Salt of LPAR1 inhibitor, crystal form of salt, composition, and pharmaceutical use thereof

Abstract

Disclosed in the present invention are a salt of an LPAR1 inhibitor, a crystal form of the salt, a composition, and pharmaceutical use thereof. The salt and the crystal form of the salt are a salt formed from compound I or a stereoisomer thereof and any one of the following acids or bases, and a crystal form thereof: succinic acid, tartaric acid, hydrochloric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid, 1,2-ethanedisulfonic acid, tris(hydroxymethyl)aminomethane, sodium hydroxide, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, lysine, diethylamine, or diethanolamine. The salts of compound I or the stereoisomer thereof and the crystal forms of the salts provided in the present invention all have stable physical and chemical properties and good biological properties, which are more conducive to the quality control of drugs and have the potential to be manufactured as a drug.

Description

A salt of an LPAR1 inhibitor, its crystal form, compositions, and pharmaceutical uses thereof.

[0001] This application claims priority to Chinese Patent Application No. 2025101207835, filed on January 24, 2025, and Chinese Patent Application No. 2025113224600, filed on September 16, 2025. The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention relates to the field of medicinal chemistry, and more specifically to a salt of an LPAR1 inhibitor, the crystal form of the salt, compositions thereof, and their pharmaceutical uses. Background Technology

[0003] Lysophosphatidic acid (monoacyl-glycerol-3-phosphate, LPA) is a class of bioactive phospholipids produced by lysophosphatidylcholine (LPC) and exerts a wide range of cellular responses, such as proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis, through a family of 7-membrane domain G protein-coupled receptors (GPCRs). These receptors are collectively referred to as LPA receptors (LPARs). LPA receptor-mediated signaling has been shown to influence many biological processes, such as wound healing, immunity, oncogenesis, angiogenesis, and neurogenesis. Aberrant upregulation of the LPA pathway has been associated with a variety of diseases. Therefore, LPA receptors may be drug targets for various diseases, including cancer, fibrosis, inflammation, pain, and cardiovascular disease.

[0004] Currently identified LPA receptors include LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6. Characterization of these six LPA receptors reveals differences in their tissue distribution and downstream signaling pathways. Lysophosphatidylcholine receptor 1 (LPAR1) is a G protein-coupled receptor that mediates the growth factor-like activity of LPA, playing a crucial role in the development of cancer, inflammation, fibrosis, neurological disorders, and urinary tract diseases. For example, silencing LPA1 with siRNA or using LPA1 antagonists can reduce tumor burden in bone and soft tissues; LPA promotes the migration of human monocytes and is associated with T cell proliferation and infiltration; LPA receptor antagonists can protect individuals from infection-induced inflammation; and upregulation of LPAR1 activity is associated with fibrosis observed in systemic scleroderma. Previous studies have shown that in mice with unilateral ureteral ligation, a model of renal fibrosis, LPA production and LPA1 expression are increased, and administration of LPA1-deficient or LPA receptor antagonist drugs can inhibit renal fibrosis. In bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis, LPA concentrations are elevated, and LPA1 is most abundant in fibroblasts, which play an important role in pulmonary fibrosis; LPA induces fibroblast migration. In mice with scleroderma and subcutaneous bleomycin administration, administration of LPA1-deficient or LPA receptor antagonist drugs can inhibit skin fibrosis. LPA and LPA1 are also associated with neuropathic pain. LPA1 can also participate in urinary system diseases by causing contraction of urethral resection specimens and prostate specimens and increasing intraurethral pressure.

[0005] Recently, LPAR1 inhibitors have been clinically studied for their association with fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis, but no small molecule inhibitors of LPAR1 have yet been marketed. Therefore, developing small molecule LPAR1 inhibitors with the desired selectivity, good biological activity, and strong metabolic stability is of great significance for the treatment of these diseases. Simultaneously, developing suitable drug formulations for these compounds, such as those that improve stability, hygroscopicity, and / or efficacy, to achieve good results in both the manufacturing and administration stages, has become an urgent technical challenge. Summary of the Invention

[0006] This invention provides a salt of compound I or its stereoisomer, wherein the salt is a salt formed by compound I or its stereoisomer with any of the following acids or bases: succinic acid, sodium hydroxide, hydrochloric acid, tartaric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid, lysine, 1,2-ethanedisulfonic acid, tris(hydroxymethyl)aminomethane, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, diethylamine, or diethanolamine;

[0007] According to the technical solution of the present invention, the stereoisomer of compound I is compound IR:

[0008] According to the technical solution of the present invention, the salt is a salt formed by compound IR with any of the following acids or bases: succinic acid, sodium hydroxide, hydrochloric acid, tartaric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid, lysine, 1,2-ethanedisulfonic acid, tris(hydroxymethyl)aminomethane, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, diethylamine, or diethanolamine.

[0009] According to the technical solution of the present invention, the salt is succinate of compound I or its stereoisomer, sodium salt of compound I or its stereoisomer, hydrochloride of compound I or its stereoisomer, tartrate of compound I or its stereoisomer, phosphate of compound I or its stereoisomer, fumarate of compound I or its stereoisomer, malate of compound I or its stereoisomer, hydrobromide of compound I or its stereoisomer, p-toluenesulfonate of compound I or its stereoisomer, benzenesulfonate of compound I or its stereoisomer, lysine salt of compound I or its stereoisomer, 1,2-ethanedisulfonate of compound I or its stereoisomer, tris(hydroxymethyl)aminomethane salt of compound I or its stereoisomer, magnesium salt of compound I or its stereoisomer, potassium salt of compound I or its stereoisomer, calcium salt of compound I or its stereoisomer, choline salt of compound I or its stereoisomer, meglumine salt of compound I or its stereoisomer, diethylamine salt of compound I or its stereoisomer, or diethanolamine salt of compound I or its stereoisomer.

[0010] According to the technical solution of the present invention, the tartaric acid is L-tartaric acid.

[0011] According to the technical solution of the present invention, in the salt of compound I or its stereoisomer, the molar ratio of the acid or base to compound I or its stereoisomer is (0.3-2):1, preferably (0.5-1.3):1, for example 0.5:1, 0.6:1, 0.8:1, 0.9:1, 1:1, 1.1:1, 1.2:1 or 1.3:1.

[0012] According to the technical solution of the present invention, the salt of compound I or its stereoisomer can be amorphous or crystalline.

[0013] According to the technical solution of the present invention, the p-toluenesulfonate, benzenesulfonate and choline salt are amorphous.

[0014] According to the technical solution of the present invention, the salt is a salt of compound IR.

[0015] According to the technical solution of the present invention, the salt of compound I or its stereoisomer is a crystal form; the crystal form is the succinate crystal form of compound I or its stereoisomer, the sodium salt crystal form of compound I or its stereoisomer, the hydrochloride crystal form of compound I or its stereoisomer, the tartrate crystal form of compound I or its stereoisomer, the phosphate crystal form of compound I or its stereoisomer, the fumarate crystal form of compound I or its stereoisomer, the malate crystal form of compound I or its stereoisomer, or the hydrobromic acid crystal form of compound I or its stereoisomer. Salt crystal form, lysine salt crystal form of compound I or its stereoisomer, 1,2-ethanedisulfonate crystal form of compound I or its stereoisomer, trihydroxymethylaminomethane salt crystal form of compound I or its stereoisomer, magnesium salt crystal form of compound I or its stereoisomer, potassium salt crystal form of compound I or its stereoisomer, calcium salt crystal form of compound I or its stereoisomer, meglumine salt crystal form of compound I or its stereoisomer, diethylamine salt crystal form of compound I or its stereoisomer, or diethanolamine salt crystal form of compound I or its stereoisomer.

[0016] According to the technical solution of the present invention, the crystal form may or may not contain a solvent, for example, the solvent is selected from organic solvents or water. Preferably, the organic solvent is selected from one, two or more of the following: isopropanol (IPA), isopropyl acetate (IPAc), methyl tert-butyl ether (MTBE), n-heptane, acetone, methanol, ethanol, 2-butanone, ethyl acetate, methyl acetate, 4-methyl-2-pentanone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, chloroform, n-hexane, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone. For example, the organic solvent is IPA, IPAc, or MTBE. The molar ratio of the organic solvent to compound I or its stereoisomer is (0.005-1):1, preferably (0.01-0.2):1; for example, 0.2:1, 0.07:1, 0.03:1, 0.02:1 or 0.01:1.

[0017] According to an embodiment of the present invention, the water may be water of crystallization or water without crystallization.

[0018] According to the technical solution of the present invention, the succinate crystal form is succinate crystal form A of compound IR.

[0019] According to the technical solution of the present invention, in the succinate crystal form A, the molar ratio of succinic acid to compound IR is (0.4-0.7):1; preferably (0.5-0.6):1; for example, 0.5:1 or 0.6:1.

[0020] According to an embodiment of the present invention, the succinate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 11.3±0.2°, 14.8±0.2°, and 20.2±0.2° in 2θ angles.

[0021] According to an embodiment of the present invention, the succinate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 14.8±0.2°, 17.0±0.2°, 18.6±0.2°, 19.6±0.2°, 20.2±0.2°, 20.8±0.2°, 22.7±0.2°, 23.8±0.2°, and 30.6±0.2° in 2θ angles.

[0022] According to an embodiment of the present invention, the succinate crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.2±0.2°, 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 12.6±0.2°, 14.8±0.2°, 17.0±0.2°, 18.0±0.2°, 18.6±0.2°, and 1... Characteristic peaks are present at 9.6±0.2°, 20.2±0.2°, 20.8±0.2°, 22.2±0.2°, 22.7±0.2°, 23.8±0.2°, 24.5±0.2°, 25.2±0.2°, 26.2±0.2°, 26.8±0.2°, 27.4±0.2°, 29.5±0.2°, and 30.6±0.2°.

[0023] According to the technical solution of the present invention, the succinate crystal form A has an X-ray powder diffraction pattern as shown in Figure 7.

[0024] According to the technical solution of the present invention, the succinate crystal form A has diffraction peaks as shown in Table 2-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0025] According to the technical solution of the present invention, the succinate crystal form A has diffraction peaks as shown in Table 2-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0026] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the succinate crystal form A has an endothermic peak at a peak temperature of approximately 150.0℃ ± 5℃. Preferably, the DSC curve of the succinate crystal form A has an endothermic peak at a peak temperature of approximately 151.5℃ ± 3℃. For example, an endothermic peak is present at a peak temperature of approximately 151.5℃. Another example is an endothermic peak at a peak temperature of approximately 150.5℃. Yet another example is an endothermic peak at a peak temperature of approximately 146.0℃. And yet another example is an endothermic peak at a peak temperature of approximately 146.5℃.

[0027] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the succinate crystal form A further exhibits an endothermic peak at a peak temperature of approximately 159.0 ± 3 °C. For example, it further exhibits an endothermic peak at a peak temperature of approximately 159.5 °C. And, for yet another example, it further exhibits an endothermic peak at a peak temperature of approximately 156.0 °C.

[0028] According to the technical solution of the present invention, the thermogravimetric analysis curve of the succinate crystal form A shows a weight loss of 0.98% ± 0.4% in the temperature range of 29.2℃ ± 3℃ to 140.0℃ ± 3℃. For example, the weight loss is 0.98% in the temperature range of 29.2℃ to 140.0℃. Another example is the weight loss of 0.63% in the temperature range of 26.4℃ to 140.0℃.

[0029] According to the technical solution of the present invention, the thermogravimetric analysis curve of the succinate crystal form A shows a weight loss of 0.51% ± 0.4% in the temperature range of 25.0℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 0.51% in the temperature range of 22.9℃ to 110.0℃.

[0030] According to the technical solution of the present invention, the succinate crystal form A has a DSC-TGA spectrum as shown in Figure 8.

[0031] According to the technical solution of the present invention, the succinate crystal form A is a rod-shaped crystal. For example, in one embodiment, the succinate crystal form A has a polarized light micrograph as shown in FIG10.

[0032] According to the technical solution of the present invention, the succinate crystal form A has the basic characteristics shown in Figure 9. 1 H-NMR spectrum.

