Salts and crystalline forms of the positive allosteric modulator of GABAA

Abstract

To provide pharmaceutical compositions for treating a disease or condition selected from among epilepsy, bipolar disorder, and anxiety.SOLUTION: A pharmaceutical composition comprises: (i) a crystal of a citrate salt of a compound represented by the formula in the figure, e.g., a crystal of a citrate salt of a compound exhibiting an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.7±0.2, 12.5±0.2 and 13.0±0.2 degrees (2θ); and a pharmaceutically acceptable carrier.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Application No. 16 / 517,369 filed on 19 July 2019 and U.S. Provisional Application No. 62 / 725,805 filed on 31 August 2018, both of which are incorporated herein by reference in their entirety.

[0002] This disclosure relates to salts of 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnane-20-one, their crystalline forms, and methods for preparing such salts and crystalline forms. [Background technology]

[0003] 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnane-20-one (compound 1) is a synthetic neuroactive steroid. Its primary molecular target is γ-aminobutyric acid type A (GABA). A It is a receptor and functions as a positive allosteric modulator (PAM) for channel function. The structural formula of compound 1 is shown below. TIFF0007911419000001.tif41170

[0004] Neuroactive steroid GABA A PAM has demonstrated clinical efficacy in epilepsy, postpartum depression, and major depression.

[0005] A salt of compound 1 that can be isolated and is stable, and a process for producing it, are needed. [Overview of the project]

[0006] This disclosure provides salts of compound 1 and methods for preparing such salts. In some embodiments, the salts of compound 1 are crystalline. This disclosure also provides pharmaceutical compositions comprising salts of compound 1.

[0007] In some embodiments, the present disclosure provides hydrobromide, citrate, malate, maleate, mesylate, phosphate, tartrate, hydrochloride, tosylate, glucuronate, ethanesulfonate, fumarate, sulfate, naphthalene-2-sulfonate, ascorbate, oxalate, naphthalene-1,5-disulfonate, malonic acid, aminosalicylic acid, benzenesulfonic acid, isethionic acid, gentisic acid, 1-hydroxy-2-naphthoate, dichloroacetate, cyclamate, and ethane-1,2-disulfonate of Compound 1.

[0008] In some embodiments, the present disclosure provides crystalline forms of hydrobromide, citrate, malate, maleate, mesylate, phosphate, tartrate, hydrochloride, tosylate, glucuronate, ethanesulfonate, fumarate, sulfate, naphthalene-2-sulfonate, ascorbate, oxalate, naphthalene-1,5-disulfonate, malonic acid, aminosalicylic acid, benzenesulfonic acid, isethionic acid, gentisic acid, 1-hydroxy-2-naphthoate, dichloroacetate, cyclamate, and ethane-1,2-disulfonate of Compound 1.

[0009] In some embodiments, the present disclosure provides hydrobromide of Compound 1. In some embodiments, the present disclosure provides a crystalline form of hydrobromide of Compound 1 (the "Compound 1 HBr salt"). In one embodiment, the present disclosure provides the Compound 1 HBr salt (Form A). In one embodiment, the present disclosure provides the Compound 1 HBr salt (Form B). In one embodiment, the present disclosure provides the Compound 1 HBr salt (Form C). In one embodiment, the present disclosure providesthe Compound 1 HBr salt (Form D). In one embodiment, the present disclosure provides the Compound 1 HBr salt (Form E).

[0010] In some embodiments, the present disclosure provides the citrate salt of Compound 1. In some embodiments, the present disclosure provides a crystalline form of the citrate salt of Compound 1 (the "Compound 1 citrate salt"). In one embodiment, the present disclosure provides the Compound 1 citrate salt (Form A). In one embodiment, the present disclosure provides the Compound 1 citrate salt (Form B). In one embodiment, the present disclosure provides the Compound 1 citrate salt (Form C).

[0011] The present disclosure also provides a method of treating a disease, disorder, or condition, comprising administering a therapeutically effective amount of a salt of Compound 1. The present disclosure provides a method of administering a salt of Compound 1. In some embodiments, the salt of Compound 1 is administered orally. In some embodiments, the disease, disorder, or condition is selected from epilepsy, postpartum depression, major depressive disorder, bipolar disorder, treatment-resistant depression, and anxiety disorders. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] [Figure 1] FIG. 1 is a diagram showing the X-ray powder diffraction (XRPD) pattern (Pattern A) of the free base of Compound 1. [Figure 2] FIG. 2 is a diagram showing the XRPD pattern of the Compound 1 HBr salt (Form A). [Figure 3] FIG. 3 is a diagram showing the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of the Compound 1 HBr salt (Form A). [Figure 4] FIG. 4 is a diagram showing the dynamic vapor sorption (DVS) isotherm plot of the Compound 1 HBr salt (Form A). [Figure 5] FIG. 5 is a diagram showing the XRPD pattern of the Compound 1 HBr salt (Form B). [Figure 6] FIG. 6 is a diagram showing the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of the Compound 1 HBr salt (Form B). [Figure 7] FIG. 7 is a diagram showing the dynamic vapor sorption (DVS) isotherm plot of the Compound 1 HBr salt (Form B). [Figure 8]Figure 8 shows the XRPD pattern of compound 1HBr salt (form C). [Figure 9] Figure 9 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1HBr salt (form C). [Figure 10] Figure 10 shows the dynamic vapor adsorption (DVS) isotherm plot of compound 1HBr salt (form C). [Figure 11] Figure 11 shows the XRPD pattern of compound 1HBr salt (form D). [Figure 12] Figure 12 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1HBr salt (form D). [Figure 13] Figure 13 shows the XRPD pattern of compound 1HBr salt (form E). [Figure 14] Figure 14 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1HBr salt (form E). [Figure 15] Figure 15 shows the XRPD pattern of compound 1 citrate (form A). [Figure 16] Figure 16 shows the DSC thermogram and TGA thermogram of compound 1 citrate (form A). [Figure 17] Figure 17 shows the DVS isotherm plot of compound 1 citrate (form A). [Figure 18] Figure 18 shows the XRPD pattern of compound 1 citrate (form B). [Figure 19] Figure 19 shows the DSC thermogram and TGA thermogram of compound 1 citrate (form B). [Figure 20] Figure 20 shows the DVS isotherm plot of compound 1 citrate (form B). [Figure 21] Figure 21 shows the XRPD pattern of compound 1 citrate (form C). [Figure 22]Figure 22 shows the XRPD pattern of compound 1 mesylate (form A). [Figure 23] Figure 23 shows the DSC thermogram and TGA thermogram of compound 1 mesylate (form A). [Figure 24] Figure 24 shows the DVS isotherm plot of compound 1 mesylate (form A). [Figure 25A] Figure 25A shows the XRPD pattern of compound 1 mesylate (form B). [Figure 25B] Figure 25B shows the XRPD pattern of compound 1 mesylate (form C). [Figure 26] Figure 26 shows the XRPD pattern of compound 1 mesylate (form D). [Figure 27] Figure 27 shows the XRPD pattern of compound 1 phosphate (form A). [Figure 28] Figure 28 shows the DSC thermogram and TGA thermogram of compound 1 phosphate (form A). [Figure 29] Figure 29 shows the DVS isotherm plot of compound 1 phosphate (form A). [Figure 30] Figure 30 shows the XRPD pattern of compound 1L(+)-tartrate (form A). [Figure 31] Figure 31 shows the DSC thermogram and TGA thermogram of compound 1L(+)-tartrate (form A). [Figure 32] Figure 32 shows the DVS isotherm plot of compound 1L(+)-tartrate (form A). [Figure 33] Figure 33 shows the XRPD pattern of compound 1L(+)-tartrate (form B). [Figure 34] Figure 34 shows the DSC thermogram and TGA thermogram of compound 1L(+)-tartrate (form B). [Figure 35] Figure 35 shows the DVS isotherm plot of compound 1L(+)-tartrate (form B). [Figure 36] Figure 36 shows the XRPD pattern of compound 1 fumarate (form A). [Figure 37] Figure 37 shows the DSC thermogram and TGA thermogram of compound 1 fumarate (form A). [Figure 38] Figure 38 shows the XRPD pattern of compound 1 fumarate (form B). [Figure 39] Figure 39 shows the DSC thermogram and TGA thermogram of compound 1 fumarate (form B). [Figure 40] Figure 40 shows the DVS isotherm plot of compound 1 fumarate (form B). [Figure 41] Figure 41 shows the XRPD pattern of compound 1 fumarate (form C). [Figure 42] Figure 42 shows the XRPD pattern of compound 1 fumarate (form D). [Figure 43] Figure 43 shows the XRPD pattern of compound 1 tosylate (form A). [Figure 44] Figure 44 shows the DSC thermogram and TGA thermogram of compound 1 tosylate (form A). [Figure 45] Figure 45 shows the DVS isotherm plot of compound 1 tosylate (form A). [Figure 46] Figure 46 shows the XRPD pattern of compound 1 tosylate (form B). [Figure 47] Figure 47 shows the XRPD pattern of compound 1 tosylate (form C). [Figure 48] Figure 48 shows the XRPD pattern of compound 1-glucuronide (form A). [Figure 49] Figure 49 shows the DSC thermogram and TGA thermogram of compound 1-glucuronide (form A). [Figure 50] Figure 50 shows the DVS isotherm plot of compound 1-glucuronide (form A). [Figure 51]Figure 51 shows the XRPD pattern of compound 1-glucuronide (form B). [Figure 52] Figure 52 shows the XRPD pattern of compound 1-ethanesulfonate (form A). [Figure 53] Figure 53 shows the DSC thermogram and TGA thermogram of compound 1-ethanesulfonate (form A). [Figure 54] Figure 54 shows the DVS isotherm plot of compound 1-ethanesulfonate (form A). [Figure 55] Figure 55 shows the XRPD pattern of compound 1 sulfate (form A). [Figure 56] Figure 56 shows the DSC thermogram and TGA thermogram of compound 1 sulfate (form A). [Figure 57] Figure 57 shows the DVS isotherm plot of compound 1 sulfate (form A). [Figure 58] Figure 58 shows the XRPD pattern of compound 1 ascorbate (form A). [Figure 59] Figure 59 shows the DSC thermogram and TGA thermogram of compound 1 ascorbate (form A). [Figure 60] Figure 60 shows the DVS isotherm plot of compound 1 ascorbate (form A). [Figure 61] Figure 61 shows the XRPD pattern of compound 1 ascorbate (form B). [Figure 62] Figure 62 shows the XRPD pattern of compound 1 napadisylate (form A). [Figure 63] Figure 63 shows the DSC thermogram and TGA thermogram of compound 1 napadisylate (form A). [Figure 64] Figure 64 shows the DVS isotherm plot of compound 1 napadisylate (form A). [Figure 65] Figure 65 shows the XRPD pattern of compound 1 napadisylate (form B). [Figure 66] Figure 66 shows the XRPD pattern of compound 1 malonate (form A). [Figure 67] Figure 67 shows the DSC thermogram and TGA thermogram of compound 1 malonate (form A). [Figure 68] Figure 68 shows the XRPD pattern of compound 1 besylate (form A). [Figure 69] Figure 69 shows the DSC thermogram and TGA thermogram of compound 1 besylate (form A). [Figure 70] Figure 70 shows the DVS isotherm plot of compound 1 besylate (form A). [Figure 71] Figure 71 shows the XRPD pattern of compound 1 besylate (form B). [Figure 72] Figure 72 shows the XRPD pattern of compound 1 isethionate (form A). [Figure 73] Figure 73 shows the DSC thermogram and TGA thermogram of compound 1-isethionate (form A). [Figure 74] Figure 74 shows the DVS isotherm plot of compound 1 isethionate (form A). [Figure 75] Figure 75 shows the XRPD pattern of compound 1 isethionate (form B). [Figure 76] Figure 76 shows the XRPD pattern of compound 1 gentisinate (form A). [Figure 77] Figure 77 shows the DSC thermogram and TGA thermogram of compound 1 gentisinate (form A). [Figure 78] Figure 78 shows the DVS isotherm plot of compound 1 gentisic acid (form A). [Figure 79] Figure 79 shows the XRPD pattern of compound 1 gentisic acid (form B). [Figure 80] Figure 80 shows the XRPD pattern of compound 1 gentisate (form C). [Figure 81] Figure 81 shows the XRPD pattern of compound 11-hydroxy-2-naphthoate (form A). [Figure 82] Figure 82 shows the DSC thermogram and TGA thermogram of compound 11-hydroxy-2-naphthoate (form A). [Figure 83] Figure 83 shows the DVS isotherm plot of compound 11-hydroxy-2-naphthoate (form A). [Figure 84] Figure 84 shows the XRPD pattern of compound 11-hydroxy-2-naphthoate (form B). [Figure 85] Figure 85 shows the XRPD pattern of compound 11-hydroxy-2-naphthoate (form C). [Figure 86] Figure 86 shows the XRPD pattern of compound 11-hydroxy-2-naphthoate (form D). [Figure 87] Figure 87 shows the XRPD pattern of compound 1 cyclamate (form A). [Figure 88] Figure 88 shows the DSC thermogram and TGA thermogram of compound 1 cyclamate (form A). [Figure 89] Figure 89 shows the DVS isotherm plot of compound 1-cyclamate (form A). [Figure 90] Figure 90 shows the XRPD pattern of compound 1-ethane-1,2-disulfonate (form A). [Figure 91] Figure 91 shows the DSC thermogram and TGA thermogram of compound 1-ethane-1,2-disulfonate (form A). [Figure 92] Figure 92 shows the DVS isotherm plot of compound 1-ethane-1,2-disulfonate (form A). [Figure 93] Figure 93 shows the XRPD pattern of compound 1-ethane-1,2-disulfonate (form B). [Figure 94]Figure 94 shows the XRPD pattern of compound 1-dichloroacetate (form A). [Figure 95] Figure 95 shows the DSC thermogram and TGA thermogram of compound 1-dichloroacetate (form A). [Figure 96] Figure 96 shows the DVS isotherm plot of compound 1-dichloroacetate (form A). [Figure 97] Figure 97 shows the XRPD pattern of compound 1L-malate (form A). [Figure 98] Figure 98 shows the DSC thermogram and TGA thermogram of compound 1L-malate (form A). [Figure 99] Figure 99 shows the DVS isotherm plot of compound 1L-malate (form A). [Figure 100] Figure 100 shows the XRPD pattern of compound 1L-malate (form B). [Figure 101] Figure 101 shows the DSC thermogram and TGA thermogram of compound 1L-malate (form B). [Figure 102] Figure 102 shows the DVS isotherm plot of compound 1L-malate (form B). [Figure 103] Figure 103 shows the XRPD pattern of compound 1 hydrochloride (form A). [Figure 104] Figure 104 shows the DSC thermogram and TGA thermogram of compound 1 hydrochloride (form A). [Figure 105] Figure 105 shows the DVS isotherm plot of compound 1 hydrochloride (form A). [Figure 106] Figure 106 shows the XRPD pattern of compound 1 hydrochloride (form B). [Figure 107] Figure 107 shows the DSC thermogram and TGA thermogram of compound 1 hydrochloride (form B). [Figure 108] Figure 108 shows the DVS isotherm plot of compound 1 hydrochloride (form B). [Figure 109] Figure 109 shows the XRPD pattern of compound 1 hydrochloride (form C). [Figure 110] Figure 110 shows the DSC thermogram and TGA thermogram of compound 1 hydrochloride (form C). [Figure 111] Figure 111 shows the DVS isotherm plot of compound 1 hydrochloride (form C). [Figure 112] Figure 112 shows the XRPD pattern of compound 1 napsylate (form A). [Figure 113] Figure 113 shows the DSC thermogram and TGA thermogram of compound 1 napsylate (form A). [Figure 114] Figure 114 shows the DVS isotherm plot of compound 1 napsylate (form A). [Figure 115] Figure 115 shows the XRPD pattern of compound 1 napsylate (form B). [Figure 116] Figure 116 shows the XRPD pattern of compound 1 oxalate (form A). [Figure 117] Figure 117 shows the DSC thermogram and TGA thermogram of compound 1 oxalate (form A). [Figure 118] Figure 118 shows the DVS isotherm plot of compound 1 oxalate (form A). [Figure 119] Figure 119 shows the XRPD pattern of compound 1 oxalate (form B). [Figure 120] Figure 120 shows the XRPD pattern of compound 1p-aminosalicylate (form A). [Figure 121] Figure 121 shows the DSC thermogram and TGA thermogram of compound 1p-aminosalicylate (form A). [Figure 122] Figure 122 shows the DVS isotherm plot of compound 1p-aminosalicylate (form A). [Figure 123]Figure 123 shows the XRPD pattern of compound 1p-aminosalicylate (form B). [Figure 124] Figure 124 shows the XRPD pattern of compound 1 maleate (form A). [Modes for carrying out the invention]

[0013] definition The term "approximately" preceding a number means a range (e.g., plus or minus 10% of that value). Unless otherwise specified in the context of this disclosure or consistent with such interpretation, for example, "approximately 50" may mean 45 to 55, and "approximately 25,000" may mean 22,500 to 27,500, etc. For example, in a list of numbers such as "approximately 49, approximately 50, approximately 55, ...", "approximately 50" means a range that extends less than half the interval between the preceding and succeeding values, e.g., greater than 49.5 and less than 52.5. Furthermore, the phrase "less than approximately..." or values ​​"greater than approximately..." should be understood in consideration of the definition of the term "approximately" presented herein. Similarly, the term "approximately" preceding a series of numbers or ranges of values ​​(e.g., "approximately 10, 20, 30" or "approximately 10-30") means all the values ​​in the series or the endpoints of the range, respectively.

[0014] Throughout this disclosure, various patents, patent applications, and publications (including non-patent literature) are referenced. These patents, patent applications, and publications are incorporated by reference in their entirety for any purpose to better illustrate the most current art known to those skilled in the art as of the date of this disclosure. In the event of any inconsistency between the cited patents, patent applications, and publications and this disclosure, this disclosure shall prevail.

[0015] For convenience, the specific terms used in this specification, the examples, and the claims are summarized here. Unless otherwise defined, all technical and scientific terms used in this disclosure have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs.

[0016] As used herein, the terms “administer,” “administering,” and “administration” refer to the direct administration of Compound 1 or a pharmaceutically acceptable salt thereof, or a composition containing Compound 1 or a pharmaceutically acceptable salt thereof, to a patient.

[0017] As used herein, the terms “aprotic solvent,” “nonprotic solvent,” or “non-protic solvent” refer to organic solvents or mixtures of organic solvents that are not readily deprotonated in the presence of strongly basic reactants. Non-exclusive examples of aprotic solvents include ethers, dimethylformamide (DMF), dimethylacetamide (DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP), formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethyl sulfoxide, propionitrile, ethyl formate, methyl acetate, methyl isobutyl ketone, hexachloroacetone, acetone, ethyl methyl ketone, methyl methyl ketone (MEK), ethyl acetate, and vinegar. This includes isopropyl acid, sulfolane, N,N-dimethylpropionamide, tetramethylurea, nitromethane, nitrobenzene, or hexamethylphosphoramide, diethoxymethane, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, furan, diethyl ether, tetrahydropyran, diisopropyl ether, dibutyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, and the like.

[0018] As used herein, the term “carrier” encompasses carriers, excipients, and diluents, and means a liquid or solid filler, diluent, excipient, solvent, or encapsulating material involved in the transport or delivery of a pharmaceutical product from one organ or part of the body to another.

[0019] The term “disability” is used in this disclosure to mean, and interchangeably with, a disease, condition, or illness, unless otherwise specified.

[0020] The terms “effective dose” and “therapeutic dose” are used interchangeably in this disclosure and refer to the amount of a compound, or a salt, solvate, or ester thereof, that can produce the intended result when administered to a patient. For example, an effective dose of a salt of compound 1 is the amount required to alleviate at least one symptom of depression in a patient. The actual amount constituting an “effective dose” or “therapeutic dose” varies depending on many factors, including but not limited to the severity of the disease, the patient’s physique and health, and the route of administration. An experienced physician can readily determine an appropriate dose using methods known in the medical field.

[0021] The term "isomer" refers to a compound that has the same chemical formula but differs in stereochemical formula, structural formula, or specific arrangement of atoms. Examples of isomers include stereoisomers, diastereomers, enantiomers, conformational isomers, rotational isomers, geometric isomers, and atropisomers.

[0022] The term "peak" refers to a line with a significant intensity in an XRPD diffractogram (or pattern) obtained from a sample using a standard XRPD acquisition method. For example, a peak is a line in an XRPD diffractogram that has an intensity of at least about 10% of the intensity of the largest peak in the XRPD diffractogram.

[0023] As used herein, the term “pharmaceutically acceptable” means a compound, material, composition, and / or dosage form that is suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, within the bounds of sound medical judgment, and that is commensurate with a reasonable benefit / risk ratio.

[0024] As used herein, the term “protic solvent” refers to a solvent or solvent mixture that can function as an acid for the purpose of protonating an unreacted strongly basic reaction intermediate. Non-exclusive examples of protic solvents include water, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1-butanol, 2-butanol, i-butyl alcohol, t-butyl alcohol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neopentyl alcohol, t-pentyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, glycerol, and the like.

[0025] As used herein, the term “salt” encompasses pharmaceutically acceptable salts commonly used to form addition salts of free bases. The properties of the salt are not of significant importance if it is pharmaceutically acceptable. The term “salt” also includes solvates of addition salts, such as hydrates, as well as polymorphs of addition salts. Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. In salts, proton transfer occurs between the free base of compound 1 and the organic or inorganic acid. However, proton transfer may be incomplete. In such cases, compound 1 and “co-former” molecules (i.e., “co-crystals”) in the solid interact by nonionic forces such as hydrogen bonds.

[0026] A cocrystal of the coformer and compound 1 is provided when the acid coformer is solid at approximately 23°C (i.e., room temperature) and there is no or partial proton transfer between compound 1 and the acid coformer. As used herein, the term “salt” encompasses the cocrystal form of compound 1.

[0027] As used herein, the term “substantially similar” means an analytical spectrum, such as an XRPD pattern or DSC thermogram, that is very similar to a reference spectrum in both peak position and peak intensity.

[0028] As used herein with respect to a patient, the term “to treat” means to improve at least one symptom of the patient’s disorder. Treating may mean curing, improving, or at least partially improving the disorder.

[0029] As used herein, the term “therapeutic effect” refers to a desired or beneficial effect provided by a method and / or composition. For example, the method for treating depression provides a therapeutic effect if the method alleviates at least one symptom of depression in a patient.

[0030] Where used herein, the symbol "≦" means "less than or equal to (not greater than)" or "less than or equal to (same as or less)." "<" means "less than (less than)." "≧" means "greater than or equal to (not less than)" or "greater than or equal to (same as or greater)." ">" means "greater than (greater than)." Furthermore, where used herein in relation to purity or impurity content, numerical values ​​include not only the exact number but also an approximate range of that number. For example, the phrase "99.0% purity" means a purity of approximately 99.0%.

[0031] Salt of compound 1 Compound 1 is a positive GABA-A allosteric modulator (PAM) of the neuroactive steroid GABA-A, possessing high potency similar to clinically-stage neuroactive steroids (alopregnanolone, ganaxolone, SAGE-217, alphaxolone). Because Compound 1 is poorly soluble at pH levels found in the lower gastrointestinal tract, its oral bioavailability may be limited.

