Salts and crystal forms of gabaa positive allosteric modulator

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 TO RELATED APPLICATIONS This application claims priority to U.S. Application No. 16 / 517,369, filed July 19, 2019, and U.S. Provisional Application No. 62 / 725,805, filed August 31, 2018, each of which is incorporated by reference in its entirety.

[0002] The present disclosure relates to salts of 3α-hydroxy-3β-methoxymethyl-21-(1′-imidazolyl)-5α-pregnan-20-one, crystalline forms thereof, and methods of preparing such salts and crystalline forms. [Background technology]

[0003] 3α-Hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnan-20-one (compound 1) is a synthetic neuroactive steroid. Its primary molecular target is the synthesis of γ-aminobutyric acid type A (GABA A ) receptor and acts as a positive allosteric modulator (PAM) of channel function. The structural formula of compound 1 is shown below. TIFF2025020120000002.tif41170

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

[0005] There is a need for isolatable, stable salts of Compound 1 and processes for making them. Summary of the Invention

[0006] The present disclosure provides salts of Compound 1 and methods for making such salts. In some embodiments, the salts of Compound 1 are crystalline. The present disclosure also provides pharmaceutical compositions comprising salts of Compound 1.

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

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

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

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

[0011] The 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 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. [Brief description of the drawings]

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

[0013] definition The term "about" immediately preceding a numerical value means a range (e.g., plus or minus 10% of the value). Unless otherwise specified or inconsistent with such interpretation in the context of this disclosure, for example, "about 50" may mean 45 to 55, "about 25,000" may mean 22,500 to 27,500, etc. For example, in a list of numerical values ​​such as "about 49, about 50, about 55, ...", "about 50" means a range that spans less than half the interval between the preceding and following values, e.g., greater than 49.5 to less than 52.5. Furthermore, the phrase "less than about..." or a value "greater than about..." should be understood in light of the definition of the term "about" provided herein. Similarly, the term "about" when preceding a series of numerical values ​​or a range of values ​​(e.g., "about 10, 20, 30" or "about 10-30") means all 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. The disclosures of these patents, patent applications, and publications are incorporated by reference in their entirety into this disclosure for all purposes in order to more fully describe the state of the art known to those skilled in the art as of the date of this disclosure. In the event of any inconsistency between a cited patent, patent application, publication, and this disclosure, this disclosure will control.

[0015] For convenience, certain terms used in the specification, examples, and claims are collected here. Unless otherwise defined, all technical and scientific terms used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0016] As used herein, the terms "administer," "administering," or "administration" refer to the direct administration of Compound 1 or a pharma- ceutically acceptable salt thereof, or a composition comprising Compound 1 or a pharma-ceutically acceptable salt thereof, to a patient.

[0017] As used herein, the terms "aprotic solvent", "nonprotic solvent", or "non-protic solvent" refer to an organic solvent or mixture of organic solvents that are not readily deprotonated in the presence of a strongly basic reactant. Non-limiting 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, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl isobutyl ketone, hexachloroacetone, acetone, ethyl methyl ketone, methyl methyl ketone (MEK), ethyl acetate, acetic acid, ethyl ether, ethyl ketone, ethyl ether ... isopropyl acetate, 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] The term "carrier" as used herein encompasses carriers, excipients, and diluents and means a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that is involved in the carrying or transport of a pharmaceutical agent from one organ or part of the body to another organ or part of the body.

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

[0020] The terms "effective amount" and "therapeutically effective amount" are used interchangeably in this disclosure and refer to an amount of a compound, or a salt, solvate, or ester thereof, that can achieve the intended result when administered to a patient. For example, an effective amount of a salt of Compound 1 is the amount necessary to reduce at least one symptom of depression in a patient. The actual amount that constitutes an "effective amount" or a "therapeutically effective amount" varies depending on many conditions, including but not limited to the severity of the disease, the size and health of the patient, and the route of administration. An experienced physician can easily determine the appropriate amount using methods known in the medical arts.

[0021] The term "isomer" refers to compounds that have the same chemical formula but different stereochemical formulas, structural formulas, or special arrangements of atoms. Examples of isomers include stereoisomers, diastereomers, enantiomers, conformational isomers, rotamers, geometric isomers, and atropisomers.

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

[0023] As used herein, the phrase "pharmacologically acceptable" refers to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0024] The term "protic solvent" as used herein refers to a solvent or mixture of solvents that can function as an acid for the purpose of protonating unreacted strongly basic reaction intermediates. Non-limiting 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] The term "salts" as used herein includes pharma- ceutically acceptable salts commonly used to form addition salts of free bases. The nature of the salt is not critical, so long as it is pharma- ceutical acceptable. The term "salts" also includes solvates of addition salts, such as hydrates, as well as polymorphs of addition salts. Suitable pharma- ceutical 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 an organic or inorganic acid. However, proton transfer may be incomplete. In such cases, compound 1 and a "co-former" molecule in the solid (i.e., a "co-crystal") interact through non-ionic forces, such as hydrogen bonding.

[0026] When an acid coformer is a solid at about 23° C. (i.e., room temperature) and there is no or partial proton transfer between Compound 1 and the acid coformer, a co-crystal of the coformer and Compound 1 is provided. As used herein, the term “salt” encompasses co-crystalline forms of Compound 1.

[0027] As used herein, the term "substantially similar" refers to an analytical spectrum, such as an XRPD pattern, DSC thermogram, etc., that is very similar to the reference spectrum in both peak positions and peak intensities.

[0028] The term "treating" as used herein with respect to a patient refers to improving at least one symptom of the patient's disorder. Treating may be curing, ameliorating, or at least partially ameliorating 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, a method of treating depression provides a therapeutic effect if the method relieves at least one symptom of depression in a patient.

[0030] As used herein, the symbol "≦" means "less than (not more than)" or "less than (equal to or less than)". "<" means "less than (less than)". "≧" means "greater than (not less than)" or "greater than (equal to or more than)". ">" means "greater than (more than)". Additionally, when used herein in connection with purity or impurity content, numerical values ​​include not only the exact number, but also the approximate range of that number. For example, the phrase "99.0% purity" means a purity of about 99.0%.

[0031] Salt of Compound 1 Compound 1 is a neuroactive steroid GABA-A positive allosteric modulator (PAM) with high potency similar to clinical stage neuroactive steroids (allopregnanolone, ganaxolone, SAGE-217, alphaxolone). Compound 1 is poorly soluble at the pH found in the lower gastrointestinal tract, which may limit the oral bioavailability of Compound 1.

[0032] The synthesis of Compound 1 is described in U.S. Publication Nos. 2004 / 034002 and 2009 / 0118248, crystalline polymorphs of the free base of Compound 1 are described in U.S. Publication No. 2006 / 0074059, and pharmaceutical compositions containing Compound 1 are described in U.S. Publication No. 2009 / 0131383, which are incorporated by reference in their entireties for all purposes.

[0033] The present disclosure provides salts of Compound 1 and crystalline forms thereof.

[0034] Crystalline salt of compound 1 In some embodiments, the disclosure provides crystalline forms of a salt 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). Although crystalline polymorphs of a particular drug substance are chemically identical to any other crystalline polymorph of that drug substance in that they contain the same atoms bonded to each other in the same way, the crystalline forms differ and may affect one or more physical properties, such as stability, solubility, melting point, bulk density, flow properties, or pharmacological properties, such as bioavailability.

[0035] In some embodiments, the crystalline form is characterized by the interlattice plane interval as determined by X-ray powder diffraction pattern (XRPD). XRPD diffractograms are usually represented as a plot of peak intensity versus peak position, i.e., the diffraction angle 2θ (2 theta) in degrees. Characteristic peaks of a particular XRPD diffractogram may be selected according to their peak position and their relative intensity so that the crystalline structure can be easily distinguished from other structures. The % intensity of a peak relative to the most intense peak may 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 will recognize that measurements of XRPD peak positions and / or intensities for a given crystalline form of the same compound will vary within a margin of error. The degree 2θ allows for a reasonable margin of error. Usually, the error is expressed as "±". For example, a degree 2θ of about "8.716±0.2" indicates a range of about 8.716+0.2, i.e., about 8.916, to about 8.716-0.2, i.e., about 8.516. Depending on the sample preparation technique, the calibration technique applied to the instrument, human operating variations, etc., those skilled in the art will recognize that the reasonable error of XRPD may be about ±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 instruments used for the XRPD analysis are provided in the Examples section.

[0038] In some embodiments, the crystalline form is characterized by differential scanning calorimetry (DSC). A DSC thermogram is typically represented as a plot of heat flow normalized in units of watts per gram ("W / g") versus temperature (°C) of a measured sample. DSC thermograms are typically evaluated for estimated onset and end (onset) temperatures, peak temperatures, and heat of fusion. Characteristic peaks in the DSC thermogram are often used as characteristic peaks to distinguish this crystalline structure from other crystalline structures.

[0039] Those skilled in the art will recognize that measurements of DSC thermograms of a given crystalline form of the same compound will vary within a margin of error. The value of the single peak characteristic value expressed in "°C" will provide an appropriate error. Usually, the error is expressed as "±". For example, a single peak characteristic value of about "53.09±2.0" indicates a range of about 53.09+2, i.e., about 55.09, to about 53.09-2, i.e., about 51.09. Depending on the sample preparation technique, the calibration technique applied to the instrument, human operating variations, etc., those skilled in the art will recognize that the appropriate error for the 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 instruments used for DSC thermogram analysis are provided in the Examples section.

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

[0042] In one embodiment, the disclosure provides Compound 1HBr salt (Form A). In some embodiments, the Compound 1HBr salt (Form A) exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 7.6, 15.2, 16.3, 19.8, and 22.9 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 (particularly, about ±0.2). In some embodiments, the Compound 1HBr salt (Form A) exhibits an XRPD including three or more peaks at about 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 Compound 1HBr salt (Form A) further comprises one or more peaks at about 15.5, 19.2, 20.6, 26.1, and 31.3 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 (particularly about ±0.2). In some embodiments, Compound 1HBr salt (Form A) exhibits an XRPD comprising the peaks shown in Table 1 below. TIFF2025020120000003.tif199170

[0043] Some embodiments provide Compound 1HBr salt (Form A), wherein Form A exhibits only three peaks within the range of 15.2±0.2 to 16.3±0.2 degrees 2θ in an XRPD pattern.

[0044] In some embodiments, the Compound 1HBr salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0045] In some embodiments, the Compound 1HBr salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 243.1° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1HBr salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0046] In some embodiments, the Compound 1HBr Salt (Form A) exhibits a TGA thermogram substantially similar to Figure 3. In some embodiments, the TGA thermogram of Compound 1HBr Salt (Form A) exhibits a weight loss of about 0.0-1.9% within 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 Figure 4. In some embodiments, the Compound 1HBr salt (Form A) exhibits a gravimetric moisture sorption of about 1.1% (by weight) at 80% relative humidity.

[0048] In one embodiment, the disclosure provides Compound 1HBr salt (Form B). In some embodiments, the Compound 1HBr salt (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.6, 16.3, 17.7, 21.4, and 23.5 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1HBr salt (Form B) further comprises one or more peaks at about 14.4, 18.7, 24.8, 27.3, and 28.2 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 (particularly, about ±0.2). In some embodiments, the Compound 1HBr salt (Form B) exhibits an XRPD comprising the peaks shown in Table 2 below. TIFF2025020120000004.tif187170

[0049] In some embodiments, the Compound 1HBr salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0050] In some embodiments, the Compound 1HBr salt (Form B) exhibits a DSC thermogram that includes an endothermic peak at about 121° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1HBr salt (Form B) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0051] In some embodiments, the Compound 1HBr Salt (Form B) exhibits a TGA thermogram substantially similar to Figure 6. In some embodiments, the TGA thermogram of Compound 1HBr Salt (Form B) exhibits a weight loss of about 0.0-3.4% within 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 Figure 7. In some embodiments, the Compound 1HBr salt (Form B) exhibits a gravimetric moisture uptake of about 0.2% (by weight) at 80% relative humidity.

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

[0054] In one embodiment, the disclosure provides Compound 1HBr salt (Form C). In some embodiments, the Compound 1HBr salt (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 6.9, 13.8, 20.8, 21.6, and 27.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1HBr salt (Form C) further comprises one or more peaks at about 8.8, 25.6, 27.5, 36.2, and 37.3 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 (particularly, about ±0.2). In some embodiments, the Compound 1HBr salt (Form C) exhibits an XRPD comprising the peaks shown in Table 3 below. TIFF2025020120000005.tif107170

[0055] In some embodiments, the Compound 1HBr salt (Form C) exhibits an XRPD substantially similar to that shown in FIG.

[0056] In some embodiments, the Compound 1HBr salt (Form C) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 141° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1HBr salt (Form C) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0057] In some embodiments, the Compound 1HBr Salt (Form C) exhibits a TGA thermogram substantially similar to Figure 9. In some embodiments, the TGA thermogram of Compound 1HBr Salt (Form C) exhibits a weight loss of about 0.0-4.1% within 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 Figure 10. In some embodiments, the Compound 1HBr salt (Form C) exhibits a gravimetric moisture uptake of about 0.25% (by weight) at 80% relative humidity.

[0059] In one embodiment, the disclosure provides Compound 1HBr salt (Form D). In some embodiments, the Compound 1HBr salt (Form D) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.7, 15.2, 15.6, 16.4, and 23.1 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1HBr salt (Form D) further comprises one or more peaks at about 18.2, 19.9, 21.3, 22.2, and 23.4 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 (particularly, about ±0.2). In some embodiments, the Compound 1HBr salt (Form D) exhibits an XRPD comprising the peaks shown in Table 4 below. TIFF2025020120000006.tif154158

[0060] In some embodiments, the Compound 1HBr salt (Form D) exhibits an XRPD substantially similar to that shown in FIG.

[0061] In some embodiments, the Compound 1HBr salt (Form D) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 248° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1HBr salt (Form D) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0062] In some embodiments, the Compound 1HBr salt (Form D) exhibits a TGA thermogram substantially similar to Figure 12. In some embodiments, the TGA thermogram of Compound 1HBr salt (Form D) exhibits a weight loss of about 0.0-1.7% within the temperature range of 29-150°C.

[0063] In some embodiments, the disclosure provides Compound 1HBr salt (Form E). In some embodiments, the Compound 1HBr salt (Form E) exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 7.6, 15.2, 16.3, 22.9, and 23.2 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 (particularly, about ±0.2). In some embodiments, the Compound 1HBr salt (Form E) exhibits an XRPD including three or more peaks at about 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 Compound 1HBr salt (Form E) further comprises one or more peaks at about 9.6, 17.4, 22.4, 23.6, and 31.2 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 (particularly about ±0.2). In some embodiments, the Compound 1HBr salt (Form E) exhibits an XRPD comprising the peaks shown in Table 5 below. TIFF2025020120000007.tif187170

[0064] Some embodiments provide Compound 1HBr salt (Form E), in which Form E exhibits only two peaks within the range of 15.2±0.2 to 16.3±0.2 degrees 2θ in an XRPD pattern.

[0065] In some embodiments, the Compound 1HBr salt (Form E) exhibits an XRPD substantially similar to that shown in FIG.

[0066] In some embodiments, the Compound 1HBr salt (Form E) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 245° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1HBr salt (Form E) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0067] In some embodiments, the Compound 1HBr Salt (Form E) exhibits a TGA thermogram substantially similar to Figure 14. In some embodiments, the TGA thermogram of Compound 1HBr Salt (Form E) exhibits a weight loss of about 0.0-0.5% within a temperature range of 28-150°C.

