Crystalline lysine acetyltransferase 6A (KAT6A) inhibitors and their use

Abstract

This specification describes the crystalline form of the small molecule lysine acetyltransferase 6A (KAT6A) inhibitor: Compound 1, as well as its pharmaceutical composition and methods of use in the treatment of diseases or conditions for which treatment with the lysine acetyltransferase 6A (KAT6A) inhibitor is beneficial. [Formula 1] JPEG2026516755000035.jpg4268

Description

[Technical Field]

[0001] cross reference This patent application claims the rights of International Application No. PCT / CN2023 / 090649, filed on 25 April 2023, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Lysine acetyltransferase 6A (KAT6A) belongs to the MYST family of acetyltransferases and was first discovered about 25 years ago. KAT6A regulates fundamental cellular processes, including gene transcription, cellular senescence, cardiac septum development, memory T-cell diversity, and the maintenance of normal hematopoietic stem cells. Dysregulation of KAT6A acetyltransferase activity or aberrant expression of KAT6A is associated with oncogenic function in many cancers, including leukemia, glioblastoma, endometrial serous carcinoma, and breast cancer. Therefore, compounds that inhibit KAT6A are potential agents for treating various cancers, particularly those in stable crystalline form. [Overview of the project]

[0003] This specification includes 2,4-dimethoxy-N-(4-methoxy-6-(thiazole-2-yloxy)benzo[d]isoxazole-3-yl)-6-methylpyridine-3-sulfonamide:

[0004] [ka] Alternatively, a solid form of a pharmaceutically acceptable salt thereof is disclosed.

[0005] In some embodiments, the solid form is crystalline.

[0006] In some embodiments, the solid form is crystalline compound 1 freeform type A, crystalline compound 1 freeform type C, crystalline compound 1 freeform type D, crystalline compound 1 freeform type E, or crystalline compound 1 freeform type F.

[0007] In some embodiments, the solid form is the free form type B of crystalline compound 1.

[0008] In some embodiments, the solid form is in the form of a salt.

[0009] In some embodiments, the solid form is sodium, potassium, ammonium, or choline salt.

[0010] In some embodiments, the solid form is in the form of an L-arginine salt. [Brief explanation of the drawing]

[0011] The features of the present invention are described in detail in the appended claims. A better understanding of the features of the present invention will be obtained by referring to the following detailed description, which includes exemplary embodiments in which the principles of the present invention are utilized, and to the accompanying drawings. [Figure 1] This shows the X-ray powder diffraction (XRPD) pattern of the free form of amorphous compound 1. [Figure 2] The X-ray powder diffraction (XRPD) pattern of compound 1 in its free form type A is shown. [Figure 3]The differential scanning calorimetry (DSC) thermogram of the free form type A of compound 1 is shown. [Figure 4] The thermogravimetric analysis (TGA) thermogram of the free form type A of compound 1 is shown. [Figure 5] The X-ray powder diffraction (XRPD) pattern of the free form type B of compound 1 is shown. [Figure 6] The differential scanning calorimetry (DSC) thermogram of the free form type B of compound 1 is shown. [Figure 7] The thermogravimetric analysis (TGA) thermogram of the free form type B of compound 1 is shown. [Figure 8] The dynamic vapor sorption (DVS) plot of the free form type B of compound 1 is shown. [Figure 9] The X-ray powder diffraction (XRPD) pattern of the free form type C of compound 1 is shown. [Figure 10] The differential scanning calorimetry (DSC) thermogram of the free form type C of compound 1 is shown. [Figure 11] The thermogravimetric analysis (TGA) thermogram of the free form type C of compound 1 is shown. [Figure 12] The X-ray powder diffraction (XRPD) pattern of the free form type D of compound 1 is shown. [Figure 13] The differential scanning calorimetry (DSC) thermogram of the free form type D of compound 1 is shown. [Figure 14] The thermogravimetric analysis (TGA) thermogram of the free form type D of compound 1 is shown. [Figure 15] The X-ray powder diffraction (XRPD) pattern of the free form type E of compound 1 is shown. [Figure 16] The differential scanning calorimetry (DSC) thermogram of the free form type E of compound 1 is shown. S [Figure 17] The thermogravimetric analysis (TGA) thermogram of the free form type E of compound 1 is shown. [Figure 18]The X-ray powder diffraction (XRPD) pattern of compound 1 in its free form type F is shown. [Figure 19] The differential scanning calorimetry (DSC) thermogram of compound 1 in its free form type F is shown. [Figure 20] The thermogravimetric analysis (TGA) thermogram of compound 1 in its free form type F is shown. [Figure 21] The X-ray powder diffraction (XRPD) pattern of type A sodium salt of compound 1 is shown. [Figure 22] The differential scanning calorimetry (DSC) thermogram of type A sodium salt of compound 1 is shown. [Figure 23] The thermogravimetric analysis (TGA) thermogram of type A sodium salt of compound 1 is shown. [Figure 24] The X-ray powder diffraction (XRPD) pattern of type B sodium salt of compound 1 is shown. [Figure 25] The X-ray powder diffraction (XRPD) pattern of the sodium salt type C of compound 1 is shown. [Figure 26] The differential scanning calorimetry (DSC) thermogram of type C sodium salt of compound 1 is shown. [Figure 27] The thermogravimetric analysis (TGA) thermogram of the sodium salt type C of compound 1 is shown. [Figure 28] The X-ray powder diffraction (XRPD) pattern of the sodium salt type D of compound 1 is shown. [Figure 29] The differential scanning calorimetry (DSC) thermogram of type D sodium salt of compound 1 is shown. [Figure 30] The thermogravimetric analysis (TGA) thermogram of type D sodium salt of compound 1 is shown. [Figure 31] The X-ray powder diffraction (XRPD) pattern of potassium salt type A of compound 1 is shown. [Figure 32] The differential scanning calorimetry (DSC) thermogram of potassium salt type A of compound 1 is shown. [Figure 33] The thermogravimetric analysis (TGA) thermogram of potassium salt type A of compound 1 is shown. [Figure 34]This shows the X-ray powder diffraction (XRPD) pattern of ammonium salt type A. [Figure 35] The differential scanning calorimetry (DSC) thermogram of compound 1's ammonium salt type A is shown. [Figure 36] The thermogravimetric analysis (TGA) thermogram of ammonium salt type A of compound 1 is shown. [Figure 37] The X-ray powder diffraction (XRPD) pattern of ammonium salt type B of compound 1 is shown. [Figure 38] The differential scanning calorimetry (DSC) thermogram of compound 1's ammonium salt type B is shown. [Figure 39] The thermogravimetric analysis (TGA) thermogram of ammonium salt type B of compound 1 is shown. [Figure 40] The X-ray powder diffraction (XRPD) pattern of ammonium salt type C of compound 1 is shown. [Figure 41] The differential scanning calorimetry (DSC) thermogram of ammonium salt type C is shown. [Figure 42] The thermogravimetric analysis (TGA) thermogram of ammonium salt type C of compound 1 is shown. [Figure 43] The X-ray powder diffraction (XRPD) pattern of type A of the L-arginine salt of compound 1 is shown. [Figure 44] The differential scanning calorimetry (DSC) thermogram of L-arginine salt type A is shown. [Figure 45] The thermogravimetric analysis (TGA) thermogram of L-arginine salt type A of compound 1 is shown. [Figure 46] This shows the X-ray powder diffraction (XRPD) pattern of type A choline salt of compound 1. [Figure 47] The differential scanning calorimetry (DSC) thermogram of type A choline salt of compound 1 is shown. [Figure 48] The thermogravimetric analysis (TGA) thermogram of type A choline salt of compound 1 is shown. Detailed description of the invention

[0012] While small molecule inhibitors are often first evaluated for their activity when dissolved in solution, solid-state characteristics such as polymorphism are also important. Polymorphic forms of a drug substance can have different physical properties, including melting point, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density. These properties can directly affect the ability to process or manufacture the drug substance and drug product. Furthermore, differences in these properties can, and often, lead to different pharmacokinetic profiles for different polymorphic forms of a drug. Therefore, polymorphism is often a crucial factor in regulatory reviews of the "sameness" of drugs from various manufacturers.

[0013] compound 1 Compound 1 is 2,4-dimethoxy-N-(4-methoxy-6-(thiazole-2-yloxy)benzo[d]isoxazole-3-yl)-6-methylpyridine-3-sulfonamide:

[0014] [ka] In some embodiments, compound 1 is in its free form. In some embodiments, compound 1 is in the form of a pharmaceutically acceptable salt. In some embodiments, compound 1 is in the form of a sodium salt. In some embodiments, compound 1 is in the form of a potassium salt. In some embodiments, compound 1 is in the form of an ammonium salt. In some embodiments, compound 1 is in the form of a choline salt. In some embodiments, compound 1 is in the form of an L-arginine salt. In some embodiments, compound 1 is in the form of a co-crystal. In some embodiments, compound 1 is in the amorphous form. In some embodiments, compound 1 is in the non-ionized form. In some embodiments, the free form of compound 1 is in the non-ionized form.

[0015] Solid form of compound 1 In one embodiment, 2,4-dimethoxy-N-(4-methoxy-6-(thiazole-2-yloxy)benzo[d]isoxazole-3-yl)-6-methylpyridine-3-sulfonamide:

[0016] [ka] A solid form of the pharmaceutically acceptable salt thereof is provided herein.

[0017] In some embodiments, the solid state is crystalline.

[0018] In some embodiments, the solid form is the free form of crystalline compound 1. In some embodiments, the solid form is free form type A of crystalline compound 1, free form type B of crystalline compound 1, or free form type D of crystalline compound 1. In some embodiments, the solid form is free form type A of crystalline compound 1. In some embodiments, the solid form is free form type B of crystalline compound 1. In some embodiments, the solid form is free form type C of crystalline compound 1. In some embodiments, the solid form is free form type D of crystalline compound 1. In some embodiments, the solid form is free form type E of crystalline compound 1. In some embodiments, the solid form is free form type F of crystalline compound 1.

[0019] In some embodiments, the solid form is free form type A of crystalline compound 1, free form type C of compound 1, free form type D of compound 1, free form type E of compound 1, or free form type F of compound 1.

[0020] To avoid misunderstanding, the term “crystalline form” is used throughout this specification to include any crystalline form comprising any one of the following forms: free form (types A, B, C, D, E, or F), sodium salt (types A, B, C, or D), potassium salt (type A), ammonium salt (types A, B, or C), L-arginine salt (type A), and choline salt (type A).

[0021] Free form type A of compound 1 This specification discloses the free form type A of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using CuKα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 2. (b) X-ray powder diffraction (XRPD) patterns with peaks at 8.0±0.2°2θ, 12.9±0.2°2θ, and 21.0±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 3, or (d) A thermogravimetric analysis (TGA) thermogram substantially identical to that shown in Figure 4, (e) these combinations This is a free form type A of compound 1, characterized by having at least one of the following:

[0022] In some embodiments of the free form type A of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 2 when measured using Cu Kα radiation.

