GABA A Salts and crystalline forms of positive allosteric modulators

Abstract

The present invention relates to salts of compound 1, crystalline forms thereof, methods of their preparation, pharmaceutical compositions thereof, and methods of their use.

Description

[0001] Cross-references to related applications

[0002] 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, both of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure relates to salts of 3α-hydroxy-3β-methoxymethyl-21-(1′-imidazolyl)-5α-pregnane-20-one, their crystalline forms, and methods for preparing such salts and crystalline forms. Background Technology

[0004] 3α-Hydroxy-3β-methoxymethyl-21-(1′-imidazolyl)-5α-pregnane-20-one (Compound 1) is a synthetic neuroactive steroid. Its primary molecular target is γ-aminobutyric acid type A (GABA). A The receptor, wherein the synthesized neuroactive steroid is used as a positive sex modulator (PAM) of channel function. The structural formula of compound 1 is as follows.

[0005]

[0006] The neuroactive steroid GABA has been proven A PAM has clinical efficacy in epilepsy, postpartum depression, and major depressive disorder.

[0007] A separable, stable salt of compound 1 and a method for its preparation are required. Summary of the Invention

[0008] This disclosure provides a salt of compound 1 and a method for preparing such a salt. In some embodiments, the salt of compound 1 is crystalline. This disclosure also provides pharmaceutical compositions comprising a salt of compound 1.

[0009] In some embodiments, this disclosure provides hydrobromide, citrate, malate, maleate, methanesulfonate, phosphate, tartrate, hydrochloride, toluenesulfonate, glucuronate, ethanesulfonate, fumarate, sulfate, naphthalene-2-sulfonate, ascorbate, oxalate, naphthalene-1,5-disulfonate, malonate, aminosalicylate, benzenesulfonate, hydroxyethylsulfonate, gentianate, 1-hydroxy-2-naphthate, dichloroacetate, cyclopentarate, and ethane-1,2-disulfonate of compound 1.

[0010] In some embodiments, the present disclosure provides a crystalline form of a hydrobromide salt, a citrate salt, a malate salt, a mesylate salt, a phosphate salt, a tartrate salt, a hydrochloride salt, a tosylate salt, a glucuronate salt, an ethanesulfonate salt, a fumarate salt, a sulfate salt, a naphthalene-2-sulfonate salt, an ascorbate salt, an oxalate salt, a naphthalene- 1,5-disulfonate salt, a malonate salt, an aminosalicylate salt, a benzenesulfonate salt, a

[0011] In some embodiments, the present disclosure provides a hydrobromide salt of Compound 1. In some embodiments, the present disclosure provides a crystalline form of a hydrobromide salt of Compound 1 (“Compound 1 HBr”). In some embodiments, the present disclosure provides Compound 1 HBr (Form A). In some embodiments, the present disclosure provides Compound 1 HBr (Form B). In some embodiments, the present disclosure provides Compound 1 HBr (Form C). In some embodiments, the present disclosure provides Compound 1 HBr (Form D). In some embodiments, the present disclosure provides Compound 1 HBr (Form E).

[0012] In some embodiments, the present disclosure provides a citrate salt of Compound 1. In some embodiments, the present disclosure provides a crystalline form of a citrate salt of Compound 1 (“Compound 1 Citrate”). In some embodiments, the present disclosure provides Compound 1 Citrate (Form A). In some embodiments, the present disclosure provides Compound 1 Citrate (Form B). In some embodiments, the present disclosure provides Compound 1 Citrate (Form C).

[0013] The present disclosure also provides methods of treating a disease, disorder, or condition comprising administering a therapeutically effective amount of a salt of Compound 1. The present disclosure provides methods of administering a salt of Compound 1. In some embodiments, a salt of Compound 1 is administered orally. In some embodiments, the disease, disorder, or condition is selected from the group consisting of epilepsy, postpartum depression, major depressive disorder, bipolar disorder, treatment-resistant depression, and anxiety. BRIEF DESCRIPTION OF DRAWINGS

[0014] FIG. 1 shows an x-ray powder diffraction (XRPD) pattern of Compound 1 free base (Pattern A).

[0015] FIG. 2 shows an XRPD pattern of Compound 1 HBr (Form A).

[0016] FIG. 3 shows a differential scanning calorimetry (DSC) thermogram and a thermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form A).

[0017] Figure 4 shows dynamic vapor sorption (DVS) isotherm plot of compound 1 HBr (Form A).

[0018] Figure 5 shows the XRPD pattern of compound 1 HBr (Form B).

[0019] Figure 6 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1 HBr (Form B).

[0020] Figure 7 shows dynamic vapor sorption (DVS) isotherm plot of compound 1 HBr (Form B).

[0021] Figure 8 shows the XRPD pattern of compound 1 HBr (Form C).

[0022] Figure 9 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1 HBr (Form C).

[0023] Figure 10 shows dynamic vapor sorption (DVS) isotherm plot of compound 1 HBr (Form C).

[0024] Figure 11 shows the XRPD pattern of compound 1 HBr (Form D).

[0025] Figure 12 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1 HBr (Form D).

[0026] Figure 13 shows the XRPD pattern of compound 1 HBr (Form E).

[0027] Figure 14 shows the differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) thermogram of compound 1 HBr (Form E).

[0028] Figure 15 shows the XRPD pattern of compound 1 citrate (Form A).

[0029] Figure 16 shows the DSC thermogram and TGA thermogram of compound 1 citrate (Form A).

[0030] Figure 17 shows the DVS isotherm plot of compound 1 citrate (Form A).

[0031] Figure 18 shows the XRPD pattern of compound 1 citrate (Form B).

[0032] Figure 19 shows the DSC thermogram and TGA thermogram of compound 1 citrate (Form B).

[0033] Figure 20 shows the DVS isotherm plot of compound 1 citrate (Form B).

[0034] Figure 21 shows the XRPD pattern for Compound 1 citrate (Form C).

[0035] Figure 22 shows the XRPD pattern for Compound 1 mesylate (Form A).

[0036] Figure 23 shows the DSC thermogram and TGA thermogram for Compound 1 mesylate (Form A).

[0037] Figure 24 shows the DVS isotherm plot for Compound 1 mesylate (Form A).

[0038] Figure 25A shows the XRPD pattern for Compound 1 mesylate (Form B).

[0039] Figure 25B shows the XRPD pattern for Compound 1 mesylate (Form C).

[0040] Figure 26 shows the XRPD pattern for Compound 1 mesylate (Form D).

[0041] Figure 27 shows the XRPD pattern for Compound 1 phosphate (Form A).

[0042] Figure 28 shows the DSC thermogram and TGA thermogram for Compound 1 phosphate (Form A).

[0043] Figure 29 shows the DVS isotherm plot for Compound 1 phosphate (Form A).

[0044] Figure 30 shows the XRPD pattern for Compound 1 L(+)-tartrate (Form A).

[0045] Figure 31 shows the DSC thermogram and TGA thermogram for Compound 1 L(+)-tartrate (Form A).

[0046] Figure 32 shows the DVS isotherm plot for Compound 1 L(+)-tartrate (Form A).

[0047] Figure 33 shows the XRPD pattern for Compound 1 L(+)-tartrate (Form B).

[0048] Figure 34 shows the DSC thermogram and TGA thermogram for Compound 1 L(+)-tartrate (Form B).

[0049] Figure 35 shows the DVS isotherm plot for Compound 1 L(+)-tartrate (Form B).

[0050] Figure 36 shows the XRPD pattern for Compound 1 fumarate (Form A).

[0051] Figure 37 shows the DSC thermogram and TGA thermogram for Compound 1 fumarate (Form A).

[0052] Figure 38 shows the XRPD pattern for Compound 1 fumarate (Form B).

[0053] Figure 39 shows the DSC thermogram and TGA thermogram for Compound 1 fumarate (Form B).

[0054] Figure 40 shows the DVS isotherm plot for Compound 1 fumarate (Form B).

[0055] Figure 41 shows the XRPD pattern for Compound 1 fumarate (Form C).

[0056] Figure 42 shows the XRPD pattern for Compound 1 fumarate (Form D).

[0057] Figure 43 shows the XRPD pattern for Compound 1 tosylate (Form A).

[0058] Figure 44 shows the DSC thermogram and TGA thermogram for Compound 1 tosylate (Form A).

[0059] Figure 45 shows the DVS isotherm plot for Compound 1 tosylate (Form A).

[0060] Figure 46 shows the XRPD pattern for Compound 1 tosylate (Form B).

[0061] Figure 47 shows the XRPD pattern for Compound 1 tosylate (Form C).

[0062] Figure 48 shows the XRPD pattern for Compound 1 glucuronate (Form A).

[0063] Figure 49 shows the DSC thermogram and TGA thermogram for Compound 1 glucuronate (Form A).

[0064] Figure 50 shows the DVS isotherm plot for Compound 1 glucuronate (Form A).

[0065] Figure 51 shows the XRPD pattern for Compound 1 glucuronate (Form B).

[0066] Figure 52 shows the XRPD pattern for Compound 1 esylate (Form A).

[0067] Figure 53 shows the DSC thermogram and TGA thermogram for Compound 1 esylate (Form A).

[0068] Figure 54 shows the DVS isotherm plot for Compound 1 esylate (Form A).

[0069] Figure 55 shows the XRPD pattern for Compound 1 sulfate (Form A).

[0070] Figure 56 shows the DSC thermogram and TGA thermogram of Compound 1 sulfate (Form A).

[0071] Figure 57 shows the DVS isotherm plot of Compound 1 sulfate (Form A).

[0072] Figure 58 shows the XRPD pattern of Compound 1 ascorbate (Form A).

[0073] Figure 59 shows the DSC thermogram and TGA thermogram of Compound 1 ascorbate (Form A).

[0074] Figure 60 shows the DVS isotherm plot of Compound 1 ascorbate (Form A).

[0075] Figure 61 shows the XRPD pattern of Compound 1 ascorbate (Form B).

[0076] Figure 62 shows the XRPD pattern of Compound 1 naphthalene disulfonate (Napadisylate) (Form A).

[0077] Figure 63 shows the DSC thermogram and TGA thermogram of Compound 1 naphthalene disulfonate (Form A).

[0078] Figure 64 shows the DVS isotherm plot of Compound 1 naphthalene disulfonate (Form A).

[0079] Figure 65 shows the XRPD pattern of Compound 1 naphthalene disulfonate (Form B).

[0080] Figure 66 shows the XRPD pattern of Compound 1 malonate (Form A).

[0081] Figure 67 shows the DSC thermogram and TGA thermogram of Compound 1 malonate (Form A).

[0082] Figure 68 shows the XRPD pattern of Compound 1 benzenesulfonate (Besylate) (Form A).

[0083] Figure 69 shows the DSC thermogram and TGA thermogram of Compound 1 benzenesulfonate (Form A).

[0084] Figure 70 shows the DVS isotherm plot of Compound 1 benzenesulfonate (Form A).

[0085] Figure 71 shows the XRPD pattern of Compound 1 benzenesulfonate (Form B).

[0086] Figure 72 shows the XRPD pattern of Compound 1 isethionate (Form A).

[0087] Figure 73 shows the DSC thermogram and TGA thermogram of Compound 1 isethionate (Form A).

[0088] Figure 74 shows the DVS isotherm plot of Compound 1 isethionate (Form A).

[0089] Figure 75 shows the XRPD pattern of Compound 1 isethionate (Form B).

[0090] Figure 76 shows the XRPD pattern of Compound 1 gentisate (Form A).

[0091] Figure 77 shows the DSC thermogram and TGA thermogram of Compound 1 gentisate (Form A).

[0092] Figure 78 shows the DVS isotherm plot of Compound 1 gentisate (Form A).

[0093] Figure 79 shows the XRPD pattern of Compound 1 gentisate (Form B).

[0094] Figure 80 shows the XRPD pattern of Compound 1 gentisate (Form C).

[0095] Figure 81 shows the XRPD pattern of Compound 1 1 -hydroxy-2-naphthoate (Form A).

[0096] Figure 82 shows the DSC thermogram and TGA thermogram of Compound 1 1 -hydroxy-2- naphthoate (Form A).

[0097] Figure 83 shows the DVS isotherm plot of Compound 1 1 -hydroxy-2-naphthoate (Form A).

[0098] Figure 84 shows the XRPD pattern of Compound 1 1 -hydroxy-2-naphthoate (Form B).

[0099] Figure 85 shows the XRPD pattern of Compound 1 1 -hydroxy-2-naphthoate (Form C).

[0100] Figure 86 shows the XRPD pattern of Compound 1 1 -hydroxy-2-naphthoate (Form D).

[0101] Figure 87 shows the XRPD pattern of Compound 1 cyclamate (Form A).

[0102] Figure 88 shows the DSC thermogram and TGA thermogram of Compound 1 cyclamate (Form A).

[0103] Figure 89 shows the DVS isotherm plot of Compound 1 cyclamate (Form A).

[0104] Figure 90 shows the XRPD pattern for Compound 1 ethane-1,2-disulfonate salt (Form A).

[0105] Figure 91 shows the DSC thermogram and TGA thermogram for Compound 1 ethane-1,2- disulfonate salt (Form A).

[0106] Figure 92 shows the DVS isotherm plot for Compound 1 ethane-1,2-disulfonate salt (Form A).

[0107] Figure 93 shows the XRPD pattern for Compound 1 ethane-1,2-disulfonate salt (Form B).

[0108] Figure 94 shows the XRPD pattern for Compound 1 dichloroacetate salt (Form A).

[0109] Figure 95 shows the DSC thermogram and TGA thermogram for Compound 1 dichloroacetate salt (Form A).

[0110] Figure 96 shows the DVS isotherm plot for Compound 1 dichloroacetate salt (Form A).

[0111] Figure 97 shows the XRPD pattern for Compound 1 L-malate salt (Form A).

[0112] Figure 98 shows the DSC thermogram and TGA thermogram for Compound 1 L-malate salt (Form A).

[0113] Figure 99 shows the DVS isotherm plot for Compound 1 L-malate salt (Form A).

[0114] Figure 100 shows the XRPD pattern for Compound 1 L-malate salt (Form B).

[0115] Figure 101 shows the DSC thermogram and TGA thermogram for Compound 1 L-malate salt (Form B).

[0116] Figure 102 shows the DVS isotherm plot for Compound 1 L-malate salt (Form B).

[0117] Figure 103 shows the XRPD pattern for Compound 1 hydrochloride salt (Form A).

[0118] Figure 104 shows the DSC thermogram and TGA thermogram for Compound 1 hydrochloride salt (Form A).

[0119] Figure 105 shows the DVS isotherm plot for Compound 1 hydrochloride salt (Form A).

[0120] Figure 106 shows the XRPD pattern for Compound 1 hydrochloride salt (Form B).

[0121] Figure 107 shows the DSC thermogram and TGA thermogram of Compound 1 hydrochloride (Form B).

[0122] Figure 108 shows the DVS isotherm plot of Compound 1 hydrochloride (Form B).

[0123] Figure 109 shows the XRPD pattern of Compound 1 hydrochloride (Form C).

[0124] Figure 110 shows the DSC thermogram and TGA thermogram of Compound 1 hydrochloride (Form C).

[0125] Figure 111 shows the DVS isotherm plot of Compound 1 hydrochloride (Form C).

[0126] Figure 112 shows the XRPD pattern of Compound 1 napsylate (Form A).

[0127] Figure 113 shows the DSC thermogram and TGA thermogram of Compound 1 napsylate (Form A).

[0128] Figure 114 shows the DVS isotherm plot of Compound 1 napsylate (Form A).

[0129] Figure 115 shows the XRPD pattern of Compound 1 napsylate (Form B).

[0130] Figure 116 shows the XRPD pattern of Compound 1 oxalate (Form A).

[0131] Figure 117 shows the DSC thermogram and TGA thermogram of Compound 1 oxalate (Form A).

[0132] Figure 118 shows the DVS isotherm plot of Compound 1 oxalate (Form A).

[0133] Figure 119 shows the XRPD pattern of Compound 1 oxalate (Form B).

[0134] Figure 120 shows the XRPD pattern of Compound 1 p-aminosalicylate (Form A).

[0135] Figure 121 shows the DSC thermogram and TGA thermogram of Compound 1 p-aminosalicylate (Form A).

[0136] Figure 122 shows the DVS isotherm plot of Compound 1 p-aminosalicylate (Form A).

[0137] Figure 123 shows the XRPD pattern of Compound 1 p-aminosalicylate (Form B).

[0138] Figure 124 shows the XRPD pattern of Compound 1 maleate (Form A). DETAILED DESCRIPTION

[0139] DEFINITIONS

[0140] The term“about” preceding a value refers to a range (e.g., ±10% of the value). For example,“about 50” can refer to 45 to 55,“about 25,000” can refer to 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise or is inconsistent with such an interpretation, For example, in a series of values such as“about 49, about 50, about 55,...”,“about 50” indicates a range that extends less than half way across 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” a value or“greater than about” a value should be understood in light of the definition of the term“about” provided herein. Similarly, the term“about” when preceding a series of values or a range of values (e.g.,“about 10, 20, 30” or“about 10-30”) refers to all values in the series, or the endpoints of the range, respectively.

[0141] Throughout this disclosure, different patents, patent applications, and publications (including non-patent publications) are referenced by author and year. The disclosures of these patents, patent applications, and publications in their entireties are hereby incorporated by reference into this disclosure for all purposes to more fully describe the state of the art as of the date of this disclosure. In the event of any inconsistencies between the disclosures in the referenced patents, patent applications, and publications and the disclosure contained herein, the disclosure contained herein is controlling.

[0142] For convenience, certain terms used in the specification, examples, and claims are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0143] The term“administer,”“administering,” or“administration,” as used herein, means directly administering a Compound 1, or a pharmaceutically acceptable salt thereof, or a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, to a patient.

[0144] The term "non-protic solvent" as used herein refers to an organic solvent or mixture of organic solvents that is not readily deprotonated in the presence of a strong basic reactant. Non-limiting examples of non-protic solvents include ethers, dimethylformamide (DMF), dimethylacetamide (DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidone (NMP), formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl isobutyl ketone, hexachloroacetone, acetone, ethyl methyl ketone, methyl ethyl ketone (MEK), ethyl acetate, isopropyl acetate, sulfolane, N,N-dimethylpropionamide, tetramethylurea, nitromethane, nitrobenzene, 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.

[0145] The term "carrier" as used herein encompasses carriers, excipients, and diluents, and refers to a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body.

[0146] The term "disorder" as used in the present disclosure means the term disease, condition, or state, and is used interchangeably with the term disease, condition, or state, unless otherwise indicated.

[0147] The terms "effective amount" and "therapeutically effective amount" are used interchangeably herein in the present disclosure and refer to the amount of a compound or salt, solvate, or ester thereof that, when administered to a patient, is capable of performing an intended result. For example, an effective amount of a salt of Compound 1 is the amount required to reduce at least one symptom of depression in a patient. The actual amount comprising an "effective amount" or "therapeutically effective amount" will vary depending on a variety of conditions including, but not limited to, the severity of the disorder, the size and health of the patient, and the route of administration. A skilled medical practitioner can readily determine the appropriate amount using methods known in the medical arts.

[0148] The term "isomer" refers to a compound having the same chemical formula but possibly a different spatial arrangement of atoms, structural formula, or stereochemistry. Examples of isomers include stereoisomers, diastereomers, enantiomers, conformers, rotamers, geometric isomers, and atropisomers.

[0149] The term "peak" means a line in an XRPD diffraction pattern (or pattern) obtained from a sample using standard XRPD collection techniques that has significant intensity. For example, a peak is a line in an XRPD diffraction pattern that has an intensity of, for example, at least about 10% of the intensity of the largest peak in the XRPD diffraction pattern.

[0150] The phrase "pharmaceutically acceptable" is used herein to refer to those 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 humans and animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit / risk ratio.

[0151] The term "protic solvent" as used herein refers to a solvent or mixture of solvents that is capable of acting as an acid to protonate any 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, n-butanol, 2-butanol, isobutanol, t-butanol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neopentyl alcohol, t-amyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, glycerol, and the like.

[0152] The term "salt" as used herein includes pharmaceutically acceptable salts of addition salts normally used for forming free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. The term "salt" also includes solvates of addition salts, such as hydrates, and polymorphs of addition salts. Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic acids or from organic acids. In the salt, a proton transfer occurs between Compound 1 free base and an organic or inorganic acid. However, in some cases, the proton transfer is not complete. In this case, the Compound 1 and the "co-former" molecules in the solid (i.e., "co-crystals") interact with each other through non-ionic forces, such as hydrogen bonding.

[0153] In the case where the acid co-former 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 co-former, a co-crystal of the co-former and Compound 1 is obtained. The term "salt" as used herein encompasses co-crystal forms of Compound 1.

[0154] The term "substantially similar" as used herein refers to an analytical spectrum, such as an XRPD pattern, a DSC thermogram, and the like, that is largely similar in peak position and peak intensity to a reference spectrum.

[0155] The term "treatment" as used herein with respect to a patient means to ameliorate at least one symptom of the patient's disorder. Treatment can be curative, ameliorative, or at least partially palliative of the disorder.

[0156] 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 for treating depression provides a therapeutic effect when the method alleviates at least one symptom of depression in a patient.

[0157] As used herein, the symbol "≤" means "not greater than" or "equal to or less than"; "<" means "less than"; "≥" means "not less than" or "equal to or greater than"; ">" means "greater than". In addition, when used herein in connection with purity or impurity content, numbers are to include not only the precise number, but also an approximate range around that number. For example, the phrase "99.0% purity" means about 99.0% purity.

[0158] Salts of Compound 1

[0159] Compound 1 is a highly potent neuroactive steroid GABA-A positive allosteric modulator (PAM) similar to the clinical stage neuroactive steroids (alphaxalone, ganaxolone, SAGE-217, alphaxolone). Compound 1 is poorly soluble at the pH found in the lower gastrointestinal tract, which can limit the oral bioavailability of Compound 1.

[0160] The synthesis of Compound 1 is described in U.S. Publication Nos. 2004 / 034002 and 2009 / 0118248; crystalline polymorphs of Compound 1 free base are described in U.S. Publication No. 2006 / 0074059, and pharmaceutical compositions comprising Compound 1 are described in U.S. Publication No. 2009 / 0131383, the entire contents of which are hereby incorporated by reference herein in their entirety for all purposes.

[0161] The present disclosure provides salts of Compound 1 and crystalline forms thereof.

[0162] Crystalline salts of Compound 1

[0163] In some embodiments, the present disclosure provides crystalline forms of salts of Compound 1. Polymorphism can be characterized as the ability of a compound to crystallize in different crystalline forms while retaining the same structural formula (i.e., the covalent bonds in the compound are the same in different crystalline forms). A crystalline polymorph of a given drug product is chemically the same as any other crystalline polymorph of that drug product, they contain the same atoms bonded to each other in the same way, but differ in their crystalline form, which affects one or more physical properties, such as stability, solubility, melting point, bulk density, flow properties, etc., or pharmacological properties such as bioavailability, etc.

[0164] In some embodiments, the crystalline forms are characterized by interplanar lattice spacing determined from X-ray powder diffraction patterns (XRPD). XRPD diffraction patterns are typically represented by a plot of peak intensity versus peak position (i.e., diffraction angle 2 theta in degrees). Characteristic peaks of a given XRPD diffraction pattern can be selected according to peak position and its relative intensity to conveniently distinguish this crystal structure from other crystal structures. The % intensity of a peak relative to the most intense peak can be expressed as I / Io. XRPD diffraction patterns described throughout the disclosure are obtained using copper K-alpha radiation.

[0165] Those skilled in the art recognize that, for a given crystalline form of the same compound, the measured values of XRPD peak position and / or intensity will vary within error limits. Values of °2 theta allow for appropriate error limits. Typically, error limits are indicated by “±”. For example, a °2 theta of about “8.716 ± 0.2” indicates a range from about 8.716 + 0.2 (i.e., about 8.916) to about 8.716 - 0.2 (i.e., about 8.516). Depending on sample preparation techniques, calibration techniques applied to the instrument, variations in human handling, and the like, those skilled in the art recognize that appropriate error limits for XRPD can be about ± 0.7; ± 0.6; ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less.

[0166] Additional details of methods and equipment for XRPD analysis are described in the Examples section.

[0167] In some embodiments, the crystalline forms are characterized by differential scanning calorimetry (DSC). DSC thermograms are typically represented by a plot of normalized heat flow in Watts per gram (“W / g”) versus measured sample temperature in degrees Celsius. DSC thermograms typically assess extrapolated onset and outset temperatures, peak temperatures, and heat of fusion. Peak characteristic values of DSC thermograms are typically used as characteristic peaks to distinguish this crystal structure from other crystal structures.

[0168] Those skilled in the art recognize that, for a given crystalline form of the same compound, the measured values of DSC thermograms will vary within error limits. Values of single peak characteristic values expressed in degrees Celsius allow for appropriate error limits. Typically, error limits are indicated by “±”. For example, a single peak characteristic value of about “53.09 ± 2.0” indicates a range from about 53.09 + 2 (i.e., about 55.09) to about 53.09 - 2 (i.e., about 51.09). Depending on sample preparation techniques, calibration techniques applied to the instrument, variations in human handling, and the like, those skilled in the art recognize that appropriate error limits for single peak characteristic values can be ± 2.5; ± 2.0; ± 1.5; ± 1.0; ± 0.5; or less.

[0169] Additional details of methods and apparatus for DSC thermogram analysis are described in the Examples section.

[0170] hydrobromide salt

[0171] In some embodiments, the present disclosure provides a hydrobromide salt of Compound 1 (“Compound 1 HBr”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 HBr.