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

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

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

[0071] In one embodiment, the disclosure provides Compound 1 citrate (Form A). In some embodiments, the Compound 1 citrate (Form A) exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 5.7, 11.9, 17.1, 20.1, 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 (particularly, about ±0.2). In some embodiments, the Compound 1 citrate (Form A) exhibits an XRPD including three or more peaks at about 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 comprises one or more peaks at about 12.7, 13.0, 13.6, 15.3, and 16.8 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 (particularly about ±0.2). In some embodiments, the Compound 1 citrate (Form A) exhibits an XRPD comprising the peaks shown in Table 6 below. TIFF2025020120000008.tif236170

[0072] In some embodiments, the Compound 1 citrate salt (Form A) has a pH of about: 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 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 salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0074] In some embodiments, the Compound 1 citrate (Form A) exhibits a DSC thermogram that includes an endothermic peak at about 89.0° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 citrate (Form A) exhibits a DSC thermogram that includes an endothermic peak at about 89.0±2.0° C. In some embodiments, the Compound 1 citrate (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 139.5° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 citrate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 139.5±2.0° C. In some embodiments, the Compound 1 citrate salt (Form A) exhibits a DSC thermogram substantially similar to that in FIG.

[0075] In some embodiments, the Compound 1 citrate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 16. In some embodiments, the TGA thermogram of Compound 1 citrate salt (Form A) exhibits a weight loss of 0.0-2.6% within a temperature range of 25-65°C.

[0076] In some embodiments, the Compound 1 citrate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 17. In some embodiments, the Compound 1 citrate salt (Form A) exhibits a gravimetric moisture uptake of about 3.6% (by weight) at 80% relative humidity.

[0077] In some embodiments, the Compound 1 citrate salt (Form A) is defined by unit cell parameters substantially similar to the following: 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, molecule / asymmetric unit 2, and a crystalline form at about 120.00 K.

[0078] In one embodiment, the disclosure provides Compound 1 citrate (Form B). In some embodiments, the Compound 1 citrate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.5, 5.7, 10.9, 16.3, and 20.5 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 citrate (Form B) further comprises one or more peaks at about 3.4, 11.8, 14.6, 17.2, and 21.1 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 (particularly, about ±0.2). In some embodiments, the Compound 1 citrate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 7 below. TIFF2025020120000009.tif106170

[0079] In some embodiments, the Compound 1 citrate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

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

[0081] In some embodiments, the Compound 1 citrate salt (Form B) exhibits a TGA thermogram substantially similar to Figure 19. In some embodiments, the TGA thermogram of Compound 1 citrate salt (Form B) exhibits a weight loss of about 0.0-4.5% within a temperature range of 25-120°C.

[0082] In some embodiments, the Compound 1 citrate salt (Form B) exhibits a DVS isotherm plot substantially similar to Figure 20. In some embodiments, the Compound 1 citrate salt (Form B) exhibits a gravimetric moisture uptake of about 2.8% (by weight) at 80% relative humidity.

[0083] In one embodiment, the disclosure provides Compound 1 citrate (Form C). In some embodiments, the Compound 1 citrate (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 15.4, 18.7, 19.7, 20.6, and 27.1 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 citrate (Form C) further comprises one or more peaks at about 13.5, 15.5, 16.2, 17.0, and 22.1 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 (particularly, about ±0.2). In some embodiments, the Compound 1 citrate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 8 below. TIFF2025020120000010.tif200170

[0084] In some embodiments, the Compound 1 citrate salt (Form C) exhibits an XRPD substantially similar to that shown in FIG.

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

[0086] In one embodiment, the disclosure provides Compound 1 mesylate (Form A). In some embodiments, the Compound 1 mesylate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.6, 7.1, 14.2, 19.1, and 25.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 mesylate (Form A) further comprises one or more peaks at about 7.7, 12.7, 17.8, 19.4, and 21.4 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 (particularly, about ±0.2). In some embodiments, the Compound 1 mesylate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 9 below. TIFF2025020120000011.tif92170

[0087] In some embodiments, the Compound 1 mesylate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0088] In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak at about 170.9° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 209.7° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG. 23.

[0089] In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 23. In some embodiments, the TGA thermogram of Compound 1 mesylate salt (Form A) exhibits a weight loss of 0.0-0.5% within a temperature range of 25-150°C.

[0090] In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 24. In some embodiments, the Compound 1 mesylate salt (Form A) exhibits a gravimetric moisture uptake of about 3.4% (by weight) at 80% relative humidity.

[0091] In one embodiment, the disclosure provides Compound 1 mesylate (Form B). In some embodiments, the Compound 1 mesylate (Form B) exhibits an XRPD that includes one or more peaks (particularly, three or more peaks) at about 7.1, 14.3, 15.9, 21.4, and 22.6 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 (particularly, about ±0.2). In some embodiments, the Compound 1 mesylate (Form B) exhibits an XRPD that includes the peaks shown in Table 10A below. TIFF2025020120000012.tif45170

[0092] In some embodiments, the Compound 1 mesylate salt (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 including one or more peaks (particularly, three or more peaks) at about 7.5, 15.0, 19.4, 22.5, and 30.2 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 (particularly, about ±0.2). In some embodiments, the Compound 1 mesylate (Form C) exhibits an XRPD including the peaks shown in Table 10B below. TIFF2025020120000013.tif42170

[0094] In some embodiments, the Compound 1 mesylate salt (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 that includes one or more peaks (particularly, three or more peaks) at about 7.4, 15.0, and 22.6 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 (particularly, about ±0.2). In some embodiments, the Compound 1 mesylate (Form D) exhibits an XRPD that includes the peaks shown in Table 11 below. TIFF2025020120000014.tif32170

[0096] In some embodiments, the Compound 1 mesylate salt (Form D) exhibits an XRPD substantially similar to that shown in FIG.

[0097] Phosphate In some embodiments, the disclosure provides a phosphate salt 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 comprising one or more peaks (particularly, three or more peaks) at about 3.3, 3.6, 5.4, 9.9, and 13.1 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 phosphate (Form A) further comprises one or more peaks at about 16.1, 17.9, 20.9, 23.7, and 26.4 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 (particularly, about ±0.2). In some embodiments, the Compound monophosphate (Form A) exhibits an XRPD comprising the peaks shown in Table 12 below. TIFF2025020120000015.tif108170

[0099] In some embodiments, the Compound monophosphate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0100] In some embodiments, the Compound monophosphate (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 217.6° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound monophosphate (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0101] In some embodiments, the Compound monophosphate (Form A) exhibits a TGA thermogram substantially similar to Figure 28. In some embodiments, the TGA thermogram of Compound monophosphate (Form A) exhibits a weight loss of 0.0-1.7% within the temperature range of 25-204°C.

[0102] In some embodiments, the Compound monophosphate (Form A) exhibits a DVS isotherm plot substantially similar to Figure 29. In some embodiments, the Compound monophosphate (Form A) exhibits a gravimetric moisture uptake of about 2.1% (by weight) at 80% relative humidity.

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

[0104] In some embodiments, the disclosure provides a crystalline form of Compound 1 tartrate. In some embodiments, the disclosure provides a crystalline form of Compound 1D(-)-tartrate. In some embodiments, the 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 comprising one or more peaks (particularly, three or more peaks) at about 3.6, 4.7, 13.9, 18.6, and 22.8 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1L(+)-tartrate (Form A) further comprises one or more peaks at about 14.6, 17.8, and 18.1 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 (particularly, about ±0.2). In some embodiments, the compound 1L(+)-tartrate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 13 below. TIFF2025020120000016.tif58170

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

[0107] In some embodiments, the compound 1L(+)-tartrate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 207.6° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1L(+)-tartrate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0108] In some embodiments, the Compound 1L(+)-tartrate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 31. In some embodiments, the TGA thermogram of Compound 1L(+)-tartrate salt (Form A) exhibits a weight loss of 0.0-1.2% within the temperature range of 25-189°C.

[0109] In some embodiments, the Compound 1L(+)-tartrate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 32. In some embodiments, the Compound 1L(+)-tartrate salt (Form A) exhibits a gravimetric moisture uptake of about 1.6% (by weight) at 80% relative humidity.

[0110] In one embodiment, the disclosure provides Compound 1L(+)-tartrate (Form B). In some embodiments, the Compound 1L(+)-tartrate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.6, 4.6, 12.4, 13.9, and 22.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1L(+)-tartrate (Form B) further comprises one or more peaks at about 14.8, 18.3, and 18.5 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 (particularly, about ±0.2). In some embodiments, the compound 1L(+)-tartrate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 14 below. TIFF2025020120000017.tif58170

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

[0112] In some embodiments, the compound 1L(+)-tartrate salt (Form B) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 207.3° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1L(+)-tartrate salt (Form B) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0113] In some embodiments, the Compound 1L(+)-tartrate salt (Form B) exhibits a TGA thermogram substantially similar to Figure 34. In some embodiments, the TGA thermogram of Compound 1L(+)-tartrate salt (Form B) exhibits a weight loss of 0.0-0.6% within the temperature range of 25-180°C.

[0114] In some embodiments, the Compound 1L(+)-tartrate salt (Form B) exhibits a DVS isotherm plot substantially similar to Figure 35. In some embodiments, the Compound 1L(+)-tartrate salt (Form B) exhibits a gravimetric moisture uptake of about 1.7% (by weight) at 80% relative humidity.

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

[0116] In one embodiment, the disclosure provides Compound 1 fumarate (Form A). In some embodiments, the Compound 1 fumarate (Form A) exhibits an XRPD that includes 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 (particularly about ±0.2). In some embodiments, the Compound 1 fumarate (Form A) exhibits an XRPD that includes the peaks shown in Table 15 below. TIFF2025020120000018.tif26170

[0117] In some embodiments, the Compound 1 fumarate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0118] In some embodiments, the Compound 1 fumarate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 87.0° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 fumarate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0119] In some embodiments, the Compound 1 fumarate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 37. In some embodiments, the TGA thermogram of Compound 1 fumarate salt (Form A) exhibits a weight loss of 0.0-0.9% within the temperature range of 25-75°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 including one or more peaks (particularly, three or more peaks) at about 3.6, 11.0, 16.2, and 17.5 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 (particularly, about ±0.2). In some embodiments, the Compound 1 fumarate (Form B) exhibits an XRPD including the peaks shown in Table 16 below. TIFF2025020120000019.tif38170

[0121] In some embodiments, the Compound 1 fumarate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0122] In some embodiments, the Compound 1 fumarate salt (Form B) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 89.9° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 fumarate salt (Form B) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0123] In some embodiments, the Compound 1 fumarate salt (Form B) exhibits a TGA thermogram substantially similar to Figure 39. In some embodiments, the TGA thermogram of Compound 1 fumarate salt (Form B) exhibits a weight loss of 0.0-1.85% within a temperature range of 25-150°C.

[0124] In some embodiments, the Compound 1 fumarate salt (Form B) exhibits a DVS isotherm plot substantially similar to Figure 40. In some embodiments, the Compound 1 fumarate salt (Form B) exhibits a gravimetric moisture uptake of about 7.2% (by weight) at 80% relative humidity.

[0125] In one embodiment, the disclosure provides compound 1 fumarate (Form C). In some embodiments, the compound 1 fumarate (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.5, 15.4, 16.7, 17.6, and 28.8 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 fumarate (Form C) further comprises one or more peaks at about 8.4, 19.7, 20.5, 22.9, and 38.1 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 (particularly, about ±0.2). In some embodiments, the Compound 1 fumarate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 17 below. TIFF2025020120000020.tif102170

[0126] In some embodiments, the Compound 1 fumarate salt (Form C) exhibits an XRPD substantially similar to that shown in FIG.

[0127] In one embodiment, the disclosure provides Compound 1 fumarate (Form D). In some embodiments, the Compound 1 fumarate (Form D) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.2, 12.2, 15.2, 15.5, and 19.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 fumarate (Form D) further comprises one or more peaks at about 10.4, 13.6, 14.2, 21.2, and 22.3 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 (particularly, about ±0.2). In some embodiments, the Compound 1 fumarate salt (Form D) exhibits an XRPD comprising the peaks shown in Table 18 below. TIFF2025020120000021.tif127170

[0128] In some embodiments, the Compound 1 fumarate salt (Form D) exhibits an XRPD substantially similar to that shown in FIG.

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

[0130] In one embodiment, the disclosure provides Compound 1 tosylate (Form A). In some embodiments, the Compound 1 tosylate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.4, 9.8, 10.3, 12.5, and 15.3 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 tosylate (Form A) further comprises one or more peaks at about 17.4, 17.9, 19.6, 23.2, and 26.0 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 (particularly, about ±0.2).

[0131] In some embodiments, the Compound 1 tosylate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 19 below. TIFF2025020120000022.tif126170

[0132] In some embodiments, the Compound 1 tosylate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0133] In some embodiments, the Compound 1 tosylate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 186.2° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 tosylate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0134] In some embodiments, the Compound 1 tosylate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 44. In some embodiments, the TGA thermogram of Compound 1 tosylate salt (Form A) exhibits a weight loss of 0.0-0.9% within the temperature range of 25-175°C.

[0135] In some embodiments, the Compound 1 tosylate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 45. In some embodiments, the Compound 1 tosylate salt (Form A) exhibits a gravimetric moisture uptake of about 1.5% (by weight) at 80% relative humidity.

[0136] In one embodiment, the disclosure provides Compound 1 tosylate (Form B). In some embodiments, the Compound 1 tosylate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 10.0, 15.2, 15.5, 17.2, and 19.4 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 tosylate (Form B) further comprises one or more peaks at about 10.3, 16.7, 19.1, 20.1, and 20.8 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 (particularly, about ±0.2).

[0137] In some embodiments, the Compound 1 tosylate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 20 below. TIFF2025020120000023.tif160170

[0138] In some embodiments, the Compound 1 tosylate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0139] In one embodiment, the disclosure provides Compound 1 tosylate (Form C). In some embodiments, the Compound 1 tosylate (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 7.4, 10.2, 12.5, 18.3, and 19.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 tosylate (Form C) further comprises one or more peaks at about 9.8, 14.7, 16.6, 17.8, and 23.2 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 (particularly, about ±0.2).

[0140] In some embodiments, the Compound 1 tosylate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 21 below. TIFF2025020120000024.tif187170

[0141] In some embodiments, the Compound 1 tosylate salt (Form C) exhibits an XRPD substantially similar to that shown in FIG.

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

[0143] In some embodiments, the disclosure provides a crystalline form of Compound 1 glucuronate. In some embodiments, the disclosure provides a crystalline form of Compound 1 D-glucuronate. In some embodiments, the disclosure provides a crystalline form of Compound 1 L-glucuronate.

[0144] In one embodiment, the disclosure provides compound 1D-glucuronate (Form A). In some embodiments, the compound 1D-glucuronate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 4.3, 12.9, 16.8, 20.2, and 20.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 1D-glucuronate (Form A) further comprises one or more peaks at about 3.3, 14.7, 17.3, 21.6, and 24.8 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 (particularly about ±0.2).

[0145] In some embodiments, the compound 1D-glucuronate (Form A) exhibits an XRPD comprising the peaks shown in Table 22 below. TIFF2025020120000025.tif123170

[0146] In some embodiments, the compound 1D-glucuronate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0147] In some embodiments, the compound 1D-glucuronate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 116.2° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1D-glucuronate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 139.3° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1D-glucuronate (Form A) exhibits a DSC thermogram substantially similar to FIG.

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

[0149] In some embodiments, the compound 1D-glucuronate (Form A) exhibits a DVS isotherm plot substantially similar to Figure 50. In some embodiments, the compound 1D-glucuronate (Form A) exhibits a gravimetric moisture uptake of about 1.4% (by weight) at 80% relative humidity.

[0150] In one embodiment, the disclosure provides compound 1D-glucuronate, Form B. In some embodiments, the compound 1D-glucuronate, Form B, exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.7, 16.7, 17.0, 20.0, and 20.4 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 1D-glucuronate (Form B) further comprises one or more peaks at about 8.5, 15.0, 19.5, 22.5, and 24.3 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 (particularly about ±0.2).

