Crystalline lysine acetyltransferase 6A (KAT6A) inhibitors and uses thereof

Abstract

(Compound 1) Described herein are crystalline forms of small molecule lysine acetyltransferase 6A (KAT6A) inhibitor Compound (1), pharmaceutical compositions thereof, and methods of use thereof in the treatment of diseases or conditions that would benefit from treatment with lysine acetyltransferase 6A (KAT6A) inhibitors.

Description

Cross-references

[0001] This patent application claims the benefit of International Application No. PCT / CN2023 / 090649, filed on April 25, 2023, the full text of which is incorporated herein by reference. Background Technology

[0002] Lysine acetyltransferase 6A (KAT6A) belongs to the MYST acetyltransferase family and was first discovered approximately 25 years ago. KAT6A controls 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 KAT6A expression is associated with oncogenic functions in many cancers, including leukemia, glioma, serous endometrial carcinoma, and breast cancer. Therefore, compounds that inhibit KAT6A (especially stable crystalline forms) are potential agents for treating a variety of cancers. Summary of the Invention

[0003] This paper discloses a 2,4-dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide. (Compound 1) or its pharmaceutically acceptable salt in solid form.

[0004] In some implementations, the solid form is a crystalline form.

[0005] In some embodiments, the solid form is free form A, free form C, free form D, free form E, or free form F of crystalline compound 1.

[0006] In some embodiments, the solid form is the free form B of crystalline compound 1.

[0007] In some implementations, the solid form is in the form of salt.

[0008] In some embodiments, the solid form is in the form of a sodium salt, potassium salt, ammonium salt, or choline salt.

[0009] In some embodiments, the solid form is in the form of L-arginine salt. Attached Figure Description

[0010] The features of the invention are specifically set forth in the appended claims. The features of the invention will be better understood by referring to the following detailed description (which sets forth illustrative embodiments applying the principles of the invention) and the accompanying drawings.

[0011] Figure 1The X-ray powder diffraction (XRPD) pattern of the free form of amorphous compound 1 is shown.

[0012] Figure 2 The X-ray powder diffraction (XRPD) pattern of the free form A of compound 1 is shown.

[0013] Figure 3 The differential scanning calorimetry (DSC) thermogram of the free form A of compound 1 is shown.

[0014] Figure 4 The thermogravimetric analysis (TGA) spectral density of the free form A of compound 1 is shown.

[0015] Figure 5 The X-ray powder diffraction (XRPD) pattern of the free form B of compound 1 is shown.

[0016] Figure 6 The differential scanning calorimetry (DSC) thermogram of the free form B of compound 1 is shown.

[0017] Figure 7 The thermogravimetric analysis (TGA) spectral density of the free form B of compound 1 is shown.

[0018] Figure 8 The dynamic vapor adsorption (DVS) diagram of the free form B of compound 1 is shown.

[0019] Figure 9 The X-ray powder diffraction (XRPD) pattern of the free form C of compound 1 is shown.

[0020] Figure 10 The differential scanning calorimetry (DSC) thermogram of the free form C of compound 1 is shown.

[0021] Figure 11 The thermogravimetric analysis (TGA) spectral density of the free form C of compound 1 is shown.

[0022] Figure 12 The X-ray powder diffraction (XRPD) pattern of the free form D of compound 1 is shown.

[0023] Figure 13 The differential scanning calorimetry (DSC) thermogram of the free form D of compound 1 is shown.

[0024] Figure 14 The thermogravimetric analysis (TGA) spectral density of the free form D of compound 1 is shown.

[0025] Figure 15 The X-ray powder diffraction (XRPD) pattern of the free form E of compound 1 is shown.

[0026] Figure 16 The differential scanning calorimetry (DSC) thermogram of the free form E of compound 1 is shown.

[0027] Figure 17 The thermogravimetric analysis (TGA) spectral density of the free form E of compound 1 is shown.

[0028] Figure 18 The X-ray powder diffraction (XRPD) pattern of the free form F of compound 1 is shown.

[0029] Figure 19 The differential scanning calorimetry (DSC) thermogram of the free form F of compound 1 is shown.

[0030] Figure 20 The thermogravimetric analysis (TGA) spectral density of the free form F of compound 1 is shown.

[0031] Figure 21 The X-ray powder diffraction (XRPD) pattern of sodium salt A of compound 1 is shown.

[0032] Figure 22 The differential scanning calorimetry (DSC) thermogram of sodium salt A of compound 1 is shown.

[0033] Figure 23 The thermogravimetric analysis (TGA) spectral density of sodium salt A of compound 1 is shown.

[0034] Figure 24 The X-ray powder diffraction (XRPD) pattern of sodium salt B of compound 1 is shown.

[0035] Figure 25 The X-ray powder diffraction (XRPD) pattern of sodium salt C of compound 1 is shown.

[0036] Figure 26 The differential scanning calorimetry (DSC) thermogram of sodium salt C of compound 1 is shown.

[0037] Figure 27 The thermogravimetric analysis (TGA) spectral density of sodium salt C of compound 1 is shown.

[0038] Figure 28 The X-ray powder diffraction (XRPD) pattern of sodium salt D of compound 1 is shown.

[0039] Figure 29 The differential scanning calorimetry (DSC) thermogram of sodium salt D of compound 1 is shown.

[0040] Figure 30 The thermogravimetric analysis (TGA) spectral density of sodium salt D of compound 1 is shown.

[0041] Figure 31 The X-ray powder diffraction (XRPD) pattern of potassium salt A of compound 1 is shown.

[0042] Figure 32 The differential scanning calorimetry (DSC) thermogram of potassium salt A of compound 1 is shown.

[0043] Figure 33 The thermogravimetric analysis (TGA) spectral density of potassium salt A of compound 1 is shown.

[0044] Figure 34 The X-ray powder diffraction (XRPD) pattern of ammonium salt type A is shown.

[0045] Figure 35 The differential scanning calorimetry (DSC) thermogram of compound 1 ammonium salt type A is shown.

[0046] Figure 36 The thermogravimetric analysis (TGA) spectral density of compound 1 ammonium salt type A is shown.

[0047] Figure 37 The X-ray powder diffraction (XRPD) pattern of compound 1 ammonium salt type B is shown.

[0048] Figure 38 The differential scanning calorimetry (DSC) thermogram of compound 1 ammonium salt type B is shown.

[0049] Figure 39 The thermogravimetric analysis (TGA) spectral density of compound 1 ammonium salt type B is shown.

[0050] Figure 40 The X-ray powder diffraction (XRPD) pattern of compound 1 ammonium salt type C is shown.

[0051] Figure 41 The differential scanning calorimetry (DSC) thermogram of ammonium salt C type is shown.

[0052] Figure 42 The thermogravimetric analysis (TGA) spectral density of compound 1 ammonium salt C type is shown.

[0053] Figure 43 The X-ray powder diffraction (XRPD) pattern of compound 1 L-arginine salt type A is shown.

[0054] Figure 44 The differential scanning calorimetry (DSC) thermogram of L-arginine salt type A is shown.

[0055] Figure 45 The thermogravimetric analysis (TGA) spectral density of compound 1 L-arginine salt type A is shown.

[0056] Figure 46The X-ray powder diffraction (XRPD) pattern of choline salt A of compound 1 is shown.

[0057] Figure 47 The differential scanning calorimetry (DSC) thermogram of choline salt A of compound 1 is shown.

[0058] Figure 48 The thermogravimetric analysis (TGA) spectral density of compound 1, choline salt A type, is shown. Detailed Implementation

[0059] While small molecule inhibitors are typically evaluated first for their activity when dissolved in solution, solid-state properties such as polymorphism are also important. Polymorphic forms of drug substances can possess 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 drug substances and drug products. Furthermore, differences in these properties can and often lead to different pharmacokinetic profiles in different polymorphic forms of a drug. Therefore, polymorphism is often a crucial factor in regulatory reviews of the 'identity' of drug products from various manufacturers.

[0060] Compound 1 Compound 1 is 2,4-dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide: (Compound 1). In some embodiments, Compound 1 exists in a free form. In some embodiments, Compound 1 exists in the form of a pharmaceutically acceptable salt. In some embodiments, Compound 1 exists in the form of a sodium salt. In some embodiments, Compound 1 exists in the form of a potassium salt. In some embodiments, Compound 1 exists in the form of an ammonium salt. In some embodiments, Compound 1 exists in the form of a choline salt. In some embodiments, Compound 1 exists in the form of an L-arginine salt. In some embodiments, Compound 1 exists in a eutectic form. In some embodiments, Compound 1 exists in an amorphous form. In some embodiments, Compound 1 exists in a non-ionized form. In some embodiments, the free form of Compound 1 is a non-ionized form.

[0061] Solid form of compound 1 In one aspect, this article provides a 2,4-dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide (Compound 1) or its pharmaceutically acceptable salt in solid form.