[0172] In one embodiment, the present disclosure provides Compound 1 HBr (Form A). In some embodiments, Compound 1 HBr (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.6, 15.2, 16.3, 19.8, and 22.9 °2theta, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form A) exhibits an XRPD comprising three or more peaks at about 7.6, 15.2, 16.3, 19.8, and 22.9 °2theta, with an error limit of ± 0.2. In some embodiments, the XRPD of Compound 1 HBr (Form A) further comprises one or more peaks at about 15.5, 19.2, 20.6, 26.1, and 31.3 °2theta, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form A) exhibits an XRPD comprising the peaks shown in Table 1 below:

[0173] Table 1. XRPD Table for Compound 1 HBr (Form A)

[0174]

[0175]

[0176]

[0177] Some embodiments provide Compound 1 HBr (Form A), wherein Form A exhibits only three peaks in the range of 15.2 ± 0.2 to 16.3 ± 0.2 °2theta in an XRPD pattern.

[0178] In some embodiments, Compound 1 HBr (Form A) exhibits an XRPD substantially similar to Figure 2.

[0179] In some embodiments, Compound 1 HBr (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 243.1 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form A) exhibits a DSC thermogram substantially similar to Figure 3.

[0180] In some embodiments, Compound 1 HBr (Form A) exhibits a TGA thermogram substantially similar to Figure 3. In some embodiments, the TGA thermogram of Compound 1 HBr (Form A) exhibits a weight loss of about 0.0 to 1.9% over the temperature range of 25 to 230 °C.

[0181] In some embodiments, Compound 1 HBr (Form A) exhibits a DVS isotherm substantially similar to Figure 4. In some embodiments, Compound 1 HBr (Form A) exhibits a weight moisture uptake of about 1.1% (by weight) at 80% relative humidity.

[0182] In one embodiment, the present disclosure provides Compound 1 HBr (Form B). In some embodiments, Compound 1 HBr (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 16.3, 17.7, 21.4, and 23.5 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 HBr (Form B) further comprises one or more peaks at about 14.4, 18.7, 24.8, 27.3, and 28.2 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form B) exhibits an XRPD comprising the peaks shown in Table 2 below:

[0183] Table 2. XRPD Table for Compound 1 HBr (Form B)

[0184]

[0185]

[0186] In some embodiments, Compound 1 HBr (Form B) exhibits an XRPD substantially similar to Figure 5.

[0187] In some embodiments, Compound 1 HC1 (Form B) exhibits a DSC thermogram comprising an endotherm at about 121 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form B) exhibits a DSC thermogram substantially similar to Figure 6.

[0188] In some embodiments, Compound 1 HC1 (Form B) exhibits a TGA thermogram substantially similar to Figure 6. In some embodiments, the TGA thermogram of Compound 1 HC1 (Form B) exhibits a weight loss of about 0.0 to 3.4% over the temperature range of 25 to 120 °C.

[0189] In some embodiments, Compound 1 HC1 (Form B) exhibits a DVS isotherm substantially similar to Figure 7. In some embodiments, Compound 1 HC1 (Form B) exhibits a weight moisture uptake of about 0.2% (by weight) at 80% relative humidity.

[0190] In some embodiments, Compound 1 HC1 (Form B) is defined by unit cell parameters substantially similar to: α = 90°; β = 90°; γ = 90°; space group P2i2i2; 1 molecule per asymmetric unit, wherein the crystalline form is at about 120 K.

[0191] In one embodiment, the present disclosure provides Compound 1 HC1 (Form C). In some embodiments, Compound 1 HC1 (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.9, 13.8, 20.8, 21.6, and 27.7 °29, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 HC1 (Form C) further comprises one or more peaks at about 8.8, 25.6, 27.5, 36.2, and 37.3 °29, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form C) exhibits an XRPD comprising the peaks shown in Table 3 below:

[0192] Table 3. XRPD Table for Compound 1 HC1 (Form C)

[0193]

[0194]

[0195] In some embodiments, Compound 1 HBr (Form C) exhibits an XRPD substantially similar to FIG. 8.

[0196] In some embodiments, Compound 1 HBr (Form C) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 141 °C, with an error margin of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form C) exhibits a DSC thermogram substantially similar to FIG. 9.

[0197] In some embodiments, Compound 1 HBr (Form C) exhibits a TGA thermogram substantially similar to FIG. 9. In some embodiments, the TGA thermogram of Compound 1 HBr (Form C) exhibits a weight loss of about 0.0 to 4.1% over the temperature range of 25 to 170 °C.

[0198] In some embodiments, Compound 1 HBr (Form C) exhibits a DVS isotherm plot substantially similar to FIG. 10. In some embodiments, Compound 1 HBr (Form C) exhibits a weight moisture uptake of about 0.25% (by weight) at 80% relative humidity.

[0199] In one embodiment, the present disclosure provides Compound 1 HBr (Form D). In some embodiments, Compound 1 HBr (Form D) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 14.7, 15.2, 15.6, 16.4, and 23.1 °2- theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 HBr (Form D) further comprises one or more peaks at about 18.2, 19.9, 21.3, 22.2, and 23.4 °2-theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HBr (Form D) exhibits an XRPD comprising the peaks set forth in Table 4 below:

[0200] Table 4. XRPD Table for Compound 1 HBr (Form D)

[0201]

[0202]

[0203]

[0204] In some embodiments, Compound 1 HC1 (Form D) exhibits an XRPD substantially similar to FIG. 11.

[0205] In some embodiments, Compound 1 HC1 (Form D) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 248 °C, with an error margin of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form D) exhibits a DSC thermogram substantially similar to FIG. 12.

[0206] In some embodiments, Compound 1 HC1 (Form D) exhibits a TGA thermogram substantially similar to FIG. 12. In some embodiments, the TGA thermogram of Compound 1 HC1 (Form D) exhibits a weight loss of about 0.0 to 1.7% over the temperature range of 29 to 150 °C.

[0207] In some embodiments, the present disclosure provides Compound 1 HC1 (Form E). In some embodiments, Compound 1 HC1 (Form E) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.6, 15.2, 16.3, 22.9, and 23.2 °2Θ, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form E) exhibits an XRPD comprising three or more peaks at about 7.6, 15.2, 16.3, 22.9, and 23.2 °2Θ, with an error margin of ± 0.2. In some embodiments, the XRPD of Compound 1 HC1 (Form E) further comprises one or more peaks at about 9.6, 17.4, 22.4, 23.6, and 31.2 °2Θ, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form E) exhibits an XRPD comprising the peaks shown in Table 5 below:

[0208] Table 5. XRPD Table for Compound 1 HC1 (Form E)

[0209]

[0210]

[0211] Some embodiments provide Compound 1 HC1 (Form E), wherein Form E exhibits only two peaks in the range of 15.2 ± 0.2 to 16.3 ± 0.2 °2Θ in an XRPD pattern.

[0212] In some embodiments, Compound 1 HC1 (Form E) exhibits an XRPD substantially similar to FIG. 13.

[0213] In some embodiments, Compound 1 HC1 (Form E) exhibits a DSC thermogram comprising an endotherm at about 245 °C (e.g., a sharp endotherm), with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 HC1 (Form E) exhibits a DSC thermogram substantially similar to FIG. 14.

[0214] In some embodiments, Compound 1 HC1 (Form E) exhibits a TGA thermogram substantially similar to FIG. 14. In some embodiments, the TGA thermogram of Compound 1 HC1 (Form E) exhibits a weight loss of about 0.0 to 0.5% over the temperature range of 28 to 150 °C.

[0215] In some embodiments, Compound 1 HC1 (Form E) is defined by unit cell parameters substantially similar to the following: α = 90°; β = 90°; γ = 90°; space group P2i2i2i; 1 molecule / asymmetric unit, where the crystalline form is at about 120 K.

[0216] In some embodiments, Compound 1 HC1 (Form E) is defined by unit cell parameters substantially similar to the following: α = 90°; β = 90°; γ = 90°; space group P2i2i2i; 1 molecule / asymmetric unit, where the crystalline form is at about 298 K.

[0217] Citrate

[0218] In some embodiments, the present disclosure provides a citrate salt of Compound 1 (“Compound 1 citrate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 citrate.

[0219] In one embodiment, the present disclosure provides compound 1 citrate salt (Form A). In some embodiments, compound 1 citrate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.7, 11.9, 17.1, 20.1, and 20.3 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form A) exhibits an XRPD comprising three or more peaks at about 5.7, 11.9, 17.1, 20.1, and 20.3 °2Θ, with a tolerance of ± 0.2. In some embodiments, the XRPD of compound 1 citrate salt (Form A) further comprises one or more peaks at about 12.7, 13.0, 13.6, 15.3, and 16.8 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 6 below:

[0220] Table 6. XRPD Table for Compound 1 Citrate Salt (Form A)

[0221]

[0222]

[0223]

[0224] In some embodiments, compound 1 citrate salt (Form A) exhibits an XRPD of peaks at 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, 13.0 ± 0.2 and 20.3 ± 0.2; or 5.7 ± 0.2, 16.8 ± 0.2 and 20.1 ± 0.2; or 5.7 ± 0.2; 20.1 ± 0.2 and 20.3 ± 0.2; or 12.5 ± 0.2, 13.0 ± 0.2 and 20.3 ± 0.2; or 12.7 ± 0.2, 13.0 ± 0.2 and 20.3 ± 0.2; or 16.8 ± 0.2, 20.1 ± 0.2 and 20.3 ± 0.2 °2Θ.

[0225] In some embodiments, Compound 1 citrate (Form A) exhibits an XRPD substantially similar to FIG. 15.

[0226] In some embodiments, Compound 1 citrate (Form A) exhibits a DSC thermogram comprising an endotherm at about 89.0 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 citrate (Form A) exhibits a DSC thermogram comprising an endotherm at about 89.0 ± 2.0 °C. In some embodiments, Compound 1 citrate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 139.5 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 citrate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 139.5 ± 2.0 °C. In some embodiments, Compound 1 HBr (Form A) exhibits a DSC thermogram substantially similar to FIG. 16.

[0227] In some embodiments, Compound 1 citrate (Form A) exhibits a TGA thermogram substantially similar to FIG. 16. In some embodiments, the TGA thermogram of Compound 1 citrate (Form A) exhibits a weight loss of 0.0 to 2.6% over the temperature range of 25 to 65 °C.

[0228] In some embodiments, Compound 1 citrate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 17. In some embodiments, Compound 1 citrate (Form A) exhibits a weight moisture uptake of about 3.6% (by weight) at 80% relative humidity.

[0229] In some embodiments, Compound 1 citrate (Form A) is defined by unit cell parameters substantially similar to: α = 73.7 (10)°; β = 76.6 (10)°; γ = 83.2 (10)°; space group P2i2i2i; 1 molecule / asymmetric unit, wherein the crystalline form is at about 120.00 K.

[0230] In an embodiment, the present disclosure provides compound 1 citrate salt (Form B). In some embodiments, compound 1 citrate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.5, 5.7, 10.9, 16.3, and 20.5 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form B) further comprises one or more peaks at about 3.4, 11.8, 14.6, 17.2, and 21.1 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 7 below:

[0231] Table 7. XRPD Table for Compound 1 Citrate Salt (Form B)

[0232]

[0233]

[0234] In some embodiments, compound 1 citrate salt (Form B) exhibits an XRPD substantially similar to FIG. 18.

[0235] In some embodiments, compound 1 citrate salt (Form B) exhibits a DSC thermogram comprising an endotherm at about 77.7 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form B) exhibits a DSC thermogram comprising an endotherm at about 121.5 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form B) exhibits a DSC thermogram comprising an endotherm at about 136.6 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 citrate salt (Form B) exhibits a DSC thermogram substantially similar to FIG. 19.

[0236] In some embodiments, Compound 1 citrate (Form B) exhibits a TGA thermogram substantially similar to FIG. 19. In some embodiments, the TGA thermogram of Compound 1 citrate (Form B) exhibits a weight loss of about 0.0 to 4.5% over the temperature range of 25 to 120 °C.

[0237] In some embodiments, Compound 1 citrate (Form B) exhibits a DVS isotherm substantially similar to FIG. 20. In some embodiments, Compound 1 citrate (Form B) exhibits a weight moisture uptake of about 2.8% (by weight) at 80% relative humidity.

[0238] In one embodiment, the present disclosure provides Compound 1 citrate (Form C). In some embodiments, Compound 1 citrate (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 15.4, 18.7, 19.7, 20.6, and 27.1 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 citrate (Form C) further exhibits an XRPD comprising one or more peaks at about 13.5, 15.5, 16.2, 17.0, and 22.1 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 citrate (Form C) exhibits an XRPD comprising the peaks set forth in Table 8 below:

[0239] Table 8. XRPD Table for Compound 1 citrate (Form C)

[0240]

[0241]

[0242]

[0243] In some embodiments, Compound 1 citrate (Form C) exhibits an XRPD substantially similar to FIG. 21.

[0244] Mesylate salt

[0245] In some embodiments, the present disclosure provides a mesylate salt of Compound 1 (“Compound 1 mesylate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 mesylate.

[0246] In one embodiment, the present disclosure provides compound 1 mesylate salt (Form A). In some embodiments, compound 1 mesylate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 7.1, 14.2, 19.1, and 25.9 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 citrate salt (Form A) further comprises one or more peaks at about 7.7, 12.7, 17.8, 19.4, and 21.4 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 mesylate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 9 below:

[0247] Table 9. XRPD Table for Compound 1 Mesylate Salt (Form A)

[0248]

[0249]

[0250] In some embodiments, compound 1 mesylate salt (Form A) exhibits an XRPD substantially similar to Figure 22.

[0251] In some embodiments, compound 1 mesylate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 170.9 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 mesylate salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 209.7 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 mesylate salt (Form A) exhibits a DSC thermogram substantially similar to Figure 23.

[0252] In some embodiments, 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 to 0.5% over the temperature range of 25 to 150 °C.

[0253] In some embodiments, Compound 1 methanesulfonic acid salt (Form A) exhibits a DVS isotherm substantially similar to FIG. 24. In some embodiments, Compound 1 methanesulfonic acid salt (Form A) exhibits a weight moisture uptake of about 3.4% by weight at 80% relative humidity.

[0254] In one embodiment, the present disclosure provides Compound 1 methanesulfonic acid salt (Form B). In some embodiments, Compound 1 methanesulfonic acid salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.1, 14.3, 15.9, 21.4, and 22.6 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 methanesulfonic acid salt (Form B) exhibits an XRPD comprising the peaks shown in Table 10 below:

[0255] Table 10A. XRPD Table for Compound 1 methanesulfonic acid salt (Form B)

[0256]

[0257]

[0258] In some embodiments, Compound 1 methanesulfonic acid salt (Form B) exhibits an XRPD substantially similar to FIG. 25A.

[0259] In some embodiments, the present disclosure provides Compound 1 methanesulfonic acid salt (Form C). In some embodiments, Compound 1 methanesulfonic acid salt (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.5, 15.0, 19.4, 22.5, and 30.2 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 methanesulfonic acid salt (Form C) exhibits an XRPD comprising the peaks shown in Table 10B below:

[0260] Table 10B. XRPD Table for Compound 1 methanesulfonic acid salt (Form C)

[0261] 2θ strength% 7.5 100 15.0 33.1 19.4 3.1 22.5 13.3 30.2 3

[0262] In some embodiments, Compound 1 methanesulfonic acid salt (Form C) exhibits an XRPD substantially similar to FIG. 25B.

[0263] In an embodiment, the present disclosure provides compound 1 mesylate salt (Form D). In some embodiments, compound 1 mesylate salt (Form D) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.4, 15.0, and 22.6 °2theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 mesylate salt (Form D) exhibits an XRPD comprising the peaks shown in Table 11 below:

[0264] Table 11. XRPD Table for Compound 1 Mesylate Salt (Form D)

[0265] 2-θ strength% 7.4 100 15.0 21.1 22.6 10

[0266] In some embodiments, compound 1 mesylate salt (Form D) exhibits an XRPD substantially similar to that of Figure 26.

[0267] Phosphate

[0268] In some embodiments, the present disclosure provides a phosphate salt of compound 1 (“compound 1 phosphate”). In some embodiments, the present disclosure provides a crystalline form of compound 1 phosphate.

[0269] In an embodiment, the present disclosure provides compound 1 phosphate salt (Form A). In some embodiments, compound 1 phosphate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.3, 3.6, 5.4, 9.9, and 13.1 °2theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 phosphate salt (Form A) further comprises one or more peaks at about 16.1, 17.9, 20.9, 23.7, and 26.4 °2theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 phosphate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 12 below:

[0270] Table 12. XRPD Table for Compound 1 Phosphate Salt (Form A)

[0271]

[0272]

[0273] In some embodiments, Compound 1 phosphate (Form A) exhibits an XRPD substantially similar to FIG. 27.

[0274] In some embodiments, Compound 1 phosphate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 217.6 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 phosphate (Form A) exhibits a DSC thermogram substantially similar to FIG. 28.

[0275] In some embodiments, Compound 1 phosphate (Form A) exhibits a TGA thermogram substantially similar to FIG. 28. In some embodiments, the TGA thermogram of Compound 1 phosphate (Form A) exhibits a weight loss of 0.0 to 1.7% over the temperature range of 25 to 204 °C.

[0276] In some embodiments, Compound 1 phosphate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 29. In some embodiments, Compound 1 phosphate (Form A) exhibits a weight moisture uptake of about 2.1% (by weight) at 80% relative humidity.

[0277] Tartrate salt

[0278] In some embodiments, the present disclosure provides a tartrate salt of Compound 1 (“Compound 1 tartrate”). In some embodiments, the present disclosure provides a D(-)-tartrate salt of Compound 1 (“Compound 1 D(-)-tartrate”). In some embodiments, the present disclosure provides a L(+)-tartrate salt of Compound 1 (“Compound 1 L(+)-tartrate”).

[0279] In some embodiments, the present disclosure provides a crystalline form of Compound 1 tartrate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 D(-)-tartrate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 L(+)-tartrate.

[0280] In an embodiment, the present disclosure provides compound 1L (+)-tartrate salt (Form A). In some embodiments, compound 1L (+)-tartrate salt exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 4.7, 13.9, 18.6, and 22.8 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1L (+)-tartrate salt (Form A) further comprises one or more peaks at about 14.6, 17.8, and 18.1 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 13 below:

[0281] Table 13. XRPD Table for Compound 1L (+)-tartrate salt (Form A)

[0282]

[0283]

[0284] In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits an XRPD substantially similar to FIG. 30.

[0285] In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 207.6 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 31.

[0286] In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 31. In some embodiments, the TGA thermogram of compound 1L (+)-tartrate salt (Form A) exhibits a weight loss of 0.0 to 1.2% over the temperature range of 25 to 189 °C.

[0287] In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits a DVS isotherm substantially similar to FIG. 32. In some embodiments, compound 1L (+)-tartrate salt (Form A) exhibits a weight moisture uptake of about 1.6% (by weight) at 80% relative humidity.

[0288] In an embodiment, the present disclosure provides compound 1L (+)-tartrate salt (Form B). In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 4.6, 12.4, 13.9, and 22.7 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1L (+)-tartrate salt (Form B) further comprises one or more peaks at about 14.8, 18.3, and 18.5 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 14 below:

[0289] Table 14. XRPD Table for Compound 1L (+)-tartrate salt (Form B)

[0290]

[0291]

[0292] In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits an XRPD substantially similar to FIG. 33.

[0293] In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 207.3 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits a DSC thermogram substantially similar to FIG. 34.

[0294] In some embodiments, compound 1L (+)-tartrate salt (Form B) exhibits a TGA thermogram substantially similar to FIG. 34. In some embodiments, the TGA thermogram of compound 1L (+)-tartrate salt (Form B) exhibits a weight loss of 0.0 to 0.6% over the temperature range of 25 to 180 °C.

[0295] In some embodiments, Compound 1L (+)-tartrate salt (Form B) exhibits a DVS isotherm substantially similar to FIG. 35. In some embodiments, Compound 1L (+)-tartrate salt (Form B) exhibits a weight moisture uptake of about 1.7% by weight at 80% relative humidity.

[0296] Fumarate salt

[0297] In some embodiments, the present disclosure provides a fumarate salt of Compound 1 (“Compound 1 fumarate salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 fumarate salt.

[0298] In one embodiment, the present disclosure provides Compound 1 fumarate salt (Form A). In some embodiments, Compound 1 fumarate salt (Form A) exhibits an XRPD comprising one or more peaks at about 3.5 and 16.0 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 fumarate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 15 below:

[0299] Table 15. XRPD table for Compound 1 fumarate salt (Form A)

[0300] 2θ strength% 3.5 100 16.0 13.4

[0301] In some embodiments, Compound 1 fumarate salt (Form A) exhibits an XRPD substantially similar to FIG. 36.

[0302] In some embodiments, Compound 1 fumarate salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 87.0 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 fumarate salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 37.

[0303] In some embodiments, Compound 1 fumarate salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 37. In some embodiments, the TGA thermogram of Compound 1 fumarate salt (Form A) exhibits a weight loss of 0.0 to 0.9% over a temperature range of 25 to 75 °C.

[0304] In some embodiments, the present disclosure provides compound 1 fumarate salt (Form B). In some embodiments, compound 1 fumarate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 11.0, 16.2, and 17.5 °2Θ (specifically, about 3.6, 11.0, 16.2, and 17.5 °2Θ) with a error limit of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2). In some embodiments, compound 1 fumarate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 16 below:

[0305] Table 16. XRPD Table for Compound 1 Fumarate Salt (Form B)

[0306] 2θ strength% 3.6 100 11.0 12.8 16.2 23.4 17.5 13.1

[0307] In some embodiments, compound 1 fumarate salt (Form B) exhibits an XRPD substantially similar to FIG. 38.

[0308] In some embodiments, compound 1 fumarate salt (Form B) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 89.9 °C with a error limit of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less (specifically, about ±0.2). In some embodiments, compound 1 fumarate salt (Form B) exhibits a DSC thermogram substantially similar to FIG. 39.

[0309] In some embodiments, compound 1 fumarate salt (Form B) exhibits a TGA thermogram substantially similar to FIG. 39. In some embodiments, the TGA thermogram of compound 1 fumarate salt (Form B) exhibits a weight loss of 0.0 to 1.85% over the temperature range of 25 to 150 °C.

[0310] In some embodiments, compound 1 fumarate salt (Form B) exhibits a DVS isotherm plot substantially similar to FIG. 40. In some embodiments, compound 1 fumarate salt (Form B) exhibits a weight moisture uptake of about 7.2% (by weight) at 80% relative humidity.

[0311] In an embodiment, the present disclosure provides Compound 1 fumarate salt (Form C). In some embodiments, Compound 1 fumarate salt (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 14.5, 15.4, 16.7, 17.6, and 28.8 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 fumarate salt (Form C) further comprises one or more peaks at about 8.4, 19.7, 20.5, 22.9, and 38.1 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 fumarate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 17 below:

[0312] Table 17. XRPD Table for Compound 1 fumarate salt (Form C)

[0313] 2θ strength% 8.4 26.2 9.8 8.9 12.9 10.2 14.5 46.3 15.4 100 16.7 36.6 17.6 44.4 19.7 21.7 20.5 27.9 21.5 12.6 22.9 20.6 23.3 8.2 25.2 15.8 25.7 12.1 27.4 14.5 28.8 41.6 38.1 28.8

[0314] In some embodiments, Compound 1 fumarate salt (Form C) exhibits an XRPD substantially similar to FIG. 41.

[0315] In an embodiment, the present disclosure provides Compound 1 fumarate salt (Form D). In some embodiments, Compound 1 fumarate salt (Form D) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.2, 12.2, 15.2, 15.5, and 19.9 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 fumarate salt (Form D) further comprises one or more peaks at about 10.4, 13.6, 14.2, 21.2, and 22.3 °2Θ, with a tolerance of about ± 0.5; ± 0.4; ± 0.3; ± 0.2; ± 0.1; ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 fumarate salt (Form D) exhibits an XRPD comprising the peaks shown in Table 18 below:

[0316] Table 18. XRPD Table for Compound 1 fumarate salt (Form D)

[0317] 2θ strength% 5.2 29.5 10.4 23.5 12.2 100 13.6 27.9 14.2 28.8 15.2 42 15.5 40 16.5 19.6 16.9 13.5 17.2 9.6 19.1 11 19.9 40.9 20.5 19.2 21.2 27.9 22.3 21.2 22.9 17.1 23.5 17.4 24.0 21.2 24.6 13.5 26.2 18.5 26.9 14.4 28.9 15.1

[0318] In some embodiments, Compound 1 fumarate salt (Form D) exhibits an XRPD substantially similar to FIG. 42.

[0319] Tosylate salt

[0320] In some embodiments, the present disclosure provides a tosylate salt of Compound 1 (“Compound 1 tosylate salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 tosylate salt.

[0321] In one embodiment, the present disclosure provides Compound 1 tosylate salt (Form A). In some embodiments, Compound 1 tosylate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.4, 9.8, 10.3, 12.5, and 15.3 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 tosylate salt (Form A) further comprises one or more peaks at about 17.4, 17.9, 19.6, 23.2, and 26.0 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0322] In some embodiments, Compound 1 tosylate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 19 below:

[0323] Table 19. XRPD Table for Compound 1 Tosylate Salt (Form A)

[0324]

[0325]

[0326] In some embodiments, Compound 1 tosylate salt (Form A) exhibits an XRPD substantially similar to FIG. 43.

[0327] In some embodiments, Compound 1 tosylate salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 186.2 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 tosylate salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 44.

[0328] In some embodiments, Compound 1 besylate (Form A) exhibits a TGA thermogram substantially similar to FIG. 44. In some embodiments, the TGA thermogram of Compound 1 besylate (Form A) exhibits a weight loss of 0.0 to 0.9% over the temperature range of 25 to 175 °C.