[0151] In some embodiments, the compound 1D-glucuronate (Form B) exhibits an XRPD comprising the peaks shown in Table 23 below. TIFF2025020120000026.tif145170

[0152] In some embodiments, the compound 1D-glucuronate (Form B) exhibits an XRPD substantially similar to that shown in FIG.

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

[0154] In one embodiment, the disclosure provides compound 1 ethanesulfonate (Form A). In some embodiments, the compound 1 ethanesulfonate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.4, 3.7, 7.6, 15.3, and 23.0 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 ethanesulfonate (Form A) further comprises one or more peaks at about 23.3 and 30.8 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 (particularly, about ±0.2).

[0155] In some embodiments, the Compound 1 ethanesulfonate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 24 below. TIFF2025020120000027.tif51170

[0156] In some embodiments, the Compound 1 ethanesulfonate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0157] In some embodiments, the compound 1 ethanesulfonate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 177.9° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1 ethanesulfonate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 207.0° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1 ethanesulfonate (Form A) exhibits a DSC thermogram substantially similar to FIG. 53.

[0158] In some embodiments, the Compound 1 ethanesulfonate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 53. In some embodiments, the TGA thermogram of Compound 1 ethanesulfonate salt (Form A) exhibits a weight loss of 0.0-2.9% within the temperature range of 25-180°C.

[0159] In some embodiments, the Compound 1 ethanesulfonate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 54. In some embodiments, the Compound 1 ethanesulfonate salt (Form A) exhibits a gravimetric moisture uptake of about 1.4% (by weight) at 80% relative humidity.

[0160] Sulfate In some embodiments, the disclosure provides a sulfate salt 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 comprising one or more peaks (particularly, three or more peaks) at about 3.6, 5.2, 7.8, 8.1, and 15.1 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 sulfate (Form A) further comprises one or more peaks at about 14.7, 17.4, 18.2, 18.4, and 19.7 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 (particularly, about ±0.2). In some embodiments, the Compound 1 sulfate (Form A) exhibits an XRPD comprising the peaks shown in Table 25 below. TIFF2025020120000028.tif89170

[0162] In some embodiments, the Compound 1 sulfate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0163] In some embodiments, the Compound 1 sulfate salt (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 167.1° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 sulfate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0164] In some embodiments, the Compound 1 sulfate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 56. In some embodiments, the TGA thermogram of Compound 1 sulfate salt (Form A) exhibits a weight loss of 0.0-1.0% within the temperature range of 25-120°C.

[0165] In some embodiments, the sulfate salt of Compound 1 (Form A) exhibits a DVS isotherm plot substantially similar to Figure 57. In some embodiments, the sulfate salt of Compound 1 (Form A) exhibits a gravimetric moisture uptake of about 6.2% (by weight) at 80% relative humidity.

[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 comprising one or more peaks (particularly, three or more peaks) at about 3.6, 5.6, 16.6, 19.6, and 19.8 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 ascorbate (Form A) further comprises one or more peaks at about 11.5, 11.9, 21.6, 24.1, and 24.5 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 (particularly, about ±0.2).

[0168] In some embodiments, the Compound 1 ascorbate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 26 below. TIFF2025020120000029.tif102170

[0169] In some embodiments, the Compound 1 ascorbate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

[0171] In some embodiments, the Compound 1 ascorbate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 59. In some embodiments, the TGA thermogram of Compound 1 ascorbate salt (Form A) exhibits a weight loss of 0.0-5.6% within a temperature range of 25-120°C.

[0172] In some embodiments, the Compound 1 ascorbate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 60. In some embodiments, the Compound 1 ascorbate salt (Form A) exhibits a gravimetric moisture uptake of about 5.7% (by weight) at 80% relative humidity.

[0173] In one embodiment, the disclosure provides Compound 1 ascorbate (Form B). In some embodiments, the Compound 1 ascorbate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.5, 16.6, 19.7, 20.1, and 28.3 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 ascorbate (Form B) further comprises one or more peaks at about 14.7 and 23.6 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 (particularly, about ±0.2).

[0174] In some embodiments, the Compound 1 ascorbate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 27 below. TIFF2025020120000030.tif51170

[0175] In some embodiments, the Compound 1 ascorbate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0176] Napadisilate In some embodiments, the disclosure provides a napadisylate salt of Compound 1 ("Compound 1 napadisylate salt"). In some embodiments, the disclosure provides a crystalline form of Compound 1 napadisylate salt.

[0177] In one embodiment, the disclosure provides compound 1 napadisylate (Form A). In some embodiments, the compound 1 napadisylate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.3, 9.4, 14.2, 16.4, and 17.8 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 napadisylate (Form A) further comprises one or more peaks at about 9.7, 17.3, 20.3, 24.4, and 26.1 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 (particularly, about ±0.2). In some embodiments, the Compound 1 napadisylate (Form A) exhibits an XRPD comprising the peaks shown in Table 28 below. TIFF2025020120000031.tif122170

[0178] In some embodiments, the Compound 1 napadisylate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0179] In some embodiments, the compound 1 napadisylate (Form A) exhibits a DSC thermogram comprising 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 (particularly about ±2.0). In some embodiments, the compound 1 napadisylate (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

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

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

[0182] In some embodiments, the disclosure provides Compound 1 napadisylate (Form B). In some embodiments, the Compound 1 napadisylate (Form B) exhibits an XRPD comprising one or more peaks (particularly, 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 napadisylate (Form B) further comprises 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 (particularly about ±0.2).

[0183] In some embodiments, the Compound 1 napadisylate (Form B) exhibits an XRPD comprising the peaks shown in Table 29 below. TIFF2025020120000032.tif85170

[0184] In some embodiments, the Compound 1 napadisylate (Form B) exhibits an XRPD substantially similar to that shown in FIG.

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

[0186] In one embodiment, the disclosure provides Compound 1 Malonate (Form A). In some embodiments, the Compound 1 Malonate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 15.1, 18.0, 18.8, 23.4, and 23.8 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 Malonate (Form A) further comprises one or more peaks at about 3.6, 13.8, 15.6, 21.4, and 27.6 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 (particularly, about ±0.2).

[0187] In some embodiments, the Compound 1 malonate (Form A) exhibits an XRPD comprising the peaks shown in Table 30 below. TIFF2025020120000033.tif122170

[0188] In some embodiments, the Compound 1 malonate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0189] In some embodiments, the Compound 1 malonate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 36.9° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 malonate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 124.6° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 malonate (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

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

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

[0192] In one embodiment, the disclosure provides Compound 1 besylate (Form A). In some embodiments, the Compound 1 besylate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.7, 15.8, 22.1, 23.2, and 26.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 besylate (Form A) further comprises one or more peaks at about 3.7, 16.2, 17.8, 19.5, and 30.4 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 (particularly, about ±0.2).

[0193] In some embodiments, the Compound 1 besylate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 31 below. TIFF2025020120000034.tif85170

[0194] In some embodiments, the Compound 1 besylate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0195] In some embodiments, the Compound 1 besylate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 194.2° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 besylate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0196] In some embodiments, the Compound 1 besylate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 69. In some embodiments, the TGA thermogram of Compound 1 besylate salt (Form A) exhibits a weight loss of 0.0-3.3% within the temperature range of 25-120°C.

[0197] In some embodiments, the Compound 1 besylate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 70. In some embodiments, the Compound 1 besylate salt (Form A) exhibits a gravimetric moisture uptake of about 4.0% (by weight) at 80% relative humidity.

[0198] In one embodiment, the disclosure provides Compound 1 besylate (Form B).

[0199] In some embodiments, the Compound 1 besylate salt (Form B) exhibits an XRPD comprising one or more peaks (particularly three or more peaks) at about 7.3, 14.7, 22.1, 23.2, and 29.6 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 (particularly about ±0.2). In some embodiments, the XRPD of the Compound 1 besylate salt (Form B) further comprises one or more peaks at about 7.9, 16.2, 16.4, 17.2, and 30.4 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 (particularly about ±0.2).

[0200] In some embodiments, the Compound 1 besylate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 32 below. TIFF2025020120000035.tif68170

[0201] In some embodiments, the Compound 1 besylate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0202] Isethionate In some embodiments, the disclosure provides an isethionate salt of Compound 1 ("Compound 1 isethionate salt"). In some embodiments, the disclosure provides a crystalline form of Compound 1 isethionate salt.

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

[0204] In some embodiments, the compound 1 isethionate (Form A) exhibits an XRPD that includes one or more peaks (particularly three or more peaks) at about 5.6, 16.7, 16.9, 18, and 20.9 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 (particularly about ±0.2). In some embodiments, the XRPD of the compound 1 isethionate (Form A) further includes one or more peaks at about 3.7, 15.7, 16.2, 20.7, and 25.1 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 (particularly about ±0.2).

[0205] In some embodiments, the Compound 1 isethionate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 33 below. TIFF2025020120000036.tif147170

[0206] In some embodiments, the Compound 1 isethionate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0207] In some embodiments, the Compound 1 isethionate salt (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 153.3° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 isethionate salt (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0208] In some embodiments, the Compound 1 isethionate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 73. In some embodiments, the TGA thermogram of Compound 1 isethionate salt (Form A) exhibits a weight loss of 0.0 to 0.0% within the temperature range of 25 to 120°C.

[0209] In some embodiments, the Compound 1 isethionate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 74. In some embodiments, the Compound 1 isethionate salt (Form A) exhibits a gravimetric moisture uptake of about 4.9% (by weight) at 80% relative humidity.

[0210] In one embodiment, the disclosure provides Compound 1 isethionate, Form B. In some embodiments, the Compound 1 isethionate, Form B, exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.5, 15.8, 17.9, 18.1, and 18.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 isethionate salt (Form B) further comprises one or more peaks at about 11.4, 13.1, 14.2, 15.0, and 17.0 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 (particularly about ±0.2).

[0211] In some embodiments, the Compound 1 isethionate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 34 below. TIFF2025020120000037.tif96170

[0212] In some embodiments, the Compound 1 isethionate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0213] Gentisate In some embodiments, the disclosure provides a gentisate salt of Compound 1 ("Compound 1 gentisate salt"). In some embodiments, the disclosure provides a crystalline form of Compound 1 gentisate salt.

[0214] In one embodiment, the disclosure provides Compound 1 gentisate (Form A). In some embodiments, the compound 1 gentisate (Form A) exhibits an XRPD comprising one or more peaks (particularly three or more peaks) at about 3.4, 3.6, 7.0, 14.6, and 21.4 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 (particularly about ±0.2). In some embodiments, the XRPD of the compound 1 gentisate (Form A) further comprises one or more peaks at about 16.0, 18.0, 18.5, 19.5, and 21.1 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 (particularly about ±0.2).

[0215] In some embodiments, the Compound 1 gentisate (Form A) exhibits an XRPD comprising the peaks shown in Table 35 below. TIFF2025020120000038.tif121170

[0216] In some embodiments, the Compound 1 gentisate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0217] In some embodiments, the compound 1 gentisate (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 117.7° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound 1 gentisate (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

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

[0219] In some embodiments, the Compound 1 gentisate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 78. In some embodiments, the Compound 1 gentisate salt (Form A) exhibits a gravimetric moisture uptake of about 3.1% (by weight) at 80% relative humidity.

[0220] In one embodiment, the disclosure provides Compound 1 gentisate (Form B). In some embodiments, the compound 1 gentisate (Form B) exhibits an XRPD comprising one or more peaks (particularly three or more peaks) at about 5.5, 10.9, 16.4, 21.9, and 22.8 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 (particularly about ±0.2). In some embodiments, the XRPD of the compound 1 gentisate (Form B) further comprises one or more peaks at about 9.2, 13.0, 17.2, 18.7, and 27.8 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 (particularly about ±0.2).

[0221] In some embodiments, the Compound 1 gentisate (Form B) exhibits an XRPD comprising the peaks shown in Table 36 below. TIFF2025020120000039.tif127170

[0222] In some embodiments, the Compound 1 gentisate (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0223] In one embodiment, the disclosure provides compound 1 gentisate (Form C). In some embodiments, the compound 1 gentisate (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.3, 15.2, 15.9, 21.4, and 26.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 gentisate (Form C) further comprises one or more peaks at about 7.6, 10.6, 13.8, 16.9, and 19.8 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 (particularly, about ±0.2).

[0224] In some embodiments, the Compound 1 gentisate (Form C) exhibits an XRPD comprising the peaks shown in Table 37 below. TIFF2025020120000040.tif97170

[0225] In some embodiments, the Compound 1 gentisate (Form C) exhibits an XRPD substantially similar to that shown in FIG.

[0226] 1-Hydroxy-2-naphthoic acid salt In some embodiments, the disclosure provides a 1-hydroxy-2-naphthoate salt of compound 1 ("compound 11-hydroxy-2-naphthoate salt"). In some embodiments, the disclosure provides a crystalline form of compound 11-hydroxy-2-naphthoate salt.

[0227] In one embodiment, the disclosure provides the compound 11-hydroxy-2-naphthoate (Form A). In some embodiments, the compound 11-hydroxy-2-naphthoate (Form A) exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 3.2, 6.2, 13.8, 21.2, and 21.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoic acid salt (Form A) further comprises one or more peaks at about 13.4, 16.2, 19.9, 20.2, and 24.7 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 (particularly about ±0.2).

[0228] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form A) exhibits an XRPD comprising the peaks shown in Table 38 below. TIFF2025020120000041.tif95170

[0229] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

[0231] In some embodiments, the compound 11-hydroxy-2-naphthoate (Form A) exhibits a TGA thermogram substantially similar to Figure 82. In some embodiments, the TGA thermogram of the compound 11-hydroxy-2-naphthoate (Form A) exhibits a weight loss of 0.0-3.6% within the temperature range of 25-120°C. In some embodiments, the compound 11-hydroxy-2-naphthoate (Form A) exhibits a DVS isotherm plot substantially similar to Figure 83. In some embodiments, the compound 11-hydroxy-2-naphthoate (Form A) exhibits a gravimetric moisture uptake of about 4.6% (by weight) at 80% relative humidity.

[0232] In one embodiment, the disclosure provides the compound 11-hydroxy-2-naphthoate, Form B. In some embodiments, the compound 11-hydroxy-2-naphthoate, Form B, exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 8.0, 8.6, 13.5, 13.8, and 20.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (Form B) further comprises one or more peaks at about 14.4, 15.2, 16.1, 21.4, and 23.8 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 (particularly about ±0.2).

[0233] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form B) exhibits an XRPD comprising the peaks shown in Table 39 below. TIFF2025020120000042.tif186170

[0234] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0235] In one embodiment, the disclosure provides the compound 11-hydroxy-2-naphthoate, Form C. In some embodiments, the compound 11-hydroxy-2-naphthoate, Form C, exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 8.5, 13.7, 14.2, 17.3, and 21.4 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (Form C) further comprises one or more peaks at about 7.7, 15.4, 20.2, 20.6, and 21.1 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 (particularly about ±0.2).

[0236] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form C) exhibits an XRPD comprising the peaks shown in Table 40 below. TIFF2025020120000043.tif135170

[0237] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form C) exhibits an XRPD substantially similar to that shown in FIG.

[0238] In one embodiment, the disclosure provides the compound 11-hydroxy-2-naphthoate, Form D. In some embodiments, the compound 11-hydroxy-2-naphthoate, Form D, exhibits an XRPD including one or more peaks (particularly, three or more peaks) at about 10.4, 12.9, 13.5, 20.4, and 20.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of the compound 11-hydroxy-2-naphthoate (Form D) further comprises one or more peaks at about 6.3, 9.1, 11.2, 13.2, and 19.9 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 (particularly about ±0.2).

[0239] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form D) exhibits an XRPD comprising the peaks shown in Table 41 below. TIFF2025020120000044.tif91170

[0240] In some embodiments, the compound 11-hydroxy-2-naphthoic acid salt (Form D) exhibits an XRPD substantially similar to that shown in FIG.