[0032] The synthesis of Compound 1 is described in U.S. Publications 2004 / 034002 and 2009 / 0118248, the crystalline polymorphs of the free base of Compound 1 are described in U.S. Publication 2006 / 0074059, and pharmaceutical compositions containing Compound 1 are described in U.S. Publication 2009 / 0131383, all of which are incorporated herein by reference in their entirety for all purposes.

[0033] This disclosure provides a salt of compound 1 and its crystalline form.

[0034] Crystalline salt of compound 1 In some embodiments, the present disclosure provides crystalline forms of salts of compound 1. Polymorphism can be characterized as the ability of a compound to crystallize into different crystalline forms while maintaining the same structural formula (i.e., the covalent bonds of the compound are the same in the different crystalline forms). A crystalline polymorph of a particular drug substance is chemically identical to any other crystalline polymorph of that drug substance in that it contains the same atoms bonded to each other in the same way, but its crystalline form differs, which may affect one or more physical properties such as stability, solubility, melting point, bulk density, and flow properties, or pharmacological properties such as bioavailability.

[0035] In some embodiments, the crystalline morphology is characterized by the interlattice plane interval determined by the X-ray powder diffraction pattern (XRPD). The XRPD diffractogram is typically represented as a plot of peak intensity versus peak position, i.e., a figure expressed in degrees with a diffraction angle of 2θ (2 theta). Characteristic peaks in a particular XRPD diffractogram may be selected according to their peak position and relative intensity so that this crystalline structure can be easily distinguished from other structures. The % intensity of a peak relative to the strongest peak can be expressed as I / Io. The XRPD diffractograms described throughout this disclosure were obtained using copper K-alpha radiation.

[0036] Those skilled in the art should recognize that measured XRPD peak positions and / or intensities for a given crystalline form of the same compound will vary within the margin of error. A frequency 2θ allows for a reasonable margin of error. Typically, the error is expressed as "±". For example, a frequency 2θ of approximately "8.716±0.2" represents a range from approximately 8.716+0.2, i.e., approximately 8.916, to approximately 8.716-0.2, i.e., approximately 8.516. Depending on sample preparation techniques, calibration techniques applied to instruments, and human operational variability, those skilled in the art will recognize that a reasonable margin of error for XRPD may be approximately ±0.7, ±0.6, ±0.5, ±0.4, ±0.3, ±0.2, ±0.1, ±0.05, or less.

[0037] Further details of the methods and equipment used for XRPD analysis are described in the Examples section.

[0038] In some embodiments, the crystalline morphology is characterized by differential scanning calorimetry (DSC). A DSC thermogram is typically represented as a plot of the temperature (°C) of the heat flux-to-measurement sample, normalized in watts per gram ("W / g"). DSC thermograms are typically evaluated for estimated start and end (generation) temperatures, peak temperature, and heat of fusion. The peak characteristic value of the DSC thermogram is often used as a characteristic peak to distinguish this crystalline structure from other crystalline structures.

[0039] Those skilled in the art should recognize that the measured values ​​of a DSC thermogram of a given crystalline form of the same compound will vary within the margin of error. A suitable error can be obtained from the single-peak characteristic value expressed in "°C". Typically, the error is expressed in "±". For example, a single-peak characteristic value of approximately "53.09±2.0" represents a range from approximately 53.09+2, i.e., approximately 55.09, to approximately 53.09-2, i.e., approximately 51.09. Depending on the sample preparation technique, the calibration technique applied to the instrument, and human operational variations, those skilled in the art will recognize that a suitable error for a single-peak characteristic value may be ±2.5, ±2.0, ±1.5, ±1.0, ±0.5, or less.

[0040] Further details of the methods and equipment used for DSC thermogram analysis are described in the Examples section.

[0041] Hydrobromide In some embodiments, the disclosure provides a hydrobromide salt of compound 1 ("compound 1HBr salt"). In some embodiments, the disclosure provides a crystalline form of compound 1HBr salt.

[0042] In one embodiment, the disclosure provides a compound 1HBr salt (Form A). In some embodiments, the compound 1HBr salt (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.6, 15.2, 16.3, 19.8, and 22.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (Form A) exhibits an XRPD containing three or more peaks at approximately 7.6, 15.2, 16.3, 19.8, and 22.9 degrees (2θ) with an error of ±0.2. In some embodiments, the XRPD of the compound 1HBr salt (Form A) further includes one or more peaks at approximately 15.5, 19.2, 20.6, 26.1, and 31.3 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (Form A) exhibits an XRPD including the peaks shown in Table 1 below. TIFF0007911419000002.tif199170

[0043] Some embodiments provide a compound 1HBr salt (morphology A) in which morphology A shows only three peaks in the XRPD pattern within the range of 15.2±0.2 to 16.3±0.2 degrees (2θ).

[0044] In some embodiments, the compound 1HBr salt (form A) exhibits an XRPD substantially similar to that shown in Figure 2.

[0045] In some embodiments, the compound 1HBr salt (Form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 243.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1HBr salt (Form A) exhibits a DSC thermogram substantially similar to that in Figure 3.

[0046] In some embodiments, the compound 1HBr salt (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 3. In some embodiments, the TGA thermogram of the compound 1HBr salt (form A) shows a weight loss of approximately 0.0–1.9% in the temperature range of 25–230°C.

[0047] In some embodiments, the compound 1HBr salt (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 4. In some embodiments, the compound 1HBr salt (form A) exhibits a gravimetric moisture sorption of approximately 1.1% (by weight) at a relative humidity of 80%.

[0048] In one embodiment, the disclosure provides a compound 1HBr salt (Form B). In some embodiments, the compound 1HBr salt (Form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 16.3, 17.7, 21.4, and 23.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1HBr salt (Form B) further includes one or more peaks at approximately 14.4, 18.7, 24.8, 27.3, and 28.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (form B) exhibits an XRPD containing the peaks shown in Table 2 below. TIFF0007911419000003.tif187170

[0049] In some embodiments, the compound 1HBr salt (form B) exhibits an XRPD substantially similar to that shown in Figure 5.

[0050] In some embodiments, the compound 1HBr salt (form B) exhibits a DSC thermogram containing an endothermic peak at approximately 121°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1HBr salt (form B) exhibits a DSC thermogram substantially similar to that in Figure 6.

[0051] In some embodiments, the compound 1HBr salt (form B) exhibits a TGA thermogram substantially similar to that in Figure 6. In some embodiments, the TGA thermogram of the compound 1HBr salt (form B) shows a weight loss of approximately 0.0–3.4% in the temperature range of 25–120°C.

[0052] In some embodiments, the compound 1HBr salt (form B) exhibits a DVS isotherm plot substantially similar to that in Figure 7. In some embodiments, the compound 1HBr salt (form B) exhibits gravimetric hygroscopic absorption of approximately 0.2% (by weight) at a relative humidity of 80%.

[0053] In some embodiments, the compound 1HBr salt (form B) is defined by unit cell parameters substantially similar to those below: a=9.3(4)Å, b=10.8(4)Å, c=25.2(11)Å, α=90°, β=90°, γ=90°, space group P212121, molecular / asymmetric unit 1, and crystalline form at approximately 120K.

[0054] In one embodiment, the disclosure provides a compound 1HBr salt (form C). In some embodiments, the compound 1HBr salt (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 6.9, 13.8, 20.8, 21.6, and 27.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1HBr salt (form C) further includes one or more peaks at approximately 8.8, 25.6, 27.5, 36.2, and 37.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (form C) exhibits an XRPD containing the peaks shown in Table 3 below. TIFF0007911419000004.tif107170

[0055] In some embodiments, the compound 1HBr salt (form C) exhibits an XRPD substantially similar to that shown in Figure 8.

[0056] In some embodiments, the compound 1HBr salt (form C) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 141°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1HBr salt (form C) exhibits a DSC thermogram substantially similar to that in Figure 9.

[0057] In some embodiments, the compound 1HBr salt (form C) exhibits a TGA thermogram substantially similar to that in Figure 9. In some embodiments, the TGA thermogram of the compound 1HBr salt (form C) shows a weight loss of approximately 0.0–4.1% in the temperature range of 25–170°C.

[0058] In some embodiments, the compound 1HBr salt (form C) exhibits a DVS isotherm plot substantially similar to that in Figure 10. In some embodiments, the compound 1HBr salt (form C) exhibits gravimetric hygroscopic hygroscopic hygroscopic hygroscopic 0.25% (by weight) at a relative humidity of 80%.

[0059] In one embodiment, the disclosure provides a compound 1HBr salt (form D). In some embodiments, the compound 1HBr salt (form D) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.7, 15.2, 15.6, 16.4, and 23.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1HBr salt (form D) further includes one or more peaks at approximately 18.2, 19.9, 21.3, 22.2, and 23.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (form D) exhibits an XRPD containing the peaks shown in Table 4 below. TIFF0007911419000005.tif154158

[0060] In some embodiments, the compound 1HBr salt (form D) exhibits an XRPD substantially similar to that shown in Figure 11.

[0061] In some embodiments, the compound 1HBr salt (form D) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 248°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1HBr salt (form D) exhibits a DSC thermogram substantially similar to that in Figure 12.

[0062] In some embodiments, the compound 1HBr salt (form D) exhibits a TGA thermogram substantially similar to that in Figure 12. In some embodiments, the TGA thermogram of the compound 1HBr salt (form D) shows a weight loss of approximately 0.0–1.7% in the temperature range of 29–150°C.

[0063] In some embodiments, the disclosure provides a compound 1HBr salt (form E). In some embodiments, the compound 1HBr salt (form E) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.6, 15.2, 16.3, 22.9, and 23.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (form E) exhibits an XRPD containing three or more peaks at approximately 7.6, 15.2, 16.3, 22.9, and 23.2 degrees (2θ) with an error of ±0.2. In some embodiments, the XRPD of the compound 1HBr salt (form E) further includes one or more peaks at approximately 9.6, 17.4, 22.4, 23.6, and 31.2 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1HBr salt (form E) exhibits an XRPD including the peaks shown in Table 5 below. TIFF0007911419000006.tif187170

[0064] Some embodiments provide a compound 1HBr salt (morphology E) in which morphology E shows only two peaks in the XRPD pattern within the range of 15.2±0.2 to 16.3±0.2 degrees (2θ).

[0065] In some embodiments, the compound 1HBr salt (form E) exhibits an XRPD substantially similar to that shown in Figure 13.

[0066] In some embodiments, the compound 1HBr salt (form E) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 245°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1HBr salt (form E) exhibits a DSC thermogram substantially similar to that in Figure 14.

[0067] In some embodiments, the compound 1HBr salt (form E) exhibits a TGA thermogram substantially similar to that in Figure 14. In some embodiments, the TGA thermogram of the compound 1HBr salt (form E) shows a weight loss of approximately 0.0–0.5% in the temperature range of 28–150°C.

[0068] In some embodiments, the compound 1HBr salt (morphology E) is defined by unit cell parameters substantially similar to those below: a=7.5(10)Å, b=15.0(2)Å, c=23.0(2)Å, α=90°, β=90°, γ=90°, space group P212121, molecular / asymmetric unit 1, and crystalline morphology at approximately 120K.

[0069] In some embodiments, the compound 1HBr salt (morphology E) is defined by unit cell parameters substantially similar to those below: a=23.3(5)Å, b=15.0(3)Å, c=7.5(10)Å, α=90°, β=90°, γ=90°, space group P212121, molecular / asymmetric unit 1, and crystalline morphology at approximately 298K.

[0070] citrate In some embodiments, the disclosure provides a citrate of Compound 1 ("Compound 1 Citrate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Citrate.

[0071] In one embodiment, the disclosure provides compound 1 citrate (form A). In some embodiments, the compound 1 citrate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.7, 11.9, 17.1, 20.1, and 20.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1 citrate (form A) exhibits an XRPD containing three or more peaks at approximately 5.7, 11.9, 17.1, 20.1, and 20.3 degrees (2θ) with an error of ±0.2. In some embodiments, the XRPD of compound 1 citrate (form A) further includes one or more peaks at approximately 12.7, 13.0, 13.6, 15.3, and 16.8 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of compound 1 citrate (form A) exhibits the peaks shown in Table 6 below. TIFF0007911419000007.tif236170

[0072] In some embodiments, the compound 1 citrate (form A) is approximately: 5.7±0.2; 12.5±0.2 and 13.0±0.2; or 5.7±0.2, 12.5±0.2, and 20.1±0.2; or 5.7±0.2; 12.5±0.2 and 20.3±0.2; or 5.7±0.2; 12.7±0.2 and 13.0±0.2; or 5.7±0.2; 12.7±0.2 and 20.3±0.2; or 5.7±0.2, 13 The XRPD shows peaks at 0.0±0.2 and 20.3±0.2; or 5.7±0.2, 16.8±0.2, and 20.1±0.2; or 5.7±0.2; 20.1±0.2 and 20.3±0.2; or 12.5±0.2, 13.0±0.2, and 20.3±0.2; or 12.7±0.2, 13.0±0.2, and 20.3±0.2; or 16.8±0.2, 20.1±0.2 and 20.3±0.2 degrees (2θ).

[0073] In some embodiments, the compound 1 citrate (form A) exhibits an XRPD substantially similar to that shown in Figure 15.

[0074] In some embodiments, the compound 1 citrate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 89.0°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 citrate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 89.0 ± 2.0°C. In some embodiments, the compound 1 citrate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 139.5°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 citrate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 139.5 ± 2.0°C. In some embodiments, the compound 1 citrate (form A) exhibits a DSC thermogram substantially similar to that in Figure 16.

[0075] In some embodiments, compound 1 citrate (form A) exhibits a TGA thermogram substantially similar to that in Figure 16. In some embodiments, the TGA thermogram of compound 1 citrate (form A) shows a weight loss of 0.0 to 2.6% in a temperature range of 25 to 65°C.

[0076] In some embodiments, compound 1 citrate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 17. In some embodiments, compound 1 citrate (form A) exhibits gravimetric hygroscopic

[0077] In some embodiments, the compound 1 citrate (form A) is defined by unit cell parameters substantially similar to those below: a=8.9(10)Å, b=12.2(10)Å, c=16.5(10)Å, α=73.7(10)°, β=76.6(10)°, γ=83.2(10)°, space group P1, molecular / asymmetric unit 2, and crystalline form at approximately 120.00K.

[0078] In one embodiment, the disclosure provides compound 1 citrate (form B). In some embodiments, the compound 1 citrate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.5, 5.7, 10.9, 16.3, and 20.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 citrate (form B) further includes one or more peaks at approximately 3.4, 11.8, 14.6, 17.2, and 21.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1 citrate (form B) exhibits an XRPD containing the peaks shown in Table 7 below. TIFF0007911419000008.tif106170

[0079] In some embodiments, the compound 1 citrate (form B) exhibits an XRPD substantially similar to that shown in Figure 18.

[0080] In some embodiments, the compound 1 citrate (form B) exhibits a DSC thermogram containing an endothermic peak at approximately 77.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 citrate (form B) exhibits a DSC thermogram containing an endothermic peak at approximately 121.5°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 citrate (form B) exhibits a DSC thermogram containing an endothermic peak at approximately 136.6°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 citrate (form B) exhibits a DSC thermogram substantially similar to that in Figure 19.

[0081] In some embodiments, compound 1 citrate (form B) exhibits a TGA thermogram substantially similar to that in Figure 19. In some embodiments, the TGA thermogram of compound 1 citrate (form B) shows a weight loss of approximately 0.0 to 4.5% in a temperature range of 25 to 120°C.

[0082] In some embodiments, compound 1 citrate (form B) exhibits a DVS isotherm plot substantially similar to that in Figure 20. In some embodiments, compound 1 citrate (form B) exhibits gravimetric hygroscopic

[0083] In one embodiment, the disclosure provides compound 1 citrate (form C). In some embodiments, the compound 1 citrate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 15.4, 18.7, 19.7, 20.6, and 27.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 citrate (form C) further includes one or more peaks at approximately 13.5, 15.5, 16.2, 17.0, and 22.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 citrate (form C) exhibits an XRPD containing the peaks shown in Table 8 below. TIFF0007911419000009.tif200170

[0084] In some embodiments, the compound 1 citrate (form C) exhibits an XRPD substantially similar to that shown in Figure 21.

[0085] Mesylate In some embodiments, the disclosure provides a mesylate of Compound 1 ("Compound 1 Mesylate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Mesylate.

[0086] In one embodiment, the disclosure provides compound 1 mesylate (form A). In some embodiments, the compound 1 mesylate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 7.1, 14.2, 19.1, and 25.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 mesylate (form A) further contains one or more peaks at approximately 7.7, 12.7, 17.8, 19.4, and 21.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 mesylate (form A) exhibits an XRPD containing the peaks shown in Table 9 below. TIFF0007911419000010.tif92170

[0087] In some embodiments, the compound 1 mesylate (form A) exhibits an XRPD substantially similar to that shown in Figure 22.

[0088] In some embodiments, the compound 1 mesylate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 170.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 mesylate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 209.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 mesylate (form A) exhibits a DSC thermogram substantially similar to that in Figure 23.

[0089] In some embodiments, the compound 1 mesylate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 23. In some embodiments, the TGA thermogram of the compound 1 mesylate (form A) shows a weight loss of 0.0 to 0.5% in a temperature range of 25 to 150°C.

[0090] In some embodiments, the compound 1 mesylate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 24. In some embodiments, the compound 1 mesylate (form A) exhibits gravimetric hygroscopic

[0091] In one embodiment, the disclosure provides compound 1 mesylate (form B). In some embodiments, the compound 1 mesylate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.1, 14.3, 15.9, 21.4, and 22.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 mesylate (form B) exhibits an XRPD containing the peaks shown in Table 10A below. TIFF0007911419000011.tif45170

[0092] In some embodiments, the compound 1 mesylate (form B) exhibits an XRPD substantially similar to that shown in Figure 25A.

[0093] In some embodiments, the disclosure provides compound 1 mesylate (form C). In some embodiments, the compound 1 mesylate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.5, 15.0, 19.4, 22.5, and 30.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 mesylate (form C) exhibits an XRPD containing the peaks shown in Table 10B below. TIFF0007911419000012.tif42170

[0094] In some embodiments, the compound 1 mesylate (form C) exhibits an XRPD substantially similar to that shown in Figure 25B.

[0095] In one embodiment, the disclosure provides compound 1 mesylate (form D). In some embodiments, the compound 1 mesylate (form D) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.4, 15.0, and 22.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 mesylate (form D) exhibits an XRPD containing the peaks shown in Table 11 below. TIFF0007911419000013.tif32170

[0096] In some embodiments, the compound 1 mesylate (form D) exhibits an XRPD substantially similar to that shown in Figure 26.

[0097] Phosphate In some embodiments, the disclosure provides a phosphate of Compound 1 ("Compound 1 Phosphate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Phosphate.

[0098] In one embodiment, the disclosure provides compound 1-phosphate (form A). In some embodiments, the compound 1-phosphate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.3, 3.6, 5.4, 9.9, and 13.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-phosphate (form A) further includes one or more peaks at approximately 16.1, 17.9, 20.9, 23.7, and 26.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 phosphate (form A) exhibits an XRPD containing the peaks shown in Table 12 below. TIFF0007911419000014.tif108170

[0099] In some embodiments, the compound 1 phosphate (form A) exhibits an XRPD substantially similar to that shown in Figure 27.

[0100] In some embodiments, the compound 1-phosphate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 217.6°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1-phosphate (form A) exhibits a DSC thermogram substantially similar to that in Figure 28.

[0101] In some embodiments, the compound 1-phosphate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 28. In some embodiments, the TGA thermogram of the compound 1-phosphate (form A) shows a weight loss of 0.0 to 1.7% in a temperature range of 25 to 204°C.

[0102] In some embodiments, the compound 1-phosphate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 29. In some embodiments, the compound 1-phosphate (form A) exhibits gravimetric hygroscopic

[0103] Tartrate In some embodiments, the Disclosure provides a tartrate of Compound 1 ("Compound 1 Tartrate"). In some embodiments, the Disclosure provides a D(-)-tartrate of Compound 1 ("Compound 1 D(-)-tartrate"). In some embodiments, the Disclosure provides a L(+)-tartrate of Compound 1 ("Compound 1 L(+)-tartrate").

[0104] In some embodiments, this disclosure provides a crystalline form of compound 1 tartrate. In some embodiments, this disclosure provides a crystalline form of compound 1D(-)-tartrate. In some embodiments, this disclosure provides a crystalline form of compound 1L(+)-tartrate.

[0105] In one embodiment, the disclosure provides compound 1L(+)-tartrate (Form A). In some embodiments, the compound 1L(+)-tartrate (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 4.7, 13.9, 18.6, and 22.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1L(+)-tartrate (Form A) further contains one or more peaks at approximately 14.6, 17.8, and 18.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1L(+)-tartrate (form A) exhibits an XRPD containing the peaks shown in Table 13 below. TIFF0007911419000015.tif58170

[0106] In some embodiments, the compound 1L(+)-tartrate (form A) exhibits an XRPD substantially similar to that shown in Figure 30.

[0107] In some embodiments, the compound 1L(+)-tartrate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 207.6°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1L(+)-tartrate (form A) exhibits a DSC thermogram substantially similar to that in Figure 31.

[0108] In some embodiments, the compound 1L(+)-tartrate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 31. In some embodiments, the TGA thermogram of the compound 1L(+)-tartrate (form A) shows a weight loss of 0.0 to 1.2% in the temperature range of 25 to 189°C.

[0109] In some embodiments, the compound 1L(+)-tartrate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 32. In some embodiments, the compound 1L(+)-tartrate (form A) exhibits gravimetric hygroscopic absorption of approximately 1.6% (by weight) at a relative humidity of 80%.

[0110] In one embodiment, the disclosure provides compound 1L(+)-tartrate (form B). In some embodiments, the compound 1L(+)-tartrate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 4.6, 12.4, 13.9, and 22.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1L(+)-tartrate (form B) further includes one or more peaks at approximately 14.8, 18.3, and 18.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1L(+)-tartrate (form B) exhibits an XRPD containing the peaks shown in Table 14 below. TIFF0007911419000016.tif58170

[0111] In some embodiments, the compound 1L(+)-tartrate (form B) exhibits an XRPD substantially similar to that shown in Figure 33.

[0112] In some embodiments, the compound 1L(+)-tartrate (form B) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 207.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1L(+)-tartrate (form B) exhibits a DSC thermogram substantially similar to that in Figure 34.

[0113] In some embodiments, the compound 1L(+)-tartrate (form B) exhibits a TGA thermogram substantially similar to that in Figure 34. In some embodiments, the TGA thermogram of the compound 1L(+)-tartrate (form B) shows a weight loss of 0.0–0.6% in the temperature range of 25–180°C.

[0114] In some embodiments, the compound 1L(+)-tartrate (form B) exhibits a DVS isotherm plot substantially similar to that in Figure 35. In some embodiments, the compound 1L(+)-tartrate (form B) exhibits gravimetric hygroscopic absorption of approximately 1.7% (by weight) at a relative humidity of 80%.

[0115] Fumarate In some embodiments, the disclosure provides a fumarate of Compound 1 ("Compound 1 Fumarate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Fumarate.

[0116] In one embodiment, the disclosure provides compound 1 fumarate (form A). In some embodiments, the compound 1 fumarate (form A) exhibits an XRPD including one or more peaks at about 3.5 and 16.0 degrees (2θ) with an error of about ±0.5, about ±0.4, about ±0.3, about ±0.2, about ±0.1, about ±0.05 or less (in particular about ±0.2). In some embodiments, the compound 1 fumarate (form A) exhibits an XRPD including the peaks shown in Table 15 below. TIFF0007911419000017.tif26170

[0117] In some embodiments, the compound 1 fumarate (form A) exhibits an XRPD substantially similar to that shown in Figure 36.