[0329] In some embodiments, Compound 1 besylate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 45. In some embodiments, Compound 1 besylate (Form A) exhibits a weight moisture uptake of about 1.5% by weight at 80% relative humidity.

[0330] In one embodiment, the present disclosure provides Compound 1 besylate (Form B). In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 10.0, 15.2, 15.5, 17.2, and 19.4 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 besylate (Form B) further comprises one or more peaks at about 10.3, 16.7, 19.1, 20.1, and 20.8 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0331] In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD comprising the peaks set forth in Table 20 below:

[0332] Table 20. XRPD Table for Compound 1 Besylate (Form B)

[0333]

[0334]

[0335] In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD substantially similar to FIG. 46.

[0336] In an embodiment, the present disclosure provides Compound 1 mesylate (Form C). In some embodiments, Compound 1 mesylate (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.4, 10.2, 12.5, 18.3, and 19.7 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 mesylate (Form C) further comprises one or more peaks at about 9.8, 14.7, 16.6, 17.8, and 23.2 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0337] In some embodiments, Compound 1 mesylate (Form C) exhibits an XRPD comprising the peaks set forth in Table 21 below:

[0338] Table 21. XRPD Table for Compound 1 mesylate (Form C)

[0339]

[0340]

[0341] In some embodiments, Compound 1 mesylate (Form C) exhibits an XRPD substantially similar to that of Figure 47.

[0342] Glucuronate

[0343] In some embodiments, the present disclosure provides a glucuronate salt of Compound 1 (“Compound 1 glucuronate”). In some embodiments, the present disclosure provides a D- glucuronate salt of Compound 1 (“Compound 1 D-glucuronate”). In some embodiments, the present disclosure provides an L-glucuronate salt of Compound 1 (“Compound 1 L- glucuronate”).

[0344] In some embodiments, the present disclosure provides a crystalline form of Compound 1 glucuronate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 D-glucuronate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 L-glucuronate.

[0345] In an embodiment, the present disclosure provides compound 1D-glucuronate (Form A). In some embodiments, compound 1D-glucuronate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 4.3, 12.9, 16.8, 20.2, and 20.9 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1D-glucuronate (Form A) further comprises one or more peaks at about 3.3, 14.7, 17.3, 21.6, and 24.8 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0346] In some embodiments, compound 1D-glucuronate (Form A) exhibits an XRPD comprising the peaks set forth in Table 22 below:

[0347] Table 22. XRPD Table for Compound 1D-glucuronate (Form A)

[0348] 2θ strength% 3.3 30.3 4.3 100 11.6 8.8 12.9 51.1 13.8 11.1 14.7 24.3 15.0 8.3 15.4 18.7 16.8 62.1 17.3 38.5 20.2 49.3 20.9 99.8 21.6 20.9 22.4 8 24.2 20 24.8 20.5 25.7 5.7 28.2 9.1 28.8 5.7 30.8 9.1 32.5 11.3

[0349] In some embodiments, compound 1D-glucuronate (Form A) exhibits an XRPD substantially similar to that of FIG. 48.

[0350] In some embodiments, compound 1D-glucuronate (Form A) exhibits a DSC thermogram comprising an endotherm at about 116.2 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1D-glucuronate (Form A) exhibits a DSC thermogram comprising an endotherm at about 139.3 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1D-glucuronate (Form A) exhibits a DSC thermogram substantially similar to that of FIG. 49.

[0351] In some embodiments, compound 1D-glucuronate (Form A) exhibits a TGA thermogram substantially similar to that of FIG. 49. In some embodiments, the TGA thermogram of compound 1D-glucuronate (Form A) exhibits a weight loss of 0.0 to 3.0% over the temperature range of 25 to 120 °C.

[0352] In some embodiments, Compound 1D-glucuronate (Form A) exhibits a DVS isotherm substantially similar to that of FIG. 50. In some embodiments, Compound 1D- glucuronate (Form A) exhibits a weight moisture uptake of about 1.4% by weight at 80% relative humidity.

[0353] In one embodiment, the present disclosure provides Compound 1D-glucuronate (Form B). In some embodiments, Compound 1D-glucuronate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 14.7, 16.7, 17.0, 20.0, and 20.4 °2Θ, with a + / - about 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2) error limit. In some embodiments, the XRPD of Compound 1D-glucuronate (Form B) further comprises one or more peaks at about 8.5, 15.0, 19.5, 22.5, and 24.3 °2Θ, with a + / - about 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2) error limit.

[0354] In some embodiments, Compound 1D-glucuronate (Form B) exhibits an XRPD comprising the peaks set forth in Table 23 below:

[0355] Table 23. XRPD Table for Compound 1D-glucuronate (Form B)

[0356]

[0357]

[0358] In some embodiments, Compound 1D-glucuronate (Form B) exhibits an XRPD substantially similar to that of FIG. 51.

[0359] Ethanesulfonate

[0360] In some embodiments, the present disclosure provides an ethanesulfonate salt of Compound 1 (“Compound 1 ethanesulfonate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 ethanesulfonate.

[0361] In an embodiment, the present disclosure provides Compound 1 besylate salt (Form A). In some embodiments, Compound 1 besylate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.4, 3.7, 7.6, 15.3, and 23.0 °2Θ, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2). In some embodiments, the XRPD of Compound 1 besylate salt (Form A) further comprises one or more peaks at about 23.3 and 30.8 °2Θ, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2).

[0362] In some embodiments, Compound 1 besylate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 24 below:

[0363] Table 24. XRPD Table for Compound 1 Besylate Salt (Form A)

[0364]

[0365]

[0366] In some embodiments, Compound 1 besylate salt (Form A) exhibits an XRPD substantially similar to that of FIG. 52.

[0367] In some embodiments, Compound 1 besylate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 177.9 °C, with error limits of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less (specifically, about ±0.2). In some embodiments, Compound 1 besylate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 207.0 °C, with error limits of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less (specifically, about ±0.2). In some embodiments, Compound 1 besylate salt (Form A) exhibits a DSC thermogram substantially similar to that of FIG. 53.

[0368] In some embodiments, Compound 1 besylate salt (Form A) exhibits a TGA thermogram substantially similar to that of FIG. 53. In some embodiments, the TGA thermogram of Compound 1 besylate salt (Form A) exhibits a weight loss of 0.0 to 2.9% over the temperature range of 25 to 180 °C.

[0369] In some embodiments, Compound 1 esylate (Form A) exhibits a DVS isotherm substantially similar to FIG. 54. In some embodiments, Compound 1 esylate (Form A) exhibits a weight moisture uptake of about 1.4% by weight at 80% relative humidity.

[0370] sulfate salt

[0371] In some embodiments, the present disclosure provides a sulfate salt of Compound 1 (“Compound 1 sulfate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 sulfate.

[0372] In one embodiment, the present disclosure provides Compound 1 sulfate (Form A). In some embodiments, Compound 1 sulfate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 5.2, 7.8, 8.1, and 15.1 °2- theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2-theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 sulfate (Form A) exhibits an XRPD comprising the peaks shown in Table 25 below:

[0373] Table 25. XRPD Table for Compound 1 sulfate (Form A)

[0374] 2θ strength% 3.6 100 5.2 39 7.8 50 8.1 16.4 14.2 9 14.7 9.6 15.1 13.6 17.4 10.3 18.2 10.6 18.4 9.4 19.7 11.3 20.8 9 21.6 8.2 24.0 8.8

[0375] In some embodiments, Compound 1 sulfate (Form A) exhibits an XRPD substantially similar to FIG. 55.

[0376] In some embodiments, Compound 1 sulfate (Form A) exhibits a DSC thermogram comprising an endotherm at about 167.1 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 sulfate (Form A) exhibits a DSC thermogram substantially similar to FIG. 56.

[0377] In some embodiments, Compound 1 sulfate (Form A) exhibits a TGA thermogram substantially similar to FIG. 56. In some embodiments, the TGA thermogram of Compound 1 sulfate (Form A) exhibits a weight loss of 0.0 to 1.0% over the temperature range of 25 to 120 °C.

[0378] In some embodiments, Compound 1 sulfate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 57. In some embodiments, Compound 1 sulfate (Form A) exhibits a weight moisture uptake of about 6.2% by weight at 80% relative humidity.

[0379] Ascorbate

[0380] In some embodiments, the present disclosure provides an ascorbate salt of Compound 1 (“Compound 1 ascorbate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 ascorbate.

[0381] In one embodiment, the present disclosure provides Compound 1 ascorbate (Form A). In some embodiments, Compound 1 ascorbate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 5.6, 16.6, 19.6, and 19.8 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0382] In some embodiments, Compound 1 ascorbate (Form A) exhibits an XRPD comprising the peaks set forth in Table 26 below:

[0383] Table 26. XRPD Table for Compound 1 Ascorbate (Form A)

[0384] 2θ strength% 3.6 28.5 5.6 31.7 9.6 9.7 11.0 8.8 11.5 13.8 11.9 13.3 14.5 12.9 16.6 100 18.9 6.3 19.6 31.9 19.8 22.5 21.6 14.7 22.1 5.1 22.9 6 23.2 10.6 24.1 15.1 24.5 21.1

[0385] In some embodiments, Compound 1 ascorbate (Form A) exhibits an XRPD substantially similar to FIG. 58.

[0386] In some embodiments, Compound 1 ascorbate (Form A) exhibits a DSC thermogram comprising an endotherm at about 46.3 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 ascorbate (Form A) exhibits a DSC thermogram comprising an endotherm at about 124.3 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 ascorbate (Form A) exhibits a DSC thermogram substantially similar to FIG. 59.

[0387] In some embodiments, Compound 1 ascorbate (Form A) exhibits a TGA thermogram substantially similar to FIG. 59. In some embodiments, the TGA thermogram of Compound 1 ascorbate (Form A) exhibits a weight loss of 0.0 to 5.6% over the temperature range of 25 to 120 °C.

[0388] In some embodiments, Compound 1 ascorbate (Form A) exhibits a DVS isotherm substantially similar to FIG. 60. In some embodiments, Compound 1 ascorbate (Form A) exhibits a weight moisture uptake of about 5.7% (by weight) at 80% relative humidity.

[0389] In one embodiment, the present disclosure provides Compound 1 ascorbate (Form B). In some embodiments, Compound 1 ascorbate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.5, 16.6, 19.7, 20.1, and 28.3 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0390] In some embodiments, Compound 1 ascorbate (Form B) exhibits an XRPD comprising the peaks set forth in Table 27 below:

[0391] Table 27. XRPD Table for Compound 1 ascorbate (Form B)

[0392] 2θ strength% 5.5 74.9 14.7 21.2 16.6 100 19.7 29.6 20.1 38 23.6 22.9 28.3 39.7

[0393] In some embodiments, Compound 1 ascorbate (Form B) exhibits an XRPD substantially similar to FIG. 61.

[0394] Napsylate

[0395] In some embodiments, the present disclosure provides a napsylate salt of Compound 1 (“Compound 1 napsylate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 napsylate.

[0396] In one embodiment, the present disclosure provides Compound 1 napsylate (Form A). In some embodiments, Compound 1 napsylate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.3, 9.4, 14.2, 16.4, and 17.8 °2- theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 napsylate (Form A) further comprises one or more peaks at about 9.7, 17.3, 20.3, 24.4, and 26.1 °2-theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 napsylate (Form A) exhibits an XRPD comprising the peaks set forth in Table 28 below:

[0397] Table 28. XRPD Table for Compound 1 napsylate (Form A)

[0398]

[0399]

[0400] In some embodiments, Compound 1 napsylate (Form A) exhibits an XRPD substantially similar to FIG. 62.

[0401] In some embodiments, Compound 1 napsylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 41.7 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 napsylate (Form A) exhibits a DSC thermogram substantially similar to FIG. 63.

[0402] In some embodiments, Compound 1 naphthalene disulfonate (Form A) exhibits a TGA thermogram substantially similar to FIG. 63. In some embodiments, the TGA thermogram of Compound 1 naphthalene disulfonate (Form A) exhibits a weight loss of 0.0 to 0.7% over the temperature range of 25 to 120 °C.

[0403] In some embodiments, Compound 1 naphthalene disulfonate (Form A) exhibits a DVS isotherm substantially similar to FIG. 64. In some embodiments, Compound 1 naphthalene disulfonate exhibits a weight moisture uptake of about 3.1% by weight at 80% relative humidity.

[0404] In some embodiments, the present disclosure provides Compound 1 naphthalene disulfonate (Form B). In some embodiments, Compound 1 naphthalene disulfonate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.0, 14.2, 18.1, 19.0, and 20.3 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 naphthalene disulfonate (Form B) further comprises one or more peaks at about 12.0, 16.9, 18.4, 19.4, and 24.1 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0405] In some embodiments, Compound 1 naphthalene disulfonate (Form B) exhibits an XRPD comprising the peaks set forth in Table 29 below:

[0406] Table 29. XRPD Table for Compound 1 naphthalene disulfonate (Form B)

[0407]

[0408]

[0409] In some embodiments, Compound 1 naphthalene disulfonate (Form B) exhibits an XRPD substantially similar to FIG. 65.

[0410] Malonate

[0411] In some embodiments, the present disclosure provides a malonate salt of Compound 1 (“Compound 1 malonate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 malonate.

[0412] In an embodiment, the present disclosure provides compound 1 malonate salt (Form A). In some embodiments, compound 1 malonate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 15.1, 18.0, 18.8, 23.4, and 23.8 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 malonate salt (Form A) further comprises one or more peaks at about 3.6, 13.8, 15.6, 21.4, and 27.6 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0413] In some embodiments, compound 1 malonate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 30 below:

[0414] Table 30. XRPD Table for Compound 1 Malonate Salt (Form A)

[0415]

[0416]

[0417] In some embodiments, compound 1 malonate salt (Form A) exhibits an XRPD substantially similar to that of FIG. 66.

[0418] In some embodiments, compound 1 malonate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 36.9 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 malonate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 124.6 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 malonate salt (Form A) exhibits a DSC thermogram substantially similar to that of FIG. 67.

[0419] In some embodiments, compound 1 malonate salt (Form A) exhibits a TGA thermogram substantially similar to that of FIG. 67. In some embodiments, the TGA thermogram of compound 1 malonate salt (Form A) exhibits a weight loss of 0.0 to 1.9% over the temperature range of 25 to 120 °C.

[0420] Benzenesulfonate

[0421] In some embodiments, the present disclosure provides a benzenesulfonic acid salt of Compound 1 (“Compound 1 benzenesulfonic acid salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 benzenesulfonic acid salt.

[0422] In one embodiment, the present disclosure provides Compound 1 benzenesulfonic acid salt (Form A). In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 14.7, 15.8, 22.1, 23.2, and 26.6 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 benzenesulfonic acid salt (Form A) further comprises one or more peaks at about 3.7, 16.2, 17.8, 19.5, and 30.4 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0423] In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 31 below:

[0424] Table 31. XRPD Table for Compound 1 benzenesulfonic acid salt (Form A)

[0425] 2θ strength% 3.3 21.9 3.7 7 7.4 100 14.7 41.9 15.8 3.5 16.2 19.3 17.2 5.7 17.8 9.1 19.5 9.3 22.1 21.4 23.2 20.6 26.6 3.8 29.6 3.6 30.4 7.3

[0426] In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits an XRPD substantially similar to FIG. 68.

[0427] In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 194.2 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 69.

[0428] In some embodiments, Compound 1 benzenesulfonic acid salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 69. In some embodiments, the TGA thermogram of Compound 1 benzenesulfonic acid salt (Form A) exhibits a weight loss of 0.0 to 0.3% over the temperature range of 25 to 120 °C.

[0429] In some embodiments, Compound 1 besylate (Form A) exhibits a DVS isotherm substantially similar to that of FIG. 70. In some embodiments, Compound 1 besylate (Form A) exhibits a weight moisture uptake of about 4.0% by weight at 80% relative humidity.

[0430] In one embodiment, the present disclosure provides Compound 1 besylate (Form B).

[0431] In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 7.3, 14.7, 22.1, 23.2, and 29.6 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 besylate (Form B) further comprises one or more peaks at about 7.9, 16.2, 16.4, 17.2, and 30.4 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0432] In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD comprising the peaks set forth in Table 32 below:

[0433] Table 32. XRPD Table for Compound 1 Besylate (Form B)

[0434] 2θ strength% 7.3 100 7.9 0.5 14.7 51.7 16.2 3.4 16.4 3.0 17.2 2.7 22.1 24.5 23.2 7.7 29.6 4.4 30.4 2.7

[0435] In some embodiments, Compound 1 besylate (Form B) exhibits an XRPD substantially similar to that of FIG. 71.

[0436] Hydroxyethylsulfonate

[0437] In some embodiments, the present disclosure provides a hydroxyethylsulfonate salt of Compound 1 (“Compound 1 hydroxyethylsulfonate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 hydroxyethylsulfonate.

[0438] In one embodiment, the present disclosure provides Compound 1 hydroxyethylsulfonate (Form A).

[0439] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.6, 16.7, 16.9, 18, and 20.9 °2Θ (specifically, three or more peaks) with an error limit of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2). In some embodiments, the XRPD of Compound 1 hydroxyethanesulfonate (Form A) further comprises one or more peaks at about 3.7, 15.7, 16.2, 20.7, and 25.1 °2Θ with an error limit of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2).

[0440] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits an XRPD comprising the peaks set forth in Table 33 below:

[0441] Table 33. XRPD Table for Compound 1 hydroxyethanesulfonate (Form A)

[0442]

[0443]

[0444] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits an XRPD substantially similar to FIG. 72.

[0445] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 153.3 °C with an error limit of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less (specifically, about ±0.2). In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits a DSC thermogram substantially similar to FIG. 73.

[0446] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits a TGA thermogram substantially similar to FIG. 73. In some embodiments, the TGA thermogram of Compound 1 hydroxyethanesulfonate (Form A) exhibits a weight loss of 0.0 to 0.0% over the temperature range of 25 to 120 °C.

[0447] In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 74. In some embodiments, Compound 1 hydroxyethanesulfonate (Form A) exhibits a weight moisture uptake of about 4.9% (by weight) at 80% relative humidity.

[0448] In an embodiment, the present disclosure provides compound 1 hydrobromide (Form B). In some embodiments, compound 1 hydrobromide (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 8.0, 9.0, 10.0, 12.0, and 13.0 °2theta, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2). In some embodiments, the XRPD of compound 1 hydrobromide (Form B) further comprises one or more peaks at about 11.0, 12.5, 14.0, 14.5, and 15.0 °2theta, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2).

[0449] In some embodiments, compound 1 hydrobromide (Form B) exhibits an XRPD comprising the peaks set forth in Table 33 below:

[0450] Table 33. XRPD Table for Compound 1 Hydrobromide (Form B)

[0451] 2θ strength% 8.5 15.7 11.4 27.1 13.1 29.2 14.2 26.5 14.5 71.4 15.0 23.4 15.8 30.5 17.0 24.0 17.9 100 18.1 54.8 18.6 75.1 19.5 14.8 22.1 14.8 24.2 16.9 27.2 15.4 27.5 10.5

[0452] In some embodiments, compound 1 hydrobromide (Form B) exhibits an XRPD substantially similar to that of FIG. 74.

[0453] Gentisate

[0454] In some embodiments, the present disclosure provides a gentisate salt of compound 1 (“compound 1 gentisate”). In some embodiments, the present disclosure provides a crystalline form of compound 1 gentisate.

[0455] In an embodiment, the present disclosure provides compound 1 gentisate (Form A). In some embodiments, compound 1 gentisate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.4, 3.6, 7.0, 14.6, and 21.4 °2theta, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2). In some embodiments, the XRPD of compound 1 gentisate (Form A) further comprises one or more peaks at about 16.0, 18.0, 18.5, 19.5, and 21.1 °2theta, with error limits of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less (specifically, about ±0.2).

[0456] In some embodiments, Compound 1 gentisate salt (Form A) exhibits an XRPD comprising the peaks shown in Table 35 below:

[0457] Table 35. XRPD table for Compound 1 gentisate salt (Form A)

[0458] 2θ strength% 3.4 100 3.6 54.6 5.3 10.1 7.0 88.3 7.6 5.8 8.1 12.3 9.0 8.2 10.9 20 14.0 18.5 14.6 42.3 16.0 30.1 16.3 25.7 18.0 40.3 18.5 28.1 19.5 31.7 19.8 11.8 21.1 39.1 21.4 48 21.8 6.8 22.8 22.4 23.3 7.8

[0459] In some embodiments, Compound 1 gentisate salt (Form A) exhibits an XRPD substantially similar to Figure 76.

[0460] In some embodiments, Compound 1 gentisate salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 117.7 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 gentisate salt (Form A) exhibits a DSC thermogram substantially similar to Figure 77.

[0461] In some embodiments, 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 to 9.0% over the temperature range of 25 to 200 °C.

[0462] In some embodiments, Compound 1 gentisate salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 78. In some embodiments, Compound 1 gentisate salt (Form A) exhibits a weight moisture uptake of about 3.1% (by weight) at 80% relative humidity.

[0463] In one embodiment, the present disclosure provides Compound 1 gentisate salt (Form B). In some embodiments, Compound 1 gentisate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.5, 10.9, 16.4, 21.9, and 22.8 °2Θ with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 gentisate salt (Form B) further comprises one or more peaks at about 9.2, 13.0, 17.2, 18.7, and 27.8 °2Θ with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0464] In some embodiments, Compound 1 gentisate salt (Form B) exhibits an XRPD comprising the peaks shown in Table 36 below:

[0465] Table 36. XRPD Table for Compound 1 gentisate salt (Form B)

[0466]

[0467]

[0468] In some embodiments, Compound 1 gentisate salt (Form B) exhibits an XRPD substantially similar to that of Figure 79.

[0469] In one embodiment, the present disclosure provides Compound 1 gentisate salt (Form C). In some embodiments, Compound 1 gentisate salt (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.3, 15.2, 15.9, 21.4, and 26.6 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 gentisate salt (Form C) further comprises one or more peaks at about 7.6, 10.6, 13.8, 16.9, and 19.8 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0470] In some embodiments, Compound 1 gentisate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 37 below:

[0471] Table 37. XRPD Table for Compound 1 gentisate salt (Form C)

[0472]

[0473]

[0474] In some embodiments, Compound 1 gentisate salt (Form C) exhibits an XRPD substantially similar to that of Figure 80.

[0475] 1-Hydroxy-2-naphthoate

[0476] In some embodiments, the present disclosure provides a 1-hydroxy-2-naphthoate salt of Compound 1 (“Compound 1 1-hydroxy-2-naphthoate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 1-hydroxy-2-naphthoate.

[0477] In an embodiment, the present disclosure provides compound 1 1-hydroxy-2-naphthalene carboxylate (Form A). In some embodiments, compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.2, 6.2, 13.8, 21.2, and 21.6 °2Theta, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) further exhibits an XRPD comprising one or more peaks at about 13.4, 16.2, 19.9, 20.2, and 24.7 °2Theta, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0478] In some embodiments, compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits an XRPD comprising the peaks set forth in Table 38 below:

[0479] Table 38. XRPD Table for Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A)

[0480]

[0481]

[0482] In some embodiments, compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits an XRPD substantially similar to that of Figure 81.

[0483] In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 57.7 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 79.1 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 116.1 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 164.7 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DSC thermogram substantially similar to FIG. 82.

[0484] In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a TGA thermogram substantially similar to FIG. 82. In some embodiments, the TGA thermogram of Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a weight loss of 0.0 to 3.6% over the temperature range of 25 to 120 °C.

[0485] In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a DVS isotherm plot substantially similar to FIG. 83. In some embodiments, Compound 1 1-hydroxy-2-naphthalene carboxylate (Form A) exhibits a weight moisture uptake of about 4.6% (by weight) at 80% relative humidity.

[0486] In an embodiment, the present disclosure provides compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B). In some embodiments, compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 8.0, 8.6, 13.5, 13.8, and 20.6 °2Q, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B) further comprises one or more peaks at about 14.4, 15.2, 16.1, 21.4, and 23.8 °2Q, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0487] In some embodiments, compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 39 below:

[0488] Table 39. XRPD Table for Compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B)

[0489]

[0490]

[0491] In some embodiments, compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form B) exhibits an XRPD substantially similar to FIG. 84.

[0492] In an embodiment, the present disclosure provides compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form C). In some embodiments, compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 8.5, 13.7, 14.2, 17.3, and 21.4 °2Q, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 1 -hydroxy-2-naphthalene sulfate salt (Form C) further comprises one or more peaks at about 7.7, 15.4, 20.2, 20.6, and 21.1 °2Q, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0493] In some embodiments, Compound 1 1 -hydroxy-2-naphthoate salt (Form C) exhibits an XRPD comprising the peaks shown in Table 40 below:

[0494] Table 40. XRPD Table for Compound 1 1 -hydroxy-2-naphthoate salt (Form C)

[0495]

[0496]

[0497] In some embodiments, Compound 1 1 -hydroxy-2-naphthoate salt (Form C) exhibits an XRPD substantially similar to Figure 85.

[0498] In one embodiment, the present disclosure provides Compound 1 1 -hydroxy-2-naphthoate salt (Form D). In some embodiments, Compound 1 1 -hydroxy-2-naphthoate salt (Form D) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 10.4, 12.9, 13.5, 20.4, and 20.9 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 1 -hydroxy-2-naphthoate salt (Form D) further comprises one or more peaks at about 6.3, 9.1, 11.2, 13.2, and 19.9 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0499] In some embodiments, Compound 1 1 -hydroxy-2-naphthoate salt (Form D) exhibits an XRPD comprising the peaks shown in Table 41 below:

[0500] Table 41. XRPD Table for Compound 1 1 -hydroxy-2-naphthoate salt (Form D)

[0501] 2θ strength% 6.3 20.2 9.1 14.6 10.4 46.3 11.2 16.5 12.1 11.3 12.9 29.9 13.2 22.5 13.5 40.5 19.5 14.4 19.9 21.1 20.4 40.1 20.9 100 22.6 7.7 28.2 6.1 31.5 5.6

[0502] In some embodiments, Compound 1 1 -hydroxy-2-naphthoate salt (Form D) exhibits an XRPD substantially similar to Figure 86.