[0023] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks as shown in Table 1 when measured using Cu Kα radiation.

[0024] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.0±0.2°2θ, 12.9±0.2°2θ, and 21.0±0.2°2θ, as measured using Cu Kα radiation.

[0025] In some embodiments of the free form type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.9±0.2°2θ, 11.3±0.2°2θ, and 18.5±0.2°2θ.

[0026] In some embodiments of the free form type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 21.9±0.2°²θ, 22.6±0.2°²θ, and 25.4±0.2°²θ.

[0027] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ, when measured using Cu Kα radiation.

[0028] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ when measured using Cu Kα radiation.

[0029] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ, when measured using Cu Kα radiation.

[0030] In some embodiments of the free form type A of compound 1, when measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ.

[0031] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ, when measured using Cu Kα radiation.

[0032] In some embodiments of the free form type A of compound 1, when measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ.

[0033] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ, when measured using Cu Kα radiation.

[0034] In some embodiments of the free form type A of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.3±0.2°2θ, 12.9±0.2°2θ, 18.5±0.2°2θ, 21.0±0.2°2θ, 21.9±0.2°2θ, 22.6±0.2°2θ, and 25.4±0.2°2θ, when measured using Cu Kα radiation.

[0035] In some embodiments of the free form type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 3.

[0036] In some embodiments of the free form type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 4.

[0037] [Table 1]

[0038] Free form type B of compound 1 This specification discloses the free form type B of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 5. (b) X-ray powder diffraction (XRPD) patterns with peaks at 12.8±0.2°2θ, 21.6±0.2°2θ, and 24.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 6, (d) Differential scanning calorimetry (DSC) thermogram showing an endothermic peak with a peak temperature of approximately 173.1°C. (e) A thermogravimetric analysis (TGA) thermogram substantially identical to that shown in Figure 7, (f) A thermogravimetric analysis (TGA) thermogram showing a mass loss of approximately 1.29% from the start of heating to approximately 150°C, or (g) combinations of these This is a free form type B of compound 1, characterized by having at least one of the following:

[0039] In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 12.8±0.2°2θ, 21.6±0.2°2θ, and 24.7±0.2°2θ. (b) Differential scanning calorimetry (DSC) thermogram showing an endothermic peak with a peak temperature of approximately 173.1°C. (c) A thermogravimetric analysis (TGA) thermogram showing a mass loss of approximately 1.29% from the start of heating up to approximately 150°C, or (d) combinations of these This is a free form type B of compound 1, characterized by having at least one of the following:

[0040] In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 5. (b) X-ray powder diffraction (XRPD) patterns with peaks at 12.8±0.2°2θ, 21.6±0.2°2θ, and 24.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 6, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 7, or (e) these combinations This is a free form type B of compound 1, characterized by having at least one of the following:

[0041] In some embodiments of the free form type B of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 5 when measured using Cu Kα radiation.

[0042] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 2 when measured using Cu Kα radiation.

[0043] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 12.8±0.2°²θ, 21.6±0.2°²θ, and 24.7±0.2°²θ when measured using Cu Kα radiation.

[0044] In some embodiments of the free form type B of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 12.0±0.2°2θ, 14.5±0.2°2θ, and 22.7±0.2°2θ.

[0045] In some embodiments of the free form type B of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 5.4±0.2°²θ, 23.0±0.2°²θ, and 27.0±0.2°²θ.

[0046] In some embodiments of the free form type B of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 22.1±0.2°²θ and 25.1±0.2°²θ.

[0047] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ, when measured using Cu Kα radiation.

[0048] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0049] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0050] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0051] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0052] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0053] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ, when measured using Cu Kα radiation.

[0054] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0055] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least nine peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

[0056] In some embodiments of the free form type B of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least 10 peaks selected from 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ, when measured using Cu Kα radiation.

[0057] In some embodiments of the free form type B of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 6.

[0058] In some embodiments of the free form type B of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 173.1°C.

[0059] In some embodiments of the free form type B of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 7.

[0060] In some embodiments of the free form type B of compound 1, the thermogravimetric analysis (TGA) thermogram shows a mass loss of approximately 1.29% from the start of heating to approximately 150°C. In some embodiments of the free form type B of compound 1, the thermogravimetric analysis (TGA) thermogram shows a mass loss of less than 1.5% from the start of heating to approximately 150°C. In some embodiments of the free form type B of compound 1, the thermogravimetric analysis (TGA) thermogram shows a mass loss of less than 2% from the start of heating to approximately 150°C.

[0061] In some embodiments of the free form type B of compound 1, the crystalline form is non-hygroscopic.

[0062] In some embodiments of the free form type B of compound 1, the crystalline form is anhydrous (anhydrate).

[0063] In some embodiments of the free form type B of compound 1, a water uptake of 0.0679% was detected at 80% RH / 25°C in the sorption curve from 0% relative humidity (RH) to 95% RH. In some embodiments of the free form type B of compound 1, water uptakes of less than 0.1%, less than 0.2%, less than 0.5%, less than 0.8%, less than 1%, or less than 2% were detected at 80% RH / 25°C in the sorption curve from 0% relative humidity (RH) to 95% RH. In some embodiments of the free form type B of compound 1, a water uptake of less than 0.1% was detected at 80% RH / 25°C in the sorption curve from 0% relative humidity (RH) to 95% RH.

[0064] [Table 2]

[0065] Free form type C of compound 1 This specification discloses the free form type C of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 9. (b) X-ray powder diffraction (XRPD) patterns with peaks at 11.3±0.2°2θ, 16.5±0.2°2θ, and 20.9±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 10. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 11, or (e) these combinations This is a free form type C of compound 1, characterized by having at least one of the following:

[0066] In some embodiments of the free form type C of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 9 when measured using Cu Kα radiation.

[0067] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 3 when measured using Cu Kα radiation.

[0068] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.3±0.2°2θ, 16.5±0.2°2θ, and 20.9±0.2°2θ when measured using Cu Kα radiation.

[0069] In some embodiments of the free form type C of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 15.4±0.2°²θ, 20.3±0.2°²θ, 21.7±0.2°²θ, and 26.9±0.2°²θ.

[0070] In some embodiments of the free form type C of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 7.7±0.2°²θ and 23.4±0.2°²θ.

[0071] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0072] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0073] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0074] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0075] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0076] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0077] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0078] In some embodiments of the free form type C of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 7.7±0.2°2θ, 11.3±0.2°2θ, 15.4±0.2°2θ, 16.5±0.2°2θ, 20.3±0.2°2θ, 20.9±0.2°2θ, 21.7±0.2°2θ, 23.4±0.2°2θ, and 26.9±0.2°2θ when measured using Cu Kα radiation.

[0079] In some embodiments of the free form type C of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 10.

[0080] In some embodiments of the free form type C of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 11.

[0081] [Table 3]

[0082] Free form type D of compound 1 This specification discloses the free form type D of compound 1. In some embodiments, the crystalline form has the following properties: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 12. (b) X-ray powder diffraction (XRPD) patterns with peaks at 7.5±0.2°2θ, 15.1±0.2°2θ, and 20.5±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 13. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 14, or (e) these combinations Compound 1 is a free form type D characterized by having at least one of the following.

[0083] In some embodiments of the free form type D of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 12 when measured using Cu Kα radiation.

[0084] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 4 when measured using Cu Kα radiation.

[0085] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.5±0.2°2θ, 15.1±0.2°2θ, and 20.5±0.2°2θ when measured using Cu Kα radiation.

[0086] In some embodiments of the free form type D of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 11.3±0.2°²θ, 16.5±0.2°²θ, and 21.5±0.2°²θ.

[0087] In some embodiments of the free form type D of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 23.3±0.2°²θ and 26.5±0.2°²θ.

[0088] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0089] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ when measured using Cu Kα radiation.

[0090] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ when measured using Cu Kα radiation.

[0091] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ when measured using Cu Kα radiation.

[0092] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0093] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0094] In some embodiments of the free form type D of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 7.5±0.2°2θ, 11.3±0.2°2θ, 15.1±0.2°2θ, 16.5±0.2°2θ, 20.5±0.2°2θ, 21.5±0.2°2θ, 23.3±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0095] In some embodiments of the free form type D of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 13.

[0096] In some embodiments of the free form type D of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 14.

[0097] [Table 4]

[0098] Free form type E of compound 1 This specification discloses the free form type E of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 15. (b) X-ray powder diffraction (XRPD) patterns with peaks at 11.5±0.2°2θ, 17.9±0.2°2θ, and 20.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 16. (d) Differential scanning calorimetry (DSC) thermogram showing an endothermic peak with a peak temperature of approximately 101.0°C. (e) Differential scanning calorimetry (DSC) thermogram having an endothermic peak with a peak temperature of approximately 109.6°C. (f) Differential scanning calorimetry (DSC) thermogram showing an exothermic peak with a peak temperature of approximately 173.4°C. (g) A thermogravimetric analysis (TGA) thermogram substantially identical to that shown in Figure 17, (h) A thermogravimetric analysis (TGA) thermogram showing a mass loss of approximately 16.63% from the start of heating to approximately 150°C, or (i) combinations of these This is a free form type E of compound 1, characterized by having at least one of the following:

[0099] In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 11.5±0.2°2θ, 17.9±0.2°2θ, and 20.7±0.2°2θ. (b) Differential scanning calorimetry (DSC) thermogram showing an endothermic peak with a peak temperature of approximately 101.0°C. (c) Differential scanning calorimetry (DSC) thermogram showing an endothermic peak with a peak temperature of approximately 109.6°C. (d) Differential scanning calorimetry (DSC) thermogram showing an exothermic peak with a peak temperature of approximately 173.4°C. (e) A thermogravimetric analysis (TGA) thermogram showing a mass loss of approximately 16.63% from the start of heating to approximately 150°C, or (f) combinations of these This is a free form type E of compound 1, characterized by having at least one of the following:

[0100] In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 15. (b) X-ray powder diffraction (XRPD) patterns with peaks at 11.5±0.2°2θ, 17.9±0.2°2θ, and 20.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 16. (d) A thermogravimetric analysis (TGA) thermogram substantially identical to that shown in Figure 17, or (e) these combinations This is a free form type E of compound 1, characterized by having at least one of the following.

[0101] In some embodiments of the free form type E of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 15 when measured using Cu Kα radiation.

[0102] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 5 when measured using Cu Kα radiation.

[0103] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.5±0.2°2θ, 17.9±0.2°2θ, and 20.7±0.2°2θ when measured using Cu Kα radiation.

[0104] In some embodiments of the free form type E of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.5±0.2°²θ, 12.9±0.2°²θ, and 21.9±0.2°²θ.

[0105] In some embodiments of the free form type E of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 19.8±0.2°²θ, 23.8±0.2°²θ, and 26.5±0.2°²θ.