[0033] According to the technical solution of the present invention, the succinate crystal form A is free of organic solvent or contains organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, acetone or MTBE, for example MTBE. More preferably, the molar ratio of the organic solvent to compound I or its stereoisomer is (0.01-0.2):1, for example 0.01:1.

[0034] According to the technical solution of the present invention, the succinate crystal form A does not contain organic solvents.

[0035] According to the technical solution of the present invention, the succinate crystal form A is a solvate, such as an organic solvate. Preferably, the succinate crystal form A is an IPA solvate, an IPAc solvate, an acetone solvate, or an MTBE solvate, such as an MTBE solvate. More preferably, in the organic solvate, the molar ratio of the organic solvent to compound I or its stereoisomer is (0.01-0.2):1, for example, 0.01:1.

[0036] According to an embodiment of the present invention, the tris(hydroxymethyl)aminomethane (Tris) salt crystal form is Tris salt crystal form A, Tris salt crystal form B or Tris salt crystal form C of compound IR.

[0037] According to the technical solution of the present invention, in the Tris salt crystal form A, the molar ratio of Tris to compound IR is (0.9-1.2):1; for example, 1:1.

[0038] According to an embodiment of the present invention, the Tris salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 17.2±0.2°, and 19.8±0.2° in 2θ angles.

[0039] According to an embodiment of the present invention, the Tris salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 11.1±0.2°, 11.7±0.2°, 12.4±0.2°, 13.2±0.2°, 14.0±0.2°, 17.2±0.2°, 18.8±0.2°, and 19.8±0.2° in 2θ angles.

[0040] According to an embodiment of the present invention, the Tris salt crystal form A, using Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 11.1±0.2°, 11.7±0.2°, 12.4±0.2°, 13.2±0.2°, 14.0±0.2°, 15.1±0.2°, 17.2±0.2°, 18.8±0.2°, 19.8±0.2°, 20.2±0.2°, 21.4±0.2°, 22.0±0.2°, 23.6±0.2°, 24.9±0.2°, 26.1±0.2°, 27.5±0.2°, 28.6±0.2°, and 29.0±0.2° in 2θ angles.

[0041] According to the technical solution of the present invention, the Tris salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 30.

[0042] According to the technical solution of the present invention, the Tris salt crystal form A has diffraction peaks as shown in Table 5-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0043] According to the technical solution of the present invention, the Tris salt crystal form A has diffraction peaks as shown in Table 5-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0044] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the Tris salt crystal form A has an endothermic peak at a peak temperature of approximately 121.6℃ ± 3℃. For example, it has an endothermic peak at a peak temperature of approximately 121.6℃.

[0045] According to the technical solution of the present invention, the thermogravimetric analysis curve of the Tris salt crystal form A shows a weight loss of 1.27% ± 0.5% in the temperature range of 28.4℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 1.27% in the temperature range of 28.4℃ to 130.0℃.

[0046] According to the technical solution of the present invention, the Tris salt crystal form A has a DSC-TGA pattern as shown in Figure 31.

[0047] According to the technical solution of the present invention, the Tris salt crystal form A is a granular crystal. For example, in one embodiment, the Tris salt crystal form A has a polarized light micrograph as shown in FIG33.

[0048] According to the technical solution of the present invention, the Tris salt crystal form A has the basic characteristics shown in Figure 32. 1 H-NMR spectrum.

[0049] According to the technical solution of the present invention, the Tris salt crystal form A does not contain organic solvent. Preferably, the organic solvent is IPA or n-heptane.

[0050] According to the technical solution of the present invention, in the Tris salt crystal form B, the molar ratio of Tris to compound IR is (0.9-1.2):1; for example, 1:1.

[0051] According to an embodiment of the present invention, the Tris salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 14.5±0.2°, 20.1±0.2°, 20.7±0.2°, and 21.8±0.2° in 2θ angles.

[0052] According to an embodiment of the present invention, the Tris salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.3±0.2°, 9.8±0.2°, 10.9±0.2°, 14.5±0.2°, 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, and 21.8±0.2° in 2θ angles.

[0053] According to an embodiment of the present invention, the Tris salt crystal form B, using Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.3±0.2°, 9.2±0.2°, 9.8±0.2°, 10.9±0.2°, 11.9±0.2°, 14.5±0.2°, 17.5±0.2°, 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, 21.8±0.2°, 26.9±0.2°, and 27.9±0.2° in 2θ angles.

[0054] According to an embodiment of the present invention, the Tris salt crystal form B is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 3.7±0.2°, 7.3±0.2°, 9.2±0.2°, 9.8±0.2°, 10.0±0.2°, 10.9±0.2°, 11.9±0.2°, 14.0±0.2°, 14.5±0.2°, 15.4±0.2°, 16.9±0.2°, and 17.5±0.2°. Characteristic peaks are present at 0.2°, 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, 21.8±0.2°, 23.2±0.2°, 24.0±0.2°, 25.5±0.2°, 26.9±0.2°, 27.5±0.2°, 27.9±0.2°, 29.2±0.2°, 33.0±0.2°, 34.3±0.2°, and 36.4±0.2°.

[0055] According to the technical solution of the present invention, the Tris salt crystal form B has an X-ray powder diffraction pattern as shown in Figure 34.

[0056] According to the technical solution of the present invention, the Tris salt crystal form B has diffraction peaks as shown in Table 5-5 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0057] According to the technical solution of the present invention, the Tris salt crystal form B has diffraction peaks as shown in Table 5-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0058] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the Tris salt crystal form B has an endothermic peak at a peak temperature of approximately 94.2℃ ± 5℃ and / or 118.7℃ ± 3℃. For example, it has endothermic peaks at peak temperatures of approximately 94.2℃ and 118.7℃. Another example is an endothermic peak at a peak temperature of approximately 97.1℃.

[0059] According to the technical solution of the present invention, the thermogravimetric analysis curve of the Tris salt crystal form B shows a weight loss of 5.73% ± 4.5% in the temperature range of 29.0℃ ± 3℃ to 120.0℃ ± 10℃. For example, the weight loss is 5.73% in the temperature range of 29.0℃ to 120.0℃. Another example is the weight loss of 1.53% in the temperature range of 26.3℃ to 110.0℃.

[0060] According to the technical solution of the present invention, the Tris salt crystal form B has a DSC-TGA pattern as shown in Figure 35.

[0061] According to the technical solution of the present invention, the Tris salt crystal form B is a rod-shaped crystal. For example, in one embodiment, the Tris salt crystal form B has a polarized light micrograph as shown in FIG37.

[0062] According to the technical solution of the present invention, the Tris salt crystal form B has the basic characteristics shown in Figure 36. 1 H-NMR spectrum.

[0063] According to the technical solution of the present invention, the Tris salt crystal form B does not contain organic solvents. Preferably, the organic solvent is acetone or n-heptane.

[0064] According to the technical solution of the present invention, in the Tris salt crystal form C, the molar ratio of Tris to compound IR is (0.9-1.2):1; for example, 1:1.

[0065] According to an embodiment of the present invention, the Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 10.3±0.2°, 13.7±0.2°, and 17.2±0.2° in 2θ angles.

[0066] According to an embodiment of the present invention, the Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 6.9±0.2°, 10.3±0.2°, 13.7±0.2°, 17.2±0.2°, and 20.2±0.2° in 2θ angles.

[0067] According to an embodiment of the present invention, the Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 5.4±0.2°, 6.9±0.2°, 10.3±0.2°, 13.7±0.2°, 17.2±0.2°, 20.2±0.2°, and 24.0±0.2° in 2θ angles.

[0068] According to the technical solution of the present invention, the Tris salt crystal form C has an X-ray powder diffraction pattern as shown in Figure 38.

[0069] According to the technical solution of the present invention, the Tris salt crystal form C exhibits diffraction peaks as shown in Table 5-7 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°.

[0070] According to the technical solution of the present invention, the Tris salt crystal form C exhibits diffraction peaks as shown in Table 5-8 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°.

[0071] According to the technical solution of the present invention, the differential scanning calorimetry curve of the Tris salt crystal form C has endothermic peaks at peak temperatures of approximately 58.9±3℃, 89.3±3℃ and 103.8±3℃; for example, it has endothermic peaks at peak temperatures of approximately 58.9℃, 89.3℃ and 103.8℃.

[0072] According to the technical solution of the present invention, the thermogravimetric analysis curve of the Tris salt crystal form C shows a weight loss of 5.83% ± 1.0% in the temperature range of 29.0℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 5.83% in the temperature range of 29.0℃ to 130.0℃.

[0073] According to the technical solution of the present invention, the Tris salt crystal form C has a DSC-TGA pattern as shown in Figure 39.

[0074] According to the technical solution of the present invention, the Tris salt crystal form C has a polarized light microstructure as shown in Figure 41.

[0075] According to the technical solution of the present invention, the Tris salt crystal form C has the basic characteristics shown in Figure 40. 1 H-NMR spectrum.

[0076] According to the technical solution of the present invention, the Tris salt crystal form C does not contain organic solvents. Preferably, the organic solvent is IPAc or n-heptane.

[0077] According to an embodiment of the present invention, the tartrate crystal form is tartrate crystal form A of compound IR.

[0078] According to the technical solution of the present invention, in the tartrate crystal form A, the molar ratio of tartaric acid to compound IR is (1.0-1.5):1; for example, 1.3:1.

[0079] According to an embodiment of the present invention, the tartrate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 14.7±0.2°, 15.0±0.2°, and 20.8±0.2° in 2θ angles.

[0080] According to an embodiment of the present invention, the tartrate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 4.1±0.2°, 7.3±0.2°, 8.3±0.2°, 11.3±0.2°, 14.7±0.2°, 15.0±0.2°, 17.2±0.2°, 19.7±0.2°, 20.2±0.2°, 20.8±0.2°, and 29.8±0.2°.

[0081] According to an embodiment of the present invention, the tartrate crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 4.1±0.2°, 7.3±0.2°, 8.3±0.2°, 11.3±0.2°, 14.7±0.2°, 15.0±0.2°, 17.2±0.2°, 17.9±0.2°, 18.6±0.2°, 19.7±0.2°, and 2... Characteristic peaks are present at 0.2±0.2°, 20.8±0.2°, 22.4±0.2°, 23.1±0.2°, 24.2±0.2°, 25.1±0.2°, 26.2±0.2°, 29.2±0.2°, 29.8±0.2°, 32.1±0.2°, 33.4±0.2°, 35.9±0.2°, 36.8±0.2°, and 37.5±0.2°.

[0082] According to the technical solution of the present invention, the tartrate crystal form A has an X-ray powder diffraction pattern as shown in Figure 3.

[0083] According to the technical solution of the present invention, the tartrate crystal form A has diffraction peaks as shown in Table 1-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0084] According to the technical solution of the present invention, the tartrate crystal form A has diffraction peaks as shown in Table 1-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0085] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the tartrate crystal form A has an endothermic peak at a peak temperature of approximately 152.5 ± 3 °C; for example, it has an endothermic peak at a peak temperature of approximately 152.5 °C. Another example is that it has an endothermic peak at a peak temperature of approximately 152.4 °C.

[0086] According to the technical solution of the present invention, the thermogravimetric analysis curve of the tartrate crystal form A shows a weight loss of 1.28% ± 1.0% in the temperature range of 28.6℃ ± 5℃ to 140.0℃ ± 10℃. For example, the weight loss is 1.28% in the temperature range of 28.6℃ to 140.0℃. Another example is the weight loss of 0.59% in the temperature range of 26.4℃ to 150.0℃.

[0087] According to the technical solution of the present invention, the tartrate crystal form A has a DSC-TGA spectrum as shown in Figure 4.

[0088] According to the technical solution of the present invention, the tartrate crystal form A is a granular crystal. For example, in one embodiment, the tartrate crystal form A has a polarized light micrograph as shown in FIG6.

[0089] According to the technical solution of the present invention, the tartrate crystal form A has the basic characteristics shown in Figure 5. 1 H-NMR spectrum.

[0090] According to the technical solution of the present invention, the tartrate crystal form A does not contain organic solvent. Preferably, the organic solvent is IPAc.

[0091] According to an embodiment of the present invention, the sodium salt crystal form is sodium salt crystal form A, sodium salt crystal form B, or sodium salt crystal form C of compound IR.