[0503] Cyclamic Acid Salt

[0504] In some embodiments, the present disclosure provides a cyclamic acid salt of Compound 1 (“Compound 1 cyclamic acid salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 cyclamic acid salt.

[0505] In an embodiment, the present disclosure provides compound 1 cyclohexane sulfamate salt (Form A). In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.6, 7.2, 18.5, 19.5, and 21.6 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 cyclohexane sulfamate salt (Form A) further comprises one or more peaks at about 14.3, 14.8, 17.2, 17.6, and 18.2 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0506] In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 42 below:

[0507] Table 42. XRPD Table for Compound 1 Cyclohexane Sulfamate Salt (Form A)

[0508] 2θ strength% 6.6 100 7.2 42.7 8.6 9.3 14.3 19.8 14.8 18.7 17.2 11.3 17.6 12.9 18.2 24.9 18.5 28.8 19.5 27 20.9 6.1 21.6 35.6 26.1 5

[0509] In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits an XRPD substantially similar to Figure 87.

[0510] In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 60.1 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 168.5 °C, with error limits of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits a DSC thermogram substantially similar to Figure 88.

[0511] In some embodiments, compound 1 cyclohexane sulfamate salt (Form A) exhibits a TGA thermogram substantially similar to Figure 88. In some embodiments, the TGA thermogram of compound 1 cyclohexane sulfamate salt (Form A) exhibits a weight loss of 0.0 to 5.1% over the temperature range of 25 to 180 °C.

[0512] In some embodiments, Compound 1 cyclosporine A salt (Form A) exhibits a DVS isotherm substantially similar to that of Figure 89. In some embodiments, Compound 1 cyclosporine A salt (Form A) exhibits a weight moisture uptake of about 7.3% by weight at 80% relative humidity.

[0513] ethane-1,2-disulfonate salt

[0514] In some embodiments, the present disclosure provides an ethane-1,2-disulfonate salt of Compound 1 (“Compound 1 ethane-1,2-disulfonate salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 ethane-1,2-disulfonate salt.

[0515] In one embodiment, the present disclosure provides Compound 1 ethane-1,2-disulfonate salt (Form A). In some embodiments, Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 16.2, 16.5, 17.5, 20.7, and 21.3 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 ethane-1,2-disulfonate salt (Form A) further comprises one or more peaks at about 3.7, 5.5, 13.8, 14.7, and 26.0 °2Theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0516] In some embodiments, Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 43 below:

[0517] Table 43. XRPD Table for Compound 1 ethane-1,2-disulfonate salt (Form A)

[0518]

[0519]

[0520] In some embodiments, Compound 1 ethane-1,2-disulfonate salt (Form A) exhibits an XRPD substantially similar to that of Figure 90.

[0521] In some embodiments, Compound 1 edisylate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 59.0 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 edisylate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 154.8 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 edisylate salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 91.

[0522] In some embodiments, Compound 1 edisylate salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 91. In some embodiments, the TGA thermogram of Compound 1 edisylate salt (Form A) exhibits a weight loss of 0.0 to 0.7% over the temperature range of 25 to 120 °C.

[0523] In some embodiments, Compound 1 edisylate salt (Form A) exhibits a DVS isotherm substantially similar to FIG. 92. In some embodiments, Compound 1 edisylate salt (Form A) exhibits a weight moisture uptake of about 12.9% (by weight) at 80% relative humidity.

[0524] In one embodiment, the present disclosure provides Compound 1 edisylate salt (Form B). In some embodiments, Compound 1 edisylate salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.5, 16.4, 17.4, 17.6, and 20.7 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 edisylate salt (Form B) further comprises one or more peaks at about 10.9, 13.7, 14.6, 21.2, and 22.1 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0525] In some embodiments, Compound 1 edisylate salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 44 below:

[0526] Table 44. XRPD Table for Compound 1 ethane-1,2-disulfonate salt (Form B)

[0527]

[0528]

[0529] In some embodiments, Compound 1 ethane-1,2-disulfonate salt (Form B) exhibits an XRPD substantially similar to FIG. 93.

[0530] Dichloroacetate

[0531] In some embodiments, the present disclosure provides a dichloroacetate salt of Compound 1 (“Compound 1 dichloroacetate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 dichloroacetate.

[0532] In one embodiment, the present disclosure provides Compound 1 dichloroacetate salt (Form A). In some embodiments, Compound 1 dichloroacetate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.4, 3.6, 16.2, 17.1, and 19.5 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 dichloroacetate salt (Form A) further comprises one or more peaks at about 8.1, 11.4, 12.8, 16.7, and 20.0 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0533] In some embodiments, Compound 1 dichloroacetate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 45 below:

[0534] Table 45. XRPD Table for Compound 1 dichloroacetate salt (Form A)

[0535] 2θ strength% 3.4 100 3.6 49.1 8.1 37.7 11.0 9.6 11.4 11.6 12.8 10.8 14.7 7.7 16.2 42.9 16.7 9.8 17.1 58.4 17.5 7.1 19.5 43.2 20.0 14.3 21.9 8.5 22.7 7.3 25.5 9.3 25.8 9.1 26.6 8.2 27.2 5.1 31.0 6.6

[0536] In some embodiments, Compound 1 dichloroacetate salt (Form A) exhibits an XRPD substantially similar to FIG. 94.

[0537] In some embodiments, Compound 1 fumarate salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 117.7 °C (e.g., a sharp endotherm), with an error boundary of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 fumarate salt (Form A) exhibits a DSC thermogram substantially similar to FIG. 95.

[0538] In some embodiments, Compound 1 fumarate salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 95. In some embodiments, the TGA thermogram of Compound 1 fumarate salt (Form A) exhibits a weight loss of 0.0 to 3.7% over the temperature range of 25 to 150 °C.

[0539] In some embodiments, Compound 1 fumarate salt (Form A) exhibits a DVS isotherm graph substantially similar to FIG. 96. In some embodiments, Compound 1 fumarate salt (Form A) exhibits a weight moisture uptake of about 1.8% by weight at 80% relative humidity.

[0540] Malate

[0541] In some embodiments, the present disclosure provides a malate salt of Compound 1 (“Compound 1 malate”). In some embodiments, the present disclosure provides a D-malate salt of Compound 1 (“Compound 1 D-malate”). In some embodiments, the present disclosure provides an L-malate salt of Compound 1 (“Compound 1 L-malate”).

[0542] In some embodiments, the present disclosure provides a crystalline form of Compound 1 malate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 D-malate. In some embodiments, the present disclosure provides a crystalline form of Compound 1 L-malate.

[0543] In an embodiment, the present disclosure provides compound 1L-malate (Form A). In some embodiments, compound 1L-malate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.2, 12.5, 14.4, 15.7, and 18.4 °2theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, compound 1L-malate (Form A) further exhibits an XRPD comprising one or more peaks at about 3.6, 6.1, 13.2, 18.9, and 21.1 °2theta, with an error margin of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0544] In some embodiments, compound 1L-malate (Form A) exhibits an XRPD comprising the peaks set forth in Table 46 below:

[0545] Table 46. XRPD Table for Compound 1L-malate (Form A)

[0546]

[0547]

[0548]

[0549] In some embodiments, compound 1L-malate (Form A) exhibits an XRPD substantially similar to Figure 97.

[0550] In some embodiments, compound 1L-malate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 120.9 °C, with an error margin of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1L-malate (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a strong endotherm) at about 142.3 °C, with an error margin of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1L-malate (Form A) exhibits a DSC thermogram substantially similar to Figure 98.

[0551] In some embodiments, Compound 1L-malate (Form A) exhibits a TGA thermogram substantially similar to FIG. 98. In some embodiments, the TGA thermogram of Compound 1L-malate (Form A) exhibits a weight loss of 0.0 to 0.7% over the temperature range of 25 to 105 °C.

[0552] In some embodiments, Compound 1L-malate (Form A) exhibits a DVS isotherm substantially similar to FIG. 99. In some embodiments, Compound 1L-malate (Form A) exhibits a water uptake of about 2.0% by weight at 80% relative humidity.

[0553] In one embodiment, the present disclosure provides Compound 1L-malate (Form B). In some embodiments, Compound 1L-malate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.6, 13.4, 17.3, 20.8, and 23.2 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0554] In some embodiments, Compound 1L-malate (Form B) exhibits an XRPD comprising the peaks set forth in Table 47 below:

[0555] Table 47. XRPD Table for Compound 1L-malate (Form B)

[0556] 2θ strength% 3.7 57.5 5.6 100 6.0 23.7 8.3 12.1 9.2 19.4 11.2 56.7 11.9 14.1 13.4 63.7 14.4 44.5 14.9 53.1 16.0 39.4 16.6 34 17.3 83.5 17.8 62.3 18.6 14.3 19.2 28.2 20.0 13.7 20.8 77.2 21.3 44.5 23.2 69 25.7 10.6 26.1 29.5

[0557] In some embodiments, Compound 1L-malate (Form B) exhibits an XRPD substantially similar to FIG. 100.

[0558] In some embodiments, Compound 1L-malate (Form B) exhibits a DSC thermogram comprising an endotherm at about 108.7 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1L-malate (Form B) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 143.3 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1L-malate (Form B) exhibits a DSC thermogram substantially similar to FIG. 101.

[0559] In some embodiments, Compound 1L-malate (Form B) exhibits a TGA thermogram substantially similar to FIG. 101. In some embodiments, the TGA thermogram of Compound 1L-malate (Form B) exhibits a weight loss of 0.0 to 1.2% over the temperature range of 25 to 120 °C.

[0560] In some embodiments, Compound 1L-malate (Form B) exhibits a DVS isotherm substantially similar to FIG. 102. In some embodiments, Compound 1L-malate (Form B) exhibits a weight moisture uptake of about 3.5% (by weight) at 80% relative humidity.

[0561] hydrochloride salt

[0562] In some embodiments, the present disclosure provides a hydrochloride salt of Compound 1 (“Compound 1 hydrochloride”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 hydrochloride.

[0563] In one embodiment, the present disclosure provides Compound 1 hydrochloride (Form A). In some embodiments, Compound 1 hydrochloride (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.6, 5.2, 14.2, 17.4, and 17.7 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0564] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits an XRPD comprising the peaks shown in Table 48 below:

[0565] Table 48. XRPD table for Compound 1 hydrochloride salt (Form A)

[0566]

[0567]

[0568] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits an XRPD substantially similar to Figure 103.

[0569] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 220.5 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2).

[0570] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 232.7 °C with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DSC thermogram substantially similar to Figure 104.

[0571] In some embodiments, 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 to 1.2% over the temperature range of 25 to 150 °C.

[0572] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DVS isotherm plot substantially similar to Figure 105. In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a weight moisture uptake of about 3.6% (by weight) at 80% relative humidity.

[0573] In one embodiment, the present disclosure provides compound 1 hydrochloride salt (Form B). In some embodiments, compound 1 hydrochloride salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.3, 7.8, 15.4, 16.6, and 23.2 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of compound 1 hydrochloride salt (Form B) further comprises one or more peaks at about 15.0, 18.8, 20.4, 23.5, and 26.5 °2Θ, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0574] In some embodiments, compound 1 hydrochloride salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 49 below:

[0575] Table 49. XRPD Table for Compound 1 Hydrochloride Salt (Form B)

[0576] 2θ strength% 3.3 58.7 4.9 12.3 7.8 34.4 9.8 14.2 15.0 25.8 15.4 100 16.6 57.7 17.6 7.3 18.8 16.1 20.4 14.6 22.7 5.8 23.2 59.2 23.5 32.2 26.5 15.4 26.9 8.4 28.4 5.8 31.7 9.3

[0577] In some embodiments, compound 1 hydrochloride salt (Form B) exhibits an XRPD substantially similar to that of Figure 106.

[0578] In some embodiments, compound 1 hydrochloride salt (Form B) exhibits a DSC thermogram comprising an endotherm at about 87.1 °C, with a tolerance of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 hydrochloride salt (Form B) exhibits a DSC thermogram comprising a strong endotherm at about 207.3 °C, with a tolerance of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, compound 1 hydrochloride salt (Form B) exhibits a DSC thermogram substantially similar to that of Figure 107.

[0579] In some embodiments, compound 1 hydrochloride salt (Form B) exhibits a TGA thermogram substantially similar to that of Figure 107. In some embodiments, the TGA thermogram of compound 1 hydrochloride salt (Form B) exhibits a weight loss of 0.0 to 0.7% over the temperature range of 25 to 120 °C.

[0580] In some embodiments, Compound 1 hydrochloride (Form B) exhibits a DVS isotherm substantially similar to Figure 108. In some embodiments, Compound 1 hydrochloride (Form B) exhibits a weight moisture uptake of about 2.9% by weight at 80% relative humidity.

[0581] In one embodiment, the present disclosure provides Compound 1 hydrochloride (Form C). In some embodiments, Compound 1 hydrochloride (Form C) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 14.6, 16.5, 18.0, 21.5, and 21.9 °2Theta, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2Theta, with a tolerance of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0582] In some embodiments, Compound 1 hydrochloride (Form C) exhibits an XRPD comprising the peaks set forth in Table 50 below:

[0583] Table 50. XRPD Table for Compound 1 Hydrochloride (Form C)

[0584] 2θ strength% 3.6 36.5 9.1 13.5 10.8 8.4 12.0 16.4 13.3 24.3 14.2 27.6 14.6 62.6 16.1 9.1 16.5 100 16.9 30.1 18.0 46.2 18.8 32.2 19.6 17.7 19.9 31.3 20.5 16.4 21.5 94.7 21.9 61.3 22.1 41.1 22.9 7.1 23.7 32 24.4 8.9

[0585] In some embodiments, Compound 1 hydrochloride (Form C) exhibits an XRPD substantially similar to Figure 109.

[0586] In some embodiments, Compound 1 hydrochloride (Form C) exhibits a DSC thermogram comprising an endotherm at about 132.9 °C, with a tolerance of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 hydrochloride (Form C) exhibits a DSC thermogram substantially similar to Figure 110.

[0587] In some embodiments, Compound 1 hydrochloride (Form C) exhibits a TGA thermogram substantially similar to Figure 110. In some embodiments, the TGA thermogram of Compound 1 hydrochloride (Form C) exhibits a weight loss of 0.0 to 3.8% over the temperature range of 25 to 120 °C.

[0588] In some embodiments, Compound 1 hydrochloride (Form C) exhibits a DVS isotherm substantially similar to that of Figure 111. In some embodiments, Compound 1 hydrochloride (Form C) exhibits a weight moisture uptake of about 0.7% by weight at 80% relative humidity.

[0589] naphthalenesulfonate salt

[0590] In some embodiments, the present disclosure provides a naphthalenesulfonate salt of Compound 1 (“Compound 1 naphthalenesulfonate salt”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 naphthalenesulfonate salt.

[0591] In one embodiment, the present disclosure provides Compound 1 naphthalenesulfonate salt (Form A). In some embodiments, Compound 1 naphthalenesulfonate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 3.4, 9.5, 16.6, 17.0, and 17.5 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 naphthalenesulfonate salt (Form A) further comprises one or more peaks at about 8.3, 8.7, 19.8, 25.0, and 25.5 °2Θ, with a error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0592] In some embodiments, Compound 1 naphthalenesulfonate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 51 below:

[0593] Table 51. XRPD Table for Compound 1 naphthalenesulfonate salt (Form A)

[0594]

[0595]

[0596] In some embodiments, Compound 1 naphthalenesulfonate salt (Form A) exhibits an XRPD substantially similar to that of Figure 112.

[0597] In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 100.1 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 202.3 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 naphthalenesulfonic acid salt exhibits a DSC thermogram substantially similar to FIG. 113.

[0598] In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form A) exhibits a TGA thermogram substantially similar to FIG. 113. In some embodiments, the TGA thermogram of Compound 1 naphthalenesulfonic acid salt exhibits a weight loss of 0.0 to 1.7% over the temperature range of 25 to 180 °C.

[0599] In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form A) exhibits a DVS isotherm substantially similar to FIG. 114. In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form A) exhibits a weight moisture uptake of about 3.9% (by weight) at 80% relative humidity.

[0600] In one embodiment, the present disclosure provides Compound 1 naphthalenesulfonic acid salt (Form B). In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 9.1, 15.6, 16.1, 18.2, and 19.7 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form B) further comprises one or more peaks at about 8.6, 12.9, 17.1, 25.8, and 26.2 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0601] In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 52 below:

[0602] Table 52. XRPD Table for Compound 1 naphthalenesulfonic acid salt (Form B)

[0603]

[0604]

[0605] In some embodiments, Compound 1 naphthalenesulfonic acid salt (Form B) exhibits an XRPD substantially similar to FIG. 115.

[0606] oxalate salt

[0607] In some embodiments, the present disclosure provides an oxalate salt of Compound 1 (“Compound 1 oxalate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 oxalate.

[0608] In one embodiment, the present disclosure provides Compound 1 oxalate (Form A). In some embodiments, Compound 1 oxalate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.1, 18.2, 19.1, 19.8, and 24.3 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 oxalate (Form A) further comprises one or more peaks at about 12.1, 13.9, 21.1, 21.7, and 24.7 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0609] In some embodiments, Compound 1 oxalate (Form A) exhibits an XRPD comprising the peaks set forth in Table 53 below:

[0610] Table 53. XRPD Table for Compound 1 oxalate (Form A)

[0611]

[0612]

[0613] In some embodiments, Compound 1 oxalate (Form A) exhibits an XRPD substantially similar to FIG. 116.

[0614] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DSC thermogram comprising an endotherm at about 163.8 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DSC thermogram comprising an endotherm (e.g., a sharp endotherm) at about 198.6 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 hydrochloride salt exhibits a DSC thermogram substantially similar to Figure 117.

[0615] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a TGA thermogram substantially similar to Figure 117. In some embodiments, the TGA thermogram of Compound 1 hydrochloride salt exhibits a weight loss of 0.0 to 0.4% over the temperature range of 25 to 150 °C.

[0616] In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a DVS isotherm substantially similar to Figure 118. In some embodiments, Compound 1 hydrochloride salt (Form A) exhibits a weight moisture uptake of about 1.4% (by weight) at 80% relative humidity.

[0617] In one embodiment, the present disclosure provides Compound 1 hydrochloride salt (Form B). In some embodiments, Compound 1 hydrochloride salt (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.0, 6.3, 18.2, 18.8, and 20.0 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 hydrochloride salt (Form B) further comprises one or more peaks at about 12.1, 12.5, 17.8, 20.7, and 23.5 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0618] In some embodiments, Compound 1 hydrochloride salt (Form B) exhibits an XRPD comprising the peaks set forth in Table 54 below:

[0619] Table 54. XRPD Table for Compound 1 Hydrochloride Salt (Form B)

[0620] 2θ strength% 6.0 37.1 6.3 56.6 9.7 13.9 9.9 13.2 12.1 27.1 12.5 34.1 13.4 23.2 14.0 22.5 14.9 22.5 16.9 21.6 17.8 30.4 18.2 47.3 18.8 100 19.8 23.4 20.0 42.9 20.7 28.3 22.7 16 23.5 33.6 25.5 9 29.5 10.2 29.9 7

[0621] In some embodiments, Compound 1 succinate salt (Form B) exhibits an XRPD substantially similar to FIG. 118.

[0622] p-aminosalicylate

[0623] In some embodiments, the present disclosure provides a p-aminosalicylate salt of Compound 1 (“Compound 1 p-aminosalicylate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 p-aminosalicylate.

[0624] In one embodiment, the present disclosure provides Compound 1 p-aminosalicylate salt (Form A). In some embodiments, Compound 1 p-aminosalicylate salt (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 5.4, 13.8, 15.7, 20.7, and 21.2 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 p-aminosalicylate salt (Form A) further comprises one or more peaks at about 12.5, 13.5, 15.3, 19.2, and 27.6 °2Θ, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0625] In some embodiments, Compound 1 p-aminosalicylate salt (Form A) exhibits an XRPD comprising the peaks set forth in Table 55 below:

[0626] Table 55. XRPD Table for Compound 1 p-aminosalicylate salt (Form A)

[0627]

[0628]

[0629] In some embodiments, Compound 1 p-aminosalicylate salt (Form A) exhibits an XRPD substantially similar to FIG. 120.

[0630] In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 97.1 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a DSC thermogram comprising an endotherm at about 146.8 °C, with an error limit of about ± 2.5; about ± 2.0; about ± 1.5; about ± 1.0; about ± 0.5; or less (specifically, about ± 0.2). In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a DSC thermogram substantially similar to FIG. 121.

[0631] In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a TGA thermogram substantially similar to FIG. 121. In some embodiments, the TGA thermogram of Compound 1 aminosalicylate (Form A) exhibits a weight loss of 0.0 to 4.0% over the temperature range of 25 to 120 °C.

[0632] In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a DVS isotherm substantially similar to FIG. 122. In some embodiments, Compound 1 aminosalicylate (Form A) exhibits a weight moisture uptake of about 4.0% (by weight) at 80% relative humidity.

[0633] In one embodiment, the present disclosure provides Compound 1 aminosalicylate (Form B). In some embodiments, Compound 1 aminosalicylate (Form B) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 12.3, 15.2, 17.3, 19.9, and 22.9 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2). In some embodiments, the XRPD of Compound 1 aminosalicylate (Form B) further comprises one or more peaks at about 6.3, 12.5, 14.8, 16.4, and 20.7 °2Θ, with an error limit of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0634] In some embodiments, Compound 1 aminosalicylate (Form B) exhibits an XRPD comprising the peaks set forth in Table 56 below:

[0635] Table 56. XRPD Table for Compound 1 aminosalicylate (Form B)

[0636] 2θ strength% 6.3 47.2 12.3 100 12.5 44.8 14.0 18 14.8 42.6 15.2 83.7 16.4 47.8 16.9 31.3 17.3 66.8 18.3 17.9 18.9 17.7 19.5 41.3 19.9 84.9 20.7 42.4 22.0 19.9 22.9 65.1 23.2 31.9 25.9 21.4 28.1 19.6 29.1 23

[0637] In some embodiments, Compound 1 aminosalicylate (Form B) exhibits an XRPD substantially similar to that of FIG. 123.

[0638] Maleate salt

[0639] In some embodiments, the present disclosure provides a maleate salt of Compound 1 (“Compound 1 maleate”). In some embodiments, the present disclosure provides a crystalline form of Compound 1 maleate.

[0640] In one embodiment, the present disclosure provides Compound 1 maleate (Form A). In some embodiments, Compound 1 maleate (Form A) exhibits an XRPD comprising one or more peaks (specifically, three or more peaks) at about 6.4, 9.5, 11.2, 13.1, 15.0, and 17.6 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, 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 °2theta, with error limits of about ± 0.5; about ± 0.4; about ± 0.3; about ± 0.2; about ± 0.1; about ± 0.05; or less (specifically, about ± 0.2).

[0641] In some embodiments, Compound 1 maleate (Form A) exhibits an XRPD comprising the peaks set forth in Table 57 below:

[0642] Table 57. XRPD Table for Compound 1 maleate (Form A)

[0643] 2θ strength% 6.4 100 8.1 24.2 9.5 74.6 11.2 54.4 11.6 24.6 12.6 31.0 13.1 57.1 14.0 39.7 15.0 86.5 16.7 46.4 17.6 65.1 19.2 44.4 23.6 21.0 24.2 16.3 24.8 15.9

[0644] In some embodiments, Compound 1 maleate (Form A) exhibits an XRPD substantially similar to that of FIG. 124.

[0645] Methods of making salts of Compound 1

[0646] Salts of Compound 1 (and crystalline forms thereof) can be prepared, for example, by mixing Compound 1 free base with an acid (e.g., hydrochloric acid) in a suitable solvent to provide a salt of Compound 1 as a suspension in a suitable solvent. In some embodiments, a salt of Compound 1 can be prepared by slow evaporation, slow cooling, or addition of an anti-solvent to a mixture of Compound 1 free base and an acid.

[0647] In some embodiments, the present disclosure provides methods of preparing a crystalline form of a salt of Compound 1. In some embodiments, a salt of Compound 1 is suspended in a suitable solvent for a time sufficient to provide a suspension of a crystalline form of a salt of Compound 1.

[0648] In some embodiments, a salt of Compound 1 is dissolved in a suitable solvent to provide a solution, and a crystalline form of a salt of Compound 1 is precipitated from the solution. In some other embodiments, a salt of Compound 1 is dissolved by heating a mixture of a salt of Compound 1 and a suitable solvent. In some other embodiments, a crystalline form of a salt of Compound 1 is precipitated from a solution by cooling the solution. In other embodiments, a crystalline form of a salt of Compound 1 is precipitated from a solution by adding an anti-solvent (i.e., a solvent that decreases the solubility of a crystalline form of a salt of Compound 1) to the solution. In yet other embodiments, a crystalline form of a salt of Compound 1 is precipitated from a solution by evaporating a portion of a suitable solvent from the solution. In certain other embodiments, a suitable solvent includes water.