[0106] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ when measured using Cu Kα radiation.

[0107] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using CuK emission.

[0108] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0109] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0110] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0111] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0112] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0113] In some embodiments of the free form type E of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.5±0.2°2θ, 11.5±0.2°2θ, 12.9±0.2°2θ, 17.9±0.2°2θ, 19.8±0.2°2θ, 20.7±0.2°2θ, 21.9±0.2°2θ, 23.8±0.2°2θ, and 26.5±0.2°2θ, when measured using Cu Kα radiation.

[0114] In some embodiments of the free form type E of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 16.

[0115] In some embodiments of the free form type E of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 101.0°C.

[0116] In some embodiments of the free form type E of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 109.6°C.

[0117] In some embodiments of the free form type E of compound 1, differential scanning calorimetry (DSC) thermograms show an exothermic peak with a peak temperature of approximately 173.4°C.

[0118] In some embodiments of the free form type E of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 17.

[0119] In some embodiments of the free form type E of compound 1, thermogravimetric analysis (TGA) thermograms show a mass loss of approximately 16.63% from the start of heating up to approximately 150°C.

[0120] [Table 5]

[0121] Free form type F of compound 1 This specification discloses free form type F of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 18. (b) X-ray powder diffraction (XRPD) patterns with peaks at 8.0±0.2°2θ, 18.3±0.2°2θ, and 25.1±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 19. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 20, or (e) these combinations This is a free form type F of compound 1, characterized by having at least one of the following:

[0122] In some embodiments of the free form type F of compound 1, the crystalline form has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 18 when measured using Cu Kα radiation.

[0123] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 6 when measured using Cu Kα radiation.

[0124] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.0±0.2°²θ, 18.3±0.2°²θ, and 25.1±0.2°²θ when measured using Cu Kα radiation.

[0125] In some embodiments of the free form type F of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 11.2±0.2°2θ, 21.0±0.2°2θ, and 25.8±0.2°2θ.

[0126] In some embodiments of the free form type F of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.9±0.2°2θ, 12.9±0.2°2θ, and 22.5±0.2°2θ.

[0127] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ when measured using Cu Kα radiation.

[0128] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0129] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0130] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0131] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0132] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0133] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0134] In some embodiments of the free form type F of compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.9±0.2°2θ, 8.0±0.2°2θ, 11.2±0.2°2θ, 12.9±0.2°2θ, 18.3±0.2°2θ, 21.0±0.2°2θ, 22.5±0.2°2θ, 25.1±0.2°2θ, and 25.8±0.2°2θ, when measured using Cu Kα radiation.

[0135] In some embodiments of the free form type F of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 19.

[0136] In some embodiments of the free form type F of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 20.

[0137] [Table 6]

[0138] Sodium salt type A of compound 1 This specification discloses the sodium salt type A of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 21. (b) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 9.2±0.2°2θ, 17.8±0.2°2θ, and 24.6±0.2°2θ. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 22. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 23, or (e) these combinations This is a sodium salt type A of compound 1, characterized by having at least one of the following:

[0139] In some embodiments of the sodium salt type A of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 21 when measured using Cu Kα radiation.

[0140] In some embodiments of the sodium salt type A of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 7 when measured using Cu Kα radiation.

[0141] In some embodiments of the sodium salt type A of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 9.2±0.2°²θ, 17.8±0.2°²θ, and 24.6±0.2°²θ, as measured using Cu Kα radiation.

[0142] In some embodiments of the sodium salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 11.1±0.2°²θ, 21.8±0.2°²θ, and 25.9±0.2°²θ.

[0143] In some embodiments of the sodium salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 20.6±0.2°²θ, 25.2±0.2°²θ, and 26.9±0.2°²θ.

[0144] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0145] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0146] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0147] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0148] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0149] In some embodiments of the sodium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0150] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0151] In some embodiments of type A of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 9.2±0.2°2θ, 11.1±0.2°2θ, 17.8±0.2°2θ, 20.6±0.2°2θ, 21.8±0.2°2θ, 24.6±0.2°2θ, 25.2±0.2°2θ, 25.9±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0152] In some embodiments of the sodium salt type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 22.

[0153] In some embodiments of the sodium salt type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 23.

[0154] [Table 7]

[0155] Sodium salt type B of compound 1 This specification discloses type B of the sodium salt of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 24. (b) X-ray powder diffraction (XRPD) patterns with peaks at 8.7±0.2°2θ, 17.4±0.2°2θ, and 22.7±0.2°2θ when measured using Cu Kα radiation, or (c) These combinations This is a sodium salt type B of compound 1, characterized by having at least one of the following:

[0156] In some embodiments of the sodium salt type B of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 24 when measured using Cu Kα radiation.

[0157] In some embodiments of the sodium salt type B of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 8 when measured using Cu Kα radiation.

[0158] In some embodiments of the sodium salt type B of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 8.7±0.2°²θ, 17.4±0.2°²θ, and 22.7±0.2°²θ, as measured using Cu Kα radiation.

[0159] In some embodiments of the sodium salt type B of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 5.3±0.2°²θ, 12.0±0.2°²θ, and 21.5±0.2°²θ.

[0160] In some embodiments of the sodium salt type B of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 14.5±0.2°²θ and 24.6±0.2°²θ.

[0161] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0162] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0163] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0164] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0165] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0166] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0167] In some embodiments of type B of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 5.3±0.2°2θ, 8.7±0.2°2θ, 12.0±0.2°2θ, 14.5±0.2°2θ, 17.4±0.2°2θ, 21.5±0.2°2θ, 22.7±0.2°2θ, and 24.6±0.2°2θ, when measured using Cu Kα radiation.

[0168] [Table 8]

[0169] Sodium salt type C of compound 1 This specification discloses the sodium salt type C of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 25. (b) X-ray powder diffraction (XRPD) patterns with peaks at 8.2±0.2°2θ, 15.4±0.2°2θ, and 21.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 26. (d) A thermogravimetric analysis (TGA) thermogram substantially identical to that shown in Figure 27, or (e) combinations of these. This is a sodium salt type C of compound 1, characterized by having at least one of the following:

[0170] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 25 when measured using Cu Kα radiation.

[0171] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 9 when measured using Cu Kα radiation.

[0172] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 8.2±0.2°²θ, 15.4±0.2°²θ, and 21.7±0.2°²θ, as measured using Cu Kα radiation.

[0173] In some embodiments of type C of the sodium salt of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 10.5±0.2°²θ, 17.5±0.2°²θ, and 24.8±0.2°²θ.

[0174] In some embodiments of type C of the sodium salt of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 5.4±0.2°²θ, 26.6±0.2°²θ, 30.2±0.2°²θ, and 31.1±0.2°²θ.

[0175] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0176] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0177] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0178] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0179] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0180] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0181] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0182] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0183] In some embodiments of type C of the sodium salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least nine peaks selected from 5.4±0.2°2θ, 8.2±0.2°2θ, 10.5±0.2°2θ, 15.4±0.2°2θ, 17.5±0.2°2θ, 21.7±0.2°2θ, 24.8±0.2°2θ, 26.6±0.2°2θ, 30.2±0.2°2θ, and 31.1±0.2°2θ, when measured using Cu Kα radiation.

[0184] In some embodiments of type C of the sodium salt of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 26.

[0185] In some embodiments of type C of the sodium salt of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 27.

[0186] [Table 9]

[0187] Sodium salt type D of compound 1 This specification discloses the sodium salt type D of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 28. (b) X-ray powder diffraction (XRPD) patterns with peaks at 9.3±0.2°2θ, 19.1±0.2°2θ, and 22.6±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 29. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 30, or (e) these combinations This is a sodium salt type D of compound 1, characterized by having at least one of the following:

[0188] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 28 when measured using Cu Kα radiation.

[0189] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 10 when measured using Cu Kα radiation.

[0190] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 9.3±0.2°²θ, 19.1±0.2°²θ, and 22.6±0.2°²θ, as measured using Cu Kα radiation.

[0191] In some embodiments of the sodium salt type D of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 5.3±0.2°²θ, 16.0±0.2°²θ, and 21.3±0.2°²θ.

[0192] In some embodiments of the sodium salt type D of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 13.0±0.2°²θ, 14.8±0.2°²θ, and 26.2±0.2°²θ.

[0193] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0194] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0195] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0196] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0197] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0198] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0199] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0200] In some embodiments of the sodium salt type D of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 5.3±0.2°2θ, 9.3±0.2°2θ, 13.0±0.2°2θ, 14.8±0.2°2θ, 16.0±0.2°2θ, 19.1±0.2°2θ, 21.3±0.2°2θ, 22.6±0.2°2θ, and 26.2±0.2°2θ, when measured using Cu Kα radiation.

[0201] In some embodiments of the sodium salt type D of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 29.

[0202] In some embodiments of the sodium salt type D of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 30.

[0203] [Table 10]

[0204] Potassium salt type A of compound 1 This specification discloses potassium salt type A of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 31. (b) X-ray powder diffraction (XRPD) patterns with peaks at 6.3±0.2°2θ, 13.3±0.2°2θ, and 20.2±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 32. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 33, or (e) these combinations This is a potassium salt type A of compound 1, characterized by having at least one of the following:

[0205] In some embodiments of the potassium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern that is substantially the same as that shown in Figure 31 when measured using Cu Kα radiation.

[0206] In some embodiments of the potassium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks found in Table 11 when measured using Cu Kα radiation.

[0207] In some embodiments of the potassium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks at 6.3 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, and 20.2 ± 0.2° 2θ when measured using Cu Kα radiation.

[0208] In some embodiments of the potassium salt type A of Compound 1, the X-ray powder diffraction (XRPD) pattern further includes peaks at 12.7 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ when measured using Cu Kα radiation.

[0209] In some embodiments of the potassium salt type A of Compound 1, the X-ray powder diffraction (XRPD) pattern further includes peaks at 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, and 27.1 ± 0.2° 2θ when measured using Cu Kα radiation.

[0210] In some embodiments of the potassium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks at 6.3 ± 0.2° 2θ, 12.7 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ± 0.2° 2θ when measured using Cu Kα radiation.

[0211] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0212] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0213] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0214] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0215] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0216] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0217] In some embodiments of the potassium salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.3±0.2°2θ, 12.7±0.2°2θ, 13.3±0.2°2θ, 16.5±0.2°2θ, 18.8±0.2°2θ, 19.7±0.2°2θ, 20.2±0.2°2θ, 26.5±0.2°2θ, and 27.1±0.2°2θ, when measured using Cu Kα radiation.

[0218] In some embodiments of the potassium salt type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 32.

[0219] In some embodiments of the potassium salt type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 33.