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

[0242] In one embodiment, the disclosure provides compound 1 cyclamate (Form A). In some embodiments, the compound 1 cyclamate (Form A) exhibits an XRPD comprising one or more peaks (particularly three or more peaks) at about 6.6, 7.2, 18.5, 19.5, and 21.6 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 (particularly about ±0.2). In some embodiments, the XRPD of compound 1 cyclamate (Form A) further comprises one or more peaks at about 14.3, 14.8, 17.2, 17.6, and 18.2 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 (particularly about ±0.2).

[0243] In some embodiments, the Compound 1 cyclamate (Form A) exhibits an XRPD comprising the peaks shown in Table 42 below. TIFF2025020120000045.tif83170

[0244] In some embodiments, the Compound 1 cyclamate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

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

[0247] In some embodiments, the Compound 1 cyclamate (Form A) exhibits a DVS isotherm plot substantially similar to Figure 89. In some embodiments, the Compound 1 cyclamate (Form A) exhibits a gravimetric moisture uptake of about 7.3% (by weight) at 80% relative humidity.

[0248] Ethane-1,2-disulfonate In some embodiments, the disclosure provides an ethane-1,2-disulfonic acid salt of Compound 1 ("Compound 1 ethane-1,2-disulfonic acid salt"). In some embodiments, the disclosure provides a crystalline form of Compound 1 ethane-1,2-disulfonic acid salt.

[0249] In one embodiment, the 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 that includes one or more peaks (particularly, three or more peaks) at about 16.2, 16.5, 17.5, 20.7, and 21.3 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 ethane-1,2-disulfonic acid salt (Form A) further comprises one or more peaks at about 3.7, 5.5, 13.8, 14.7, and 26.0 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 (particularly about ±0.2).

[0250] In some embodiments, the Compound 1 ethane-1,2-disulfonic acid salt (Form A) exhibits an XRPD comprising the peaks shown in Table 43 below. TIFF2025020120000046.tif123170

[0251] In some embodiments, the Compound 1 ethane-1,2-disulfonic acid salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

[0253] In some embodiments, the Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 91. In some embodiments, the TGA thermogram of Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits a weight loss of 0.0-0.7% within the temperature range of 25-120°C.

[0254] In some embodiments, the Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 92. In some embodiments, the Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits a gravimetric moisture uptake of about 12.9% (by weight) at 80% relative humidity.

[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 that includes one or more peaks (particularly, three or more peaks) at about 5.5, 16.4, 17.4, 17.6, and 20.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 ethane-1,2-disulfonate salt (Form B) further comprises one or more peaks at about 10.9, 13.7, 14.6, 21.2, and 22.1 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 (particularly about ±0.2).

[0256] In some embodiments, the Compound 1 ethane-1,2-disulfonic acid salt (Form B) exhibits an XRPD comprising the peaks shown in Table 44 below. TIFF2025020120000047.tif130170

[0257] In some embodiments, the Compound 1 ethane-1,2-disulfonic acid salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0258] Dichloroacetate In some embodiments, the disclosure provides a dichloroacetate salt of Compound 1 ("Compound 1 dichloroacetate"). In some embodiments, the disclosure provides a 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 comprising one or more peaks (particularly, three or more peaks) at about 3.4, 3.6, 16.2, 17.1, and 19.5 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 dichloroacetate (Form A) further comprises one or more peaks at about 8.1, 11.4, 12.8, 16.7, and 20.0 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 (particularly, about ±0.2).

[0260] In some embodiments, the Compound 1 dichloroacetate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 45 below. TIFF2025020120000048.tif116170

[0261] In some embodiments, the Compound 1 dichloroacetate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0262] In some embodiments, the Compound 1 dichloroacetate (Form A) exhibits a DSC thermogram that includes an endothermic peak (e.g., a sharp endothermic peak) at about 117.7° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 dichloroacetate (Form A) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0263] In some embodiments, the Compound 1 dichloroacetate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 95. In some embodiments, the TGA thermogram of Compound 1 dichloroacetate salt (Form A) exhibits a weight loss of 0.0-3.7% within the temperature range of 25-150°C.

[0264] In some embodiments, the Compound 1 dichloroacetate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 96. In some embodiments, the Compound 1 dichloroacetate salt (Form A) exhibits a gravimetric moisture uptake of about 1.8% (by weight) at 80% relative humidity.

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

[0266] In some embodiments, the disclosure provides a crystalline form of Compound 1 Malate. In some embodiments, the disclosure provides a crystalline form of Compound 1D-Malate. In some embodiments, the 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 comprising one or more peaks (particularly, three or more peaks) at about 3.2, 12.5, 14.4, 15.7, and 18.4 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1L-Malate (Form A) further comprises one or more peaks at about 3.6, 6.1, 13.2, 18.9, and 21.1 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 (particularly, about ±0.2).

[0268] In some embodiments, the Compound 1L-Malate (Form A) exhibits an XRPD comprising the peaks shown in Table 46 below. TIFF2025020120000049.tif221170

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

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

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

[0272] In some embodiments, the Compound 1L-Malate (Form A) exhibits a DVS isotherm plot substantially similar to Figure 99. In some embodiments, the Compound 1L-Malate (Form A) exhibits a gravimetric moisture uptake of about 2.0% (by weight) at 80% relative humidity.

[0273] In one embodiment, the disclosure provides Compound 1L-Malate (Form B). In some embodiments, the Compound 1L-Malate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.6, 13.4, 17.3, 20.8, and 23.2 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1L-Malate (Form B) further comprises one or more peaks at about 3.7, 11.2, 14.4, 14.9, and 17.8 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 (particularly, about ±0.2).

[0274] In some embodiments, the Compound 1L-Malate (Form B) exhibits an XRPD comprising the peaks shown in Table 47 below. TIFF2025020120000050.tif127170

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

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

[0277] In some embodiments, the Compound 1L-Malate (Form B) exhibits a TGA thermogram substantially similar to Figure 101. In some embodiments, the TGA thermogram of Compound 1L-Malate (Form B) exhibits a weight loss of 0.0-1.2% within the temperature range of 25-120°C.

[0278] In some embodiments, the Compound 1L-Malate (Form B) exhibits a DVS isotherm plot substantially similar to Figure 102. In some embodiments, the Compound 1L-Malate (Form B) exhibits a gravimetric moisture uptake of about 3.5% (by weight) at 80% relative humidity.

[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 comprising one or more peaks (particularly, three or more peaks) at about 3.6, 5.2, 14.2, 17.4, and 17.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 hydrochloride (Form A) further comprises one or more peaks at about 12.8, 13.4, 14.9, 18.9, and 20.4 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 (particularly, about ±0.2).

[0281] In some embodiments, the Compound 1 hydrochloride salt (Form A) exhibits an XRPD comprising the peaks shown in Table 48 below. TIFF2025020120000051.tif122170

[0282] In some embodiments, the Compound monohydrochloride (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

[0284] In some embodiments, the Compound 1 hydrochloride salt (Form A) exhibits a TGA thermogram substantially similar to Figure 104. In some embodiments, the TGA thermogram of Compound 1 hydrochloride salt (Form A) exhibits a weight loss of 0.0-1.2% within the temperature range of 25-150°C.

[0285] In some embodiments, the Compound 1 hydrochloride salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 105. In some embodiments, the Compound 1 hydrochloride salt (Form A) exhibits a gravimetric moisture uptake of about 3.6% (by weight) at 80% relative humidity.

[0286] In one embodiment, the disclosure provides Compound 1 hydrochloride (Form B). In some embodiments, the Compound 1 hydrochloride (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.3, 7.8, 15.4, 16.6, and 23.2 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 hydrochloride (Form B) further comprises one or more peaks at about 15.0, 18.8, 20.4, 23.5, and 26.5 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 (particularly, about ±0.2).

[0287] In some embodiments, the Compound monohydrochloride (Form B) exhibits an XRPD comprising the peaks shown in Table 49 below. TIFF2025020120000052.tif104170

[0288] In some embodiments, the Compound monohydrochloride (Form B) exhibits an XRPD substantially similar to that shown in FIG.

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

[0290] In some embodiments, the Compound 1 hydrochloride salt (Form B) exhibits a TGA thermogram substantially similar to Figure 107. In some embodiments, the TGA thermogram of Compound 1 hydrochloride salt (Form B) exhibits a weight loss of 0.0-0.7% within the temperature range of 25-120°C.

[0291] In some embodiments, the Compound 1 hydrochloride salt (Form B) exhibits a DVS isotherm plot substantially similar to Figure 108. In some embodiments, the Compound 1 hydrochloride salt (Form B) exhibits a gravimetric moisture uptake of about 2.9% (by weight) at 80% relative humidity.

[0292] In one embodiment, the disclosure provides Compound 1 hydrochloride (Form C). In some embodiments, the Compound 1 hydrochloride (Form C) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 14.6, 16.5, 18.0, 21.5, and 21.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 hydrochloride (Form C) further comprises one or more peaks at about 3.6, 18.8, 19.9, 22.1, and 23.7 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 (particularly, about ±0.2).

[0293] In some embodiments, the Compound monohydrochloride (Form C) exhibits an XRPD comprising the peaks shown in Table 50 below. TIFF2025020120000053.tif122170

[0294] In some embodiments, the Compound monohydrochloride (Form C) exhibits an XRPD substantially similar to that shown in FIG.

[0295] In some embodiments, the Compound 1 hydrochloride salt (Form C) exhibits a DSC thermogram comprising an endothermic peak at about 132.9° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the Compound 1 hydrochloride salt (Form C) exhibits a DSC thermogram substantially similar to that shown in FIG.

[0296] In some embodiments, the Compound 1 hydrochloride salt (Form C) exhibits a TGA thermogram substantially similar to Figure 110. In some embodiments, the TGA thermogram of Compound 1 hydrochloride salt (Form C) exhibits a weight loss of 0.0-3.8% within the temperature range of 25-120°C.

[0297] In some embodiments, the Compound 1 hydrochloride salt (Form C) exhibits a DVS isotherm plot substantially similar to Figure 111. In some embodiments, the Compound 1 hydrochloride salt (Form C) exhibits a gravimetric moisture uptake of about 0.7% (by weight) at 80% relative humidity.

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

[0299] In one embodiment, the disclosure provides compound 1 napsylate (Form A). In some embodiments, the compound 1 napsylate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 3.4, 9.5, 16.6, 17.0, and 17.5 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 napsylate (Form A) further comprises one or more peaks at about 8.3, 8.7, 19.8, 25.0, and 25.5 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 (particularly, about ±0.2).

[0300] In some embodiments, the Compound 1 napsylate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 51 below. TIFF2025020120000054.tif68170

[0301] In some embodiments, the Compound 1 napsylate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

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

[0303] In some embodiments, the Compound 1 napsylate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 113. In some embodiments, the TGA thermogram of Compound 1 napsylate salt (Form A) exhibits a weight loss of 0.0-1.7% within the temperature range of 25-180°C.

[0304] In some embodiments, the Compound 1 napsylate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 114. In some embodiments, the Compound 1 napsylate salt (Form A) exhibits a gravimetric moisture uptake of about 3.9% (by weight) at 80% relative humidity.

[0305] In one embodiment, the disclosure provides Compound 1 napsylate (Form B). In some embodiments, the Compound 1 napsylate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 9.1, 15.6, 16.1, 18.2, and 19.7 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound 1 napsylate (Form B) further comprises one or more peaks at about 8.6, 12.9, 17.1, 25.8, and 26.2 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 (particularly, about ±0.2).

[0306] In some embodiments, the Compound 1 napsylate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 52 below. TIFF2025020120000055.tif71170

[0307] In some embodiments, the Compound 1 napsylate salt (Form B) exhibits an XRPD substantially similar to that shown in FIG.

[0308] Oxalates In some embodiments, the disclosure provides an oxalate salt 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 Mono Oxalate (Form A). In some embodiments, the Compound Mono Oxalate (Form A) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 6.1, 18.2, 19.1, 19.8, and 24.3 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound Mono Oxalate (Form A) further comprises one or more peaks at about 12.1, 13.9, 21.1, 21.7, and 24.7 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 (particularly, about ±0.2).

[0310] In some embodiments, the Compound monooxalate (Form A) exhibits an XRPD comprising the peaks shown in Table 53 below. TIFF2025020120000056.tif133170

[0311] In some embodiments, the Compound monooxalate (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0312] In some embodiments, the compound monooxalate (Form A) exhibits a DSC thermogram comprising an endothermic peak at about 163.8° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound monooxalate (Form A) exhibits a DSC thermogram comprising an endothermic peak (e.g., a sharp endothermic peak) at about 198.6° C. with an error of about ±2.5, about ±2.0, about ±1.5, about ±1.0, about ±0.5 or less (particularly about ±2.0). In some embodiments, the compound monooxalate exhibits a DSC thermogram substantially similar to that shown in FIG. 117.

[0313] In some embodiments, the Compound monooxalate (Form A) exhibits a TGA thermogram substantially similar to Figure 117. In some embodiments, the TGA thermogram of Compound monooxalate (Form A) exhibits a weight loss of 0.0-0.4% within the temperature range of 25-150°C.

[0314] In some embodiments, the Compound monooxalate (Form A) exhibits a DVS isotherm plot substantially similar to that in Figure 118. In some embodiments, the Compound monooxalate (Form A) exhibits a gravimetric moisture uptake of about 1.4% (by weight) at 80% relative humidity.

[0315] In one embodiment, the disclosure provides Compound Mono Oxalate (Form B). In some embodiments, the Compound Mono Oxalate (Form B) exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 6.0, 6.3, 18.2, 18.8, and 20.0 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 (particularly, about ±0.2). In some embodiments, the XRPD of Compound Mono Oxalate (Form B) further comprises one or more peaks at about 12.1, 12.5, 17.8, 20.7, and 23.5 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 (particularly, about ±0.2).

[0316] In some embodiments, the Compound monooxalate (Form B) exhibits an XRPD comprising the peaks shown in Table 54 below. TIFF2025020120000057.tif122170

[0317] In some embodiments, the Compound Monooxalate (Form B) exhibits an XRPD substantially similar to that shown in FIG.

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

[0319] In one embodiment, the disclosure provides compound 1p-aminosalicylate, Form A. In some embodiments, the compound 1p-aminosalicylate, Form A, exhibits an XRPD comprising one or more peaks (particularly, three or more peaks) at about 5.4, 13.8, 15.7, 20.7, and 21.2 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1p-aminosalicylate (Form A) further comprises one or more peaks at about 12.5, 13.5, 15.3, 19.2, and 27.6 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 (particularly about ±0.2).

[0320] In some embodiments, the compound 1p-aminosalicylate (Form A) exhibits an XRPD comprising the peaks shown in Table 55 below. TIFF2025020120000058.tif142170

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

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

[0323] In some embodiments, the compound 1p-aminosalicylate (Form A) exhibits a TGA thermogram substantially similar to Figure 121. In some embodiments, the TGA thermogram of the compound 1p-aminosalicylate (Form A) exhibits a weight loss of 0.0-4.0% within 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 Figure 122. In some embodiments, the compound 1p-aminosalicylate (Form A) exhibits a gravimetric moisture uptake of about 4.0% (by weight) at 80% relative humidity.

[0325] In one embodiment, the disclosure provides compound 1p-aminosalicylate, Form B. In some embodiments, the compound 1p-aminosalicylate, Form B, exhibits an XRPD that includes one or more peaks (particularly, three or more peaks) at about 12.3, 15.2, 17.3, 19.9, and 22.9 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1p-aminosalicylate (Form B) further comprises one or more peaks at about 6.3, 12.5, 14.8, 16.4, and 20.7 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 (particularly about ±0.2).

[0326] In some embodiments, the compound 1p-aminosalicylate (Form B) exhibits an XRPD comprising the peaks shown in Table 56 below. TIFF2025020120000059.tif117170

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

[0328] Maleate In some embodiments, the disclosure provides a maleate salt 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 comprising one or more peaks (particularly, three or more peaks) at about 6.4, 9.5, 11.2, 13.1, 15.0, and 17.6 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 (particularly, about ±0.2). In some embodiments, the XRPD of compound 1 maleate (Form A) further comprises one or more peaks at about 11.2, 12.6, 14.0, 16.7, and 19.2 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 (particularly, about ±0.2).

