3°, about 18.8°, about 21.2°, about 21.9°, about 22.5°, about 23.7°, and about 24.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 16.9°, about 17.9°, about 20.3°, about 23.0°, about 23.2°, and about 24.0° 2θ.

[0253] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.3°, about 25.7°, about 26.1°, about 28.3°, about 29.3°, about 29.5°, and about 30.5° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.9°, about 26.4°, about 27.2°, about 27.9°, about 28.8°, about 29.0°, about 30.0°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2θ.

[0254] In certain embodiments, Form VIII of the compound of Formula (I) has an azimuthal angle of about 8.9°, about 11.4°, about 13.1°, about 14.0°, about 14.3°, about 16.0°, about 16.9°, about 17.3°, about 17.9°, about 18.8°, about 20.3°, about 21.2°, about 21.9°, about 22.5°, about 23.0°, about 23.2°, about 23.7°, about 24.0°, about 24.2°, about 25.3°, about 25.7° , about 25.9°, about 26.1°, about 26.4°, about 27.2°, about 27.9°, about 28.3°, about 28.8°, about 29.0°, about 29.3°, about 29.5°, about 30.0°, about 30.5°, about 30.9°, about 31.4°, about 31.6°, about 32.1°, about 32.4°, about 33.4°, about 34.0°, about 34.3°, and about 34.6° 2θ.

[0255] In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.9°±0.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.4°±0.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.1°±0.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.0°±0.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.3°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising peaks at 8.9°±0.3°, 11.4°±0.3°, 13.1°±0.3°, 14.0°±0.3°, and 14.3°±0.3° 2θ.

[0256] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0°±0.3°, 17.3°±0.3°, 18.8°±0.3°, 21.2°±0.3°, 21.9°±0.3°, 22.5°±0.3°, 23.7°±0.3°, and 24.2°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.9°±0.3°, 17.9°±0.3°, 20.3°±0.3°, 23.0°±0.3°, 23.2°±0.3°, and 24.0°±0.3° 2θ.

[0257] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.3°±0.3°, 25.7°±0.3°, 26.1°±0.3°, 28.3°±0.3°, 29.3°±0.3°, 29.5°±0.3°, and 30.5°±0.3° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.9°±0.3°, 26.4°±0.3°, 27.2°±0.3°, 27.9°±0.3°, 28.8°±0.3°, 29.0°±0.3°, 30.0°±0.3°, 30.9°±0.3°, 31.4°±0.3°, 31.6°±0.3°, 32.1°±0.3°, 32.4°±0.3°, 33.4°±0.3°, 34.0°±0.3°, 34.3°±0.3°, and 34.6°±0.3°2θ.

[0258] In certain embodiments, Form VIII of the compound of Formula (I) is at 8.9°±0.3°, 11.4°±0.3°, 13.1°±0.3°, 14.0°±0.3°, 14.3°±0.3°, 16.0°±0.3°, 16.9°±0.3°, 17.3°±0.3°, 17.9°±0.3°, 18.8°±0.3°, 20.3°±0.3°, 21.2°±0.3°, 21.9°±0.3°, 22.5°±0.3°, 23.0°±0.3°, 23.2°±0.3°, 23.7°±0.3°, 24.0°±0.3°, 24.2°±0.3°, 25.3°±0.3°, 25.7°±0.3° , 25.9°±0.3°, 26.1°±0.3°, 26.4°±0.3°, 27.2°±0.3°, 27.9°±0.3°, 28.3°±0.3°, 28.8°±0.3°, 29.0°±0.3°, 29.3°±0.3°, 29.5°±0.3°, 30.0°±0.3°, 30.5°±0.3°, 30.9°±0.3°, 31.4°±0.3°, 31.6°±0.3°, 32.1°±0.3°, 32.4°±0.3°, 33.4°±0.3°, 34.0°±0.3°, 34.3°±0.3°, and 34.6°±0.3° 2θ.

[0259] In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 8.9°±0.2°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 11.4°±0.2°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 13.1°±0.2°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.0°±0.2°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising a peak at 14.3°±0.2°2θ. In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising peaks at 8.9°±0.2°, 11.4°±0.2°, 13.1°±0.2°, 14.0°±0.2°, and 14.3°±0.2° 2θ.

[0260] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.0°±0.2°, 17.3°±0.2°, 18.8°±0.2°, 21.2°±0.2°, 21.9°±0.2°, 22.5°±0.2°, 23.7°±0.2°, and 24.2°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 16.9°±0.2°, 17.9°±0.2°, 20.3°±0.2°, 23.0°±0.2°, 23.2°±0.2°, and 24.0°±0.2° 2θ.

[0261] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.3°±0.2°, 25.7°±0.2°, 26.1°±0.2°, 28.3°±0.2°, 29.3°±0.2°, 29.5°±0.2°, and 30.5°±0.2° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from 25.9°±0.2°, 26.4°±0.2°, 27.2°±0.2°, 27.9°±0.2°, 28.8°±0.2°, 29.0°±0.2°, 30.0°±0.2°, 30.9°±0.2°, 31.4°±0.2°, 31.6°±0.2°, 32.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 34.0°±0.2°, 34.3°±0.2°, and 34.6°±0.2°2θ.

[0262] In certain embodiments, Form VIII of the compound of Formula (I) is at 8.9°±0.2°, 11.4°±0.2°, 13.1°±0.2°, 14.0°±0.2°, 14.3°±0.2°, 16.0°±0.2°, 16.9°±0.2°, 17.3°±0.2°, 17.9°±0.2°, 18.8°±0.2°, 20.3°±0.2°, 21.2°±0.2°, 21.9°±0.2°, 22.5°±0.2°, 23.0°±0.2°, 23.2°±0.2°, 23.7°±0.2°, 24.0°±0.2°, 24.2°±0.2°, 25.3°±0.2°, 25.7°±0.2° , 25.9°±0.2°, 26.1°±0.2°, 26.4°±0.2°, 27.2°±0.2°, 27.9°±0.2°, 28.3°±0.2°, 28.8°±0.2°, 29.0°±0.2°, 29.3°±0.2°, 29.5°±0.2°, 30.0°±0.2°, 30.5°±0.2°, 30.9°±0.2°, 31.4°±0.2°, 31.6°±0.2°, 32.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 34.0°±0.2°, 34.3°±0.2°, and 34.6°±0.2° 2θ.

[0263] In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 18.

[0264] In certain embodiments, Form VIII of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0265] In certain embodiments, Form VIII of the compound of Formula (I) exists in a monoclinic crystal system. In certain embodiments, Form VIII of the compound of Formula (I) exists in a monoclinic crystal system and has the P1211 space group. In certain embodiments, Form VIII of the compound of Formula (I) is characterized by the crystallographic unit cell parameters shown in Table 8.

[0266] [Table 8]

[0267] (F) Form IX

[0268] In one embodiment, Form IX of the compound of Formula (I) is provided.

[0269] In certain embodiments, Form IX of the compound of formula (I) is a crystalline acetone solvate. In certain embodiments, Form IX of the compound of formula (I) is a crystalline monoacetone solvate.

[0270] In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising a peak at about 7.1°2θ. In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising a peak at about 9.5°2θ. In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising a peak at about 10.5°2θ. In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising a peak at about 13.1°2θ. In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising a peak at about 14.3°2θ. In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising peaks at about 7.1°, about 9.5°, about 10.5°, about 13.1°, and about 14.3°2θ.

[0271] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 15.6°, about 16.2°, about 18.0°, about 18.9°, about 21.1°, and about 24.8° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 18.8°, about 19.6°, about 21.4°, about 21.9°, about 22.5°, about 22.8°, and about 24.5° 2θ.

[0272] In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.3°, about 25.8°, about 26.4°, about 27.0°, about 28.2°, about 31.4°, about 31.8°, and about 33.0° 2θ. In certain embodiments, the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 26.6°, about 28.7°, about 29.1°, about 29.2°, about 30.7°, about 33.3°, about 34.3°, and about 34.8° 2θ.