[0062] In some implementations, the solid form is a crystalline form.

[0063] In some embodiments, the solid form is the free form of crystalline compound 1. In some embodiments, the solid form is free form A, free form B, or free form D of crystalline compound 1. In some embodiments, the solid form is free form A of crystalline compound 1. In some embodiments, the solid form is free form B of crystalline compound 1. In some embodiments, the solid form is free form C of crystalline compound 1. In some embodiments, the solid form is free form D of crystalline compound 1. In some embodiments, the solid form is free form E of crystalline compound 1. In some embodiments, the solid form is free form F of crystalline compound 1.

[0064] In some embodiments, the solid form is crystalline compound 1 free form type A, compound 1 free form type C, compound 1 free form type D, compound 1 free form type E, or compound 1 free form type F.

[0065] To avoid ambiguity, the term "crystalline form" is used throughout the instruction manual to include any 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).

[0066] Compound 1 in free form, type A This document discloses compound 1 in its free form, type A. In some embodiments, the crystalline form is compound 1 in its free form, type A, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 2 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 8.0 ± 0.2° 2θ, 12.9 ± 0.2° 2θ and 21.0 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 3 The results are essentially the same; or (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 4 The images shown are basically the same; (e) Its combination.

[0067] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 2 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0068] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 1.

[0069] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0070] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 6.9 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, and 18.5 ± 0.2° 2θ.

[0071] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θ.

[0072] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0073] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0074] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0075] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0076] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0077] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0078] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0079] In some embodiments of the free form A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0080] In some embodiments of the free form A of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 3 The results are basically the same.

[0081] In some embodiments of compound 1 in its free form, type A, thermogravimetric analysis (TGA) chromatograms and Figure 4 The results are basically the same.

[0082] Table 1: XRPD peaks of compound 1 in its free form, type A

[0083] Compound 1 in free form, type B This document discloses compound 1 in its free form, type B. In some embodiments, the crystalline form is compound 1 in its free form, type B, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 5 The images shown are basically the same; (b) As 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; (c) Differential scanning calorimetry (DSC) thermogram and Figure 6 The images shown are basically the same; (d) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 173.1 °C; (e) Thermogravimetric analysis (TGA) thermogram and Figure 7 The images shown are basically the same; (f) Thermogravimetric analysis (TGA) thermograms show that the mass loss is approximately 1.29% from the start of heating until approximately 150°C; or (g) Its combination.

[0084] In some embodiments, the crystalline form is the free form B of compound 1, characterized by having at least one of the following properties: (a) As 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) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 173.1 °C; (c) Thermogravimetric analysis (TGA) thermograms show that the mass loss is approximately 1.29% from the start of heating until approximately 150°C; or (d) Its combination.

[0085] In some embodiments, the crystalline form is the free form B of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 5 The images shown are basically the same; (b) As 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; (c) Differential scanning calorimetry (DSC) thermogram and Figure 6 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 7 The results are essentially the same; or (e) Its combination.

[0086] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 5 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0087] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 2.

[0088] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0089] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ.

[0090] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 5.4 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ.

[0091] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 22.1 ± 0.2° 2θ and 25.1 ± 0.2° 2θ.

[0092] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0093] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0094] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0095] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0096] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0097] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0098] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0099] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0100] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0101] In some embodiments of the free form B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0102] In some embodiments of compound 1 in its free form, type B, differential scanning calorimetry (DSC) thermograms and Figure 6 The results are basically the same.

[0103] In some embodiments of the free form B of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 173.1 °C.

[0104] In some embodiments of compound 1 in its free form, type B, thermogravimetric analysis (TGA) chromatograms and Figure 7 The results are basically the same.

[0105] In some embodiments of the free form B of compound 1, thermogravimetric analysis (TGA) thermograms show a mass loss of approximately 1.29% from the start of heating up to approximately 150°C. In some embodiments of the free form B of compound 1, TGA thermograms show a mass loss of less than 1.5% from the start of heating up to approximately 150°C. In some embodiments of the free form B of compound 1, TGA thermograms show a mass loss of less than 2% from the start of heating up to approximately 150°C.

[0106] In some embodiments of compound 1 in its free form B, the crystalline form is non-hygroscopic.

[0107] In some embodiments of compound 1 in its free form B, the crystalline form is anhydrous.

[0108] In some embodiments of the free form B of compound 1, 0.0679% water absorption was detected in the adsorption profile from 0%RH to 95%RH at 80% relative humidity (RH) / 25°C. In some embodiments of the free form B of compound 1, less than 0.1%, less than 0.2%, less than 0.5%, less than 0.8%, less than 1%, or less than 2% water absorption was detected in the adsorption profile from 0%RH to 95%RH at 80% relative humidity (RH) / 25°C. In some embodiments of the free form B of compound 1, less than 0.1% water absorption was detected in the adsorption profile from 0%RH to 95%RH at 80% relative humidity (RH) / 25°C.

[0109] Table 2: XRPD peaks of compound 1 in its free form, type B

[0110] Compound 1 in free form, type C This document discloses compound 1 in its free form, type C. In some embodiments, the crystalline form is compound 1 in its free form, type C, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 9 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 11.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ and 20.9 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 10 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 11 The results are essentially the same; or (e) Its combination.

[0111] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 9 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0112] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 3.

[0113] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0114] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern 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.

[0115] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 7.7 ± 0.2° 2θ and 23.4 ± 0.2° 2θ.

[0116] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0117] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0118] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0119] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0120] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0121] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0122] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0123] In some embodiments of the free form C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0124] In some embodiments of the free form C of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 10 The results are basically the same.

[0125] In some embodiments of compound 1 in its free form, type C, thermogravimetric analysis (TGA) pyrometry spectra and Figure 11 The results are basically the same.

[0126] Table 3: XRPD peaks of the free C-form of compound 1

[0127] Compound 1 in free form, type D This document discloses compound 1 in its free form, type D. In some embodiments, the crystalline form is compound 1 in its free form, type D, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 12 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 7.5 ± 0.2° 2θ, 15.1 ± 0.2° 2θ and 20.5 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 13 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 14 The results are essentially the same; or (e) Its combination.

[0128] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 12 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0129] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 4.

[0130] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0131] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 11.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 21.5 ± 0.2° 2θ.

[0132] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 23.3 ± 0.2° 2θ and 26.5 ± 0.2° 2θ.

[0133] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0134] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0135] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0136] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0137] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0138] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0139] In some embodiments of the free form D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0140] In some embodiments of compound 1 in its free form, D-type, differential scanning calorimetry (DSC) thermograms and Figure 13 The results are basically the same.

[0141] In some embodiments of compound 1 in its free form, D, thermogravimetric analysis (TGA) chromatograms and Figure 14 The results are basically the same.

[0142] Table 4: XRPD peaks of the free form D of compound 1

[0143] Compound 1 in free form, type E This document discloses compound 1 in its free form, type E. In some embodiments, the crystalline form is compound 1 in its free form, type E, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 15 The images shown are basically the same; (b) As 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; (c) Differential scanning calorimetry (DSC) thermogram and Figure 16 The images shown are basically the same; (d) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 101.0 °C; (e) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 109.6 °C; (f) The exothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 173.4 °C; (g) Thermogravimetric analysis (TGA) thermal spectrum and Figure 17 The images shown are basically the same; (h) Thermogravimetric analysis (TGA) thermograms show that the mass loss is approximately 16.63% from the start of heating until approximately 150°C; or (i) Its combination.

[0144] In some embodiments, the crystalline form is the free form E of compound 1, characterized by having at least one of the following properties: (a) As 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) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 101.0 °C; (c) The endothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 109.6 °C; (d) The exothermic peak in the differential scanning calorimetry (DSC) thermogram has a peak temperature of approximately 173.4 °C; (e) Thermogravimetric analysis (TGA) thermograms show that the mass loss is approximately 16.63% from the start of heating up to approximately 150°C; or (f) Its combination.

[0145] In some embodiments, the crystalline form is the free form E of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 15 The images shown are basically the same; (b) As 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; (c) Differential scanning calorimetry (DSC) thermogram and Figure 16 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 17 The results are essentially the same; or (e) Its combination.

[0146] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 15 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0147] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 5.

[0148] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0149] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 6.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 21.9 ± 0.2° 2θ.

[0150] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 19.8 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ.

[0151] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0152] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0153] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0154] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0155] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0156] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0157] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0158] In some embodiments of the free form E of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0159] In some embodiments of the free form E of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 16 The results are basically the same.

[0160] In some embodiments of the free form E of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 101.0 °C.

[0161] In some embodiments of the free form E of compound 1, the differential scanning calorimetry (DSC) thermogram shows an endothermic peak with a peak temperature of approximately 109.6 °C.