[0092] According to the technical solution of the present invention, in the sodium salt crystal form A, the molar ratio of sodium ions to compound IR is (0.7-1.2):1; for example, 0.9:1.

[0093] According to an embodiment of the present invention, the sodium salt crystal form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction, expressed in 2θ angles, has characteristic peaks at 6.2±0.2°, 13.1±0.2°, 13.3±0.2°, 21.1±0.2°, and 23.2±0.2°.

[0094] According to an embodiment of the present invention, the sodium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, 14.9±0.2°, 21.1±0.2°, and 23.2±0.2°.

[0095] According to an embodiment of the present invention, the sodium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 11.2±0.2°, 11.8±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, 14.9±0.2°, 15.6±0.2°, 17.8±0.2°, 18.6±0.2°, 19.5±0.2°, 21.1±0.2°, 23.2±0.2°, and 25.1±0.2°.

[0096] According to an embodiment of the present invention, the sodium salt crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 11.2±0.2°, 11.8±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, and 14... Characteristic peaks are present at 0.9±0.2°, 15.6±0.2°, 17.8±0.2°, 18.6±0.2°, 19.5±0.2°, 20.5±0.2°, 21.1±0.2°, 22.4±0.2°, 23.2±0.2°, 25.1±0.2°, 25.6±0.2°, 28.9±0.2°, and 31.1±0.2°.

[0097] According to the technical solution of the present invention, the sodium salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 18.

[0098] According to the technical solution of the present invention, the sodium salt crystal form A has diffraction peaks as shown in Table 4-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0099] According to the technical solution of the present invention, the sodium salt crystal form A has diffraction peaks as shown in Table 4-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0100] According to the technical solution of the present invention, the differential scanning calorimetry curve of the sodium salt crystal form A has an endothermic peak at a peak temperature of approximately 143.8 ± 3 °C; for example, it has an endothermic peak at a peak temperature of approximately 143.8 °C.

[0101] According to the technical solution of the present invention, the thermogravimetric analysis curve of the sodium salt crystal form A shows a weight loss of 2.95% ± 1.0% in the temperature range of 28.6℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 2.95% in the temperature range of 28.6℃ to 130.0℃.

[0102] According to the technical solution of the present invention, the sodium salt crystal form A has a DSC-TGA spectrum as shown in Figure 19.

[0103] According to the technical solution of the present invention, the sodium salt crystal form A is a granular crystal. For example, in one embodiment, the sodium salt crystal form A has a polarized light micrograph as shown in FIG21.

[0104] According to the technical solution of the present invention, the sodium salt crystal form A has the basic characteristics shown in Figure 20. 1 H-NMR spectrum.

[0105] According to the technical solution of the present invention, the sodium salt crystal form A does not contain organic solvent. Preferably, the organic solvent is IPA or n-heptane.

[0106] According to the technical solution of the present invention, in the sodium salt crystal form B, the molar ratio of sodium ions to compound IR is (0.4-0.8):1; for example, 0.6:1.

[0107] According to an embodiment of the present invention, the sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, and 15.5±0.2° in 2θ angles.

[0108] According to an embodiment of the present invention, the sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, 15.5±0.2°, 18.9±0.2°, 19.8±0.2°, 20.4±0.2°, 21.2±0.2°, 24.5±0.2°, and 25.0±0.2°.

[0109] According to an embodiment of the present invention, the sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 3.2±0.2°, 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, 15.5±0.2°, 17.9±0.2°, 18.9±0.2°, 19.8±0.2°, 20.4±0.2°, 21.2±0.2°, 22.1±0.2°, 23.9±0.2°, 24.5±0.2°, 25.0±0.2°, and 26.4±0.2°.

[0110] According to the technical solution of the present invention, the sodium salt crystal form B has an X-ray powder diffraction pattern as shown in Figure 22.

[0111] According to the technical solution of the present invention, the sodium salt crystal form B has diffraction peaks as shown in Table 4-5 using Cu-Kα radiation and X-ray powder diffraction expressed in 2θ angle, with an error range of ±0.2°.

[0112] According to the technical solution of the present invention, the sodium salt crystal form B has diffraction peaks as shown in Table 4-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0113] According to the technical solution of the present invention, the differential scanning calorimetry curve of the sodium salt crystal form B has an endothermic peak at a peak temperature of about 142.6 ± 3 °C; for example, it has an endothermic peak at a peak temperature of about 142.6 °C.

[0114] According to the technical solution of the present invention, the differential scanning calorimetry curve of the sodium salt crystal form B has an exothermic peak at a peak temperature of about 178.1 ± 3 °C; for example, it has an exothermic peak at a peak temperature of about 178.1 °C.

[0115] According to the technical solution of the present invention, the thermogravimetric analysis curve of the sodium salt crystal form B shows a weight loss of 2.39% ± 1.0% in the temperature range of 25.9℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 2.39% in the temperature range of 25.9℃ to 120.0℃.

[0116] According to the technical solution of the present invention, the sodium salt crystal form B has a DSC-TGA spectrum as shown in Figure 23.

[0117] According to the technical solution of the present invention, the sodium salt crystal form B is a granular crystal. For example, in one embodiment, the sodium salt crystal form B has a polarized light micrograph as shown in FIG25.

[0118] According to the technical solution of the present invention, the sodium salt crystal form B has the basic characteristics shown in Figure 24. 1H-NMR spectrum.

[0119] According to the technical solution of the present invention, the sodium salt crystal form B does not contain organic solvents. Preferably, the organic solvent is IPAc or n-heptane.

[0120] According to the technical solution of the present invention, in the sodium salt crystal form C, the molar ratio of sodium ions to compound IR is (0.9-1.2):1; for example, 1:1.

[0121] According to an embodiment of the present invention, the sodium salt crystal form C, when irradiated with Cu-Kα, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 13.1±0.2°, 13.3±0.2°, 17.4±0.2°, 17.9±0.2°, 21.1±0.2°, and 23.2±0.2° in 2θ angles.

[0122] According to an embodiment of the present invention, the sodium salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 11.2±0.2°, 11.9±0.2°, 13.1±0.2°, 13.3±0.2°, 14.0±0.2°, 17.4±0.2°, 17.9±0.2°, 18.4±0.2°, 19.6±0.2°, 20.6±0.2°, 21.1±0.2°, 22.7±0.2°, 23.2±0.2°, 25.0±0.2°, and 27.9±0.2°.

[0123] According to an embodiment of the present invention, the sodium salt crystal form C is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 6.2±0.2°, 10.2±0.2°, 10.8±0.2°, 11.2±0.2°, 11.9±0.2°, 12.4±0.2°, 13.1±0.2°, 13.3±0.2°, 14.0±0.2°, 17.4±0.2°, 17.9±0.2°, 1 Characteristic peaks are present at 8.4±0.2°, 19.3±0.2°, 19.6±0.2°, 20.6±0.2°, 21.1±0.2°, 22.3±0.2°, 22.7±0.2°, 23.2±0.2°, 23.8±0.2°, 25.0±0.2°, 25.7±0.2°, 27.9±0.2°, 28.9±0.2°, 31.1±0.2°, and 33.4±0.2°.

[0124] According to the technical solution of the present invention, the sodium salt crystal form C has an X-ray powder diffraction pattern as shown in Figure 26.

[0125] According to the technical solution of the present invention, the sodium salt crystal form C has diffraction peaks as shown in Table 4-8 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0126] According to the technical solution of the present invention, the sodium salt crystal form C has diffraction peaks as shown in Table 4-9 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0127] According to the technical solution of the present invention, the differential scanning calorimetry curve of the sodium salt crystal form C has endothermic peaks at peak temperatures of approximately 137.7±3℃ and 243.7±3℃; for example, it has endothermic peaks at peak temperatures of approximately 137.7℃ and 243.7℃.

[0128] According to the technical solution of the present invention, the thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 3.61% ± 1.0% in the temperature range of 26.4℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 3.61% in the temperature range of 26.4℃ to 130.0℃.

[0129] According to the technical solution of the present invention, the thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 5.59% ± 1.0% in the temperature range of 130.0℃ ± 3℃ to 210.0℃ ± 3℃. For example, the weight loss is 5.59% in the temperature range of 130.0℃ to 210.0℃.

[0130] According to the technical solution of the present invention, the sodium salt crystal form C has a DSC-TGA spectrum as shown in Figure 27.

[0131] According to the technical solution of the present invention, the sodium salt crystal form C is a granular crystal. For example, in one embodiment, the sodium salt crystal form C has a polarized light micrograph as shown in FIG29.

[0132] According to the technical solution of the present invention, the sodium salt crystal form C has the basic characteristics shown in Figure 28. 1 H-NMR spectrum.

[0133] According to the technical solution of the present invention, the sodium salt crystal form C contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, acetone or MTBE; for example, IPA. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.01:1.

[0134] According to the technical solution of the present invention, the sodium salt crystal form C is a solvate, preferably an organic solvate. Preferably, the sodium salt crystal form C is an IPA solvate, IPAc solvate, acetone solvate, or MTBE solvate; for example, an IPA solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.01:1.

[0135] According to an embodiment of the present invention, the hydrochloride crystal form is either hydrochloride crystal form A or hydrochloride crystal form B of compound IR.

[0136] According to an embodiment of the present invention, the hydrochloride crystal form is the hydrochloride crystal form A of compound IR.

[0137] According to the technical solution of the present invention, in the hydrochloride crystal form A, the molar ratio of hydrochloric acid to compound IR is (0.9-1.2):1; for example, 1:1 or 1.1:1; and even more for example, 1:1.

[0138] According to an embodiment of the present invention, the hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, and 12.9±0.2° in 2θ angles.

[0139] According to an embodiment of the present invention, the hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, 11.5±0.2°, 11.9±0.2°, 12.9±0.2°, 15.5±0.2°, 20.7±0.2°, 23.1±0.2°, 24.4±0.2°, and 28.0±0.2° in 2θ angles.

[0140] According to an embodiment of the present invention, the hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, 10.8±0.2°, 11.5±0.2°, 11.9±0.2°, 12.9±0.2°, 14.8±0.2°, 15.5±0.2°, 18.4±0.2°, 19.1±0.2°, 19.8±0.2°, 20.7±0.2°, 23.1±0.2°, 24.4±0.2°, 24.9±0.2°, 26.1±0.2°, 28.0±0.2°, and 30.2±0.2°.

[0141] According to the technical solution of the present invention, the hydrochloride crystal form A has an X-ray powder diffraction pattern as shown in Figure 11.

[0142] According to the technical solution of the present invention, the hydrochloride crystal form A has diffraction peaks as shown in Table 3-2 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0143] According to the technical solution of the present invention, the hydrochloride crystal form A has diffraction peaks as shown in Table 3-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0144] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the hydrochloride crystal form A has an endothermic peak at a peak temperature of approximately 109.3 ± 3 °C; for example, it has an endothermic peak at a peak temperature of approximately 109.3 °C. Another example is that it has an endothermic peak at a peak temperature of approximately 110.3 °C.

[0145] According to the technical solution of the present invention, the differential scanning calorimetry curve of the hydrochloride crystal form A further has an endothermic peak at a peak temperature of about 49.9±3℃; for example, it has an endothermic peak at a peak temperature of about 49.9℃.

[0146] According to the technical solution of the present invention, the thermogravimetric analysis curve of the hydrochloride crystal form A shows a weight loss of 7.02% ± 1.0% in the temperature range of 29.0℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 7.02% in the temperature range of 29.0℃ to 120.0℃.

[0147] According to the technical solution of the present invention, the hydrochloride crystal form A has a DSC-TGA spectrum as shown in Figure 12.

[0148] According to the technical solution of the present invention, the hydrochloride crystal form A has a polarized light microstructure as shown in Figure 14.

[0149] According to the technical solution of the present invention, the hydrochloride crystal form A has the basic characteristics shown in Figure 13. 1 H-NMR spectrum.

[0150] According to the technical solution of the present invention, the hydrochloride crystal form A does not contain organic solvent. Preferably, the organic solvent is MTBE.

[0151] According to the technical solution of the present invention, the hydrochloride crystal form A is a hydrate.