[0273] In certain embodiments, Form IX of the compound of Formula (I) has an average molecular weight of about 7.1°, about 9.5°, about 10.5°, about 13.1°, about 14.3°, about 15.6°, about 16.2°, about 18.0°, about 18.8°, about 18.9°, about 19.6°, about 21.1°, about 21.4°, about 21.9°, about 22.5°, about 22.8°, about 24.5°, or about 24. 2θ, about 25.8°, about 25.2°, about 25.3°, about 25.8°, about 26.4°, about 26.6°, about 27.0°, about 28.2°, about 28.7°, about 29.1°, about 29.2°, about 30.7°, about 31.4°, about 31.8°, about 33.0°, about 33.3°, about 34.3°, and about 34.8° 2θ.

[0274] In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern comprising one or more diffraction peaks (2θ) disclosed in Table 19.

[0275] In certain embodiments, Form IX of the compound of Formula (I) has an XRPD pattern substantially identical to that shown in FIG.

[0276] In certain embodiments, Form IX of the compound of Formula (I) exists in the monoclinic crystal system. In certain embodiments, Form IX of the compound of Formula (I) exists in the monoclinic crystal system and has the P1211 space group. In certain embodiments, Form IX of the compound of Formula (I) is characterized by the crystallographic unit cell parameters shown in Table 9.

[0277] [Table 9]

[0278] (4) Chemical purity of the crystalline form of the compound of formula (I)

[0279] In certain embodiments, the crystalline form of the compound of Formula (I) described herein has a chemical purity of about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 95%, about 85% to about 90%, or about 90% to about 95%.

[0280] In certain embodiments, the crystalline form of the compound of Formula (I) described herein has a chemical purity of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, or at least 99.9%.

[0281] In certain embodiments, the crystalline form of the compound of Formula (I) described herein has a chemical purity of about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, about 99.9%, or about 100%.

[0282] Pharmaceutical Composition

[0283] In one aspect, provided herein are pharmaceutical compositions generally comprising a compound of Formula (I) (e.g., a crystalline form of the compound of Formula (I) described herein, e.g., Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of Formula (I)) and a pharmaceutically acceptable excipient for the treatment of a condition, disease, or disorder described herein.

[0284] In various embodiments, provided herein are pharmaceutical compositions containing a crystalline form of the compound of Formula (I) described herein (e.g., Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X) and a pharmaceutically acceptable excipient.

[0285] In various embodiments, pharmaceutical compositions are provided that contain two or more crystalline forms of the compound of Formula (I) described herein and pharmaceutically acceptable excipients thereof.

[0286] In certain embodiments, the pharmaceutical compositions described herein can be administered in unit dosage form and can be prepared by any method known in the art of pharmacy. The amount of the compound of formula (I) (e.g., a crystalline form of the compound of formula (I) described herein, such as Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of formula (I)) present in a single dosage form can vary depending on the patient being treated and / or the particular mode of administration.

[0287] The pharmaceutical compositions provided herein can be administered by a variety of routes, including, but not limited to, oral (enteral), parenteral (by injection), rectal, transdermal, intradermal, intrathecal, subcutaneous (SC), intravenous (IV), intramuscular (IM), and intranasal administration.

[0288] The pharmaceutical compositions provided herein can also be administered chronically ("chronic administration"). Chronic administration refers to the administration of a compound or pharmaceutical composition thereof over an extended period of time, including continuous administration for, for example, 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or for the remainder of a subject's life. In certain embodiments, chronic administration is intended to provide a constant level of a compound (e.g., a compound of Formula (I)) in the blood, e.g., within a therapeutic range, over an extended period of time.

[0289] The pharmaceutical compositions provided herein can be provided in unit dosage forms to facilitate accurate administration.The term "unit dosage form" refers to a physically discrete unit suitable as a unitary dosage for human subjects and other mammals, each unit containing a predetermined amount of active ingredient calculated to produce a desired therapeutic effect, together with suitable pharmaceutical excipients.Typical unit dosage forms include pre-filled, pre-measured ampoules or syringes for liquid pharmaceutical compositions, and pills, tablets, capsules, etc. for solid pharmaceutical compositions.

[0290] Pharmaceutical compositions suitable for oral administration can be provided as discrete dosage forms such as, but not limited to, tablets (e.g., chewable tablets), caplets, capsules, liquids (e.g., flavored syrups), and the like. These dosage forms contain predetermined amounts of the active ingredient and can be prepared by pharmaceutical techniques well known to those skilled in the art. See generally, Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing, Easton PA (1990).

[0291] The oral dosage forms provided herein are prepared by intimately mixing the active ingredient with at least one excipient according to conventional pharmaceutical compounding techniques. The excipients can take various forms depending on the dosage form desired for administration. For example, suitable excipients for oral liquid or aerosol dosage forms include, but are not limited to, water, glycols, oils, alcohols, flavorings, preservatives, and coloring agents. Suitable excipients for solid oral dosage forms (e.g., powders, tablets, capsules, and caplets) include, but are not limited to, fillers, diluents, granulating agents, lubricants, binders, and disintegrants.

[0292] In various embodiments, the pharmaceutical compositions described herein may be in oral dosage forms such as tablets or capsules, in which case solid excipients are used.In certain embodiments, tablets can be coated by standard aqueous or non-aqueous techniques.Such dosage forms can be prepared by any pharmaceutical method.In general, pharmaceutical compositions and dosage forms are prepared by uniformly and intimately mixing active ingredients with liquid carriers, finely divided solid carriers, or both, and then shaping into desired shapes as needed.

[0293] In certain embodiments, the compound of Formula (I) (e.g., a crystalline form of the compound of Formula (I) described herein, such as Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, Form IX, or Form X of the compound of Formula (I)) can be administered as the sole active agent or in combination with other active agents.

[0294] Although the description of pharmaceutical compositions provided herein primarily relates to pharmaceutical compositions suitable for administration to humans, those skilled in the art will understand that such compositions are generally suitable for administration to any type of animal. Modifications of pharmaceutical compositions suitable for administration to humans to make them suitable for administration to a variety of animals are well known, and a veterinary pharmacologist of ordinary skill can design and / or perform such modifications using routine experimentation. General considerations for the formulation and / or manufacture of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy 21 st ed., Lippincott Williams & Wilkins, 2005.

[0295] Second active agent

[0296] The compounds provided herein (e.g., compounds of Formula (I)) can be combined with other pharmacologically active compounds ("second active agents") in the methods and compositions provided herein. Certain combinations may act synergistically in treating specific types of diseases or disorders, and the pathologies and symptoms associated with such diseases or disorders. The compounds provided herein (e.g., compounds of Formula (I)) may also have the effect of mitigating adverse effects associated with certain second active agents, and vice versa.

[0297] The methods and compositions provided herein can use one or more second active ingredients or agents. The second active agent can be a large molecule (e.g., a protein) or a small molecule (e.g., a synthetic inorganic, organometallic, or organic molecule).

[0298] The compounds provided herein (e.g., compounds of Formula (I)) and the second active agent can be administered to patients simultaneously or sequentially by the same or different administration routes. The appropriateness of the administration route adopted for a particular active agent depends on the active agent itself (e.g., whether it can be orally administered without being decomposed before entering the bloodstream) and the disease to be treated. One of the administration routes for the compounds provided herein is oral administration. The administration route of the second active agent or component is known to those skilled in the art. For example, see Physicians' Desk Reference (60th edition, 2006).

[0299] In another embodiment, the second active agent is administered intravenously or subcutaneously once or twice daily in an amount of about 1 to about 1000 mg, about 5 to about 500 mg, about 10 to about 350 mg, or about 50 to about 200 mg. The specific amount of the second active agent will depend on the specific agent used, the type of disease being treated or managed, the severity and stage of the disease, and the amount of the compound described herein and any additional active agents co-administered to the patient.

[0300] As described elsewhere herein, also included herein are methods for reducing, treating, and / or preventing adverse or undesirable effects associated with conventional therapies, including, but not limited to, surgery, chemotherapy, radiation therapy, hormone therapy, biological therapy, and immunotherapy. The compounds provided herein (e.g., compounds of Formula (I) and other active ingredients) can be administered to a patient before, during, or after the onset of adverse effects associated with conventional therapy. [Example]

[0301] In order that the disclosure described herein may be more fully understood, the following examples are set forth: The synthetic and biological examples described in this application are provided to illustrate the compounds, pharmaceutical compositions, and methods described herein, and should not be construed as limiting the scope thereof in any way.