[0162] In some embodiments of the free form E of compound 1, the differential scanning calorimetry (DSC) thermogram shows an exothermic peak with a peak temperature of approximately 173.4 °C.

[0163] In some embodiments of compound 1 in its free form E, thermogravimetric analysis (TGA) chromatograms and Figure 17 The results are basically the same.

[0164] In some embodiments of the free form E of compound 1, thermogravimetric analysis (TGA) thermograms showed a mass loss of approximately 16.63% from the start of heating up to approximately 150°C.

[0165] Table 5: XRPD peaks of the free form E of compound 1

[0166] Compound 1 in free form, F type This document discloses the free form F of compound 1. In some embodiments, the crystalline form is the free form F of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 18 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 8.0 ± 0.2° 2θ, 18.3 ± 0.2° 2θ and 25.1 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 19 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 20 The results are essentially the same; or (e) Its combination.

[0167] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form exhibits the same characteristics as... Figure 18 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0168] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 6.

[0169] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0170] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 11.2 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, and 25.8 ± 0.2° 2θ.

[0171] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 6.9 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 22.5 ± 0.2° 2θ.

[0172] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0173] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0174] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0175] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0176] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0177] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0178] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0179] In some embodiments of the free form F of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0180] In some embodiments of the free form F of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 19 The results are basically the same.

[0181] In some embodiments of the free form F of compound 1, thermogravimetric analysis (TGA) pyrometry results are compared with... Figure 20 The results are basically the same.

[0182] Table 6: XRPD peaks of the free form F of compound 1

[0183] Sodium salt of compound 1, type A This document discloses a sodium salt A type of compound 1. In some embodiments, the crystalline form is a sodium salt A type of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 21 The images shown are basically the same; (b) As 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) Differential scanning calorimetry (DSC) thermogram and Figure 22 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 23 The results are essentially the same; or (e) Its combination.

[0184] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 21 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0185] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 7.

[0186] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0187] In some embodiments of the sodium salt type A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 11.1 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, and 25.9 ± 0.2° 2θ.

[0188] In some embodiments of the sodium salt type A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 20.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ.

[0189] In some embodiments of the sodium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0190] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0191] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0192] In some embodiments of the sodium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0193] In some embodiments of sodium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0194] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0195] In some embodiments of sodium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0196] In some embodiments of the sodium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0197] In some embodiments of sodium salt A of compound 1, the differential scanning calorimetry (DSC) thermogram is compared with... Figure 22 The results are basically the same.

[0198] In some embodiments of sodium salt type A of compound 1, the thermogravimetric analysis (TGA) chromatogram is consistent with... Figure 23 The results are basically the same.

[0199] Table 7: XRPD peaks of sodium salt A of compound 1

[0200] Sodium salt of compound 1, type B This document discloses sodium salt type B of compound 1. In some embodiments, the crystalline form is sodium salt type B of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 24 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 8.7 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ; or (c) Its combination.

[0201] In some embodiments of sodium salt B of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 24 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0202] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 8.

[0203] In some embodiments of sodium salt B of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0204] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 5.3 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, and 21.5 ± 0.2° 2θ.

[0205] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 14.5 ± 0.2° 2θ and 24.6 ± 0.2° 2θ.

[0206] In some embodiments of sodium salt B of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0207] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0208] In some embodiments of sodium salt B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0209] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0210] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0211] In some embodiments of sodium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0212] In some embodiments of sodium salt B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0213] Table 8: XRPD peaks of sodium salt B of compound 1

[0214] Sodium salt of compound 1, type C This document discloses a sodium salt C form of compound 1. In some embodiments, the crystalline form is a sodium salt C form of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 25 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 8.2 ± 0.2° 2θ, 15.4 ± 0.2° 2θ and 21.7 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 26 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 27 The results are essentially the same; or (e) Its combination.

[0215] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 25 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0216] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 9.

[0217] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0218] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 10.5 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, and 24.8 ± 0.2° 2θ.

[0219] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern 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.

[0220] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0221] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form 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.

[0222] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0223] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0224] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0225] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0226] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0227] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0228] In some embodiments of the sodium salt C of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0229] In some embodiments of sodium salt C of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 26 The results are basically the same.

[0230] In some embodiments of sodium salt C of compound 1, the thermogravimetric analysis (TGA) chromatogram is compared with... Figure 27 The results are basically the same.

[0231] Table 9: XRPD peaks of sodium salt C of compound 1

[0232] Sodium salt of compound 1, type D This document discloses a sodium salt D form of compound 1. In some embodiments, the crystalline form is a sodium salt D form of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 28 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 9.3 ± 0.2° 2θ, 19.1 ± 0.2° 2θ and 22.6 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 29 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 30 The results are essentially the same; or (e) Its combination.

[0233] In some embodiments of sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 28 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0234] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 10.

[0235] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0236] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 5.3 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, and 21.3 ± 0.2° 2θ.

[0237] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, and 26.2 ± 0.2° 2θ.

[0238] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0239] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0240] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0241] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0242] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0243] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0244] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0245] In some embodiments of the sodium salt D of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0246] In some embodiments of sodium salt D of compound 1, the differential scanning calorimetry (DSC) thermogram is compared with... Figure 29 The results are basically the same.

[0247] In some embodiments of sodium salt D of compound 1, the thermogravimetric analysis (TGA) chromatogram is compared with... Figure 30 The results are basically the same.

[0248] Table 10: XRPD peaks of sodium salt D of compound 1

[0249] Compound 1 potassium salt type A This document discloses potassium salt type A of compound 1. In some embodiments, the crystalline form is potassium salt type A of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 31 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 6.3 ± 0.2° 2θ, 13.3 ± 0.2° 2θ and 20.2 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 32 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 33 The results are essentially the same; or (e) Its combination.

[0250] In some embodiments of potassium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 31 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0251] In some embodiments of potassium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 11.

[0252] In some embodiments of the potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0253] In some embodiments of the potassium salt type A of compound 1, as measured using Cu Kα radiation, 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.

[0254] In some embodiments of the potassium salt type A of compound 1, as measured using Cu Kα radiation, 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.

[0255] In some embodiments of the potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns with 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.

[0256] In some embodiments of potassium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0257] In some embodiments of potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0258] In some embodiments of potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0259] In some embodiments of potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0260] In some embodiments of potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0261] In some embodiments of potassium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0262] In some embodiments of potassium salt A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0263] In some embodiments of potassium salt A of compound 1, differential scanning calorimetry (DSC) thermograms and Figure 32 The results are basically the same.

[0264] In some embodiments of potassium salt A of compound 1, thermogravimetric analysis (TGA) pyrometry spectra are compared with... Figure 33 The results are basically the same.

[0265] Table 11: XRPD peaks of potassium salt A of compound 1

[0266] Compound 1 ammonium salt type A This document discloses a compound 1 ammonium salt type A. In some embodiments, the crystalline form is compound 1 ammonium salt type A, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 34 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ and 21.8 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 35 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 36 The results are essentially the same; or (e) Its combination.

[0267] In some embodiments of compound 1 ammonium salt type A, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 34 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0268] In some embodiments of compound 1 ammonium salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 12.

[0269] In some embodiments of compound 1 ammonium salt type A, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns with peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, and 21.8 ± 0.2° 2θ.

[0270] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 6.0 ± 0.2° 2θ, 16.2 ± 0.2° 2θ, and 18.2 ± 0.2° 2θ.

[0271] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 20.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ± 0.2° 2θ.

[0272] In some embodiments of compound 1 ammonium salt type A, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0273] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form 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.

[0274] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0275] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0276] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0277] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0278] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0279] In some embodiments of the ammonium salt type A of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0280] In some embodiments of compound 1 ammonium salt type A, the differential scanning calorimetry (DSC) thermogram and Figure 35 The results are basically the same.

[0281] In some embodiments of compound 1 ammonium salt type A, the thermogravimetric analysis (TGA) chromatogram and Figure 36 The results are basically the same.

[0282] Table 12: XRPD peaks of compound 1 ammonium salt type A

[0283] Compound 1 ammonium salt type B This document discloses a compound 1 ammonium salt type B. In some embodiments, the crystalline form is a compound 1 ammonium salt type B, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 37 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 6.5 ± 0.2° 2θ, 14.7 ± 0.2° 2θ and 26.1 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 38 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 39 The results are essentially the same; or (e) Its combination.

[0284] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 37 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0285] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 13.

[0286] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has 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.

[0287] In some embodiments of the ammonium salt type B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 13.0 ± 0.2° 2θ and 19.5 ± 0.2° 2θ.

[0288] In some embodiments of the ammonium salt type B of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 18.1 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ.