[0649] In some embodiments, a salt of Compound 1 is heated to provide a melt, and the melt is cooled to provide a crystalline form of a salt of Compound 1. In some embodiments, a salt of Compound 1 is compressed (e.g., 5 mPa for 5 minutes) at a pressure and for a time sufficient to provide a crystalline form of a salt of Compound 1. In some embodiments, a salt of Compound 1 is ground (e.g., using a mortar and pestle or a grinder) to provide a crystalline form of a salt of Compound 1. In some other embodiments, a salt of Compound 1 is ground in the presence of a suitable solvent to provide a crystalline form of a salt of Compound 1. In some embodiments, a salt of Compound 1 is subjected to relative humidity and temperature (e.g., at 45 °C at 75% relative humidity) for a time sufficient to provide a crystalline form of a salt of Compound 1.

[0650] In some embodiments, a suitable solvent includes an aprotic solvent. In some embodiments, the aprotic solvent includes at least one solvent selected from the group consisting of dimethylformamide (DMF), dimethylacetamide (DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP), formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl ethyl ketone (MEK), hexachloroacetone, acetone, ethyl methyl ketone, ethyl acetate, sulfolane, N,N-dimethylpropionamide, tetramethylurea, nitromethane, nitrobenzene, hexamethylphosphoramide, diethoxymethane, tetrahydrofuran, toluene, 1,3-dioxane, 1,4-dioxane, furan, diethyl ether, tetrahydropyran, diisopropyl ether, dibutyl ether, ethyleneglycol dimethyl ether, ethyleneglycol diethyl ether, diethyleneglycol dimethyl ether, diethyleneglycol diethyl ether, triethyleneglycol dimethyl ether, anisole, 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.

[0651] In some embodiments, a suitable solvent includes a protic solvent. In some embodiments, the protic solvent includes at least one solvent selected from the group consisting of water, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, n-butanol, 2-butanol, isobutanol, t-butanol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol, neopentyl alcohol, t-amyl alcohol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, and glycerol. In some embodiments, the protic solvent includes a mixture of 2-propanol and water.

[0652] In some embodiments, a suitable solvent is a single solvent. In some embodiments, the solvent is a mixture of solvents. In some embodiments, a suitable solvent is a mixture of a protic solvent and an aprotic solvent.

[0653] In certain embodiments, the compound 1 salt (or crystalline form of the salt) is isolated after preparation. Isolation of the salt (or crystalline form of the salt) can be accomplished using methods such as filtration, decantation, centrifugation, or other suitable isolation techniques.

[0654] In certain embodiments, the isolated salt (or crystalline form of the salt) is optionally washed with a liquid such as an antisolvent, acetonitrile, methanol, ethanol, ethyl acetate, methyl ethyl ketone, acetone, tetrahydrofuran, or a combination thereof.

[0655] In certain embodiments, the salts of Compound 1 prepared by the above embodiments are substantially pure. For example, in some embodiments, the chemical purity of the salts of Compound 1 (e.g., Compound 1 hydrochloride) can include at least about 99.9%, about 99.8%, about 99.7%, about 99.6%, about 99.5%, about 99.4%, about 99.3%, about 99.2%, about 99.1%, about 99.0%, about 98%, about 97%, about 96%, or about 95% of the salt of Compound 1. Chemical purity can be determined using methods known to those of skill in the art (e.g., HPLC chromatography with a suitable solvent and detection at 210 nm wavelength). In some embodiments, substantial purity is determined on a weight percent basis. In some embodiments, substantial purity is determined on an area under the curve basis.

[0656] In some embodiments, the salts of Compound 1 prepared by the above embodiments are crystalline. In certain embodiments, the crystalline salts of Compound 1 prepared by the above embodiments are substantially pure. For example, in some embodiments, the polymorphic purity of the crystalline salts of Compound 1 (e.g., Compound 1 hydrochloride) can include at least about 99.9%, about 99.8%, about 99.7%, about 99.6%, about 99.5%, about 99.4%, about 99.3%, about 99.2%, about 99.1%, about 99.0%, about 98%, about 97%, about 96%, about 95%, about 94%, about 93%, about 92%, about 91%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, or about 50% of the single crystal form (e.g., Compound 1 hydrochloride (Form A)). Polymorphic purity can be determined using methods known to those of skill in the art (including X-ray powder crystallography 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, and the like, the entire contents of which are hereby incorporated by reference).

[0657] In some embodiments, the salts of Compound 1 prepared from the above embodiments are epimerically enriched at one or more positions compared to the epimeric purity of the starting material of Compound 1 free base. For example, in some embodiments, the salts of Compound 1 can comprise 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-beta: 17-alpha epimers of Compound 1. In some embodiments, the salts of Compound 1 can comprise 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 3-alpha-hydroxy: 3-beta-hydroxy 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 starting material of Compound 1 free base.

[0658] Pharmaceutical compositions

[0659] In one aspect, the present disclosure provides pharmaceutical compositions comprising a salt of Compound 1. In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide, Compound 1 citrate, Compound 1 L-malate, Compound 1 mesylate, Compound 1 phosphate, Compound 1 L(+)-tartrate, Compound 1 hydrochloride, Compound 1 tosylate, Compound 1 glucuronate, or Compound 1 ethanesulfonate. In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide (Form A). In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide (Form B). In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide (Form C). In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide (Form D). In some embodiments, the salt of Compound 1 is Compound 1 hydrobromide (Form E). In some embodiments, the salt of Compound 1 is Compound 1 citrate (Form A). In some embodiments, the salt of Compound 1 is Compound 1 citrate (Form B). In some embodiments, the salt of Compound 1 is Compound 1 citrate (Form C).

[0660] The compositions can be administered by a suitable route including, but not limited to, oral, parenteral, rectal, topical, and local. The compositions can be in liquid, semi-liquid, or solid form, and can be formulated in a manner suitable for each route of administration using methods known to those skilled in the art.

[0661] Dosage forms for oral administration include, for example, solid dosage forms (e.g., tablets, capsules, pills, granules, etc.) and liquid dosage forms (e.g., oral solutions, oral suspensions, syrups, etc.).

[0662] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a salt of Compound 1 or solvate thereof and a pharmaceutically acceptable excipient.

[0663] Methods of use

[0664] In one aspect, the present application provides a method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a salt of Compound 1.

[0665] In some embodiments, the disease or disorder is depression. In some embodiments, the disease or disorder is treatment-resistant depression. In some embodiments, the disease or disorder is postpartum depression. In some embodiments, the disease or disorder is major depressive disorder. In some embodiments, the disease or disorder is bipolar disorder. In some embodiments, the disease or disorder is epilepsy. In some embodiments, the disease or disorder is anxiety.

[0666] Examples

[0667] The present application is further illustrated by reference to the following examples. However, it is to be understood that these examples, like the embodiments described above, are illustrative and are not to be construed as limiting the scope of the present application in any manner.

[0668] “EtOAc” refers to ethyl acetate. “(m)DSC” refers to (modulated) differential scanning calorimetry. “ACN” refers to acetonitrile. “AR” refers to analytical reagent. “DCM” refers to dichloromethane. “DMF” refers to dimethylformamide. “DMSO” refers to dimethyl sulfoxide. “DI” refers to distilled. “DSC” refers to differential scanning calorimetry. “DVS” refers to dynamic vapor sorption. “e.q.” refers to equivalent. “EtOH” refers to ethanol. “FaSSIF” refers to fasted state simulated intestinal fluid. “FeSSIF” refers to fed state simulated intestinal fluid. “1H-NMR” refers to proton nuclear magnetic resonance. “IPA” refers to isopropyl alcohol. “IPAC” refers to isopropyl acetate. “IPE” refers to diisopropyl ether. “LC” refers to low crystallinity. “MEK” refers to methyl ethyl ketone. “MeOH” refers to methanol. “MIBK” refers to methyl isobutyl ketone. “MTBE” refers to methyl tert-butyl ether. “NMR” refers to nuclear magnetic resonance. “PLM” refers to polarized light microscopy. “RH” refers to relative humidity. “RRT” refers to relative retention time. “RT” refers to room temperature. “RT(min)” refers to retention time. “SGF” refers to simulated gastric fluid. “TGA” refers to thermogravimetric analysis. “THF” refers to tetrahydrofuran. “UPLC” refers to ultra-performance liquid chromatography. “XRPD” refers to X-ray powder diffractometer.

[0669] In some cases, the following method is used to determine Compound 1: acid in Compound 1 salts described herein by ion chromatography (IC): ratio: 25 pL of a 10.0 pg / mL sample or standard is injected into a Dionex IonPac AG18 column at a flow rate of 1.0 mL / min and detected by a Thermo ICS-2100 conductivity detector. The ASRS-4mm suppressor is set to 38 mA and the column temperature is 30 °C. The chromatographic elution is 15 mM KOH with a total run time of 20 minutes.

[0670] X-ray powder diffraction patterns are collected on a Rigaku D / Max-2200 / PC or Bruker D8 Advance powder diffractometer. Copper K-alpha X-rays The sample is irradiated. The sample is scanned in continuous mode from 3° to 40°, with a sample rotation speed of 15 rpm and a scan rate of 10° / min.

[0671] Single crystal X-ray analysis: Single crystal X-ray diffraction data are obtained using a Rigaku XtaLAB Synergy-R (Cu) (Micro-Max007HF Cu mode, Cu K-alpha: Hypix6000 HE detector).

[0672] The following SCXRD instrument parameters are used:

[0673]

[0674] Suitable single crystals with good diffraction quality are isolated from bulk crystalline samples and wrapped in Paratone-N (an oil-based cryoprotectant). The crystals are mounted in random orientation on polyester film loops and immersed in a nitrogen stream at the temperature specified in the examples below. Preliminary checks and data collection are performed on a Rigaku XtaLAB Synergy R (Cu K-alpha radiation, ) diffractometer and analyzed using the CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software package.

[0675] The structure was solved using Intrinsic Phasing in the ShelXT (Sheldrick, GMA Pryst. 2015, A71, 3-8.) structure parsing program, and the structure was further refined using the ShelXL (Version 2017 / 1; Shelrick, GMA Pryst. 2015, C71, 3-8) refinement package for the F-type structures contained in OLEX2 (Dolomanov, OV, Bouhrhis, LJ, Gildea, RJ, Howard, JAK & Puschmann, HJ Appl. Cryst. 2009, 42, 339-341). 2 Refinement was performed using full matrix least squares. All non-hydrogen atoms underwent anisotropic refinement. The positions of hydrogen atoms bonded to carbon atoms were geometrically calculated and refined using a riding model, but hydrogen atoms bonded to nitrogen and oxygen atoms were freely refined based on a difference Fourier map.

[0676] DSC data were collected on a TA Q2000. For each sample analyzed, approximately 1 mg of sample was placed in a sealed aluminum dish with a pinhole and heated from 25°C to 250°C at a rate of 10°C / min.

[0677] TGA data were collected on a TA Q5000. For each sample analyzed, approximately 4 mg of material was placed in an open platinum dish and heated from 30 °C to 300 °C or <80% by weight at a rate of 10 °C / min.

[0678] Dynamic vapor adsorption (DVS) was performed using the SMS DVS Advantage 1 system. For each sample analyzed, approximately 10 mg of material was transferred to the DVS instrument, and the weight change relative to atmospheric humidity at 25°C was recorded using the following parameters: equilibrium dm / dt: 0.01% / min (duration: 10 min and maximum: 180 min); drying was set to 0% RH for 120 min; RH (%) measurement step size was 10%, and the RH (%) measurement step size range was 0–90–0%.

[0679] Collection on a Bruker 400MHz magnet 1 ¹H-NMR. For each sample analyzed, approximately 6 mg of material was dissolved in 0.6 mL of d6-DMSO for analysis. As is known to those skilled in the art, 1The relative ppm shifts and integral values of H-NMR resonances can vary depending on various sample factors, including, for example, water content in d6-DMSO, ionic concentration in the sample, etc. Thus, the H-NMR values reported in the following examples should not be considered characteristic of the respective salt and polymorphic form. 1 H-NMR values should not be considered characteristic of the respective salt and polymorphic form.

[0680] UPLC data were collected by injecting 0.5 μΐ^of sample or standard into a Waters Acquity UPLC Shield RP18 column at a flow rate of 0.8 mL / min by Agilent 1290 UPLC (detection wavelength: 210 nm). The column was equilibrated with mobile phase A, which consisted of 0.1% H3PO4 in water. Mobile phase B was acetonitrile (CAN). The chromatographic elution program was as follows: one minute wait after re-equilibration, total run time of 6 minutes:

[0681] Time (min) A(％) B(％) 0 90 10 4 10 90 5 10 90

[0682] The crystalline salts described herein were characterized by polarized light microscopy. In some embodiments, the crystalline salts described herein exhibit birefringence, which is indicative of crystallinity.

[0683] Example 1: Preparation of the hydrobromide salt of Compound 1

[0684] The following exemplary method can be used to prepare the hydrobromide salt of Compound 1 from Compound 1.

[0685] Compound 1HBr (form A):

[0686] To ethanol (2.84 kg, 9% w / w water) was added Compound 1 (1.2 kg). An additional portion of ethanol (0.95 kg, 9% w / w 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 μιη filter and cooled to an internal temperature of less than 30 °C. With the solution containing 48% w / w aqueous HBr (523 g) and the addition of acetone (940 g), the temperature was maintained below 30 °C and stirred for 1 h. Acetone (8.47 kg) was added, the resulting slurry was cooled to 0-5 °C and stirred for 1 h. The solids were collected by filtration and washed with acetone (1.88 kg). The resulting solids were dried under vacuum at 50 °C to give Compound 1 HBr salt (1.17 kg, 82% yield).

[0687] The resulting solids were Compound 1 HBr (Form A). The ratio of Compound 1 : HBr in Compound 1 HBr (Form A) was 1 : 1.02 as determined by ion chromatography. XPRD is shown in Figure 2; DSC and TGA are shown in Figure 3; and DVS is shown in Figure 4.

[0688] Compound 1HBr (form B):

[0689] One gram of Compound 1 HBr (Form A) was suspended in 20 mL of a 0.603 water activity solution (14.5% water in acetone, v / v) to yield a 50 mg / mL suspension. The suspension was stirred at 700 rpm and maintained at 50 °C for 26 hours. The suspension was centrifuged and the precipitate was collected. The obtained wet product was dried under vacuum at 30 °C for three days to yield a powder with a 70.82% yield. The ratio of Compound 1 :HBr in Compound 1 HBr (Form B) was 1 :1.01 as determined by ion chromatography. XPRD is shown in Figure 5; DSC and TGA are shown in Figure 6; and DVS is shown in Figure 7.

[0690] Compound 1HBr (in form C):

[0691] Five hundred milligrams of Compound 1 HBr (Form A) was dissolved in 4.5 mL of DMSO to yield 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. After that time, the precipitated material was isolated. The obtained wet product was dried under vacuum at 30 °C for three days to yield a powder with a 66.1% yield. The ratio of Compound 1 :HBr in Compound 1 HBr (Form C) was 1 :1.09 as determined by ion chromatography. XPRD is shown in Figure 8; DSC and TGA are shown in Figure 9; and DVS is shown in Figure 10.

[0692] Compound 1HBr (form D):

[0693] Form D was observed by VT-XRPD when Form B was heated to 160 °C. XRPD is shown in Figure 11; TGA and DSC are shown in Figure 12.

[0694] Compound 1HBr (Form E):

[0695] In a 20 mL vial with a stir bar, a solution of Compound 1 (1.00 g, 1.0 eq) in EtOH (5 mL) was stirred at 60 °C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 eq) was added to the mixture and stirred at 60 °C for 1 hour. 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 hour. The mixture was kept in an ice bath for 30 minutes, then filtered, the solid was collected, and dried under vacuum at 25 °C overnight to give Compound 1 HBr (876 mg, 73.7% yield). XRPD is shown in Figure 13; DSC and TGA are shown in Figure 14.

[0696] General process for preparing compound 1HBr

[0697] The following general procedure was followed to prepare Compound 1 HBr.

[0698] General Process 1

[0699] In a 20 mL vial with a stir bar, a solution of Compound 1 (1.00 g, 1.0 eq) in solvent (15 mL, 15 mL / g of Compound 1) was stirred at 60 °C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 eq) was added to the reaction and stirred at 60 °C for 1 hour. The reaction was cooled to 25 °C and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes (process 1-2 was kept at 25 °C) and then filtered, the solid was collected, and dried under vacuum at 25 °C overnight to give Compound 1 HBr.

[0700] General Process 2

[0701] In a 20 mL vial with a stir bar, a solution of Compound 1 (1.00 g, 1.0 eq) in solvent (15 mL, 15 mL / g of Compound 1) was stirred at 60 °C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 eq) was added to the reaction and stirred at 60 °C for 1 hour. The reaction was cooled to 25 °C and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes (process 1-2 was kept at 25 °C) and then filtered, the solid was collected, and dried under vacuum at 25 °C overnight to give Compound 1 HBr.

[0702] General Process 3

[0703] In a 20 mL vial with a stir bar, a solution of Compound 1 (1.00 g, 1.0 eq) in EtOH (5 mL, 5 mL / g of Compound 1) was stirred at 60 °C for 30 minutes. HBr (48% w / w in water, 0.3 mL, 1.1 eq) was added to the mixture and stirred at 60 °C for 1 hour. The reaction mixture was cooled to 25 °C and then an anti-solvent (5 mL, 5 mL / g of Compound 1) was added to the reaction mixture and stirred for 1 hour. The mixture was kept in an ice bath for 30 minutes and then filtered, the solid was collected, and dried under vacuum at 25 °C overnight to give Compound 1 HBr.

[0704] The following table summarizes the preparation of Compound 1 HBr according to the general procedure:

[0705]

[0706]

[0707] Chemical and physical stability testing

[0708] For each salt, about 5 mg of compound was added to an 8 mL glass vial with a perforated aluminum foil cap and held at 60 °C, 40 °C / 75% RH for 1 week. To perform the photostability testing, the compound in vials without caps was held in a photostability chamber and exposed to a total illumination of 1.2 million lux-hours, while samples in vials completely covered with aluminum foil were considered the dark control. The appearance was recorded by visual inspection, followed by purity assessment and XPRD data collection on the residual solids.

[0709] The following table shows the chemical and physical stability test results for Compound 1 HBr (Form A), Compound 1 HBr (Form B), Compound 1 HBr (Form C), and Compound 1 Free Base:

[0710]

[0711]

[0712] Dissolution testing in simulated gastric and intestinal fluids

[0713] For each salt, about 4-6 mg of Compound 1 or the salt was added to a 2 mL vial in triplicate. Then 1 mL of a biorelevant medium (SGF, FaSSIF, or FeSSIF) was added to the vial. All vials were placed on a thermomixer and held at 37 °C while shaking at 700 rpm. If the compound was completely dissolved in the medium, more compound was added until the system became a suspension, and no additional material was added if the concentration of the compound exceeded 25 mg / mL. After 24 hours of shaking at 37 °C, 300 μL of the suspension was separated from each system for analysis. The samples were centrifuged at 12,000 rpm for 5 minutes, and the supernatant was analyzed by UPLC after dilution 10 times by ACN:H2O (4 / 1, v / v). The final pH of the biorelevant medium was measured and recorded. The following table shows the dissolution results (mg / mL) for Compound 1 HBr (Form A), Compound 1 HBr (Form B), Compound 1 HBr (Form C), and Compound 1 Free Base in biorelevant solutions:

[0714]

[0715] Single crystal X-ray analysis of Compound 1 HBr Form B

[0716] Bulk single crystals of Compound 1 hydrobromide Form B for SCXRD characterization were crystallized from a MeOH / MEK (1:3, v / v) solvent mixture by slow evaporation.

[0717] Characterization of the salt by PLM and XRPD indicated that it was Compound 1 HBr Form B.

[0718] Cell parameters and orientation matrix were retrieved and refined (least squares refinement) for data collection by CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software using the setting angles of 45416 reflections in the range 3.488° < Θ < 75.836°. The minimum diffraction angle (Θ) of the data collected at 120.00 K was 3.506° and the maximum diffraction angle (Θ) was 68.243°. The final completeness was 100%. The average I / σ of the data was 91.7 and the maximum resolution obtained was 0.68 A.

[0719] The following table provides SCXRD data obtained by the methods described herein.

[0720]

[0721]

[0722] Single Crystal X-ray Analysis of Compound 1 HBr Form E

[0723] Bulk single crystals of Compound 1 hydrobromide Form E for SCXRD characterization were crystallized by slow evaporation method from a MeOH / MEK (1:3, v / v) solvent mixture. Characterization of the salt by PLM and XRPD indicated that it was Compound 1 HBr Form E.

[0724] Data collection at 120K : Cell parameters and orientation matrix were retrieved and refined (least squares refinement) for data collection by CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software using the setting angles of 10196 reflections in the range 3.499° < Θ < 75.657°. The minimum diffraction angle (Θ) of the data collected at 120.00(10) K was 3.508° and the maximum diffraction angle (Θ) was 66.553°. The final completeness was 100%. The average I / σ of the data was 19.3 and the maximum resolution obtained was 0.68 A.

[0725] Data collection at room temperature : Cell parameters and orientation matrix were retrieved and refined (least squares refinement) for data collection by CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software using the setting angles of 17551 reflections in the range 3.483° < Θ < 75.825°. The minimum diffraction angle (Θ) of the data collected at room temperature was 3.496° and the maximum diffraction angle (Θ) was 66.597°. The final completeness was 100%. The average I / σ of the data was 40.0 and the maximum resolution obtained was 0.68 A.

[0726] The following table provides SCXRD data obtained by the methods described herein.

[0727]

[0728]

[0729] Example 2: Preparation of Compound 1 citrate salt

[0730] The following exemplary method can be used to prepare Compound 1 citrate salt from Compound 1.

[0731] Compound 1 citrate (form A):

[0732] To a mixture of ethanol (2.37 kg, 9% w / w water) and isopropyl acetate (2.61 kg) was added Compound 1 (1 kg). A further portion of ethanol (0.39 kg, 9% w / w water) and isopropyl acetate (0.44 kg) was added. The resulting mixture was heated to 55-65 °C with stirring until a solution was obtained. The resulting solution was passed through a 10 pm filter. A solution of citric acid monohydrate (541 g) in ethanol (0.79 kg, 9% w / w water) and isopropyl acetate (0.87 kg) was added with stirring. A further portion of ethanol (0.39 kg) and isopropyl acetate (0.44 kg) was used to transfer the citric acid into the reactor. The resulting mixture was cooled to 0-5 °C with stirring for 1 h 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).

[0733] The resulting solid was Compound 1 citrate salt (Form A). The ratio of Compound 1 : citric acid in Compound 1 citrate salt (Form A) was 1 : 1.02 as determined by HPLC. XPRD is shown in Figure 15; DSC and TGA are shown in Figure 16; and DVS is shown in Figure 17.

[0734] In deuterated DMSO by 1 Compound 1 citrate salt (Form A) was analysed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, 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).

[0735] Compound 1 citrate (form B):

[0736] A 500 mg sample of Compound 1 citrate (Form A) was dissolved in 4.0 mL of a 0.901 water activity solution (65% water in acetone, v / v) to yield a 125 mg / mL suspension. The suspension was stirred at 300 rpm and maintained 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 one day to yield a powder with a 56.9% yield. The ratio of Compound 1 : citric acid in Compound 1 citrate (Form B) was determined to be 1 : 1.17 by ion chromatography. XRPD is shown in Figure 18; DSC and TGA are shown in Figure 19; and DVS is shown in Figure 20.

[0737] A 500 mg sample of Compound 1 citrate (Form A) was dissolved in 4.0 mL of a 0.901 water activity solution (65% water in acetone, v / v) to yield a 125 mg / mL suspension. The suspension was stirred at 300 rpm and maintained 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 one day to yield a powder with a 56.9% yield. The ratio of Compound 1 : citric acid in Compound 1 citrate (Form B) was determined to be 1 : 1.17 by ion chromatography. XRPD is shown in Figure 18; DSC and TGA are shown in Figure 19; and DVS is shown in Figure 20. 1 Compound 1 citrate (Form B) was analyzed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, DMSO-d6): δ 0.53-0.79 (m, 7H) 0.85-1.76 (m, 24H) 1.99-2.14 (m, 3H) 2.32-2.35 (m, 1H) 2.61-2.74 (m, 6H) 3.00-3.09 (m, 2H) 4.89-5.13 (m, 1H) 6.99 (s, 1H) 7.11 (s, 1H) 7.74 (s, 1H).

[0738] Compound 1 citrate (form C):

[0739] A sample of Compound 1 citrate Form A was stirred as a suspension in acetonitrile at 50 °C. The resulting solids were isolated by filtration.

[0740] General process for preparing compound 1 citrate

[0741] The following general procedure was performed to prepare Compound 1 citrate.

[0742] General Process A

[0743] To a 20 mL vial equipped with a stir bar was added Compound 1 (1.00 g, 1.0 eq) and solvent or co-solvent. The resulting mixture was heated to 60 °C for 30 minutes. To the mixture at 60 °C was added a solution of citric acid monohydrate (0.54 g, 1.1 eq) in solvent or co-solvent (pre-heated to dissolve) and stirred for 1 hour. The reaction was cooled to 25 °C and stirred overnight. The suspension was filtered and the wet cake was washed with acetone. The solids were collected and dried under vacuum at 25 °C overnight to give Compound 1 citrate.

[0744] General Process A-2

[0745] To a 20 mL vial equipped with a stir bar was added compound 1 (1.00 g, 1.0 eq) and co-solvent (10 mL, 10 mL / g compound 1). The resulting mixture was heated to 60 °C for 30 minutes. To the mixture at 60 °C was added a solution of citric acid monohydrate (0.54 g, 1.1 eq) in co-solvent (2 mL, 2 mL / g compound 1) (pre-heated to dissolve) and stirred for 1 hour. The reaction was cooled to 0 °C (no precipitate). 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.