[0118] In some embodiments, the compound 1 fumarate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 87.0°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 fumarate (form A) exhibits a DSC thermogram substantially similar to that in Figure 37.

[0119] In some embodiments, compound 1 fumarate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 37. In some embodiments, the TGA thermogram of compound 1 fumarate (form A) shows a weight loss of 0.0 to 0.9% in a temperature range of 25 to 75°C.

[0120] In some embodiments, the disclosure provides compound 1 fumarate (form B). In some embodiments, the compound 1 fumarate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 11.0, 16.2, and 17.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 fumarate (form B) exhibits an XRPD containing the peaks shown in Table 16 below. TIFF0007911419000018.tif38170

[0121] In some embodiments, the compound 1 fumarate (form B) exhibits an XRPD substantially similar to that shown in Figure 38.

[0122] In some embodiments, the compound 1 fumarate (form B) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 89.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 fumarate (form B) exhibits a DSC thermogram substantially similar to that in Figure 39.

[0123] In some embodiments, compound 1 fumarate (form B) exhibits a TGA thermogram substantially similar to that in Figure 39. In some embodiments, the TGA thermogram of compound 1 fumarate (form B) shows a weight loss of 0.0 to 1.85% in a temperature range of 25 to 150°C.

[0124] In some embodiments, compound 1 fumarate (form B) exhibits a DVS isotherm plot substantially similar to that in Figure 40. In some embodiments, compound 1 fumarate (form B) exhibits gravimetric hygroscopic

[0125] In one embodiment, the disclosure provides compound 1 fumarate (form C). In some embodiments, the compound 1 fumarate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.5, 15.4, 16.7, 17.6, and 28.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 fumarate (form C) further includes one or more peaks at approximately 8.4, 19.7, 20.5, 22.9, and 38.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2). In some embodiments, the compound 1 fumarate (form C) exhibits an XRPD containing the peaks shown in Table 17 below. TIFF0007911419000019.tif102170

[0126] In some embodiments, the compound 1 fumarate (form C) exhibits an XRPD substantially similar to that shown in Figure 41.

[0127] In one embodiment, the disclosure provides compound 1 fumarate (form D). In some embodiments, the compound 1 fumarate (form D) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.2, 12.2, 15.2, 15.5, and 19.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 fumarate (form D) further includes one or more peaks at approximately 10.4, 13.6, 14.2, 21.2, and 22.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 fumarate (form D) exhibits an XRPD containing the peaks shown in Table 18 below. TIFF0007911419000020.tif127170

[0128] In some embodiments, the compound 1 fumarate (form D) exhibits an XRPD substantially similar to that shown in Figure 42.

[0129] Tosylate In some embodiments, the disclosure provides a tosylate of Compound 1 ("Compound 1 Tosylate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Tosylate.

[0130] In one embodiment, the disclosure provides compound 1 tosylate (form A). In some embodiments, the compound 1 tosylate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.4, 9.8, 10.3, 12.5, and 15.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 tosylate (form A) further contains one or more peaks at approximately 17.4, 17.9, 19.6, 23.2, and 26.0 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0131] In some embodiments, the compound 1 tosylate (form A) exhibits an XRPD containing the peaks shown in Table 19 below. TIFF0007911419000021.tif126170

[0132] In some embodiments, the compound 1 tosylate (form A) exhibits an XRPD substantially similar to that shown in Figure 43.

[0133] In some embodiments, the compound 1 tosylate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 186.2°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 tosylate (form A) exhibits a DSC thermogram substantially similar to that in Figure 44.

[0134] In some embodiments, the compound 1 tosylate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 44. In some embodiments, the TGA thermogram of the compound 1 tosylate (form A) shows a weight loss of 0.0 to 0.9% in a temperature range of 25 to 175°C.

[0135] In some embodiments, the compound 1 tosylate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 45. In some embodiments, the compound 1 tosylate (form A) exhibits gravimetric hygroscopic

[0136] In one embodiment, the disclosure provides compound 1 tosylate (form B). In some embodiments, the compound 1 tosylate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 10.0, 15.2, 15.5, 17.2, and 19.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 tosylate (form B) further contains one or more peaks at approximately 10.3, 16.7, 19.1, 20.1, and 20.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0137] In some embodiments, the compound 1 tosylate (form B) exhibits an XRPD containing the peaks shown in Table 20 below. TIFF0007911419000022.tif160170

[0138] In some embodiments, the compound 1 tosylate (form B) exhibits an XRPD substantially similar to that shown in Figure 46.

[0139] In one embodiment, the disclosure provides compound 1 tosylate (form C). In some embodiments, the compound 1 tosylate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 7.4, 10.2, 12.5, 18.3, and 19.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 tosylate (form C) further includes one or more peaks at approximately 9.8, 14.7, 16.6, 17.8, and 23.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0140] In some embodiments, the compound 1 tosylate (form C) exhibits an XRPD containing the peaks shown in Table 21 below. TIFF0007911419000023.tif187170

[0141] In some embodiments, the compound 1 tosylate (form C) exhibits an XRPD substantially similar to that shown in Figure 47.

[0142] Glucuronate In some embodiments, the Disclosure provides a glucuronate of Compound 1 ("Compound 1 Glucuronate"). In some embodiments, the Disclosure provides a D-glucuronate of Compound 1 ("Compound 1 D-Glucuronate"). In some embodiments, the Disclosure provides a L-glucuronate of Compound 1 ("Compound 1 L-Glucuronate").

[0143] In some embodiments, this disclosure provides a crystalline form of compound 1-glucuronide. In some embodiments, this disclosure provides a crystalline form of compound 1D-glucuronide. In some embodiments, this disclosure provides a crystalline form of compound 1L-glucuronide.

[0144] In one embodiment, the disclosure provides compound 1D-glucuronide (form A). In some embodiments, the compound 1D-glucuronide (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 4.3, 12.9, 16.8, 20.2, and 20.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1D-glucuronide (form A) further includes one or more peaks at approximately 3.3, 14.7, 17.3, 21.6, and 24.8 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0145] In some embodiments, the compound 1D-glucuronide (form A) exhibits an XRPD containing the peaks shown in Table 22 below. TIFF0007911419000024.tif123170

[0146] In some embodiments, the compound 1D-glucuronide (form A) exhibits an XRPD substantially similar to that shown in Figure 48.

[0147] In some embodiments, the compound 1D-glucuronide (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 116.2°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1D-glucuronide (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 139.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1D-glucuronide (form A) exhibits a DSC thermogram substantially similar to that in Figure 49.

[0148] In some embodiments, the compound 1D-glucuronide (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 49. In some embodiments, the TGA thermogram of the compound 1D-glucuronide (form A) shows a weight loss of 0.0 to 3.0% in a temperature range of 25 to 120°C.

[0149] In some embodiments, the compound 1D-glucuronate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 50. In some embodiments, the compound 1D-glucuronate (form A) exhibits gravimetric hygroscopic

[0150] In one embodiment, the disclosure provides compound 1D-glucuronide (form B). In some embodiments, the compound 1D-glucuronide (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.7, 16.7, 17.0, 20.0, and 20.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1D-glucuronate (form B) further includes one or more peaks at approximately 8.5, 15.0, 19.5, 22.5, and 24.3 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0151] In some embodiments, the compound 1D-glucuronide (form B) exhibits an XRPD containing the peaks shown in Table 23 below. TIFF0007911419000025.tif145170

[0152] In some embodiments, the compound 1D-glucuronide (form B) exhibits an XRPD substantially similar to that shown in Figure 51.

[0153] Ethanolate In some embodiments, the disclosure provides an ethanesulfonate of Compound 1 ("Compound 1 Ethanesulfonate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Ethanesulfonate.

[0154] In one embodiment, the disclosure provides compound 1-ethanesulfonate (Form A). In some embodiments, the compound 1-ethanesulfonate (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.4, 3.7, 7.6, 15.3, and 23.0 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-ethanesulfonate (Form A) further includes one or more peaks at approximately 23.3 and 30.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0155] In some embodiments, the compound 1-ethanesulfonate (form A) exhibits an XRPD containing the peaks shown in Table 24 below. TIFF0007911419000026.tif51170

[0156] In some embodiments, the compound 1-ethanesulfonate (form A) exhibits an XRPD substantially similar to that shown in Figure 52.

[0157] In some embodiments, the compound 1-ethanesulfonate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 177.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-ethanesulfonate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 207.0°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-ethanesulfonate (form A) exhibits a DSC thermogram substantially similar to that in Figure 53.

[0158] In some embodiments, the compound 1-ethanesulfonate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 53. In some embodiments, the TGA thermogram of the compound 1-ethanesulfonate (form A) shows a weight loss of 0.0 to 2.9% in a temperature range of 25 to 180°C.

[0159] In some embodiments, the compound 1-ethanesulfonate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 54. In some embodiments, the compound 1-ethanesulfonate (form A) exhibits gravimetric hygroscopic

[0160] Sulfate In some embodiments, the disclosure provides a sulfate of Compound 1 ("Compound 1 Sulfate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Sulfate.

[0161] In one embodiment, the disclosure provides compound 1 sulfate (form A). In some embodiments, the compound 1 sulfate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 5.2, 7.8, 8.1, and 15.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 sulfate (form A) further includes one or more peaks at approximately 14.7, 17.4, 18.2, 18.4, and 19.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the compound 1 sulfate (form A) exhibits an XRPD containing the peaks shown in Table 25 below. TIFF0007911419000027.tif89170

[0162] In some embodiments, the compound 1 sulfate (form A) exhibits an XRPD substantially similar to that shown in Figure 55.

[0163] In some embodiments, the compound 1 sulfate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 167.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 sulfate (form A) exhibits a DSC thermogram substantially similar to that in Figure 56.

[0164] In some embodiments, the compound 1 sulfate (form A) exhibits a TGA thermogram substantially similar to that in Figure 56. In some embodiments, the TGA thermogram of the compound 1 sulfate (form A) shows a weight loss of 0.0 to 1.0% in a temperature range of 25 to 120°C.

[0165] In some embodiments, compound 1 sulfate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 57. In some embodiments, compound 1 sulfate (form A) exhibits gravimetric hygroscopic

[0166] Ascorbate In some embodiments, the Disclosure provides compound 1 ascorbate ("compound 1 ascorbate"). In some embodiments, the Disclosure provides a crystalline form of compound 1 ascorbate.

[0167] In one embodiment, the disclosure provides compound 1 ascorbate (form A). In some embodiments, the compound 1 ascorbate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 5.6, 16.6, 19.6, and 19.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 ascorbate (form A) further includes one or more peaks at approximately 11.5, 11.9, 21.6, 24.1, and 24.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0168] In some embodiments, the compound 1 ascorbate (form A) exhibits an XRPD containing the peaks shown in Table 26 below. TIFF0007911419000028.tif102170

[0169] In some embodiments, the compound 1 ascorbate (form A) exhibits an XRPD substantially similar to that shown in Figure 58.

[0170] In some embodiments, the compound 1 ascorbate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 46.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 ascorbate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 124.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 ascorbate (form A) exhibits a DSC thermogram substantially similar to that in Figure 59.

[0171] In some embodiments, compound 1 ascorbate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 59. In some embodiments, the TGA thermogram of compound 1 ascorbate (form A) shows a weight loss of 0.0 to 5.6% in a temperature range of 25 to 120°C.

[0172] In some embodiments, compound 1 ascorbate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 60. In some embodiments, compound 1 ascorbate (form A) exhibits gravimetric hygroscopic

[0173] In one embodiment, the disclosure provides compound 1 ascorbate (form B). In some embodiments, the compound 1 ascorbate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.5, 16.6, 19.7, 20.1, and 28.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 ascorbate (form B) further includes one or more peaks at approximately 14.7 and 23.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0174] In some embodiments, the compound 1 ascorbate (form B) exhibits an XRPD containing the peaks shown in Table 27 below. TIFF0007911419000029.tif51170

[0175] In some embodiments, the compound 1 ascorbate (form B) exhibits an XRPD substantially similar to that shown in Figure 61.

[0176] Napadisylate In some embodiments, the disclosure provides napadisylate of compound 1 ("compound 1 napadisylate"). In some embodiments, the disclosure provides the crystalline form of compound 1 napadisylate.

[0177] In one embodiment, the disclosure provides compound 1 napadisylate (form A). In some embodiments, the compound 1 napadisylate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.3, 9.4, 14.2, 16.4, and 17.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of compound 1 napadisylate (form A) further contains one or more peaks at approximately 9.7, 17.3, 20.3, 24.4, and 26.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, compound 1 napadisylate (form A) exhibits an XRPD containing the peaks shown in Table 28 below. TIFF0007911419000030.tif122170

[0178] In some embodiments, compound 1 napadisylate (form A) exhibits an XRPD substantially similar to that shown in Figure 62.

[0179] In some embodiments, the compound 1 napadisylate (Form A) exhibits a DSC thermogram with an endothermic peak at about 41.7 °C with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (in particular, about ±2.0). In some embodiments, the compound 1 napadisylate (Form A) exhibits a DSC thermogram substantially similar to FIG. 63.

[0180] In some embodiments, the compound 1 napadisylate (Form A) exhibits a TGA thermogram substantially similar to FIG. 63. In some embodiments, the TGA thermogram of the compound 1 napadisylate (Form A) shows a weight loss of 0.0 - 0.7% within the temperature range of 25 - 120 °C.

[0181] In some embodiments, the compound 1 napadisylate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 64. In some embodiments, the compound 1 napadisylate shows a gravimetric moisture absorption of about 3.1% (by weight) at a relative humidity of 80%.

[0182] In some embodiments, the present disclosure provides a compound 1 napadisylate (Form B). In some embodiments, the compound 1 napadisylate (Form B) exhibits an XRPD with one or more peaks (in particular, three or more peaks) at about 6.0, 14.2, 18.1, 19.0, and 20.3 degrees (2θ) with an error of about ±0.5, about ±0.4, about ±0.3, about ±0.2, about ±0.1, about ±0.05 or less (in particular, about ±0.2). In some embodiments, the XRPD of the compound 1 napadisylate (Form B) further includes one or more peaks at about 12.0, 16.9, 18.4, 19.4, and 24.1 degrees (2θ) with an error of about ±0.5, about ±0.4, about ±0.3, about ±0.2, about ±0.1, about ±0.05 or less (in particular, about ±0.2).

[0183] In some embodiments, the compound 1 napadisylate (Form B) exhibits an XRPD including the peaks shown in Table 29 below. <s TIFF0007911419000031.tif85170

[0184] In some embodiments, compound 1 napadisylate (form B) exhibits an XRPD substantially similar to that shown in Figure 65.

[0185] Maronate In some embodiments, the disclosure provides a malonate of Compound 1 ("Compound 1 Malonate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Malonate.

[0186] In one embodiment, the disclosure provides compound 1-malonate (form A). In some embodiments, the compound 1-malonate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 15.1, 18.0, 18.8, 23.4, and 23.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-malonate (form A) further contains one or more peaks at approximately 3.6, 13.8, 15.6, 21.4, and 27.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0187] In some embodiments, the compound 1 malonate (form A) exhibits an XRPD containing the peaks shown in Table 30 below. TIFF0007911419000032.tif122170

[0188] In some embodiments, the compound 1 malonate (form A) exhibits an XRPD substantially similar to that shown in Figure 66.

[0189] In some embodiments, the compound 1-malonate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 36.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-malonate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 124.6°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-malonate (form A) exhibits a DSC thermogram substantially similar to that in Figure 67.

[0190] In some embodiments, the compound 1-malonate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 67. In some embodiments, the TGA thermogram of the compound 1-malonate (form A) shows a weight loss of 0.0 to 1.9% in a temperature range of 25 to 120°C.

[0191] Besilate In some embodiments, the disclosure provides a besylate of Compound 1 ("Compound 1 Besylate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Besylate.

[0192] In one embodiment, the disclosure provides compound 1 besilate (form A). In some embodiments, the compound 1 besilate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.7, 15.8, 22.1, 23.2, and 26.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 besilate (form A) further contains one or more peaks at approximately 3.7, 16.2, 17.8, 19.5, and 30.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0193] In some embodiments, the compound 1 besylate (form A) exhibits an XRPD containing the peaks shown in Table 31 below. TIFF0007911419000033.tif85170

[0194] In some embodiments, the compound 1 besylate (form A) exhibits an XRPD substantially similar to that shown in Figure 68.

[0195] In some embodiments, the compound 1 besylate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 194.2°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 besylate (form A) exhibits a DSC thermogram substantially similar to that in Figure 69.

[0196] In some embodiments, the compound 1-besilate (form A) exhibits a TGA thermogram substantially similar to that in Figure 69. In some embodiments, the TGA thermogram of the compound 1-besilate (form A) shows a weight loss of 0.0 to 3.3% in a temperature range of 25 to 120°C.

[0197] In some embodiments, compound 1 besilate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 70. In some embodiments, compound 1 besilate (form A) exhibits gravimetric hygroscopic

[0198] In one embodiment, the present disclosure provides compound 1 besylate (form B).

[0199] In some embodiments, the compound 1 besylate (Form B) exhibits an XRPD that includes one or more peaks (particularly, three or more peaks) at approximately 7.3, 14.7, 22.1, 23.2, and 29.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (particularly, approximately ±0.2). In some embodiments, the XRPD of the compound 1 besylate (Form B) further includes one or more peaks at approximately 7.9, 16.2, 16.4, 17.2, and 30.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (particularly, approximately ±0.2).

[0200] In some embodiments, the compound 1 besylate (Form B) exhibits an XRPD that includes the peaks shown in Table 32 below. TIFF0007911419000034.tif68170

[0201] In some embodiments, the compound 1 besylate (Form B) exhibits an XRPD that is substantially similar to FIG. 71.

[0202] Isethionate In some embodiments, the present disclosure provides an isethionate of compound 1 (“compound 1 isethionate”). In some embodiments, the present disclosure provides a crystalline form of compound 1 isethionate.

[0203] In one embodiment, the present disclosure provides compound 1 isethionate (Form A).

[0204] In some embodiments, the compound 1 isethionate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.6, 16.7, 16.9, 18, and 20.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 isethionate (form A) further contains one or more peaks at approximately 3.7, 15.7, 16.2, 20.7, and 25.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0205] In some embodiments, the compound 1 isethionate (form A) exhibits an XRPD containing the peaks shown in Table 33 below. TIFF0007911419000035.tif147170

[0206] In some embodiments, the compound 1 isethionate (form A) exhibits an XRPD substantially similar to that shown in Figure 72.

[0207] In some embodiments, the compound 1 isethionate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 153.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 isethionate (form A) exhibits a DSC thermogram substantially similar to that in Figure 73.

[0208] In some embodiments, compound 1-isethionate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 73. In some embodiments, the TGA thermogram of compound 1-isethionate (form A) shows a weight loss of 0.0 to 0.0% in a temperature range of 25 to 120°C.

[0209] In some embodiments, compound 1-isethionate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 74. In some embodiments, compound 1-isethionate (form A) exhibits gravimetric hygroscopic

[0210] In one embodiment, the disclosure provides compound 1 isethionate (form B). In some embodiments, the compound 1 isethionate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.5, 15.8, 17.9, 18.1, and 18.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of compound 1 isethionate (form B) further includes one or more peaks at approximately 11.4, 13.1, 14.2, 15.0, and 17.0 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0211] In some embodiments, the compound 1 isethionate (form B) exhibits an XRPD containing the peaks shown in Table 34 below. TIFF0007911419000036.tif96170

[0212] In some embodiments, compound 1 isethionate (form B) exhibits an XRPD substantially similar to that shown in Figure 75.

[0213] Gentisidine salt In some embodiments, the disclosure provides a gentisic acid salt of Compound 1 ("Compound 1 Gentisic Acid"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Gentisic Acid.

[0214] In one embodiment, the present disclosure provides compound 1 gentisinate (form A). In some embodiments, the compound 1 gentisic acid salt (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.4, 3.6, 7.0, 14.6, and 21.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 gentisic acid salt (form A) further contains one or more peaks at approximately 16.0, 18.0, 18.5, 19.5, and 21.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0215] In some embodiments, the compound 1 gentisinate (form A) exhibits an XRPD containing the peaks shown in Table 35 below. TIFF0007911419000037.tif121170

[0216] In some embodiments, the compound 1 gentisinate (form A) exhibits an XRPD substantially similar to that shown in Figure 76.

[0217] In some embodiments, the compound 1 gentisate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 117.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 gentisate (form A) exhibits a DSC thermogram substantially similar to that in Figure 77.

[0218] In some embodiments, the compound 1-gentisate (form A) exhibits a TGA thermogram substantially similar to that in Figure 77. In some embodiments, the TGA thermogram of the compound 1-gentisate (form A) shows a weight loss of 0.0 to 9.0% in a temperature range of 25 to 200°C.

[0219] In some embodiments, compound 1-gentisate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 78. In some embodiments, compound 1-gentisate (form A) exhibits gravimetric hygroscopic absorption of approximately 3.1% (by weight) at a relative humidity of 80%.

[0220] In one embodiment, the present disclosure provides compound 1 gentisic acid salt (form B). In some embodiments, the compound 1 gentisic acid salt (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.5, 10.9, 16.4, 21.9, and 22.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 gentisic acid salt (form B) further contains one or more peaks at approximately 9.2, 13.0, 17.2, 18.7, and 27.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0221] In some embodiments, the compound 1 gentisinate (form B) exhibits an XRPD containing the peaks shown in Table 36 below. TIFF0007911419000038.tif127170

[0222] In some embodiments, the compound 1 gentisinate (form B) exhibits an XRPD substantially similar to that shown in Figure 79.

[0223] In one embodiment, the disclosure provides compound 1-gentisate (form C). In some embodiments, the compound 1-gentisate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.3, 15.2, 15.9, 21.4, and 26.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-gentisate (form C) further contains one or more peaks at approximately 7.6, 10.6, 13.8, 16.9, and 19.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0224] In some embodiments, the compound 1 gentisinate (form C) exhibits an XRPD containing the peaks shown in Table 37 below. TIFF0007911419000039.tif97170

[0225] In some embodiments, the compound 1 gentisinate (form C) exhibits an XRPD substantially similar to that shown in Figure 80.

[0226] 1-Hydroxy-2-Naphthoate In some embodiments, the disclosure provides 1-hydroxy-2-naphthoate of compound 1 ("compound 11-hydroxy-2-naphthoate"). In some embodiments, the disclosure provides crystalline forms of compound 11-hydroxy-2-naphthoate.

[0227] In one embodiment, the disclosure provides compound 11-hydroxy-2-naphthoate (form A). In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.2, 6.2, 13.8, 21.2, and 21.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (form A) further includes one or more peaks at approximately 13.4, 16.2, 19.9, 20.2, and 24.7 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0228] In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits an XRPD containing the peaks shown in Table 38 below. TIFF0007911419000040.tif95170

[0229] In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits an XRPD substantially similar to that shown in Figure 81.

[0230] In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 57.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 79.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 116.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 164.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DSC thermogram substantially similar to that in Figure 82.