[0289] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0290] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0291] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0292] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0293] In some embodiments of compound 1 ammonium salt type B, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0294] In some embodiments of the ammonium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0295] In some embodiments of the ammonium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0296] In some embodiments of the ammonium salt type B of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0297] In some embodiments of compound 1 ammonium salt type B, the differential scanning calorimetry (DSC) thermogram and Figure 38 The results are basically the same.

[0298] In some embodiments of compound 1 ammonium salt type B, the thermogravimetric analysis (TGA) chromatogram and Figure 39 The results are basically the same.

[0299] Table 13: XRPD peak table of compound 1 ammonium salt type B

[0300] Compound 1 ammonium salt C type This document discloses a C-type ammonium salt of compound 1. In some embodiments, the crystalline form is the C-type ammonium salt of compound 1, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 40 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 6.1 ± 0.2° 2θ, 15.6 ± 0.2° 2θ and 24.4 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 41 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 42 The results are essentially the same; or (e) Its combination.

[0301] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 40 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0302] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 14.

[0303] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has 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.

[0304] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 13.0 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, and 25.7 ± 0.2° 2θ.

[0305] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 12.2 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, and 22.1 ± 0.2° 2θ.

[0306] In some embodiments of the 1 ammonium salt type C of compound, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0307] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0308] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0309] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0310] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0311] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0312] In some embodiments of the ammonium salt C type of compound 1, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0313] In some embodiments of the 1 ammonium salt C type of compound, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0314] In some embodiments of compound 1 ammonium salt type C, differential scanning calorimetry (DSC) thermograms and Figure 41 The results are basically the same.

[0315] In some embodiments of compound 1 ammonium salt type C, the thermogravimetric analysis (TGA) chromatogram is compared with... Figure 42 The results are basically the same.

[0316] Table 14: XRPD peaks of compound 1 ammonium salt C type

[0317] Compound 1 L-arginine salt type A This document discloses compound 1, L-arginine salt type A. In some embodiments, the crystalline form of compound 1, L-arginine salt type A is characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 43 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 11.0 ± 0.2° 2θ, 13.7 ± 0.2° 2θ and 18.6 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 44 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 45 The results are essentially the same; or (e) Its combination.

[0318] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 43 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0319] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 15.

[0320] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has 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.

[0321] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 6.1 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, and 15.3 ± 0.2° 2θ.

[0322] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ.

[0323] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0324] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form 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.

[0325] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0326] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0327] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0328] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0329] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0330] In some embodiments of compound 1 L-arginine salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0331] In some embodiments of compound 1 L-arginine salt type A, the differential scanning calorimetry (DSC) thermogram and Figure 44 The results are basically the same.

[0332] In some embodiments of compound 1 L-arginine salt type A, the thermogravimetric analysis (TGA) chromatogram and Figure 45 The results are basically the same.

[0333] Table 15: XRPD peaks of compound 1 L-arginine salt type A

[0334] Compound 1, choline salt type A This document discloses compound 1 choline salt type A. In some embodiments, the crystalline form is compound 1 choline salt type A, characterized by having at least one of the following properties: (a) X-ray powder diffraction (XRPD) pattern as measured using Cu Kα radiation and Figure 46 The images shown are basically the same; (b) As measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern has peaks at 11.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ and 20.6 ± 0.2° 2θ; (c) Differential scanning calorimetry (DSC) thermogram and Figure 47 The images shown are basically the same; (d) Thermogravimetric analysis (TGA) thermal spectra and Figure 48 The results are essentially the same; or (e) Its combination.

[0335] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has the same characteristics as... Figure 46 The X-ray powder diffraction (XRPD) patterns shown are essentially the same.

[0336] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with the peaks seen in Table 16.

[0337] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has 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.

[0338] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 12.5 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, and 24.0 ± 0.2° 2θ.

[0339] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the X-ray powder diffraction (XRPD) pattern further includes peaks at 5.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, and 22.9 ± 0.2° 2θ.

[0340] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has X-ray powder diffraction (XRPD) patterns 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.

[0341] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form 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.

[0342] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0343] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0344] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0345] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0346] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0347] In some embodiments of compound 1 choline salt type A, as measured using Cu Kα radiation, the crystalline form has an X-ray powder diffraction (XRPD) pattern with 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.

[0348] In some embodiments of compound 1 choline salt type A, differential scanning calorimetry (DSC) thermograms and Figure 47 The results are basically the same.

[0349] In some embodiments of compound 1 choline salt type A, thermogravimetric analysis (TGA) chromatograms and Figure 48 The results are basically the same.

[0350] Table 16: XRPD peaks of choline salt A type of compound 1

[0351] Treatment This document discloses a method for treating a disease that benefits from the inhibition of KAT6A, the method comprising administering the 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 administering a pharmaceutical composition comprising the crystalline form disclosed herein.

[0352] This document discloses a method for treating diseases or conditions associated with KAT6A, comprising 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 method comprises administering a pharmaceutical composition comprising the crystalline form disclosed herein.

[0353] In some embodiments, a method of treating cancer in a mammal in need includes administering the crystalline form disclosed herein to the mammal. In some embodiments, the crystalline form is the free form, type B, of compound 1.

[0354] In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein (e.g., the crystalline form being free form type B of compound 1), wherein the cancer is selected from lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, melanoma of the skin or eye, 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 bowel cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, hematologic malignancies, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvis cancer, central nervous system (CNS) tumors, primary CNS lymphoma, spinal axis tumors, glioblastoma, brainstem glioma, pituitary adenoma, or a combination of two or more of the aforementioned cancers. In some implementations, the method is a method of treating breast cancer in a mammal in need, which includes administering the crystalline free form of compound 1, type B, to the mammal.

[0355] In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein (e.g., the crystalline form being the free form type B of compound 1), 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's lymphoma. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is ER-positive breast cancer. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is glioblastoma. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is non-small cell lung cancer (NSCLC). In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is small cell lung cancer (SCLC). In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is melanoma. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is ovarian cancer. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is prostate cancer. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is pancreatic cancer. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is colorectal cancer (CRC). In some embodiments, a method of treating cancer in a mammal in need includes administering the crystalline form disclosed herein to the mammal, wherein the cancer is hepatocellular carcinoma (HCC). In some embodiments, a method of treating cancer in a mammal in need includes administering the crystalline form disclosed herein to the mammal, wherein the cancer is renal cell carcinoma (RCC). In some embodiments, a method of treating cancer in a mammal in need includes administering the crystalline form disclosed herein to the mammal, wherein the cancer is leukemia.In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is lymphoma. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is multiple myeloma. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is acute lymphoblastic leukemia (ALL). In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is acute myeloid leukemia (AML). In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is chronic lymphocytic leukemia (CLL). In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is chronic myeloid leukemia (CML). In some embodiments, a method for treating cancer in a mammal in need includes administering the crystalline form disclosed herein to the mammal, wherein the cancer is non-Hodgkin's 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 in need, including administering the free crystalline form type B of compound 1 to the mammal.

[0356] In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal the crystalline form disclosed herein, wherein the cancer is a solid tumor with KAT6A / 6B amplification or overexpression, or leukemia or a solid tumor having a KAT6A / 6B fusion protein resulting from a chromosomal translocation. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal the crystalline form disclosed herein, wherein the cancer is a solid tumor with KAT6A / 6B amplification or overexpression. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal the crystalline form disclosed herein, wherein the cancer is leukemia or a solid tumor having a KAT6A / 6B fusion protein resulting from a chromosomal translocation. In some embodiments, the crystalline form is the free form type B of compound 1.

[0357] In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer is a MYST-overexpressing cancer. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses more than one KAT from the MYST family. In some embodiments, a method of treating cancer in a mammal in need includes administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses more than one KAT from the MYST family, wherein the more than one KAT is selected from TIP60, KAT6A, KAT6B, HBO1, and MOF. In some embodiments, the crystalline form is the free form B of compound 1.

[0358] In some embodiments, a method for treating cancer in a mammal in need includes administering to the mammal the crystalline form disclosed herein, wherein the cancer is a cancer that overexpresses a bromine domain. In some embodiments, a method for treating cancer that overexpresses a bromine domain in a mammal in need includes administering to the mammal the crystalline form disclosed herein, wherein the cancer overexpresses one or more bromine domain 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 B of compound 1.

[0359] Dosage In some embodiments, the composition containing the compounds described herein is administered for preventative and / or therapeutic treatment. In some therapeutic applications, the composition is administered to a patient who already has a disease or condition in an amount sufficient to cure the disease or condition or at least partially stop at least one symptom of the disease or condition. The effective amount for this purpose depends on the severity and course of the disease or condition, prior therapy, the patient's health status, weight and response to the drug, and the judgment of the attending physician. The therapeutically effective amount may optionally be determined by methods including, but not limited to, dose escalation and / or dose range clinical trials.