[0746] General Process B

[0747] To a 20 mL vial equipped with a stir bar was added compound 1 (1.00 g, 1.0 eq) and EtOH (3.5 mL, 3.5 mL / g compound 1). The resulting mixture was heated to 60 °C for 30 minutes. To the mixture at 60 °C was added a solution of citric acid monohydrate (0.54 g, 1.1 eq) in EtOH (1.5 mL, 1.5 mL / g compound 1) (pre-heated to dissolve), and stirred for 1 hour. 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 then stirred for 1 hour. The mixture was stirred at 25 °C overnight. The reaction was cooled to 0 °C and then stirred for 1 hour. The suspension was filtered and the wet cake was washed with acetone. The solid was collected and dried under vacuum at 25 °C overnight to give compound 1 citrate.

[0748] General Process C

[0749] To a 20 mL vial equipped with a stir bar was added compound 1 (1.00 g, 1.0 eq) and EtOH (3.5 mL, 3.5 mL / g compound 1). The resulting mixture was heated to 60 °C for 30 minutes. To the mixture at 60 °C was added a solution of citric acid monohydrate (0.54 g, 1.1 eq) in EtOH (1.5 mL, 1.5 mL / g compound 1) (pre-heated to dissolve), and stirred for 1 hour. 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 then stirred for 1 hour. The mixture was stirred at 25 °C overnight. The reaction was cooled to 0 °C and then stirred for 1 hour. The suspension was filtered and the wet cake was washed with acetone. The solid was collected and dried under vacuum at 25 °C overnight to give compound 1 citrate.

[0750] The following table summarizes the preparation of compound 1 citrate according to these general procedures:

[0751]

[0752]

[0753] Chemical and physical stability testing

[0754] Chemical and physical stability testing was performed using the procedures shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 citrate (Form A), Compound 1 citrate (Form B), and Compound 1 free base:

[0755]

[0756]

[0757] ICH stability testing of Compound 1 citrate (Form A):

[0758] Compound 1 citrate (Form A) was tested for stability according to the ICH guidelines for accelerated stability studies. The following table shows the results of the accelerated stability studies. At the 3 month time point, the data show that the assay, purity, and polymorphic stability of Compound 1 citrate (Form A) were maintained.

[0759]

[0760] Dissolution testing in simulated gastric and intestinal fluids

[0761] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedures shown in Example 1. The following table shows the results of the dissolution (mg / mL) of Compound 1 citrate (Form A), Compound 1 citrate (Form B), and Compound 1 free base in biorelevant solutions:

[0762]

[0763]

[0764] Single crystal X-ray structure of Compound 1 citrate Form A

[0765] A bulk single crystal sample of Compound 1 citrate Form A for SCXRD characterization was crystallized from a THF solvent mixture by slow evaporation.

[0766] Characterization of the salt by PLM and XRPD indicated that it was Compound 1 citrate Form A.

[0767] Cell parameters and orientation matrix for data collection were retrieved and refined (least squares refinement) by CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software using 64393 reflections set angles in the range 3.7580° < Θ < 75.8720°. The minimum diffraction angle (Θ) of the data collected at 120.00 K was 3.785° and the maximum diffraction angle (Θ) was 66.597°. The final completeness was 99.3%. The average I / σ of the data was 81.3 and the maximum resolution obtained was

[0768] The following table provides SCXRD data obtained by the methods described herein.

[0769]

[0770] Example 3: Preparation of the mesylate salt of Compound 1

[0771] The mesylate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0772] Compound 1, methanesulfonate (form A) :

[0773] Compound 1 was dissolved in 10.0 mL EtOAc at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1 hour. Then 1.1 equivalent 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 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with EtOAc. The obtained wet product was dried under vacuum at 35 °C for 22 hours to give 234.52 mg of powder with a yield of 94.1%.

[0774] The resulting solid was Compound 1 mesylate salt (Form A). The ratio of Compound 1 : methanesulfonic acid in Compound 1 mesylate salt (Form A) was 1 : 1.08 as determined by ion chromatography. XPRD is shown in Figure 22; DSC and TGA are shown in Figure 23; and DVS is shown in Figure 24.

[0775] Compound 1 mesylate salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1 Compound 1 mesylate salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1HNMR (400 MHz, 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).

[0776] Compound 1 methanesulfonate (form B):

[0777] Compound 1 was dissolved in 10.0 mL EtOAc at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1 hour. Then 1.1 equivalent of methanesulfonic acid in EtOAc (1.027 mL, 0.5 mol / L) was added to the solution of Compound 1 and incubated at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with EtOAc. The obtained wet product was dried in vacuum at 35 °C for 22 hours to give 234.52 mg of powder with a yield of 94.1%.

[0778] The obtained solid was Compound 1 methanesulfonate salt (Form B). XPRD is shown in Figure 25A.

[0779] Compound 1, methanesulfonate (form C):

[0780] Compound 1 methanesulfonate salt (Form C) was prepared using solvent ACN solvent and methanesulfonic acid. For liquid counterion, 50 mg of Compound 1 was weighed into a 2 mL vial, then 743 μL of solvent was added into the vial. Then 1.1 equivalent of counterion solution of the corresponding solvent (257 μL, concentration: 0.5 mol / L) was added into the vial. The vial was placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with stirring at 900 rpm, the vial was cooled to 25 °C. After 1 hour at 25 °C, the solid in the suspension was separated by centrifugation and dried in a vacuum oven at 30 °C overnight.

[0781] The obtained solid was Compound 1 methanesulfonate salt (Form C). XPRD is shown in Figure 25B.

[0782] Compound 1, methanesulfonate (form D):

[0783] About 5 mg of Compound 1 mesylate salt (Form A) was added to an 8 mL glass vial with a porous aluminum foil cap and held at 60 °C, 40 °C / 75% RH for 1 week. The appearance was recorded by visual inspection, followed by purity assessment and XPRD data collection on the residual solid. The resulting solid was Compound 1 mesylate salt (Form D). The dried solid was characterized by PLM and XRPD.

[0784] XPRD is shown in Figure 26.

[0785] Chemical and physical stability testing

[0786] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 mesylate salt (Form A) and Compound 1 free base:

[0787]

[0788] Dissolution testing in simulated gastric and intestinal fluids

[0789] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 mesylate salt (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[0790]

[0791] Example 4: Preparation of a phosphate salt of Compound 1

[0792] A phosphate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0793] About 200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60 °C while stirring at 500 rpm and held at 60 °C for 1.5 hours. A solution of 1.1 equivalents of phosphoric acid in acetone (1.027 mL, 0.5 mol / L) was then added to the Compound 1 solution and incubated at 60 °C for 3 hours, then cooled to 25 °C and held at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 30 °C for 42 hours to give 233.51 mg of powder with a yield of 93.3%.

[0794] The resulting solid was Compound 1 phosphate salt (Form A). The ratio of Compound 1 : phosphoric acid in Compound 1 phosphate salt (Form A) was 1 : 0.9 as determined by ion chromatography. XPRD is shown in Figure 27; DSC and TGA are shown in Figure 28; and DVS is shown in Figure 29.

[0795] Chemical and physical stability testing

[0796] Chemical and physical stability testing was performed using the procedure shown in Example 1. The table below shows the results of the chemical and physical stability testing of Compound 1 Phosphate (Form A) and Compound 1 Free Base:

[0797]

[0798] Dissolution testing in simulated gastric and intestinal fluids

[0799] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The table below shows the results of the dissolution (mg / mL) of Compound 1 Phosphate (Form A) and Compound 1 Free Base in biorelevant solutions:

[0800]

[0801]

[0802] Example 5: Preparation of L(+)-Tartaric Acid Salt of Compound 1

[0803] The L(+)-Tartaric Acid Salt of Compound 1 can be prepared from Compound 1 using the following exemplary methods.

[0804] Compound 1L(+)-tartrate (form A) :

[0805] Compound 1 (200 mg) was dissolved in 10.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent 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 maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 30 °C for 42 hours to give 237.95 mg of powder with a yield of 85.9%.

[0806] The resulting solid was Compound 1 L(+)-Tartaric Acid Salt (Form A). The ratio of Compound 1 : Tartaric acid in Compound 1 L(+)-Tartaric Acid Salt (Form A) was 1 : 1.15 as determined by ion chromatography. XRPD is shown in Figure 30; DSC and TGA are shown in Figure 31; and DVS is shown in Figure 32.

[0807] by 1 Compound 1 L(+)-Tartaric Acid Salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1H NMR (400 MHz, DMSO-de): 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).

[0808] Compound 1L(+)-tartrate (form B) :

[0809] Compound 1 was dissolved in 10.0 mL EtOAc at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1 hour. Then 1.1 equivalent of L(+)-tartaric acid powder (77 mg, 0.5 mmol) was added to the RX-0001175 solution and incubated at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with EtOAc. The obtained wet product was dried under vacuum at 35 °C for 22 hours to obtain 254.08 mg of powder with a yield of 91.7%.

[0810] The obtained solid was Compound 1 L(+)-tartrate salt (Form B). The ratio of Compound 1 : tartaric acid in Compound 1 L(+)-tartrate salt (Form B) was 1 : 1.19 as determined by ion chromatography. XRPD is shown in Figure 33; DSC and TGA are shown in Figure 34; and DVS is shown in Figure 35.

[0811] The chemical and physical stability tests were performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability tests for Compound 1 L(+)-tartrate salt (Form A), Compound 1 L(+)-tartrate salt (Form B), and Compound 1 free base: 1 H-NMR analysis of Compound 1 L(+)-tartrate salt (Form B) gave the following chemical shifts: 1 H NMR (400 MHz, DMSO-de): 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).

[0812] Chemical and physical stability tests

[0813] The chemical and physical stability tests were performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability tests for Compound 1 L(+)-tartrate salt (Form A), Compound 1 L(+)-tartrate salt (Form B), and Compound 1 free base:

[0814]

[0815] Dissolution testing in simulated gastric and intestinal fluids

[0816] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1L (+)-tartrate (Form A), Compound 1L (+)-tartrate (Form B), and Compound 1 free base in biorelevant solutions:

[0817]

[0818]

[0819] Example 6: Preparation of a fumarate salt of Compound 1

[0820] A fumarate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0821] Compound 1, fumarate (form A) :

[0822] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1L (+)-tartrate (Form A), Compound 1L (+)-tartrate (Form B), and Compound 1 free base in biorelevant solutions:

[0823] The resulting solid was Compound 1 fumarate salt (Form A). The ratio of Compound 1 : fumarate in Compound 1 fumarate salt (Form A) was 1 : 1.37 as determined by ion chromatography. XRPD is shown in Figure 36, and DSC and TGA are shown in Figure 37.

[0824] by ion chromatography in deuterated DMSO 1 H-NMR analysis of Compound 1 fumarate salt (Form A) gave the following chemical shifts: 1H NMR (400 MHz, 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).

[0825] Compound 1, fumarate (form B) :

[0826] Compound 1 was dissolved in 10.0 mL of ethyl acetate at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1 hour. Then 1.1 equivalent of fumaric acid powder (60 mg, 0.51 mmol) was added to the solution of Compound 1. The solution was maintained at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. During the cooling process, the clear solution became a suspension. The suspension was then centrifuged, the precipitate was collected, and dried in vacuum at 35 °C for 22 hours to give 156.78 mg of powder with a yield of 60.4%.

[0827] The resulting solid was Compound 1 fumarate salt (Form B). The ratio of Compound 1 : fumaric acid in Compound 1 fumarate salt (Form B) was 1 : 1.55 as determined by ion chromatography. XRPD is shown in Figure 38, DSC and TGA are shown in Figure 39; and DVS is shown in Figure 40.

[0828] 1 H NMR (400 MHz, 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).

[0829] Compound 1, fumarate (form C) :

[0830] Compound 1 and 1.1 equivalent of counterion of fumaric acid in solid form were weighed into 2 mL vials, respectively, then 1 mL of solvent ACN was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in the suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 48 hours.

[0831] The resulting solid was Compound 1 fumarate salt (Form C). The dried solid was characterized by PLM and XRPD.

[0832] XPRD is shown in Figure 41.

[0833] Compound 1, fumarate (form D)

[0834] About 5 mg of Compound 1 fumarate salt (Form A) was added to an 8 mL glass vial with a porous aluminum foil cap and held at 60 °C, 40 °C / 75% RH for 1 week. The appearance was recorded by visual inspection and subsequently the residual solid was subjected to purity assessment and XRPD data collection. The resulting solid was Compound 1 fumarate salt (Form D). The dried solid was characterized by PLM and XRPD. XPRD is shown in Figure 42.

[0835] Chemical and Physical Stability Testing

[0836] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of chemical and physical stability testing for Compound 1 fumarate salt (Form A) and Compound 1 free base:

[0837]

[0838] Dissolution Testing in Simulated Gastric and Intestinal Fluid

[0839] Dissolution testing in simulated gastric and intestinal fluid was performed using the procedure shown in Example 1. The following table shows the results of dissolution (mg / mL) for Compound 1 fumarate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0840]

[0841]

[0842] Example 7: Preparation of the Tosylate Salt of Compound 1

[0843] The tosylate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0844] Compound 1, toluenesulfonate (form A)

[0845] ​​200 mg of compound 1 was dissolved in 10.0 mL of ACN at 60 °C while stirring at 500 rpm and maintaining the solution at 60 °C for 1 hour. Then, 1.1 equivalents of a solution of p-toluenesulfonic acid in ACN (1.027 mL, 0.5 mol / L) was added to the compound 1 solution, and the mixture was incubated at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ACN. The obtained wet product was dried under vacuum at 35 °C for 22 hours to give a powder of 141.85 g, with a yield of 49.2%.

[0846] The obtained solid was compound 1 toluenesulfonate (form A). Ion chromatography determined that the ratio of compound 1 to toluenesulfonic acid in compound 1 toluenesulfonate (form A) was 1:1.09. XPRD is shown in Figure 43; DSC and TGA are shown in Figure 44; and DVS is shown in Figure 45.

[0847] In deuterated DMSO, through 1 H-NMR analysis of compound 1 toluenesulfonate (form A) yielded the following chemical shifts: 1 HNMR (400MHz, DMSO-d6): δ0.50-0.79(m,7H)1.98-2.15(m,3H)2.28(s,4H)2.49(s,23H)2.60-2.76(m,1H)3.0 3(s,2H)3.21-3.34(m,5H)4.85-5.45(m,2H)7.10(d,J=7.78Hz,2H)7.45(s,1H)7.46-7.73(m,3H)8.99(s,1H).

[0848] Compound 1, toluenesulfonate (form B) :

[0849] 50 mg of compound 1 and 1.1 equivalents of the counterion of p-toluenesulfonic acid in solid form were weighed into separate 2 mL vials, and then 1 mL of EtOAc solvent was added to each vial. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After maintaining the temperature at 50 °C for 18 hours with constant stirring at 900 rpm, the vials were cooled to 25 °C. After maintaining the temperature at 25 °C for 1 hour, the solids in the suspension were separated by centrifugation and dried overnight in a vacuum oven at 30 °C.

[0850] The resulting solid was compound 1 toluenesulfonate (form B). The XPRD is shown in Figure 46.

[0851] Compound 1, toluenesulfonate (form C) :

[0852] About 5 mg of Compound 1 tosylate salt (Form A) was added to an 8 mL glass vial with a porous aluminum foil cap and held at 60 °C, 40 °C / 75% RH for 1 week. The appearance was recorded by visual inspection, followed by purity assessment and XPRD data collection on the residual solid. The resulting solid was Compound 1 tosylate salt (Form C). The dried solid was characterized by PLM and XRPD.

[0853] The resulting solid was Compound 1 tosylate salt (Form C). XPRD is shown in Figure 47.

[0854] Chemical and physical stability testing

[0855] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of chemical and physical stability testing for Compound 1 tosylate salt (Form A) and Compound 1 free base:

[0856]

[0857]

[0858] Dissolution testing in simulated gastric and intestinal fluids

[0859] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of dissolution (mg / mL) for Compound 1 tosylate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0860]

[0861] Example 8: Preparation of glucuronate salt of Compound 1

[0862] The following exemplary method can be used to prepare a glucuronate salt of Compound 1 from Compound 1.

[0863] Compound 1, glucuronide (form A) :

[0864] About 500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and held at 60 °C for 1.5 hours. Then 1.1 equivalent 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 held at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried at 25 °C under vacuum for 72 hours to give 739.32 mg of powder with a yield of 98.76%.

[0865] The resulting solid was Compound 1 glucuronate salt (Form A). The ratio of Compound 1 : glucuronic acid in Compound 1 glucuronate salt (Form A) was 1 : 1.09 as determined by ion chromatography. XRPD is shown in Figure 48; DSC and TGA are shown in Figure 49; and DVS is shown in Figure 50.

[0866] In deuterated DMSO by 1 H-NMR analysis of Compound 1 glucuronate salt (Form A) gave the following chemical shifts: 1 H-NMR analysis of Compound 1 glucuronate salt (Form A) gave the following chemical shifts:

[0867] Chemical and physical stability testing

[0868] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing for Compound 1 glucuronate salt (Form A) and Compound 1 free base:

[0869]

[0870] Dissolution testing in simulated gastric and intestinal fluids

[0871] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution (mg / mL) for Compound 1 glucuronate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0872]

[0873] Compound 1, glucuronide (form B) :

[0874] Into separate 2 mL vials, 50 mg of Compound 1 and 1.1 equivalents of the counterion of D-glucuronic acid in solid form were weighed. Then, 1 mL of solvent EtOAc / ACN was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0875] The dried solids were characterized by PLM and XRPD (Figure 51).

[0876] Example 9: Preparation of ethanesulfonic acid salt of Compound 1

[0877] The ethanesulfonic acid salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0878] Into separate 2 mL vials, 50 mg of Compound 1 and 1.1 equivalents of the counterion of D-glucuronic acid in solid form were weighed. Then, 1 mL of solvent EtOAc / ACN was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0879] The resulting solid was Compound 1 ethanesulfonic acid salt (Form A). The ratio of Compound 1 : ethanesulfonic acid in Compound 1 ethanesulfonic acid salt (Form A) was 1 : 1.17 as determined by ion chromatography. XPRD is shown in Figure 52; DSC and TGA are shown in Figure 53; and DVS is shown in Figure 54.

[0880] In deuterated DMSO by 1 Compound 1 ethanesulfonic acid salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, DMSO-d6) δ ppm 0.52 - 0.81 (m, 7 H) 0.83 - 1.78 (m, 25 H) 1.99 - 2.17 (m, 3 H) 2.39 (q, J=7.42 Hz, 2 H) 2.69 - 2.80 (m, 1 H) 3.05 (s, 2 H) 3.43 (br s, 4 H) 5.11 - 5.46 (m, 2 H) 7.54 - 7.77 (m, 2 H) 9.02 (s, 1 H).

[0881] Chemical and physical stability testing

[0882] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 esylate (Form A) and Compound 1 free base:

[0883]

[0884] Dissolution testing in simulated gastric and intestinal fluids

[0885] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 esylate (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[0886]

[0887] Example 10: Preparation of a sulfate salt of Compound 1

[0888] A sulfate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0889] Two hundred mg of Compound 1 was dissolved in 10.0 mL of ACN at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1 hour. Then 1.1 equivalent of a solution 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 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The suspension was centrifuged, the precipitate was collected, and washed with ACN. The obtained wet product was dried under vacuum at 35 °C for 22 hours to give 177.38 mg of powder with a yield of 70.9%.

[0890] The resulting solid was Compound 1 sulfate salt (Form A). The ratio of Compound 1 :sulfuric acid in Compound 1 sulfate salt (Form A) was 1 :1.03 as determined by ion chromatography. XRPD is shown in Figure 55; DSC and TGA are shown in Figure 56; and DVS is shown in Figure 57.

[0891] Chemical and physical stability testing

[0892] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 sulfate salt (Form A) and Compound 1 free base:

[0893]

[0894]

[0895] Dissolution testing in simulated gastric and intestinal fluids

[0896] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1 sulfate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0897]

[0898] Example 11: Preparation of Ascorbate Salt of Compound 1

[0899] The ascorbate salt of Compound 1 can be prepared from Compound 1 using the following exemplary methods.

[0900] Compound 1 ascorbate (form A):

[0901] Compound 1 (500 mg) was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent 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 maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 25 °C for 72 hours to give 264.1 mg of powder with a yield of 36.3%.

[0902] The resulting solid was Compound 1 ascorbate salt (Form A). The ratio of Compound 1 : ascorbic acid in Compound 1 ascorbate salt (Form A) was 1 :0.98 as determined by ion chromatography. XRPD is shown in Figure 58; DSC and TGA are shown in Figure 59; and DVS is shown in Figure 60.

[0903] In deuterated DMSO by 1 Compound 1 ascorbate salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, DMSO-d6) δ ppm 0.51-0.81 (m, 7H) 0.83-1.76 (m, 22H) 1.98-2.14 (m, 4H) 2.33 (br s, 1H) 2.64-2.72 (m, 1H) 3.04 (s, 2H) 3.25 (s, 3H) 3.41-3.45 (m, 3H) 3.73 (br t, 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).

[0904] Chemical and physical stability testing

[0905] Chemical and physical stability testing was performed using the procedure shown in Example 1. The table below shows the results of the chemical and physical stability testing of Compound 1 ascorbate (Form A) and Compound 1 free base:

[0906]

[0907]

[0908] Dissolution testing in simulated gastric and intestinal fluids

[0909] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The table below shows the results of the dissolution (mg / mL) of Compound 1 ascorbate (Form A) and Compound 1 free base in biorelevant solutions:

[0910]

[0911] Compound 1 ascorbate (form B) :

[0912] Fifty mg of Compound 1 and 1.1 equivalents of the counterion of ascorbic acid in solid form were weighed into 2 mL vials, respectively, followed by the addition of 1 mL of ACN solvent to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0913] The dried solids obtained were characterized by PLM and XRPD.

[0914] Example 12: Preparation of the naphthalene disulfonate salt of Compound 1

[0915] The naphthalene disulfonate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0916] Compound 1 naphthalene disulfonate salt (Form A)

[0917] Five hundred mg of Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. A solution of 1.1 equivalents of naphthalene-1,5-disulfonic acid tetrahydrate (2.565 mL, 0.5 mol / L) in acetone was then added to the Compound 1 solution and incubated at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The wet product obtained was dried in a vacuum oven at 25 °C for 72 hours to give 675.62 mg of a light pink powder with a yield of 69.38%.

[0918] The resulting solid was Compound 1 naphthalene-1,5-disulfonate salt (Form A). The ratio of Compound 1 : naphthalene-1,5-disulfonic acid in Compound 1 naphthalene-1,5-disulfonate salt (Form A) was 1 :0.7 as determined by ion chromatography. XRPD is shown in Figure 62; DSC and TGA are shown in Figure 63; and DVS is shown in Figure 64.

[0919] Compound 1 naphthalene-1,5-disulfonate salt (Form A) was analyzed by H-NMR in deuterated DMSO to give the following chemical shifts: 1 Compound 1 naphthalene-1,5-disulfonate salt (Form A) was analyzed by H-NMR in deuterated DMSO to give the following chemical shifts: 1 H-NMR (400 MHz, 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).

[0920] Chemical and physical stability testing

[0921] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing for Compound 1 naphthalene-1,5-disulfonate salt (Form A) and Compound 1 free base:

[0922]

[0923] Dissolution testing in simulated gastric and intestinal fluids

[0924] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution (mg / mL) for Compound 1 naphthalene-1,5-disulfonate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0925]

[0926]

[0927] Compound 1 naphthalene-1,5-disulfonate salt (Form B):

[0928] Into separate 2 mL vials, 50 mg of Compound 1 and 1.1 equivalents of the counterion of naphthalene-1,5-disulfonic acid tetrahydrate in solid form were weighed out, then 1 mL of the solvent IPA / water (95 / 5, V / V) was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in the suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0929] The dried solids were characterized by PLM and XRPD (Figure 65).

[0930] Example 13: Preparation of the malonate salt of Compound 1

[0931] The malonate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0932] Into a 60 mL vial, 500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then a solution of 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 maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried in a vacuum oven at 25 °C for 72 hours.

[0933] The resulting solid was Compound 1 malonate salt (Form A). The ratio of Compound 1 : malonic acid in Compound 1 malonate salt (Form A) was 1 : 1.28 as determined by ion chromatography. XPRD is shown in Figure 66; and DSC and TGA are shown in Figure 67.

[0934] In deuterated DMSO by 1 Compound 1 malonate salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, DMSO-d6) δ ppm 0.50 - 0.79 (m, 7 H) 0.84 - 1.75 (m, 20 H) 1.91 (s, 1 H) 2.00 - 2.12 (m, 2 H) 2.65 - 2.73 (m, 1 H) 3.04 (s, 2 H) 3.13 (s, 3 H) 4.92 - 5.15 (m, 2 H) 7.03 - 7.20 (m, 2 H) 7.91 (s, 1 H).

[0935] Chemical and physical stability testing

[0936] Chemical and physical stability testing was performed using the procedure shown in Example 1. The table below shows the results of the chemical and physical stability testing of Compound 1 malonate (Form A) and Compound 1 free base:

[0937]

[0938]

[0939] Dissolution testing in simulated gastric and intestinal fluids

[0940] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The table below shows the results of the dissolution (mg / mL) of Compound 1 malonate (Form A) and Compound 1 free base in biorelevant solutions:

[0941]

[0942] Example 14: Preparation of the benzenesulfonate salt of Compound 1

[0943] The benzenesulfonate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0944] Compound 1 benzenesulfonate salt (Form A)

[0945] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent 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 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 25 °C for 72 hours to give 654.68 mg of powder with a yield of 92.56%.