[0220] [Table 11]

[0221] Ammonium salt type A of Compound 1 This specification discloses ammonium salt type A of Compound 1. In some embodiments, the crystalline form has the following characteristics: (a) An X-ray powder diffraction (XRPD) pattern substantially the same as that shown in Figure 34 when measured using Cu Kα radiation, (b) An X-ray powder diffraction (XRPD) pattern having peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, and 21.8 ± 0.2° 2θ when measured using Cu Kα radiation, (c) A differential scanning calorimetry (DSC) thermogram substantially the same as that shown in Figure 35, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 36, or (e) A combination of these Ammonium salt type A of Compound 1, characterized by having at least one of the above.

[0222] In some embodiments of ammonium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as that shown in Figure 34 when measured using Cu Kα radiation.

[0223] In some embodiments of ammonium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks as found in Table 12 when measured using Cu Kα radiation.

[0224] In some embodiments of ammonium salt type A of Compound 1, the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, and 21.8 ± 0.2° 2θ when measured using Cu Kα radiation.

[0225] In some embodiments of the ammonium salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.0±0.2°2θ, 16.2±0.2°2θ, and 18.2±0.2°2θ.

[0226] In some embodiments of compound 1's ammonium salt type A, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 20.9±0.2°²θ, 22.6±0.2°²θ, and 23.2±0.2°²θ.

[0227] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, as measured using Cu Kα radiation.

[0228] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0229] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0230] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0231] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0232] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0233] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0234] In some embodiments of compound 1's ammonium salt type A, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.0±0.2°2θ, 11.9±0.2°2θ, 16.2±0.2°2θ, 16.8±0.2°2θ, 18.2±0.2°2θ, 20.9±0.2°2θ, 21.8±0.2°2θ, 22.6±0.2°2θ, and 23.2±0.2°2θ, when measured using Cu Kα radiation.

[0235] In some embodiments of the ammonium salt type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 35.

[0236] In some embodiments of the ammonium salt type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 36.

[0237] [Table 12]

[0238] Ammonium salt type B of compound 1 This specification discloses ammonium salt type B of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 37. (b) X-ray powder diffraction (XRPD) patterns with peaks at 6.5±0.2°2θ, 14.7±0.2°2θ, and 26.1±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 38. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 39, or (e) these combinations Compound 1 is an ammonium salt type B characterized by having at least one of the following:

[0239] In some embodiments of the ammonium salt type B of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 37 when measured using Cu Kα radiation.

[0240] In some embodiments of compound 1's ammonium salt type B, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks as shown in Table 13, when measured using Cu Kα radiation.

[0241] In some embodiments of compound 1's ammonium salt type B, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 6.5±0.2°²θ, 14.7±0.2°²θ, and 26.1±0.2°²θ, as measured using Cu Kα radiation.

[0242] In some embodiments of compound 1's ammonium salt type B, the X-ray powder diffraction (XRPD) pattern further includes peaks at 13.0±0.2°²θ and 19.5±0.2°²θ when measured using Cu Kα radiation.

[0243] In some embodiments of compound 1's ammonium salt type B, the X-ray powder diffraction (XRPD) patterns, when measured using Cu Kα radiation, further include peaks at 18.1±0.2°²θ, 20.1±0.2°²θ, and 26.9±0.2°²θ.

[0244] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0245] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0246] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0247] In some embodiments of compound 1's ammonium salt type B, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0248] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0249] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0250] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0251] In some embodiments of ammonium salt type B of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.5±0.2°2θ, 13.0±0.2°2θ, 14.7±0.2°2θ, 18.1±0.2°2θ, 19.5±0.2°2θ, 20.1±0.2°2θ, 26.1±0.2°2θ, and 26.9±0.2°2θ, when measured using Cu Kα radiation.

[0252] In some embodiments of the ammonium salt type B of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 38.

[0253] In some embodiments of the ammonium salt type B of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 39.

[0254] [Table 13]

[0255] Ammonium salt type C of compound 1 This specification discloses ammonium salt type C of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 40. (b) X-ray powder diffraction (XRPD) patterns with peaks at 6.1±0.2°2θ, 15.6±0.2°2θ, and 24.4±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 41, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 42, or (e) combinations of these. Compound 1 is an ammonium salt type C characterized by having at least one of the following:

[0256] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 40 when measured using Cu Kα radiation.

[0257] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 14 when measured using Cu Kα radiation.

[0258] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 6.1±0.2°²θ, 15.6±0.2°²θ, and 24.4±0.2°²θ, as measured using Cu Kα radiation.

[0259] In some embodiments of the ammonium salt type C of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 13.0±0.2°²θ, 19.2±0.2°²θ, and 25.7±0.2°²θ.

[0260] In some embodiments of the ammonium salt type C of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 12.2±0.2°²θ, 14.0±0.2°²θ, and 22.1±0.2°²θ.

[0261] In some embodiments of compound 1's ammonium salt type C, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, as measured using Cu Kα radiation.

[0262] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0263] In some embodiments of compound 1's ammonium salt type C, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0264] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0265] In some embodiments of compound 1's ammonium salt type C, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0266] In some embodiments of compound 1's ammonium salt type C, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0267] In some embodiments of the ammonium salt type C of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0268] In some embodiments of compound 1's ammonium salt type C, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.1±0.2°2θ, 12.2±0.2°2θ, 13.0±0.2°2θ, 14.0±0.2°2θ, 15.6±0.2°2θ, 19.2±0.2°2θ, 22.1±0.2°2θ, 24.4±0.2°2θ, and 25.7±0.2°2θ, when measured using Cu Kα radiation.

[0269] In some embodiments of the ammonium salt type C of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 41.

[0270] In some embodiments of the ammonium salt type C of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 42.

[0271] [Table 14]

[0272] Compound 1L-Arginine Salt Type A This specification discloses compound 1 L-arginine salt type A. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 43. (b) X-ray powder diffraction (XRPD) patterns with peaks at 11.0±0.2°2θ, 13.7±0.2°2θ, and 18.6±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 44. (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 45, or (e) these combinations Compound 1 is a L-arginine salt type A characterized by having at least one of the following.

[0273] In some embodiments of the L-arginine salt type A of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as shown in Figure 43 when measured using Cu Kα radiation.

[0274] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 15 when measured using Cu Kα radiation.

[0275] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 11.0±0.2°²θ, 13.7±0.2°²θ, and 18.6±0.2°²θ, as measured using Cu Kα radiation.

[0276] In some embodiments of the L-arginine salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.1±0.2°²θ, 12.6±0.2°²θ, and 15.3±0.2°²θ.

[0277] In some embodiments of the L-arginine salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 19.6±0.2°²θ, 20.5±0.2°²θ, and 21.7±0.2°²θ.

[0278] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0279] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0280] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0281] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0282] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0283] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0284] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0285] In some embodiments of type A of the L-arginine salt of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ, when measured using Cu Kα radiation.

[0286] In some embodiments of the L-arginine salt type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 44.

[0287] In some embodiments of the L-arginine salt type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 45.

[0288] [Table 15]

[0289] Choline salt type A of compound 1 This specification discloses choline salt type A of compound 1. In some embodiments, the crystalline form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 46. (b) X-ray powder diffraction (XRPD) patterns with peaks at 11.4±0.2°2θ, 18.2±0.2°2θ, and 20.6±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 47, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 48, or (e) these combinations This is a choline salt type A of compound 1, characterized by having at least one of the following.

[0290] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 46 when measured using Cu Kα radiation.

[0291] In some embodiments of the choline salt type A of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks shown in Table 16 when measured using Cu Kα radiation.

[0292] In some embodiments of the choline salt type A of compound 1, the crystalline morphology exhibits an X-ray powder diffraction (XRPD) pattern with peaks at 11.4±0.2°²θ, 18.2±0.2°²θ, and 20.6±0.2°²θ, as measured using Cu Kα radiation.

[0293] In some embodiments of the choline salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 12.5±0.2°2θ, 19.2±0.2°2θ, and 24.0±0.2°2θ.

[0294] In some embodiments of the choline salt type A of compound 1, the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 5.3±0.2°²θ, 15.4±0.2°²θ, and 22.9±0.2°²θ.

[0295] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, as measured using Cu Kα radiation.

[0296] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least two peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0297] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least three peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0298] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least four peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0299] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least five peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0300] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least six peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0301] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least seven peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0302] In some embodiments of the choline salt type A of compound 1, the crystalline morphology has an X-ray powder diffraction (XRPD) pattern having at least eight peaks selected from 5.3±0.2°2θ, 11.4±0.2°2θ, 12.5±0.2°2θ, 15.4±0.2°2θ, 18.2±0.2°2θ, 19.2±0.2°2θ, 20.6±0.2°2θ, 22.9±0.2°2θ, and 24.0±0.2°2θ, when measured using Cu Kα radiation.

[0303] In some embodiments of the choline salt type A of compound 1, the differential scanning calorimetry (DSC) thermogram is substantially the same as that shown in Figure 47.

[0304] In some embodiments of the choline salt type A of compound 1, the thermogravimetric analysis (TGA) thermogram is substantially the same as that shown in Figure 48.

[0305] [Table 16]

[0306] Treatment method This specification discloses a method for treating a disease in which inhibition of KAT6A is beneficial, the method comprising the step of administering a crystalline form disclosed herein. In some embodiments, the crystalline form is the free form type B of compound 1. In some embodiments, the method comprises the step of administering a pharmaceutical composition comprising a crystalline form disclosed herein.

[0307] This specification discloses methods for treating diseases or disorders related to KAT6A, the methods comprising the step of administering to a subject the crystalline form disclosed herein. In some embodiments, the crystalline form is the free form type B of compound 1. In some embodiments, the methods comprise the step of administering a pharmaceutical composition comprising the crystalline form disclosed herein.

[0308] In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein. In some embodiments, the crystalline form is the free form type B of compound 1.

[0309] In some embodiments, the method for treating cancer in mammals requiring treatment comprises the step of administering to the mammal a crystalline form disclosed herein (for example, the crystalline form is the free form type B of compound 1), wherein the cancer is lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous melanoma or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, gastric cancer, hepatocellular carcinoma, colon cancer, breast cancer, endometrial cancer, cervical cancer, vaginal cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, hematological malignancies, chronic leukemia or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney cancer or ureteral cancer, renal cell carcinoma, renal pelvis cancer, neoplasms of the central nervous system The cancers are selected from (CNS) system (CNS), primary CNS lymphoma, spinal axial tumor, glioblastoma, brainstem glioblastoma, pituitary adenoma, or a combination of two or more of the aforementioned cancers. In some embodiments, the method is a method for treating breast cancer in a mammal that requires it, the method comprising the step of administering to the mammal a crystalline free form type B of compound 1.