[0360] In preventative applications, a composition containing the compounds described herein is administered to a patient who is susceptible to or otherwise at risk of a particular disease, condition, or illness. This amount is defined as the “preventative effective amount or dose.” In this use, the exact amount also depends on the patient’s health status, weight, etc. When used on a patient, the effective amount for this purpose will depend on the severity and course of the disease, condition, or illness, prior treatments, the patient’s health status and response to the medication, and the judgment of the attending physician. In one aspect, preventative treatment comprises administering a pharmaceutical composition containing the compounds described herein or pharmaceutically acceptable salts thereof to a mammal who has previously experienced at least one symptom or risk factor of a treated disease and is currently in remission, to prevent recurrence of symptoms of the disease or illness.

[0361] In some implementation schemes in which the patient’s condition does not improve, the compound is administered long-term (i.e. for an extended period of time, including a patient’s entire life) at the physician’s discretion in order to improve or otherwise control or limit the symptoms of the patient’s disease or condition.

[0362] Further embodiments exist in any of the foregoing aspects, wherein an effective amount of 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 locally to a mammal; and / or (f) administered to a mammal neither systemically nor locally.

[0363] Application route Suitable 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, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary, intrathecal, intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injection.

[0364] Pharmaceutical Compositions / Formulations The compounds described herein, alone or in combination with pharmaceutically acceptable carriers, excipients, or diluents, are administered to subjects in need according to standard pharmaceutical practice. In one embodiment, the compounds disclosed herein may be administered to animals. These compounds may be administered orally or parenterally, including via intravenous, intramuscular, intraperitoneal, subcutaneous, rectal, and topical routes.

[0365] On the other hand, this document provides pharmaceutical compositions comprising the crystalline form disclosed herein and at least one pharmaceutically acceptable excipient.

[0366] 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 formulation. Appropriate formulation depends on the chosen route of administration. For example, summaries of the pharmaceutical compositions described herein can be found in Remington: The Science and Practice of Pharmacy, 19th edition (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., editors, Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th edition (Lippincott Williams & Wilkins 1999), the contents of which are incorporated herein by reference.

[0367] In some implementations, pharmaceutically acceptable excipients are selected from carriers, binders, fillers, suspending agents, flavoring agents, sweeteners, disintegrants, dispersants, surfactants, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, penetration enhancers, humectants, defoamers, antioxidants, preservatives, and any combination thereof.

[0368] The pharmaceutical compositions described herein are administered to the target via appropriate routes of administration, including but not limited to oral, parenteral (e.g., intravenous, subcutaneous, intramuscular), intranasal, buccal, topical, rectal, or transdermal administration. The pharmaceutical formulations described herein include, but are not limited to, aqueous liquid dispersions, liquids, gels, syrups, elixirs, slurries, suspensions, self-emulsifying dispersions, solid solutions, liposome dispersions, aerosols, solid oral dosage forms, powders, immediate-release formulations, controlled-release formulations, rapidly dissolving formulations, tablets, capsules, pills, powders, sugar-coated pills, effervescent formulations, lyophilized formulations, delayed-release formulations, extended-release formulations, pulsatile-release formulations, multi-particle formulations, and mixtures of immediate-release and controlled-release formulations.

[0369] Pharmaceutical compositions comprising the compounds described herein or their pharmaceutically acceptable salts or solvates are manufactured in a conventional manner, for example, by way of example only, through conventional mixing, dissolving, granulation, pilling, grinding, emulsifying, encapsulating, embedding, or compressing processes.

[0370] A pharmaceutical composition for oral use is obtained by mixing one or more solid excipients with one or more of the compounds described herein, optionally grinding the resulting mixture, and processing the granular mixture after adding suitable excipients (if desired) to obtain tablets or sugar-coated pellet cores. Suitable excipients include, for example, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, astragalus gum, methylcellulose, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose; or other fillers such as polyvinylpyrrolidone (PVP or povidone) or calcium phosphate. If desired, disintegrants such as croscarmellose sodium, polyvinylpyrrolidone, agar, or alginate or its salts, such as sodium alginate, are added. In some embodiments, dyes or pigments are added to the coating of the tablets or sugar-coated pellets for identification or for characterizing different combinations of active compound dosages.

[0371] Orally administered pharmaceutical compositions include push-in capsules made of gelatin and sealed soft capsules made of gelatin and plasticizers such as glycerin or sorbitol. Push-in capsules contain the active ingredient, mixed with fillers such as lactose, binders such as starch, and / or lubricants such as talc or magnesium stearate, and optionally, stabilizers. In soft capsules, the active compound is dissolved or suspended in a suitable liquid, such as fatty oil, liquid paraffin, or liquid polyethylene glycol. In some embodiments, stabilizers are added.

[0372] Pharmaceutical compositions intended for parenteral use are formulated as infusions or injections. In some embodiments, pharmaceutical compositions suitable for injection or infusion comprise sterile aqueous solutions, dispersions, or sterile powders containing the compounds described herein or their pharmaceutically acceptable salts or solvates. In some embodiments, the pharmaceutical composition comprises a liquid carrier. In some embodiments, the liquid carrier is a solvent or liquid dispersion medium, including, for example, water, saline, ethanol, polyols (e.g., glycerol, propylene glycol, liquid polyethylene glycol, etc.), vegetable oils, non-toxic glycerides, and any combination thereof. In some embodiments, the pharmaceutical composition further comprises a preservative to prevent microbial growth.

[0373] definition Unless otherwise stated, the following terms as used in this application have the following definitions. The use of the term "including" and other forms such as "include," "includes," and "included" is non-limiting. Section headings used herein are for typographical purposes only and should not be construed as limiting the subject matter.

[0374] As used herein, the term “acceptable” means that a formulation, composition or ingredient will not have a lasting harmful effect on the overall health of the person being treated.

[0375] As used herein, the terms “administer,” “administering,” “administration,” etc., refer to methods that can be used to deliver a compound or composition to a desired site of biological action. These methods include, but are not limited to, oral administration, duodenal administration, parenteral administration (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, or infusion), local administration, and rectal administration. Those skilled in the art are familiar with administration techniques that can be used with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

[0376] As used herein, the term "effective amount" or "therapeutic effective amount" refers to an adequate quantity of an applied agent or compound that will, to a certain extent, alleviate one or more symptoms of the disease or condition being treated. Results include reduction and / or relief of the signs, symptoms, or cause of the disease, or any other desired alteration of the biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising the compounds disclosed herein required to achieve a clinically significant reduction in the symptoms of a disease. In any case, the appropriate "effective" amount may optionally be determined using techniques such as dose escalation studies.

[0377] As used herein, the term "enhance" (or "enhancing") refers to increasing or prolonging a desired effect in terms of potency or duration. Therefore, in relation to enhancing the effect of a therapeutic agent, the term "enhancement" refers to the ability to increase or prolong the effect of another therapeutic agent on the system in terms of potency or duration. As used herein, "enhancing effective amount" refers to an amount sufficient to enhance the effect of another therapeutic agent on the desired system.

[0378] The term "object" or "patient" encompasses mammals. Examples of mammals include, but are not limited to, any member of the class Mammalia: humans; non-human primates such as chimpanzees and other apes and monkeys; livestock such as cattle, horses, sheep, goats, and pigs; domesticated animals such as rabbits, dogs, and cats; and laboratory animals, including rodents such as rats, mice, and guinea pigs. In one respect, mammals are humans.

[0379] The term “treatment” as used herein includes the preventive and / or therapeutic relief, reduction or improvement of at least one symptom of a disease or condition, prevention of new symptoms, suppression of a disease or condition (e.g., preventing the development of a disease or condition), relief of a disease or condition, promotion of the resolution of a disease or condition, relief of conditions caused by a disease or condition, or cessation of symptoms of a disease or condition.

[0380] The term "about" refers to a statistically significant range of a value (such as a stated concentration range, time range, molecular weight, particle size, temperature, or pH). This range may be within the order of magnitude of the indicated value or range, commonly within 10%, more commonly within 5%, and even more commonly within 3%. Sometimes, this range may be within the typical experimental error of the standard methods used to measure and / or determine a given value or range. The permissible deviation covered by the term "about" will depend on the specific system studied and is readily understood by one of ordinary skill in the art. Whenever a range is mentioned in this application, each integer within that range is also considered an embodiment of this disclosure. In this disclosure, whether or not the term "about" is used, it refers to within 10%, appropriately within 5%, and particularly within 1% of a given value or range.

[0381] If multiple diffraction patterns are available, particle statistics (PS) and / or preferred orientation (PO) can be evaluated. Consistent relative intensities between XRPD patterns from multiple diffractometers indicate good orientation statistics. Alternatively, the observed XRPD pattern can be compared with an XRPD pattern calculated based on the single-crystal structure, if available. Two-dimensional scattering patterns using an area detector can also be used to evaluate PS / PO. If the effects of both PS and PO are determined to be negligible, the XRPD pattern represents the average powder intensity of the sample, and significant peaks can be identified as "representative peaks." Generally, the larger the amount of data collected to determine representative peaks, the more confident one is in classifying those peaks.