[0330] In some embodiments, the Compound 1 maleate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 57 below. TIFF2025020120000060.tif94170

[0331] In some embodiments, the Compound 1 maleate salt (Form A) exhibits an XRPD substantially similar to that shown in FIG.

[0332] Method for preparing a salt of compound 1 Salts of Compound 1 (and crystalline forms thereof) can be prepared, for example, by mixing Compound 1 free base and an acid (such as hydrochloric acid) in a suitable solvent to provide the Compound 1 salt as a suspension in the suitable solvent. In some embodiments, salts of Compound 1 may be prepared by slow evaporation, slow cooling, or addition of an anti-solvent to a mixture of Compound 1 free base and an acid.

[0333] In some embodiments, the disclosure provides a method of making 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 a 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 a 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 still other embodiments, the crystalline form of the salt of Compound 1 precipitates from the solution by adding an anti-solvent (i.e., a solvent that reduces the solubility of the crystalline form of the salt of Compound 1) to the solution. In still other embodiments, 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 comprises water.

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

[0336] In some embodiments, the suitable solvent comprises 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, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl methyl ketone (MEK), hexachloroacetone, acetone, ethyl methyl ketone, ethyl acetate, sulfolane, N,N-dichloro ... The aprotic solvent may include 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 comprises a protic solvent. In some embodiments, the protic solvent comprises 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 comprises 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 protic and aprotic solvents.

[0339] In certain embodiments, the salts (or crystalline forms of the salts) of Compound 1 are isolated after they are prepared. Isolation of the salts (or crystalline forms of the salts) can be accomplished using methods such as filtration, decantation, centrifugation, or other suitable separation techniques.

[0340] In certain embodiments, the isolated salt (or a crystalline form of the salt) is optionally washed with a liquid such as an anti-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 above embodiments is substantially pure. For example, in some embodiments, the chemical purity of the salt of Compound 1 (e.g., Compound 1 hydrochloride) may comprise 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. 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 with detection at a wavelength of 210 nm). In some embodiments, the substantial purity is determined on a weight percent (%) basis. In some embodiments, the substantial purity is determined on an area under the curve basis.

[0342] In some embodiments, the salt of Compound 1 prepared according to the above embodiments is crystalline. In certain embodiments, the crystalline salt of Compound 1 prepared according to the above embodiments is substantially pure. For example, in some embodiments, the polymorphic purity of the crystalline salt of Compound 1 (e.g., Compound 1 hydrochloride) may comprise 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 a single crystalline form (e.g., Compound 1 hydrochloride (Form A)). Polymorphic purity may be determined using methods known to those of skill 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 salts of Compound 1 prepared according to the above embodiments are epimerically enriched at one or more positions compared to the epimeric purity of the Compound 1 free base starting material. For example, in some embodiments, the salts of Compound 1 may contain 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 of the 17-β epimer:17α epimer of Compound 1. In some embodiments, the salts of Compound 1 may contain 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 of the 3α-hydroxy:3β-hydroxy of Compound 1. In some embodiments, the epimeric purity of the salts of Compound 1 described herein is substantially the same as the epimeric purity of the Compound 1 free base starting material.

[0344] Pharmaceutical Compositions In one aspect, the 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 salt (Form B). In some embodiments, the salt of Compound 1 is Compound 1 citrate salt (Form C).

[0345] The compositions may be administered by any suitable route, including, but not limited to, oral, parenteral, rectal, topical, and local. The compositions may be in liquid, semi-liquid, or solid form and may be formulated in a manner appropriate for each route of administration using methods known to those of skill 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 of Compound 1 or a solvate thereof and a pharma- ceutically acceptable excipient.

[0348] How to use In one aspect, the invention provides a method of treating a disease or condition in a subject in need thereof, 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. EXAMPLES

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

[0351] "EtOAc" 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 dimethylsulfoxide. "DI" means distilled. "DSC" means differential scanning calorimetry. "DVS" means dynamic vapor sorption. "eq" means equivalent. "EtOH" means ethyl alcohol. "FaSSIF" means simulated intestinal fluid in the fasted state. "FeSSIF" means simulated intestinal fluid in the 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 polarized light microscopy. "RH" means relative humidity. "RRT" means relative retention time. "RT" means room temperature. "RT (min)" means retention time. "SGF" means simulated gastric fluid. "TGA" means thermogravimetric analysis. "THF" means tetrahydrofuran. "UPLC" means ultra performance liquid chromatography. "XRPD" means X-ray powder diffractometer.

[0352] In some cases, the Compound 1:acid ratio in the salts of Compound 1 described herein was determined by ion chromatography (IC) using the following method: 25 μL of 10.0 μg / mL sample or standard was injected onto 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-4 mm suppressor was set at 38 mA and the column temperature was 30° C. Chromatographic elution was with 15 mM KOH with a total run time of 20 minutes.

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

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

[0355] The following SCXRD instrument parameters were used: TIFF2025020120000061.tif56170

[0356] Suitable single crystals of good diffraction quality were isolated from block crystal samples and wrapped in Paraton N (an oil-based cryoprotectant). Crystals were mounted in mylar loops in random orientation and immersed in a nitrogen stream at temperatures specified in the examples below. Preliminary examination and data collection were performed on a Rigaku XtaLAB Synergy R (copper Kα radiation, λ = 1.54184 Å) diffractometer and analyzed with the CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software package.

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

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

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

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

[0361] 1H-NMR was collected on a Bruker 400 MHz magnet. For each sample analyzed, approximately 6 mg of material was dissolved in 0.6 mL of d6-DMSO and analyzed. As known to those skilled in the art, 1 The relative ppm shifts and integrals of H-NMR resonances may vary depending on various sample factors, including, for example, the water content in d6-DMSO, the ion concentrations in the sample, etc. Thus, the relative ppm shifts and integrals of H-NMR resonances reported in the following examples may vary depending on various sample factors, including, for example, the water content in d6-DMSO, the ion concentrations in the sample, etc. 1 1 H-NMR values ​​should not be considered characteristic for each salt and polymorphic form.

[0362] UPLC data was collected on an Agilent 1290 UPLC (detection wavelength: 210 nm) by injecting 0.5 μL of sample or standard onto a Waters Acquity UPLC Shield RP18 column at a flow rate of 0.8 mL / min. The column was equilibrated with mobile phase A containing 0.1% H3PO4 in water. Mobile phase B was acetonitrile (ACN). Chromatographic elution was programmed as follows, with an additional minute for re-equilibration and a total run time of 6 minutes: TIFF2025020120000062.tif32170

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

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

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

[0366] The resulting solid is Compound 1 HBr salt (Form A). The ratio of Compound 1:HBr in Compound 1 HBr salt (Form A) is 1:1.02 as determined by ion chromatography. XPRD is shown in FIG. 2, DSC and TGA are shown in FIG. 3, and DVS is shown in FIG. 4.

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

[0368] 1 g of Compound 1HBr salt (Form A) was suspended in 20 mL of a solution with a water activity of 0.603 (14.5% water in acetone (v / v)) to produce 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 dried under vacuum at 30° C. for 3 days to give a powder with a yield of 70.82%. The ratio of Compound 1:HBr in Compound 1HBr salt (Form B) is 1:1.01 as determined by ion chromatography. XPRD is shown in FIG. 5, DSC and TGA are shown in FIG. 6, and DVS is shown in FIG. 7.

[0369] Compound 1 HBr Salt (Form C):

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

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

[0372] Form D is observed by VT-XRPD when Form B is heated to 160° C. The XRPD is shown in FIG. 11 and the TGA and DSC are shown in FIG.

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

[0374] Compound 1 (1.00 g, 1.0 equiv.) was stirred in EtOH (5 mL) in a 20 mL vial with a stir bar at 60° C. for 30 min. HBr (48% (w / w) in water, 0.3 mL, 1.1 equiv.) was added to the mixture and stirred at 60° C. for 1 h. The reaction mixture was cooled to 25° C. and ethyl acetate anti-solvent (5 mL) was added to the reaction mixture and stirred for 1 h. The mixture was kept in an ice bath for 30 min, followed by filtration and collection of the solid and drying in vacuum at 25° C. overnight to give compound 1HBr (876 mg, 73.7% yield). The XRPD is shown in FIG. 13 and the DSC and TGA are shown in FIG. 14.

[0375] General procedure for preparing compound 1HBr

[0376] To prepare compound 1HBr, the following general procedure was carried out.

[0377] General Procedure 1

[0378] Compound 1 (1.00 g, 1.0 equiv.) was stirred in solvent (15 mL, 15 mL / g (compound 1)) at 60° C. for 30 min in a 20 mL vial with a stir bar. HBr (48% w / w in water, 0.3 mL, 1.1 equiv.) was added to the reaction and stirred at 60° C. for 1 h. The reaction was cooled to 25° C. and stirred for 1 h. The mixture was kept in an ice bath for 30 min (steps 1 and 2 were kept at 25° C.), followed by filtration and collection of the solid, which was dried under vacuum at 25° C. overnight to give compound 1HBr.

[0379] General Procedure 2

[0380] Compound 1 (1.00 g, 1.0 equiv.) was stirred in solvent (3.5 mL, 3.5 mL / g (compound 1)) at 60° C. for 30 min in a 20 mL vial with a stir bar. HBr (48% w / w in water, 0.3 mL, 1.1 equiv.) in acetone (3.5 mL, 3.5 mL / g (compound 1)) was added to the reaction and stirred at 60° C. for 1 h. The reaction was cooled to 25° C. and stirred for 1 h. The mixture was kept in an ice bath for 30 min, followed by filtration and collection of the solid and drying under vacuum at 25° C. overnight to give compound 1HBr.

[0381] General Procedure 3

[0382] In a 20 mL vial with a stir bar, compound 1 (1.00 g, 1.0 equiv.) was stirred in EtOH (5 mL, 5 mL / g (compound 1)) at 60° C. for 30 min. HBr (48% (w / w) in water, 0.3 mL, 1.1 equiv.) was added to the mixture and stirred at 60° C. for 1 h. The reaction mixture was cooled to 25° C., then anti-solvent (5 mL, 5 mL / g (compound 1)) was added to the reaction mixture and stirred for 1 h. The mixture was kept in an ice bath for 30 min, followed by filtration, and the solid was collected and dried under vacuum at 25° C. overnight to obtain compound 1 HBr salt.

[0383] The following table summarizes the preparation of Compound 1HBr salts according to these general procedures. TIFF2025020120000063.tif210170

[0384] Chemical and physical stability tests

[0385] For each salt, approximately 5 mg of compound was added to an 8 mL glass vial with an aluminum foil cap containing multiple holes and kept at 60 °C, 40 °C / 75% RH for 1 week. For photostability testing, compounds in uncapped vials were kept in a photostability chamber and exposed to a total light intensity of 1.2 million lux hours, while samples in vials completely covered with aluminum foil were considered as dark controls. Visual appearance observations were recorded followed by purity assessment of the residual solids and XPRD data collection.

[0386] The chemical and physical stability test results for Compound 1 HBr salt (Form A), Compound 1 HBr salt (Form B), Compound 1 HBr salt (Form C), and Compound 1 free base are shown in the table below. TIFF2025020120000064.tif119170

[0387] Solubility tests in simulated gastric and intestinal fluids For each salt, approximately 4-6 mg of compound 1 or its salt was added to a 2 mL vial in triplicate. Then, 1 mL of biorelevant medium (SGF, FaSSIF, or FeSSIF) was added to each vial. All vials were placed in a thermomixer and kept at 37 °C with shaking at 700 rpm. If the compound was completely dissolved in the medium, additional compound was added until the culture was in suspension. If the concentration of the compound exceeded 25 mg / mL, no additional material was added. After shaking for 24 h at 37 °C, 300 μL of suspension was isolated from each culture and analyzed. Samples were centrifuged at 12000 rpm for 5 min and diluted 10-fold with ACN:H2O (4 / 1, V / V), after which the supernatant was analyzed by UPLC. The final pH value of the biorelevant medium was measured and recorded. The solubility results (mg / mL) in biorelevant solutions for Compound 1 HBr salt (Form A), Compound 1 HBr salt (Form B), Compound 1 HBr salt (Form C), and Compound 1 free base are shown in the table below. TIFF2025020120000065.tif61170

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

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

[0390] Characterization of the salt by PLM and XRPD indicated that the single crystal was Compound 1HBr salt (Form B).

[0391] The cell parameters and orientation matrix for data collection were obtained and adjusted (by least squares fitting) using set angles of 45416 reflections in the range of 3.488°<θ<75.836° with CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software. Data were collected at 120.00 K up to a minimum diffraction angle (θ) of 3.506° and a maximum diffraction angle (θ) of 68.243°. The final completeness is 100%. The average I / σ of the data was 91.7 and the maximum resolution achieved was 0.83 Å.

[0392] The SCXRD data obtained by the methods described herein are presented in the table below. TIFF2025020120000066.tif87170

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

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

[0395] Data collection at 120 K: Cell parameters and orientation matrices for data collection were obtained and adjusted (by least squares fitting) using set angles of 10196 reflections in the range of 3.499°<θ<75.657° with CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software. Data were collected at 120.00(10) K up to a minimum diffraction angle (θ) of 3.508° and a maximum diffraction angle (θ) of 66.553°. The final completeness is 100%. The average I / σ of the data was 19.3 and the maximum resolution achieved was 0.84 Å.

[0396] Data collection at room temperature: Cell parameters and orientation matrices for data collection were obtained and adjusted (by least squares fitting) using set angles of 17551 reflections in the range of 3.483°<θ<75.825° with CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software. Data were collected at room temperature up to a minimum diffraction angle (θ) of 3.496° and a maximum diffraction angle (θ) of 66.597°. The final completeness is 99.8%. The average I / σ of the data was 40.0 and the maximum resolution achieved was 0.84 Å.

[0397] The SCXRD data obtained by the methods described herein are presented in the table below. TIFF2025020120000067.tif85170

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

[0399] Compound 1 Citrate Salt (Form A):

[0400] Compound 1 (1 kg) was charged to a mixture of ethanol (2.37 kg, 9% (w / w) in water) and isopropyl acetate (2.61 kg). An additional amount of ethanol (0.39 kg, 9% (w / w) in water) and isopropyl acetate (0.44 kg) was charged. 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) in water) and isopropyl acetate (0.87 kg) was charged with stirring. An additional amount of ethanol (0.39 kg) and isopropyl acetate (0.44 kg) was used to quantify the transfer of citric acid to the reactor. The resulting mixture was cooled to 0-5° C. for 1 hour with stirring, and the resulting solid was collected by filtration, washed with isopropyl acetate (1.29 kg), and dried under vacuum at 50° C. to give compound 1 citrate salt (1.174 kg, 81% yield).

[0401] The resulting solid was Compound 1 citrate (Form A). The ratio of citric acid in Compound 1:Compound 1 citrate (Form A) is 1:1.02 as measured by HPLC. XPRD is shown in FIG. 15, DSC and TGA are shown in FIG. 16, and DVS is shown in FIG. 17.

[0402] Compound 1 citrate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 Salt (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 in acetone (v / v)) to produce a 125 mg / mL suspension. The suspension was stirred at 300 rpm and kept at 50° C. for 3 days. The suspension was centrifuged and the precipitate was collected. The wet crude product was dried under vacuum at 30° C. for 1 day to give a powder with a yield of 56.9%. The ratio of Compound 1:citric acid in Compound Citrate (Form B) is 1:1.17 as determined by ion chromatography. XPRD is shown in FIG. 18, DSC and TGA are shown in FIG. 19, and DVS is shown in FIG. 20.