[0231] In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 82. In some embodiments, the TGA thermogram of the compound 11-hydroxy-2-naphthoate (form A) shows a weight loss of 0.0 to 3.6% in a temperature range of 25 to 120°C. In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 83. In some embodiments, the compound 11-hydroxy-2-naphthoate (form A) exhibits gravimetric hygroscopic absorption of approximately 4.6% (by weight) at a relative humidity of 80%.

[0232] In one embodiment, the present disclosure provides compound 11-hydroxy-2-naphthoate (form B). In some embodiments, the compound 11-hydroxy-2-naphthoate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 8.0, 8.6, 13.5, 13.8, and 20.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (form B) further includes one or more peaks at approximately 14.4, 15.2, 16.1, 21.4, and 23.8 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0233] In some embodiments, the compound 11-hydroxy-2-naphthoate (form B) exhibits an XRPD containing the peaks shown in Table 39 below. TIFF0007911419000041.tif186170

[0234] In some embodiments, the compound 11-hydroxy-2-naphthoate (form B) exhibits an XRPD substantially similar to that shown in Figure 84.

[0235] In one embodiment, the present disclosure provides compound 11-hydroxy-2-naphthoate (form C). In some embodiments, the compound 11-hydroxy-2-naphthoate (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 8.5, 13.7, 14.2, 17.3, and 21.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (form C) further includes one or more peaks at approximately 7.7, 15.4, 20.2, 20.6, and 21.1 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0236] In some embodiments, the compound 11-hydroxy-2-naphthoate (form C) exhibits an XRPD containing the peaks shown in Table 40 below. TIFF0007911419000042.tif135170

[0237] In some embodiments, the compound 11-hydroxy-2-naphthoate (form C) exhibits an XRPD substantially similar to that shown in Figure 85.

[0238] In one embodiment, the present disclosure provides compound 11-hydroxy-2-naphthoate (form D). In some embodiments, the compound 11-hydroxy-2-naphthoate (form D) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 10.4, 12.9, 13.5, 20.4, and 20.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (form D) further includes one or more peaks at approximately 6.3, 9.1, 11.2, 13.2, and 19.9 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0239] In some embodiments, the compound 11-hydroxy-2-naphthoate (form D) exhibits an XRPD containing the peaks shown in Table 41 below. TIFF0007911419000043.tif91170

[0240] In some embodiments, the compound 11-hydroxy-2-naphthoate (form D) exhibits an XRPD substantially similar to that shown in Figure 86.

[0241] Cyclamate In some embodiments, the disclosure provides a cyclamate of Compound 1 ("Compound 1 Cyclamate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Cyclamate.

[0242] In one embodiment, the disclosure provides compound 1-cyclamate (form A). In some embodiments, the compound 1-cyclamate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 6.6, 7.2, 18.5, 19.5, and 21.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-cyclamate (form A) further contains one or more peaks at approximately 14.3, 14.8, 17.2, 17.6, and 18.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0243] In some embodiments, the compound 1 cyclamate (form A) exhibits an XRPD containing the peaks shown in Table 42 below. TIFF0007911419000044.tif83170

[0244] In some embodiments, the compound 1 cyclamate (form A) exhibits an XRPD substantially similar to that shown in Figure 87.

[0245] In some embodiments, the compound 1 cyclamate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 60.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 cyclamate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 168.5°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 cyclamate (form A) exhibits a DSC thermogram substantially similar to that in Figure 88.

[0246] In some embodiments, compound 1-cyclamate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 88. In some embodiments, the TGA thermogram of compound 1-cyclamate (form A) shows a weight loss of 0.0 to 5.1% in a temperature range of 25 to 180°C.

[0247] In some embodiments, compound 1-cyclamate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 89. In some embodiments, compound 1-cyclamate (form A) exhibits gravimetric hygroscopic

[0248] Ethane-1,2-disulfonate In some embodiments, the disclosure provides ethane-1,2-disulfonate of compound 1 ("compound 1ethane-1,2-disulfonate"). In some embodiments, the disclosure provides the crystalline form of compound 1ethane-1,2-disulfonate.

[0249] In one embodiment, the present disclosure provides compound 1-ethane-1,2-disulfonate (Form A). In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 16.2, 16.5, 17.5, 20.7, and 21.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-ethane-1,2-disulfonate (form A) further includes one or more peaks at approximately 3.7, 5.5, 13.8, 14.7, and 26.0 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0250] In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits an XRPD containing the peaks shown in Table 43 below. TIFF0007911419000045.tif123170

[0251] In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits an XRPD substantially similar to that shown in Figure 90.

[0252] In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits a DSC thermogram containing an endothermic peak at approximately 59.0°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits a DSC thermogram containing an endothermic peak at approximately 154.8°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1-ethane-1,2-disulfonate (Form A) exhibits a DSC thermogram substantially similar to that in Figure 91.

[0253] In some embodiments, the compound 1-ethane-1,2-disulfonate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 91. In some embodiments, the TGA thermogram of the compound 1-ethane-1,2-disulfonate (form A) shows a weight loss of 0.0 to 0.7% in a temperature range of 25 to 120°C.

[0254] In some embodiments, the compound 1-ethane-1,2-disulfonate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 92. In some embodiments, the compound 1-ethane-1,2-disulfonate (form A) exhibits gravimetric hygroscopic

[0255] In one embodiment, the disclosure provides compound 1-ethane-1,2-disulfonate (Form B). In some embodiments, the compound 1-ethane-1,2-disulfonate (Form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.5, 16.4, 17.4, 17.6, and 20.7 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-ethane-1,2-disulfonate (form B) further includes one or more peaks at approximately 10.9, 13.7, 14.6, 21.2, and 22.1 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0256] In some embodiments, the compound 1-ethane-1,2-disulfonate (form B) exhibits an XRPD containing the peaks shown in Table 44 below. TIFF0007911419000046.tif130170

[0257] In some embodiments, the compound 1-ethane-1,2-disulfonate (form B) exhibits an XRPD substantially similar to that shown in Figure 93.

[0258] dichloroacetate In some embodiments, the disclosure provides the dichloroacetate of Compound 1 ("Compound 1 Dichloroacetate"). In some embodiments, the disclosure provides the crystalline form of Compound 1 Dichloroacetate.

[0259] In one embodiment, the disclosure provides compound 1-dichloroacetate (Form A). In some embodiments, the compound 1-dichloroacetate (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.4, 3.6, 16.2, 17.1, and 19.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1-dichloroacetate (Form A) further includes one or more peaks at approximately 8.1, 11.4, 12.8, 16.7, and 20.0 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0260] In some embodiments, the compound 1-dichloroacetate (form A) exhibits an XRPD containing the peaks shown in Table 45 below. TIFF0007911419000047.tif116170

[0261] In some embodiments, the compound 1-dichloroacetate (form A) exhibits an XRPD substantially similar to that shown in Figure 94.

[0262] In some embodiments, the compound 1-dichloroacetate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 117.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1-dichloroacetate (form A) exhibits a DSC thermogram substantially similar to that in Figure 95.

[0263] In some embodiments, the compound 1-dichloroacetate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 95. In some embodiments, the TGA thermogram of the compound 1-dichloroacetate (form A) shows a weight loss of 0.0 to 3.7% in a temperature range of 25 to 150°C.

[0264] In some embodiments, compound 1-dichloroacetate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 96. In some embodiments, compound 1-dichloroacetate (form A) exhibits gravimetric hygroscopic absorption of approximately 1.8% (by weight) at a relative humidity of 80%.

[0265] Malate In some embodiments, the Disclosure provides the D-malate of Compound 1 ("Compound 1 Malate"). In some embodiments, the Disclosure provides the malate of Compound 1 ("Compound 1 Malate"). In some embodiments, the Disclosure provides the L-malate of Compound 1 ("Compound 1 L-malate").

[0266] In some embodiments, this disclosure provides a crystalline form of compound 1-malate. In some embodiments, this disclosure provides a crystalline form of compound 1D-malate. In some embodiments, this disclosure provides a crystalline form of compound 1L-malate.

[0267] In one embodiment, the disclosure provides compound 1L-malate (Form A). In some embodiments, the compound 1L-malate (Form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.2, 12.5, 14.4, 15.7, and 18.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1L-malate (Form A) further includes one or more peaks at approximately 3.6, 6.1, 13.2, 18.9, and 21.1 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0268] In some embodiments, the compound 1L-malate (form A) exhibits an XRPD containing the peaks shown in Table 46 below. TIFF0007911419000048.tif221170

[0269] In some embodiments, the compound 1L-malate (form A) exhibits an XRPD substantially similar to that shown in Figure 97.

[0270] In some embodiments, the compound 1L-malate (Form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 120.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1L-malate (Form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 142.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1L-malate (Form A) exhibits a DSC thermogram substantially similar to that in Figure 98.

[0271] In some embodiments, the compound 1L-malate (form A) exhibits a TGA thermogram substantially similar to that in Figure 98. In some embodiments, the TGA thermogram of the compound 1L-malate (form A) exhibits a weight loss of 0.0 to 0.7% in a temperature range of 25 to 105°C.

[0272] In some embodiments, the compound 1L-malate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 99. In some embodiments, the compound 1L-malate (form A) exhibits gravimetric hygroscopic absorption of approximately 2.0% (by weight) at a relative humidity of 80%.

[0273] In one embodiment, the disclosure provides compound 1L-malate (form B). In some embodiments, the compound 1L-malate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.6, 13.4, 17.3, 20.8, and 23.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1L-malate (form B) further includes one or more peaks at approximately 3.7, 11.2, 14.4, 14.9, and 17.8 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0274] In some embodiments, the compound 1L-malate (form B) exhibits an XRPD containing the peaks shown in Table 47 below. TIFF0007911419000049.tif127170

[0275] In some embodiments, the compound 1L-malate (form B) exhibits an XRPD substantially similar to that shown in Figure 100.

[0276] In some embodiments, the compound 1L-malate (Form B) exhibits a DSC thermogram containing an endothermic peak at approximately 108.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1L-malate (Form B) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 143.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1L-malate (Form B) exhibits a DSC thermogram substantially similar to that in Figure 101.

[0277] In some embodiments, the compound 1L-malate (form B) exhibits a TGA thermogram substantially similar to that in Figure 101. In some embodiments, the TGA thermogram of the compound 1L-malate (form B) shows a weight loss of 0.0 to 1.2% in a temperature range of 25 to 120°C.

[0278] In some embodiments, the compound 1L-malate (form B) exhibits a DVS isotherm plot substantially similar to that in Figure 102. In some embodiments, the compound 1L-malate (form B) exhibits gravimetric hygroscopic

[0279] Hydrochloride In some embodiments, the disclosure provides a hydrochloride salt of Compound 1 ("Compound 1 Hydrochloride"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Hydrochloride.

[0280] In one embodiment, the disclosure provides compound 1 hydrochloride (form A). In some embodiments, the compound 1 hydrochloride (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.6, 5.2, 14.2, 17.4, and 17.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 hydrochloride (form A) further contains one or more peaks at approximately 12.8, 13.4, 14.9, 18.9, and 20.4 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0281] In some embodiments, the compound 1 hydrochloride (form A) exhibits an XRPD containing the peaks shown in Table 48 below. TIFF0007911419000050.tif122170

[0282] In some embodiments, the compound 1 hydrochloride (form A) exhibits an XRPD substantially similar to that shown in Figure 103.

[0283] In some embodiments, the compound 1 hydrochloride (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 225.0°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 hydrochloride (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 232.7°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 hydrochloride (form A) exhibits a DSC thermogram substantially similar to that in Figure 104.

[0284] In some embodiments, the compound 1 hydrochloride (form A) exhibits a TGA thermogram substantially similar to that in Figure 104. In some embodiments, the TGA thermogram of the compound 1 hydrochloride (form A) shows a weight loss of 0.0 to 1.2% in a temperature range of 25 to 150°C.

[0285] In some embodiments, the compound 1 hydrochloride (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 105. In some embodiments, the compound 1 hydrochloride (form A) exhibits gravimetric hygroscopic absorption of approximately 3.6% (by weight) at a relative humidity of 80%.

[0286] In one embodiment, the disclosure provides compound 1 hydrochloride (form B). In some embodiments, the compound 1 hydrochloride (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.3, 7.8, 15.4, 16.6, and 23.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 hydrochloride (form B) further includes one or more peaks at approximately 15.0, 18.8, 20.4, 23.5, and 26.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0287] In some embodiments, the compound 1 hydrochloride (form B) exhibits an XRPD containing the peaks shown in Table 49 below. TIFF0007911419000051.tif104170

[0288] In some embodiments, the compound 1 hydrochloride (form B) exhibits an XRPD substantially similar to that shown in Figure 106.

[0289] In some embodiments, the compound 1 hydrochloride (form B) exhibits a DSC thermogram with an endothermic peak at approximately 87.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 hydrochloride (form B) exhibits a DSC thermogram with a sharp endothermic peak at approximately 207.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 hydrochloride (form B) exhibits a DSC thermogram substantially similar to that in Figure 107.

[0290] In some embodiments, the compound 1 hydrochloride (form B) exhibits a TGA thermogram substantially similar to that in Figure 107. In some embodiments, the TGA thermogram of the compound 1 hydrochloride (form B) shows a weight loss of 0.0 to 0.7% in a temperature range of 25 to 120°C.

[0291] In some embodiments, Compound 1 hydrochloride (Form B) exhibits a DVS isotherm plot substantially similar to that in Figure 108. In some embodiments, Compound 1 hydrochloride (Form B) exhibits gravimetric hygroscopic

[0292] In one embodiment, the disclosure provides compound 1 hydrochloride (form C). In some embodiments, the compound 1 hydrochloride (form C) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 14.6, 16.5, 18.0, 21.5, and 21.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 hydrochloride (form C) further includes one or more peaks at approximately 3.6, 18.8, 19.9, 22.1, and 23.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0293] In some embodiments, the compound 1 hydrochloride (form C) exhibits an XRPD containing the peaks shown in Table 50 below. TIFF0007911419000052.tif122170

[0294] In some embodiments, the compound 1 hydrochloride (form C) exhibits an XRPD substantially similar to that shown in Figure 109.

[0295] In some embodiments, the compound 1 hydrochloride (form C) exhibits a DSC thermogram containing an endothermic peak at approximately 132.9°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (in particular, approximately ±2.0). In some embodiments, the compound 1 hydrochloride (form C) exhibits a DSC thermogram substantially similar to that in Figure 110.

[0296] In some embodiments, the compound 1 hydrochloride (form C) exhibits a TGA thermogram substantially similar to that in Figure 110. In some embodiments, the TGA thermogram of the compound 1 hydrochloride (form C) shows a weight loss of 0.0 to 3.8% in a temperature range of 25 to 120°C.

[0297] In some embodiments, compound 1 hydrochloride (form C) exhibits a DVS isotherm plot substantially similar to that in Figure 111. In some embodiments, compound 1 hydrochloride (form C) exhibits gravimetric hygroscopic hygroscopic hygroscopic 0.7% (by weight) at a relative humidity of 80%.

[0298] Napsylates In some embodiments, the disclosure provides napsylate of compound 1 ("compound 1 napsylate"). In some embodiments, the disclosure provides a crystalline form of compound 1 napsylate.

[0299] In one embodiment, the disclosure provides compound 1 napsylate (form A). In some embodiments, the compound 1 napsylate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 3.4, 9.5, 16.6, 17.0, and 17.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 napsylate (form A) further includes one or more peaks at approximately 8.3, 8.7, 19.8, 25.0, and 25.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05, or less (in particular, approximately ±0.2).

[0300] In some embodiments, the compound 1 napsylate (form A) exhibits an XRPD containing the peaks shown in Table 51 below. TIFF0007911419000053.tif68170

[0301] In some embodiments, the compound 1 napsylate (form A) exhibits an XRPD substantially similar to that shown in Figure 112.

[0302] In some embodiments, compound 1 napsylate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 100.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, compound 1 napsylate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 202.3°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, compound 1 napsylate exhibits a DSC thermogram substantially similar to that in Figure 113.

[0303] In some embodiments, compound 1 napsylate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 113. In some embodiments, the TGA thermogram of compound 1 napsylate (form A) shows a weight loss of 0.0 to 1.7% in a temperature range of 25 to 180°C.

[0304] In some embodiments, compound 1 napsylate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 114. In some embodiments, compound 1 napsylate (form A) exhibits gravimetric hygroscopic

[0305] In one embodiment, the disclosure provides compound 1 napsylate (form B). In some embodiments, the compound 1 napsylate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 9.1, 15.6, 16.1, 18.2, and 19.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 napsylate (form B) further contains one or more peaks at approximately 8.6, 12.9, 17.1, 25.8, and 26.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0306] In some embodiments, the compound 1 napsylate (form B) exhibits an XRPD containing the peaks shown in Table 52 below. TIFF0007911419000054.tif71170

[0307] In some embodiments, the compound 1 napsylate (form B) exhibits an XRPD substantially similar to that shown in Figure 115.

[0308] Oxalate In some embodiments, the disclosure provides an oxalate of Compound 1 ("Compound 1 Oxalate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Oxalate.

[0309] In one embodiment, the disclosure provides compound 1 oxalate (form A). In some embodiments, the compound 1 oxalate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 6.1, 18.2, 19.1, 19.8, and 24.3 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 oxalate (form A) further includes one or more peaks at approximately 12.1, 13.9, 21.1, 21.7, and 24.7 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0310] In some embodiments, the compound 1 oxalate (form A) exhibits an XRPD containing the peaks shown in Table 53 below. TIFF0007911419000055.tif133170

[0311] In some embodiments, the compound 1 oxalate (form A) exhibits an XRPD substantially similar to that shown in Figure 116.

[0312] In some embodiments, the compound 1 oxalate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 163.8°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 oxalate (form A) exhibits a DSC thermogram containing an endothermic peak (e.g., a sharp endothermic peak) at approximately 198.6°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1 oxalate exhibits a DSC thermogram substantially similar to that in Figure 117.

[0313] In some embodiments, the compound 1-oxalate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 117. In some embodiments, the TGA thermogram of the compound 1-oxalate (form A) shows a weight loss of 0.0 to 0.4% in a temperature range of 25 to 150°C.

[0314] In some embodiments, compound 1 oxalate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 118. In some embodiments, compound 1 oxalate (form A) exhibits gravimetric hygroscopic

[0315] In one embodiment, the disclosure provides compound 1 oxalate (form B). In some embodiments, the compound 1 oxalate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 6.0, 6.3, 18.2, 18.8, and 20.0 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 oxalate (form B) further includes one or more peaks at approximately 12.1, 12.5, 17.8, 20.7, and 23.5 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0316] In some embodiments, the compound 1 oxalate (form B) exhibits an XRPD containing the peaks shown in Table 54 below. TIFF0007911419000056.tif122170

[0317] In some embodiments, the compound 1 oxalate (form B) exhibits an XRPD substantially similar to that shown in Figure 119.

[0318] p-aminosalicylate In some embodiments, the disclosure provides a p-aminosalicylate of compound 1 ("compound 1p-aminosalicylate"). In some embodiments, the disclosure provides a crystalline form of compound 1p-aminosalicylate.

[0319] In one embodiment, the disclosure provides a compound 1p-aminosalicylate (form A). In some embodiments, the compound 1p-aminosalicylate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 5.4, 13.8, 15.7, 20.7, and 21.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1p-aminosalicylate (form A) further includes one or more peaks at approximately 12.5, 13.5, 15.3, 19.2, and 27.6 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0320] In some embodiments, the compound 1p-aminosalicylate (form A) exhibits an XRPD containing the peaks shown in Table 55 below. TIFF0007911419000057.tif142170

[0321] In some embodiments, the compound 1p-aminosalicylate (form A) exhibits an XRPD substantially similar to that shown in Figure 120.

[0322] In some embodiments, the compound 1p-aminosalicylate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 97.1°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1p-aminosalicylate (form A) exhibits a DSC thermogram containing an endothermic peak at approximately 146.8°C with an error of approximately ±2.5, approximately ±2.0, approximately ±1.5, approximately ±1.0, approximately ±0.5 or less (particularly approximately ±2.0). In some embodiments, the compound 1p-aminosalicylate (form A) exhibits a DSC thermogram substantially similar to that in Figure 121.

[0323] In some embodiments, the compound 1p-aminosalicylate (form A) exhibits a TGA thermogram substantially similar to that shown in Figure 121. In some embodiments, the TGA thermogram of the compound 1p-aminosalicylate (form A) shows a weight loss of 0.0–4.0% in the temperature range of 25–120°C.

[0324] In some embodiments, the compound 1p-aminosalicylate (form A) exhibits a DVS isotherm plot substantially similar to that in Figure 122. In some embodiments, the compound 1p-aminosalicylate (form A) exhibits gravimetric hygroscopic absorption of approximately 4.0% (by weight) at a relative humidity of 80%.

[0325] In one embodiment, the disclosure provides compound 1p-aminosalicylate (form B). In some embodiments, the compound 1p-aminosalicylate (form B) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 12.3, 15.2, 17.3, 19.9, and 22.9 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1p-aminosalicylate (form B) further includes one or more peaks at approximately 6.3, 12.5, 14.8, 16.4, and 20.7 degrees (2θ) with errors of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0326] In some embodiments, the compound 1p-aminosalicylate (form B) exhibits an XRPD containing the peaks shown in Table 56 below. TIFF0007911419000058.tif117170

[0327] In some embodiments, the compound 1p-aminosalicylate (form B) exhibits an XRPD substantially similar to that shown in Figure 123.

[0328] maleate In some embodiments, the disclosure provides a maleate of Compound 1 ("Compound 1 Maleate"). In some embodiments, the disclosure provides a crystalline form of Compound 1 Maleate.

[0329] In one embodiment, the disclosure provides compound 1 maleate (form A). In some embodiments, the compound 1 maleate (form A) exhibits an XRPD containing one or more peaks (in particular, three or more peaks) at approximately 6.4, 9.5, 11.2, 13.1, 15.0, and 17.6 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2). In some embodiments, the XRPD of the compound 1 maleate (form A) further contains one or more peaks at approximately 11.2, 12.6, 14.0, 16.7, and 19.2 degrees (2θ) with an error of approximately ±0.5, approximately ±0.4, approximately ±0.3, approximately ±0.2, approximately ±0.1, approximately ±0.05 or less (in particular, approximately ±0.2).

[0330] In some embodiments, the compound 1 maleate (form A) exhibits an XRPD containing the peaks shown in Table 57 below. TIFF0007911419000059.tif94170

[0331] In some embodiments, the compound 1 maleate (form A) exhibits an XRPD substantially similar to that shown in Figure 124.

[0332] Method for preparing a salt of compound 1 A salt of compound 1 (and its crystalline form) can be prepared, for example, by mixing the free base of compound 1 and an acid (such as hydrochloric acid) in a suitable solvent to provide the salt of compound 1 as a suspension in the suitable solvent. In some embodiments, the salt of compound 1 may be prepared by slow evaporation of a mixture of the free base of compound 1 and an acid, slow cooling, or by adding a poor solvent to the mixture.

[0333] In some embodiments, the present disclosure provides a method for preparing a crystalline form of a salt of compound 1. In some embodiments, the salt of compound 1 is suspended in a suitable solvent for a time sufficient to provide a suspension of the crystalline form of the salt of compound 1.