[0310] In some embodiments, a method for treating a mammal requiring treatment for cancer, the method comprising the step of administering to the mammal a crystalline form disclosed herein (for example, the crystalline form is the free form type B of compound 1), where the cancer is ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC), non-small cell lung cancer (SCLC), melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), leukemia, lymphoma or multiple myeloma, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CLL) The cancers are selected from leukemia (CML) and non-Hodgkin lymphoma. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being ER-positive breast cancer. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being glioblastoma. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being non-small cell lung cancer (NSCLC). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being small cell lung cancer (SCLC).In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being melanoma. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being ovarian cancer. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being prostate cancer. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being pancreatic cancer. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being colorectal cancer (CRC). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being hepatocellular carcinoma (HCC). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being renal cell carcinoma (RCC). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being leukemia. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being lymphoma. In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being multiple myeloma.In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being acute lymphoblastic leukemia (ALL). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being acute myeloid leukemia (AML). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being chronic lymphocytic leukemia (CLL). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being chronic myeloid leukemia (CML). In some embodiments, the method is a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being non-Hodgkin lymphoma. In some embodiments, the crystalline form is the free form type B of compound 1. In some embodiments, the method is a method for treating ER-positive breast cancer in a mammal requiring treatment for ER-positive breast cancer, the method comprising the step of administering the crystalline free form type B of compound 1 to the mammal.

[0311] In some embodiments, the method is a method for treating cancer in mammals requiring treatment, comprising the step of administering to the mammal a crystalline form disclosed herein, wherein the cancer is a solid tumor having amplification or overexpression of KAT6A / 6B, or a leukemia or solid tumor having a KAT6A / 6B fusion protein arising from a chromosomal translocation. In some embodiments, the crystalline form is the free form type B of compound 1.

[0312] In some embodiments, the method is a method for treating cancer in a mammal requiring cancer treatment, comprising the step of administering to the mammal a crystalline form disclosed herein, wherein the cancer is a MYST-overexpressing cancer. In some embodiments, the method is a method for treating cancer in a mammal requiring cancer treatment, comprising the step of administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses one or more KATs of the MYST family. In some embodiments, the method is a method for treating cancer in a mammal requiring cancer treatment, comprising the step of administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses one or more KATs of the MYST family selected from TIP60, KAT6A, KAT6B, HBO1, and MOF. In some embodiments, the crystalline form is the free form type B of compound 1.

[0313] In some embodiments, the method provides a method for treating cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer being a bromodomain overexpressing cancer. In some embodiments, the method provides a method for treating bromodomain overexpressing cancer in a mammal requiring treatment, the method comprising the step of administering to the mammal a crystalline form disclosed herein, the cancer overexpressing one or more bromodomain proteins selected from BRD2, BRD3, BRD4, BRD7, BRD8, BRD9, BRDT, TAF1 / TAF1L, TFIID, SMARC2, and SMARC4. In some embodiments, the crystalline form is the free form type B of compound 1.

[0314] Administration In certain embodiments, compositions containing the compound(s) described herein are administered for prophylactic and / or therapeutic purposes. In certain therapeutic uses, the composition is administered to a patient already suffering from a disease or illness in an amount sufficient to cure or at least partially suppress at least one of the symptoms of the disease or illness. The effective dose for this use will vary depending on the severity and course of the disease or illness, previous treatments, the patient's health status, weight, and response to the drug, as well as the judgment of the physician administering the treatment. The therapeutically effective dose may be determined by methods including, but not limited to, dose-escalation and / or dose-ranging clinical trials.

[0315] For prophylactic use, compositions containing the compounds described herein are administered to patients who are susceptible to, or otherwise at risk of, a particular disease, disorder, or illness. Such amounts are defined as “prophylactically effective amounts or doses.” In this use, the exact amount will vary depending on the patient’s health condition, weight, etc. When used in patients, the effective amount for this use will vary depending on the severity and course of the disease, disorder, or illness, previous treatments, the patient’s health condition and response to the drug, and the judgment of the treating physician. In one embodiment, prophylactic treatment involves administering a pharmaceutical composition containing the compounds described herein or a pharmaceutically acceptable salt thereof to a mammal that has previously experienced at least one symptom or risk factor of the disease being treated and is currently in remission, in order to prevent the recovery of the disease or symptoms of the illness.

[0316] In certain embodiments where the patient's disease does not improve, the compound may, at the physician's discretion, be administered chronically, i.e., over a long period including throughout the patient's lifetime, to improve, or otherwise control or limit the symptoms of the patient's disease or illness.

[0317] Any of the embodiments described herein is a further embodiment in which the compound described herein, or a pharmaceutically acceptable salt thereof, is (a) administered systemically to a mammal and / or (b) administered orally to a mammal and / or (c) administered intravenously to a mammal and / or (d) administered by injection to a mammal and / or (e) administered topically to a mammal and / or (f) administered non-systemically or locally to a mammal.

[0318] Route of administration Appropriate routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ocular, pulmonary, transmucosal, transdermal, vaginal, ocular, nasal, and topical administration. Furthermore, as merely an example, parenteral delivery includes intramuscular, subcutaneous, intravenous, intrathecal injection, as well as intrathecal, direct ventricle, intraperitoneal, intralymphatic, and intranasal injection.

[0319] Pharmaceutical composition / formulation The compounds described herein are administered to subjects requiring them, in accordance with standard pharmacopoeias, either alone or in combination with pharmaceutically acceptable carriers, excipients, or diluents, in pharmaceutical compositions. In one embodiment, the compounds of the present invention may be administered to animals. The compounds may be administered orally or parenterally, including via intravenous, intramuscular, intraperitoneal, subcutaneous, rectal, and topical routes of administration.

[0320] In another embodiment, the Specified herein provides a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0321] Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate the processing of the active compound into a pharmaceutically usable preparation. The appropriate formulation varies depending on the chosen route of administration. Outlines of the pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999), and these documents are incorporated herein by reference with respect to such disclosures.

[0322] In some embodiments, pharmaceutically acceptable excipients are selected from carriers, binders, fillers, suspensions, flavorings, sweeteners, disintegrants, dispersants, surfactants, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, penetration enhancers, wetting agents, defoamers, antioxidants, preservatives, and any combination thereof.

[0323] The pharmaceutical compositions described herein are administered to a subject by an appropriate route of administration, including but not limited to oral, parenteral (e.g., intravenous, subcutaneous, intramuscular), intranasal, buccal, surface, rectal, or transdermal routes. The pharmaceutical formulations described herein include, but are not limited to, aqueous liquid dispersants, liquids, gels, syrups, elixirs, slurries, suspensions, self-emulsifying dispersants, solid solutions, liposome dispersants, aerosols, solid oral dosage forms, powders, immediate-release formulations, controlled-release formulations, rapid-release formulations, tablets, capsules, pills, powders, sugar-coated tablets, effervescent formulations, lyophilized formulations, delayed-release formulations, sustained-release formulations, pulsed-release formulations, multi-particle formulations, and mixed immediate and controlled-release formulations.

[0324] Pharmaceutical compositions comprising the compounds described herein, or pharmaceutically acceptable salts or solvates thereof, may be prepared in a conventional manner, such as by conventional mixing, dissolution, granulation, sugar-coated tablet preparation, powdering, emulsification, encapsulation, encapsulation, or compression processes, just as an example.

[0325] Pharmaceutical compositions for oral use are obtained by mixing one or more solid excipients with one or more compounds described herein, optionally grinding the resulting mixture, adding appropriate adjuvants as needed, and then processing the granular mixture to obtain a tablet or sugar-coated tablet core. Suitable excipients include fillers such as sugars including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, or others such as polyvinylpyrrolidone (PVP or povidone) or calcium phosphate. Disintegrants such as cross-linked croscarmellose sodium, polyvinylpyrrolidone, agar, or salts thereof such as alginic acid or sodium alginate are added as needed. In some embodiments, dyes or pigments are added to the coating agent of the tablet or sugar-coated tablet to identify or characterize combinations of different doses of the active compound.

[0326] Orally administered pharmaceutical compositions include push-fit capsules made of gelatin, and soft-seal capsules made of gelatin and a plasticizer such as glycerol or sorbitol. Push-fit capsules contain the active ingredient in a mixture with a filler such as lactose, a binder such as starch, and / or a lubricant such as talc or magnesium stearate, and optionally a stabilizer. In soft capsules, the active compound is dissolved or suspended in a suitable liquid such as fatty oil, liquid paraffin, or liquid polyethylene glycols. In some embodiments, a stabilizer is added.

[0327] Pharmaceutical compositions for parenteral use are formulated as infusions or injections. In some embodiments, a pharmaceutical composition suitable for injection or infusion comprises a sterile aqueous solution or dispersion or sterile powder containing a compound described herein or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the pharmaceutical composition comprises a liquid carrier. In some embodiments, the liquid carrier is a solvent or liquid dispersion medium comprising, for example, water, saline solution, ethanol, polyols (e.g., glycerol, propylene glycol, liquid polyethylene glycol, etc.), vegetable oils, non-toxic glyceryl esters, and any combination thereof. In some embodiments, the pharmaceutical composition further comprises an antiseptic to prevent microbial growth.

[0328] definition Unless otherwise stated, the following terms used in this application have the definitions given below. The use of the term “including,” as well as other forms such as “include,” “includes,” and “included,” is not limiting. Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described herein.

[0329] As used herein, the term “acceptable” with respect to a formulation, composition, or component means that it does not cause any lasting adverse effects on the overall health of the subject being treated.

[0330] The terms “administer,” “administering,” and “administration,” as used herein, refer to methods that may be used to enable the delivery of a compound or composition to a desired biological site of action. These methods include, but are not limited to, oral routes, intradural routes, parenteral injections (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, or infusion), topical administration, and rectal administration. Those skilled in the art will be familiar with the administration techniques that may be employed in conjunction with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

[0331] The terms “effective amount” or “therapeutic effective amount,” as used herein, refer to a sufficient amount of an agent or compound administered that will, to some extent, alleviate one or more symptoms of the disease or illness being treated. The results include reduction and / or mitigation of the signs, symptoms, or causes of the disease, or any other desired change in the biological system. For example, “effective amount” for therapeutic use is the amount of a composition containing the compound disclosed herein required to provide a clinically significant reduction in disease symptoms. The appropriate “effective” amount in any individual case may, at their discretion, be determined using techniques such as a dose escalation study.

[0332] The terms “enhance” or “enhancing,” as used herein, mean increasing or extending a desired effect in either potency or duration. Therefore, with respect to enhancing the effect of a therapeutic agent, “enhancing” refers to the ability to increase or extend the effect of another therapeutic agent on a system in either potency or duration. “Enhancing-effective amount,” as used herein, refers to an appropriate amount for enhancing the effect of another therapeutic agent in a desired system.

[0333] The terms “subject” or “patient” encompass mammals. Examples of mammals include, but are not limited to, any members of the experimental animals, including the Mammalian class: humans, non-human primates such as chimpanzees, as well as other apes and monkey species, farm animals such as cattle, horses, sheep, goats, and pigs, domestic animals such as rabbits, dogs, and cats, and rodents such as rats, mice, and guinea pigs. In one aspect, a mammal is a human.