[0302] Common analytical methods

[0303] Single crystal structure determination

[0304] Single crystal X-ray data for Forms I-IX of the compound of Formula (I) were obtained using a Bruker D8 single crystal X-ray diffractometer system (λ=1.54180 Å). Frames were integrated with the narrow frame algorithm in the Bruker SAINT software package. The structure of each crystalline form was solved and refined using the Bruker SHELXTL software package.

[0305] Characterization by X-ray powder diffraction (XRPD)

[0306] XRPD data were recorded at room temperature using one of three methods:

[0307] Method 1: XRPD patterns were acquired using an Aeris X-ray diffractometer (Malvern PANalytical BV, Almelo, The Netherlands) with Cu Kα radiation (λ = 1.54 Å) through a Ni monochromator at 40 kV and 15 mA. Data were collected over a 2θ angle range of 3° to 40° in continuous scan mode with a step size of 0.02° and a dwell time of 149 seconds. The sample was loaded onto a zero-background holder and gently pressed with a clean glass slide to ensure the sample surface was flush with the holder surface. Diffractograms were analyzed and plotted using HighScore Plus software (v5.0; Malvern PANalytical BV, Almelo, The Netherlands).

[0308] Method 2: XRPD data were collected using a Bruker D2 Phaser benchtop X-ray powder diffractometer (Bruker, Billerica, MA, USA) equipped with a solid-state LynxEye (1D mode) detector using Cu Kα radiation (λ = 1.54184 Å). Samples were prepared on a Si low-background holder. Samples were used either as is or ground with a mortar and pestle.

[0309] Method 3: Alternatively, XRPD patterns were generated from single crystal X-ray diffraction data using the Cambridge Crystallographic Data Centre (CCDC) Mercury 2022.2.0 (Build 353591) according to the method described in C.F. Macrae et al., J. Appl. Cryst., 53, 2020, 226-235.

[0310] Differential scanning calorimetry (DSC)

[0311] DSC experiments were performed using one of two settings:

[0312] Method 1: The sample cell of a Discovery DSC 2500 instrument (TA® Instruments, New Castle, DE, USA) equipped with a cooling system (RCS90) was purged with dry nitrogen at a flow rate of 50 mL / min. An accurately weighed sample (2–5 mg) was placed in a Tzero sealed container and scanned over the desired temperature range (typically 25–300 °C) at a heating rate of 10 °C / min.

[0313] Method 2: The sample was placed in a 40 μL aluminum pan in a DSC3 instrument (Mettler Toledo, Columbus, Ohio, USA). The temperature was increased from 25°C to 300°C at a rate of 5°C / min. STAR was used for data processing. e software (Mettler Toledo, Columbus, OH, USA) was used.

[0314] Thermogravimetric analysis (TGA)

[0315] The sample was weighed and placed in an aluminum pan in the sample cell of a Discovery TGA 5500 instrument (TA® Instruments, New Castle, DE, USA) or a Shimadzu DTG-60 instrument (Shimadzu Scientific Instruments, Inc., Columbia, MD, USA) equipped with TRIOS software (version 5.0). The sample cell was then purged with dry nitrogen at a flow rate of 15 mL / min. Data were recorded using a heating rate of 10 °C / min over the range of 25 to 350 °C.

[0316] Dynamic Vapor Sorption (DVS)

[0317] Moisture sorption / desorption data were collected using a DVS-intrinsic vapor sorption analyzer (Surface Measurement Systems NA, Allentown, PA, USA) equipped with DVS-intrinsic control software (version 1.0.5.1). Samples were not dried prior to analysis. Adsorption and desorption data were collected under a nitrogen purge over a range of 5% to 98% relative humidity (RH) in 10% RH increments. The equilibrium criteria used for analysis were a weight change of less than 0.005% in 10 minutes, with a maximum equilibration time of 3 hours.

[0318] Karl Fischer moisture determination (KF)

[0319] KF measurements were performed using a Metrohm 756 coulometer (Metrohm, Riverview, FL, USA). The compound (approximately 60 mg, accurately weighed) was dissolved in 3 mL of anhydrous tetrahydrofuran and placed in a vial. The vial was capped and shaken by hand until the compound dissolved to form a clear solution. An aliquot of this solution (approximately 0.6 mL, accurately weighed) was injected into the KF apparatus. Measurements were performed in triplicate, and the average water content (ppm) was determined to calculate the percentage of water in the solid material.

[0320] Example 1: (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Synthesis of [H]-2,6-piperidinedione

[0321] Reaction temperatures are given as internal temperatures. Intermediates, reagents, and solvents were used as commercially available.

[0322] Preparation of 2-methyl-6-nitro-4H-3,1-benzoxazin-4-one [ka]

[0323] 2-Amino-5-nitrobenzoic acid (399.6 g, 2.195 mol, 1.0 equiv.) was mixed with acetic anhydride (800 mL, 8.47 mol, 3.86 equiv.) and heated to 120 °C in an oil bath for 2 h. The resulting mixture was cooled to 25 ± 5 °C overnight. After cooling to 0–5 °C, the mixture was held at the same temperature for 3 h. The solid was collected by filtration and washed with methyl tert-butyl ether (MTBE, 200 mL × 3) to give a wet cake (417.5 g). The wet cake was dried under reduced pressure at 50 ± 5 °C for 18 h to give 2-methyl-6-nitro-4H-3,1-benzoxazin-4-one (384.1 g). Quantitative nuclear magnetic resonance spectroscopy (QNMR) indicated that the product titer was 99.4% (w / w). 1 H NMR (deuterated dimethyl sulfoxide (DMSO-d6) δ (ppm): 2.40 (s, 3H), 7.75-7.80 (dd, 1H), 7.86-7.93 (dd, 1H), 8.00-8.08 (t, 1H).

[0324] Preparation of 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione [ka]

[0325] 2-Methyl-6-nitro-4H-3,1-benzoxazin-4-one (429.1 g, 2.08 mol, 1.0 equiv.) was charged to a 20 L jacketed reactor. 3-Amino-2,6-piperidinedione hydrochloride (445.4 g, 2.71 mol, 1.3 equiv.) was then added, followed by 2 L of isopropyl acetate. The resulting mixture was stirred at 25 ± 5 °C. A solution of propylphosphonic anhydride (T3P) in ethyl acetate (2.478 L, 4.16 mol, 2.0 equiv.) was pumped into the reactor, followed by isopropyl acetate (500 mL) to rinse the pump. The resulting mixture was heated to 88 ± 5 °C. After 32 h, an additional solution of T3P in ethyl acetate (197 mL, 0.15 equiv.) was charged to the reactor, heated to 88 ± 5 °C, and maintained for 24 h. After a total reaction time of 56 hours, the mixture was cooled to 25±5° C. and the solid was collected by filtration. The wet cake was washed with isopropyl acetate (960 mL×3) and dried under reduced pressure with a nitrogen sweep at 25±5° C. to constant weight (approximately 24 hours) to give 789.2 g of 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione with a titer of 72.5% w / w (by QNMR), which was used directly in the next synthetic step.

[0326] 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3- 2 Preparation of [H]-2,6-piperidinedione [ka]

[0327] A 20 L jacketed reactor was charged with 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione (761.6 g, 72.5% w / w titer, 1.559 mol). Under a nitrogen atmosphere, anhydrous acetonitrile (4356 g, 10 v / w) was added via cannula, followed by triethylamine (3842 g, 37.4 mol, 24 equiv.), and then chlorotrimethylsilane (1420 g, 12.47 mol, 8 equiv.) was added again via cannula. The resulting slurry was heated to 57 ± 3 °C and maintained at that temperature for 18 hours. A small sample was taken and quenched with deuterium oxide (DO). 1 Analysis by 1 H NMR showed almost complete disappearance of the starting material (2% based on the relative area of ​​the resonance corresponding to the proton of the chiral center).