[0152] According to an embodiment of the present invention, the hydrochloride crystal form is the hydrochloride crystal form B of compound IR.

[0153] According to the technical solution of the present invention, in the hydrochloride crystal form B, the molar ratio of hydrochloric acid to compound IR is (0.9-1.2):1; for example, 1:1.

[0154] According to an embodiment of the present invention, the hydrochloride crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 10.0±0.2°, 11.0±0.2°, 11.8±0.2°, and 13.8±0.2° in 2θ angles.

[0155] According to an embodiment of the present invention, the hydrochloride crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.8±0.2°, 10.0±0.2°, 11.0±0.2°, 11.8±0.2°, 13.8±0.2°, 14.5±0.2°, 15.4±0.2°, 15.7±0.2°, 20.9±0.2°, and 25.1±0.2° in 2θ angles.

[0156] According to an embodiment of the present invention, the hydrochloride crystal form B is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 5.0±0.2°, 6.9±0.2°, 7.8±0.2°, 10.0±0.2°, 10.2±0.2°, 11.0±0.2°, 11.8±0.2°, 12.2±0.2°, 12.9±0.2°, and 13.8±0.2°. Characteristic peaks are present at 2°, 14.1±0.2°, 14.5±0.2°, 15.4±0.2°, 15.7±0.2°, 18.1±0.2°, 18.5±0.2°, 20.6±0.2°, 20.9±0.2°, 21.2±0.2°, 22.7±0.2°, 24.2±0.2°, 25.1±0.2°, and 25.8±0.2°.

[0157] According to an embodiment of the present invention, the hydrochloride crystal form B is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 5.0±0.2°, 6.9±0.2°, 7.8±0.2°, 10.0±0.2°, 10.2±0.2°, 11.0±0.2°, 11.8±0.2°, 12.2±0.2°, 12.9±0.2°, 13.8±0.2°, 14.1±0.2°, 14.5±0.2°, 15.4±0.2°, and 15.7±0.2°. Characteristic peaks are present at 2°, 18.1±0.2°, 18.5±0.2°, 19.5±0.2°, 20.6±0.2°, 20.9±0.2°, 21.2±0.2°, 22.7±0.2°, 23.4±0.2°, 24.2±0.2°, 24.5±0.2°, 25.1±0.2°, 25.8±0.2°, 27.4±0.2°, 27.9±0.2°, 29.7±0.2°, 31.2±0.2°, and 32.3±0.2°.

[0158] According to the technical solution of the present invention, the hydrochloride crystal form B has an X-ray powder diffraction pattern as shown in Figure 15.

[0159] According to the technical solution of the present invention, the hydrochloride crystal form B has diffraction peaks as shown in Table 3-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°.

[0160] According to the technical solution of the present invention, the hydrochloride crystal form B has diffraction peaks as shown in Table 3-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0161] According to the technical solution of the present invention, the differential scanning calorimetry curve of the hydrochloride crystal form B has an endothermic peak at a peak temperature of about 110.1 ± 3 °C; for example, it has an endothermic peak at a peak temperature of about 110.1 °C.

[0162] According to the technical solution of the present invention, the thermogravimetric analysis curve of the hydrochloride crystal form B shows a weight loss of 7.27% ± 2.0% in the temperature range of 25.5℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 7.27% in the temperature range of 25.5℃ to 110.0℃.

[0163] According to the technical solution of the present invention, the hydrochloride crystal form B has a DSC-TGA spectrum as shown in Figure 16.

[0164] According to the technical solution of the present invention, the hydrochloride crystal form B has the basic characteristics shown in Figure 17. 1 H-NMR spectrum.

[0165] According to the technical solution of the present invention, the hydrochloride crystal form B does not contain organic solvent. Preferably, the organic solvent is DCM.

[0166] According to an embodiment of the present invention, the phosphate crystal form is phosphate crystal form A of compound IR.

[0167] According to the technical solution of the present invention, in the phosphate crystal form A, the molar ratio of phosphoric acid to compound IR is (0.7-1.1):1; for example, 0.9:1.

[0168] According to an embodiment of the present invention, the phosphate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.1±0.2°, 14.5±0.2°, 14.8±0.2°, and 16.7±0.2° in 2θ angles.

[0169] According to an embodiment of the present invention, the phosphate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.2±0.2°, 7.1±0.2°, 14.5±0.2°, 14.8±0.2°, 16.7±0.2°, 19.2±0.2°, 22.3±0.2°, 24.8±0.2°, 29.2±0.2°, and 30.2±0.2° in 2θ angles.

[0170] According to an embodiment of the present invention, the phosphate crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 4.2±0.2°, 7.1±0.2°, 8.3±0.2°, 11.1±0.2°, 14.5±0.2°, 14.8±0.2°, 16.7±0.2°, 18.0±0.2°, 18.9±0.2°, 19.2±0.2°, and 20°. Characteristic peaks are present at 0.1±0.2°, 21.9±0.2°, 22.3±0.2°, 23.0±0.2°, 23.9±0.2°, 24.8±0.2°, 25.2±0.2°, 25.7±0.2°, 27.7±0.2°, 29.2±0.2°, 30.2±0.2°, 31.7±0.2°, 33.2±0.2°, and 33.7±0.2°.

[0171] According to the technical solution of the present invention, the phosphate crystal form A has an X-ray powder diffraction pattern as shown in Figure 42.

[0172] According to the technical solution of the present invention, the phosphate crystal form A has diffraction peaks as shown in Table 6-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0173] According to the technical solution of the present invention, the phosphate crystal form A has diffraction peaks as shown in Table 6-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0174] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the phosphate crystal form A has endothermic peaks at peak temperatures of approximately 75.6±3℃, 139.4±3℃, and 146.3±3℃. For example, endothermic peaks are present at peak temperatures of approximately 75.6℃, 139.4℃, and 146.3℃.

[0175] According to the technical solution of the present invention, the thermogravimetric analysis curve of the phosphate crystal form A shows a weight loss of 2.26% ± 1.0% in the temperature range of 23.8℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 2.26% in the temperature range of 23.8℃ to 120.0℃.

[0176] According to the technical solution of the present invention, the phosphate crystal form A has a DSC-TGA spectrum as shown in Figure 43.

[0177] According to the technical solution of the present invention, the phosphate crystal form A is crystal particles of varying sizes.

[0178] According to the technical solution of the present invention, the phosphate crystal form A does not contain organic solvent. Preferably, the organic solvent is MTBE.

[0179] According to an embodiment of the present invention, the fumarate crystal form is fumarate crystal form A of compound IR.

[0180] According to the technical solution of the present invention, in the fumarate crystal form A, the molar ratio of fumaric acid to compound IR is (0.6-1.0):1; for example, 0.8:1.

[0181] According to an embodiment of the present invention, the fumarate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 11.3±0.2°, 14.7±0.2°, and 14.9±0.2° in 2θ angles.

[0182] According to an embodiment of the present invention, the fumarate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 14.7±0.2°, 14.9±0.2°, 18.7±0.2°, 19.6±0.2°, 20.1±0.2°, 22.8±0.2°, and 28.8±0.2° in 2θ angles.

[0183] According to an embodiment of the present invention, the fumarate crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.2±0.2°, 7.2±0.2°, 8.1±0.2°, 8.4±0.2°, 11.3±0.2°, 12.6±0.2°, 14.7±0.2°, 14.9±0.2°, 15.1±0.2°, 17.0±0.2°, 18.0±0.2°, 18.7±0.2°, and 19.6±0.2°. Characteristic peaks are present at 2°, 20.1±0.2°, 21.0±0.2°, 21.7±0.2°, 22.2±0.2°, 22.8±0.2°, 23.9±0.2°, 24.5±0.2°, 25.4±0.2°, 26.2±0.2°, 26.8±0.2°, 27.5±0.2°, 28.8±0.2°, 29.4±0.2°, 30.5±0.2°, 32.5±0.2°, and 34.4±0.2°.

[0184] According to the technical solution of the present invention, the fumarate crystal form A has an X-ray powder diffraction pattern as shown in Figure 44.

[0185] According to the technical solution of the present invention, the fumarate crystal form A has diffraction peaks as shown in Table 6-5 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0186] According to the technical solution of the present invention, the fumarate crystal form A has diffraction peaks as shown in Table 6-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0187] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the fumarate crystal form A has an endothermic peak at a peak temperature of approximately 157.7 ± 3 °C. For example, it has an endothermic peak at a peak temperature of approximately 157.7 °C.

[0188] According to the technical solution of the present invention, the thermogravimetric analysis curve of the fumarate crystal form A shows a weight loss of 2.25% ± 1.0% in the temperature range of 28.9℃ ± 3℃ to 140.0℃ ± 3℃. For example, the weight loss is 2.25% in the temperature range of 28.9℃ to 140.0℃.

[0189] According to the technical solution of the present invention, the fumarate crystal form A has a DSC-TGA spectrum as shown in Figure 45.

[0190] According to the technical solution of the present invention, the fumarate crystal form A is a rod-shaped crystal.

[0191] According to the technical solution of the present invention, the fumarate crystal form A does not contain organic solvents. Preferably, the organic solvent is MTBE.

[0192] According to an embodiment of the present invention, the malate crystal form is malate crystal form A of compound IR.

[0193] According to the technical solution of the present invention, in the malate crystal form A, the molar ratio of malic acid to compound IR is (0.3-0.7):1; for example, 0.5:1.

[0194] According to an embodiment of the present invention, the malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.8±0.2°, 14.3±0.2°, and 15.2±0.2° in 2θ angles.

[0195] According to an embodiment of the present invention, the malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.8±0.2°, 11.4±0.2°, 14.3±0.2°, 15.2±0.2°, 16.5±0.2°, 19.4±0.2°, and 24.4±0.2° in 2θ angles.

[0196] According to an embodiment of the present invention, the malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 4.5±0.2°, 6.8±0.2°, 8.9±0.2°, 11.4±0.2°, 14.3±0.2°, 15.2±0.2°, 16.5±0.2°, 18.0±0.2°, 19.0±0.2°, 19.4±0.2°, 20.6±0.2°, 21.8±0.2°, 22.3±0.2°, 23.7±0.2°, 24.4±0.2°, 26.2±0.2°, 26.6±0.2°, 27.8±0.2°, and 29.1±0.2°.

[0197] According to the technical solution of the present invention, the malate crystal form A has an X-ray powder diffraction pattern as shown in Figure 46.

[0198] According to the technical solution of the present invention, the malate crystal form A has diffraction peaks as shown in Table 6-7 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°.

[0199] According to the technical solution of the present invention, the malate crystal form A has diffraction peaks as shown in Table 6-8 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°.

[0200] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the malate crystal form A has an endothermic peak at a peak temperature of approximately 147.9 ± 3 °C. For example, it has an endothermic peak at a peak temperature of approximately 147.9 °C.

[0201] According to the technical solution of the present invention, the thermogravimetric analysis curve of the malate crystal form A shows a weight loss of 0.40% ± 0.1% in the temperature range of 29.0℃ ± 3℃ to 140.0℃ ± 3℃. For example, the weight loss is 0.40% in the temperature range of 29.0℃ to 140.0℃.

[0202] According to the technical solution of the present invention, the malate crystal form A has a DSC-TGA spectrum as shown in Figure 47.

[0203] According to the technical solution of the present invention, the malate crystal form A is a rod-shaped crystal.

[0204] According to the technical solution of the present invention, the malate crystal form A does not contain organic solvents. Preferably, the organic solvent is MTBE.

[0205] According to an embodiment of the present invention, the hydrobromide crystal form is either hydrobromide crystal form A or hydrobromide crystal form B of compound IR.

[0206] According to the technical solution of the present invention, in the hydrobromide crystal form A, the molar ratio of hydrobromic acid to compound IR is (0.7-1.1):1; for example, 0.9:1.

[0207] According to an embodiment of the present invention, the hydrobromide crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 10.0±0.2°, 15.0±0.2°, and 26.1±0.2° in 2θ angles.

[0208] According to an embodiment of the present invention, the hydrobromide crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 5.0±0.2°, 7.7±0.2°, 10.0±0.2°, 10.9±0.2°, 11.7±0.2°, 15.0±0.2°, 18.4±0.2°, 20.0±0.2°, 20.4±0.2°, 21.9±0.2°, 22.6±0.2°, 25.0±0.2°, 26.1±0.2°±0.2°, 29.7±0.2°, and 31.2±0.2°.