[0405] Compound 1 citrate (Form B) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave the following chemical shifts: 1 H NMR (400MHz, 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 salt (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 salt

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

[0410] General Procedure A

[0411] A 20 mL vial equipped with a stir bar was charged with compound (1.00 g, 1.0 equiv.) and solvent or co-solvent. The resulting mixture was heated to 60° C. for 30 min. To the mixture, citric acid monohydrate (0.54 g, 1.1 equiv.) was added in the solvent or co-solvent (pre-heated and dissolved) at 60° C. and stirred for 1 h. The reaction 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 dried under vacuum at 25° C. overnight to give compound 1 citrate salt.

[0412] General Procedure A-2

[0413] A 20 mL vial equipped with a stir bar was charged with compound (1.00 g, 1.0 equiv.) and co-solvent (10 mL, 10 mL / g (compound 1)). The resulting mixture was heated to 60° C. for 30 min. To the mixture was added citric acid monohydrate (0.54 g, 1.1 equiv.) in co-solvent (2 mL, 2 mL / g (compound 1)) (pre-heated to dissolve) at 60° C. and stirred for 1 h. The reaction 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 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 dried under vacuum at 25° C. overnight to give compound 1 citrate salt.

[0414] General Procedure B

[0415] A 20 mL vial equipped with a stir bar was charged with compound (1.00 g, 1.0 equiv.) and EtOH (3.5 mL, 3.5 mL / g (compound 1)). The resulting mixture was heated to 60° C. for 30 min. To the mixture was added citric acid monohydrate (0.54 g, 1.1 equiv.) in EtOH (1.5 mL, 1.5 mL / g (compound 1)) (preheated to dissolve) at 60° C. and stirred for 1 h. The reaction was cooled to 25° C. and anti-solvent (5 mL, 5 mL / g (compound 1)) was added at 25° C. The reaction was cooled to 0° C. and stirred for 1 h. The mixture was stirred at 25° C. overnight. The reaction was cooled to 0° C. and then stirred for 1 h. The suspension was filtered and the wet cake was washed with acetone. The solid was collected and dried under vacuum at 25° C. overnight to give compound 1 citrate salt.

[0416] General Procedure C

[0417] A 250 mL 4-neck flask equipped with a mechanical stirrer (5.5 cm blade, 100 rpm), thermometer, and nitrogen (N2) inlet was charged with compound 1 (5.00 g, 1.0 equiv.) and EtOH / IPAc (1:1, 40 mL, 8 mL / g (compound 1)). The resulting mixture was heated to 60° C. for 30 min. To the mixture was added citric acid monohydrate (2.73 g, 1.1 equiv.) in EtOH / IPAc (1:1, 10 mL, 2 mL / g (compound 1)) (preheated to dissolve) at 60° C. and stirred for 1 h. The reaction was cooled to 25° C. and then stirred for 1 h. The reaction was cooled to 0° C. and then stirred for 30 min. The suspension was filtered and the wet cake was washed with acetone. The solid was collected and dried under vacuum at 50° C. overnight to give compound 1 citrate salt.

[0418] The following table summarizes the preparation of Compound 1 citrate salt according to these general procedures. TIFF2025020120000068.tif135170

[0419] Chemical and physical stability tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 citrate salt (Form A), Compound 1 citrate salt (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000069.tif110170

[0420] ICH Stability Study of Compound 1 Citrate Salt (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 show that the assay, purity, and polymorphic stability of Compound 1 citrate (Form A) are maintained. TIFF2025020120000070.tif72170

[0421] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) in biorelevant solutions for Compound 1 citrate salt (Form A), Compound 1 citrate salt (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000071.tif55170

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

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

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

[0425] The cell parameters and orientation matrix for data collection were obtained and adjusted (by least squares fitting) using set angles of 64393 reflections in the range of 3.7580°<θ<75.8720° with CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software. Data were collected at 120.00 K up to a minimum diffraction angle (θ) of 3.785° and a maximum diffraction angle (θ) of 66.597°. The final completeness is 99.3%. The average I / σ of the data was 81.3 and the maximum resolution achieved was 0.84 Å.

[0426] The SCXRD data obtained by the methods described herein are presented in the table below. TIFF2025020120000072.tif94170

[0427] Example 3: Preparation of the mesylate salt of compound 1 The mesylate salt 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 EtOAc at 60° C. with stirring at 500 rpm and kept at 60° C. for 1 h. Subsequently, 1.1 equivalents of methanesulfonic acid in EtOAc (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged and the precipitate was collected and washed with EtOAc. The resulting wet product was dried in vacuum at 35° C. for 22 h to give 234.52 mg of powder with a yield of 94.5%.

[0429] The resulting solid is Compound 1 mesylate (Form A). The ratio of methanesulfonic acid in Compound 1:Compound 1 mesylate (Form A) is 1:1.08 as measured by ion chromatography. XPRD is shown in FIG. 22, DSC and TGA are shown in FIG. 23, and DVS is shown in FIG. 24.

[0430] Compound 1 mesylate (Form A) was dissolved in deuterated DMSO. 1Analysis by H-NMR gave 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 EtOAc at 60° C. with stirring at 500 rpm and kept at 60° C. for 1 h. Subsequently, 1.1 equivalents of methanesulfonic acid in EtOAc (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged and the precipitate was collected and washed with EtOAc. The resulting wet product was dried in vacuum at 35° C. for 22 h to give 234.52 mg of powder with a yield of 94.1%.

[0432] The resulting 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 liquid counterions, 50 mg of Compound 1 was weighed into a 2 mL vial, followed by addition of 743 μL of solvent to the vial. Then, 1.1 equivalents of the counterion solution in the corresponding solvent (257 μL, concentration: 0.5 mol / L) was added to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. for 18 hours with stirring at 900 rpm, the vial was cooled to 25° C. After being held at 25° C. for 1 hour, the solids in the suspension were isolated by centrifugation and dried overnight at 30° C. in a vacuum oven.

[0434] The resulting 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 a multi-hole aluminum foil cap and kept at 60° C., 40° C. / 75% RH for 1 week. Visual appearance observations were recorded, followed by purity assessment of the remaining solids and XPRD data collection. The resulting solid is Compound 1 mesylate (Form D). The dried solid was characterized by PLM and XRPD.

[0437] The XPRD is shown in Figure 26.

[0438] Chemical and physical stability tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 mesylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000073.tif78170

[0439] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 mesylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000074.tif47170 Example 4: Preparation of the phosphate salt of compound 1

[0440] The phosphate salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of phosphoric acid in acetone (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 30° C. for 42 h, yielding 233.51 mg of powder with a yield of 93.3%.

[0442] The resulting solid is Compound 1 phosphate (Form A). The ratio of phosphoric acid in Compound 1:Compound 1 phosphate (Form A) is 1:0.9 as measured by ion chromatography. XPRD is shown in FIG. 27, DSC and TGA are shown in FIG. 28, and DVS is shown in FIG. 29.

[0443] Chemical and physical stability tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 phosphate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000075.tif76170

[0444] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 phosphate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000076.tif46170 Example 5: Preparation of L(+)-tartrate salt of compound 1

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

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

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

[0448] Compound 1L (+)-tartrate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 salt (form B): 200 mg of compound 1 was dissolved in 10.0 mL of EtOAc at 60° C. with stirring at 500 rpm and kept at 60° C. for 1 h. Subsequently, 1.1 equivalents of L(+)-tartaric acid powder (77 mg, 0.5 mmol) was added to the RX-0001175 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged and the precipitate was collected and washed with EtOAc. The resulting wet product was dried in vacuum at 35° C. for 22 h, giving 254.08 mg of powder with a yield of 91.7%.

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

[0451] Compound 1L (+)-tartrate (form B) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1L(+)-tartrate (Form A), Compound 1L(+)-tartrate (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000077.tif111170

[0453] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) in biorelevant solutions for Compound 1L(+)-tartrate (Form A), Compound 1L(+)-tartrate (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000078.tif56170

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

[0455] Compound 1 fumarate salt (Form A): 200 mg of compound 1 was dissolved in 10.0 mL of acetone at 60° C. with stirring at 500 rpm and kept at 60° C. for 1.5 hours. 1.1 equivalents of fumaric acid powder (60 mg, 0.51 mmol) was added to the compound 1 and incubated at 60° C. for 3 hours, then cooled to 25° C. and kept at 25° C. for 20 hours. Then, 2 volumes of heptane were added to the acetone mixture to form a suspension. The suspension was centrifuged and the precipitate was collected and then vacuum dried at 25° C. for 42 hours to obtain 75.58 mg of powder with a yield of 29.1%.

[0456] The resulting solid is Compound 1 fumarate (Form A). The ratio of fumaric acid in Compound 1:Compound 1 fumarate (Form A) is 1:1.37 as determined by ion chromatography. The XPRD is shown in FIG. 36, and the DSC and TGA are shown in FIG. 37.

[0457] Compound 1 fumarate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 kept at 60° C. for 1 hour. 1.1 equivalents of fumaric acid powder (60 mg, 0.51 mmol) was added to the solution of compound 1. The solution was kept at 60° C. for 3 hours, then cooled to 25° C. and kept at 25° C. for 20 hours. During the cooling process, the clear solution became a suspension. The suspension was then centrifuged, and the precipitate was collected and then vacuum dried at 35° C. for 22 hours, giving 156.78 mg of powder with a yield of 60.4%.

[0459] The resulting solid is Compound 1 fumarate (Form B). The ratio of fumaric acid in Compound 1:Compound 1 fumarate (Form B) is 1:1.55 as measured by ion chromatography. XPRD is shown in FIG. 38, DSC and TGA are shown in FIG. 39, and DVS is shown in FIG. 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 fumaric acid counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of solvent ACN to the vial. The vials were placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vials were cooled to 25° C. After being held 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 resulting solid is Compound 1 fumarate salt, Form C. The dried solid was characterized by PLM and XRPD.

[0463] The XPRD is shown in Figure 41.

[0464] Compound 1 fumarate salt (form D): Approximately 5 mg of Compound 1 fumarate (Form A) was added to an 8 mL glass vial with a multi-hole aluminum foil cap and kept at 60° C., 40° C. / 75% RH for 1 week. Visual appearance observations were recorded, followed by purity assessment of the remaining solids and XPRD data collection. The resulting solid is Compound 1 fumarate (Form D). The dried solid was characterized by PLM and XRPD. The XPRD is shown in FIG. 42.

[0465] Chemical and physical stability tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 fumarate salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000079.tif78170

[0466] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 fumarate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000080.tif41170

[0467] Example 7: Preparation of the tosylate salt of compound 1 The tosylate salt 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 kept at 60° C. for 1 h. Subsequently, 1.1 equivalents of p-toluenesulfonic acid in ACN (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged and the precipitate was collected and washed with ACN. The resulting wet product was dried in vacuum at 35° C. for 22 h to give 141.85 mg of powder with a yield of 49.2%.

[0469] The resulting solid is Compound 1 tosylate (Form A). The ratio of toluenesulfonic acid in Compound 1:Compound 1 tosylate (Form A) is 1:1.09 as measured by ion chromatography. XPRD is shown in FIG. 43, DSC and TGA are shown in FIG. 44, and DVS is shown in FIG. 45.

[0470] Compound 1 tosylate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 paratoluenesulfonic acid counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of EtOAc solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held at 25° C. for 1 hour, the solids in the suspension were isolated by centrifugation and dried overnight at 30° C. in a vacuum oven.

[0472] The resulting 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 a multi-hole aluminum foil cap and kept at 60° C., 40° C. / 75% RH for 1 week. Visual appearance observations were recorded, followed by purity assessment of the remaining solids and XPRD data collection. The resulting solid is Compound 1 tosylate (Form C). The dried solid was characterized by PLM and XRPD.

[0474] The resulting solid is Compound 1 tosylate (Form C). The XPRD is shown in Figure 47.

[0475] Chemical and physical stability tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 tosylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000081.tif77170

[0476] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 tosylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000082.tif45170

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

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

[0479] The resulting solid is Compound 1 glucuronate (Form A). The ratio of glucuronic acid in Compound 1:Compound 1 glucuronate (Form A) is 1:1.09 as determined by ion chromatography. XPRD is shown in FIG. 48, DSC and TGA are shown in FIG. 49, and DVS is shown in FIG. 50.

[0480] Compound 1 glucuronate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 glucuronate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000083.tif75170

[0482] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) in biorelevant solutions for Compound 1 glucuronate (Form A), Compound 1 glucuronate (Form A), and Compound 1 free base are shown in the table below. TIFF2025020120000084.tif40170 Compound 1 Glucuronide (Form B)

[0483] 50 mg of compound 1 and 1.1 equivalents of solid D-glucuronic acid counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of EtOAc / ACN solvent to the vial. The vials were placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vials were cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 51).

[0485] Example 9: Preparation of the ethanesulfonic acid salt of compound 1 The ethanesulfonic acid salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of ethanesulfonic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h, yielding 546.88 mg of powder with a yield of 84.68%.

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

[0488] Compound 1 ethanesulfonate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 ethanesulfonate salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000085.tif74170

[0490] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 ethanesulfonate salt (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000086.tif41170

[0491] Example 10: Preparation of the sulfate salt of compound 1 The sulfate salt 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 kept at 60° C. for 1 h. Subsequently, 1.1 equivalents of sulfuric acid in ACN (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged and the precipitate was collected and washed with ACN. The resulting wet product was dried in vacuum at 35° C. for 22 h to give 177.38 mg of powder with a yield of 70.9%.

[0493] The resulting solid is Compound 1 sulfate (Form A). The ratio of sulfuric acid in Compound 1:Compound 1 sulfate (Form A) is 1:1.03 as determined by ion chromatography. XPRD is shown in FIG. 55, DSC and TGA are shown in FIG. 56, and DVS is shown in FIG. 57.

[0494] Chemical and physical stability tests

[0495] Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 sulfate salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000087.tif78170

[0496] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 sulfate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000088.tif45170

[0497] Example 11: Preparation of the ascorbate salt of compound 1 The ascorbate salt 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 kept at 60° C. for 1.5 hours. Subsequently, 1.1 equivalents of ascorbic acid powder (226 mg) was added to the compound 1 solution and incubated at 60° C. for 3 hours, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 hours to give 264.1 mg of powder with a yield of 36.3%.

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

[0500] Compound 1 ascorbate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 ascorbate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000089.tif78170

[0502] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 ascorbate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000090.tif41170

[0503] Compound 1 Ascorbate (Form B): 50 mg of compound 1 and 1.1 equivalents of solid ascorbic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of ACN solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 resulting dried solid was characterized by PLM and XRPD (Figure 61).

[0505] Example 12: Preparation of napadisylate salt of compound 1 The napadisylate salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of naphthalene-1,5-disulfonic acid tetrahydrate in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 675.62 mg of pale pink powder in 69.38% yield.

[0507] The resulting solid is Compound 1 napadisylate (Form A). The ratio of naphthalene-1,5-disulfonic acid in Compound 1: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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 napadisylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000091.tif78170

[0510] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 napadisylate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000092.tif43170

[0511] Compound 1 napadisylate (form B) 50 mg of compound 1 and 1.1 equivalents of solid naphthalene-1,5-disulfonic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 65).

[0513] Example 13: Preparation of the malonate salt of compound 1 The malonate salt 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 kept at 60° C. for 1.5 hours. Subsequently, 1.1 equivalents of malonic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 hours, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried under vacuum at 25° C. for 72 hours.

[0515] The resulting solid is Compound 1 malonate (Form A). The ratio of malonic acid in Compound 1:Compound 1 malonate (Form A) is 1:1.28 as determined by ion chromatography. The XPRD is shown in FIG. 66, and the DSC and TGA are shown in FIG. 67.

[0516] Compound 1 malonate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 malonate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000093.tif77170

[0518] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 malonate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000094.tif41170

[0519] Example 14: Preparation of the besylate salt of compound 1 The besylate salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of benzenesulfonic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h, yielding 654.68 mg of powder with a yield of 92.56%.