[0334] In some embodiments, a salt of compound 1 is dissolved in a suitable solvent to provide a solution, and the crystalline form of the salt of compound 1 precipitates from the solution. In some further embodiments, the salt of compound 1 is dissolved by heating a mixture of the salt of compound 1 and a suitable solvent. In some further embodiments, the crystalline form of the salt of compound 1 precipitates from the solution by cooling the solution. In yet another embodiment, the crystalline form of the salt of compound 1 precipitates from the solution by adding a poor solvent (i.e., a solvent that reduces the solubility of the crystalline form of the salt of compound 1) to the solution. In yet another embodiment, the crystalline form of the salt of compound 1 precipitates from the solution by evaporating a portion of the suitable solvent from the solution. In certain further embodiments, the suitable solvent includes water.

[0335] In some embodiments, a salt of compound 1 is heated to provide a molten form, and the molten form is cooled to provide a crystalline form of the salt of compound 1. In some embodiments, the salt of compound 1 is compressed for a sufficient pressure and time (e.g., 5 mPa for 5 minutes) to provide a crystalline form of the salt of compound 1. In some embodiments, the salt of compound 1 is ground (e.g., using a mortar and pestle or a mill) to provide a crystalline form of the salt of compound 1. In some further embodiments, the salt of compound 1 is ground in the presence of a suitable solvent to obtain a crystalline form of the salt of compound 1. In some embodiments, the salt of compound 1 is exposed to a sufficient time, relative humidity, and temperature (e.g., 45°C at 75% relative humidity) to provide a crystalline form of the salt of compound 1.

[0336] In some embodiments, the suitable solvent includes an aprotic solvent. In some embodiments, the aprotic solvent is dimethylformamide (DMF), dimethylacetamide (DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP), formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethyl sulfoxide, propionitrile, ethyl formate, methyl acetate, methyl methyl ketone (MEK), hexachloroacetone, acetone, ethyl methyl ketone, ethyl acetate, sulfolane, N,N-di The aprotic solvent comprises at least one selected from methylpropionamide, tetramethylurea, nitromethane, nitrobenzene, or hexamethylphosphoramide, diethoxymethane, tetrahydrofuran, toluene, 1,3-dioxane, 1,4-dioxane, furan, diethyl ether, tetrahydropyran, diisopropyl ether, dibutyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, and t-butyl methyl ether. In some embodiments, the aprotic solvent is acetone. In some embodiments, the aprotic solvent is ethyl acetate. In some embodiments, the aprotic solvent is acetonitrile.

[0337] In some embodiments, the suitable solvent includes a protic solvent. In some embodiments, the protic solvent includes at least one selected from water, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1-butanol, 2-butanol, i-butyl alcohol, t-butyl alcohol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neopentyl alcohol, t-pentyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, and glycerol. In some embodiments, the protic solvent includes a mixture of 2-propanol and water.

[0338] In some embodiments, the suitable solvent is a single solvent. In some embodiments, the solvent is a mixture of solvents. In some embodiments, the suitable solvent is a mixture of a protic solvent and an aprotic solvent.

[0339] In certain embodiments, the salts (or crystalline forms of the salts) of compound 1 are isolated after they have been prepared. The isolation of the salts (or crystalline forms of the salts) can be achieved using methods such as filtration, decantation, centrifugation, or other suitable separation techniques.

[0340] In certain embodiments, the isolated salt (or crystalline form of the salt) is optionally washed with a liquid such as a poor solvent, acetonitrile, methanol, ethanol, ethyl acetate, methyl ethyl ketone, acetone, tetrahydrofuran, or a combination thereof.

[0341] In certain embodiments, the salt of compound 1 prepared according to the embodiments described above is substantially pure. For example, in some embodiments, the chemical purity of the salt of compound 1 (e.g., compound 1 hydrochloride) may contain at least about 99.9%, about 99.8%, about 99.7%, about 99.6%, about 99.5%, about 99.4%, about 99.3%, about 99.2%, about 99.1%, about 99.0%, about 98%, about 97%, about 96%, or about 95% of the salt of compound 1. The chemical purity can be determined using methods known to those skilled in the art (e.g., HPLC chromatography using a suitable solvent and a column that detects a wavelength of 210 nm). In some embodiments, the substantial purity is determined on a weight percentage (%) basis. In some embodiments, the substantial purity is determined on a curve area basis.

[0342] In some embodiments, the salt of compound 1 prepared according to the embodiments described above is crystalline. In certain embodiments, the crystalline salt of compound 1 prepared according to the embodiments described above is substantially pure. For example, in some embodiments, the polymorphic purity of the crystalline salt of compound 1 (e.g., compound 1 hydrochloride) may include at least about 99.9%, about 99.8%, about 99.7%, about 99.6%, about 99.5%, about 99.4%, about 99.3%, about 99.2%, about 99.1%, about 99.0%, about 98%, about 97%, about 96%, about 95%, about 94%, about 93%, about 92%, about 91%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, or about 50% of the single-crystal form (e.g., compound 1 hydrochloride (form A)). Polymorphic purity may be determined using methods known to those skilled in the art (in particular, X-ray powder crystallography as described in "Shah, B., et al., Analytical techniques for quantification of amorphous / crystalline phases in pharmaceutical solids, J. Pharm. Sci. 2006, 95(8), pages 1641-1665," which is incorporated herein by reference in its entirety).

[0343] In some embodiments, the salt of compound 1 prepared according to the embodiments described above is epimerically concentrated at one or more positions compared to the epimer purity of the compound 1 free base starting material. For example, in some embodiments, the salt of compound 1 may contain the 17-β epimer:17α epimer of compound 1 in at least about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 13:1, about 14:1, about 15:1, or about 20:1. In some embodiments, the salt of compound 1 may contain the 3α-hydroxy:3β-hydroxy of compound 1 in at least about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 13:1, about 14:1, about 15:1, or about 20:1. In some embodiments, the epimer purity of the salt of compound 1 described herein is substantially the same as the epimer purity of the compound 1 free base starting material.

[0344] Pharmaceutical composition In one embodiment, the present disclosure provides a pharmaceutical composition comprising a salt of compound 1. In some embodiments, the salt of compound 1 is compound 1 hydrobromide, compound 1 citrate, compound 1 L-malate, compound 1 mesylate, compound 1 phosphate, compound 1 L(+)-tartrate, compound 1 hydrochloride, compound 1 tosylate, compound 1 glucuronate, or compound 1 ethanesulfonate. In some embodiments, the salt of compound 1 is compound 1 hydrobromide (form A). In some embodiments, the salt of compound 1 is compound 1 hydrobromide (form B). In some embodiments, the salt of compound 1 is compound 1 hydrobromide (form C). In some embodiments, the salt of compound 1 is compound 1 hydrobromide (form D). In some embodiments, the salt of compound 1 is compound 1 hydrobromide (form E). In some embodiments, the salt of compound 1 is compound 1 citrate (form A). In some embodiments, the salt of compound 1 is compound 1 citrate (form B). In some embodiments, the salt of compound 1 is compound 1 citrate (form C).

[0345] The composition may be administered by appropriate routes, including but not limited to oral, parenteral, rectal, topical, and local administration. The composition may be in liquid, semi-liquid, or solid form and may be formulated in a manner suitable for each route of administration using methods known to those skilled in the art.

[0346] Oral dosage forms include, for example, solid dosage forms (tablets, capsules, pills, granules, etc.) and liquid dosage forms (oral solutions, oral suspensions, syrups, etc.).

[0347] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a salt or solvate of compound 1 and a pharmaceutically acceptable excipient.

[0348] How to use In one embodiment, the present invention provides a method for treating a disease or condition in a subject requiring treatment, comprising administering a therapeutically effective amount of a salt of compound 1 to the subject.

[0349] In some embodiments, the disease or condition is depression. In some embodiments, the disease or condition is treatment-resistant depression. In some embodiments, the disease or condition is postpartum depression. In some embodiments, the disease or condition is major depressive disorder. In some embodiments, the disease or condition is bipolar disorder. In some embodiments, the disease or condition is epilepsy. In some embodiments, the disease or condition is anxiety disorder. [Examples]

[0350] The present invention will be further described with reference to the following embodiments. However, it should be noted that these embodiments, like the embodiments described above, are illustrative and should not be construed as limiting the scope of the present invention.

[0351] ",''" means ethyl acetate. "(m)DSC" means (modulated) differential scanning calorimetry. "ACN" means acetonitrile. "AR" means analytically pure. "DCM" means dichloromethane. "DMF" means dimethylformamide. "DMSO" means dimethyl sulfoxide. "DI" means distilled. "DSC" means differential scanning calorimetry. "DVS" means dynamic vapor adsorption. "eq" means equivalent. "EtOH" means ethyl alcohol. "FaSSIF" means simulated intestinal fluid in a fasted state. "FeSSIF" means simulated intestinal fluid in a fed state. "1H-NMR" means proton nuclear magnetic resonance. "IPA" means isopropanol. "IPAC" means isopropyl acetate. "IPE" means diisopropyl ether. "LC" means low crystallinity. "MEK" means methyl methyl ketone. "MeOH" means methyl alcohol. "MIBK" means methyl isobutyl ketone. "MTBE" means methyl t-butyl ether. "NMR" means nuclear magnetic resonance. "PLM" means polarizing microscope. "RH" means relative humidity. "RRT" means relative retention time. "RT" means room temperature. "RT(min)" means retention time. "SGF" means simulated gastric juice. "TGA" means thermogravimetric analysis. "THF" means tetrahydrofuran. "UPLC" means ultrafast liquid chromatography. "XRPD" means X-ray powder diffractometer.

[0352] In some cases, the compound 1:acid ratio in the salt of compound 1 described herein was determined by ion chromatography (IC) using the following method: 25 μL of a 10.0 μg / mL sample or standard was injected into a Dionex IonPac AG18 column at a flow rate of 1.0 mL / min and detected with a Thermo ICS-2100 conductivity detector. The ASRS-4mm suppressor was set to 38 mA and the column temperature was 30°C. Elution by chromatography was performed with 15 mM KOH, and the total run time was 20 minutes.

[0353] X-ray powder diffraction patterns were collected using a Rigaku D / Max-2200 / PC or Bruker D8 Advance powder diffractometer. Copper K-alpha X-rays (λ=1.54179Å) were irradiated onto the sample using a generator operating at 40kV / 40mA. The sample was scanned in continuous mode from 3° to 40°, with a sample rotation speed of 15rpm and a scan speed of 10° / min.

[0354] Single-crystal X-ray analysis: Single-crystal X-ray diffraction data was obtained using a Rigaku XtaLAB Synergy-R(Cu) diffractometer (Micro-Max007HF Cu mode, CuKa:λ=1.54184Å, Hypix6000HE detector).

[0355] The following SCXRD device parameters were used. TIFF0007911419000060.tif56170

[0356] Suitable single crystals with good diffraction quality were separated from block-shaped crystal samples and wrapped in Paraton N (an oil-based antifreeze). The crystals were mounted in random orientations in Mylar loops and immersed in a nitrogen stream at the temperatures specified in the following examples. Preliminary inspections and data acquisition were performed using a Rigaku XtaLAB Synergy R (copper Kα radiation, λ=1.54184Å) diffractometer, and the data was analyzed using the CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software package.

[0357] The structure was analyzed using the ShelXT (Sheldrick, GMActa Cryst.2015, A71,3-8) structural analysis program with the intrinsic phasing method, and the refinement package ShelXL (Version 2017 / 1; Sheldrick, GMActa Cryst.2015, C71,3-8) was used to analyze F included in OLEX2. 2 The matrix was refined using full matrix least squares (Dolomanov, OV, Bourhis, LJ, Gildea, RJ, Howard, JAK & Puschmann, HJ Appl. Cryst. 2009, 42, 339-341). All non-hydrogen atoms were anisotropically purified. The positions of hydrogen atoms bonded to carbon atoms were calculated geometrically and adjusted using a Riding model, while hydrogen atoms bonded to nitrogen and oxygen atoms were freely adjusted based on difference Fourier maps.

[0358] DSC data were collected using a TA Q2000. For each sample analyzed, approximately 1 mg of the sample was placed in a sealed aluminum pan with a pinhole and heated to 25°C to 250°C, with the temperature increased at a rate of 10°C / min.

[0359] TGA data were collected using a TA Q5000. For each sample analyzed, approximately 4 mg of the material was placed in an open platinum pan and heated to 30°C to 300°C or to <80% by weight at a rate of 10°C / min.

[0360] Dynamic vapor adsorption (DVS) was performed using the SMS DVS Advantage 1 system. For each sample analyzed, approximately 10 mg of material was transferred to the DVS instrument, and the weight change against atmospheric humidity at 25°C was recorded using the following parameters: equilibrium dm / dt: 0.01% / min (minimum: 10 min, maximum: 180 min), drying setting 0% RH for 120 minutes, RH(%) measurement step at 10%, and RH(%) measurement step range of 0-90-0%.

[0361] 1¹H-NMR was collected using a Bruker 400 MHz magnet. For each sample to be analyzed, approximately 6 mg of the material was dissolved in 0.6 mL of d6-DMSO and analyzed. As is known to those skilled in the art, 1 The relative ppm shift and integral values ​​of the 1H-NMR resonance can vary depending on various sample factors, including, for example, the water content in d6-DMSO and the ion concentration in the sample. Therefore, as reported in the following examples... 1 ¹H-NMR values ​​should not be considered characteristic of each salt and polymorph.

[0362] UPLC data was collected by injecting 0.5 μL of sample or standard material into a Waters Acquity UPLC Shield RP18 column at a flow rate of 0.8 mL / min using an Agilent 1290 UPLC (detection wavelength: 210 nm). The column was equilibrated with mobile phase A containing 0.1% H3PO4 aqueous solution. Mobile phase B was acetonitrile (ACN). Elution by chromatography was programmed as follows, with an additional minute for re-equilibrium, for a total execution time of 6 minutes. TIFF0007911419000061.tif32170

[0363] The crystalline salts described herein were characterized by polarized light microscopy. In some embodiments, the crystalline salts described herein exhibit birefringence, which indicates the degree of crystallinity.

[0364] Example 1: Preparation of hydrobromide of compound 1 The hydrobromide salt of compound 1 can be prepared from compound 1 using the following exemplary method.

[0365] Compound 1HBr salt (form A): Compound 1 (1.2 kg) was added to ethanol (2.84 kg, 9% (w / w) water). Ethanol (0.95 kg, 9% (w / w) water) was added, and the mixture was heated to an internal temperature of 55-65°C while stirring until a solution was obtained. The obtained solution was passed through a 10 μm filter and cooled to an internal temperature of less than 30°C. A solution consisting of 48% (w / w) HBr aqueous solution (523 g) and acetone (940 g) was stirred for 1 hour while maintaining a temperature of less than 30°C. Acetone (8.47 kg) was added, and the resulting slurry was cooled to 0-5°C and stirred for 1 hour. The solid was collected by filtration and washed with acetone (1.88 kg). The obtained solid was dried under vacuum at 50°C to obtain the HBr salt of compound 1 (1.17 kg, yield 82%).

[0366] The obtained solid is compound 1HBr salt (form A). As determined by ion chromatography, the ratio of compound 1:HBr in compound 1HBr salt (form A) is 1:1.02. XPRD is shown in Figure 2, DSC and TGA are shown in Figure 3, and DVS is shown in Figure 4.

[0367] Compound 1HBr salt (form B):

[0368] 1 g of compound 1HBr salt (form A) was suspended in 20 mL of a water activity 0.603 solution (14.5% water (v / v) in acetone) to prepare a 50 mg / mL suspension. The suspension was stirred at 700 rpm and held at 50°C for 26 hours. The suspension was centrifuged and the precipitate was collected. The resulting wet product was vacuum-dried at 30°C for 3 days to obtain a powder in 70.82% yield. The compound 1:HBr ratio in compound 1HBr salt (form B) is 1:1.01, as determined by ion chromatography. XPRD is shown in Figure 5, DSC and TGA are shown in Figure 6, and DVS is shown in Figure 7.

[0369] Compound 1HBr salt (form C):

[0370] 500 mg of compound 1HBr salt (form A) was dissolved in 4.5 mL of DMSO to prepare a clear solution, and then 31.5 mL of water (poor solvent) was added to the DMSO solution. The solution was left at room temperature for 7 days. The precipitated substance was then isolated. The resulting wet product was vacuum-dried at 30°C for 3 days to obtain a powder in 66.1% yield. As determined by ion chromatography, the compound 1:HBr ratio in compound 1HBr salt (form C) is 1:1.09. XPRD is shown in Figure 8, DSC and TGA are shown in Figure 9, and DVS is shown in Figure 10.

[0371] Compound 1HBr salt (form D):

[0372] When morphology B is heated to 160°C, morphology D is observed by VT-XRPD. The XRPD is shown in Figure 11, and the TGA and DSC are shown in Figure 12.

[0373] Compound 1HBr salt (form E):

[0374] Compound 1 (1.00 g, 1.0 equivalent) was stirred in EtOH (5 mL) in a 20 mL vial with a stirring bar at 60°C for 30 minutes. HBr (48% (w / w) in water, 0.3 mL, 1.1 equivalents) was added to the mixture and stirred at 60°C for 1 hour. The reaction mixture was cooled to 25°C, ethyl acetate (5 mL) was added to the reaction mixture and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes, then filtered, the solid was collected, and vacuum-dried overnight at 25°C to obtain Compound 1HBr (876 mg, yield 73.7%). The XRPD is shown in Figure 13, and the DSC and TGA are shown in Figure 14.

[0375] General procedure for preparing compound 1HBr

[0376] The following general procedure was followed to prepare compound 1HBr.

[0377] General procedure 1

[0378] Compound 1 (1.00 g, 1.0 equivalent) was stirred in a 20 mL vial with a stirring bar in solvent (15 mL, 15 mL / g (compound 1)) at 60°C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 equivalents) was added to the reaction and stirred at 60°C for 1 hour. The reaction mixture was cooled to 25°C and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes (procedures 1 and 2 were kept at 25°C), then filtered, the solid was collected, and the mixture was vacuum-dried overnight at 25°C to obtain compound 1 HBr.

[0379] General procedure 2

[0380] Compound 1 (1.00 g, 1.0 equivalent) was stirred in solvent (3.5 mL, 3.5 mL / g (compound 1)) in a 20 mL vial with a stirring rod at 60°C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 equivalents) in acetone (3.5 mL, 3.5 mL / g (compound 1)) was added to the reaction and stirred at 60°C for 1 hour. The reaction mixture was cooled to 25°C and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes, then filtered, the solid was collected, and the mixture was vacuum-dried overnight at 25°C to obtain compound 1 HBr.

[0381] General procedure 3

[0382] Compound 1 (1.00 g, 1.0 equivalent) was stirred in EtOH (5 mL, 5 mL / g (compound 1)) in a 20 mL vial with a stirring bar at 60°C for 30 minutes. HBr (48% (w / w) in water, 0.3 mL, 1.1 equivalents) was added to the mixture and stirred at 60°C for 1 hour. The reaction mixture was cooled to 25°C, and then the poor solvent (5 mL, 5 mL / g (compound 1)) was added to the reaction mixture and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes, then filtered, the solid was collected, and vacuum-dried overnight at 25°C to obtain the compound 1 HBr salt.

[0383] The following table summarizes the preparation of compound 1HBr salts using these general procedures. TIFF0007911419000062.tif210170

[0384] Chemical and physical stability testing

[0385] For each salt, approximately 5 mg of the compound was added to an 8 mL glass vial with a multi-hole aluminum foil cap and kept at 60°C and 40°C / 75% RH for one week. In the photostability test, the compounds in the capless vials were kept in a photostability chamber and exposed to a total illumination of 1.2 million lux hours, while the samples in the aluminum foil-covered vials were treated as a dark-temperature control. After recording visual observations, the purity of the residual solids was evaluated and XPRD data was collected.

[0386] The results of chemical and physical stability tests for compound 1HBr salt (form A), compound 1HBr salt (form B), compound 1HBr salt (form C), and compound 1 free base are shown in the table below. TIFF0007911419000063.tif119170

[0387] Solubility tests in simulated gastric fluid and intestinal fluid. For each salt, approximately 4-6 mg of compound 1 or its salt was added in a triple 2 mL vial. Next, 1 mL of bio-related medium (SGF, FaSSIF, or FeSSIF) was added to each vial. All vials were placed in a thermomixer and kept at 37°C while shaking at 700 rpm. If the compound was completely dissolved in the medium, additional compound was added until the culture system became a suspension. If the compound concentration exceeded 25 mg / mL, no additional material was added. After shaking at 37°C for 24 hours, 300 μL suspension was isolated from each culture system and analyzed. The samples were centrifuged at 12000 rpm for 5 minutes, diluted 10-fold with ACN:H2O (4 / 1, V / V), and the supernatant was analyzed by UPLC. The final pH value of the bio-related medium was measured and recorded. The following table shows the solubility (mg / mL) results for compound 1HBr salt (form A), compound 1HBr salt (form B), compound 1HBr salt (form C), and compound 1 free base in biologically relevant solutions. TIFF0007911419000064.tif61170

[0388] Single-crystal X-ray analysis of compound 1HBr salt (form B)

[0389] Block-shaped single crystals of the hydrobromide salt (form B) of compound 1, which was used for characterizing SCXRD, were crystallized by slow evaporation from a MeOH / MEK (1:3, v / v) solvent mixture.

[0390] PLM and XRPD characterization of the salt indicated that the single crystal is compound 1HBr salt (form B).

[0391] Using CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software, cell parameters and direction matrices for data acquisition were obtained and adjusted (by least squares method) using 45,416 reflection setting angles in the range of 3.488° < θ < 75.836°. Data was acquired up to a minimum diffraction angle (θ) of 3.506° and a maximum diffraction angle (θ) of 68.243° at 120.00K. The final integrity is 100%. The mean I / σ of the data was 91.7, and the maximum resolution achieved was 0.83 Å.

[0392] The SCXRD data obtained by the method described herein are shown in the table below. TIFF0007911419000065.tif87170

[0393] Single-crystal X-ray analysis of compound 1HBr salt (form E)

[0394] Block-shaped single crystals of compound 1 hydrobromide (form E), used for SCXRD characterization, were crystallized from a MeOH / MEK (1:3, v / v) solvent mixture by slow evaporation. Characterization of the salt by PLM and XRPD showed that the crystals were compound 1HBr salt (form E).

[0395] Data acquisition at 120K: Using CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software, cell parameters and direction matrices for data acquisition were obtained and adjusted (adjusted by least squares method) using 10,196 set reflection angles in the range of 3.499° < θ < 75.657°. Data was acquired up to a minimum diffraction angle (θ) of 3.508° and a maximum diffraction angle (θ) of 66.553° at 120.00(10)K. The final integrity is 100%. The mean I / σ of the data was 19.3, and the maximum resolution achieved was 0.84 Å.

[0396] Data acquisition at room temperature: Using CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software, cell parameters and direction matrices for data acquisition were obtained and adjusted (adjusted by least squares method) using 17551 set reflection angles in the range of 3.483° < θ < 75.825°. Data were acquired up to a minimum diffraction angle (θ) of 3.496° and a maximum diffraction angle (θ) of 66.597° at room temperature. The final integrity was 99.8%. The mean I / σ of the data was 40.0, and the maximum resolution achieved was 0.84 Å.