[0382] In terms of their existence, a "characteristic peak" is a subset of representative peaks and is used to distinguish one crystalline polymorph from another (polymorphs are crystalline forms with the same chemical composition). Characteristic peaks are determined by evaluating, within ±0.2° 2θ, which representative peaks (if any) are present in one crystalline polymorph of the compound compared to all other known crystalline polymorphs of the compound. Not all crystalline polymorphs of a compound necessarily possess at least one characteristic peak.

[0383] The term "preferred orientation" used in this paper refers to an extreme case of a non-random distribution of crystallites in a solid-state form. In XRPD, the ideal sample is homogeneous, and the crystallites are randomly distributed within the bulk solid. In a truly random sample, every possible reflection from a given set of planes will have an equal number of crystallites contributing to it. However, this is not the case when the solid-state form is in a preferred orientation. Therefore, comparing the intensity of a random orientation diffraction pattern with that of a preferred orientation can appear completely different. Quantitative analysis based on intensity ratios can be severely distorted by preferred orientation. Careful sample preparation is important to reduce the occurrence of preferred orientation.

[0384] The term "substantially identical" used herein to refer to a graph is intended to mean that the graph is considered to represent the type and kind of characteristic data obtained by a person skilled in the art taking into account acceptable deviations. Such deviations may be caused by factors related to sample size, sample preparation, the specific instrument used, operating conditions, and other experimental conditions known in the art. For example, those skilled in the art will understand that the endothermic onset temperature and peak temperature measured by differential scanning calorimetry (DSC) may differ significantly in different experiments. For example, those skilled in the art can readily identify whether two X-ray diffraction patterns or two DSC thermograms are substantially identical. In some embodiments, two X-ray diffraction patterns are considered substantially identical when the characteristic peaks differ by no more than ±0.2° 2-θ.

[0385] 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 also include salts of monobasic acids, dibasic acids, etc.

[0386] Dosage In some embodiments, the composition comprising the crystalline form described herein is administered for preventative and / or therapeutic treatment. In some therapeutic applications, the composition is administered to a patient who already has a disease or condition in an amount sufficient to cure or at least partially stop at least one symptom of the disease or condition. The effective amount for this purpose depends on the severity and course of the disease or condition, prior therapy, the patient's health status, weight, and response to the drug, as well as the judgment of the attending physician. The therapeutically effective amount may optionally be determined by methods including, but not limited to, dose escalation and / or dose range clinical trials.

[0387] In some implementation schemes in which the patient’s condition does not improve, the compound is administered long-term (i.e. for an extended period of time, including a patient’s entire life) at the physician’s discretion in order to improve or otherwise control or limit the symptoms of the patient’s disease or condition.

[0388] The amount of a given drug corresponding to such a quantity varies depending on factors such as the specific compound, the disease condition and its severity, and the identity of the person or host requiring treatment (e.g., weight, sex). Nevertheless, the quantity is determined based on the specific circumstances of the case, including, for example, the specific drug administered, the route of administration, the condition being treated, and the person or host being treated.

[0389] However, generally, the dosage used for adult treatment is typically in the range of 0.01 mg to 5000 mg per day. In one aspect, the dosage used for adult treatment is about 1 mg to about 1000 mg per day. In one embodiment, the required dosage is conveniently presented as a single dose or as fractions administered simultaneously or at appropriate intervals, for example, as two, three, four or more sub-dose administrations per day.

[0390] In one embodiment, the daily dose suitable for the crystalline form described herein or a pharmaceutically acceptable salt thereof is from about 0.01 to about 50 mg / kg of body weight. In some embodiments, the amount of active ingredient in the daily dose or dosage form may be lower or higher than the range indicated herein, depending on various variables in the individual treatment regimen. In various embodiments, the daily dose and unit dose vary depending on many variables, including but not limited to the activity of the compound used, the disease or condition to be treated, the method of administration, the individual's requirements, the severity of the disease or condition being treated, and the judgment of the healthcare professional.

[0391] Further embodiments exist in any of the foregoing aspects, wherein an effective amount of the crystalline form 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 locally to a mammal; and / or (f) administered to a mammal neither systemically nor locally.

[0392] Further embodiments exist in any of the foregoing aspects, which include a single application of an effective amount of the crystalline form disclosed herein, including further embodiments in which (i) the compound is applied once daily; or (ii) the compound is applied multiple times a day to mammals. Example

[0393] The following embodiments are provided for illustrative purposes only and do not limit the scope of the claims provided herein.

[0394] Example 1: Preparation of Compound 1 in its free form, type A

[0395] 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). Then, amyl nitrite (25.8 g, 220 mmol) was added to the reaction mixture at 0 °C, and the mixture was stirred at 25 °C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography to give 1-2 (4.4 g, 27% yield) as a yellow oil. LCMS: 276.1 [M+H] + .

[0396] 1,3-Dichloro-5,5-dimethylhydantoin (858 mg, 4.36 mmol) was added to a mixture of 1-2 (1.00 g, 3.63 mmol) in MeCN (20 mL), AcOH (2.5 mL), and water (5 mL) at -15 °C. The reaction mixture was stirred at -15–25 °C for 1 h. 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 rapid silica gel chromatography to give 1-3 (660 mg, 72% yield) as a white solid. LCMS: 251.9 [M+H] + .

[0397] 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-J009-1 Pd G3 (0.9 g, 0.97 mmol), and K2CO3 (8.9 g, 64.4 mmol, 100 mesh) were added. The reaction mixture was stirred at 150 °C and N2 for 48 h. The mixture was filtered and concentrated. The resulting residue was purified by rapid silica gel chromatography to give 1-5 (2.5 g, 32% yield) as a yellow solid. LCMS: 239.1 [M+H] + .

[0398] Sodium methoxide (2.49 g, 46.18 mmol) was added to a THF (110 mL) solution of 1-5 (11 g, 46.18 mmol). The reaction mixture was stirred at room temperature and under N2 for 1 h. Water was added. The mixture was extracted with DCM. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and filtered. The residue was purified by rapid silica gel chromatography to give 1-6 (8.6 g, 74% yield) as a yellow solid. LCMS: 251.1 [M+H] + .

[0399] 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 at 70 °C and N₂ for 6 h. The mixture was concentrated. Water was added. The mixture was extracted with DCM. The combined organic phases were washed with brine, dried over anhydrous Na₂SO₄, and filtered. The residue was purified by rapid silica gel chromatography to give 1-7 (4.8 g, 53%) as a white solid. LCMS: 264.1 [M+H] + .

[0400] Add 1-3 (7.2 g, 28 mmol) to a solution of 1-7 (5 g, 19 mmol) in 50 mL of MeCN. Stir the mixture at 25 °C for 1 h. Add DMSO (150 mg, 1.9 mmol) and 3,5-dimethylpyridine (6.1 g, 57 mmol). Stir the reaction mixture at 25 °C for 1.5 h. Then concentrate the mixture. First, purify the resulting residue by rapid silica gel chromatography to obtain a solid, then lyophilize the solid (MeCN / H2O) to give compound 1 as a white solid. Samples of this white solid were taken for XRPD, DSC, TGA, and other assays. 1 H-NMR and LCMS analysis. LCMS: 479.2 [M+H]+. 1 H NMR (400 MHz, DMSO-) d 6 ) δ 10.13 (s, 1H), 7.37-7.31 (m, 2H), 7.26 (d, J = 1.6 Hz, 1H), 6.89 (d, J = 1.6 Hz, 1H), 6.82 (s, 1H), 3.89 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 2.39 (s, 3H).

[0401] The XRPD image of the obtained solid is shown below. Figure 2 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 1. The DSC and TGA results are as follows. Figure 3 and Figure 4 As shown.

[0402] The inhibition of KAT6A enzyme activity by compound 1 was determined using a 384-well radiometric assay. Compound 1 was serially diluted 10 times in DMSO, and then 200 nL volumes were transferred to 384-well plates via Echo (Labcyte). 10 μL of 2x 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 aliquoted into the plates, except for the low control wells (where 10 μL of assay buffer was transferred). The plates were incubated at room temperature for 15 min, and then 10 μL of 2x […] was added to each well. 3 [H]-acetyl-CoA (Ac-CoA) and substrate peptide mixed solution (500 nM (KAT6A) in assay buffer) 3 The reaction was initiated with H]-Ac-CoA (PerkinElmer) and 800 nM (KAT6A) biotinylated H4 (1-30) peptide (GL Biochem). The plate was incubated at room temperature for 60 min (KAT6A) and then the reaction was terminated by adding 10 μL of stop solution (cold Ac-CoA in 1x assay buffer (Cayman)). 25 μL of the reaction from each well was transferred to a Flashplate (PerkinElmer) and incubated for another 1 h at room temperature. The plate was read on Microbeta and the percentage of inhibition for each compound-treated well was calculated according to the formula inh% = (Max - sample) / (Max - Min) * 100, where Max is the signal from the high control wells with the enzyme and Min is the signal from the low control wells with only assay buffer. The inh% data were further fitted in XL-Fit to obtain IC50 values ​​using a 4-parameter logic (4PL) sigmoid curve model. The IC50 for compound 1 with KAT6A was 5.9 nM.