[0328] The entire reaction mixture was then cooled to 25±5°C. The solid (triethylamine hydrochloride) was removed by filtration and washed with anhydrous acetonitrile (3 L). A 20 L jacketed reactor was washed with deionized water and acetonitrile and dried with a strong nitrogen stream for 20 minutes. DO (950 g, 30 equiv.) was added to a dry 20 L jacketed reactor and cooled to 5–10°C. The filtrate was then added to DO in small portions using a pump to maintain the internal reactor temperature below 45°C (maximum observed temperature was 35°C). The resulting slurry was stirred at 25±5°C for 4 hours, then cooled to -4°C and stirred for 2 days (over the weekend). After warming to 25±5°C, the mixture was concentrated under reduced pressure to approximately 3.5 L, maintaining the temperature below 35°C. Deionized water (3.5 L, 6.4 volumes) was then added to the mixture, and 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3- 2 H-2,6-piperidinedione was precipitated. The solid was filtered and the wet cake was washed with deionized water (1 L x 5). A sample was taken and 1H NMR analysis indicated that the deuteration rate at the chiral centers was approximately 94%. The resulting wet cake was dried under reduced pressure at 25±5°C with a nitrogen sweep for 18 hours to give the product (425 g, titer 99.6% w / w by QNMR, purity 97.6% by HPLC). 1 H NMR (DMSO-d6) δ (ppm): 2.12 - 2.20 (m, 1 H), 2.51 - 2.62 (m, 2H), 2.66 (s, 3H), 2.72 - 2.88 (m, 1H), 5.30 (m, 0.06 H), 7.78 - 7.86 (2 dd, 2 H), 7.93 - 7.99 (t, 1 H), 11.07 (s, 1 H)

[0329] 3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2 Preparation of [H]-2,6-piperidinedione [ka]

[0330] Racemic 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3- 2 [H]-2,6-piperidinedione (193.8 g, 0.611 mol, 1.0 equiv.) was placed in a Parr reactor. N,N-Dimethylacetamide (DMAc, 1.5 L, 7.5 v / w) and wet 10% palladium on carbon (Pd / C; 19.3 g, 18 mmol, 0.03 equiv.) were added. The reaction mixture was heated at 50°C under a hydrogen atmosphere at 50 psi for 1.5 hours until the hydrogen gas flow rate dropped below 1 sccm. The mixture was cooled to room temperature, and the unfiltered mixture was transferred to a container.

[0331] The second batch of racemic 3-(2-methyl-5-nitro-4-oxo-3H-quinazolin-3-yl)-[3- 2 H]-2,6-piperidinedione (196.7 g, 0.611 mol, 1.0 equiv) was treated similarly and the resulting unfiltered mixture was combined with the material from the first batch.

[0332] After filtering through a Celite pad, the filtrate was placed in a 20 L reactor. Deionized water (600 mL) was added and the resulting mixture was heated to 40° C. 3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2 Seed crystals (3.0 g) of [H]-2,6-piperidinedione were added to the reactor, followed by deionized water (3.2 L total). The mixture was cooled to 20°C. The resulting solid was collected by filtration. The solid was washed with a DMAc:HO mixture (1:1 v / v; 1000 mL) and then with deionized water (3 x 800 mL). The resulting wet cake was dried at 25 ± 5°C under reduced pressure with a nitrogen sweep for 18 hours to give the product (272 g, 75% yield). QNMR analysis indicated the titer of the solid was 98% w / w, with a yield of 75%. 1 H NMR (DMSO-d6) δ (ppm): 2.10 - 2.23 (m, 1 H), 2.47-2.53 (m, 5 H), 2.76 - 2.86 (m, 1 H), 5.25-5.38 (dd, 0.05 H), 6.53 - 6.59 (ddd, 2 H), 7.01 (br s, 2H), 7.32 - 7.37 (t, 1 H), 10.97 (br s, 1 H)

[0333] (S)-3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2 Preparation of [H]-2,6-piperidinedione [ka]

[0334] Racemic 3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2 [H]-2,6-piperidinedione (287.1 g, 1.0 mol) and D-dibutyltin diacetate (D-DBTA; 895.8 g) were placed in a 20 L jacketed reactor. Acetonitrile (18.8 L, 65 volumes) was added and stirred at 25 °C for 15 minutes. (S)-3-(2-methyl-5-amino-4-oxo-3H-quinazolin-3-yl)-[3- 2Seed crystals (2.36 g) of the D-DBTA salt of [H]-2,6-piperidinedione were added to the mixture, which was then heated to 55°C over 45 minutes and maintained at 55°C for an additional 30 minutes. The reaction mixture was then cooled stepwise (20 steps of 20 minutes each) to 20°C over approximately 6 hours according to a secondary cooling curve and stirred at 20°C overnight. A sample of the resulting solid was taken, and the chiral purity was determined by chiral HPLC, which indicated that the chiral ratio of the solid was approximately 96:4 (S:R). The solid was collected by filtration and washed with three portions of a 25 mg / mL D-DBTA solution in acetonitrile (3.5 L, 12 volumes). The chiral purity of the wet cake was 98.6% (chiral HPLC).

[0335] The wet cake was placed in a container and slurried with a portion of 2-methyltetrahydrofuran (MeTHF, total volume 5.8 L, 20 volumes), which was then placed in a 20 L jacketed reactor. The remaining MeTHF was added to the reactor, followed by 1.86 L (6.5 volumes) of 8% aqueous sodium bicarbonate solution. The mixture was stirred for 5 minutes and allowed to settle for 5 minutes. The aqueous layer was separated and extracted twice with additional MeTHF (1.8 L, 6.5 volumes). The organic layer was combined with the MeTHF extract and washed twice with 4% sodium bicarbonate solution (435 mL, 1.5 volumes) and deionized water (580 mL, 2 volumes). The organic phase was then concentrated to approximately 900 mL (3 volumes) by vacuum distillation, maintaining the temperature below 35°C (maximum observed temperature 25°C). MeTHF (600 mL, 2 volumes) was added to the mixture, and the solvent was removed by distillation. The resulting solid (160.6 g) was collected by filtration. The filtrate (~375 mL) was extracted with MeTHF (375 mL, 2 x 375 mL) and concentrated under reduced pressure to give an additional solid material (1.6 g). The two solids were combined, and MeTHF (300 mL) was added. The resulting slurry was placed in a 20 L jacketed reactor, and isopropanol (IPA, 4.350 L, 15 vol) was added to the reactor using a pump over 30 minutes. The slurry was held at 4 °C overnight. The batch was then concentrated under reduced pressure to ~2.5 L (8.5 vol), maintaining a temperature below 35 °C. The resulting mixture was stirred at 20 °C for 1 hour. The solid was collected by filtration and washed with IPA (290 mL, 1 vol x 2). The resulting wet cake was dried at 25 ± 5 °C under reduced pressure with a nitrogen sweep for 18 hours to give the title compound as a crystalline off-white solid (105 g). 1 H NMR (pyridine-d5) δ (ppm): 2.20 (m, 1 H), 2.67 (s, 3 H), 2.91 (m, 2 H), 3.08 (m, 1 H), 5.35 (dd, 0.06 H), 6.79 (d, 1 H), 7.02 (d, 1 H), 7.43 (t, 1 H), 7.66 (br s, 2 H), 13.12 (s, 1 H). Purity: 99.8% (HPLC). Chiral purity: 98.4% (chiral HPLC). Deuterium content at C3: 94.0% ( 1H NMR). Water content: 1.2% (Karl Fischer). The resulting crystalline material was shown by XRPD to be a mixture of anhydrous Form I and monohydrate Form II, as shown in Example 3 below.

[0336] Example 2: (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Preparation and characterization of crystalline forms IX of the free base of [H]-2,6-piperidinedione

[0337] Crystalline Form I is (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 A glassy form of the free base of [H]-2,6-piperidinedione (obtained by separating a racemic mixture using chiral supercritical fluid chromatography as described by Jacques et al., Proc Natl Acad Sci USA 2015, 112, E1471-E1479) was obtained by stirring and sonicating in isopropanol until a white slurry was obtained. The resulting white solid (anhydrous Form I) was filtered and dried under reduced pressure.

[0338] Form II was prepared as follows: SP-3164 (prepared as described in Example 1 and obtained during isolation of the free base by extraction, (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2A solution of 596 g of [H]-2,6-piperidinedione free base in MeTHF (8.7 g) was concentrated under reduced pressure to 50 g. MeTHF (140 mL) was added, and the mixture was further concentrated to approximately 25 g. Isopropanol (50 mL) was then added, and the heterogeneous mixture was sonicated for approximately 2 minutes to form a white slurry. The solvent was evaporated under reduced pressure to a weight of approximately 25 g. Fresh isopropanol (50 mL) was added, and the mixture was allowed to settle for approximately 5 minutes. The solid was filtered through a fritted funnel and washed with 15 mL of IPA. The filter cake was dried to constant weight under a nitrogen atmosphere for 1 hour. The resulting off-white solid (6.5 g) was crushed with a mortar and pestle at room temperature and above 50% relative humidity (RH). Single crystal X-ray diffraction analysis indicated the product to be monohydrate Form II.