[0397] The SCXRD data obtained by the method described herein are shown in the table below. TIFF0007911419000066.tif85170

[0398] Example 2: Preparation of citrate of compound 1 The citrate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0399] Compound 1 citrate (form A):

[0400] Compound 1 (1 kg) was added to a mixture of ethanol (2.37 kg, 9% (w / w) water) and isopropyl acetate (2.61 kg). Additional ethanol (0.39 kg, 9% (w / w) water) and isopropyl acetate (0.44 kg) were added. The resulting mixture was heated to 55-65°C with stirring until a solution was obtained. The resulting solution was passed through a 10 μm filter. A solution of citric acid monohydrate (541 g) in ethanol (0.79 kg, 9% (w / w) water) and isopropyl acetate (0.87 kg) was added with stirring. The transfer of citric acid to the reactor was quantified using additional ethanol (0.39 kg) and isopropyl acetate (0.44 kg). The resulting mixture was cooled to 0-5°C for 1 hour while stirring, the resulting solid was collected by filtration, washed with isopropyl acetate (1.29 kg), and dried under vacuum at 50°C to obtain compound 1 citrate (1.174 kg, yield 81%).

[0401] The obtained solid was compound 1 citrate (form A). The ratio of compound 1 to citrate in compound 1 citrate (form A) was 1:1.02, as measured by HPLC. The XPRD is shown in Figure 15, the DSC and TGA are shown in Figure 16, and the DVS is shown in Figure 17.

[0402] Compound 1 citrate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6):δ 0.48-0.88(m,7H)2.03-2.22(m,2H)2.46-2.86(m,28H)3.00-3.17(m,3H) 3.19-3.46(m,5H)4.74-5.35(m,2H)7.09(s,1H)7.19(s,1H)7.86(s,1H).

[0403] Compound 1 citrate (form B):

[0404] 500 mg of Compound 1 citrate (Form A) was dissolved in 4.0 mL of a solution with a water activity of 0.901 (65% water (v / v) in acetone) to form a suspension of 125 mg / mL. The suspension was stirred at 300 rpm and held at 50 °C for 3 days. The suspension was centrifuged and the precipitate was collected. The wet crude product was vacuum dried at 30 °C for 1 day to obtain a powder with a yield of 56.9%. As determined by ion chromatography, the ratio of Compound 1:citric acid in Compound 1 citrate (Form B) is 1:1.17. XPRD is shown in Figure 18, DSC and TGA are shown in Figure 19, and DVS is shown in Figure 20.

[0405] Compound 1 citrate (Form B) was analyzed by 1 1H-NMR in deuterated DMSO, and the following chemical shifts were observed: 1 1H NMR (400 MHz, DMSO-d6): δ 0.53 - 0.79 (m, 7H) 0.85 - 1.76 (m, 24H) 1.99 - 2.14 (m, 3H) 2.32 - 2.35 (m, 1H) 2.61 - 2.74 (m, 6H) 3.00 - 3.09 (m, 2H) 4.89 - 5.13 (m, 1H) 6.99 (s, 1H) 7.11 (s, 1H) 7.74 (s, 1H).

[0406] Compound 1 citrate (Form C):

[0407] A sample of Compound 1 citrate (Form A) was stirred as a suspension in acetonitrile at 50 °C. The resulting solid was isolated by filtration.

[0408] General procedure for preparing Compound 1 citrate

[0409] To prepare Compound 1 citrate, the following general procedure was carried out.

[0410] General procedure A

[0411] The compound (1.00 g, 1.0 equivalent) and solvent or co-solvent were placed in a 20 mL vial equipped with a stirring bar. The resulting mixture was heated at 60°C for 30 minutes. To the mixture, citric acid monohydrate (0.54 g, 1.1 equivalents) was added at 60°C in the solvent or co-solvent (preheated and dissolved), and the mixture was stirred for 1 hour. The reaction mixture was cooled to 25°C and stirred overnight. The suspension was filtered, and the wet cake was washed with acetone. The solid was collected and vacuum-dried overnight at 25°C to obtain compound 1 citrate.

[0412] General procedure A-2

[0413] In a 20 mL vial equipped with a stirring rod, the compound (1.00 g, 1.0 equivalent) and co-solvent (10 mL, 10 mL / g (compound 1)) were placed. The resulting mixture was heated at 60°C for 30 minutes. To the mixture, citric acid monohydrate (0.54 g, 1.1 equivalents) was added at 60°C in co-solvent (2 mL, 2 mL / g (compound 1)) (preheated to dissolve), and the mixture was stirred for 1 hour. The reaction mixture was cooled to 0°C (no ppt). The mixture was dried under vacuum, and co-solvent (3 mL, 3 mL / g (compound 1)) was added at 60°C. The reaction mixture was cooled to 25°C and stirred overnight. The suspension was filtered, and the wet cake was washed with acetone. The solid was collected and vacuum-dried overnight at 25°C to obtain compound 1 citrate.

[0414] General Procedure B

[0415] In a 20 mL vial equipped with a stirring rod, compound (1.00 g, 1.0 equivalent) and EtOH (3.5 mL, 3.5 mL / g (compound 1)) were placed. The resulting mixture was heated at 60°C for 30 minutes. To the mixture, citric acid monohydrate (0.54 g, 1.1 equivalents) was added at 60°C in EtOH (1.5 mL, 1.5 mL / g (compound 1)) (preheated and dissolved), and the mixture was stirred for 1 hour. The reaction mixture was cooled to 25°C, and poor solvent (5 mL, 5 mL / g (compound 1)) was added at 25°C. The reaction mixture was cooled to 0°C and stirred for 1 hour. The mixture was stirred overnight at 25°C. The reaction mixture was cooled to 0°C and then stirred for 1 hour. The suspension was filtered, and the wet cake was washed with acetone. The solid was collected and vacuum-dried overnight at 25°C to obtain compound 1 citrate.

[0416] General Procedure C

[0417] Compound 1 (5.00 g, 1.0 equivalent) and EtOH / IPAc (1:1, 40 mL, 8 mL / g (compound 1)) were placed in a 250 mL four-necked flask equipped with a mechanical stirrer (5.5 cm stirring blade, 100 rpm), a thermometer, and a nitrogen (N2) inlet. The resulting mixture was heated to 60°C for 30 minutes. To the mixture, citric acid monohydrate (2.73 g, 1.1 equivalents) was added at 60°C in EtOH / IPAc (1:1, 10 mL, 2 mL / g (compound 1)) (preheated and dissolved), and the mixture was stirred for 1 hour. The reaction mixture was cooled to 25°C and then stirred for 1 hour. The reaction mixture was cooled to 0°C and then stirred for 30 minutes. The suspension was filtered, and the wet cake was washed with acetone. The solid was collected and vacuum-dried overnight at 50°C to obtain compound 1 citrate.

[0418] The following table summarizes the preparation of compound 1 citrate using these general procedures. TIFF0007911419000067.tif135170

[0419] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 citrate (Form A), Compound 1 citrate (Form B), and Compound 1 free base are shown in the table below. TIFF0007911419000068.tif110170

[0420] ICH stability test of compound 1 citrate (form A) The stability of compound 1 citrate (form A) was tested according to ICH guidelines for accelerated stability studies. The results of the accelerated stability study are shown in the table below. At 3 months, the data indicate that the assay, purity, and polymorphic stability of compound 1 citrate (form A) are maintained. TIFF0007911419000069.tif72170

[0421] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 citrate (form A), Compound 1 citrate (form B), and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000070.tif55170

[0422] Single-crystal X-ray structure of compound 1 citrate (form A)

[0423] The block-shaped single-crystal sample compound 1 citrate (form A), used for SCXRD characterization, was crystallized from THF solvent by slow evaporation.

[0424] Characterization of the salt by PLM and XRPD indicated that the crystals were compound 1 citrate (form A).

[0425] Using CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software, cell parameters and direction matrices for data acquisition were obtained and adjusted (by least squares method) using 64,393 set reflection angles in the range of 3.7580° < θ < 75.8720°. Data was acquired up to a minimum diffraction angle (θ) of 3.785° and a maximum diffraction angle (θ) of 66.597° at 120.00K. The final integrity was 99.3%. The mean I / σ of the data was 81.3, and the maximum resolution achieved was 0.84 Å.

[0426] The SCXRD data obtained by the method described herein are shown in the table below. TIFF0007911419000071.tif94170

[0427] Example 3: Preparation of the mesylate of Compound 1 The mesylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0428] Compound 1 mesylate (form A): 200 mg of compound 1 was dissolved in 10.0 mL of ethyl acetate at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. Subsequently, 1.1 equivalents of methanesulfonic acid in ethyl acetate (1.027 mL, 0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ethyl acetate. The resulting wet product was vacuum-dried at 35°C for 22 hours to obtain 234.52 mg of powder in 94.5% yield.

[0429] The obtained solid is compound 1 mesylate (form A). The ratio of methanesulfonic acid in compound 1 mesylate (form A) is 1:1.08, as determined by ion chromatography. XPRD is shown in Figure 22, DSC and TGA are shown in Figure 23, and DVS is shown in Figure 24.

[0430] Compound 1 mesylate (form A) is prepared with deuterated DMSO. 1Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6): δ 0.54-0.81(m,7H)0.84(t,J=7.44 Hz,1H)1.84-2.17(m,3H)2.31(s,3H)2.41-2.59(m,20H)2.65-2.83(m,1H)3.05(s,2H)3.22-3.48(m,1H)3.23 -3.51(m,6H)4.96-5.52(m,1H)4.96-5.52(m,1H)7.62(s,1H)7.55-7.64(m,1H)7.62-7.77(m,1H)9.01(s,1H).

[0431] Compound 1 mesylate (form B): 200 mg of compound 1 was dissolved in 10.0 mL of ethyl acetate at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. Subsequently, 1.1 equivalents of methanesulfonic acid in ethyl acetate (1.027 mL, 0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ethyl acetate. The resulting wet product was vacuum-dried at 35°C for 22 hours to obtain 234.52 mg of powder in 94.1% yield.

[0432] The obtained solid is compound 1 mesylate (form B). The XPRD is shown in Figure 25A.

[0433] Compound 1 mesylate (form C): Compound 1 mesylate (form C) was prepared using ACN solvent and methanesulfonic acid. For the liquid counterion, 50 mg of Compound 1 was weighed into a 2 mL vial, followed by the addition of 743 μL of solvent to the vial. Then, 1.1 equivalents of the corresponding solvent counterion solution (257 μL, concentration: 0.5 mol / L) was added to the vial. The vial was placed on a thermomix with a stirring rod and heated to 50°C. After maintaining the temperature at 50°C with stirring at 900 rpm for 18 hours, the vial was cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried overnight in a vacuum oven at 30°C.

[0434] The obtained solid is compound 1 mesylate (form C). The XPRD is shown in Figure 25B.

[0435] Compound 1 mesylate (form D):

[0436] Approximately 5 mg of compound 1-mesylate (form A) was added to an 8 mL glass vial with an aluminum foil cap containing multiple holes and kept at 60°C and 40°C / 75% RH for one week. After visual observation of the appearance, the purity of the residual solids was evaluated and XPRD data was collected. The obtained solid was compound 1-mesylate (form D). The dried solid was characterized by PLM and XRPD.

[0437] XPRD is shown in Figure 26.

[0438] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 mesylate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000072.tif78170

[0439] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 mesylate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000073.tif47170 Example 4: Preparation of phosphate of compound 1

[0440] The phosphate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0441] 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of phosphoric acid in acetone (1.027 mL, 0.5 mol / L) were added to the compound 1 solution, and the mixture was incubated at 60°C for 3 hours. Then, it was cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 30°C for 42 hours to obtain 233.51 mg of powder in a yield of 93.3%.

[0442] The obtained solid is compound 1 phosphate (form A). The ratio of phosphate in compound 1 to compound 1 phosphate (form A) is 1:0.9, as determined by ion chromatography. XPRD is shown in Figure 27, DSC and TGA are shown in Figure 28, and DVS is shown in Figure 29.

[0443] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 phosphate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000074.tif76170

[0444] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 phosphate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000075.tif46170 Example 5: Preparation of L(+)-tartrate of compound 1

[0445] The L(+)-tartrate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0446] Compound 1L(+)-tartrate (Form A): 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of L(+)-tartaric acid powder (77 mg, 0.5 mmol) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 30°C for 42 hours to obtain 237.95 mg of powder in 85.9% yield.

[0447] The obtained solid is compound 1L(+)-tartrate (form A). The ratio of tartaric acid in compound 1 to compound 1L(+)-tartrate (form A) is 1:1.15, as determined by ion chromatography. XPRD is shown in Figure 30, DSC and TGA are shown in Figure 31, and DVS is shown in Figure 32.

[0448] Compound 1L (+)-tartrate (form A) was prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6):δ 0.49-0.84(m,7H)0.90-1.75(m,21H)1.94-2.21(m,3H)2.35-2.58(m,14H)2.66-2.80(m,1H)3.10 (s,2H)3.23-3.34(m,3H)4.24-4.39(m,2H)4.80-5.19(m,2H)6.98(s,1H)7.12(s,1H)7.67(s,1H).

[0449] Compound 1L(+)-tartrate (Form B): 200 mg of compound 1 was dissolved in 10.0 mL of ethyl acetate at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. Subsequently, 1.1 equivalents of L(+)-tartaric acid powder (77 mg, 0.5 mmol) were added to the RX-0001175 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ethyl acetate. The resulting wet product was vacuum-dried at 35°C for 22 hours to obtain 254.08 mg of powder in 91.7% yield.

[0450] The obtained solid is compound 1L(+)-tartrate (form B). The ratio of tartaric acid in compound 1 to compound 1L(+)-tartrate (form B) is 1:1.19, as determined by ion chromatography. XPRD is shown in Figure 33, DSC and TGA are shown in Figure 34, and DVS is shown in Figure 35.

[0451] Compound 1L (+)-tartrate (form B) was prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6):δ 0.50-0.82(m,6H)1.91-2.22(m,2H)3.03(s,2H)3.24(s,2H)3.14-3.53(m,1H)4.27(s,2H)4.54-5.21(m,2H)6.71-7.18(m,2H)7.59(s,1H).

[0452] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for compound 1L(+)-tartrate (form A), compound 1L(+)-tartrate (form B), and compound 1 free base are shown in the table below. TIFF0007911419000076.tif111170

[0453] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1L(+)-tartrate (Form A), Compound 1L(+)-tartrate (Form B), and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000077.tif56170

[0454] Example 6: Preparation of fumarate of compound 1 The fumarate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0455] Compound 1 fumarate (form A): 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. 1.1 equivalents of fumaric acid powder (60 mg, 0.51 mmol) were added to compound 1, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. Subsequently, twice the volume of heptane was added to the acetone mixture to produce a suspension. This suspension was centrifuged, the precipitate was collected, and then vacuum-dried at 25°C for 42 hours to obtain 75.58 mg of powder in a yield of 29.1%.

[0456] The obtained solid is compound 1 fumarate (form A). The ratio of compound 1 to fumaric acid in compound 1 fumarate (form A) is 1:1.37, as determined by ion chromatography. The XPRD is shown in Figure 36, and the DSC and TGA are shown in Figure 37.

[0457] Compound 1 fumarate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6):δ 0.45-0.80(m,7H)1.97-2.13(m,3H)2.47-2.58(m,12H)2.63-2.78(m,1H)2.63-2.78(m,1H)3.04(s,2H) 3.25(s,3H)4.80-5.14(m,1H)4.80-5.14(m,1H)6.63(s,3H)6.91(s,1H)7.05(s,1H)7.52-7.69(m,1H).

[0458] Compound 1 fumarate (form B): 200 mg of compound 1 was dissolved in 10.0 mL of ethyl acetate at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. 1.1 equivalents of fumaric acid powder (60 mg, 0.51 mmol) were added to the solution of compound 1. The solution was held at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. During the cooling process, the clear solution became a suspension. This suspension was then centrifuged, the precipitate was collected, and the mixture was vacuum-dried at 35°C for 22 hours to obtain 156.78 mg of powder in a yield of 60.4%.

[0459] The obtained solid is compound 1 fumarate (form B). The ratio of compound 1 to fumaric acid in compound 1 fumarate (form B) is 1:1.55, as determined by ion chromatography. XPRD is shown in Figure 38, DSC and TGA are shown in Figure 39, and DVS is shown in Figure 40.

[0460] 1 H NMR (400MHz, DMSO-d6):δ 0.43-0.79(m,8H)1.88-2.13(m,2H)3.03(s,2H)3.10-3.39(m,4H)4.38- 5.21(m,3H)6.61(s,2H)6.59-6.64(m,1H)6.74-7.16(m,2H)7.56(s,1H).

[0461] Compound 1 fumarate (form C): 50 mg of compound 1 and 1.1 equivalents of solid fumarate counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of solvent ACN to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 48 hours.

[0462] The obtained solid was compound 1 fumarate (form C). The dried solid was characterized using PLM and XRPD.

[0463] XPRD is shown in Figure 41.

[0464] Compound 1 fumarate (form D): Approximately 5 mg of compound 1 fumarate (form A) was added to an 8 mL glass vial with an aluminum foil cap containing multiple holes and kept at 60°C and 40°C / 75% RH for one week. After visual inspection and recording, the purity of the residual solids was evaluated and XPRD data was collected. The obtained solid was compound 1 fumarate (form D). The dried solid was characterized by PLM and XRPD. The XPRD is shown in Figure 42.

[0465] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 fumarate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000078.tif78170

[0466] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 fumarate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000079.tif41170

[0467] Example 7: Preparation of tosylate of compound 1 The tosylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0468] Compound 1 tosylate (form A): 200 mg of compound 1 was dissolved in 10.0 mL of ACN at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. Subsequently, 1.1 equivalents of p-toluenesulfonic acid in 1.027 mL of ACN (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ACN. The resulting wet product was vacuum-dried at 35°C for 22 hours to obtain 141.85 mg of powder in a yield of 49.2%.

[0469] The obtained solid is compound 1 tosylate (form A). The ratio of compound 1 to toluenesulfonic acid in compound 1 tosylate (form A) is 1:1.09, as determined by ion chromatography. XPRD is shown in Figure 43, DSC and TGA are shown in Figure 44, and DVS is shown in Figure 45.

[0470] Compound 1 tosylate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6):δ 0.50-0.79(m,7H)1.98-2.15(m,3H)2.28(s,4H)2.49(s,23H)2.60-2.7 6(m,1H)3.03(s,2H)3.21-3.34(m,5H)4.85-5.45(m,2H)7.10(d,J=7.78 Hz,2H)7.45(s,1H)7.46-7.73(m,3H)8.99(s,1H).

[0471] Compound 1 tosylate (form B): 50 mg of compound 1 and 1.1 equivalents of solid p-toluenesulfonic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of ÃO solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried overnight in a vacuum oven at 30°C.

[0472] The obtained solid is compound 1 tosylate (form B). The XPRD is shown in Figure 46.

[0473] Compound 1 tosylate (form C): Approximately 5 mg of compound 1 tosylate (form A) was added to an 8 mL glass vial with an aluminum foil cap containing multiple holes and kept at 60°C and 40°C / 75% RH for one week. After visual inspection and recording, the purity of the residual solids was evaluated and XPRD data was collected. The obtained solid was compound 1 tosylate (form C). The dried solid was characterized using PLM and XRPD.

[0474] The obtained solid is compound 1 tosylate (form C). The XPRD is shown in Figure 47.

[0475] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 tosylate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000080.tif77170

[0476] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 tosylate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000081.tif45170

[0477] Example 8: Preparation of glucuronide of compound 1 The glucuronide of compound 1 can be prepared from compound 1 using the following exemplary method.

[0478] Compound 1 glucuronide (form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of D-glucuronic acid solid (248.62 mg) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 739.32 mg of powder in 98.76% yield.

[0479] The obtained solid is compound 1 glucuronate (form A). The ratio of glucuronic acid in compound 1 to compound 1 glucuronate (form A) is 1:1.09, as determined by ion chromatography. XPRD is shown in Figure 48, DSC and TGA are shown in Figure 49, and DVS is shown in Figure 50.

[0480] Compound 1 glucuronate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.49-0.81(m,7H)0.83-1.73(m,22H)1.98-2.13(m,2H)2.68(br t,J=8.76 Hz,1H)2.90-3.08(m,3H)3.10-3.20(m,2H)3.57(d,J=9.76 Hz,1H)3.95-4.14(m,2H)4.33(d,J=7.75 Hz,1H)4.78-5.11(m,4H)6.51(brs,1H)6.88(s,1H)7.03(s,1H)7.54(s,1H).

[0481] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 glucuronate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000082.tif75170

[0482] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 glucuronate (form A), Compound 1 glucuronate (form A), and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000083.tif40170 Compound 1 Glucuronate (Form B)

[0483] 50 mg of compound 1 and 1.1 equivalents of solid D-glucuronic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  / ACN solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0484] The dried solids were characterized using PLM and XRPD (Figure 51).

[0485] Example 9: Preparation of ethanesulfonate of compound 1 The ethanesulfonate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0486] 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of ethanesulfonic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 546.88 mg of powder in 84.68% yield.

[0487] The obtained solid is compound 1 ethanesulfonate (form A). The ratio of compound 1 to ethanesulfonic acid in compound 1 ethanesulfonate (form A) is 1:1.17, as determined by ion chromatography. XPRD is shown in Figure 52, DSC and TGA are shown in Figure 53, and DVS is shown in Figure 54.

[0488] Compound 1 ethanesulfonate (form A) is prepared using deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.52-0.81(m,7H)0.83-1.78(m,25H)1.99-2.17(m,3H)2.39(q,J7.42 Hz,2H)2.69-2.80(m,1H)3.05(s,2H)3.43(brs,4H)5.11-5.46(m,2H)7.54-7.77(m,2H)9.02(s,1H).

[0489] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 ethanesulfonate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000084.tif74170

[0490] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 ethanesulfonate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000085.tif41170

[0491] Example 10: Preparation of sulfate of compound 1 The sulfate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0492] 200 mg of compound 1 was dissolved in 10.0 mL of ACN at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1 hour. Subsequently, 1.1 equivalents of sulfuric acid in 1.027 mL of ACN (0.5 mol / L) were added to the compound 1 solution, and the mixture was incubated at 60°C for 3 hours. Then, it was cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ACN. The resulting wet product was vacuum-dried at 35°C for 22 hours to obtain 177.38 mg of powder in a yield of 70.9%.

[0493] The obtained solid is compound 1 sulfate (form A). The ratio of compound 1 to sulfuric acid in compound 1 sulfate (form A) is 1:1.03, as determined by ion chromatography. The XPRD is shown in Figure 55, the DSC and TGA are shown in Figure 56, and the DVS is shown in Figure 57.

[0494] Chemical and physical stability testing

[0495] Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 sulfate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000086.tif78170

[0496] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 sulfate (form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000087.tif45170

[0497] Example 11: Preparation of ascorbate of compound 1 The ascorbate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0498] Compound 1: Ascorbate (Form A): 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of ascorbic acid powder (226 mg) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 264.1 mg of powder in a yield of 36.3%.

[0499] The obtained solid is compound 1 ascorbate (form A). The ratio of compound 1 to ascorbic acid in compound 1 ascorbate (form A) is 1:0.98, as determined by ion chromatography. XPRD is shown in Figure 58, DSC and TGA are shown in Figure 59, and DVS is shown in Figure 60.

[0500] Compound 1 ascorbate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.51-0.81(m,7H)0.83-1.76(m,22H)1.98-2.14(m,4H)2.33(brs,1H)2.6 4-2.72(m,1H)3.04(s,2H)3.25(s,3H)3.41-3.45(m,3H)3.73(brt,J=7.65 Hz,1H)4.71(d,J=1.51 Hz,1H)4.87-5.11(m,3H)6.98(s,1H)7.10(s,1H)7.71(s,1H).