[0403] The permeability of compound 1 was determined in a Caco-2 assay. Caco-2 cells purchased from ATCC were used at a concentration of 1 x 10⁻⁶. 5 cells / cm 2Cells were seeded onto polyethylene (PET) membranes in 96-well Corning Insert plates, and the culture medium was changed every 4–5 days until days 21–28 to allow for confluence of cell monolayers. The transport buffer used in this study was HBSS containing 10.0 mM HEPES at pH 7.40 ± 0.05. Compound 1 was tested in duplicate at 2.00 μM. The final DMSO concentration was adjusted to less than 1%. The plates were incubated for 2 hours at 37 ± 1 °C with 5% CO2 under saturated humidity without shaking. All samples were then centrifuged at 3200 xg for 10 min after mixing with acetonitrile containing the internal standard. The concentrations of the tested and control compounds in the starting, donor, and recipient solutions were quantified by LC-MS / MS using the analyte / internal standard peak area ratio. Following the transport assay, fluorescent yellow rejection assays were used to determine the integrity of the Caco-2 cell monolayer. The permeability results of Compound 1 and PF-9363 are shown in the table below.

[0404]

[0405] *PF-9363 is Example 98 in WO2020 / 254946 A1, which has the following structure: .

[0406] Example 2: Preparation of the amorphous free form of compound 1 400.2 mg of compound 1 in its free form, 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 plot of the obtained solid is shown below. Figure 1 As shown. It is the amorphous form of compound (I).

[0407] Example 3: Alternative preparation of compound 1 type A Approximately 20 mg of the amorphous free form 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). Water was added to the solution and the mixture was magnetically stirred until a precipitate formed. The obtained precipitate was separated for XRPD analysis. XRPD plot and... Figure 2 It is identical and has been identified as compound 1, type A.

[0408] Example 4: Preparation of Compound 1 in its free form, type B Compound 1 in its free form A (50 mg) was slurried in MeOH (0.5 mL) at room temperature (RT) for 6 days to obtain compound 1 in its free form B. The solids were separated by centrifugation and air-dried at RT prior to characterization. Samples were taken for XRPD, DSC, TGA, 1H-NMR, and DVS analysis.

[0409] XRPD diagram as follows Figure 5 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 2. Figure 7 The TGA curves show that the weight loss is 1.29% at temperatures up to 150°C. Figure 6 The DSC curve in the image shows an endothermic point at 173.1℃ (peak temperature). 1 The 1H NMR spectrum showed no obvious residual organic solvent. Based on the limited weight loss of TGA and pure DSC, it is speculated that the free form B is an anhydrous product. Figure 8 The DVS plot shows that at 80% relative humidity (RH) / 25°C, 0.0679% water absorption was detected in the adsorption curve from 0%RH to 95%RH, indicating that the free form of compound 1, free form B, is non-hygroscopic.

[0410] Example 5: Preparation of Compound 1 C-type Approximately 20 mg of the amorphous free 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). Water was added to the solution and the mixture was magnetically stirred until a precipitate formed. The resulting precipitate was separated for use in XRPD, DSC, TGA, and... 1 H NMR analysis.

[0411] The XRPD image of the obtained solid is shown below. Figure 9 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 3. The DSC and TGA results are as follows. Figure 10 and Figure 11 As shown.

[0412] Example 6: Preparation of Compound 1 D form Approximately 20 mg of the amorphous free 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). Heptane was added, and the solution was magnetically stirred until a precipitate formed. The resulting precipitate was separated for use in XRPD, DSC, TGA, and... 1 H NMR analysis.

[0413] The XRPD image of the obtained solid is shown below. Figure 12As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 4. The DSC and TGA results are as follows. Figure 13 and Figure 14 As shown.

[0414] Example 7: Preparation of Compound 1 E type Approximately 20 mg of compound 1 in its free form, type A, was dissolved in 0.5 mL of toluene in an HPLC vial at 50 °C. After cooling back to RT and evaporation at RT, a precipitate formed. The solid was separated by centrifugation and air-dried at RT for XRPD, DSC, TGA, and... 1 H-NMR analysis.

[0415] XRPD diagram as follows Figure 15 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 5. Figure 16 The TGA curves show that the weight loss is 16.63% at temperatures up to 150°C. Figure 17 The DSC curves show three endothermic points at 101.0, 109.6, and 173.4 °C, and one exothermic point at 104.0 °C (peak temperature).

[0416] Example 8: Preparation of Compound 1 F type Approximately 20 mg of compound 1 in its free form, type A, was suspended in 0.5 mL of MEK. The suspension was stirred and cyclically cooled for 4 days, ranging from 50 °C to 5 °C. The temperature was first raised to 50 °C at a rate of 4.5 °C / min, then equilibrated for 2 hours, followed by cooling to 5 °C at a rate of 0.1 °C / min and holding isothermally at 5 °C for 2 hours. The final step involved cooling to 5 °C at a rate of 0.1 °C / min and holding isothermally at 5 °C. The resulting solid was separated and air-dried for use in XRPD, DSC, TGA, and [other processes]. 1 H NMR analysis.

[0417] The XRPD image of the obtained solid is shown below. Figure 18 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 6. The DSC and TGA results are as follows. Figure 19 and Figure 20 As shown.

[0418] Example 9: Preparation of sodium salt A of compound 1 Sodium salt type A was obtained by slurrying the free form B and NaOH (1 equivalent) in acetone / H2O (19:1, v:v) at -20°C for 1 day. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0419] The XRPD image of the obtained solid is shown below. Figure 21As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 7. The DSC and TGA results are as follows. Figure 22 and Figure 23 As shown.

[0420] Example 10: Preparation of sodium salt type B of compound 1 Sodium salt B was obtained by slurrying the free form B and NaOH (1 equivalent) in EtOAc at RT for 3 days. XRPD stacking showed the peak of the free form B.

[0421] The XRPD image of the obtained solid is shown below. Figure 24 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 8.

[0422] Example 11: Preparation of sodium salt C of compound 1 Sodium salt C was obtained by slurrying sodium salt B and its free form with NaOH (approximately 1 equivalent) in EtOAc at RT for 2 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0423] The XRPD image of the obtained solid is shown below. Figure 25 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 9. The DSC and TGA results are as follows. Figure 26 and Figure 27 As shown.

[0424] Example 12: Preparation of sodium salt D of compound 1 Sodium salt D was obtained by slurrying the free form B and NaOH (2 equivalents) in IPA at RT. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0425] The XRPD image of the obtained solid is shown below. Figure 28 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 10. The DSC and TGA results are as follows. Figure 29 and Figure 30 As shown.

[0426] Example 13: Preparation of potassium salt A of compound 1 Potassium salt type A was obtained by slurrying free form B and KOH (1 equivalent) in acetone / H2O (19:1, v:v) at RT for 3 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0427] The XRPD image of the obtained solid is shown below. Figure 31 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 11. The DSC and TGA results are as follows. Figure 32 and Figure 33 As shown.

[0428] Example 14: Preparation of Compound 1 Ammonium Salt Type A Ammonium salt type A was obtained by slurrying free form B and ammonia (1 equivalent) in acetone / H2O (19:1, v:v) at RT for 3 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0429] The XRPD image of the obtained solid is shown below. Figure 34 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 12. The DSC and TGA results are as follows. Figure 35 and Figure 36 As shown.

[0430] Example 15: Preparation of Compound 1 Ammonium Salt Type B Ammonium salt B was obtained by slurrying the free form B and ammonia (1 equivalent) in EtOAc at RT for 3 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0431] The XRPD image of the obtained solid is shown below. Figure 37 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 13. The DSC and TGA results are as follows. Figure 38 and Figure 39 As shown.

[0432] Example 16: Preparation of Compound 1 Ammonium Salt C Ammonium salt C was obtained by slurrying the free form B and ammonia (1 equivalent) in IPA at RT for 3 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0433] The XRPD image of the obtained solid is shown below. Figure 40 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 14. The DSC and TGA results are as follows. Figure 41 and Figure 42 As shown.