[0339] Form III was prepared by precipitation of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 The free base of [H]-2,6-piperidinedione (200 mg, prepared as described in Example 1) was obtained by dissolving in MeTHF (4 mL). Isopropanol (2 mL) was added while the temperature was raised to 60° C. The mixture was left at that temperature for 16 hours (overnight). It was then cooled to 20° C. and heptane (5 mL) was added. The formed crystalline material (Form III) was filtered and dried under reduced pressure under nitrogen (100 mg, white powder).

[0340] To prepare single crystals of solid crystalline Forms I-IX, (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Approximately 30 mg of the free base of [H]-2,6-piperidinedione (Form I, prepared as described above in this Example) was dissolved in a minimum amount of each of the solvents listed below (Table 10) with heating at 80° C. The resulting solution was cooled to room temperature and the solvent was slowly evaporated until a crystalline solid was formed.

[0341] [Table 10]

[0342] (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 When anhydrous crystalline Form I of the free base of [H]-2,6-piperidinedione was slurried in ethyl acetate at 40° C. for approximately 3 hours, anhydrous crystalline Form X was formed.

[0343] For each of Forms I-IX, single crystals were analyzed by X-ray diffraction to determine the crystal structure and unit cell. Calculated XRPD data (generated from single crystal X-ray data for Forms I-IX and from powders for Forms I and X) are shown in Figures 1-10, and 2θ angles are listed in Tables 11-20 (Forms I-X). X-ray crystal structures (ORTEP diagrams) are shown in Figures 11-19, and unit cell parameters are listed in Tables 21-29.

[0344] [Table 11-1] [Table 11-2]

[0345] [Table 12-1] [Table 12-2]

[0346] [Table 13-1] [Table 13-2]

[0347] [Table 14-1] [Table 14-2]

[0348] Table 15-1 Table 15-2

[0349] Table 16-1 Table 16-2

[0350] Table 17-1 Table 17-2 Table 17-3

[0351] Table 18-1 Table 18-2

[0352] Table 19-1 Table 19-2

[0353] Table 20-1 Table 20-2

[0354] Table 21

[0355] Table 22

[0356] Table 23

[0357] Table 24

[0358] Table 25

[0359] Table 26

[0360] Table 27

[0361] Table 28

[0362] Table 29

[0363] Additional DSC, TGA, and dynamic vapor sorption (DVS) data were obtained for Forms I and X and are shown in Figures 20-23. The TGA data for Form I showed no weight loss between room temperature and 150 °C (Figure 20). The DSC data (Figure 20) showed two endothermic peaks at 243.19 °C (onset temperature 238.03 °C) and 273.90 °C (onset temperature 271.55 °C). The DVS data for Form I (Figure 21) showed water adsorption at approximately 45% relative humidity, after which it plateaued. The discrepancy between the desorption and adsorption curves suggested some hysteresis, suggesting that the solid retained moisture. XRPD of the solid after DVS suggested that the resulting material may be a mixture of Form I and Form II (anhydrate and monohydrate). The TGA of the solid after DVS showed a weight loss of 1.69% below 100 °C. TGA data for Form X showed no weight loss between room temperature and 150°C (Figure 22). DSC data showed two endothermic peaks at 242.35°C (onset peak 235.84°C) and 282.71°C (onset peak 281.87°C) (Figure 22). DVS data analysis showed no significant hygroscopicity and very limited hysteresis was observed (Figure 23). XRPD data for material recovered after one cycle of the DVS experiment was substantially similar to the data before the experiment, indicating that the material was stable and remained Form X.

[0364] Example 3: (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Characterization of the crystalline free base of [H]-2,6-piperidinedione

[0365] Characterization by powder X-ray diffraction

[0366] The XRPD trace of the crystalline product of Example 1 is shown in Figure 24. It is characterized by peaks at 2θ angles of 7.25, 10.35, 11.08, 12.02, 13.56, 13.77, 14.13, 14.54, 15.47, 15.8, 17.47, 19.83, 20.72, 21.25, 21.90, 23.33, 24.22, 25.77, 26.79, 28.33, 29.23, 30.45, and 33.10. It is a mixture of crystalline Form I and Form II (see Example 3).

[0367] Characterization by differential scanning calorimetry

[0368] The differential scanning calorimetry (DSC) curve for the crystalline material of Example 1 is shown in Figure 25. The DSC curve exhibited an endothermic response with an onset and peak at about 241°C and about 243°C, followed by an exothermic response with an onset and peak at about 245°C and about 246°C, and a second endothermic response with an onset and peak at about 253°C and about 258°C, respectively.

[0369] Characterization by thermogravimetric analysis

[0370] The thermogravimetric analysis (TGA) results for the crystalline material of Example 1 are shown in FIG.

[0371] TGA data showed a mass loss of 1.2% between 60 and 140°C, with thermal decomposition occurring at temperatures above 210°C.

[0372] Example 4: (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Solubility of the crystalline free base of H]-2,6-piperidinedione

[0373] The compound ((S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 H]-2,6-piperidinedione (anhydrous crystalline form I), (RS)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2[H]-2,6-piperidinedione, or (RS)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione, was suspended in a selected solvent (water, methanol, ethanol, 2-propanol, tetrahydrofuran, acetonitrile, acetone, 2-methyltetrahydrofuran) or solvent mixture (2-methyltetrahydrofuran saturated with water; water saturated with 2-methyltetrahydrofuran) in an HPLC vial. The sample was stirred overnight (approximately 14 hours) at room temperature (approximately 20 to 25 °C). The solution was then separated from the solid by centrifuging the mixture in a centrifuge vial equipped with a filter. The resulting clear solution was quantitatively diluted with methanol (MeOH), and the concentration of the solute was measured using chiral HPLC (Table 30).

[0374] [Table 30]

[0375] Crystalline (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 Solubility data in various solvents for crystalline (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3-H]-2,6-piperidinedione (Form I) and the corresponding deuterated and protonated racemates are shown in Table 31. 2 H]-2,6-piperidinedione (Form I) was observed to have increased solubility compared to the protonated and deuterated racemates.

[0376] [Table 31]

[0377] (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2The solubilities of crystalline forms I, II, III, and X of the free base of [H]-2,6-piperidinedione were compared (water, 20°C). As shown in Table 32, (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 The solubility of the free base of [H]-2,6-piperidinedione is largely independent of crystalline form.

[0378] [Table 32]

[0379] Example 5: Pharmacokinetic (PK) study

[0380] The purpose of the pharmacokinetic (PK) study was to evaluate the efficacy and safety of (S)-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-[3- 2 The objective of this study was to evaluate and compare the PK profiles of [H]-2,6-piperidinedione (formula I, deuterated (S)-enantiomer, dS) and RS-3-(5-amino-2-methyl-4-oxo-3H-quinazolin-3-yl)-2,6-piperidinedione (protonated racemate, h-rac).

[0381] Mouse PK

[0382] CB.17 severe combined immunodeficiency (SCID) female mice (8–12 weeks old) were administered a single oral gavage dose of either the protonated racemate (h-rac, 30 mg / kg) or the deuterated (S)-enantiomer (dS, 15 mg / kg; approximately 10% protonated enantiomer). Both compounds were prepared in 0.5% w / v aqueous hydroxypropyl methylcellulose at concentrations of 3 mg / mL for h-rac and 1.5 mg / mL for dS, respectively. Plasma samples were collected from three mice per group at 0.25, 0.5, 1, 2, 4, 8, and 24 hours post-dose. Plasma samples were prepared by MTBE liquid-liquid extraction using ondansetron as an internal standard (ISTD) and subjected to quantitative analysis. MTBE was evaporated under a stream of nitrogen, and the residue was reconstituted in a 1% v / v solution of water and acetonitrile (20:80 v / v) in acetic acid. The analysis was performed by chiral liquid chromatography coupled with tandem mass spectrometry (LC / MS-MS) on a Daicel ChiralPakIE-3 column using an isocratic LC method (eluent: a 20:80 (v / v) mixture of water and acetonitrile containing 0.1% (v / v) acetic acid). ISTD-normalized peak areas of the deuterated enantiomers were corrected for interference from natural isotopes of the protonated analytes. Concentrations were obtained by interpolation from a standard curve constructed in mouse plasma using a standard solution of the analyte. Data were plotted in Excel 2013 (Microsoft Corp, Redmond, WA) and analyzed within Excel using the PKSolver add-in (version 2.0, described in Zhang Y. et al., Comput. Methods Programs Biomed. 99 (2010), 306-314) to determine exposure (area under the curve, AUC) and elimination half-life (t 1 / 2 ) were determined. The PK profile is shown in Figure 27 and selected PK parameters are shown in Table 34.