[0501] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 ascorbate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000088.tif78170

[0502] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 ascorbate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000089.tif41170

[0503] Compound 1: Ascorbate (Form B): 50 mg of compound 1 and 1.1 equivalents of solid ascorbic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of ACN solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0504] The obtained dried solid was characterized using PLM and XRPD (Figure 61).

[0505] Example 12: Preparation of napadisylate of compound 1 Napadisylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0506] Compound 1: Napadisylate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of naphthalene-1,5-disulfonic acid tetrahydrate in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 675.62 mg of pale pink powder in a yield of 69.38%.

[0507] The obtained solid is compound 1 napadisylate (form A). The ratio of naphthalene-1,5-disulfonic acid in compound 1 napadisylate (form A) is 1:0.7, as determined by ion chromatography. XPRD is shown in Figure 62, DSC and TGA are shown in Figure 63, and DVS is shown in Figure 64.

[0508] Compound 1 napadisylate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.51-0.81(m,7H)0.85-1.76(m,21H)2.00-2.15(m,2H)2.34(s,1H)2.64-2.78(m,1H)3.05(s ,2H)3.25(s,4H)5.16-5.38(m,2H)7.37-7.45(m,1H)7.62(s,1H)7.68(s,1H)7.93(d,J=6.88 Hz,1H)8.86(d,J=8.63 Hz,1H)9.01(s,1H).

[0509] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 napadisylate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000090.tif78170

[0510] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 napadisylate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000091.tif43170

[0511] Compound 1: Napadisylate (Form B) 50 mg of compound 1 and 1.1 equivalents of solid naphthalene-1,5-disulfonic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0512] The dried solids were characterized using PLM and XRPD (Figure 65).

[0513] Example 13: Preparation of malonate of compound 1 The malonate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0514] 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of malonic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours.

[0515] The obtained solid is compound 1 malonate (form A). The ratio of compound 1 to malonic acid in compound 1 malonate (form A) is 1:1.28, as determined by ion chromatography. The XPRD is shown in Figure 66, and the DSC and TGA are shown in Figure 67.

[0516] Compound 1 malonate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6) δ ppm 0.50-0.79(m,7H)0.84-1.75(m,20H)1.91(s,1H)2.00-2.12(m,2H)2.65-2.73( m,1H)3.04(s,2H)3.13(s,3H)4.92-5.15(m,2H)7.03-7.20(m,2H)7.91(s,1H).

[0517] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 malonate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000092.tif77170

[0518] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 malonate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000093.tif41170

[0519] Example 14: Preparation of besylate of compound 1 The besylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0520] Compound 1 besylate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of benzenesulfonic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 654.68 mg of powder in a yield of 92.56%.

[0521] The obtained solid is compound 1 besilate (form A). The ratio of compound 1 to benzenesulfonic acid in compound 1 besilate (form A) is 1:0.94, as determined by ion chromatography. XPRD is shown in Figure 68, DSC and TGA are shown in Figure 69, and DVS is shown in Figure 70.

[0522] Compound 1 besylate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.53-0.80(m,7H)0.83-1.78(m,21H)1.99-2.15(m,3H)2.29-2.3(m,1H)2.56(brs,1H)2.66-2.77(m,1H) 3.05(s,2H)3.25(s,4H)4.03(brs,1H)5.15-5.39(m,2H)7.27-7.36(m,3H)7.55-7.70(m,4H)8.97(s,1H).

[0523] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 besylate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000094.tif78170

[0524] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 besylate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000095.tif40170

[0525] Compound 1 besylate (form B) 50 mg of compound 1 and 1.1 equivalents of solid benzenesulfonic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of ACN solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0526] The obtained dried solid was characterized using PLM and XRPD (Figure 71).

[0527] Example 15: Preparation of isethionate salt of compound 1 The isethionate salt of compound 1 can be prepared from compound 1 using the following exemplary method.

[0528] Compound 1: Iseshionate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of 2-hydroxyethanesulfonic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 493.12 mg of powder in a yield of 74.64%.

[0529] The obtained solid is compound 1 isethionate (form A). The ratio of compound 1 to 2-hydroxyethanesulfonic acid in compound 1 isethionate (form A) was 1:1.09 as determined by ion chromatography. XPRD is shown in Figure 72, DSC and TGA are shown in Figure 73, and DVS is shown in Figure 74.

[0530] Compound 1 isethionate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6) δ ppm 0.53-0.81(m,7H)0.84-1.78(m,22H)2.01-2.15(m,3H)2.34(br s,1H)2.61(t,J=6.82 Hz,2H)2.66-2.78(m,1H)3.05(s,2H)3.25(s,3H)3.63(t,J=6.75 Hz,2H)5.14-5.38(m,2H)7.58-7.69(m,2H)8.99(s,1H).

[0531] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 isethionate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000096.tif77170

[0532] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 isethionate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000097.tif40170

[0533] Compound 1: Iseshionate (Form B) 50 mg of compound 1 was weighed into a 2 mL vial, followed by the addition of 743 μL of IPA / water (95 / 5, V / V) solvent to the vial. Then, 1.1 equivalents of 2-hydroxyethanesulfonic acid counterions (257 μL, concentration: 0.5 mol / L) were added to the vial. The vial was placed on a thermomix with a stirring rod and heated to 50°C. After maintaining the temperature at 50°C with constant stirring at 500 rpm for 21 hours, the vial was cooled to 25°C. After holding at 25°C for 1 hour, the vial showed a clear solution. The solvent was evaporated in a vacuum oven at 30°C.

[0534] The obtained solid material was characterized using PLM and XRPD (Figure 75).

[0535] Example 16: Preparation of gentisinate of compound 1 The gentisic acid salt of compound 1 can be prepared from compound 1 using the following exemplary method.

[0536] Compound 1: Gentisidine salt (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of gentisic acid in acetone (2.565 mL, 0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 281.5 mg of powder in a yield of 31.39%.

[0537] The obtained solid is compound 1 gentisic acid salt (form A). The ratio of gentisic acid in compound 1 to compound 1 gentisic acid salt (form A) is 1:1.03, as determined by ion chromatography. XPRD is shown in Figure 76, DSC and TGA are shown in Figure 77, and DVS is shown in Figure 78.

[0538] Compound 1 gentisate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.53-0.80(m,7H)0.85-1.72(m,20H)2.00-2.13(m,5H)2.66-2.74(m,1H)3.04(s,2H)4.02(brs,1H)4.90-5.12(m,2H)6.71(d,J=8.76 Hz,1H)6.88(dd,J=8.82,3.06 Hz,1H)7.03(s,1H)7.13-7.17(m,2H)7.78-7.86(m,1H)7.81(s,1H)9.01(brs,1H).

[0539] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 gentisic acid (Form A) and Compound 1 free base are shown in the table below.

[0540] Compound 1: Gentisidine salt (Form B) 50 mg of compound 1 and 1.1 equivalents of solid gentisic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of ÃO solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0541] The dried solids were characterized using PLM and XRPD (Figure 79).

[0542] Compound 1: Gentisidine salt (Form C) 50 mg of compound 1 and 1.1 equivalents of solid gentisic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0543] The dried solids were characterized using PLM and XRPD (Figure 80).

[0544] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 gentisate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000099.tif39170

[0545] Example 17: Preparation of 1-hydroxy-2-naphthoate of compound 1 The 1-hydroxy-2-naphthoate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0546] Compound 11-hydroxy-2-naphthoic acid (form A) 500 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of 1-hydroxy-2-naphthoic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 675.36 mg of powder in a yield of 68.15%.

[0547] The obtained solid is compound 11-hydroxy-2-naphthoic acid (form A). The ratio of compound 1 to 1-hydroxy-2-naphthoic acid in compound 11-hydroxy-2-naphthoic acid (form A) is 1:1.15, as determined by ion chromatography. XPRD is shown in Figure 81, DSC and TGA are shown in Figure 82, and DVS is shown in Figure 83.

[0548] Compound 11-hydroxy-2-naphthoic acid (form A) is converted to deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.49-0.79(m,7H)0.82-1.76(m,22H)1.96-2.16(m,4H)2.63-2.76(m,1H)2.95-3.11(m,2H) 4.98-5.22(m,2H)7.19-7.32(m,3H)7.46-7.62(m,2H)7.72-7.86(m,2H)8.16-8.29(m,2H).

[0549] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for compound 11-hydroxy-2-naphthoic acid (form A) and compound 1 free base are shown in the table below. TIFF0007911419000100.tif73170

[0550] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of compound 11-hydroxy-2-naphthoate (form A) and compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000101.tif40170

[0551] Compound 11-hydroxy-2-naphthoic acid (form B) 50 mg of compound 1 and 1.1 equivalents of solid 1-hydroxy-2-naphthoic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0552] The dried solids were characterized using PLM and XRPD (Figure 84).

[0553] Compound 11-hydroxy-2-naphthoic acid (form C) 50 mg of compound 1 and 1.1 equivalents of solid 1-hydroxy-2-naphthoic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of ACN solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0554] The dried solids were characterized using PLM and XRPD (Figure 85).

[0555] Compound 11-hydroxy-2-naphthoic acid (form D) 50 mg of compound 1 and 1.1 equivalents of solid 1-hydroxy-2-naphthoic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0556] The dried solids were characterized using PLM and XRPD (Figure 86).

[0557] Example 18: Preparation of cyclamate salt of compound 1 The cyclamate salt of compound 1 can be prepared from compound 1 using the following exemplary method.

[0558] 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of cyclamic acid in acetone (2.565 mL, 0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 715.81 mg of powder in a yield of 74.48%.

[0559] The obtained solid is compound 1 cyclamate (form A). The ratio of cyclamic acid in compound 1 to compound 1 cyclamate (form A) is 1:1.00, as determined by ion chromatography. XPRD is shown in Figure 87, DSC and TGA are shown in Figure 88, and DVS is shown in Figure 89.

[0560] Compound 1 cyclamate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.49-0.80(m,7H)0.84-1.77(m,30H)1.83-2.14(m,5H)2.65-2.74(m,1H)2.90-3.09(m,3 H)3.35-3.60(m,2H)4.03(brs,1H)4.87-5.16(m,2H)6.97-7.18(m,2H)7.54-7.91(m,3H).

[0561] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 cyclamate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000102.tif72170

[0562] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 cyclamate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000103.tif39170

[0563] Example 19: Preparation of ethane-1,2-disulfonate of compound 1 The ethane-1,2-disulfonate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0564] Compound 1-ethane-1,2-disulfonate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of ethane-1,2-disulfonic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 704.45 mg of powder in a yield of 71.61%.

[0565] The obtained solid is compound 1-ethane-1,2-disulfonate (form A). The ratio of compound 1 to ethane-1,2-disulfonic acid in compound 1-ethane-1,2-disulfonate (form A) is 1:2.4, as determined by ion chromatography. XPRD is shown in Figure 90, DSC and TGA are shown in Figure 91, and DVS is shown in Figure 92.

[0566] Compound 1-ethane-1,2-disulfonate (Form A) is prepared using deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6) δ ppm 0.52-0.79(m,7H)0.82-1.77(m,22H)1.97-2.15(m,2H)2.58-2.78(m,4H) 3.03(s,2H)3.23(s,4H)5.13-5.40(m,2H)7.56-7.71(m,2H)9.00(s,1H).

[0567] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 ethane-1,2-disulfonate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000104.tif73170

[0568] Compound 1-ethane-1,2-disulfonate (Form B) 50 mg of compound 1 and 1.1 equivalents of solid ethane-1,2-disulfonic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  / IPA / water (95 / 5, V / V) solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was kept at 50°C with constant stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0569] The dried solids were characterized using PLM and XRPD (Figure 93).

[0570] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 ethane-1,2-disulfonate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000105.tif41170

[0571] Example 20: Preparation of dichloroacetate of compound 1 The dichloroacetate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0572] 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of dichloroacetic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 559.98 mg of powder in a yield of 83.41%.

[0573] The obtained solid is compound 1 dichloroacetate (form A). The ratio of compound 1 to dichloroacetic acid in compound 1 dichloroacetate (form A) is 1:1.14, as determined by ion chromatography. XPRD is shown in Figure 94, DSC and TGA are shown in Figure 95, and DVS is shown in Figure 96.

[0574] Compound 1 dichloroacetate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.46-0.79(m,7H)0.82-1.75(m,21H)1.96-2.15(m,2H)2.62-2.75(m,1H)3.02(s,2H)4.98-5.27(m,3H)6.30(s,1H)7.31(d,J=12.80 Hz,2H)8.32(s,1H).

[0575] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 dichloroacetate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000106.tif73170

[0576] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 dichloroacetate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000107.tif43170

[0577] Example 21: Preparation of L-malate of compound 1 The L-malate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0578] Compound 1L-malate (Form A): 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of L-malic acid in acetone (1.027 mL, 0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held at 25°C for 20 hours. The solution was evaporated with nitrogen to remove the organic solvent. The resulting wet product was vacuum-dried at 25°C for 42 hours to obtain 230.93 mg of powder in 85.9% yield.

[0579] The obtained solid is compound 1L-malate (form A). The ratio of compound 1 to malic acid in compound 1L-malate (form A) is 1:1.35, as determined by ion chromatography. XPRD is shown in Figure 97, DSC and TGA are shown in Figure 98, and DVS is shown in Figure 99.

[0580] Compound 1L-malate (form A) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6):δ 0.57-0.86(m,4H)0.70-0.86(m,4H)0.89-1.79(m,21H)2.00-2.21(m,3H)2.33-2.78(m,13H)3.10(s,2H)3.31(s,3H)4.28(dd,J=7.32,5.44 Hz,1H)4.85-5.19(m,2H) 7.00(s,1H)7.13(s,1H)7.53-7.84(m,1H).

[0581] Compound 1L-malate (Form B): 10 g of compound 1 was suspended in 350 mL of acetone at 60°C with stirring at 200 rpm and held at 60°C for 0.5 hours. Subsequently, 1.1 equivalents of L-malic acid in 50 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C, and held at 25°C for 72 hours with the vial open. The suspension was centrifuged, the precipitate was collected, and then vacuum-dried at 30°C for 24 hours to obtain 4.44 g of powder in a yield of 33.86%.

[0582] The obtained solid is compound 1L-malate (form B). The ratio of malic acid in compound 1:compound 1L-malate (form B) is 1:1.26, as determined by ion chromatography. XPRD is shown in Figure 100, DSC and TGA are shown in Figure 101, and DVS is shown in Figure 102.

[0583] Compound 1L-malate (form B) is prepared in deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1 H NMR (400MHz, DMSO-d6) δ ppm 0.45-0.79(m,7H)0.83-1.73(m,20H)1.98-2.12(m,2H)2.43(dd,J=15.69,7.40 Hz,1H)2.56-2.72(m,2H)3.04(s,2H)4.22(dd,J=7.28,5.52 Hz,1H)4.86-5.10(m,2H)6.94(s,1H)7.07(s,1H)7.65(s,1H).

[0584] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1L-malate (Form A), Compound 1L-malate (Form B), and Compound 1 free base are shown in the table below. TIFF0007911419000108.tif110170

[0585] Solubility tests in simulated gastric fluid and intestinal fluid.

[0586] Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1L-malate (Form A), Compound 1L-malate (Form B), and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000109.tif55170

[0587] Example 22: Preparation of the hydrochloride salt of compound 1 The hydrochloride salt of compound 1 can be prepared from compound 1 using the following exemplary method.

[0588] Compound 1 hydrochloride (form A): 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of hydrochloric acid in acetone (1.027 mL, 0.5 mol / L) were added to the compound 1 solution, and the mixture was incubated at 60°C for 3 hours. Then, it was cooled to 25°C and held at 25°C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 42 hours to obtain 168.15 mg of powder in a yield of 76.9%.

[0589] The obtained solid is compound 1 hydrochloride (form A). The ratio of compound 1 to hydrochloric acid in compound 1 hydrochloride (form A) is 1:0.94, as determined by ion chromatography. XPRD is shown in Figure 103, DSC and TGA are shown in Figure 104, and DVS is shown in Figure 105.

[0590] Compound 1 hydrochloride (form B): 500 mg of hydrochloride (form A) was dissolved in 4.0 mL of ethanol at 50°C. The solution was filtered, and then 6.25 times the volume of heptane was added dropwise to prepare a suspension. This suspension was continuously stirred at 500 rpm and maintained at 50°C for 24 hours. The suspension was centrifuged, the precipitate was collected, and then vacuum-dried at 30°C for 24 hours to obtain 365 mg of powder in a yield of 73.0%.

[0591] The obtained solid was compound 1 hydrochloride (form B). The ratio of compound 1 to hydrochloric acid in compound 1 hydrochloride (form B) was 1:0.96, as determined by ion chromatography. The XPRD is shown in Figure 106, the DSC and TGA are shown in Figure 107, and the DVS is shown in Figure 108.

[0592] Compound 1 hydrochloride (form C): 300 mg of hydrochloride (form A) was suspended in 6.0 mL of a water activity 0.901 solution while stirring at 700 rpm at 50°C to produce a clear solution. Next, 200 mg of hydrochloride was added to produce a suspension. The suspension was maintained under constant stirring at 700 rpm and held at 50°C for one week. This suspension was centrifuged, the precipitate was collected, and then vacuum-dried at 30°C for 24 hours to obtain 400 mg of powder in 80.0% yield.

[0593] The obtained solid is compound 1 hydrochloride (form C). The ratio of compound 1 to hydrochloric acid in compound 1 hydrochloride (form C) is 1:0.97, as determined by ion chromatography. XPRD is shown in Figure 109, DSC and TGA are shown in Figure 110, and DVS is shown in Figure 111.

[0594] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 hydrochloride (Form A), Compound 1 hydrochloride (Form B), Compound 1 hydrochloride (Form C), and Compound 1 free base are shown in the table below. TIFF0007911419000110.tif140170

[0595] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 hydrochloride (form A), Compound 1 hydrochloride (form B), Compound 1 hydrochloride (form C), and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000111.tif46158

[0596] Example 22: Preparation of napsylate of compound 1 The napsylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0597] Compound 1: Napsylate (Form A): 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of naphthalene-2-sulfonic acid hydrate in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 690.41 mg of powder in 89.17% yield.

[0598] The obtained solid is compound 1 napsylate (form A). The ratio of compound 1 to naphthalene-2-sulfonic acid in compound 1 napsylate (form A) is 1:1.04, as determined by ion chromatography. XPRD is shown in Figure 112, DSC and TGA are shown in Figure 113, and DVS is shown in Figure 114.

[0599] Compound 1 napsylate (form A) is prepared with deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6) δ ppm 0.51-0.80(m,8H)0.82-1.77(m,25H)2.33(br d,J=1.75 Hz,2H)2.54-2.78(m,3H)3.05(s,3H)3.20-3.30(m,6H)4.04(brs,1H)5.15 -5.36(m,2H)7.49-7.73(m,5H)7.83-8.01(m,3H)8.14(s,1H)8.94(s,1H).

[0600] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 napsylate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000112.tif77170

[0601] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 napsylate (Form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000113.tif43170

[0602] Compound 1: Napsylate (Form B): 50 mg of compound 1 and 1.1 equivalents of solid naphthalene-2-sulfonic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  / ACN solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was maintained at 50°C with stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0603] The obtained dried solids were characterized using PLM and XRPD (Figure 115).

[0604] Example 23: Preparation of oxalate of compound 1 The oxalate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0605] Compound 1: Oxalate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of oxalic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 595.76 mg of powder in a yield of 96.32%.

[0606] The obtained solid is compound 1 oxalate (form A). The ratio of compound 1 to oxalic acid in compound 1 oxalate (form A) is 1:0.91, as determined by ion chromatography. XPRD is shown in Figure 116, DSC and TGA are shown in Figure 117, and DVS is shown in Figure 118.

[0607] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for Compound 1 oxalate (Form A) and Compound 1 free base are shown in the table below. TIFF0007911419000114.tif78170

[0608] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of Compound 1 oxalate (form A) and Compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000115.tif39170

[0609] Compound 1: Oxalate (Form B) 50 mg of compound 1 and 1.1 equivalents of solid oxalic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was maintained at 50°C with stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0610] The dried solids were characterized using PLM and XRPD (Figure 119).

[0611] Example 24: Preparation of p-aminosalicylate of compound 1 The p-aminosalicylate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0612] Compound 1p-aminosalicylate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60°C with stirring at 500 rpm, and the mixture was held at 60°C for 1.5 hours. Subsequently, 1.1 equivalents of 4-aminosalicylic acid in 2.565 mL of acetone (0.5 mol / L) were added to the compound 1 solution, incubated at 60°C for 3 hours, then cooled to 25°C and held overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The resulting wet product was vacuum-dried at 25°C for 72 hours to obtain 583.32 mg of powder in a yield of 83.37%.

[0613] The obtained solid is compound 1p-aminosalicylate (form A). The ratio of compound 1 to 4-aminosalicylic acid in compound 1p-aminosalicylate (form A) is 1:1.03, as determined by ion chromatography. XPRD is shown in Figure 120, DSC and TGA are shown in Figure 121, and DVS is shown in Figure 122.

[0614] Compound 1p-aminosalicylate (form A) is converted to deuterated DMSO. 1 Analysis by H-NMR revealed the following chemical shifts: 1H NMR (400MHz, DMSO-d6) δ ppm 0.51-0.80(m,7H)0.83-1.74(m,22H)1.97-2.15(m,3H)2.34(s,1H)2.68(brt,J=8.69 Hz,1H)2.99-3.09(m,2H)3.25(s,4H)4.83-5.10(m,2H)5.88-6.11(m,3H)6.76(t,J=8.19 Hz,1H)6.90(s,1H)7.04(s,1H)7.42(d,J=8.63 Hz,1H)7.57(s,1H).

[0615] Chemical and physical stability testing Chemical and physical stability tests were performed using the procedure described in Example 1. The results of the chemical and physical stability tests for compound 1 p-aminosalicylate (form A) and compound 1 free base are shown in the table below. TIFF0007911419000116.tif77170

[0616] Solubility tests in simulated gastric fluid and intestinal fluid. Solubility tests in simulated gastric and intestinal fluids were performed using the procedure described in Example 1. The solubility results (mg / mL) of compound 1 p-aminosalicylate (form A) and compound 1 free base in biologically relevant solutions are shown in the table below. TIFF0007911419000117.tif56170

[0617] Compound 1p-aminosalicylate (form B) 50 mg of compound 1 and 1.1 equivalents of solid 4-aminosalicylic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of  / ACN solvent to the vials. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was maintained at 50°C with stirring at 500 rpm for 21 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30°C for 18 hours.

[0618] The dried solids were characterized using PLM and XRPD (Figure 123).

[0619] Example 25: Preparation of maleate of compound 1 The maleate of compound 1 can be prepared from compound 1 using the following exemplary method.

[0620] Compound 1 maleate (form A): 50 mg of compound 1 and 1.1 equivalents of solid maleic acid counterions were weighed separately into 2 mL vials, followed by the addition of 1 mL of acetone solvent to each vial. The vials were placed on a thermomix with a stirring rod and heated to 50°C. The mixture was maintained at 50°C with stirring at 900 rpm for 18 hours, after which the vials were cooled to 25°C. After holding at 25°C for 1 hour, the solids in the suspension were isolated by centrifugation and dried overnight in a vacuum oven at 30°C.