[0334] The terms “treat,” “treating,” or “treatment,” as used herein, include reducing, improving, or alleviating at least one symptom of a disease or illness; preventing further symptoms; inhibiting a disease or illness, for example, stopping the onset of a disease or illness; relieving a disease or illness; causing regression of a disease or illness; relieving illness caused by a disease or illness; and stopping the symptoms of a disease or illness, preventively and / or therapeutically.

[0335] The term "about" means a statistically significant range of a value, such as a stated concentration range, time frame, molecular weight, particle size, temperature, or pH. Such a range may be within one order of magnitude, typically within 10%, more typically within 5%, and even more typically within 3% of the indicated value or range. In some cases, such a range may be within the experimental error typical of the standard method used to measure and / or determine a given value or range. The permissible variation encompassed by the term "about" depends on the particular system under consideration and will be readily apparent to those skilled in the art. Whenever a range is enumerated in this application, any integer within that range is also contemplated as an embodiment of the disclosure. Wherever words such as "about" are used, or whether they are used, in the context of the disclosure, they mean within 10%, appropriately within 5%, and especially within 1% of a given value or range.

[0336] When multiple diffraction patterns are available, particle statistics (PS) and / or preferred orientation (PO) can be evaluated. Consistency of relative intensity between XRPD patterns from multiple diffractometers indicates good orientation statistics. Alternatively, the observed XRPD pattern can be compared to a calculated XRPD pattern based on the single crystal structure, if available. Two-dimensional scattering patterns using area detectors can also be used to evaluate PS / PO. If both PS and PO effects are determined to be negligible, the XRPD pattern represents the powder average intensity of the sample, and prominent peaks can be identified as "representative peaks." Generally, the more data collected to determine representative peaks, the greater the confidence in the classification of those peaks.

[0337] Characteristic peaks are a subset of representative peaks, insofar as they exist, and are used to distinguish one crystalline polymorph from another (a polymorph that is a crystalline form with the same chemical composition). Characteristic peaks are determined by evaluating which representative peaks, if any, are present in one crystalline polymorph of a compound within a range of ±0.2°²θ compared to all other known crystalline polymorphs of that compound. Not all crystalline polymorphs of a compound necessarily have at least one characteristic peak.

[0338] The term "preferential orientation," as used herein, refers to an extreme case of the non-random distribution of crystallites in solid-state form. In XRPD, an ideal sample is homogeneous, and crystallites are randomly distributed within the bulk solid. In a truly random sample, each possible reflection from a given set of planes has an equal number of microcrystals contributing to it. However, this is not the case when the solid-state form is in a preferred orientation. Therefore, comparing the intensities of randomly oriented diffraction patterns with those of a preferred orientation can appear completely different. Quantitative analysis that relies on intensity ratios is greatly distorted by preferred orientation. Careful sample preparation is crucial to reduce the incidence of preferred orientation.

[0339] The term “substantially the same,” when used herein to refer to a figure, is intended to mean that the figure is considered to represent the type and kind of characteristic data that can be obtained by a person skilled in the art, taking into account deviations permissible in the art. Such deviations may be caused by factors relating to variations in sample size, sample preparation, the specific apparatus used, operation conditions, and other experimental conditions known in the art. For example, a person skilled in the art can understand that the endothermic onset temperature and peak temperature measured by differential scanning calorimetry (DSC) may vary significantly from experiment to experiment. For example, a person skilled in the art can easily identify whether two X-ray diffraction patterns or two DSC thermograms are substantially the same. In some embodiments, two X-ray diffraction patterns are considered substantially the same if their characteristic peaks do not vary by more than ±0.2°²-θ.

[0340] As used herein, salts of compound 1 include compounds in which the corresponding acid is in an ionized, non-ionized, associated, or unassociated form. In some embodiments, the corresponding acid is in an ionized and / or associated form. In some embodiments, the corresponding acid is in a non-ionized and / or unassociated form. Salts of compound 1 include forms such as mono-acids and di-acids of the salt.

[0341] Administration In certain embodiments, compositions containing the crystalline forms described herein are administered for prophylactic and / or therapeutic purposes. In certain therapeutic uses, the composition is administered to a patient already suffering from a disease or illness in an amount sufficient to cure or at least partially suppress at least one of the symptoms of the disease or illness. The effective dose for this use will vary depending on the severity and course of the disease or illness, previous treatments, the patient's health status, weight, and response to the drug, as well as the judgment of the physician administering the treatment. The therapeutically effective dose may be determined by methods including, but not limited to, dose escalation and / or dose-finding clinical trials, at the discretion of the physician administering the treatment.

[0342] In certain embodiments where the patient's disease does not improve, the compound may, at the physician's discretion, be administered chronically, i.e., over a long period including throughout the patient's lifetime, to improve, or otherwise control or limit the symptoms of the patient's disease or illness.

[0343] The amount of a given drug corresponding to such a quantity varies depending on factors such as the specific compound, the state and severity of the disease, and the identity of the subject or host requiring treatment (e.g., weight, sex). Nevertheless, it is determined according to the specific circumstances surrounding the case, including, for example, the specific drug administered, the route of administration, the disease being treated, and the subject or host being treated.

[0344] However, generally, doses used for adult human treatment typically range from 0.01 mg to 5000 mg per day. In one embodiment, doses used for adult human treatment range from approximately 1 mg to approximately 1000 mg per day. In one embodiment, the desired dose is conveniently presented as a single dose or as divided doses administered simultaneously or at appropriate intervals, for example, as subdoses two, three, four, or more times per day.

[0345] In one embodiment, the daily dose suitable for the crystalline form or pharmaceutically acceptable salt described herein is approximately 0.01 to approximately 50 mg / kg per body weight. In some embodiments, the daily dose, or the amount of active substance in the dosage form, is lower or higher than the range shown herein, based on many variables relating to the individual treatment regimen. In various embodiments, the daily dose and unit dose are modified according to a number of variables, including, but not limited to, the activity of the compound used, the disease or illness being treated, the mode of administration, the requirements of the individual subject, the severity of the disease or illness being treated, and the judgment of the practicing physician.

[0346] A further embodiment is that, in any of the embodiments described herein, an effective amount of the crystalline form or a pharmaceutically acceptable salt thereof is administered (a) systemically to a mammal and / or (b) orally to a mammal and / or (c) intravenously to a mammal and / or (d) by injection to a mammal and / or (e) topically to a mammal and / or (f) non-systemically or topically to a mammal.

[0347] Further embodiments of any of the above-described embodiments include a single dose of an effective amount of crystalline form disclosed herein, wherein (i) the compound is administered once daily, or (ii) the compound is administered to a mammal multiple times a day. [Examples]

[0348] The following examples are provided for illustrative purposes only and are not intended to limit the scope of the claims provided herein.

[0349] Example 1: Preparation of Type A free form of compound 1

[0350] [ka] Dibenzyl disulfide (29.3 g, 119 mmol) and L-ascorbic acid (5.24 g, 29.8 mmol) were added to a mixture of 1-1 (10.0 g, 59.5 mmol) in MeCN (100 mL). Isoamyl nitrite (25.8 g, 220 mmol) was then added to the reaction mixture at 0°C, and the reaction mixture was stirred at 25°C for 12 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography to obtain 1-2 (4.4 g, 27% yield) as a yellow oil. Lcms: 276.1 [M+H] + .

[0351] To a mixture of 1-2 (1.00 g, 3.63 mmol) in MeCN (20 mL), AcOH (2.5 mL), and water (5 mL), 1,3-dichloro-5,5-dimethylhydantoin (858 mg, 4.36 mmol) was added at -15°C. The reaction mixture was stirred at -15 to 25°C for 1 hour. Water (10 mL) was added to the mixture. The mixture was extracted with DCM (20 mL x 3). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography to obtain 1-3 (660 mg, 72% yield) as a white solid. Lcms: 251.9 [M+H] + .

[0352] To a solution of 1-4 (5 g, 32.2 mmol) in xylene (30 mL), 2-bromo-1,3-thiazole (15.9 g, 96.7 mmol), Josiphos SL-J009-1Pd G3 (0.9 g, 0.97 mmol), and K2CO3 (8.9 g, 64.4 mmol, 100 mesh) were added. The reaction mixture was stirred under N2 at 150°C for 48 hours. The mixture was filtered and concentrated. The resulting residue was purified by flash silica gel chromatography to obtain 1-5 (2.5 g, 32% yield) as a yellow solid. Lcms: 239.1 [M+H] + .

[0353] Sodium methanolate (2.49 g, 46.18 mmol) was added to a solution of 1-5 (11 g, 46.18 mmol) in THF (110 mL). The reaction mixture was stirred under N2 at room temperature for 1 hour. Water was added. The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and filtered. The residue was purified by flash silica gel chromatography to obtain 1-6 (8.6 g, yield 74%) as a yellow solid. Lcms: 251.1 [M+H] + .

[0354] To a solution of 1-6 (8.6 g, 34.37 mmol) in MeCN (90 mL) and H2O (10 mL), 1,1,3,3-tetramethylguanidine (23.75 g, 206.19 mmol) and N-hydroxyacetamide (7.74 g, 103.10 mmol) were added. The reaction mixture was stirred under N2 at 70°C for 6 hours. The mixture was concentrated. Water was added. The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and filtered. The residue was purified by flash silica gel chromatography to obtain 1-7 (4.8 g, 53%) as a white solid. Lcms: 264.1 [M + H] + .

[0355] To a solution of 1-7 (5 g, 19 mmol) in MeCN (50 mL), 1-3 (7.2 g, 28 mmol) was added. The mixture was stirred at 25°C for 1 hour. DMSO (150 mg, 1.9 mmol) and 3,5-lutidine (6.1 g, 57 mmol) were added. The reaction mixture was stirred at 25°C for 1.5 hours. The mixture was then concentrated. The resulting residue was first purified by flash silica gel chromatography to obtain a solid, which was then lyophilized (MeCN / H2O) to obtain compound 1 as a white solid. Samples of the white solid were taken for XRPD, DSC, TGA, 1H-NMR, and LCMS analysis. Lcms: 479.2[M+H] +. 1H NMR(400MHz,DMSO-d6)δ 10.13(s,1H),7.37-7.31(m,2H),7.26(d,J=1.6Hz,1H),6.89(d,J=1.6H z,1H),6.82(s,1H),3.89(s,3H),3.84(s,3H),3.82(s,3H)2.39(s,3H).

[0356] The XRPD pattern of the obtained solid is shown in Figure 2. The major peaks in the XRPD pattern and their related intensities are shown in Table 1. The DSC and TGA results are shown in Figures 3 and 4.