[0383] [Table 34]

[0384] After administration of the protonated racemate, exposure to the hS and hR enantiomers was stereoselective, with hS accounting for approximately 39% of total exposure. Following dS administration, exposure to the protonated enantiomers hS and hR accounted for approximately 14% of total exposure, closely matching the amount of protonated compound in the administered substance. PK parameters following dS administration showed little to no deuterium / hydrogen (D / H) exchange, with exposure to the administered enantiomer (h-S + dS) accounting for approximately 96% of total exposure. Finally, exposure to the administered enantiomer following dS administration was approximately twice that of the same enantiomer following administration of twice the dose of h-rac, indicating a higher bioavailability of dS than h-rac.

[0385] Rat PK

[0386] Male Sprague-Dawley (SD) rats (6-8 weeks old) were fasted overnight and administered a single oral gavage dose of either the protonated racemate (h-rac, 300 mg / kg) or the deuterated (S)-enantiomer (dS, 150 mg / kg) in 0.5% carboxymethylcellulose and 0.25% polysorbate 80 solution. Plasma samples were collected from three rats per group at 0.0833, 0.25, 0.5, 1, 2, 4, 8, and 24 hours post-dose. Samples suitable for quantitative analysis by LC / MS-MS were prepared by protein precipitation using warfarin as an internal standard (ISTD). LC / MS-MS sample analysis was performed by isocratically eluting 1 μL samples on a Daicel ChiralPak IE-3 column (4.6 × 150 mm, 3 μm) using an 80:20 mixture of water and acetonitrile containing 0.1% (v / v) formic acid at 0.7 mL / min, followed by MS-MS detection. ISTD-normalized peak areas of the deuterated enantiomers were corrected for interference from the natural isotopes of the corresponding protonated analytes (if present in the same sample). Concentrations of the deuterated and protonated enantiomers were obtained by interpolation from a standard curve constructed in rat plasma using a standard solution of the analyte. Data were plotted in Excel version 2208 (Microsoft Corp, Redmond, WA) and analyzed by non-compartmental methods using Phoenix WinNonlin version 8.3 (Certara LP, Princeton, NJ, USA) to calculate exposure (area under the curve, AUC) and elimination half-life (t 1 / 2 ) were determined. The PK profile is shown in Figure 28 and selected PK parameters are shown in Table 35.

[0387] [Table 35]

[0388] Similar to mice, exposure to the hS and hR enantiomers after h-rac administration was stereoselective, with hS accounting for approximately 41% of total exposure. Exposure to the protonated enantiomers hS and hR after dS administration accounted for approximately 14% of total exposure, closely matching the amount of protonated compound in the administered substance. PK parameters after dS administration showed little to no D / H exchange, with exposure to the administered enantiomer (h-S + dS) accounting for approximately 95% of total exposure. Finally, exposure to the administered enantiomer after dS administration was approximately 4.8-fold higher than exposure to the same enantiomer after administration of twice the dose of h-rac, indicating a higher bioavailability of dS than h-rac.

[0389] Monkey's penalty kick

[0390] Cynomolgus monkeys (2.5-6 years old, 3 males and 3 females) fasted overnight were administered a single oral gavage dose of the protonated racemate (h-rac, 1.5 mg / kg) followed by the deuterated (S)-enantiomer (dS, 0.25 and 0.75 mg / kg). Both h-rac and dS were prepared in 0.5% carboxymethylcellulose and 0.25% polysorbate 80 aqueous solution. Each dose of dS was administered after a 7-day washout period. Plasma samples were serially collected from all animals before and after each dose at 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Samples suitable for quantitative analysis by LC / MS-MS were prepared by protein precipitation using warfarin as the ISTD. LC / MS-MS sample analysis was performed by isocratically eluting 5 μL samples on a Daicel ChiralPak IE-3 column (4.6 × 150 mm, 3 μm) using an 80:20 mixture of water and acetonitrile containing 0.1% (v / v) formic acid at 0.7 mL / min, followed by MS-MS detection. ISTD-normalized peak areas of the deuterated enantiomers were corrected for interference from the natural isotopes of the corresponding protonated analytes, if present in the same sample. Concentrations of the deuterated and protonated enantiomers were obtained by interpolation from a standard curve constructed in monkey plasma using a standard solution of the analyte. Data were plotted in Excel version 2208 (Microsoft Corp, Redmond, WA) and analyzed by non-compartmental methods using Phoenix WinNonlin version 8.3 (Certara LP, Princeton, NJ, USA) to calculate exposure (area under the curve, AUC) and elimination half-life (t 1 / 2 PK parameters were determined, including the PK profile shown in Figure 29 and selected PK parameters shown in Table 36.

[0391] [Table 36]

[0392] Similar to mice and rats, exposure to the h-rac enantiomers hS and hR is stereoselective, with hS accounting for approximately 40% of total exposure. Exposure to the protonated enantiomers hS and hR following dS administration accounts for approximately 10–14% of total exposure, closely resembling the amount of protonated compound in the administered substance. PK parameters following dS administration show little or no D / H exchange, with exposure to the administered enantiomer (h-S + dS) accounting for approximately 95–100% of total exposure. Exposure to the administered enantiomer following dS administration is similar to exposure to the same enantiomer following a double dose of h-rac (2573 h.ng / mL following dS administration and 2880 h.ng / mL following h-rac administration). Interestingly, the elimination half-lives of dS and hS after dS administration are approximately half of that of hS after h-rac administration, whereas the elimination half-life of hR is similar. max As indicated by the difference in C , the concentrations of dS and hS after dS administration reached their peaks approximately twice as quickly as those of hS after h-rac administration. max ) and the sum of dS and hS after dS administration, C max is the C of hS after h-rac administration max (d-S+hS after dS administration was 474ng / mL, and hS after h-rac administration was 267ng / mL).

[0393] Incorporation by Reference

[0394] This application references various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. In the event of a conflict between any of the incorporated references and this specification, this specification will control. Furthermore, certain embodiments of the present disclosure that fall within the prior art may be expressly excluded from any one or more of the claims. Such embodiments may be deemed known to those of ordinary skill in the art and may therefore be excluded even if not expressly excluded herein. Certain embodiments of the present disclosure may be excluded from any claim for any reason, whether or not related to the existence of prior art.

[0395] equivalent

[0396] The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. Accordingly, the foregoing embodiments are to be considered in all respects as illustrative and not limiting of the invention described herein. The scope of the invention is, therefore, indicated by the appended claims, rather than the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

1. A crystalline form of the compound of formula (I). 【Chemistry 1】

2. 2. The crystalline form of claim 1, wherein said crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 11.0 degrees 2θ.

3. 2. The crystalline form of claim 1, wherein said crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 11.9 degrees 2θ.

4. 2. The crystalline form of claim 1, wherein said crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1 degrees 2θ.

5. 5. The crystalline form of any one of claims 1 to 4, wherein said crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 11.0°, about 11.9°, and about 14.1° 2θ.

6. 6. The crystalline form of any one of claims 2 to 5, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.7°, about 21.1°, about 21.5°, about 23.5°, about 24.0°, and about 24.7° 2θ.

7. 7. The crystalline form of any one of claims 2 to 6, wherein the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.9°, about 29.2°, about 31.1°, about 32.5°, about 33.7°, and about 34.5° 2θ.

8. The crystalline form of any one of claims 2 to 7, wherein about means ±0.3° 2θ.

9. The crystalline form of any one of claims 2 to 7, wherein about means ±0.2 degrees 2θ.

10. 10. The crystalline form of any one of claims 1 to 9, wherein said crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 1.

11. 10. The crystalline form of any one of claims 1 to 9, wherein said crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 3.

12. 10. The crystalline form of any one of claims 1 to 9, wherein said crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 10.