[0621] The obtained dried solid was characterized using PLM and XRPD (Figure 124). Example 26: Attempt to prepare a salt of compound 1 The following acids formed amorphous salts under several conditions. TIFF0007911419000118.tif68158

[0622] TIFF0007911419000119.tif167170

[0623] Experimental conditions: For each of the 20 acids listed in the table above, four solvents (acetone, siRNA, ACN, and IPA / water (95 / 5, V / V)) were used according to the following procedure to determine whether an isolable salt of compound 1 could be obtained by a particular solvent-acid combination.

[0624] Approximately 50 mg of compound 1 and 1.1 molar equivalents of acid were placed in a 2 mL vial. Approximately 1 mL of solvent was added to the vial. The vial was placed in a thermomixer with a stirring rod and heated to 50°C. After stirring at 50°C for 21 hours (500 rpm), the vial was cooled to 25°C and held at 25°C for 1 hour, and the vial was monitored for solid formation. After stirring for approximately 1 hour, no solids were obtained in any of the experiments. In each experiment, the solvent was evaporated in a vacuum oven at 30°C. Under these conditions, none of the acids listed in the table above provided an isolable salt of compound 1.

[0625] Example 27: Properties of the salt of compound 1 The bulk density, tap density, Carr's index, and Hausner ratio were measured for compound 1 citrate (form A), compound 1 phosphate (form A), compound 1 tartrate (form A), compound 1 HBr salt (form A), and compound 1 free base (form A). The results are shown in the table below. TIFF0007911419000120.tif58170

[0626] Among the tested forms, the physical properties of compound 1 citrate (form A) are optimal for the preparation of solid pharmaceutical dosage forms (such as tablets) and for the economical storage of active pharmaceutical ingredients (APIs) (i.e., bulk density).

[0627] Compressibility is an important property of APIs; generally, highly compressible APIs are compressed into tablet formulations more easily than less compressible APIs. The Kerr index is a measure of the compressibility of a powder; a low Kerr index indicates high compressibility, while a high Kerr index indicates low compressibility. Compound 1 citrate (form A) has a significantly lower Kerr index compared to the other polymorphs tested and exhibits the best compressibility among the tested forms.

[0628] The flow properties of APIs are crucial in many pharmaceutical operations, including compounding with excipients, tablet compression, capsule filling, and scaling up production. The Hausner ratio is an indicator of the flow properties of a powder. A high Hausner ratio indicates poor powder flowability, while a low Hausner ratio indicates good flowability. Compound 1 citrate (form A) has a significantly lower Hausner ratio compared to the other polymorphs tested and exhibits the best flow properties among the tested forms.

[0629] Manufacturability of citrate (Form A): Compound 1 citrate (Form A) exhibits excellent manufacturability and was produced on a kilogram scale (Example 2). Large-scale synthesis is possible using pharmaceutically acceptable solvents and does not require seeding of Compound 1 citrate (Form A) for crystallization.

[0630] Stability of citrate (Form A): Compound 1 citrate (Form A) is stable under high temperature and high humidity conditions for at least 3 months (see Example 2), making it suitable for APIs.

[0631] Preparation of HBr salt (Form A): Compound 1HBr salt (Form A) exhibits excellent manufacturability and was produced on a kilogram scale (Example 1). Large-scale synthesis is possible using pharmaceutically acceptable solvents and does not require seeding of compound 1HBr salt (Form A) for crystallization.

[0632] Reference All references, articles, publications, patents, patent gazettes, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, references to references, articles, publications, patents, patent publications, and patent applications cited herein should not be construed as an endorsement or any form of suggestion that they constitute valid prior art or form part of common technical knowledge in any country of the world. Embodiment 1. Crystal morphology A of the citrate of compound 1, wherein morphology A exhibits an X-ray powder diffraction (XRPD) pattern using copper K-alpha radiation, with three or more peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ). 2. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, and 17.1±0.2 degrees (2θ) using copper K-alpha radiation. 3. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, and 20.1±0.2 degrees (2θ) using copper K-alpha radiation. 4. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 5. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 17.1±0.2, and 20.1±0.2 degrees (2θ) using copper K-alpha radiation. 6. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 17.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 7. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 8. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 11.9±0.2, 17.1±0.2, and 20.1±0.2 degrees (2θ) using copper K-alpha radiation. 9. Embodiment A is a crystalline form A of the citrate of Embodiment 1, exhibiting an X-ray powder diffraction (XRPD) pattern with peaks at approximately 11.9±0.2, 17.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 10. The crystalline form A of the citrate of Embodiment 1 shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 11.9±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 11. Embodiment A is a crystalline form A of the citrate of Embodiment 1, showing an X-ray powder diffraction (XRPD) pattern with peaks at approximately 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 12. Embodiment A is a crystalline form A of the citrate of Embodiment 1, exhibiting an X-ray powder diffraction (XRPD) pattern using copper K-alpha radiation that includes four or more peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ). 13. The crystalline form A of the citrate according to Embodiment 12, wherein the morphology A shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, and 20.1±0.2 degrees (2θ) using copper K-alpha radiation. 14. The crystalline form A of the citrate according to Embodiment 12, wherein the morphology A shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 15. The crystalline form A of the citrate according to Embodiment 12, wherein the morphology A shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 16. The crystalline form A of the citrate according to Embodiment 12, wherein the morphology A shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 17. The crystalline form A of the citrate according to Embodiment 12, wherein the morphology A shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 18. The crystalline form A of the citrate of Embodiment 12 shows an X-ray powder diffraction (XRPD) pattern with peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ) using copper K-alpha radiation. 19. The crystalline form A of any one of the preceding embodiments of a citrate further includes one or more peaks at approximately 12.7±0.2, 13.0±0.2, 13.6±0.2, 15.3±0.2, and 16.8±0.2 degrees (2θ) using copper K-alpha radiation, e.g., two or more peaks, e.g., three or more peaks, e.g., four or more peaks, e.g., five or more peaks. 20. Crystalline form A of any one of embodiments 1 to 18 of the citrate, further including an additional peak at approximately 12.7 ± 0.2 degrees (2θ) using copper K-alpha radiation. 21. Crystalline form A of any one of embodiments 1 to 18 and 20 of the citrate, further including an additional peak at approximately 13.0 ± 0.2 degrees (2θ) using copper K-alpha radiation. 22. Crystalline form A of any one of embodiments 1-18, 20, and 21 of the citrate, further including an additional peak at approximately 13.6 ± 0.2 degrees (2θ) using copper K-alpha radiation. 23. Crystalline form A of any one of embodiments 1-18 and 20-22 of the citrate, further including an additional peak at approximately 15.3 ± 0.2 degrees (2θ) using copper K-alpha radiation. 24. Crystalline form A of any one of embodiments 1-18 and 20-23 of the citrate, further including an additional peak at approximately 16.8 ± 0.2 degrees (2θ) using copper K-alpha radiation. 25. The XRPD pattern is substantially as observed in Figure 15, crystalline morphology A of any one of the preceding embodiments of the citrate. 26. The crystalline form A of any one of the preceding embodiments of citrate having unit cell parameters substantially similar to the following at 120K: a = 8.9 Å b = 12.2 Å c = 16.5 Å α = 73.7° β = 76.6° γ = 83.2° space group P1, Molecular / Asymmetric Unit 2. 27. The crystalline form A of the citrate of Embodiment 26 has the following unit cell parameters at 120K: a = 8.9 ± 0.5 Å b = 12.2 ± 0.5 Å c = 16.5 ± 0.5 Å α = 73.7 ± 2° β = 76.6 ± 2° γ = 83.2 ± 2° space group P1, Molecular / Asymmetric Unit 2. 28. The crystalline form A of the citrate of Embodiment 27 has the following unit cell parameters at 120K: a = 8.9 ± 0.3 Å b = 12.2 ± 0.3 Å c = 16.5 ± 0.3 Å α = 73.7 ± 1° β = 76.6 ± 1° γ = 83.2 ± 1° space group P1, Molecular / Asymmetric Unit 2. 29. The crystalline form A of the citrate of Embodiment 28 has the following unit cell parameters at 120K: a = 8.9 ± 0.2 Å b = 12.2 ± 0.2 Å c = 16.5 ± 0.2 Å α = 73.7 ± 0.5° β = 76.6 ± 0.5° γ = 83.2 ± 0.5° space group P1, Molecular / Asymmetric Unit 2. 30. The above-mentioned form A is a crystalline form A of a citrate from any one of the preceding embodiments, showing a differential scanning calorimetry thermogram having a peak value at approximately 89.0 ± 2.0 °C or approximately 139.5 ± 2.0 °C. 31. The above-mentioned form A is a crystalline form A of any one of the preceding embodiments of a citrate, showing a differential scanning calorimetry thermogram having a peak value at approximately 89.0 ± 2.0 °C. 32. The above-mentioned form A is a crystalline form A of any one of the preceding embodiments of a citrate, showing a differential scanning calorimetry thermogram having a peak value at approximately 139.5 ± 2.0 °C. 33. A pharmaceutical composition comprising a citrate of any one of the prior embodiments and a pharmaceutically acceptable carrier. 34. The pharmaceutical composition of Embodiment 33, wherein the composition is in the form of a tablet. 35. Hydrobromide salt of compound 1. 36. The hydrobromide salt of Embodiment 35, wherein at least about 80% by weight of the salt is crystalline. 37. A hydrobromide salt of Embodiment 35, wherein at least about 80% by weight of the salt is in single-crystal form. 38. The hydrobromide salt of Embodiment 35, wherein at least about 95% by weight of the salt is crystalline. 39. The hydrobromide salt of Embodiment 35, wherein at least about 95% by weight of the salt is in single-crystal form. 40. A hydrobromide salt according to any one of embodiments 36 to 39, wherein the crystalline form is form A. 41. Embodiment A is a hydrobromide salt of Embodiment 40, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 7.6±0.2, 15.2±0.2, 16.3±0.2, 19.8±0.2, and 22.9±0.2 degrees (2θ). 42. The hydrobromide salt of Embodiment 41, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 15.5±0.2, 19.2±0.2, 20.6±0.2, 26.1±0.2, and 31.3±0.2 degrees (2θ). 43. Embodiment A is a hydrobromide of embodiment 40, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 2. 44. Embodiment A is a hydrobromide salt of any one of embodiments 40 to 43, showing a differential scanning calorimetry thermogram having a peak value at approximately 243.1 ± 2.0°C. 45. Embodiment A is any one of embodiments 40 to 43 of the hydrobromide salt, which exhibits a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 3. 46. ​​Embodiment A is any one of embodiments 40 to 43 of the hydrobromide salt, showing a thermogravimetric thermogram substantially similar to that of Figure 3. 47. A hydrobromide salt according to any one of embodiments 36 to 39, wherein the crystalline form is form E. 48. Embodiment E is a hydrobromide of Embodiment 47, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 7.6±0.2, 15.2±0.2, 16.3±0.2, 22.9±0.2, and 23.2±0.2 degrees (2θ). 49. The hydrobromide salt of Embodiment 48, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 9.6±0.2, 17.4±0.2, 22.4±0.2, 23.6±0.2, and 31.2±0.2 degrees (2θ). 50. Embodiment E is a hydrobromide of Embodiment 47, exhibiting an X-ray powder diffraction pattern substantially similar to that of Figure 13. 51. Embodiment E is any one of the hydrobromide salts from Embodiments 47 to 50, showing a differential scanning calorimetry thermogram having a peak value at approximately 245.0 ± 2.0°C. 52. Embodiment E is any one of the hydrobromide salts of Embodiments 47 to 50, exhibiting a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 14. 53. Embodiment E is any one of the hydrobromide salts of Embodiments 47 to 50, showing a thermogravimetric thermogram substantially similar to that of Figure 14. 54. Citrate of compound 1. 55. The citrate of Embodiment 54, wherein at least about 80% by weight of the salt is crystalline. 56. The citrate of Embodiment 54, wherein at least about 80% by weight of the salt is in single-crystal form. 57. The citrate of Embodiment 54, wherein at least about 95% by weight of the salt is crystalline. 58. The citrate of Embodiment 54, wherein at least about 95% by weight of the salt is in crystalline form. 59. A citrate according to any one of embodiments 55 to 58, wherein the crystalline form is form A. 60. Embodiment A is a citrate of Embodiment 59, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees (2θ). 61. The citrate of Embodiment 60, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 12.7±0.2, 13.0±0.2, 13.6±0.2, 15.3±0.2, and 16.8±0.2 degrees (2θ). 62. Embodiment A is a citrate of embodiment 59, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 15. 63. Embodiment A is a citrate according to any one of embodiments 59 to 62, showing a differential scanning calorimetry thermogram having a peak value at approximately 89.0 ± 2.0°C or approximately 139.5 ± 2.0°C. 64. Embodiment A is any one of embodiments 59 to 63 of the citrate, which exhibits a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 16. 65. Embodiment A is any one of embodiments 59 to 63, showing a thermogravimetric thermogram substantially similar to that of Figure 16. 66. L-malate of compound 1. 67. The L-malate salt of Embodiment 66, wherein at least about 80% by weight of the salt is crystalline. 68. The L-malate of Embodiment 66, wherein at least about 80% by weight of the salt is in single-crystal form. 69. The L-malate of Embodiment 66, wherein at least about 95% by weight of the salt is crystalline. 70. The L-malate of Embodiment 66, wherein at least about 95% by weight of the salt is in single-crystal form. 71. One L-malate salt from any one of embodiments 67 to 70, wherein the crystalline form is form A. 72. Embodiment A is the L-malate of Embodiment 71, which exhibits an X-ray powder diffraction pattern including three or more peaks at approximately 3.2±0.2, 12.5±0.2, 14.4±0.2, 15.7±0.2, and 18.4±0.2 degrees (2θ). 73. The L-malate of Embodiment 72, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 3.6±0.2, 6.1±0.2, 13.2±0.2, 18.9±0.2, and 21.1±0.2 degrees (2θ). 74. Embodiment A is an L-malate of Embodiment 71, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 97. 75. Embodiment A is one of the L-malate salts of embodiments 71 to 74, showing a differential scanning calorimetry thermogram having a peak value at approximately 120.9 ± 2.0°C or approximately 142.3 ± 2.0°C. 76. Embodiment A is any one of embodiments 71 to 75 of L-malate, which exhibits a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 98. 77. Embodiment A is any one of the L-malate salts of embodiments 71 to 76, showing a thermogravimetric thermogram substantially similar to that of Figure 98. 78. Mesylate of Compound 1. 79. The mesylate of Embodiment 78, wherein at least about 80% by weight of the salt is crystalline. 80. The mesylate of Embodiment 78, wherein at least about 80% by weight of the salt is in single-crystal form. 81. The mesylate of Embodiment 78, wherein at least about 95% by weight of the salt is crystalline. 82. The mesylate of Embodiment 78, wherein at least about 95% by weight of the salt is in single-crystal form. 83. A mesylate salt according to any one of embodiments 79 to 82, wherein the crystalline form is form A. 84. Embodiment A is a mesylate of Embodiment 83, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 3.6±0.2, 7.1±0.2, 14.2±0.2, 19.1±0.2, and 25.9±0.2 degrees (2θ). 85. The mesylate of Embodiment 84, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 7.7±0.2, 12.7±0.2, 17.8±0.2, 19.4±0.2, and 21.4±0.2 degrees (2θ). 86. Embodiment A is a mesylate of embodiment 83, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 22. 87. Embodiment A is a mesylate of any one of embodiments 83 to 86, showing a differential scanning calorimetry thermogram having a peak value at approximately 170.9 ± 2.0 °C or approximately 209.7 ± 2.0 °C. 88. Embodiment A is any one of embodiments 83 to 87, which exhibits a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 23. 89. Embodiment A is any one of embodiments 83 to 88, showing a thermogravimetric thermogram substantially similar to that of Figure 23. 90. L(+)-tartrate of compound 1. 91. The L(+)-tartrate of Embodiment 90, wherein at least about 80% by weight of the salt is crystalline. 92. L(+)-tartrate of Embodiment 90, wherein at least about 80% by weight of the salt is in single-crystal form. 93. The L(+)-tartrate of Embodiment 90, wherein at least about 95% by weight of the salt is crystalline. 94. L(+)-tartrate of Embodiment 90, wherein at least about 95% by weight of the salt is in single-crystal form. 95. One L(+)-tartrate salt from any of embodiments 91 to 94, wherein the crystalline form is form A. 96. Embodiment A of the L(+)-tartrate of Embodiment 95, which exhibits an X-ray powder diffraction pattern including three or more peaks at approximately 3.6±0.2, 4.7±0.2, 13.9±0.2, 18.6±0.2, and 22.8±0.2 degrees (2θ). 97. The L(+)-tartrate of Embodiment 96, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 14.6±0.2, 17.8±0.2, and 18.1±0.2 degrees (2θ). 98. Embodiment A is an L(+)-tartrate of Embodiment 95, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 30. 99. Embodiment A is one of the L(+)-tartrates from embodiments 95 to 98, showing a differential scanning calorimetry thermogram having a peak value at approximately 207.6 ± 2.0°C. 100. Embodiment A is one of any of embodiments 95 to 99 of L(+)-tartrate, exhibiting a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 31. 101. Embodiment A is one of any one of embodiments 95 to 100, showing a thermogravimetric thermogram substantially similar to that of Figure 31, of L(+)-tartrate. 102. One L(+)-tartrate salt from any of embodiments 91 to 94, wherein the crystalline form is form B. 103. Embodiment B is the L(+)-tartrate of Embodiment 102, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 3.6±0.2, 4.6±0.2, 12.4±0.2, 13.9±0.2, and 22.7±0.2 degrees (2θ). 104. The L(+)-tartrate of Embodiment 103, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 14.8±0.2, 18.3±0.2, and 18.5±0.2 degrees (2θ). 105. Embodiment B is an L(+)-tartrate of Embodiment 103, which exhibits an X-ray powder diffraction pattern substantially similar to that of Figure 33. 106. Embodiment B is one of the L(+)-tartrates from embodiments 102 to 105, showing a differential scanning calorimetry thermogram having a peak value at approximately 207.3 ± 2.0°C. 107. Embodiment B is one of the L(+)-tartrates of embodiments 102 to 106, showing a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 34. 108. Embodiment B is an L(+)-tartrate of any one of embodiments 102 to 107, showing a thermogravimetric thermogram substantially similar to that of Figure 34. 109. Phosphate of compound 1. 110. The phosphate of Embodiment 109, wherein at least about 80% by weight of the salt is crystalline. 111. The phosphate of Embodiment 109, wherein at least about 80% by weight of the salt is in single-crystal form. 112. The phosphate of Embodiment 109, wherein at least about 95% by weight of the salt is crystalline. 113. The phosphate of Embodiment 109, wherein at least about 95% by weight of the salt is in single-crystal form. 114. A phosphate salt according to any one of embodiments 110 to 113, wherein the crystalline form is form A. 115. Embodiment A is a phosphate of Embodiment 114, exhibiting an X-ray powder diffraction pattern with three or more peaks at approximately 3.3±0.2, 3.6±0.2, 5.4±0.2, 9.9±0.2, and 13.1±0.2 degrees (2θ). 116. The phosphate of Embodiment 115, wherein the X-ray powder diffraction pattern further includes one or more peaks at approximately 16.1±0.2, 17.9±0.2, 20.9±0.2, 23.7±0.2, and 26.4±0.2 degrees (2θ). 117. Embodiment A is a phosphate of embodiment 114, exhibiting an X-ray powder diffraction pattern substantially similar to that of Figure 27. 118. The phosphate according to any one of embodiments 114 to 118, wherein embodiment A shows a differential scanning calorimetry thermogram having a peak value at approximately 217.6 ± 2.0°C. 119. Embodiment A is any one of embodiments 114 to 117, showing a differential scanning calorimetry thermogram pattern substantially similar to that of Figure 28. 120. Embodiment A is one of the phosphates of embodiments 114 to 119, showing a thermogravimetric thermogram substantially similar to that of Figure 28. 121. A pharmaceutical composition comprising one salt of any of embodiments 35 to 120 and a pharmaceutically acceptable carrier. 122. The pharmaceutical composition of Embodiment 121, wherein the composition is a tablet. 123. A method for treating depression, comprising administering to a patient in need of such treatment a therapeutically effective amount of any one salt of any one embodiment 1 to 32 and 35 to 120 or any one composition of any one embodiment 33, 34, 121 and 122. 124. The method of Embodiment 123, wherein the depression is selected from major depressive disorder, postpartum depression, and treatment-resistant depression. 125. A method for a disease or condition selected from epilepsy, bipolar disorder, and anxiety disorder, comprising administering to a patient in need an effective amount of any one salt of any one embodiment 1-32 and 35-120 or any one composition of any one embodiment 33, 34, 121, and 122.

Claims

1. A pharmaceutical composition for treating a disease or condition selected from epilepsy, bipolar disorder, and anxiety disorder, wherein the pharmaceutical composition is: (i) Formula: A crystalline form of the compound citrate, 5.7±0.2, 12.5±0.2, and 13.0±0.2; or 5.7±0.2, 12.5±0.2, and 20.1±0.2; or 5.7±0.2, 12.5±0.2, and 20.3±0.2; or 5.7±0.2, 12.7±0.2, and 13.0±0.2; or 5.7±0.2, 12.7±0.2, and 20.3±0.2; or 5.7±0.2, 13.0±0.2, and 20.3±0.2; or 12.5 ± 0.2, 13.0 ± 0.2, and 20.3 ± 0.2; or 12.7±0.2, 13.0±0.2, and 20.3±0.2 degrees (2θ) A pharmaceutical composition comprising (ii) a crystalline citrate of a compound exhibiting an X-ray powder diffraction (XRPD) pattern including a peak; and a pharmaceutically acceptable carrier.

2. A pharmaceutical composition according to claim 1, characterized in that the citrate crystals exhibit an XRPD pattern including peaks at 5.7±0.2, 12.7±0.2, and 20.3±0.2 degrees (2θ).

3. In the pharmaceutical composition according to claim 1 or 2, the citrate crystal has the following unit cell parameters: a = 8.9 Å b = 12.2 Å c = 16.5 Å α＝７３．７° β＝７６．６° γ = 83.2° space group P1, Molecular / Asymmetric Unit 2, (This is based on approximately 120K.) A pharmaceutical composition characterized by being defined by [the following].

4. A pharmaceutical composition according to claim 1, characterized in that the citrate crystals exhibit a differential scanning calorimetry thermogram having a peak value at 89.0 ± 2.0°C or 139.5 ± 2.0°C.

5. A pharmaceutical composition according to claim 1, characterized in that the pharmaceutical composition is in the form of an orally administered dosage form.

6. A pharmaceutical composition according to claim 5, characterized in that the pharmaceutical composition is in the form of a tablet.

7. A pharmaceutical composition according to claim 2, characterized in that the citrate crystals exhibit an XRPD pattern further including a peak at 13.0 ± 0.2 degrees (2θ).

8. A pharmaceutical composition according to claim 2, characterized in that the citrate crystals exhibit an XRPD pattern further including a peak at 11.9 ± 0.2 degrees (2θ).

9. A pharmaceutical composition according to claim 2, characterized in that the citrate crystals exhibit an XRPD pattern further including a peak at 20.3 ± 0.2 degrees (2θ).

10. A pharmaceutical composition according to claim 2, characterized in that the citrate crystals exhibit an XRPD pattern further including a peak at 17.1 ± 0.2 degrees (2θ).

11. A pharmaceutical composition according to claim 1, characterized in that the disease or condition is epilepsy.

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