[0357] The inhibition of KAT6A enzyme activity by compound 1 was determined using a radiometric 384-well format assay. Ten-point serial dilutions of compound 1 were performed in DMSO, and then 200 nL of each were transferred to a 384-well assay plate using Echo(Labcyte). 10 μL of 2× enzyme solution (5 nM KAT6A (Active Motif)) in assay buffer (50 mM Tris-HCl pH 8.0, 50 mM KCl, 0.1 mM EDTA, 5% glycerol, 1 mM DTT) was dispensed into the assay plate, excluding the low control wells to which 10 μL of assay buffer had been transferred. After incubating the plate at room temperature for 15 minutes, 10 μL of 2×[ 3 [H]-acetyl coenzyme A (Ac-CoA) and substrate peptide mixed solution (500 nM (KAT6A) in assay buffer) 3The reaction was initiated by adding 1 / H-Ac-CoA (PerkinElmer) and 800nM (KAT6A) biotinylated H4(1-30) peptide (GL Biochem) to each well. The plate was incubated at room temperature for 60 minutes (KAT6A), and then the reaction was stopped by adding 10 μL of stop solution (cold Ac-CoA (Cayman) in 1× assay buffer). 25 μL of the reaction mixture from each well was transferred to a flashplate (PerkinElmer) and incubated at room temperature for a further 1 hour. The plate was read using Microbeta, and the inhibition percentage for each compound-treated well was calculated based on the formula inh% = (Max - sample) / (Max - Min) * 100, where Max is the signal from the high control well containing the enzyme and Min is the signal from the low control well containing only assay buffer. The inh% data was further fitted using XL-Fit to obtain the IC50 value using a 4-parameter logistic (4PL) sigmoid curve model. The IC50 of KAT6A for compound 1 is 5.9 nM.

[0358] The permeability of compound 1 was determined by a Caco-2 assay. Caco-2 cells purchased from ATCC were seeded at 1 × 10⁵ cells / cm² on a polyethylene membrane (PET) in a 96-well Corning Insert plate, and the medium was refreshed every 4-5 days from day 21 to day 28 to allow for confluent cell monolayer formation. The transport buffer used in this study was HBSS containing 10.0 mM HEPES at pH 7.40 ± 0.05. Compound 1 was tested bidirectionally and in duplicate at 2.00 μM. The final DMSO concentration was adjusted to less than 1%. The plates were incubated in a CO₂ incubator at 37 ± 1°C, 5% CO₂, and saturated humidity for 2 hours without shaking. All samples, after being mixed with acetonitrile containing an internal standard, were centrifuged at 3200 x g for 10 minutes. The concentrations of the test compound and control compound in the starting solution, donor solution, and receiver solution were quantified by LC-MS / MS using the analyte / internal standard peak area ratio. Following the transport assay, a Lucifer yellow rejection assay was applied to determine the integrity of the Caco-2 cell monolayer. The permeability results for compound 1 and PF-9363 are shown in the table below.

[0359] [Table 17] *PF-9363 has the following structure:

[0360] [ka] This is Example 98 in WO2020 / 254946 A1, which has the following characteristics.

[0361] Example 2: Preparation of Freeform Amorphous of Compound 1 400.2 mg of freeform Compound 1 Type A was dissolved in 5 mL of DCM and filtered through a 0.45 μm PTFE membrane. The clear solution was concentrated to dryness by rotary evaporation at 40 °C. A sample of the white solid was taken for XRPD. The XRPD pattern of the obtained solid is shown in Figure 1. This is the amorphous form of Compound (I).

[0362] Example 3: Alternative Preparation of Compound 1 Type A Approximately 20 mg of freeform amorphous of Compound 1 was weighed into a 20 mL glass vial and dissolved in ACN to obtain a clear solution (the suspension was filtered through a 0.45 μm PTFE membrane). The solution was magnetically stirred while adding water until a precipitate appeared. The obtained precipitate was isolated for XRPD analysis. The XRPD pattern was the same as that in Figure 2, and it was confirmed to be Compound 1 Type A.

[0363] Example 4: Preparation of Freeform Type B of Compound 1 Freeform Compound 1 Type A (50 mg) in MeOH (0.5 mL) was slurried at room temperature (RT) for 6 days to obtain freeform Type B of Compound 1. The solid was isolated by centrifugation and air dried at room temperature. Before characterization, samples were taken for XRPD, DSC, TGA, 1H-NMR, and DVS analysis.

[0364] The XRPD pattern is shown in Figure 5. The main peaks in the XRPD pattern and their relative intensities are shown in Table 2. The TGA curve in Figure 7 showed a weight loss of 1.29% up to 150 °C. The DSC curve in Figure 6 showed one endotherm at 173.1 °C (peak temperature). 1The 1H NMR spectrum did not show any apparent residual organic solvent. Based on limited TGA weight loss and pure (neat) DSC, the free form type B was inferred to be anhydrous. The DVS plot in Figure 8 shows that in the sorption curve from 0% relative humidity (RH) to 95% RH, a water absorption rate of 0.0679% was detected at RH80% / 25°C, indicating that the free form type B of free form compound 1 is non-hygroscopic.

[0365] Example 5: Preparation of type C of compound 1 Approximately 20 mg of the free amorphous form of compound 1 was weighed into a 20 mL glass vial and dissolved in 1,4-dioxane to obtain a clear solution (the suspension was filtered through a 0.45 μm PTFE membrane). The solution was magnetically stirred while adding water until a precipitate appeared. The resulting precipitate was subjected to XRPD, DSC, TGA, and 1 It was isolated for 1H NMR analysis.

[0366] The XRPD pattern of the obtained solid is shown in Figure 9. The major peaks in the XRPD pattern and their associated intensities are shown in Table 3. The DSC and TGA results are shown in Figures 10 and 11.

[0367] Example 6: Preparation of type D of compound 1 Approximately 20 mg of free amorphous form of compound 1 was weighed into a 20 mL glass vial and dissolved in 2-MeTHF to obtain a clear solution (the suspension was filtered through a 0.45 μm PTFE membrane). The solution was magnetically stirred while adding n-heptane until a precipitate appeared. The resulting precipitate was subjected to XRPD, DSC, TGA, and 1 It was isolated for 1H NMR analysis.

[0368] The XRPD pattern of the obtained solid is shown in Figure 12. The major peaks in the XRPD pattern and their associated intensities are shown in Table 4. The DSC and TGA results are shown in Figures 13 and 14.

[0369] Example 7: Preparation of type E of compound 1 Approximately 20 mg of free compound 1, type A, was dissolved in 0.5 mL of toluene in an HPLC vial at 50°C. After cooling to room temperature and evaporation at room temperature, a precipitate appeared. The resulting solid was isolated by centrifugation and subjected to XRPD, DSC, TGA, and 1 The sample was air-dried at room temperature for H-NMR analysis.

[0370] The XRPD pattern is shown in Figure 15. The major peaks in the XRPD pattern and their associated intensities are shown in Table 5. The TGA curve in Figure 16 showed a weight loss of 16.63% up to 150°C. The DSC curve in Figure 17 showed three endothermic peaks at 101.0°C, 109.6°C, and 173.4°C, and one exothermic peak at 104.0°C (peak temperature).

[0371] Example 8: Preparation of type F of compound 1 Approximately 20 mg of free compound 1, type A, was suspended in 0.5 mL of MEK. The suspension was stirred and subjected to a temperature cycle for 4 days. The temperature range was 50°C to 5°C. The temperature was first heated to 50°C at a rate of 4.5°C / min, then equilibrated for 2 hours, then cooled to 5°C at a rate of 0.1°C / min, and held isothermally at 5°C for 2 hours. The final step was cooling to 5°C at a rate of 0.1°C / min and held isothermally at 5°C. The resulting solid was isolated and subjected to XRPD, DSC, TGA, and 1 Air-dried for 1H NMR analysis.

[0372] The XRPD pattern of the obtained solid is shown in Figure 18. The major peaks in the XRPD pattern and their associated intensities are shown in Table 6. The DSC and TGA results are shown in Figures 19 and 20.

[0373] Example 9: Preparation of sodium salt type A of compound 1 Sodium salt type A was obtained by a 1-day -20°C slurry of free form type B and NaOH (1 equivalent) in acetone / H2O (19:1, v:v). The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0374] The XRPD pattern of the obtained solid is shown in Figure 21. The major peaks in the XRPD pattern and their associated intensities are shown in Table 7. The DSC and TGA results are shown in Figures 22 and 23.

[0375] Example 10: Preparation of sodium salt type B of compound 1 Sodium salt type B was obtained by a 3-day room-temperature slurry (3-day RT slurry) of free form type B and NaOH (1 equivalent) in SiO. XRPD overlay showed that a peak for free form type B was observed.

[0376] The XRPD pattern of the obtained solid is shown in Figure 24. The main peaks in the XRPD pattern and their associated intensities are shown in Table 8.

[0377] Example 11: Preparation of sodium salt type C of compound 1 Sodium salt type C was obtained at room temperature for 2 days via sodium salt type B and the free form of the slurry in SiO2, as well as NaOH (approximately 1 equivalent). The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0378] The XRPD pattern of the obtained solid is shown in Figure 25. The major peaks in the XRPD pattern and their associated intensities are shown in Table 9. The DSC and TGA results are shown in Figures 26 and 27.

[0379] Example 12: Preparation of sodium salt type D of compound 1 Sodium salt type D was obtained from a slurry of free form type B and NaOH (2 equivalents) in IPA at room temperature. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0380] The XRPD pattern of the obtained solid is shown in Figure 28. The main peaks in the XRPD pattern and their associated intensities are shown in Table 10. The DSC and TGA results are shown in Figures 29 and 30.

[0381] Example 13: Preparation of potassium salt type A of compound 1 Potassium salt type A was obtained by a slurry of free form type B and KOH (1 equivalent) in acetone / H2O (19:1, v:v) at room temperature for 3 days. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0382] The XRPD pattern of the obtained solid is shown in Figure 31. The major peaks in the XRPD pattern and their associated intensities are shown in Table 11. The DSC and TGA results are shown in Figures 32 and 33.

[0383] Example 14: Preparation of ammonium salt type A of compound 1 Ammonium salt type A was obtained by slurrying free form type B and ammonia (1 equivalent) in acetone / H2O (19:1, v:v) at room temperature for 3 days. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0384] The XRPD pattern of the obtained solid is shown in Figure 34. The major peaks in the XRPD pattern and their associated intensities are shown in Table 12. The DSC and TGA results are shown in Figures 35 and 36.

[0385] Example 15: Preparation of ammonium salt type B of compound 1 Ammonium salt type B was obtained from a slurry of free form type B and ammonia (1 equivalent) in HCl at room temperature for 3 days. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0386] The XRPD pattern of the obtained solid is shown in Figure 37. The main peaks in the XRPD pattern and their associated intensities are shown in Table 13. The DSC and TGA results are shown in Figures 38 and 39.