[0209] According to the technical solution of the present invention, the hydrobromide crystal form A has an X-ray powder diffraction pattern as shown in Figure 48.

[0210] According to the technical solution of the present invention, the hydrobromide crystal form A has diffraction peaks as shown in Table 6-9 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0211] According to the technical solution of the present invention, the hydrobromide crystal form A has diffraction peaks as shown in Table 6-10 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0212] According to the technical solution of the present invention, the differential scanning calorimetry curve of the hydrobromide crystal form A has endothermic peaks at peak temperatures of approximately 55.5±3℃ and 112.0±3℃; for example, it has endothermic peaks at peak temperatures of approximately 55.5℃ and 112.0℃.

[0213] According to the technical solution of the present invention, the thermogravimetric analysis curve of the hydrobromide crystal form A shows a weight loss of 3.28% ± 1.0% in the temperature range of 29.2℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 3.28% in the temperature range of 29.2℃ to 130.0℃.

[0214] According to the technical solution of the present invention, the hydrobromide crystal form A has a DSC-TGA spectrum as shown in Figure 49.

[0215] According to the technical solution of the present invention, the hydrobromide crystal form A is an irregular blocky crystal.

[0216] According to the technical solution of the present invention, the hydrobromide crystal form A contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; for example, MTBE. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.03:1.

[0217] According to the technical solution of the present invention, the hydrobromide crystal form A is a solvate, preferably an organic solvate. Preferably, the hydrobromide crystal form A is an IPA solvate, an IPAc solvate, a n-heptane solvate, an acetone solvate, or an MTBE solvate; for example, an IPAc solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.03:1.

[0218] According to the technical solution of the present invention, in the hydrobromide crystal form B, the molar ratio of hydrobromic acid to compound IR is (0.8-1.2):1; for example, 1:1.

[0219] According to an embodiment of the present invention, the hydrobromide crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.6±0.2°, 8.8±0.2°, 19.9±0.2°, 20.7±0.2°, and 26.1±0.2° in 2θ angles.

[0220] According to an embodiment of the present invention, the hydrobromide crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 6.6±0.2°, 8.8±0.2°, 12.5±0.2°, 12.6±0.2°, 13.9±0.2°, 14.3±0.2°, 15.2±0.2°, 15.4±0.2°, 19.2±0.2°, 19.6±0.2°, 19.9±0.2°, 20.7±0.2°, 21.1±0.2°, 23.3±0.2°, and 26.1±0.2°.

[0221] According to an embodiment of the present invention, the hydrobromide crystal form B is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 6.6±0.2°, 8.8±0.2°, 10.2±0.2°, 11.7±0.2°, 12.5±0.2°, 12.6±0.2°, 13.9±0.2°, 14.3±0.2°, 15.2±0.2°, 15.4±0.2°, 15.9±0.2°, 1 Characteristic peaks are present at 6.5±0.2°, 17.7±0.2°, 18.5±0.2°, 19.2±0.2°, 19.6±0.2°, 19.9±0.2°, 20.7±0.2°, 21.1±0.2°, 22.0±0.2°, 23.3±0.2°, 24.3±0.2°, 26.1±0.2°, 29.9±0.2°, 27.4±0.2°, and 29.9±0.2°.

[0222] According to the technical solution of the present invention, the hydrobromide crystal form B has an X-ray powder diffraction pattern as shown in Figure 50.

[0223] According to the technical solution of the present invention, the hydrobromide crystal form B has diffraction peaks as shown in Table 6-11 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0224] According to the technical solution of the present invention, the hydrobromide crystal form B has diffraction peaks as shown in Table 6-12 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0225] According to the technical solution of the present invention, the differential scanning calorimetry curve of the hydrobromide crystal form B has endothermic peaks at peak temperatures of approximately 93.0±3℃ and 145.9±3℃; for example, it has endothermic peaks at peak temperatures of approximately 93.0℃ and 145.9℃.

[0226] According to the technical solution of the present invention, the thermogravimetric analysis curve of the hydrobromide crystal form B shows a weight loss of 4.82% ± 1.0% in the temperature range of 29.2℃ ± 3℃ to 90.0℃ ± 3℃. For example, the weight loss is 4.82% in the temperature range of 29.2℃ to 90.0℃.

[0227] According to the technical solution of the present invention, the thermogravimetric analysis curve of the hydrobromide crystal form B shows a weight loss of 1.07% ± 0.5% in the temperature range of 90.0℃ ± 3℃ to 130.0℃ ± 3℃. For example, the weight loss is 1.07% in the temperature range of 90.0℃ to 130.0℃.

[0228] According to the technical solution of the present invention, the hydrobromide crystal form B has a DSC-TGA spectrum as shown in Figure 51.

[0229] According to the technical solution of the present invention, the hydrobromide crystal form B is a granular crystal.

[0230] According to the technical solution of the present invention, the hydrobromide crystal form B contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; for example, MTBE. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.01:1.

[0231] According to the technical solution of the present invention, the hydrobromide crystal form B is a solvate, preferably an organic solvate. Preferably, the hydrobromide crystal form B is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate, or MTBE solvate; for example, an MTBE solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.01:1.

[0232] According to the technical solution of the present invention, the 1,2-ethanedisulfonate crystal form is the 1,2-ethanedisulfonate crystal form A of compound IR.

[0233] According to the technical solution of the present invention, in the 1,2-ethanedisulfonate crystal form A, the molar ratio of 1,2-ethanedisulfonic acid to compound IR is (0.6-1.0):1; for example, 0.8:1.

[0234] According to an embodiment of the present invention, the 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.4±0.2°, 8.2±0.2°, 11.0±0.2°, and 11.2±0.2° in 2θ angles.

[0235] According to an embodiment of the present invention, the 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 3.9±0.2°, 6.4±0.2°, 7.8±0.2°, 8.2±0.2°, 11.0±0.2°, 11.2±0.2°, 12.9±0.2°, 16.0±0.2°, 17.1±0.2°, 17.7±0.2°, 21.5±0.2°, 23.0±0.2°, and 24.2±0.2°.

[0236] According to an embodiment of the present invention, the 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.9±0.2°, 6.4±0.2°, 7.8±0.2°, 8.2±0.2°, 11.0±0.2°, 11.2±0.2°, 12.3±0.2°, 12.9±0.2°, 14.2±0.2°, 16.0±0.2°, 17.1±0.2°, 17.7±0.2°, 18.3±0.2°, 19.0±0.2°, 19.9±0.2°, 21.5±0.2°, 23.0±0.2°, 24.2±0.2°, 24.7±0.2°, and 28.9±0.2° in 2θ angles.

[0237] According to the technical solution of the present invention, the 1,2-ethylenedisulfonate crystal form A has an X-ray powder diffraction pattern as shown in Figure 70.

[0238] According to the technical solution of the present invention, the 1,2-ethanedisulfonate crystal form A has diffraction peaks as shown in Table 8-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°.

[0239] According to the technical solution of the present invention, the 1,2-ethanedisulfonate crystal form A has diffraction peaks as shown in Table 8-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0240] According to the technical solution of the present invention, the differential scanning calorimetry curve of the 1,2-ethanedisulfonate crystal form A has endothermic peaks at peak temperatures of approximately 60.8±3℃, 134.0±3℃ and 152.2±3℃; for example, it has endothermic peaks at peak temperatures of approximately 60.8℃, 134.0℃ and 152.2℃.

[0241] According to the technical solution of the present invention, the thermogravimetric analysis curve of the 1,2-ethanedisulfonate crystal form A shows a weight loss of 8.15% ± 2.0% in the temperature range of 23.8℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 8.15% in the temperature range of 23.8℃ to 110.0℃.

[0242] According to the technical solution of the present invention, the 1,2-ethylenedisulfonate crystal form A has a DSC-TGA spectrum as shown in Figure 71.

[0243] According to the technical solution of the present invention, the 1,2-ethylenedisulfonate crystal form A has the basic characteristics shown in Figure 72. 1 H-NMR spectrum.

[0244] According to the technical solution of the present invention, the 1,2-ethanedisulfonate crystal form A does not contain organic solvents. Preferably, the organic solvent is one or two of ACN, THF, EtOAc, DCM, or n-heptane.

[0245] According to an embodiment of the present invention, the magnesium salt crystal form is magnesium salt crystal form A of compound IR.

[0246] According to the technical solution of the present invention, in the magnesium salt crystal form A, the molar ratio of magnesium ions to compound IR is (0.4-0.8):1; for example, 0.6:1.

[0247] According to an embodiment of the present invention, the magnesium salt crystal form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction, expressed in 2θ angles, has characteristic peaks at 4.4±0.2°, 8.7±0.2°, 9.8±0.2°, 11.5±0.2°, 13.1±0.2° and 18.6±0.2°.

[0248] According to an embodiment of the present invention, the magnesium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, 15.0±0.2°, 17.2±0.2°, 17.4±0.2°, 18.2±0.2°, 18.6±0.2°, and 19.5±0.2°.

[0249] According to an embodiment of the present invention, the magnesium salt crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.1±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, and 14. Characteristic peaks are present at 7±0.2°, 15.0±0.2°, 15.3±0.2°, 17.2±0.2°, 17.4±0.2°, 18.2±0.2°, 18.6±0.2°, 19.0±0.2°, 19.5±0.2°, 20.1±0.2°, 25.6±0.2°, 33.0±0.2°, and 38.0±0.2°.

[0250] According to an embodiment of the present invention, the magnesium salt crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.1±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, 14.1±0.2°, 14.7±0.2°, 15.0±0.2°, 15.3±0.2°, 17.2±0.2°, and 17. Characteristic peaks are present at 4±0.2°, 18.2±0.2°, 18.6±0.2°, 19.0±0.2°, 19.5±0.2°, 20.1±0.2°, 21.8±0.2°, 23.1±0.2°, 23.5±0.2°, 24.0±0.2°, 25.0±0.2°, 25.6±0.2°, 26.2±0.2°, 28.2±0.2°, 29.8±0.2°, 33.0±0.2°, 34.6±0.2°, and 38.0±0.2°.

[0251] According to the technical solution of the present invention, the magnesium salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 52.

[0252] According to the technical solution of the present invention, the magnesium salt crystal form A has diffraction peaks as shown in Table 7-3 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0253] According to the technical solution of the present invention, the magnesium salt crystal form A has diffraction peaks as shown in Table 7-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0254] According to the technical solution of the present invention, the differential scanning calorimetry curve of the magnesium salt crystal form A has endothermic peaks at peak temperatures of approximately 92.5±3℃, 128.6±3℃ and 166.5±3℃; for example, it has endothermic peaks at peak temperatures of approximately 92.5℃, 128.6℃ and 166.5℃.

[0255] According to the technical solution of the present invention, the thermogravimetric analysis curve of the magnesium salt crystal form A shows a weight loss of 2.85% ± 1.0% in the temperature range of 28.4℃ ± 3℃ to 100.0℃ ± 3℃. For example, the weight loss is 2.85% in the temperature range of 28.4℃ to 100.0℃.

[0256] According to the technical solution of the present invention, the thermogravimetric analysis curve of the magnesium salt crystal form A shows a weight loss of 1.94% ± 0.5% in the temperature range of 100.0℃ ± 3℃ to 150.0℃ ± 3℃. For example, the weight loss is 1.94% in the temperature range of 100℃ to 150℃.

[0257] According to the technical solution of the present invention, the magnesium salt crystal form A has a DSC-TGA spectrum as shown in Figure 53.

[0258] According to the technical solution of the present invention, the magnesium salt crystal form A is a rod-shaped crystal.

[0259] According to the technical solution of the present invention, the magnesium salt crystal form A does not contain organic solvents. Preferably, the organic solvent is acetone or n-heptane.

[0260] According to an embodiment of the present invention, the potassium salt crystal form is potassium salt crystal form A of compound IR.

[0261] According to the technical solution of the present invention, in the potassium salt crystal form A, the molar ratio of potassium ions to compound IR is (0.6-1.0):1; for example, 0.8:1.