13. 10. The crystalline form of any one of claims 1 to 9, wherein said crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 2.

14. 13. The crystalline form of any one of claims 1 to 12, wherein said crystalline form of the compound of formula (I) is an anhydrous crystalline form.

15. 14. The crystalline form of any one of claims 1 to 9 and 13, wherein said crystalline form of the compound of formula (I) is a crystalline hydrate.

16. An anhydrous crystalline form of the compound of formula (I). 【Chemistry 2】

17. 17. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.9 degrees 2θ.

18. 17. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9 degrees 2θ.

19. 17. The anhydrous crystalline form of claim 16, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1 degrees 2θ.

20. 20. The anhydrous crystalline form of any one of claims 16 to 19, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern comprising peaks at about 10.9°, about 11.9°, and about 14.1° 2θ.

21. 21. The anhydrous crystalline form of any one of claims 17-20, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 18.7°, about 19.7°, about 21.2°, about 21.6°, about 23.3°, about 24.1°, and about 24.6° 2θ.

22. 22. The anhydrous crystalline form of any one of claims 17-21, wherein the XRPD pattern further comprises one or more peaks selected from about 26.4°, about 27.1°, about 28.8°, about 29.2°, about 30.6°, about 31.1°, about 32.4°, about 33.0°, about 33.8°, and about 34.7° 2θ.

23. 23. The anhydrous crystalline form of any one of claims 17 to 22, wherein about means ±0.3 degrees 2θ.

24. 23. The anhydrous crystalline form of any one of claims 17 to 22, wherein about means ±0.2 degrees 2θ.

25. 25. The anhydrous crystalline form of any one of claims 16 to 24, wherein said anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 1.

26. 25. The anhydrous crystalline form of any one of claims 16 to 24, wherein said anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 3.

27. 25. The anhydrous crystalline form of any one of claims 16 to 24, wherein the anhydrous crystalline form of the compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 10.

28. Form I of the compound of formula (I). 【Transformation 3】

29. 29. Form I of the compound of formula (I) according to claim 28, wherein said Form I of the compound of formula (I) is an anhydrous crystalline form.

30. 30. Form I of the compound of formula (I) according to claim 28 or claim 29, wherein said Form I of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.3° 2θ.

31. 30. Form I of compound of formula (I) according to claim 28 or claim 29, wherein said Form I of compound of formula (I) has an XRPD pattern comprising a peak at about 11.0° 2θ.

32. 30. Form I of the compound of formula (I) according to claim 28 or claim 29, wherein said Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 11.9° 2θ.

33. 30. Form I of the compound of formula (I) according to claim 28 or claim 29, wherein said Form I of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.7° 2θ.

34. 30. Form I of compound of formula (I) according to claim 28 or claim 29, wherein said Form I of compound of formula (I) has an XRPD pattern comprising a peak at about 14.0° 2θ.

35. 30. Form I of compound of formula (I) according to claim 28 or claim 29, wherein said Form I of compound of formula (I) has an XRPD pattern comprising a peak at about 14.8° 2θ.

36. 36. The compound of claim 28, wherein said Form I of compound of formula (I) has an XRPD pattern comprising one or more peaks selected from about 10.3°, about 11.0°, about 11.9°, about 13.7°, about 14.0°, and about 14.8° 2θ.

37. 37. Form I of compound of formula (I) according to any one of claims 29 to 36, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 17.4°, about 20.6°, about 21.1°, about 23.2°, and about 24.1° 2θ.

38. 38. Form I of compound of formula (I) according to any one of claims 29 to 37, wherein the XRPD pattern further comprises one or more peaks selected from about 17.6°, about 18.7°, about 19.7°, about 21.6°, about 23.0°, about 23.7°, and about 24.6° 2θ.

39. 39. Form I of compound of formula (I) according to any one of claims 29 to 38, wherein the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.8°, about 28.2°, about 30.3°, about 30.5°, and about 33.0° 2θ.

40. 40. Form I of compound of formula (I) according to any one of claims 29 to 39, wherein the XRPD pattern further comprises one or more peaks selected from about 25.6°, about 27.1°, about 28.9°, about 29.2°, about 30.9°, about 31.1°, about 32.1°, about 32.4°, about 33.8°, about 34.0°, about 34.5°, and about 34.7° 2θ.

41. Form I of the compound of formula (I) according to any one of claims 30 to 40, wherein about means ±0.3° 2θ.

42. Form I of the compound of formula (I) according to any one of claims 30 to 40, wherein about means ±0.2° 2θ.

43. 43. Form I of compound of formula (I) according to any one of claims 28 to 42, wherein said Form I of compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 1A.

44. 44. Form I of compound of formula (I) according to any one of claims 28 to 43, wherein said Form I of compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising one or more endotherms with peak onset temperatures at about 238°C and about 273.9°C.

45. 45. Form I of compound of formula (I) according to any one of claims 28 to 44, wherein said Form I of compound of formula (I) has a DSC thermogram substantially identical to that shown in Figure 20.

46. 46. ​​The compound of formula (I) according to any one of claims 28 to 45, wherein said compound of formula (I) Form I exhibits a mass change of about 3% by weight or less when the relative humidity is varied between 0% and about 80%.

47. 47. Form I of compound of formula (I) according to any one of claims 28 to 46, wherein said Form I of compound of formula (I) has a moisture sorption isotherm substantially identical to that shown in Figure 21.

48. Form III of the compound of formula (I). 【Chemistry 4】

49. 49. Form III of the compound of formula (I) according to claim 48, wherein said Form III of the compound of formula (I) is an anhydrous crystalline form.

50. 50. Form III of the compound of formula (I) according to claim 48 or claim 49, wherein said Form III of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.7° 2θ.

51. 50. Form III of the compound of formula (I) according to claim 48 or claim 49, wherein said Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9 degrees 2θ.

52. 50. Form III of compound of formula (I) according to claim 48 or claim 49, wherein said Form III of compound of formula (I) has an XRPD pattern comprising a peak at about 11.9°2θ.

53. 50. Form III of the compound of formula (I) according to claim 48 or claim 49, wherein said Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 12.2 degrees 2θ.

54. 50. Form III of the compound of formula (I) according to claim 48 or claim 49, wherein said Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 13.3° 2θ.

55. 50. Form III of the compound of formula (I) according to claim 48 or claim 49, wherein said Form III of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.3° 2θ.

56. 56. Form III of compound of formula (I) according to any one of claims 48 to 55, wherein said Form III of compound of formula (I) has an XRPD pattern comprising peaks at about 10.7°, about 10.9°, about 11.9°, about 12.2°, about 13.3°, and about 14.3° 2θ.

57. 57. Form III of compound of formula (I) according to any one of claims 50 to 56, wherein the XRPD pattern further comprises one or more peaks selected from about 15.1°, about 19.0°, about 19.3°, about 21.8°, and about 24.9° 2θ.

58. 58. Form III of compound of formula (I) according to any one of claims 50-57, wherein the XRPD pattern further comprises one or more peaks selected from about 16.0°, about 16.2°, about 16.8°, about 18.7°, about 19.9°, about 20.2°, about 21.2°, about 21.5°, about 22.7°, about 23.5°, about 24.0°, about 24.5°, and about 24.7° 2θ.

59. 59. Form III of compound of formula (I) according to any one of claims 50-58, wherein the XRPD pattern further comprises one or more peaks selected from about 26.1°, about 26.4°, about 26.7°, about 26.9°, about 29.1°, about 32.3°, about 32.5°, about 33.1°, and about 34.1°2θ.

60. 59. Form III of compound of formula (I) according to any one of claims 50-58, wherein the XRPD pattern further comprises one or more peaks selected from about 27.7°, about 28.3°, about 28.6°, about 28.8°, about 29.6°, about 30.3°, about 30.6°, about 31.0°, about 31.4°, about 32.8°, about 33.6°, about 33.8°, about 34.3°, and about 34.5° 2θ.

61. Form III of the compound of formula (I) according to any one of claims 50 to 60, wherein about means ±0.3° 2θ.

62. Form III of the compound of formula (I) according to any one of claims 50 to 60, wherein about means ±0.2° 2θ.

63. 63. Form III of compound of formula (I) according to any one of claims 48 to 62, wherein said Form III of compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 3.