[0946] The obtained solid was Compound 1 benzenesulfonate salt (Form A). The ratio of Compound 1 : benzenesulfonic acid in Compound 1 benzenesulfonate salt (Form A) was 1 :0.94 as determined by ion chromatography. XPRD is shown in Figure 68; DSC and TGA are shown in Figure 69; and DVS is shown in Figure 70.

[0947] In deuterated DMSO by 1 H-NMR analysis of Compound 1 benzenesulfonate salt (Form A) gave the following chemical shifts: 1HNMR (400 MHz, DMSO-d6) δ ppm 0.53-0.80 (m, 7H) 0.83-1.78 (m, 21H) 1.99-2.15 (m, 3H) 2.29-2.36 (m, 1H) 2.56 (br s, 1H) 2.66-2.77 (m, 1H) 3.05 (s, 2H) 3.25 (s, 4H) 4.03 (br s, 1H) 5.15-5.39 (m, 2H) 7.27-7.36 (m, 3H) 7.55-7.70 (m, 4H) 8.97 (s, 1H).

[0948] Chemical and physical stability testing

[0949] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 besylate (Form A) and Compound 1 free base:

[0950]

[0951] Dissolution testing in simulated gastric and intestinal fluids

[0952] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 besylate (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[0953]

[0954] Compound 1 besylate (Form B)

[0955] Fifty mg of Compound 1 and 1.1 equivalents of the counterion of the solid form of benzenesulfonic acid were weighed into 2 mL vials, respectively, followed by the addition of 1 mL of ACN solvent to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0956] The dried solids obtained were characterized by PLM and XRPD (Figure 71).

[0957] Example 15: Preparation of the isethionate salt of Compound 1

[0958] The isethionate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[0959] Compound 1 isethionate (Form A)

[0960] Dissolve 500 mg of Compound 1 in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then add 1.1 equivalents of 2-hydroxyethanesulfonic acid in acetone (2.565 mL, 0.5 mol / L) to the Compound 1 solution and incubate at 60 °C for 3 hours, then cool to 25 °C and maintain at 25 °C overnight. Centrifuge the suspension, collect the precipitate, and wash with acetone. Dry the obtained wet product at 25 °C under vacuum for 72 hours to obtain 493.12 mg of powder with a yield of 74.64%.

[0961] The resulting solid is Compound 1 hydroxyethylsulfonate (Form A). The ratio of Compound 1 : 2-hydroxyethanesulfonic acid in Compound 1 hydroxyethylsulfonate (Form A) was determined to be 1 : 1.09 by ion chromatography. XPRD is shown in Figure 72; DSC and TGA are shown in Figure 73; and DVS is shown in Figure 74.

[0962] Dissolve 500 mg of Compound 1 in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then add 1.1 equivalents of 2-hydroxyethanesulfonic acid in acetone (2.565 mL, 0.5 mol / L) to the Compound 1 solution and incubate at 60 °C for 3 hours, then cool to 25 °C and maintain at 25 °C overnight. Centrifuge the suspension, collect the precipitate, and wash with acetone. Dry the obtained wet product at 25 °C under vacuum for 72 hours to obtain 493.12 mg of powder with a yield of 74.64%. 1 H-NMR analysis of Compound 1 hydroxyethylsulfonate (Form A) gave the following chemical shifts: 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.53 - 0.81 (m, 7 H) 0.84 - 1.78 (m, 22 H) 2.01 - 2.15 (m, 3 H) 2.34 (br s, 1 H) 2.61 (t, J = 6.82 Hz, 2 H) 2.66 - 2.78 (m, 1 H) 3.05 (s, 2 H) 3.25 (s, 3 H) 3.63 (t, J = 6.75 Hz, 2 H) 5.14 - 5.38 (m, 2 H) 7.58 - 7.69 (m, 2 H) 8.99 (s, 1 H).

[0963] Chemical and physical stability testing

[0964] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 hydroxyethylsulfonate (Form A) and Compound 1 free base:

[0965]

[0966] Dissolution testing in simulated gastric and intestinal fluids

[0967] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution (mg / mL) of Compound 1 hydroxyethylsulfonate (Form A) and Compound 1 free base in biorelevant solutions:

[0968]

[0969] Dissolution testing in simulated gastric and intestinal fluids

[0970] Compound 1 isethionate (Form B)

[0971] Compound 1 was weighed into a 2 mL vial at 50 mg, then 743 μL of solvent IPA / water (95 / 5, V / V) was added to the vial. Then 1.1 equivalents of the counterion of 2-hydroxyethanesulfonic acid (257 μL, concentration: 0.5 mol / L) was added to the vial. The vial was placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vial was cooled to 25 °C. After 1 hour at 25 °C, the vial showed a clear solution. The solvent was evaporated by vacuum oven at 30 °C.

[0972] The dried solid obtained was characterized by PLM and XRPD (Figure 75).

[0973] Example 16: Preparation of the gentisate salt of Compound 1

[0974] The following exemplary method can be used to prepare the gentisate salt of Compound 1 from Compound 1.

[0975] Compound 1 gentisate (Form A)

[0976] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and keeping at 60 °C for 1.5 hours. Then 1.1 equivalents of a solution 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, the precipitate was collected, and washed with acetone. The wet product obtained was dried in vacuum at 25 °C for 72 hours to give 281.5 mg of powder with a yield of 31.39%.

[0977] The solid obtained was Compound 1 gentisate (Form A). The ratio of Compound 1 : gentisic acid in Compound 1 gentisate (Form A) was 1 : 1.03 as determined by ion chromatography. XPRD is shown in Figure 76; DSC and TGA are shown in Figure 77; and DVS is shown in Figure 78.

[0978] in deuterated DMSO by 1 Compound 1 gentisate (Form A) was analyzed by H-NMR to give the following chemical shifts: 1HNMR (400 MHz, DMSO-d6) δ ppm 0.53 - 0.80 (m, 7 H) 0.85 - 1.72 (m, 20 H) 2.00 - 2.13 (m, 5 H) 2.66 - 2.74 (m, 1 H) 3.04 (s, 2 H) 4.02 (br s, 1 H) 4.90 - 5.12 (m, 2 H) 6.71 (d, J=8.76 Hz, 1 H) 6.88 (dd, J=8.82, 3.06 Hz, 1 H) 7.03 (s, 1 H) 7.13 - 7.17 (m, 2 H) 7.78 - 7.86 (m, 1 H) 7.81 (s, 1 H) 9.01 (br s, 1 H).

[0979] Chemical and physical stability testing

[0980] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing for Compound 1 gentisate salt (Form A) and Compound 1 free base:

[0981]

[0982]

[0983] Compound 1 gentisate salt (Form B)

[0984] Fifty mg of Compound 1 and 1.1 equivalents of the counterion of gentisic acid in solid form were separately weighed into 2 mL vials, followed by the addition of 1 mL of EtOAc solvent to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were isolated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0985] The dried solids were characterized by PLM and XRPD (Figure 79).

[0986] Compound 1 gentisate salt (Form C)

[0987] Fifty mg of Compound 1 and 1.1 equivalents of the counterion of gentisic acid in solid form were separately weighed into 2 mL vials, followed by the addition of 1 mL of IPA / water (95 / 5, V / V) solvent to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were isolated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[0988] The dried solids were characterized by PLM and XRPD (Figure 80).

[0989] Dissolution testing in simulated gastric and intestinal fluids

[0990] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1 gentisate salt (Form A) and Compound 1 free base in biorelevant solutions:

[0991]

[0992]

[0993] Example 17: Preparation of Compound 1 1-hydroxy-2-naphthoate salt

[0994] Compound 1 1-hydroxy-2-naphthoate salt can be prepared from Compound 1 using the following exemplary method.

[0995] Compound 1 1-hydroxy-2-naphthoate salt (Form A)

[0996] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent of 1-hydroxy-2-naphthoic acid salt 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 maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 25 °C for 72 hours to give 675.36 mg of powder with a yield of 68.15%.

[0997] The obtained solid was Compound 1 1-hydroxy-2-naphthoate salt (Form A). The ratio of Compound 1 : 1-hydroxy-2-naphthoic acid in Compound 1 1-hydroxy-2-naphthoate salt (Form A) was determined to be 1 : 1.15 by ion chromatography. XPRD is shown in Figure 81; DSC and TGA are shown in Figure 82; and DVS is shown in Figure 83.

[0998] by ion chromatography in deuterated DMSO 1 H-NMR analysis of Compound 1 1-hydroxy-2-naphthoate salt (Form A) gave the following chemical shifts: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.49 - 0.79 (m, 7 H) 0.82 - 1.76 (m, 22 H) 1.96 - 2.16 (m, 4 H) 2.63 - 2.76 (m, 1 H) 2.95 - 3.11 (m, 2 H) 4.98 - 5.22 (m, 2 H) 7.19 - 7.32 (m, 3 H) 7.46 - 7.62 (m, 2 H) 7.72 - 7.86 (m, 2 H) 8.16 - 8.29 (m, 2 H).

[0999] Chemical and physical stability testing

[1000] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing for Compound 1 1-hydroxy-2-naphthoate salt (Form A) and Compound 1 free base:

[1001]

[1002] Dissolution testing in simulated gastric and intestinal fluids

[1003] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution (mg / mL) for Compound 1 1-hydroxy-2-naphthoate salt (Form A) and Compound 1 free base in biorelevant solutions:

[1004]

[1005] Compound 1 1-hydroxy-2-naphthoate salt (Form B)

[1006] Compound 1 1-hydroxy-2-naphthoate salt (Form B)

[1007] The dried solids were characterized by PLM and XRPD (Figure 84).

[1008] Compound 1 1-hydroxy-2-naphthoate salt (Form B)

[1009] Compound 1 and 1.1 equivalents of the counterion of 1-hydroxy-2-naphthoic acid in solid form were each weighed into a 2 mL vial, then 1 mL of ACN solvent was added to the vial. The vial was placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vial was cooled to 25 °C. After 1 hour at 25 °C, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1010] The dried solids were characterized by PLM and XRPD (Figure 85).

[1011] Compound 1 1-hydroxy-2-naphthoate salt (Form D)

[1012] Compound 1 and 1.1 equivalents of the counterion of 1-hydroxy-2-naphthoic acid in solid form were each weighed into a 2 mL vial, then 1 mL of ACN solvent was added to the vial. The vial was placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C with constant stirring at 900 rpm, the vial was cooled to 25 °C. After 1 hour at 25 °C, the solids in the suspension were isolated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1013] The dried solids were characterized by PLM and XRPD (Figure 86).

[1014] Example 18: Preparation of the cyclamic acid salt of Compound 1

[1015] The following exemplary method can be used to prepare the cyclamic acid salt of Compound 1 from Compound 1.

[1016] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then a solution of 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 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried in a vacuum oven at 25 °C for 72 hours to give 715.81 mg of powder with a yield of 74.48%.

[1017] The resulting solid was Compound 1 cyclamic acid salt (Form A). The ratio of Compound 1 : cyclamic acid in Compound 1 cyclamic acid salt (Form A) was 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.

[1018] in deuterated DMSO by 1H-NMR analysis of Compound 1 cyclamate salt (Form A) gave the following chemical shifts: 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.49 - 0.80 (m, 7 H) 0.84 - 1.77 (m, 30 H) 1.83 - 2.14 (m, 5 H) 2.65 - 2.74 (m, 1 H) 2.90 - 3.09 (m, 3 H) 3.35 - 3.60 (m, 2 H) 4.03 (br s, 1 H) 4.87 - 5.16 (m, 2 H) 6.97 - 7.18 (m, 2 H) 7.54 - 7.91 (m, 3 H).

[1019] Chemical and physical stability testing

[1020] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 cyclamate salt (Form A) and Compound 1 free base:

[1021]

[1022] Dissolution testing in simulated gastric and intestinal fluids

[1023] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 cyclamate salt (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[1024]

[1025] Example 19: Preparation of ethane-1,2-disulfonate salt of Compound 1

[1026] The ethane-1,2-disulfonate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[1027] Compound 1 ethane-1,2-disulfonate salt (Form A)

[1028] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent 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 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 25 °C for 72 hours to give 704.45 mg of powder with a yield of 71.61%.

[1029] The resulting solid was Compound 1 ethanesulfonic acid salt (Form A). The ratio of Compound 1 : ethanesulfonic acid in Compound 1 ethanesulfonic acid salt (Form A) was 1 :2.4 as determined by ion chromatography. The XRPD is shown in Figure 90; the DSC and TGA are shown in Figure 91; and the DVS is shown in Figure 92.

[1030] In deuterated DMSO by 1 H-NMR analysis of Compound 1 ethanesulfonic acid salt (Form A) gave the following chemical shifts: 1 H NMR (400 MHz, 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).

[1031] Chemical and physical stability testing

[1032] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 ethanesulfonic acid salt (Form A) and Compound 1 free base:

[1033]

[1034] Compound 1 ethanesulfonic acid salt (Form B)

[1035] Into 2 mL vials, 50 mg of Compound 1 and 1.1 equivalents of the counterion of ethanesulfonic acid in solid form were weighed separately, then 1 mL of solvent EtOAc / IPA / water (95 / 5, V / V) was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 18 hours at 50 °C under constant stirring at 900 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1036] The dried solids were characterized by PLM and XRPD (Figure 93).

[1037] Dissolution testing in simulated gastric and intestinal fluids

[1038] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 ethanesulfonic acid salt (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[1039]

[1040] Example 20: Preparation of the dichloroacetate salt of Compound 1

[1041] The dichloroacetate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[1042] Compound 1 (500 mg) was dissolved in acetone (16.0 mL) at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent of a solution 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 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried under vacuum at 25 °C for 72 hours to give 559.98 mg of powder with a yield of 83.41%.

[1043] The resulting solid was Compound 1 dichloroacetate salt (Form A). The ratio of Compound 1 : dichloroacetic acid in Compound 1 dichloroacetate salt (Form A) was 1 : 1.14 as determined by ion chromatography. XRPD is shown in Figure 94; DSC and TGA are shown in Figure 95; and DVS is shown in Figure 96.

[1044] In deuterated DMSO by 1 H-NMR analysis of Compound 1 dichloroacetate (Form A) gave the following chemical shifts: 1 H NMR (400 MHz, DMSO-d6) δ ppm 0.46 - 0.79 (m, 7 H) 0.82 - 1.75 (m, 21 H) 1.96 - 2.15 (m, 2 H) 2.62 - 2.75 (m, 1 H) 3.02 (s, 2 H) 4.98 - 5.27 (m, 3 H) 6.30 (s, 1 H) 7.31 (d, J=12.80 Hz, 2 H) 8.32 (s, 1 H).

[1045] Chemical and physical stability testing

[1046] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 dichloroacetate salt (Form A) and Compound 1 free base:

[1047]

[1048]

[1049] Solubility testing in simulated gastric and intestinal fluids

[1050] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1 dichloroacetate (Form A) and Compound 1 free base in biorelevant solutions:

[1051]

[1052] Example 21: Preparation of L-malate salt of Compound 1

[1053] The L-malate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[1054] Compound 1L-malate (Form A)

[1055] Compound 1 was dissolved in 10.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then 1.1 equivalent 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 hours, then cooled to 25 °C and maintained at 25 °C for 20 hours. The solution was evaporated by nitrogen to remove the organic solvent. The obtained wet product was dried at 25 °C under vacuum for 42 hours to give 230.93 mg of powder with a yield of 85.9%.

[1056] The obtained solid was Compound 1 L-malate salt (Form A). The ratio of Compound 1 : malic acid in Compound 1 L-malate salt (Form A) was 1 : 1.35 as determined by ion chromatography. XRPD is shown in Figure 97; DSC and TGA are shown in Figure 98; and DVS is shown in Figure 99.

[1057] In deuterated DMSO by 1 Compound 1 L-malate salt (Form A) was analyzed by H-NMR to give the following chemical shifts: 1 H-NMR (400 MHz, 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).

[1058] Compound 1L-malate (form B)

[1059] ​​10 g of compound 1 was suspended in 350 mL of acetone at 60 °C with stirring at 200 rpm and maintained at 60 °C for 0.5 h. Then, 50 mL of a 1.1 equivalent L-malic acid solution in acetone (0.5 mol / L) was added to the compound 1 suspension, and the mixture was incubated at 60 °C for 3 h. The mixture was then cooled to 25 °C and kept open at 25 °C for 72 h in a vial. The suspension was centrifuged, the precipitate was collected, and dried under vacuum at 30 °C for 24 h to give 4.44 g of powder, with a yield of 33.86%.

[1060] The obtained solid was compound 1L-malate (form B). Ion chromatography determined that the ratio of compound 1 to malic acid in compound 1L-malate (form B) was 1:1.26. XPRD is shown in Figure 100; DSC and TGA are shown in Figure 101; and DVS is shown in Figure 102.

[1061] In deuterated DMSO, through 1 H-NMR analysis of compound 1L-malate (form B) yielded the following chemical shifts: 1 HNMR(400MHz,DMSO-d6)δppm 0.45-0.79(m,7H)0.83-1.73(m,20H)1.98-2.12(m,2H)2.43(dd,J=15.69,7.40Hz,1H)2.56-2.72(m, 2H)3.04(s,2H)4.22(dd,J=7.28,5.52Hz,1H)4.86-5.10(m,2H)6.94(s,1H)7.07(s,1H)7.65(s,1H).

[1062] Chemical and physical stability tests

[1063] Chemical and physical stability tests were performed using the process shown in Example 1. The table below shows the chemical and physical stability test results for Compound 1 L-malate (Form A), Compound 1 L-malate (Form B), and Compound 1 free base:

[1064]

[1065] Solubility test in simulated gastric and intestinal fluids

[1066] Solubility tests in simulated gastric and intestinal fluids were performed using the procedure shown in Example 1. The table below shows the solubility results (mg / mL) of Compound 1 L-malate (Form A), Compound 1 L-malate (Form B), and Compound 1 free base in biologically relevant solutions:

[1067]

[1068] Example 22: Preparation of hydrochloride salt of Compound 1

[1069] The following exemplary method can be used to prepare the hydrochloride salt of Compound 1 from Compound 1.

[1070] Compound 1 hydrochloride (form A) :

[1071] Dissolve 200 mg of Compound 1 in 10.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then add 1.1 equivalents of a solution of hydrochloric acid in acetone (1.027 mL, 0.5 mol / L) to the Compound 1 solution and incubate at 60 °C for 3 hours, then cool to 25 °C and maintain at 25 °C for 20 hours. Centrifuge the suspension, collect the precipitate, and wash with acetone. Dry the obtained wet product at 25 °C under vacuum for 42 hours to obtain 168.15 mg of powder with a yield of 76.9%.

[1072] The resulting solid is Compound 1 hydrochloride salt (Form A). The ratio of Compound 1 : hydrochloric acid in Compound 1 hydrochloride salt (Form A) was determined to be 1 : 0.94 by ion chromatography. XPRD is shown in Figure 103; DSC and TGA are shown in Figure 104; and DVS is shown in Figure 105.

[1073] Compound 1 hydrochloride (form B) :

[1074] Dissolve 500 mg of the hydrochloride salt (Form A) in 4.0 mL of ethanol at 50 °C. Filter the solution, then add a 6.25-fold volume of heptane dropwise to the solution, resulting in a suspension. Maintain the suspension under constant stirring at 500 rpm and at 50 °C for 24 hours. Then centrifuge the suspension, collect the precipitate, and dry at 30 °C under vacuum for 24 hours to obtain 365 mg of powder with a yield of 73.0%.

[1075] The resulting solid is Compound 1 hydrochloride salt (Form B). The ratio of Compound 1 : hydrochloric acid in Compound 1 hydrochloride salt (Form B) was determined to be 1 : 0.96 by ion chromatography. XPRD is shown in Figure 106; DSC and TGA are shown in Figure 107; and DVS is shown in Figure 108.

[1076] Compound 1 hydrochloride (form C) :

[1077] A suspension of 300 mg of the hydrochloride salt (Form A) was prepared in 6.0 mL of a 0.901 water activity solution at 50 °C with stirring at 700 rpm to produce a clear solution. Then 200 mg of the hydrochloride salt was added to produce a suspension. The suspension was maintained at constant stirring at 700 rpm and at 50 °C for 1 week. The suspension was then centrifuged, the precipitate was collected, and dried at 30 °C for 24 hours to give 400 mg of a powder, a yield of 80.0%.

[1078] The resulting solid was Compound 1 hydrochloride salt (Form C). The ratio of Compound 1 : hydrochloric acid in Compound 1 hydrochloride salt (Form C) was 1 : 0.97 as determined by ion chromatography. XRPD is shown in Figure 109; DSC and TGA are shown in Figure 110; and DVS is shown in Figure 111.

[1079] Chemical and physical stability testing

[1080] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing for Compound 1 hydrochloride salt (Form A), Compound 1 hydrochloride salt (Form B), Compound 1 hydrochloride salt (Form C), and Compound 1 free base:

[1081]

[1082]

[1083] Dissolution testing in simulated gastric and intestinal fluids

[1084] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution (mg / mL) for Compound 1 hydrochloride salt (Form A), Compound 1 hydrochloride salt (Form B), Compound 1 hydrochloride salt (Form C), and Compound 1 free base in biorelevant solutions:

[1085]

[1086] Example 22: Preparation of naphthalenesulfonic acid salt of Compound 1

[1087] The naphthalenesulfonic acid salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[1088] Compound 1, naphthalenesulfonate (form A) :

[1089] Dissolve 500 mg of Compound 1 in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then add 1.1 equivalents of naphthalene-2-sulfonic acid hydrate in acetone (2.565 mL, 0.5 mol / L) to the Compound 1 solution and incubate at 60 °C for 3 hours, then cool to 25 °C and maintain at 25 °C overnight. Centrifuge the suspension, collect the precipitate, and wash with acetone. Dry the obtained wet product at 25 °C under vacuum for 72 hours to obtain 690.41 mg of powder with a yield of 89.17%.

[1090] The resulting solid is Compound 1 naphthalenesulfonic acid salt (Form A). The ratio of Compound 1 : naphthalene-2-sulfonic acid in Compound 1 naphthalenesulfonic acid salt (Form A) was determined to be 1 : 1.04 by ion chromatography. XRPD is shown in Figure 112; DSC and TGA are shown in Figure 113; and DVS is shown in Figure 114.

[1091] In deuterated DMSO by 1 H-NMR analysis of Compound 1 naphthalenesulfonic acid salt (Form A) gave the following chemical shifts: 1 H-NMR analysis of Compound 1 naphthalenesulfonic acid salt (Form A) gave the following chemical shifts:

[1092] Chemical and physical stability testing

[1093] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of chemical and physical stability testing for Compound 1 naphthalenesulfonic acid salt (Form A) and Compound 1 free base:

[1094]

[1095] Dissolution testing in simulated gastric and intestinal fluids

[1096] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of dissolution (mg / mL) for Compound 1 naphthalenesulfonic acid salt (Form A) and Compound 1 free base in biorelevant solutions:

[1097]

[1098] Dissolution testing in simulated gastric and intestinal fluids Compound 1 naphthalenesulfonate (form B):

[1099] Into separate 2 mL vials, 50 mg of Compound 1 and 1.1 equivalents of the counterion of naphthalene-2-sulfonic acid hydrate in solid form were weighed. Then, 1 mL of solvent EtOAc / ACN was added to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in the suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1100] The dried solids were characterized by PLM and XRPD (Figure 115).

[1101] Example 23: Preparation of oxalate salt of Compound 1

[1102] The oxalate salt of Compound 1 can be prepared from Compound 1 using the following exemplary process.

[1103] Compound 1 oxalate salt (Form A)

[1104] Into a 2 mL vial, 500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. Then, a solution of 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 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried in a vacuum oven at 25 °C for 72 hours to give 595.76 mg of powder with a yield of 96.32%.

[1105] The obtained solid was Compound 1 oxalate salt (Form A). The ratio of Compound 1 :oxalic acid in Compound 1 oxalate salt (Form A) was 1 :0.91 as determined by ion chromatography. XPRD is shown in Figure 116; DSC and TGA are shown in Figure 117; and DVS is shown in Figure 118.

[1106] Chemical and physical stability testing

[1107] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 oxalate salt (Form A) and Compound 1 free base:

[1108]

[1109] Dissolution testing in simulated gastric and intestinal fluids

[1110] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the dissolution results (mg / mL) for Compound 1 oxalate (Form A) and Compound 1 free base in biorelevant solutions:

[1111]

[1112] Compound 1 oxalate (Form B):

[1113] Compound 1 and 1.1 equivalents of the counterion of oxalic acid in solid form were each weighed into 2 mL vials, followed by the addition of 1 mL of EtOAc solvent to the vials. The vials were placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C with constant stirring at 500 rpm, the vials were cooled to 25 °C. After 1 hour at 25 °C, the solids in suspension were separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1114] The dried solids were characterized by PLM and XRPD (Figure 119).

[1115] Example 24: Preparation of the p-aminosalicylate salt of Compound 1

[1116] The p-aminosalicylate salt of Compound 1 can be prepared from Compound 1 using the following exemplary method.

[1117] Compound 1 p-aminosalicylate (Form A):

[1118] Compound 1 was dissolved in 16.0 mL of acetone at 60 °C while stirring at 500 rpm and maintaining at 60 °C for 1.5 hours. A solution of 1.1 equivalents of 4-aminosalicylic acid in acetone (2.565 mL, 0.5 mol / L) was then added to the Compound 1 solution and incubated at 60 °C for 3 hours, then cooled to 25 °C and maintained at 25 °C overnight. The suspension was centrifuged, the precipitate was collected, and washed with acetone. The obtained wet product was dried in a vacuum oven at 25 °C for 72 hours to give 583.32 mg of powder with a yield of 83.37%.