[0262] According to an embodiment of the present invention, the potassium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 8.2±0.2°, and 9.5±0.2°, expressed in 2θ angles.

[0263] According to an embodiment of the present invention, the potassium salt crystal form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction, expressed in 2θ angles, has characteristic peaks at 4.1±0.2°, 4.4±0.2°, 8.2±0.2°, 9.5±0.2°, 11.5±0.2°, 12.7±0.2°, 14.6±0.2°, 17.9±0.2°, and 25.2±0.2°.

[0264] According to an embodiment of the present invention, the potassium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 4.1±0.2°, 4.4±0.2°, 5.8±0.2°, 8.2±0.2°, 8.7±0.2°, 9.5±0.2°, 10.0±0.2°, 10.3±0.2°, 11.5±0.2°, 12.7±0.2°, 13.1±0.2°, 14.6±0.2°, 15.4±0.2°, 17.4±0.2°, 17.9±0.2°, 22.1±0.2°, 24.5±0.2°, and 25.2±0.2°.

[0265] According to an embodiment of the present invention, the potassium salt crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 4.1±0.2°, 4.4±0.2°, 5.1±0.2°, 5.8±0.2°, 7.0±0.2°, 8.2±0.2°, 8.7±0.2°, 9.5±0.2°, 10.0±0.2°, 10.3±0.2°, 11.5±0.2°, 12.2±0.2°, 12.7±0.2°, 13.1±0.2°, 13.9±0.2°, and 14.6±0.2°. Characteristic peaks are present at 0.2°, 15.4±0.2°, 16.5±0.2°, 17.4±0.2°, 17.9±0.2°, 18.9±0.2°, 19.5±0.2°, 21.1±0.2°, 22.1±0.2°, 23.5±0.2°, 24.5±0.2°, 24.7±0.2°, 25.2±0.2°, 26.5±0.2°, 27.1±0.2°, 27.9±0.2°, 30.6±0.2°, 32.4±0.2°, and 35.5±0.2°.

[0266] According to the technical solution of the present invention, the potassium salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 54.

[0267] According to the technical solution of the present invention, the potassium salt crystal form A has diffraction peaks as shown in Table 7-5 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0268] According to the technical solution of the present invention, the potassium salt crystal form A has diffraction peaks as shown in Table 7-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0269] According to the technical solution of the present invention, the differential scanning calorimetry curve of the potassium salt crystal form A has endothermic peaks at peak temperatures of approximately 67.6±3℃ and 119.1±3℃; for example, it has endothermic peaks at peak temperatures of approximately 67.6℃ and 119.1℃.

[0270] According to the technical solution of the present invention, the differential scanning calorimetry curve of the potassium salt crystal form A has an exothermic peak at a peak temperature of about 160.2 ± 3 °C; for example, it has an exothermic peak at a peak temperature of about 160.2 °C.

[0271] According to the technical solution of the present invention, the thermogravimetric analysis curve of the potassium salt crystal form A shows a weight loss of 10.48% ± 1.0% in the temperature range of 21.2℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 10.48% in the temperature range of 21.2℃ to 110.0℃.

[0272] According to the technical solution of the present invention, the potassium salt crystal form A has a DSC-TGA spectrum as shown in Figure 55.

[0273] According to the technical solution of the present invention, the potassium salt crystal form A is a rod-shaped crystal.

[0274] According to the technical solution of the present invention, the potassium salt crystal form A contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone and MTBE. For example, MTBE. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.02:1.

[0275] According to the technical solution of the present invention, the potassium salt crystal form A is a solvate, preferably an organic solvate. Preferably, the potassium salt crystal form A is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate, or MTBE solvate; for example, an MTBE solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.02:1.

[0276] According to an embodiment of the present invention, the calcium salt crystal form is calcium salt crystal form A of compound IR.

[0277] According to the technical solution of the present invention, in the calcium salt crystal form A, the molar ratio of calcium ions to compound IR is (1.0-1.4):1; for example, 1.2:1.

[0278] According to an embodiment of the present invention, the calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, and 12.0±0.2° in 2θ angles.

[0279] According to an embodiment of the present invention, the calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, 12.0±0.2°, 14.8±0.2°, 15.9±0.2°, and 18.1±0.2° in 2θ angles.

[0280] According to an embodiment of the present invention, the calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, 12.0±0.2°, 12.7±0.2°, 14.1±0.2°, 14.8±0.2°, 15.9±0.2°, 16.8±0.2°, 18.1±0.2°, 20.9±0.2°, 24.5±0.2°, 25.7±0.2°, 26.5±0.2°, and 34.2±0.2° in 2θ angles.

[0281] According to the technical solution of the present invention, the calcium salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 56.

[0282] According to the technical solution of the present invention, the calcium salt crystal form A has diffraction peaks as shown in Table 7-7 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0283] According to the technical solution of the present invention, the calcium salt crystal form A has diffraction peaks as shown in Table 7-8 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0284] According to the technical solution of the present invention, the differential scanning calorimetry curve of the calcium salt crystal form A has endothermic peaks at peak temperatures of approximately 55.0±3℃ and 137.3±3℃; for example, it has endothermic peaks at peak temperatures of approximately 55.0℃ and 137.3℃.

[0285] According to the technical solution of the present invention, the thermogravimetric analysis curve of the calcium salt crystal form A shows a weight loss of 4.21% ± 1.0% in the temperature range of 28.5℃ ± 3℃ to 100.0℃ ± 3℃. For example, the weight loss is 4.21% in the temperature range of 28.5℃ to 100.0℃.

[0286] According to the technical solution of the present invention, the calcium salt crystal form A has a DSC-TGA spectrum as shown in Figure 57.

[0287] According to the technical solution of the present invention, the calcium salt crystal form A is a crystal particle of varying size.

[0288] According to the technical solution of the present invention, the calcium salt crystal form A does not contain organic solvents. Preferably, the organic solvent is acetone or n-heptane.

[0289] According to an embodiment of the present invention, the crystal form of the meglumine salt is either crystal form A or crystal form B of the meglumine salt of compound IR.

[0290] According to the technical solution of the present invention, in the meglumine salt crystal form A, the molar ratio of meglumine to compound IR is (0.8-1.2):1; for example, 1:1.

[0291] According to an embodiment of the present invention, the meglumine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 9.8±0.2°, 13.2±0.2°, and 17.2±0.2° in 2θ angles.

[0292] According to an embodiment of the present invention, the meglumine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.1±0.2°, 9.8±0.2°, 13.2±0.2°, 17.2±0.2°, and 20.8±0.2° in 2θ angles.

[0293] According to the technical solution of the present invention, the meglumine salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 58.

[0294] According to the technical solution of the present invention, the meglumine salt crystal form A has diffraction peaks as shown in Table 7-9 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0295] According to the technical solution of the present invention, the meglumine salt crystal form A has diffraction peaks as shown in Table 7-10 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0296] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the meglumine salt crystal form A has endothermic peaks at peak temperatures of approximately 64.4±3℃ and 121.8±3℃; for example, it has endothermic peaks at peak temperatures of approximately 64.4℃ and 121.8℃.

[0297] According to the technical solution of the present invention, the thermogravimetric analysis curve of the meglumine salt crystal form A shows a weight loss of 11.34% ± 1.0% in the temperature range of 23.4℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 11.34% in the temperature range of 23.4℃ to 120.0℃.

[0298] According to the technical solution of the present invention, the meglumine salt crystal form A has a DSC-TGA spectrum as shown in Figure 59.

[0299] According to the technical solution of the present invention, the meglumine salt crystal form A is composed of crystal particles of varying sizes.

[0300] According to the technical solution of the present invention, the meglumine salt crystal form A contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; for example, MTBE. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.2:1.

[0301] According to the technical solution of the present invention, the meglumine salt crystal form A is a solvate, preferably an organic solvate. Preferably, the meglumine salt crystal form A is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate, or MTBE solvate; for example, an MTBE solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.2:1.

[0302] According to the technical solution of the present invention, in the meglumine salt crystal form B, the molar ratio of meglumine to compound IR is (0.8-1.2):1; for example, 1:1.

[0303] According to an embodiment of the present invention, the meglumine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.6±0.2°, 6.1±0.2°, 9.7±0.2°, and 13.8±0.2° in 2θ angles.

[0304] According to an embodiment of the present invention, the meglumine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 4.6±0.2°, 6.1±0.2°, 9.7±0.2°, 11.9±0.2°, 13.8±0.2°, 14.5±0.2°, 18.2±0.2°, and 21.0±0.2°.

[0305] According to the technical solution of the present invention, the meglumine salt crystal form B has an X-ray powder diffraction pattern as shown in Figure 60.

[0306] According to the technical solution of the present invention, the meglumine salt crystal form B has diffraction peaks as shown in Table 7-11 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0307] According to the technical solution of the present invention, the meglumine salt crystal form B has diffraction peaks as shown in Table 7-12 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0308] According to the technical solution of the present invention, the differential scanning calorimetry (DSC) curve of the meglumine salt crystal form B has endothermic peaks at peak temperatures of approximately 49.2±3℃, 68.1±3℃ and 95.0±3℃; for example, it has endothermic peaks at peak temperatures of approximately 49.2℃, 68.1℃ and 95.0℃.

[0309] According to the technical solution of the present invention, the thermogravimetric analysis curve of the meglumine salt crystal form B shows a weight loss of 5.44% ± 1.0% in the temperature range of 28.5℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 5.44% in the temperature range of 28.5℃ to 120.0℃.

[0310] According to the technical solution of the present invention, the meglumine salt crystal form B has a DSC-TGA spectrum as shown in Figure 61.

[0311] According to the technical solution of the present invention, the meglumine salt crystal form B consists of crystal particles of varying sizes.

[0312] According to the technical solution of the present invention, the meglumine salt crystal form B does not contain organic solvents. Preferably, the organic solvent is IPAc or n-heptane.

[0313] According to an embodiment of the present invention, the lysine salt crystal form is lysine salt crystal form A and lysine salt crystal form B of compound IR.

[0314] According to the technical solution of the present invention, in the lysine salt crystal form A, the molar ratio of lysine to compound IR is (0.8-1.2):1; for example, 1:1.

[0315] According to an embodiment of the present invention, the lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, and 14.0±0.2° in 2θ angles.

[0316] According to an embodiment of the present invention, the lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, 14.0±0.2°, 15.0±0.2°, 17.6±0.2°, 19.8±0.2°, and 22.1±0.2° in 2θ angles.

[0317] According to an embodiment of the present invention, the lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 6.0±0.2°, 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, 14.0±0.2°, 15.0±0.2°, 17.6±0.2°, 19.8±0.2°, 22.1±0.2°, 24.0±0.2°, and 30.7±0.2°.

[0318] According to the technical solution of the present invention, the lysine salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 62.

[0319] According to the technical solution of the present invention, the lysine salt crystal form A has diffraction peaks as shown in Table 7-13 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0320] According to the technical solution of the present invention, the lysine salt crystal form A has diffraction peaks as shown in Table 7-14 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0321] According to the technical solution of the present invention, the differential scanning calorimetry curve of the lysine salt crystal form A has endothermic peaks at peak temperatures of approximately 77.5±3℃, 103.3±3℃ and 141.5±3℃; for example, it has endothermic peaks at peak temperatures of approximately 77.5℃, 103.3℃ and 141.5℃.

[0322] According to the technical solution of the present invention, the thermogravimetric analysis curve of the lysine salt crystal form A shows a weight loss of 8.00% ± 1.0% in the temperature range of 28.4℃ ± 3℃ to 80.0℃ ± 3℃. For example, a weight loss of 8.00% in the temperature range of 28.4℃ to 80.0℃.

[0323] According to the technical solution of the present invention, the thermogravimetric analysis curve of the lysine salt crystal form A shows a weight loss of 6.89% ± 1.0% in the temperature range of 80.0℃ ± 3℃ to 150.0℃ ± 3℃. For example, the weight loss is 6.89% in the temperature range of 80.0℃ to 150.0℃.

[0324] According to the technical solution of the present invention, the lysine salt crystal form A has a DSC-TGA spectrum as shown in Figure 63.