64. Form X of the compound of formula (I). 【Transformation 5】

65. 65. Form X of the compound of formula (I) according to claim 64, wherein said Form X of the compound of formula (I) is an anhydrous crystalline form.

66. 66. Form X of the compound of formula (I) according to claim 64 or claim 65, wherein said Form X of the compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 10.6 degrees 2θ.

67. 66. Form X of the compound of formula (I) according to claim 64 or claim 65, wherein said Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 10.9 degrees 2θ.

68. 66. Form X of compound of formula (I) according to claim 64 or claim 65, wherein said Form X of compound of formula (I) has an XRPD pattern comprising a peak at about 12.0 degrees 2θ.

69. 66. Form X of the compound of formula (I) according to claim 64 or claim 65, wherein said Form X of the compound of formula (I) has an XRPD pattern comprising a peak at about 14.1 degrees 2θ.

70. 66. Form X of compound of formula (I) according to claim 64 or claim 65, wherein said Form X of compound of formula (I) has an XRPD pattern comprising a peak at about 14.5° 2θ.

71. 71. Form X of compound of formula (I) according to any one of claims 64-70, wherein said Form X of compound of formula (I) has an XRPD pattern comprising peaks at about 10.6°, about 10.9°, about 12.0°, about 14.1°, and about 14.5° 2θ.

72. 72. Form X of compound of formula (I) according to any one of claims 66-71, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 19.1°, about 21.9°, and about 24.1° 2θ.

73. 73. Form X of compound of formula (I) according to any one of claims 66-72, wherein the XRPD pattern further comprises one or more peaks selected from about 17.5°, about 18.0°, about 18.8°, about 19.7°, about 20.7°, about 21.2°, about 21.6°, about 22.3°, about 23.3°, and about 24.6° 2θ.

74. 74. Form X of compound of formula (I) according to any one of claims 66-73, wherein the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 27.3°, about 29.0°, about 29.2°, about 30.8°, and about 31.1° 2θ.

75. 75. Form X of compound of formula (I) according to any one of claims 66-74, wherein the XRPD pattern further comprises one or more peaks selected from about 25.8°, about 26.4°, about 28.7°, about 30.6°, about 32.4°, about 33.0°, about 33.5°, about 33.9°, and about 34.7° 2θ.

76. Form X of the compound of formula (I) according to any one of claims 66 to 75, wherein about means ±0.3° 2θ.

77. Form X of the compound of formula (I) according to any one of claims 66 to 75, wherein about means ±0.2 degrees 2θ.

78. 78. Form X of compound of formula (I) according to any one of claims 64 to 77, wherein said Form X of compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 10.

79. 79. Form X of compound of formula (I) according to any one of claims 64-78, wherein said Form X of compound of formula (I) has a differential scanning calorimetry (DSC) thermogram comprising one or more endotherms with peak onset temperatures at about 235.8°C and about 281.9°C.

80. 80. Form X of compound of formula (I) according to any one of claims 64 to 79, wherein said Form X of compound of formula (I) has a DSC thermogram substantially identical to that shown in Figure 22.

81. 81. The compound of formula (I) of any one of claims 64 to 80, wherein said compound of formula (I) of form X exhibits a mass change of about 3% by weight or less when the relative humidity is varied between 0% and about 80%.

82. 82. Form X of compound of formula (I) according to any one of claims 64 to 81, wherein said Form X of compound of formula (I) has a moisture sorption isotherm substantially identical to that shown in Figure 23.

83. A crystalline hydrate of the compound of formula (I). 【Transformation 6】

84. 84. The crystalline hydrate of claim 83, wherein the crystalline hydrate is a crystalline monohydrate.

85. Form II of the compound of formula (I). 【Transformation 7】

86. 86. Form II of the compound of formula (I) according to claim 85, wherein said Form II of the compound of formula (I) is a crystalline hydrate.

87. 87. Form II of the compound of formula (I) according to claim 85 or 86, wherein said Form II of the compound of formula (I) is a crystalline monohydrate.

88. 88. Form II of compound of formula (I) according to any one of claims 85 to 87, wherein said Form II of compound of formula (I) has an X-ray powder diffraction (XRPD) pattern comprising a peak at about 6.9 degrees 2θ.

89. 88. Form II of compound of formula (I) according to any one of claims 85 to 87, wherein said Form II of compound of formula (I) has an XRPD pattern comprising a peak at about 11.2 degrees 2θ.

90. 88. Form II of compound of formula (I) according to any one of claims 85 to 87, wherein said Form II of compound of formula (I) has an XRPD pattern comprising a peak at about 11.7 degrees 2θ.

91. 88. Form II of compound of formula (I) according to any one of claims 85 to 87, wherein said Form II of compound of formula (I) has an XRPD pattern comprising a peak at about 13.9 degrees 2θ.

92. 88. Form II of compound of formula (I) according to any one of claims 85 to 87, wherein said Form II of compound of formula (I) has an XRPD pattern comprising a peak at about 14.3 degrees 2θ.

93. 93. Form II of compound of formula (I) according to any one of claims 85 to 92, wherein said Form II of compound of formula (I) has an XRPD pattern comprising peaks at about 6.9°, about 11.2°, about 11.7°, about 13.9°, and about 14.3° 2θ.

94. 94. Form II of compound of formula (I) according to any one of claims 88-93, wherein the XRPD pattern further comprises one or more peaks selected from about 15.3°, about 15.5°, about 17.4°, about 20.9°, about 22.3°, and about 23.6° 2θ.

95. 95. Form II of compound of formula (I) according to any one of claims 88-94, wherein the XRPD pattern further comprises one or more peaks selected from about 17.9°, about 19.7°, about 21.4°, about 22.8°, about 23.8°, and about 24.9° 2θ.

96. 96. Form II of compound of formula (I) according to any one of claims 88-95, wherein the XRPD pattern further comprises one or more peaks selected from about 25.2°, about 25.5°, about 25.7°, about 26.4°, about 27.0°, about 27.5°, about 28.1°, about 28.2°, and about 28.8° 2θ.

97. 97. Form II of compound of formula (I) according to any one of claims 88-96, wherein the XRPD pattern further comprises one or more peaks selected from about 28.6°, about 29.2°, about 29.9°, about 31.3°, about 31.4°, about 31.9°, about 32.6°, about 33.7°, and about 34.3° 2θ.

98. Form II of the compound of formula (I) according to any one of claims 88 to 97, wherein about means ±0.3° 2θ.

99. Form II of the compound of formula (I) according to any one of claims 88 to 97, wherein about means ±0.2° 2θ.

100. 100. Form II of compound of formula (I) according to any one of claims 85 to 99, wherein said Form II of compound of formula (I) has an XRPD pattern substantially identical to that shown in Figure 2.

101. 1. A pharmaceutical composition comprising: (i) Crystalline forms of the compound of formula (I) 【Transformation 8】 and; (ii) a pharmaceutically acceptable excipient; A pharmaceutical composition comprising:

102. 102. The pharmaceutical composition of claim 101, wherein said crystalline form of compound of formula (I) is a crystalline form of compound of formula (I) according to any one of claims 1 to 15.

103. 1. A pharmaceutical composition comprising: (i) Anhydrous crystalline form of the compound of formula (I) 【Chemistry 9】 and; (ii) a pharmaceutically acceptable excipient; A pharmaceutical composition comprising:

104. The pharmaceutical composition of claim 103, wherein said anhydrous crystalline form of the compound of formula (I) is an anhydrous crystalline form of the compound of formula (I) according to any one of claims 16 to 27.

105. 1. A pharmaceutical composition comprising: (i) Crystalline hydrate of the compound of formula (I) 【Chemistry 10】 and; (ii) a pharmaceutically acceptable excipient; A pharmaceutical composition comprising:

106. 106. The pharmaceutical composition of claim 105, wherein said crystalline hydrate of a compound of formula (I) is a crystalline hydrate of a compound of formula (I) as defined in claim 83 or 84.

107. 1. A pharmaceutical composition comprising: (i) Form I of the compound of formula (I) according to any one of claims 28 to 47, Form II of the compound of formula (I) according to any one of claims 85 to 100, Form III of the compound of formula (I) according to any one of claims 48 to 63, or Form X of the compound of formula (I) according to any one of claims 64 to 82. 【Chemistry 11】 ; and (ii) a pharmaceutically acceptable excipient; A pharmaceutical composition comprising:

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