[1119] The resulting solid was Compound 1 p-aminosalicylate (Form A). The ratio of Compound 1 : 4-aminosalicylic acid in Compound 1 p-aminosalicylate (Form A) was determined to be 1 : 1.03 by ion chromatography. XPRD is shown in Figure 120; DSC and TGA are shown in Figure 121; and DVS is shown in Figure 122.

[1120] by 1 H-NMR analysis of Compound 1 p-aminosalicylate (Form A) gave the following chemical shifts: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.51 - 0.80 (m, 7 H) 0.83 - 1.74 (m, 22 H) 1.97 - 2.15 (m, 3 H) 2.34 (s, 1 H) 2.68 (br t, J=8.69 Hz, 1 H) 2.99 - 3.09 (m, 2 H) 3.25 (s, 4 H) 4.83 - 5.10 (m, 2 H) 5.88 - 6.11 (m, 3 H) 6.76 (t, J=8.19 Hz, 1 H) 6.90 (s, 1 H) 7.04 (s, 1 H) 7.42 (d, J=8.63 Hz, 1 H) 7.57 (s, 1 H).

[1121] Chemical and physical stability testing

[1122] Chemical and physical stability testing was performed using the procedure shown in Example 1. The following table shows the results of the chemical and physical stability testing of Compound 1 aminosalicylate (Form A) and Compound 1 free base:

[1123]

[1124]

[1125] Dissolution testing in simulated gastric and intestinal fluids

[1126] Dissolution testing in simulated gastric and intestinal fluids was performed using the procedure shown in Example 1. The following table shows the results of the dissolution of Compound 1 aminosalicylate (Form A) and Compound 1 free base in biorelevant solutions (mg / mL):

[1127]

[1128] Compound 1 aminosalicylate (Form B):

[1129] Into a 2 mL vial was weighed 50 mg of Compound 1 and 1.1 equivalents of the counterion of 4-aminosalicylic acid in solid form, respectively, followed by the addition of 1 mL of solvent EtOAc / ACN to the vial. The vial was placed on a hot mixer with a stir bar and heated to 50 °C. After 21 hours at 50 °C under constant stirring at 500 rpm, the vial was cooled to 25 °C. After 1 hour at 25 °C, the solid in suspension was separated by centrifugation and dried in a vacuum oven at 30 °C for 18 hours.

[1130] The dried solid was characterized by PLM and XRPD (Figure 123).

[1131] Example 25: Preparation of the maleate salt of Compound 1

[1132] The following exemplary method can be used to prepare the maleate salt of Compound 1 from Compound 1.

[1133] Compound 1 maleate (form A):

[1134] about 50 mg of Compound 1 and 1.1 molar equivalents of the acid were placed in a 2 mL vial. About 1 mL of solvent was added to the vial. The vial was placed on a hot mixer 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 monitored for the formation of a solid in the vial. After about an hour of stirring, no experiments provided a solid. For each experiment, the solvent was evaporated in a vacuum oven at 30 °C. Under these conditions, none of the acids listed in the above table provided an isolatable salt of Compound 1.

[1135] The dried solid obtained was characterized by PLM and XRPD (Figure 124).

[1136] Example 26: Attempts to prepare salts of Compound 1

[1137] The following acids formed non-crystalline salts under some conditions:

[1138] acid solvent Maleic acid Ethyl acetate; IPA / water (95:5 V:V) L-malic acid IPA / Water (95:5 V:V) Succinic acid Acetone; ACN; IPA / water (95:5 V:V) Naphthalene-2-sulfonic acid IPA / Water (95:5 V:V) ascorbic acid IPA / Water (95:5 V:V) salicylic acid Acetone; ACN; IPA / water (95:5 V:V) lactic acid acetone 2-Hydroxyethanesulfonic acid Acetone, Ethyl Acetate D-mandelic acid Acetone; ACN; IPA / water (95:5 V:V) Cyclopyralid IPA / Water (95:5 V:V) dichloroacetic acid Ethyl acetate; ACN; IPA / water (95:5 V:V)

[1139] While multiple conditions were attempted (shown below), the acids in the following table did not provide isolatable salts of Compound 1.

[1140]

[1141]

[1142] Experimental Conditions: For each of the twenty acids listed in the above table, the following procedure was used to determine if an isolatable salt of Compound 1 was provided by a particular solvent-acid combination.

[1143] about 50 mg of Compound 1 and 1.1 molar equivalents of the acid were placed in a 2 mL vial. About 1 mL of solvent was added to the vial. The vial was placed on a hot mixer 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 monitored for the formation of a solid in the vial. After about an hour of stirring, no experiments provided a solid. For each experiment, the solvent was evaporated in a vacuum oven at 30 °C. Under these conditions, none of the acids listed in the above table provided an isolatable salt of Compound 1.

[1144] Example 27. Properties of salts of Compound 1

[1145] The bulk density, tapped density, Carr Index, and Hausner Ratio of Compound 1 citrate (Form A); Compound 1 phosphate (Form A); Compound 1 tartrate (Form A); Compound 1 HBr (Form A); and Compound 1 free base (Form A) were determined. The results are shown in the table below.

[1146]

[1147]

[1148] Among the forms tested, the physical properties of Compound 1 citrate (Form A) are most suitable for the preparation of solid pharmaceutical dosage forms (e.g., tablets) and for the economical storage of the active pharmaceutical ingredient (API) (i.e., because of its high bulk density).

[1149] Compressibility is an important property of an API, and generally, an API with higher compressibility is more easily compressed into a tablet than an API with lower compressibility. The Carr Index is an indicator of the compressibility of a powder, with a low Carr Index indicating that the powder has good compressibility and a high Carr Index indicating that the powder has poor compressibility. The Carr Index of Compound 1 citrate (Form A) is much lower than the Carr Index of the other polymorphs tested, indicating that the compressibility is best among the forms tested.

[1150] The flowability of an API is important in many pharmaceutical operations, such as mixing with excipients, tablet compression, capsule filling, and scale-up of production. The Hausner Ratio is an indicator of the flowability of a powder. A high Hausner Ratio indicates that the powder has poor flowability, and a low Hausner Ratio indicates that the flowability is good. The Hausner Ratio of Compound 1 citrate (Form A) is much lower than the Hausner Ratio of the other polymorphs tested, indicating that the flowability is best among the forms tested.

[1151] Manufacturability of citrate (Form A): Compound 1 citrate (Form A) has excellent manufacturability and has been prepared on a kilogram scale (Example 2). The large-scale synthesis utilizes pharmaceutically acceptable solvents and does not require seeding with Compound 1 citrate (Form A).

[1152] Stability of citrate (Form A): Compound 1 citrate (Form A) is stable for at least 3 months under high temperature and high humidity conditions (see Example 2), which is ideal for an API.

[1153] Manufacturability of HBr (Form A): Compound 1 HBr (Form A) has excellent manufacturability and has been prepared on a kilogram scale (Example 1). The large-scale synthesis utilizes pharmaceutically acceptable solvents and does not require seeding with Compound 1 HBr (Form A).

[1154] INCORPORATION BY REFERENCE

[1155] All references, articles, publications, patents, patent publications, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate material came from a reference, article, publication, patent, patent publication, or patent application cited herein by virtue of prior application.

[1156] Implementation Plan

[1157] 1. A crystalline Form A of the citrate salt of Compound 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising three or more peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 11.9 ± 0.2, 17.1 ± 0.2, 20.1 ± 0.2, and 20.3 ± 0.2, using copper K-alpha radiation.

[1158] 2. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 11.9 ± 0.2, and 17.1 ± 0.2, using copper K-alpha radiation.

[1159] 3. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 11.9 ± 0.2, and 20.1 ± 0.2, using copper K-alpha radiation.

[1160] 4. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 11.9 ± 0.2, and 20.3 ± 0.2, using copper K-alpha radiation.

[1161] 5. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 17.1 ± 0.2, and 20.1 ± 0.2, using copper K-alpha radiation.

[1162] 6. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks, in degrees two-theta, at approximately 5.7 ± 0.2, 17.1 ± 0.2, and 20.3 ± 0.2, using copper K-alpha radiation.

[1163] 7. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 5.7 ± 0.2, 20.1 ± 0.2, and 20.3 ± 0.2 °2Θ using copper K-alpha radiation.

[1164] 8. The crystalline Form A of the citrate salt of embodiment 1, wherein the 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 °2Θ using copper K-alpha radiation.

[1165] 9. The crystalline Form A of the citrate salt of embodiment 1, wherein the 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 °2Θ using copper K-alpha radiation.

[1166] 10. The crystalline Form A of the citrate salt of embodiment 1, wherein the 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 °2Θ using copper K-alpha radiation.

[1167] 11. The crystalline Form A of the citrate salt of embodiment 1, wherein the Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising peaks at about 17.1 ± 0.2, 20.1 ± 0.2, and 20.3 ± 0.2 °2Θ using copper K-alpha radiation.

[1168] 12. The crystalline Form A of the citrate salt of embodiment 1, wherein the 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 °2Θ using copper K-alpha radiation.

[1169] 13. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1170] 14. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1171] 15. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1172] 16. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1173] 17. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1174] 18. The crystalline Form A of the citrate salt of embodiment 12, wherein the 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 °2Θ using copper K-alpha radiation.

[1175] 19. The crystalline Form A of the citrate salt of any of the preceding embodiments, further comprising one or more peaks, e.g., two or more peaks, e.g., three or more peaks, e.g., four or more peaks, e.g., 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 °2Θ using copper K-alpha radiation.

[1176] 20. The crystalline Form A of the citrate salt of any of embodiments 1-18, further comprising an additional peak at about 12.7 ± 0.2 °2Θ using copper K-alpha radiation.

[1177] 21. The crystalline Form A of the citrate salt of any of embodiments 1-18 and 20, further comprising an additional peak at about 13.0 ± 0.2 °2Θ using copper K-alpha radiation.

[1178] 22. The crystalline Form A of the citrate salt of any of embodiments 1-18, 20, and 21, further comprising an additional peak at about 13.6 ± 0.2 °2Θ using copper K-alpha radiation.

[1179] 23. The crystalline Form A of the citrate salt of any of embodiments 1-18 and 20-22, further comprising an additional peak at about 15.3 ± 0.2 °2Θ using copper K-alpha radiation.

[1180] 24. The crystalline Form A of citrate of any one of embodiments 1-18 and 20-23, further comprising an additional peak at about 16.8 ± 0.2° 2Θ using copper K-alpha radiation.

[1181] 25. The crystalline Form A of citrate of any one of the preceding embodiments, wherein the XRPD pattern is substantially as observed in FIG. 15.

[1182] 26. The crystalline Form A of citrate of any one of the preceding embodiments, which Form A has substantially similar unit cell parameters at 120 K as

[1183]

[1184]

[1185]

[1186]

[1187] α = 73.7°

[1188] β = 76.6°

[1189] γ = 83.2°

[1190] space group PI,

[1191] molecules / asymmetric unit 2.

[1192] 27. The crystalline Form A of citrate of embodiment 26, wherein the Form A has unit cell parameters at 120 K as follows:

[1193]

[1194]

[1195]

[1196] α = 73.7 ± 2°

[1197] β = 76.6 ± 2°

[1198] γ = 83.2 ± 2°

[1199] space group PI,

[1200] molecules / asymmetric unit 2.

[1201] 28. The crystalline Form A of citrate of embodiment 27, wherein the Form A has unit cell parameters at 120 K as follows:

[1202] ​

[1203]

[1204]

[1205] a = 73.7 ± 1°

[1206] b = 76.6 ± 1°

[1207] g = 83.2 ± 1°

[1208] Space group PI,

[1209] Molecules / asymmetric unit 2.

[1210] 29. The crystalline Form A of citrate of Embodiment 28, wherein the Form A has the unit cell parameters at 120 K:

[1211]

[1212]

[1213]

[1214] a = 73.7 ± 0.5°

[1215] b = 76.6 ± 0.5°

[1216] g = 83.2 ± 0.5°

[1217] Space group PI,

[1218] Molecules / asymmetric unit 2.

[1219] 30. The crystalline Form A of citrate of any of the preceding embodiments, 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.

[1220] 31. The crystalline Form A of citrate of any of the preceding embodiments, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 89.0 ± 2.0 °C.

[1221] 32. The crystalline Form A of citrate of any of the preceding embodiments, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 139.5 ± 2.0 °C.

[1222] 33. A pharmaceutical composition comprising the citrate of any of the preceding embodiments and a pharmaceutically acceptable carrier.

[1223] 34. The pharmaceutical composition of embodiment 33, wherein the composition is a tablet.

[1224] 35. A hydrobromide salt of compound 1.

[1225] 36. The hydrobromide salt of embodiment 35, wherein at least about 80% by weight of the salt is crystalline.

[1226] 37. The hydrobromide salt of embodiment 35, wherein at least about 80% by weight of the salt is in single crystal form.

[1227] 38. The hydrobromide salt of embodiment 35, wherein at least about 95% by weight of the salt is crystalline.

[1228] 39. The hydrobromide salt of embodiment 35, wherein at least about 95% by weight of the salt is in single crystal form.

[1229] 40. The hydrobromide salt of any one of embodiments 36-39, wherein the crystalline form is Form A.

[1230] 41. The hydrobromide salt of embodiment 40, wherein the Form A exhibits an X-ray powder diffraction pattern with 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 °2Θ.

[1231] 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 °2Θ.

[1232] 43. The hydrobromide salt of embodiment 40, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to Figure 2.

[1233] 44. The hydrobromide salt of any one of embodiments 40-43, wherein the Form A exhibits a differential scanning calorimetry thermogram with a peak at about 243.1 ± 2.0 °C.

[1234] 45. The hydrobromide salt of any one of embodiments 40-43, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to Figure 3.

[1235] 46. The hydrobromide salt of any one of embodiments 40-43, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to Figure 3.

[1236] 47. The hydrobromide salt of any one of embodiments 36-39, wherein the crystalline form is Form E.

[1237] 48. The hydrobromide salt of embodiment 47, wherein the 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 °2Θ.

[1238] 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 °2Θ.

[1239] 50. The hydrobromide salt of embodiment 47, wherein the Form E exhibits an X- ray powder diffraction pattern substantially similar to FIG. 13.

[1240] 51. The hydrobromide salt of any one of embodiments 47-50, wherein the Form E exhibits a differential scanning calorimetry thermogram having a peak at about 245.0 ± 2.0 °C.

[1241] 52. The hydrobromide salt of any one of embodiments 47-50, wherein the Form E exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 14.

[1242] 53. The hydrobromide salt of any one of embodiments 47-50, wherein the Form E exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 14.

[1243] 54. A citrate salt of Compound 1.

[1244] 55. The hydrobromide salt of embodiment 54, wherein at least about 80% by weight of the salt is crystalline.

[1245] 56. The hydrobromide salt of embodiment 54, wherein at least about 80% by weight of the salt is in single crystal form.

[1246] 57. The hydrobromide salt of embodiment 54, wherein at least about 95% by weight of the salt is crystalline.

[1247] 58. The hydrobromide salt of embodiment 54, wherein at least about 95% by weight of the salt is in crystalline form.

[1248] 59. The citrate salt of any one of embodiments 55-58, wherein the crystalline form is Form A.

[1249] 60. The citrate salt of embodiment 59, wherein the 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 °2Θ.

[1250] 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 °2Θ.

[1251] 62. The citrate salt of embodiment 59, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to FIG. 15.

[1252] 63. The citrate salt of any one of embodiments 59-62, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 89.0 ± 2.0 °C or at about 139.5 ± 2.0 °C.

[1253] 64. The citrate salt of any one of embodiments 59-63, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 16.

[1254] 65. The citrate salt of any one of embodiments 59-63, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 16.

[1255] 66. An L-malate salt of Compound 1.

[1256] 67. The L-malate salt of embodiment 66, wherein at least about 80% by weight of the salt is crystalline.

[1257] 68. The L-malate salt of embodiment 66, wherein at least about 80% by weight of the salt is in a single crystalline form.

[1258] 69. The L-malate salt of embodiment 66, wherein at least about 95% by weight of the salt is crystalline.

[1259] 70. The L-malate salt of embodiment 66, wherein at least about 95% by weight of the salt is in a single crystalline form.

[1260] 71. The L-malate salt of any one of embodiments 67-70, wherein the crystalline form is Form A.

[1261] 72. The L-malate salt of embodiment 71, wherein the Form A exhibits an X-ray powder diffraction pattern of 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 °2Θ.

[1262] 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 °29.

[1263] 74. The L-malate salt of embodiment 73, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to FIG. 97.

[1264] 75. The L-malate salt of any one of embodiments 71-74, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 120.9 ± 2.0 °C or at about 142.3 ± 2.0 °C.

[1265] 76. The L-malate salt of any one of embodiments 71-75, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 98.

[1266] 77. The L-malate salt of any one of embodiments 71-76, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 98.

[1267] 78. A mesylate salt of Compound 1.

[1268] 79. The mesylate salt of embodiment 78, wherein at least about 80% by weight of the salt is crystalline.

[1269] 80. The mesylate salt of embodiment 78, wherein at least about 80% by weight of the salt is in single crystal form.

[1270] 81. The mesylate salt of embodiment 78, wherein at least about 95% by weight of the salt is crystalline.

[1271] 82. The mesylate salt of embodiment 78, wherein at least about 95% by weight of the salt is in single crystal form.

[1272] 83. The mesylate salt of any one of embodiments 79-82, wherein the crystalline form is Form A.

[1273] 84. The mesylate salt of embodiment 83, wherein the Form A exhibits an X-ray powder diffraction pattern of 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 °29.

[1274] 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 °29.

[1275] 86. The mesylate salt of embodiment 83, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to FIG. 22.

[1276] 87. The mesylate salt of any one of embodiments 83-86, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 170.9 ± 2.0 °C or at about 209.7 ± 2.0 °C.

[1277] 88. The mesylate salt of any one of embodiments 83-87, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 23.

[1278] 89. The mesylate salt of any one of embodiments 83-88, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 23.

[1279] 90. An L(+)-tartrate salt of Compound 1.

[1280] 91. The L(+)-tartrate salt of embodiment 90, wherein at least about 80% by weight of the salt is crystalline.

[1281] 92. The L(+)-tartrate salt of embodiment 90, wherein at least about 80% by weight of the salt is in a single crystalline form.

[1282] 93. The L(+)-tartrate salt of embodiment 90, wherein at least about 95% by weight of the salt is crystalline.

[1283] 94. The L(+)-tartrate salt of embodiment 90, wherein at least about 95% by weight of the salt is in a single crystalline form.

[1284] 95. The L(+)-tartrate salt of any one of embodiments 91-94, wherein the crystalline form is Form A.

[1285] 96. The L(+)-tartrate salt of embodiment 95, wherein the 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 °2Θ.

[1286] 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 °2Θ.

[1287] 98. The L(+)-tartrate salt of embodiment 95, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to FIG. 30.

[1288] 99. The L(+)-tartrate salt of any one of embodiments 95-98, wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak at about 207.6 ± 2.0 °C.

[1289] 100. The L(+)-tartrate salt of any one of embodiments 95-99, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 31.

[1290] 101. The L(+)-tartrate salt of any one of embodiments 95-100, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 31.

[1291] 102. The L(+)-tartrate salt of any one of embodiments 91-94, wherein the crystalline form is Form B.

[1292] 103. The L(+)-tartrate salt of embodiment 102, wherein the Form B exhibits an X-ray powder diffraction pattern with 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 °2Θ.

[1293] 104. The L(+)-tartrate salt of embodiment 103, wherein the X-ray powder diffraction pattern further comprises three or more peaks at about 14.8 ± 0.2, 18.3 ± 0.2, and 18.5 ± 0.2 °2Θ.

[1294] 105. The L(+)-tartrate salt of embodiment 103, wherein the Form B exhibits an X-ray powder diffraction pattern substantially similar to FIG. 33.

[1295] 106. The L(+)-tartrate salt of any one of embodiments 102-105, wherein the Form B exhibits a differential scanning calorimetry thermogram having a peak at about 207.3 ± 2.0 °C.

[1296] 107. The L(+)-tartrate salt of any one of embodiments 102-106, wherein the Form B exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 34.

[1297] 108. The L(+)-tartrate salt of any one of embodiments 102-107, wherein the Form B exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 34.

[1298] 109. A phosphate salt of Compound 1.

[1299] 110. The phosphate salt of embodiment 109, wherein at least about 80% by weight of the salt is crystalline.

[1300] 111. The phosphate salt of embodiment 109, wherein at least about 80% by weight of the salt is in single crystal form.

[1301] 112. The phosphate salt of embodiment 109, wherein at least about 95% by weight of the salt is crystalline.

[1302] 113. The phosphate salt of embodiment 109, wherein at least about 95% by weight of the salt is in single crystal form.

[1303] 114. The phosphate salt of any one of embodiments 110-113, wherein the crystalline form is Form A.

[1304] 115. The phosphate salt of embodiment 114, wherein the Form A exhibits an X-ray powder diffraction pattern with 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 °2Θ.

[1305] 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 °2Θ.

[1306] 117. The phosphate salt of embodiment 114, wherein the Form A exhibits an X-ray powder diffraction pattern substantially similar to FIG. 27.

[1307] 118. The phosphate salt of any one of embodiments 114-117, wherein the Form A exhibits a differential scanning calorimetry thermogram with a peak at about 217.6 ± 2.0 °C.

[1308] 119. The phosphate salt of any one of embodiments 114-118, wherein the Form A exhibits a differential scanning calorimetry thermogram substantially similar to FIG. 28.

[1309] 120. The L(+)-tartrate salt of any one of embodiments 114-119, wherein the Form A exhibits a thermogravimetric analysis thermogram substantially similar to FIG. 28.

[1310] 121. A pharmaceutical composition comprising the salt of any one of embodiments 35-120 and a pharmaceutically acceptable carrier.

[1311] 122. The pharmaceutical composition of embodiment 121, wherein the composition is a tablet.

[1312] 123. A method of 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.

[1313] 124. The method of embodiment 123, wherein the depression is selected from major depressive disorder, postpartum depression, and treatment-resistant depression.

[1314] 125. A method of treating a disease or condition selected from epilepsy, bipolar disorder, and anxiety comprising administering to a patient in need thereof an 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.

Claims

1. A crystalline Form A of a citrate salt of 3a-hydroxy-3b-methoxymethyl-21-(1'- imidazolyl)-5a-pregnan-20-one, 3a-hydroxy-3b-methoxymethyl-21-(1'- imidazolyl)-5a-pregnan-20-one having the formula ###0001### wherein said Form A exhibits an X-ray powder diffraction pattern using copper K-alpha radiation comprising peaks at 5.7 ± 0.2, 12.5 ± 0.2, 20.1 ± 0.2, 11.9 ± 0.2, 12.7 ± 0.2, 13.0 ± 0.2, 13.6 ± 0.2, 15.3 ± 0.2, 16.8 ± 0.2, 17.1 ± 0.2, 20.3 ± 0.2, 25.8 ± 0.2 degrees two-theta.

2. The crystalline Form A of a citrate salt according to claim 1, said Form A having unit cell parameters at 120 K substantially similar to the following: γ = 83.2° α＝73.7° β＝76.6° space group PI, molecules / asymmetric unit 2.

3. The crystalline Form A of a citrate salt according to claim 2, wherein said Form A has unit cell parameters at 120 K as follows: γ = 83.2 ± 2° α＝73.7±2° β＝76.6±2° space group PI, molecules / asymmetric unit 2.

4. The crystalline Form A of a citrate salt according to claim 3, wherein said Form A has unit cell parameters at 120 K as follows: γ = 83.2 ± 1° α＝73.7±1° β＝76.6±1° space group PI, molecules / asymmetric unit 2.

5. The crystalline Form A of a citrate salt according to claim 4, wherein said Form A has unit cell parameters at 120 K as follows: γ = 83.2 ± 0.5° α＝73.7±0.5° β＝76.6±0.5° space group PI, molecules / asymmetric unit 2.

6. The crystalline Form A of a citrate salt according to claim 1, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak at 89.0 ± 2.0 °C or 139.5 ± 2.0 °C.

7. The crystalline Form A of a citrate salt according to claim 1, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak at 89.0 ± 2.0 °C.

8. The crystalline Form A of a citrate salt according to claim 1, wherein said Form A exhibits a differential scanning calorimetry thermogram having a peak at 139.5 ± 2.0 °C.

9. A pharmaceutical composition comprising the crystalline Form A of a citrate salt according to any one of claims 1-8 and a pharmaceutically acceptable carrier.

10. The pharmaceutical composition according to claim 9, wherein the composition is a tablet.

11. Use of a pharmaceutical composition comprising the crystalline Form A of a citrate salt according to any one of claims 1-8 and a pharmaceutically acceptable carrier for the manufacture of a medicament for the treatment of a disease or disorder selected from the group consisting of depression, epilepsy, bipolar disorder, and anxiety.

12. A crystalline Form A of a citrate salt of 3a-hydroxy-3b-methoxymethyl-21-(1'- imidazolyl)-5a-pregnan-20-one, 3a-hydroxy-3b-methoxymethyl-21-(1'- imidazolyl)-5a-pregnan-20-one having the formula ###0002### ​ The X-ray powder diffraction pattern thereof is substantially as observed in Figure 15.

13. A crystalline Form A of the citrate salt of 3α-hydroxy-3β-methoxymethyl-21-(1'- imidazolyl)-5α-pregnan-20-one, 3α-hydroxy-3β-methoxymethyl-21-(1'- imidazolyl)-5α-pregnan-20-one having the formula wherein said Form A exhibits an X-ray powder diffraction pattern using copper K-alpha radiation comprising the peaks at °2Θ

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