[0521] The resulting solid is Compound 1 besylate (Form A). The ratio of benzenesulfonic acid in Compound 1:Compound 1 besylate (Form A) is 1:0.94 as determined by ion chromatography. XPRD is shown in FIG. 68, DSC and TGA are shown in FIG. 69, and DVS is shown in FIG. 70.

[0522] Compound 1 besylate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 besylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000095.tif78170

[0524] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 besylate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000096.tif40170

[0525] Compound 1 besylate (form B) 50 mg of compound 1 and 1.1 equivalents of solid benzenesulfonic acid counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of ACN solvent to the vial. The vials were placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 500 rpm for 21 hours, the vials were cooled to 25° C. After being held 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 resulting dried solid was characterized by PLM and XRPD (Figure 71).

[0527] Example 15: Preparation of the 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 Isethionate (Form A) 500 mg of compound 1 was dissolved in 16.0 mL of acetone at 60° C. with stirring at 500 rpm and kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of 2-hydroxyethanesulfonic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 493.12 mg of powder with a yield of 74.64%.

[0529] The resulting solid is Compound 1 isethionate salt (Form A). The ratio of 2-hydroxyethanesulfonic acid in Compound 1:Compound 1 isethionate salt (Form A) is 1:1.09 as determined by ion chromatography. The XPRD is shown in Figure 72, the DSC and TGA are shown in Figure 73, and the DVS is shown in Figure 74.

[0530] Compound 1 isethionate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 isethionate salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000097.tif77170

[0532] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 isethionate salt (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000098.tif40170

[0533] Compound 1 Isethionate (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 counterion (257 μL, concentration: 0.5 mol / L) were added to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 resulting solid was characterized by PLM and XRPD (Figure 75).

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

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

[0537] The resulting solid is Compound 1 gentisate (Form A). The ratio of gentisic acid in Compound 1: Compound 1 gentisate (Form A) is 1:1.03 as measured 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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests TIFF2025020120000099.tif73170 Chemical and physical stability testing was performed using the procedures described in Example 1. The results of chemical and physical stability testing of Compound 1 gentisate (Form A) and Compound 1 free base are shown in the table below.

[0540] Compound 1 gentisate (form B) 50 mg of compound 1 and 1.1 equivalents of solid gentisic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of EtOAc solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 79).

[0542] Compound 1 gentisate (form C) 50 mg of compound 1 and 1.1 equivalents of solid gentisic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 80).

[0544] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 gentisate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000100.tif39170

[0545] Example 17: Preparation of 1-hydroxy-2-naphthoic acid salt of compound 1 The 1-hydroxy-2-naphthoic acid salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of 1-hydroxy-2-naphthoic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 675.36 mg of powder with a yield of 68.15%.

[0547] The resulting solid is compound 11-hydroxy-2-naphthoic acid (Form A). The ratio of compound 1:1-hydroxy-2-naphthoic acid in compound 11-hydroxy-2-naphthoic acid salt (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] The compound 11-hydroxy-2-naphthoic acid (form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability tests were performed using the procedures described in Example 1. The results of 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. TIFF2025020120000101.tif73170

[0550] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 11-hydroxy-2-naphthoate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000102.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 counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of EtOAc solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by 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 counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of ACN solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by 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 counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of cyclamic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 715.81 mg of powder with a yield of 74.48%.

[0559] The resulting solid is Compound 1 cyclamate (Form A). The ratio of cyclamic acid in Compound 1: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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 cyclamate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000103.tif72170

[0562] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 cyclamate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000104.tif39170

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

[0564] Compound 1 Ethane-1,2-disulfonic acid 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of ethane-1,2-disulfonic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 704.45 mg of powder with a yield of 71.61%.

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

[0566] Compound 1 ethane-1,2-disulfonic acid salt (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 ethane-1,2-disulfonic acid salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000105.tif73170

[0568] Compound 1 Ethane-1,2-disulfonic acid salt (Form B) 50 mg of compound 1 and 1.1 equivalents of solid ethane-1,2-disulfonic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of EtOAc / IPA / water (95 / 5, V / V) solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with constant stirring at 900 rpm for 18 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 93).

[0570] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 ethane-1,2-disulfonic acid salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000106.tif41170

[0571] Example 20: Preparation of the dichloroacetate salt of compound 1 The dichloroacetate salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of dichloroacetic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h, giving 559.98 mg of powder with a yield of 83.41%.

[0573] The resulting solid is Compound 1 dichloroacetate (Form A). The ratio of dichloroacetic acid in Compound 1: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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 dichloroacetate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000107.tif73170

[0576] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 dichloroacetate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000108.tif43170

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

[0578] Compound 1 L-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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of L-malic acid in acetone (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The solution was evaporated by nitrogen to remove the organic solvent. The resulting wet product was dried under vacuum at 25° C. for 42 h to give 230.93 mg of powder with a yield of 85.9%.

[0579] The resulting solid is Compound 1L-Malate (Form A). The ratio of malic acid in Compound 1: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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 1 L-Malate (Form B): 10 g of compound 1 was suspended in 350 mL of acetone at 60° C. with stirring at 200 rpm and kept at 60° C. for 0.5 h. Subsequently, 1.1 equivalents of L-malic acid in acetone (50 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. with the vial open for 72 h. The suspension was centrifuged and the precipitate was collected and then vacuum dried at 30° C. for 24 h, giving 4.44 g of powder with a yield of 33.86%.

[0582] The resulting 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. The XPRD is shown in Figure 100, the DSC and TGA are shown in Figure 101, and the DVS is shown in Figure 102.

[0583] Compound 1L-malate (Form B) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1L-malate (Form A), Compound 1L-malate (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000109.tif110170

[0585] Solubility tests in simulated gastric and intestinal fluids

[0586] Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) in biorelevant solutions for Compound 1L-malate (Form A), Compound 1L-malate (Form B), and Compound 1 free base are shown in the table below. TIFF2025020120000110.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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of hydrochloric acid in acetone (1.027 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. for 20 h. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 42 h, yielding 168.15 mg of powder with a yield of 76.9%.

[0589] The resulting solid is Compound 1 hydrochloride (Form A). The ratio of hydrochloric acid in Compound 1: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 the hydrochloride salt (Form A) was dissolved in 4.0 mL of ethanol at 50 °C. The solution was filtered and then 6.25 volumes of heptane were added dropwise to the solution to produce a suspension. This suspension was kept under constant stirring at 500 rpm and held at 50 °C for 24 hours. The suspension was centrifuged and the precipitate was collected and then vacuum dried at 30 °C for 24 hours to give 365 mg of powder in 73.0% yield.

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

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

[0593] The resulting solid is Compound 1 hydrochloride (Form C). The ratio of hydrochloric acid in Compound 1: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 tests Chemical and physical stability testing was performed using the procedures described in Example 1. The chemical and physical stability testing results 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. TIFF2025020120000111.tif140170

[0595] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) in biorelevant solutions 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. TIFF2025020120000112.tif46158

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

[0597] Compound 1 napsylate 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of naphthalene-2-sulfonic acid hydrate in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h to give 690.41 mg of powder with a yield of 89.17%.

[0598] The resulting solid is Compound 1 napsylate (Form A). The ratio of naphthalene-2-sulfonic acid in Compound 1: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) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 napsylate salt (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000113.tif77170

[0601] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 napsylate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000114.tif43170

[0602] Compound 1 napsylate salt (form B): 50 mg of compound 1 and 1.1 equivalents of solid naphthalene-2-sulfonic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of EtOAc / ACN solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 resulting dried solid was characterized by PLM and XRPD (Figure 115).

[0604] Example 23: Preparation of the oxalate salt of compound 1 The oxalate salt 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 kept at 60° C. for 1.5 h. Subsequently, 1.1 equivalents of oxalic acid in acetone (2.565 mL, 0.5 mol / L) was added to the compound 1 solution and incubated at 60° C. for 3 h, then cooled to 25° C. and kept at 25° C. overnight. The suspension was centrifuged, and the precipitate was collected and washed with acetone. The resulting wet product was dried in vacuum at 25° C. for 72 h, yielding 595.76 mg of powder with a yield of 96.32%.

[0606] The resulting solid is Compound 1 oxalate (Form A). The ratio of oxalic acid in Compound 1:Compound 1 oxalate (Form A) is 1:0.91 as measured 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 oxalate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000115.tif78170

[0608] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. Solubility results (mg / mL) in biorelevant solutions for Compound 1 oxalate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000116.tif39170

[0609] Compound 1 Oxalate (Form B) 50 mg of compound 1 and 1.1 equivalents of solid oxalic acid counterion were weighed into a 2 mL vial separately, followed by addition of 1 mL of EtOAc solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 119).

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

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

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

[0614] Compound 1 p-aminosalicylate (Form A) was dissolved in deuterated DMSO. 1 Analysis by H-NMR gave 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 tests Chemical and physical stability studies were performed using the procedures described in Example 1. The results of chemical and physical stability studies of Compound 1 p-aminosalicylate (Form A) and Compound 1 free base are shown in the table below. TIFF2025020120000117.tif77170

[0616] Solubility tests in simulated gastric and intestinal fluids Solubility studies in simulated gastric and intestinal fluids were performed using the procedures described in Example 1. The solubility results (mg / mL) of Compound 1 p-aminosalicylate (Form A) and Compound 1 free base in biorelevant solutions are shown in the table below. TIFF2025020120000118.tif56170

[0617] Compound 1 p-aminosalicylate (Form B) 50 mg of compound 1 and 1.1 equivalents of solid 4-aminosalicylic acid counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of EtOAc / ACN solvent to the vial. The vial was placed on a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with stirring at 500 rpm for 21 hours, the vial was cooled to 25° C. After being held 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 solid was characterized by PLM and XRPD (Figure 123).

[0619] Example 25: Preparation of the maleate salt of compound 1 The maleate salt 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 counterion were weighed into 2 mL vials individually, followed by addition of 1 mL of acetone solvent to the vial. The vials were placed in a thermomixer with a stir bar and heated to 50° C. After being held at 50° C. with stirring at 900 rpm for 18 hours, the vials were cooled to 25° C. After being held 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 resulting dried solid was characterized by PLM and XRPD (Figure 124). Example 26: Attempted preparation of a salt of compound 1 The following acids formed amorphous salts under some conditions: TIFF2025020120000119.tif68158

[0622] TIFF2025020120000120.tif167170

[0623] Experimental Conditions: For each of the 20 acids listed in the table above, the following procedure was followed using four solvents (acetone, EtOAc, ACN, and IPA / water (95 / 5, V / V)) to determine whether an isolable salt of compound 1 could be obtained with a particular solvent and 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 stir bar and heated to 50° C. After stirring (500 rpm) at 50° C. for 21 hours, the vial was cooled to 25° C. and held at 25° C. for 1 hour, and the vial was monitored for the formation of solids. After approximately 1 hour of stirring, 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 salts of Compound 1 The bulk density, tap density, Carr's Index, and Hausner Ratio of 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) were measured.The results are shown in the following table. TIFF2025020120000121.tif58170

[0626] Of the forms tested, the physical properties of Compound 1 citrate salt (Form A) are optimal for the preparation of solid pharmaceutical dosage forms (such as tablet formulations) and economical storage of the active pharmaceutical ingredient (API) (i.e., bulk density).

[0627] Compressibility is an important property of an API, and generally, APIs with high compressibility are more easily compressed into tablet formulations than APIs with low compressibility. The Carr index is a measure of powder compressibility, with a lower Carr index indicating high powder compressibility and a higher Carr index indicating low powder compressibility. Compound 1 citrate (Form A) has a significantly lower Carr index compared to the other polymorphs tested, and exhibits the best compressibility of the forms tested.

[0628] The flow properties of APIs are of great importance in many pharmaceutical operations, including compounding with excipients, compressing tablets, filling capsules, and scale-up of manufacturing. The Hausner ratio is an indicator of the flow properties of a powder. A high Hausner ratio indicates poor powder flow, whereas a low Hausner ratio indicates good flow. Compound 1 citrate (Form A) has a significantly lower Hausner ratio compared to the other polymorphs tested, demonstrating the best flow properties among the forms tested.

[0629] Manufacturability of the citrate salt (Form A): Compound 1 citrate salt (Form A) has excellent manufacturability and has been produced on a kilogram scale (Example 2). Large-scale synthesis utilizes pharma- ceutically acceptable solvents and does not require seeding of Compound 1 citrate salt (Form A) for crystallization.

[0630] Stability of the Citrate Salt (Form A): Compound 1 citrate salt (Form A) is stable to high temperature and humidity conditions for at least three months (see Example 2), making it desirable for an API.

[0631] Preparation of HBr Salt (Form A): Compound 1 HBr Salt (Form A) has excellent manufacturability and has been prepared on a kilogram scale (Example 1). Large-scale synthesis utilizes pharma- ceutically acceptable solvents and does not require seeding of Compound 1 HBr Salt (Form A) for crystallization.