[0325] According to the technical solution of the present invention, the lysine salt crystal form A is crystal particles of varying sizes.

[0326] According to the technical solution of the present invention, the lysine salt crystal form A does not contain organic solvents. Preferably, the organic solvent is acetone or n-heptane.

[0327] According to the technical solution of the present invention, in the lysine salt crystal form B, the molar ratio of lysine to compound IR is (0.8-1.2):1; for example, 1:1.

[0328] According to an embodiment of the present invention, the lysine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks at 10.3±0.2° and 19.9±0.2° in X-ray powder diffraction at an angle of 2θ.

[0329] According to the technical solution of the present invention, the lysine salt crystal form B has an X-ray powder diffraction pattern as shown in Figure 64.

[0330] According to the technical solution of the present invention, the lysine salt crystal form B has diffraction peaks as shown in Table 7-15 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0331] According to the technical solution of the present invention, the lysine salt crystal form B has diffraction peaks as shown in Table 7-16 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°.

[0332] According to the technical solution of the present invention, the differential scanning calorimetry curve of the lysine salt crystal form B has an endothermic peak at a peak temperature of about 131.0 ± 3 °C; for example, it has an endothermic peak at a peak temperature of about 131.0 °C.

[0333] According to the technical solution of the present invention, the thermogravimetric analysis curve of the lysine salt crystal form B shows a weight loss of 7.17% ± 1.0% in the temperature range of 23.9℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 7.17% in the temperature range of 23.9℃ to 110.0℃.

[0334] According to the technical solution of the present invention, the lysine salt crystal form B has a DSC-TGA spectrum as shown in Figure 65.

[0335] According to the technical solution of the present invention, the lysine salt crystal form B is a bulk crystal.

[0336] According to the technical solution of the present invention, the lysine salt crystal form B contains an organic solvent. Preferably, the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; for example, MTBE. Preferably, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.07:1.

[0337] According to the technical solution of the present invention, the lysine salt crystal form B is a solvate, preferably an organic solvate. Preferably, the lysine salt crystal form B is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate, or MTBE solvate; for example, an MTBE solvate. Preferably, in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1, for example, 0.07:1.

[0338] According to an embodiment of the present invention, the diethylamine salt crystal form is the diethylamine salt crystal form A of compound IR.

[0339] According to the technical solution of the present invention, in the diethylamine salt crystal form A, the molar ratio of diethylamine to compound IR is (0.8-1.2):1; for example, 1:1.

[0340] According to an embodiment of the present invention, the diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 13.3±0.2°, 15.4±0.2°, 16.2±0.2°, 18.1±0.2°, and 21.7±0.2° in 2θ angles.

[0341] According to an embodiment of the present invention, the diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 5.9±0.2°, 9.8±0.2°, 11.0±0.2°, 11.7±0.2°, 12.5±0.2°, 13.3±0.2°, 15.1±0.2°, 15.4±0.2°, 16.2±0.2°, 18.1±0.2°, 21.7±0.2°, 22.8±0.2°, and 23.6±0.2°.

[0342] According to an embodiment of the present invention, the diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 5.9±0.2°, 9.8±0.2°, 11.0±0.2°, 11.7±0.2°, 12.5±0.2°, 13.3±0.2°, 15.1±0.2°, 15.4±0.2°, 16.2±0.2°, 17.6±0.2°, 18.1±0.2°, 19.2±0.2°, 20.9±0.2°, 21.7±0.2°, 22.8±0.2°, 23.6±0.2°, 24.0±0.2°, 25.7±0.2°, 26.5±0.2°, 27.9±0.2°, and 29.6±0.2°.

[0343] According to the technical solution of the present invention, the diethylamine salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 66.

[0344] According to the technical solution of the present invention, the diethylamine salt crystal form A has diffraction peaks as shown in Table 7-17 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0345] According to the technical solution of the present invention, the diethylamine salt crystal form A has diffraction peaks as shown in Table 7-18 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0346] According to the technical solution of the present invention, the differential scanning calorimetry curve of the diethylamine salt crystal form A has endothermic peaks at peak temperatures of approximately 119.7±3℃ and 152.0±3℃; for example, it has endothermic peaks at peak temperatures of approximately 119.7℃ and 152.0℃.

[0347] According to the technical solution of the present invention, the thermogravimetric analysis curve of the diethylamine salt crystal form A shows a weight loss of 8.01% ± 1.0% in the temperature range of 24.9℃ ± 3℃ to 120.0℃ ± 3℃. For example, the weight loss is 8.01% in the temperature range of 24.9℃ to 120.0℃.

[0348] According to the technical solution of the present invention, the diethylamine salt crystal form A has a DSC-TGA spectrum as shown in Figure 67.

[0349] According to the technical solution of the present invention, the diethylamine salt crystal form A consists of crystal particles of varying sizes.

[0350] According to the technical solution of the present invention, the diethylamine salt crystal form A does not contain organic solvent. Preferably, the organic solvent is acetone or n-heptane.

[0351] According to an embodiment of the present invention, the diethanolamine salt crystal form is the diethanolamine salt crystal form A of compound IR.

[0352] According to the technical solution of the present invention, in the diethanolamine salt crystal form A, the molar ratio of diethanolamine to compound IR is (0.8-1.2):1; for example, 1:1.

[0353] According to an embodiment of the present invention, the diethanolamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 10.5±0.2°, 13.1±0.2°, 16.9±0.2°, 19.7±0.2°, and 22.2±0.2° in 2θ angles.

[0354] According to an embodiment of the present invention, the diethanolamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 8.9±0.2°, 10.5±0.2°, 13.1±0.2°, 16.9±0.2°, 17.8±0.2°, 19.0±0.2°, 19.7±0.2°, 22.2±0.2°, 23.6±0.2°, 24.5±0.2°, and 24.9±0.2°.

[0355] According to an embodiment of the present invention, the diethanolamine salt crystal form A is subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, is performed at 7.7±0.2°, 8.9±0.2°, 10.5±0.2°, 13.1±0.2°, 14.0±0.2°, 15.5±0.2°, 15.8±0.2°, 16.9±0.2°, 17.8±0.2°, 19.0±0.2°, 19.7±0.2°, 20.1±0.2°, 20.5±0.2°, 21.1±0.2°, and 21.4±0.2°. Characteristic peaks are present at 21.9±0.2°, 22.2±0.2°, 22.6±0.2°, 23.0±0.2°, 23.6±0.2°, 24.3±0.2°, 24.5±0.2°, 24.9±0.2°, 25.8±0.2°, 26.4±0.2°, 26.8±0.2°, 27.3±0.2°, 28.1±0.2°, 28.5±0.2°, 29.4±0.2°, 30.0±0.2°, 33.1±0.2°, 34.2±0.2°, and 38.0±0.2°.

[0356] According to the technical solution of the present invention, the diethanolamine salt crystal form A has an X-ray powder diffraction pattern as shown in Figure 68.

[0357] According to the technical solution of the present invention, the diethanolamine salt crystal form A has diffraction peaks as shown in Table 7-19 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0358] According to the technical solution of the present invention, the diethanolamine salt crystal form A has diffraction peaks as shown in Table 7-20 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°.

[0359] According to the technical solution of the present invention, the differential scanning calorimetry curve of the diethanolamine salt crystal form A has an endothermic peak at a peak temperature of about 120.4 ± 3 °C; for example, it has an endothermic peak at a peak temperature of about 120.4 °C.

[0360] According to the technical solution of the present invention, the thermogravimetric analysis curve of the diethanolamine salt crystal form A shows a weight loss of 0.59% ± 0.1% in the temperature range of 25.6℃ ± 3℃ to 110.0℃ ± 3℃. For example, the weight loss is 0.59% in the temperature range of 25.6℃ to 110.0℃.

[0361] According to the technical solution of the present invention, the diethanolamine salt crystal form A has a DSC-TGA spectrum as shown in Figure 69.

[0362] According to the technical solution of the present invention, the diethanolamine salt crystal form A is crystal particles of varying sizes.

[0363] According to the technical solution of the present invention, the diethanolamine salt crystal form A does not contain organic solvent. Preferably, the organic solvent is MTBE.

[0364] The present invention also provides a method for preparing a salt or crystal form of the above-mentioned compound I or its stereoisomer, comprising the following steps: mixing compound I or its stereoisomer with an acid or a base and reacting the mixture in a solvent to obtain a salt or crystal form of the compound I or its stereoisomer.

[0365] According to an embodiment of the present invention, the acid is succinic acid, hydrochloric acid, tartaric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid, or 1,2-ethanedisulfonic acid.

[0366] According to an embodiment of the present invention, the base is sodium hydroxide, tris(hydroxymethyl)aminomethane, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, lysine, diethylamine, or diethanolamine.

[0367] According to an embodiment of the present invention, the molar ratio of the acid or base to compound I or its stereoisomer is (0.5-2.5):1. For example, it is 0.65:1, 0.75:1, 1:1, 1.1:1 or 2:1. More specifically, it is 1:1, 1.1:1 or 2:1.

[0368] According to an embodiment of the present invention, the solvent is an organic solvent or water. Preferably, the organic solvent is one, two or more of the following: IPA, IPAc, MTBE, n-heptane, acetone, methanol, ethanol, 2-butanone, ethyl acetate, methyl acetate, 4-methyl-2-pentanone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, chloroform, n-hexane, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, or N-methylpyrrolidone, or a mixture of any one or two of the above solvents with n-heptane.

[0369] More preferably, the volume ratio of the solvent to the mass of compound I or its stereoisomer is (20-100) mL:1g, for example, 20mL:1g, 25mL:1g, 35mL:1g, 50mL:1g or 75mL:1g.

[0370] According to an embodiment of the present invention, when the solvent is IPAc, the tartrate crystal form A, succinate crystal form A, phosphate crystal form A, fumarate crystal form A, malate crystal form A, or hydrobromide crystal form A is obtained.

[0371] According to an embodiment of the present invention, when the solvent is MTBE, the following crystal forms are obtained: tartrate crystal form A, succinate crystal form A, hydrochloride crystal form A, sodium salt crystal form B, Tris salt crystal form B, phosphate crystal form A, fumarate crystal form A, malate crystal form A, hydrobromide crystal form B, potassium salt crystal form A, meglumine salt crystal form A, low-crystallinity lysine salt crystal form B, diethylamine salt crystal form A, or diethanolamine salt crystal form A.

[0372] According to an embodiment of the present invention, when the solvent is a mixed solvent of ethyl acetate and n-heptane, preferably when the solvent is a mixed solvent of ethyl acetate and n-heptane in a volume ratio of 1:3, the hydrochloride crystal form A or the 1,2-ethanedisulfonate crystal form A is obtained.

[0373] According to an embodiment of the present invention, when the solvent is a mixed solvent of tetrahydrofuran and n-heptane, preferably, when the solvent is a mixed solvent of tetrahydrofuran and n-heptane in a volume ratio of 1:2, the hydrochloride crystal form B or the 1,2-ethanedisulfonate crystal form A is obtained.

[0374] According to an embodiment of the present invention, when the solvent is a mixed solvent of dichloromethane and n-heptane, preferably when the solvent is a mixed solvent of dichloromethane and n-heptane in a volume ratio of 1:2, the hydrochloride crystal form B is obtained.

[0375] According to an embodiment of the present invention, when the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, the sodium salt crystal form A, sodium salt crystal form C, Tris salt crystal form A, low crystallinity potassium salt crystal form A, calcium salt crystal form A, meglumine salt crystal form A, lysine salt crystal form A, diethylamine salt crystal form A, or diethanolamine salt crystal form A are obtained.

[0376] According to an embodiment of the present invention, when the solvent is a mixed solvent of IPAc and n-heptane, preferably, when the solvent is a mixed solvent of IPAc and n-heptane in a volume ratio of 1:2, the sodium salt crystal form B, Tris salt crystal form C, potassium salt crystal form A, meglumine salt crystal form B, diethylamine salt crystal form A, or diethanolamine salt crystal form A are obtained.

[0377] According to an embodiment of the present invention, when the solvent is a mixed solvent of IPAc and n-heptane, preferably when the solvent is a mixed solvent of IPAc and n-heptane in a volume ratio of 1:1, the benzenesulfonate (amorphous) is obtained.