[0434] Example 17: Preparation of Compound 1 L-Arginine Salt Type A L-arginine salt type A was obtained by slurrying the free form B and arginine (1 equivalent) in acetone / H2O (19:1, v:v) at RT for 3 days. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0435] The XRPD image of the obtained solid is shown below. Figure 43 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 15. The DSC and TGA results are as follows. Figure 44 and Figure 45 As shown.

[0436] Example 18: Preparation of choline salt A type of compound 1 Choline salt A was obtained by slurrying the free form B and choline (2 equivalents) in IPA under RT. The solid was separated by centrifugation and dried under RT vacuum before characterization.

[0437] The XRPD image of the obtained solid is shown below. Figure 46 As shown in the figure. The main peak and its associated intensity in the XRPD plot are shown in Table 16. The DSC and TGA results are as follows. Figure 47 and Figure 48 As shown.

[0438] Solvent abbreviation 1

[0439] Analysis methods for free forms Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) TGA data was collected using TA Instruments' Discovery TGA 5500. DSC was performed using TA Instruments' Discovery DSC 2500. Detailed parameters used are as follows.

[0440]

[0441] X-ray powder diffractometer (XRPD) For XRPD analysis, a PANalytical Empyrean and an X'Pert3 X-ray powder diffractometer were used. The XRPD parameters used are listed below.

[0442]

[0443] Dynamic vapor adsorption (DVS) DVS was measured using SMS (Surface Measurement Systems) DVS Intrinsic. The relative humidity at 25°C was calibrated based on the deliquescence points of LiCl, Mg(NO3)2, and KCl. The parameters for the DVS test are listed below.

[0444]

[0445] 1 H-NMR Solution NMR was collected using DMSO-d6 as the solvent on a Bruker 400M NMR spectrometer. Detailed parameters used are listed below.

[0446]

[0447] High-performance liquid chromatography (HPLC) An Agilent 1260 with a VWD detector was used, and detailed chromatographic conditions are listed below.

[0448]

[0449] Salt analysis methods Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) TGA data was collected using TA Instruments' Discovery TGA 5500. DSC was performed using TA Instruments' Discovery DSC 2500. Detailed parameters used are as follows.

[0450]

[0451] X-ray powder diffractometer (XRPD) For XRPD analysis, PANalytical Empyrean and X'Pert were used. 3 X-ray powder diffractometer. The XRPD parameters used are listed below.

[0452]

[0453] Dynamic vapor adsorption (DVS) Dynamic vapor adsorption was performed using ADVENTURE series DVS at 25°C under nitrogen purge. Approximately 30 mg of material was used. The sample was analyzed using the following methods: From 0%RH to 95%RH, increase by 10%RH each time (5% increase from 90%RH to 95%RH). From 95%RH to 0%RH, reduce RH by 10% each time (reducing by 5% from 95%RH to 90%RH). 1 H-NMR Collection was performed using a Bruker 400M in DMSO-d6 solvent. 1 H NMR data.

[0454] High-performance liquid chromatography (HPLC) An Agilent 1260 with a VWD detector was used, and detailed chromatographic conditions are listed below.

[0455]

[0456] IC Analysis Using Thermo Scientific with a conductivity detector TM Dionex TM AquionTM The ion chromatography (IC) system 1100 is described below, along with detailed chromatographic conditions.

[0457]

Claims

1. A solid state form of 2,4-dimethoxy-N-(4-methoxy-6-(thiazol-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridazine-3-sulfonamide (Compound 1) or a pharmaceutically acceptable salt thereof.

1. A solid state form of 2,4-dimethoxy-N-(4-methoxy-6-(thiazol-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridazine-3-sulfonamide (Compound 1) or a pharmaceutically acceptable salt thereof.

2. The solid form of claim 1, wherein the solid form is a crystalline form.

3. The solid form of claim 1 or 2, wherein the solid form is crystalline Compound 1 Free Form Type A, crystalline Compound 1 Free Form Type C, crystalline Compound 1 Free Form Type D, crystalline Compound 1 Free Form Type E, or crystalline Compound 1 Free Form Type F.

4. The solid form of claim 1 or 2, wherein the solid form is crystalline Compound 1 Free Form Type B.

5. The solid form of claim 1 or 2, wherein the solid form is a form of a salt.

6. The solid form of claim 1 or 2, wherein the solid form is a form of a sodium salt, a potassium salt, an ammonium salt, or a choline salt.

7. The solid form of claim 1 or 2, wherein the solid form is a form of an L-arginine salt.

8. The crystalline form of claim 2, wherein the crystalline form is Compound 1 Free Form Type B, which is characterized by has at least one of the following properties: (a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Ka radiation; (b) an X-ray powder diffraction (XRPD) pattern having peaks at 12.8 ± 0.2° 2Q, 21.6 ± 0.2° 2Q, and 24.7 ± 0.2° 2Q as measured using Cu Ka radiation; (c) a differential scanning calorimetry (DSC) thermogram substantially the same as shown in FIG. 6; (d) a thermogravimetric thermal analysis (TGA) thermogram substantially the same as shown in FIG. 7; or (e) a combination thereof.

9. The crystalline form of claim 8, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Ka radiation.

10. The crystalline form of claim 8 or 9, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks found in Table 2 as measured using Cu Ka radiation.

11. The crystalline form of any one of claims 8 to 10, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern having peaks at 12.8 ± 0.2° 2Q, 21.6 ± 0.2° 2Q, and 24.7 ± 0.2° 2Q as measured using Cu Ka radiation.

12. The crystalline form of any one of claims 8 to 11, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.0 ± 0.2° 2Q, 14.5 ± 0.2° 2Q, and 22.7 ± 0.2° 2Q as measured using Cu Ka radiation.

13. The crystalline form of any one of claims 8 to 12, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.4 ± 0.2° 2Q, 23.0 ± 0.2° 2Q, and 27.0 ± 0.2° 2Q as measured using Cu Ka radiation.

14. The crystalline form of any one of claims 8-13, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 22.1 ± 0.2° 2Q and 25.1 ± 0.2° 2Q, as measured using Cu Ka radiation.

15. The crystalline form of any one of claims 8-10, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4 ± 0.2° 2Q, 12.0 ± 0.2° 2Q, 12.8 ± 0.2° 2Q, 14.5 ± 0.2° 2Q, 21.6 ± 0.2° 2Q, 22.1 ± 0.2° 2Q, 22.7 ± 0.2° 2Q, 23.0 ± 0.2° 2Q, 24.7 ± 0.2° 2Q, 25.1 ± 0.2° 2Q, and 27.0 ± 0.2° 2Q, as measured using Cu Ka radiation.

16. The crystalline form of any one of claims 8-15, wherein the crystalline form is non-hygroscopic.

17. The crystalline form of any one of claims 8-16, wherein the crystalline form is an anhydrate.

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

19. The crystalline form of claim 2, wherein the crystalline form is Compound 1 L-arginine Salt Form A, characterized by has at least one of the following properties: (a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43, as measured using Cu Ka radiation; (b) an X-ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2Q, 13.7 ± 0.2° 2Q, and 18.6 ± 0.2° 2Q, as measured using Cu Ka radiation; (c) a differential scanning calorimetry (DSC) thermogram substantially the same as shown in FIG. 44; (d) a thermogravimetric analysis (TGA) thermogram substantially the same as shown in FIG. 45; or (e) a combination thereof.

20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43, as measured using Cu Ka radiation.

21. The crystalline form of claim 19 or 20, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks as seen in Table 15, as measured using Cu Ka radiation.

22. The crystalline form of any one of claims 19-21, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2Q, 13.7 ± 0.2° 2Q, and 18.6 ± 0.2° 2Q, as measured using Cu Ka radiation.

23. The crystalline form of any one of claims 19-22, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.1 ± 0.2° 2Q, 12.6 ± 0.2° 2Q, and 15.3 ± 0.2° 2Q, as measured using Cu Ka radiation.

24. The crystalline form of any one of claims 19-23, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 19.6 ± 0.2° 2Q, 20.5 ± 0.2° 2Q, and 21.7 ± 0.2° 2Q, as measured using Cu Ka radiation.

25. The crystalline form of any one of claims 19-21, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2Q, 11.0 ± 0.2° 2Q, 12.6 ± 0.2° 2Q, 13.7 ± 0.2° 2Q, 15.3 ± 0.2° 2Q, 18.6 ± 0.2° 2Q, 19.6 ± 0.2° 2Q, 20.5 ± 0.2° 2Q, and 21.7 ± 0.2° 2Q, as measured using Cu Ka radiation.

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

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

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

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

30. A method of treating cancer in a mammal in need thereof, the method comprising administering to the mammal the crystalline form of any one of claims 2-25, or a pharmaceutically acceptable salt thereof.

31. A method of treating cancer in a mammal in need thereof, the method comprising administering to the mammal the pharmaceutical composition of claim 26.

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

33. The method of 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 lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and non-Hodgkin's lymphoma.

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

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