[0387] Example 16: Preparation of ammonium salt type C of compound 1 Ammonium salt type C was obtained from a slurry of free form type B and ammonia (1 equivalent) in IPA at room temperature for 3 days. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0388] The XRPD pattern of the obtained solid is shown in Figure 40. The major peaks in the XRPD pattern and their associated intensities are shown in Table 14. The DSC and TGA results are shown in Figures 41 and 42.

[0389] Example 17: Preparation of compound 1L-arginine salt type A L-arginine salt type A was obtained from a slurry of free form type B and arginine (1 equivalent) in acetone / H2O (19:1, v:v) at room temperature for 3 days. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0390] The XRPD pattern of the obtained solid is shown in Figure 43. The major peaks in the XRPD pattern and their associated intensities are shown in Table 15. The DSC and TGA results are shown in Figures 44 and 45.

[0391] Example 18: Preparation of choline salt type A of compound 1 Choline salt type A was obtained from a slurry of free form type B and choline (2 equivalents) in IPA at room temperature. The solid was isolated by centrifugation and vacuum-dried at room temperature before characterization.

[0392] The XRPD pattern of the obtained solid is shown in Figure 46. The major peaks in the XRPD pattern and their associated intensities are shown in Table 16. The DSC and TGA results are shown in Figures 47 and 48.

[0393] [Table 18]

[0394] Methods for analyzing free forms Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) TGA data was collected using a Discovery TGA 5500 from TA Instruments. DSC was performed using a Discovery DSC2500 from TA Instruments. The detailed parameters used are listed below.

[0395] [Table 19]

[0396] X-ray powder diffractometer (XRPD) For XRPD analysis, PANalytical Empyrean and X'Pert 3 An X-ray powder diffractometer was used. The XRPD parameters used are listed below.

[0397] [Table 20]

[0398] Dynamic water vapor sorption (DVS) DVS was measured using an SMS (Surface Measurement Systems) DVS Intrinsic. Relative humidity at 25°C was calibrated against the deliquescence points of LiCl, Mg(NO3)2, and KCl. The parameters for the DVS test are listed below.

[0399] [Table 21]

[0400] 1H-NMR Solution NMR was collected using a Bruker 400M NMR spectrometer with DMSO-d6 as the solvent. The detailed parameters used are listed below.

[0401] [Table 22]

[0402] High-performance liquid chromatography (HPLC) Using an Agilent 1260 equipped with a VWD detector, the detailed chromatography conditions are listed below.

[0403] [Table 23]

[0404] Methods of salt analysis Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) TGA data was collected using a Discovery TGA 5500 from TA Instruments. DSC was performed using a Discovery DSC2500 from TA Instruments. The detailed parameters used are listed below.

[0405] [Table 24]

[0406] X-ray powder diffractometer (XRPD) For XRPD analysis, PANalytical Empyrean and X'Pert 3 An X-ray powder diffractometer was used. The XRPD parameters used are listed below.

[0407] [Table 25]

[0408] Dynamic water vapor sorption (DVS) Dynamic water vapor sorption was performed using the ADVENTURE series DVS at 25°C under a nitrogen blow. Approximately 30 milligrams of material were used. The sample was analyzed using the following method. 0% relative humidity to 95% relative humidity, and in 10% increments (90% to 95% relative humidity, 5% relative humidity) 95% relative humidity to 0% relative humidity, and 10% relative humidity in increments of 95% to 90% relative humidity, and 5% relative humidity.

[0409] 1 H-NMR 1 ¹H NMR data were obtained using a Bruker 400M in DMSO-d6 solvent.

[0410] High-performance liquid chromatography (HPLC) Using an Agilent 1260 equipped with a VWD detector, the detailed chromatography conditions are listed below.

[0411] [Table 26]

[0412] IC analysis Using a Thermo Scientific® Dionex® Aquion® Ion Chromatography (IC) System 1100 equipped with a conductivity detector, the detailed chromatography conditions are listed below.

[0413] [Table 27]

Claims

1. 2,4-dimethoxy-N-(4-methoxy-6-(thiazole-2-yloxy)benzo[d]isoxazole-3-yl)-6-methylpyridine-3-sulfonamide: 【Chemistry 1】 or a pharmaceutically acceptable solid form of the salt thereof.

2. The solid form according to claim 1, which is a crystalline form.

3. The solid form according to claim 1 or 2, wherein the free form of crystalline compound 1 is type A, type C, type D, type E, or type F of free form of crystalline compound 1.

4. The solid form according to claim 1 or 2, which is the free form type B of the crystalline compound 1.

5. The solid form according to claim 1 or 2, which is in the form of a salt.

6. The solid form according to claim 1 or 2, which is in the form of sodium, potassium, ammonium, or a choline salt.

7. The solid form according to claim 1 or 2, which is in the form of an L-arginine salt.

8. The aforementioned crystal form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 5. (b) X-ray powder diffraction (XRPD) pattern with peaks at 12.8±0.2°2θ, 21.6±0.2°2θ, and 24.7±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 6, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 7, or (e) these combinations The crystalline form according to claim 2, which is a free form type B of compound 1, characterized by having at least one of the following.

9. The crystal morphology according to claim 8, which, when measured using Cu Kα radiation, has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 5.

10. The crystal morphology according to claim 8 or 9, having an X-ray powder diffraction (XRPD) pattern with peaks as shown in Table 2 when measured using Cu Kα radiation.

11. The crystal morphology according to any one of claims 8 to 10, having an X-ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2°²θ, 21.6 ± 0.2°²θ, and 24.7 ± 0.2°²θ when measured using Cu Kα radiation.

12. The crystalline morphology according to any one of claims 8 to 11, wherein the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 12.0 ± 0.2°²θ, 14.5 ± 0.2°²θ, and 22.7 ± 0.2°²θ.

13. The crystalline morphology according to any one of claims 8 to 12 further includes peaks at 5.4±0.2°2θ, 23.0±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

14. The crystal morphology according to any one of claims 8 to 13, wherein the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 22.1 ± 0.2°²θ and 25.1 ± 0.2°²θ.

15. The crystal morphology according to any one of claims 8 to 10, having an X-ray powder diffraction (XRPD) pattern with peaks at 5.4±0.2°2θ, 12.0±0.2°2θ, 12.8±0.2°2θ, 14.5±0.2°2θ, 21.6±0.2°2θ, 22.1±0.2°2θ, 22.7±0.2°2θ, 23.0±0.2°2θ, 24.7±0.2°2θ, 25.1±0.2°2θ, and 27.0±0.2°2θ when measured using Cu Kα radiation.

16. The crystalline form according to any one of claims 8 to 15, which is non-hygroscopic.

17. The crystalline form according to any one of claims 8 to 16, wherein it is an anhydrous substance.

18. The crystalline form according to any one of claims 8 to 17, wherein a water absorption rate of 0.0679% is detected at 80% RH / 25°C in an sorption curve from 0% relative humidity (RH) to 95% RH.

19. The aforementioned crystal form has the following characteristics: (a) When measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern is substantially the same as that shown in Figure 43. (b) X-ray powder diffraction (XRPD) pattern with peaks at 11.0±0.2°2θ, 13.7±0.2°2θ, and 18.6±0.2°2θ when measured using Cu Kα radiation. (c) A differential scanning calorimetry (DSC) thermogram substantially identical to that shown in Figure 44, (d) A thermogravimetric analysis (TGA) thermogram substantially the same as that shown in Figure 45, or (e) these combinations The crystalline form according to claim 2, which is an L-arginine salt type A of compound 1, characterized by having at least one of the following.

20. The crystal morphology according to claim 19, which, when measured using Cu Kα radiation, has substantially the same X-ray powder diffraction (XRPD) pattern as that shown in Figure 43.

21. The crystal morphology according to claim 19 or 20, having an X-ray powder diffraction (XRPD) pattern with peaks as shown in Table 15 when measured using Cu Kα radiation.

22. The crystal morphology according to any one of claims 19 to 21, having an X-ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2°²θ, 13.7 ± 0.2°²θ, and 18.6 ± 0.2°²θ when measured using Cu Kα radiation.

23. The crystalline morphology according to any one of claims 19 to 22, wherein the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 6.1 ± 0.2°²θ, 12.6 ± 0.2°²θ, and 15.3 ± 0.2°²θ.

24. The crystalline morphology according to any one of claims 19 to 23, wherein the X-ray powder diffraction (XRPD) pattern, when measured using Cu Kα radiation, further includes peaks at 19.6 ± 0.2°²θ, 20.5 ± 0.2°²θ, and 21.7 ± 0.2°²θ.

25. The crystal morphology according to any one of claims 19 to 21, having an X-ray powder diffraction (XRPD) pattern with peaks at 6.1±0.2°2θ, 11.0±0.2°2θ, 12.6±0.2°2θ, 13.7±0.2°2θ, 15.3±0.2°2θ, 18.6±0.2°2θ, 19.6±0.2°2θ, 20.5±0.2°2θ, and 21.7±0.2°2θ when measured using Cu Kα radiation.

26. A pharmaceutical composition comprising a crystalline form or a pharmaceutically acceptable salt thereof according to any one of claims 2 to 25, and at least one pharmaceutically acceptable excipient.

27. A method for inhibiting lysine acetyltransferase 6A (KAT6A) in a target subject, the method comprising the step of administering to the target subject a crystalline form or a pharmaceutically acceptable salt thereof according to any one of claims 2 to 25, or a pharmaceutical composition according to claim 26.

28. A method for regulating lysine acetyltransferase 6A (KAT6A) activity in a subject of interest, the method comprising the step of administering to the subject a crystalline form or a pharmaceutically acceptable salt thereof according to any one of claims 2 to 25, or a pharmaceutical composition according to claim 26.

29. The method according to claim 27 or 28, wherein the subject has cancer.

30. A method for treating cancer in a mammal requiring treatment for cancer, the method comprising the step of administering to the mammal a crystalline form described in any one of claims 2 to 25, or a pharmaceutically acceptable salt thereof.

31. A method for treating cancer in a mammal requiring treatment for cancer, the method comprising the step of administering the pharmaceutical composition according to claim 26 to the mammal.

32. The method according to any one of claims 29 to 31, wherein the cancer is selected from lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous melanoma or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, hepatocellular carcinoma, colon cancer, breast cancer, endometrial cancer, cervical cancer, vaginal cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, hematological malignancies, chronic leukemia or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney cancer or ureteral cancer, renal cell carcinoma, renal pelvis cancer, central nervous system (CNS) neoplasm, primary CNS lymphoma, spinal axial tumor, glioblastoma, brainstem glioma, pituitary adenoma, or two or more combinations of the aforementioned cancers.

33. The method according to any one of claims 29 to 31, wherein the cancer is selected from ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), leukemia, lymphoma or multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and non-Hodgkin lymphoma.

34. The method according to any one of claims 29 to 31, wherein the cancer is a solid tumor having KAT6A / 6B amplification or overexpression, or a leukemia or solid tumor having a KAT6A / 6B fusion protein arising from a chromosomal translocation.

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