[0632] Incorporation by Reference All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, mention of any reference, article, publication, patent, patent publication, or patent application cited herein should not be considered as an admission or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world. Embodiment 1. Crystalline Form A of the citrate salt of Compound 1, said Form A exhibiting an X-ray powder diffraction (XRPD) pattern containing three or more peaks at about 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. 2. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 17.1±0.2 degrees 2θ using Copper K-alpha radiation. 3. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 20.1±0.2 degrees 2θ using Copper K-alpha radiation. 4. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 20.3±0.2 degrees 2θ using Copper K-alpha radiation. 5. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 17.1±0.2, and 20.1±0.2 degrees 2θ. 6. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 5.7±0.2, 17.1±0.2, and 20.3±0.2 degrees 2θ using Copper K-alpha radiation. 7. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 20.1±0.2, and 20.3±0.2 degrees 2θ. 8. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 11.9±0.2, 17.1±0.2, and 20.1±0.2 degrees 2θ using Copper K-alpha radiation. 9. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 11.9±0.2, 20.1±0.2, and 20.3±0.2 degrees 2θ using Copper K-alpha radiation. 11. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern using Copper K-alpha radiation comprising peaks at about 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees 2θ. 12. The crystalline Form A of the Citrate Salt of embodiment 1, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising four or more peaks at about 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. 13. The crystalline form A of the Citrate Salt of embodiment 12, wherein said form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 12, wherein said form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 12, wherein said form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 12, wherein said form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 12, wherein said form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 Salt of embodiment 12, wherein said Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 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 the Citrate Salt of any one of the preceding embodiments, wherein said Form A further comprises one or more peaks, such as two or more peaks, such as three or more peaks, such as four or more peaks, for example, five peaks, at about 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. 20. The crystalline form A of the Citrate Salt of any one of embodiments 1-18, further comprising an additional peak at about 12.7±0.2 degrees 2θ using Copper K-alpha radiation. 21. Crystalline form A of the Citrate Salt of any one of embodiments 1-18 and 20, further comprising an additional peak at about 13.0±0.2 degrees 2θ using Copper K-alpha radiation. 22. Crystalline form A of the Citrate Salt of any one of embodiments 1-18, 20, and 21, further comprising an additional peak at about 13.6±0.2 degrees 2θ using Copper K-alpha radiation. 23. Crystalline form A of the Citrate Salt of any one of embodiments 1-18 and 20-22, further comprising an additional peak at about 15.3±0.2 degrees 2θ using Copper K-alpha radiation. 24. Crystalline form A of the Citrate Salt of any one of embodiments 1-18 and 20-23, further comprising an additional peak at about 16.8±0.2 degrees 2θ using Copper K-alpha radiation. 25. The crystalline form A of the Citrate Salt of any one of the preceding embodiments, wherein said XRPD pattern is substantially as observed in FIG. 15. 26. The crystalline Form A of the Citrate Salt of any one of the preceding embodiments, wherein Form A has unit cell parameters at 120 K substantially similar to the following: a=8.9Å b=12.2Å c=16.5Å α=73.7° β=76.6° γ=83.2° space group P1, Molecule / Asymmetric Unit 2. 27. The crystalline Form A of the Citrate Salt of embodiment 26, wherein Form A has unit cell parameters at 120 K as follows: a=8.9±0.5Å b=12.2±0.5Å c=16.5±0.5Å α=73.7±2° β=76.6±2° γ=83.2±2° space group P1, Molecule / Asymmetric Unit 2. 28. The crystalline Form A of the Citrate Salt of embodiment 27, wherein Form A has unit cell parameters at 120 K as follows: a=8.9±0.3Å b=12.2±0.3Å c=16.5±0.3Å α=73.7±1° β=76.6±1° γ=83.2±1° space group P1, Molecule / Asymmetric Unit 2. 29. The crystalline Form A of the Citrate Salt of embodiment 28, wherein Form A has unit cell parameters at 120 K as follows: a=8.9±0.2Å b=12.2±0.2Å c=16.5±0.2Å α=73.7±0.5° β=76.6±0.5° γ=83.2±0.5° space group P1, Molecule / Asymmetric Unit 2. 30. The crystalline Form A of the Citrate Salt of any one of the preceding embodiments, wherein Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 89.0±2.0° C. or about 139.5±2.0° C. 31. The crystalline Form A of the Citrate Salt of any one of the preceding embodiments, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 89.0±2.0° C. 32. The crystalline Form A of the Citrate Salt of any one of the preceding embodiments, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 139.5±2.0° C. 33. A pharmaceutical composition comprising the citrate salt of any one of the preceding embodiments and a pharma- ceutically acceptable carrier. 34. The pharmaceutical composition of embodiment 33, wherein the composition is 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. The hydrobromide salt of embodiment 35, wherein at least about 80% by weight of said salt is in a single crystalline 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 a single crystalline form. 40. The hydrobromide salt of any one of embodiments 36-39, wherein said crystalline form is form A. 41. The hydrobromide salt of embodiment 40, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 comprises one or more peaks at about 15.5±0.2, 19.2±0.2, 20.6±0.2, 26.1±0.2, and 31.3±0.2 degrees 2θ. 43. The hydrobromide salt of embodiment 40, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 44. The hydrobromide salt of any one of embodiments 40-43, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 243.1±2.0° C. 45. The hydrobromide salt of any one of embodiments 40-43, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 46. ​​The hydrobromide salt of any one of embodiments 40-43, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that in FIG. 47. The hydrobromide salt of any one of embodiments 36-39, wherein the crystalline form is form E. 48. The hydrobromide salt of embodiment 47, wherein Form E exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 comprises one or more peaks at about 9.6±0.2, 17.4±0.2, 22.4±0.2, 23.6±0.2, and 31.2±0.2 degrees 2θ. 50. The hydrobromide salt of embodiment 47, wherein said Form E exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 51. The hydrobromide salt of any one of embodiments 47-50, wherein Form E exhibits a differential scanning calorimetry thermogram having a peak value at about 245.0±2.0° C. 52. The hydrobromide salt of any one of embodiments 47-50, wherein said Form E exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 53. The hydrobromide salt of any one of embodiments 47-50, wherein said Form E exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 14. 54. Citrate salt of compound 1. 55. The citrate salt of embodiment 54, wherein at least about 80% by weight of the salt is crystalline. 56. The citrate salt of embodiment 54, wherein at least about 80% by weight of the salt is in a single crystalline form. 57. The citrate salt of embodiment 54, wherein at least about 95% by weight of the salt is crystalline. 58. The citrate salt of embodiment 54, wherein at least about 95% by weight of the salt is in crystalline form. 59. The Citrate Salt of any one of embodiments 55-58, wherein the crystalline form is Form A. 60. The Citrate Salt of embodiment 59, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 60, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 12.7±0.2, 13.0±0.2, 13.6±0.2, 15.3±0.2, and 16.8±0.2 degrees 2θ. 62. The citrate salt of embodiment 59, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 63. The Citrate Salt of any one of embodiments 59-62, wherein Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 89.0±2.0°C or about 139.5±2.0°C. 64. The Citrate Salt of any one of embodiments 59-63, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 16. 65. The Citrate Salt of any one of embodiments 59-63, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that in FIG. 16. 66. L-Malate salt 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 salt of embodiment 66, wherein at least about 80% by weight of the salt is in a single crystalline form. 69. The L-malate salt of embodiment 66, wherein at least about 95% by weight of the salt is crystalline. 70. The L-malate salt of embodiment 66, wherein at least about 95% by weight of the salt is in a single crystalline form. 71. The L-malate salt of any one of embodiments 67-70, wherein the crystalline form is form A. 72. The L-malate salt of embodiment 71, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 72, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 3.6±0.2, 6.1±0.2, 13.2±0.2, 18.9±0.2, and 21.1±0.2 degrees 2θ. 74. The L-malate salt of embodiment 71, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 97. 75. The L-malate salt of any one of embodiments 71-74, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 120.9±2.0° C. or about 142.3±2.0° C. 76. The L-malate salt of any one of embodiments 71-75, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 98. 77. The L-malate salt of any one of embodiments 71-76, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that in FIG. 98. 78. Mesylate salt of compound 1. 79. The mesylate salt of embodiment 78, wherein at least about 80% by weight of the salt is crystalline. 80. The mesylate salt of embodiment 78, wherein at least about 80% by weight of said salt is in a single crystalline form. 81. The mesylate salt of embodiment 78, wherein at least about 95% by weight of the salt is crystalline. 82. The mesylate salt of embodiment 78, wherein at least about 95% by weight of said salt is in a single crystalline form. 83. The mesylate salt of any one of embodiments 79-82, wherein said crystalline form is form A. 84. The mesylate salt of embodiment 83, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 84, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 7.7±0.2, 12.7±0.2, 17.8±0.2, 19.4±0.2, and 21.4±0.2 degrees 2θ. 86. The mesylate salt of embodiment 83, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 87. The mesylate salt of any one of embodiments 83-86, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 170.9±2.0° C. or about 209.7±2.0° C. 88. The mesylate salt of any one of embodiments 83-87, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 23. 89. The mesylate salt of any one of embodiments 83-88, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that in FIG. 23. 90. L(+)-tartrate salt of compound 1. 91. The L(+)-tartrate salt of embodiment 90, wherein at least about 80% by weight of the salt is crystalline. 92. The L(+)-tartrate salt of embodiment 90, wherein at least about 80% by weight of said salt is in a single crystalline form. 93. The L(+)-tartrate salt of embodiment 90, wherein at least about 95% by weight of the salt is crystalline. 94. The L(+)-tartrate salt of embodiment 90, wherein at least about 95% by weight of the salt is in a single crystalline form. 95. The L(+)-tartrate salt of any one of embodiments 91-94, wherein the crystalline form is form A. 96. The L(+)-tartrate salt of embodiment 95, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 96, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 14.6±0.2, 17.8±0.2, and 18.1±0.2 degrees 2θ. 98. The L(+)-tartrate salt of embodiment 95, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 99. The L(+)-tartrate salt of any one of embodiments 95-98, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 207.6±2.0° C. 100. The L(+)-tartrate salt of any one of embodiments 95-99, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 101. The L(+)-tartrate salt of any one of embodiments 95-100, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that shown in FIG. 102. The L(+)-tartrate salt of any one of embodiments 91-94, wherein the crystalline form is form B. 103. The L(+)-tartrate salt of embodiment 102, wherein Form B exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 103, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 14.8±0.2, 18.3±0.2, and 18.5±0.2 degrees 2θ. 105. The L(+)-tartrate salt of embodiment 103, wherein said Form B exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 106. The L(+)-tartrate salt of any one of embodiments 102-105, wherein said Form B exhibits a differential scanning calorimetry thermogram having a peak value at about 207.3±2.0° C. 107. The L(+)-tartrate salt of any one of embodiments 102-106, wherein said Form B exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 108. The L(+)-tartrate salt of any one of embodiments 102-107, wherein said Form B exhibits a thermogravimetric analysis thermogram substantially similar to that shown in FIG. 109. Phosphate of compound 1. 110. The phosphate salt of embodiment 109, wherein at least about 80% by weight of the salt is crystalline. 111. The phosphate salt of embodiment 109, wherein at least about 80% by weight of the salt is in a single crystalline form. 112. The phosphate salt of embodiment 109, wherein at least about 95% by weight of the salt is crystalline. 113. The phosphate salt of embodiment 109, wherein at least about 95% by weight of the salt is in a single crystalline form. 114. The phosphate salt of any one of embodiments 110-113, wherein the crystalline form is form A. 115. The phosphate salt of embodiment 114, wherein Form A exhibits an X-ray powder diffraction pattern comprising three or more peaks at about 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 salt of embodiment 115, wherein the X-ray powder diffraction pattern further comprises one or more peaks at about 16.1±0.2, 17.9±0.2, 20.9±0.2, 23.7±0.2, and 26.4±0.2 degrees 2θ. 117. The phosphate salt of embodiment 114, wherein said Form A exhibits an X-ray powder diffraction pattern substantially similar to that shown in FIG. 118. The phosphate Salt of any one of embodiments 114-118, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 217.6±2.0° C. 119. The phosphate salt of any one of embodiments 114-117, wherein said Form A exhibits a differential scanning calorimetry thermogram pattern substantially similar to that in FIG. 28. 120. The phosphate Salt of any one of embodiments 114-119, wherein said Form A exhibits a thermogravimetric analysis thermogram substantially similar to that in FIG. 28. 121. A pharmaceutical composition comprising the salt of any one of embodiments 35 to 120 and a pharma- ceutically 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 thereof a therapeutically effective amount of the salt of any one of embodiments 1-32 and 35-120, or the composition of any one of embodiments 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 treating a disease or condition selected from epilepsy, bipolar disorder, and anxiety, comprising administering to a patient in need thereof an effective amount of a salt of any one of embodiments 1-32 and 35-120 or a composition of any one of embodiments 33, 34, 121, and 122.

Claims

1. Crystalline Form A of the citrate salt of Compound 1.

2. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein Form A exhibits an X-ray powder diffraction (XRPD) pattern using copper K-alpha radiation comprising peaks at about 5.7±0.2, 12.5±0.2, and 13.0±0.2 degrees two-theta.

3. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 12.5±0.2, and 20.1±0.2 degrees 2θ using Copper K-alpha radiation.

4. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 12.5±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

5. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 12.7±0.2, and 13.0±0.2 degrees 2θ using Copper K-alpha radiation.

6. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 12.7±0.2, and 20.3±0.2 degrees 2θ using copper K-alpha radiation.

7. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 13.0±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

8. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 16.8±0.2, and 20.1±0.2 degrees two-theta using copper K-alpha radiation.

9. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

10. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 12.5±0.2, 13.0±0.2, and 20.3±0.2 degrees 2θ using Copper K-alpha radiation.

11. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 12.7±0.2, 13.0±0.2, and 20.3±0.2 degrees 2θ using Copper K-alpha radiation.

12. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 16.8±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

13. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

14. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising three or more peaks at about 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using Copper K-alpha radiation.

15. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 17.1±0.2 degrees two-theta using copper K-alpha radiation.

16. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 20.1±0.2 degrees 2θ using Copper K-alpha radiation.

17. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 11.9±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

18. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 17.1±0.2, and 20.1±0.2 degrees two-theta using copper K-alpha radiation.

19. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 17.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

20. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

21. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 11.9±0.2, 17.1±0.2, and 20.1±0.2 degrees two-theta using copper K-alpha radiation.

22. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 11.9±0.2, 17.1±0.2, and 20.3±0.2 degrees 2θ using copper K-alpha radiation.

23. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 11.9±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

24. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern comprising peaks at about 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta using copper K-alpha radiation.

25. 2. The crystalline Form A of the Citrate Salt of claim 1, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation that includes four or more peaks at about 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta.

26. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 11.9±0.2, 17.1±0.2, and 20.1±0.2 degrees two-theta.

27. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 11.9±0.2, 17.1±0.2, and 20.3±0.2 degrees two-theta.

28. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 11.9±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta.

29. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta.

30. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta.

31. 26. The crystalline Form A of the Citrate Salt of claim 25, wherein the Form A exhibits an XRPD pattern using Copper K-alpha radiation comprising peaks at about 5.7±0.2, 11.9±0.2, 17.1±0.2, 20.1±0.2, and 20.3±0.2 degrees two-theta.

32. 32. The crystalline form A of the Citrate Salt of any one of claims 1 to 31, wherein the form A further comprises three or more peaks at about 12.7±0.2, 13.0±0.2, 13.6±0.2, 15.3±0.2, and 16.8±0.2 degrees two-theta using Copper K-alpha radiation.

33. 32. The crystalline form A of the Citrate Salt of any one of claims 1 to 31, further comprising an additional peak at about 12.7±0.2 degrees 2θ using Copper K-alpha radiation.

34. 34. Crystalline Form A of the Citrate Salt of any one of claims 1 to 31 and 33, further comprising an additional peak at about 13.0±0.2 degrees 2θ using Copper K-alpha radiation.

35. 35. The crystalline form A of the Citrate Salt of any one of claims 1 to 31, 33, and 34, further comprising an additional peak at about 13.6±0.2 degrees 2θ using Copper K-alpha radiation.

36. 36. Crystalline Form A of the Citrate Salt according to any one of claims 1 to 31 and 33 to 35, further comprising an additional peak at about 15.3±0.2 degrees 2θ using Copper K-alpha radiation.

37. 37. Crystalline Form A of the Citrate Salt according to any one of claims 1 to 31 and 33 to 36, further comprising an additional peak at about 16.8±0.2 degrees 2θ using Copper K-alpha radiation.

38. 38. The crystalline form A of the Citrate Salt of any one of claims 1 to 37, wherein the XRPD pattern is substantially as observed in Figure 15.

39. 39. The crystalline Form A of the Citrate Salt of any one of claims 1 to 38, wherein Form A has unit cell parameters at 120K substantially similar to the following: a=8.9 Å b = 12.2 Å c=16.5 Å α＝７３．７° β＝７６．６° γ=83.2° space group P1, Molecule / asymmetric unit 2.

40. 40. The crystalline Form A of the Citrate Salt of claim 39, wherein Form A has unit cell parameters at 120K as follows: a = 8.9 ± 0.5 Å b=12.2±0.5Å c=16.5±0.5Å α＝７３．７±２° β＝７６．６±２° γ=83.2±2° space group P1, Molecule / asymmetric unit 2.

41. 41. The crystalline Form A of the Citrate Salt of claim 40, wherein Form A has unit cell parameters at 120K as follows: a = 8.9 ± 0.3 Å b=12.2±0.3Å c=16.5±0.3Å α＝７３．７±１° β＝７６．６±１° γ=83.2±1° space group P1, Molecule / asymmetric unit 2.

42. 42. The crystalline Form A of the Citrate Salt of claim 41, wherein Form A has unit cell parameters at 120K as follows: a = 8.9 ± 0.2 Å b=12.2±0.2Å c=16.5±0.2Å α＝７３．７±０．５° β＝７６．６±０．５° γ=83.2±0.5° space group P1, Molecule / asymmetric unit 2.

43. 43. The crystalline Form A of the Citrate Salt of any one of claims 1 to 42, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 89.0±2.0°C or about 139.5±2.0°C.

44. 44. The crystalline Form A of the Citrate Salt of any one of claims 1 to 43, wherein Form A exhibits a differential scanning calorimetry thermogram with a peak at about 89.0±2.0°C.

45. 45. The crystalline Form A of the Citrate Salt of any one of claims 1 to 44, wherein Form A exhibits a differential scanning calorimetry thermogram having a peak at about 139.5±2.0°C.

46. 46. ​​A pharmaceutical composition comprising the citrate salt of any one of claims 1 to 45 and a pharma- ceutically acceptable carrier.

47. 47. The pharmaceutical composition of claim 46, wherein the composition is a tablet.

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