[0378] According to an embodiment of the present invention, when the solvent is a mixed solvent of MTBE and n-heptane, preferably when the solvent is a mixed solvent of MTBE and n-heptane in a volume ratio of 1:1, the p-toluenesulfonate (amorphous) is obtained.

[0379] According to an embodiment of the present invention, when the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, and the molar ratio of the base (e.g., NaOH) to compound IR is 1:1, the sodium salt crystal form A is obtained.

[0380] According to an embodiment of the present invention, when the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, and the molar ratio of the base (e.g., NaOH) to compound IR is 1.1:1, the sodium salt crystal form C is obtained.

[0381] According to an embodiment of the present invention, when the solvent is a mixed solvent of acetone and n-heptane, preferably, when the solvent is a mixed solvent of acetone and n-heptane in a volume ratio of 1:4, Tris salt crystal form B, magnesium salt crystal form A, calcium salt crystal form A, meglumine salt crystal form B, lysine salt crystal form A, or diethylamine salt crystal form A are obtained.

[0382] According to an embodiment of the present invention, when the solvent is IPA, the tartrate crystal form A, succinate crystal form A, fumarate crystal form B, or malate crystal form A is obtained.

[0383] According to an embodiment of the present invention, when the solvent is ACN or dichloromethane, 1,2-ethanedisulfonate crystal form A is obtained.

[0384] More preferably, the mixed solvent is a mixed solvent of IPA and n-heptane, a mixed solvent of IPAc and n-heptane, a mixed solvent of acetone and n-heptane, a mixed solvent of MTBE and n-heptane, a mixed solvent of tetrahydrofuran and n-heptane, a mixed solvent of ethanol and n-heptane, a mixed solvent of ethyl acetate and n-heptane, or a mixed solvent of dichloromethane and n-heptane.

[0385] According to an embodiment of the present invention, when compound I or its stereoisomer reacts with an acid in a solvent, the solvent is an organic solvent, which is one, two or more of IPA, IPAc, MTBE, EtOAc, THF, DCM, ACN or EtOH, or a mixture of any of the above solvents and n-heptane. Preferably, in the mixed solvent, the volume ratio of any of the solvents IPA, IPAc, MTBE, EtOAc, THF, DCM or EtOH to n-heptane is 1:(1-5); more preferably 1:(1-3); more preferably 1:(1-2); for example, 1:1, 1:2 or 1:3.

[0386] For example, the solvent used to prepare succinates and crystal forms of compound I or its stereoisomers is selected from IPA, IPAc or MTBE.

[0387] For example, the solvent used to prepare the tartrate salt and crystal form of compound I or its stereoisomers is selected from IPA, IPAc or MTBE.

[0388] According to an embodiment of the present invention, when compound I or its stereoisomer reacts with a base in a solvent, the solvent is an organic solvent, which is one, two or more of IPA, IPAc, MTBE, n-heptane or acetone, or a mixture of any of the above solvents and n-heptane. Preferably, in the mixed solvent, the volume ratio of any of the solvents IPA, IPAc, MTBE, n-heptane or acetone to n-heptane is 1:(1-5); more preferably 1:(2-4); for example, 1:2 or 1:4.

[0389] More preferably, the organic solvent is a mixture of IPA and n-heptane, a mixture of IPAc and n-heptane, a mixture of acetone and n-heptane, or MTBE.

[0390] For example, the solvent for preparing the trihydroxymethylaminomethane salt of compound I or its stereoisomer and its crystal form is selected from a mixed solvent of IPA and n-heptane (the volume ratio of IPA to n-heptane is 1:2), a mixed solvent of IPAc and n-heptane (the volume ratio of IPAc to n-heptane is 1:2), a mixed solvent of acetone and n-heptane (the volume ratio of acetone to n-heptane is 1:4), or MTBE.

[0391] For example, the solvent for preparing the sodium salt of compound I or its stereoisomer and its crystal form is selected from a mixed solvent of IPA and n-heptane (the volume ratio of IPA to n-heptane is 1:2), a mixed solvent of IPAc and n-heptane (the volume ratio of IPAc to n-heptane is 1:2), or MTBE.

[0392] According to an embodiment of the present invention, the reaction temperature is -20 to 50°C, preferably 5 to 50°C. For example, it is -20°C, 5°C, or 20 to 30°C.

[0393] The present invention also provides a pharmaceutical composition comprising a salt of the above-described compound I or a stereoisomer thereof.

[0394] According to the technical solution of the present invention, the pharmaceutical composition further contains a pharmaceutically acceptable carrier.

[0395] According to the technical solution of the present invention, the pharmaceutical composition may further contain a second active ingredient, such as one, two or more of the following: LPAR1 inhibitor, LPAR2 inhibitor, LPAR3 inhibitor, ROCK inhibitor, FAAH inhibitor, TGF-β inhibitor, ACC inhibitor, ASK-1 inhibitor, FXR agonist, GLP-1 agonist, PPARα agonist, VEGFR inhibitor, FGFR inhibitor, PDGFR inhibitor, ATX inhibitor, GPR84 agonist, PASK inhibitor, CFTR agonist, JAK1 inhibitor, ADAMTS5 inhibitor, TOL2 / 3 inhibitor, CTGF inhibitor, αv-β6 / αv-β1 antagonist, JNK1 inhibitor, mineralocorticoid receptor antagonist, Nrf2 activator, chymotrypsin inhibitor, PDE inhibitor, NOX1 / 4 inhibitor, leukotriene receptor antagonist, thromboxane receptor antagonist, SLC22A12 inhibitor, sGC inhibitor, xanthine oxidase inhibitor, or TGFP antagonist.

[0396] The present invention also provides the use of the above-mentioned compound I or its stereoisomer salt or pharmaceutical composition in formulation preparation.

[0397] The present invention also provides a formulation comprising a salt of the above-described compound I or a stereoisomer thereof, or a pharmaceutical composition thereof.

[0398] According to the technical solution of the present invention, the formulation is an LPAR1 inhibitor.

[0399] The present invention also provides the use of a salt of the above-mentioned compound I or its stereoisomer, a pharmaceutical composition, and a formulation in the preparation of a medicament for the prevention and / or treatment of LPAR1-mediated diseases or conditions.

[0400] Preferably, the drug is an LPAR1 inhibitor.

[0401] Preferably, the disease or condition is a fibrotic disease, a respiratory disease, pain, a nervous system disease, a cardiovascular disease, an inflammatory disease, a kidney disease, a liver disease, an eye disease, cancer, a gastrointestinal disease, a urinary system disease, a metabolic disease, or transplant rejection.

[0402] Preferably, the fibrotic diseases include, but are not limited to: pulmonary fibrosis (especially idiopathic pulmonary fibrosis and progressive pulmonary fibrosis), renal fibrosis, liver fibrosis, skin fibrosis, intestinal fibrosis, ocular fibrosis, cardiac fibrosis, and pancreatic fibrosis.

[0403] Preferably, the respiratory diseases include, but are not limited to: interstitial lung disease (ILD), idiopathic interstitial pneumonia (IIP), asthma, chronic obstructive pulmonary disease (COPD), bronchospasm, cough, chronic cough, respiratory failure, silicosis, acute lung injury, and acute respiratory distress.

[0404] Preferably, the kidney disease includes, but is not limited to: acute kidney injury, chronic kidney disease, and diabetic nephropathy.

[0405] Preferably, the liver diseases include, but are not limited to: alcoholic steatohepatitis, non-alcoholic fatty liver disease (NAFLD), acute hepatitis, chronic hepatitis, cirrhosis, impaired liver function, primary biliary cirrhosis, etc.; the non-alcoholic fatty liver disease (NAFLD) may be non-alcoholic steatohepatitis (NASH).

[0406] Preferably, the inflammatory diseases include, but are not limited to: autoimmune diseases, inflammation, arthritis, rheumatoid arthritis, scleroderma, Raynaud's phenomenon, chronic pruritus, lupus, cryptogenic fibrotic alveolitis, psoriasis, systemic sclerosis, and collagen vascular diseases.

[0407] Preferably, the neurological diseases include, but are not limited to: Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, traumatic brain injury, epilepsy, mental illness, and sleep disorders.

[0408] Preferably, the cardiovascular and cerebrovascular diseases include, but are not limited to: collagen vascular diseases, myocardial infarction, stroke, thrombosis, arteriosclerosis, heart failure, and hypertension.

[0409] Preferably, the gastrointestinal diseases include, but are not limited to: colitis, inflammatory bowel disease, digestive tract diseases, and gastrointestinal dysfunction.

[0410] Preferably, the pain includes, but is not limited to: cancer pain, neuropathic pain, inflammatory pain, surgical pain, visceral pain, toothache, premenstrual pain, central pain, pain caused by burns, migraine, cluster headache, and chronic pain.

[0411] Preferably, the urinary system diseases include urinary incontinence, dysuria, cystitis, benign prostatic hyperplasia, urinary disorders associated with benign prostatic hyperplasia, bladder neck sclerosis, and hypoactive bladder.

[0412] Preferably, the eye disease includes macular degeneration and diabetic retinopathy.

[0413] Preferably, the cancers include, but are not limited to: breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, intestinal cancer, liver cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, and tumor metastasis.

[0414] Preferably, the metabolic disease includes, but is not limited to, osteoporosis.

[0415] According to the technical solution of the present invention, the disease or condition is interstitial lung disease, pulmonary fibrosis (especially idiopathic pulmonary fibrosis), liver fibrosis, kidney fibrosis, non-alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis), psoriasis, or scleroderma.

[0416] The present invention also provides a method for preventing and / or treating LPAR1-mediated diseases or conditions, comprising administering a therapeutically effective amount of a salt of the above-described compound I or a stereoisomer thereof, the crystal form of the salt, a pharmaceutical composition or preparation thereof to a subject.

[0417] Terminology Definitions and Explanations

[0418] Unless otherwise stated, the following terms appearing in this specification and claims have the following meanings:

[0419] The terms “including,” “comprising,” “having,” “containing,” or “involving,” as used herein, and their other variations thereof, are inclusive or open-ended and do not exclude other unlisted elements or method steps.

[0420] As used herein, the term “about” means that a person skilled in the art would consider the value to be within an acceptable standard error, such as ±0.05, ±0.1, ±0.2, ±0.3, ±1, ±2, or ±3.

[0421] Unless otherwise stated, the numerical ranges described in this specification and claims are equivalent to describing at least each of the specific numerical values. For example, the numerical range "1-10" is equivalent to describing each of the numerical values ​​in the range "1-10".

[0422] Unless otherwise stated, "more" means 3 or more, such as 3, 4, 5, 6, 7, 8 or 9.

[0423] The term "crystal form" refers to a crystal form that has the same chemical composition but a different spatial arrangement of molecules and / or ions that form crystals. In some cases, crystal forms can be characterized by known techniques, including XRPD crystallography, solid-state nuclear magnetic resonance (ssNMR) spectroscopy, DSC, or some combination of these techniques. Crystal forms produce characteristic XRPD spectra with well-defined peaks.

[0424] The term "amorphous" refers to a solid form that is not crystalline and consists of molecules and / or ions. Amorphous solids do not exhibit definite X-ray powder diffraction patterns with clear maximum values.

[0425] The term "basically as shown in the figure X-ray powder diffraction pattern" means that at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%, or at least 95%, or at least 99% of the major peaks shown in the X-ray powder diffraction pattern appear in the X-ray powder diffraction pattern; the major peaks refer to the peaks with a relative intensity greater than 10%, preferably greater than 20%, and more preferably greater than 30%, with the highest peak as a reference (the relative intensity of the highest peak is specified as 100%).

[0426] The term "room temperature" refers to a temperature of 20-30°C.

[0427] The term "solvate" refers to a substance formed by combining the compound of this invention with a stoichiometric or non-stoichiometric solvent. The solvent molecules in the solvate can exist in an ordered or disordered arrangement. The solvents include, but are not limited to, water, methanol, ethanol, IPA, IPAc, n-heptane, acetone, or MTBE. For example, the solvate can be a hydrate, an IPA solvate, an IPAc solvate, a n-heptane solvate, an acetone solvate, or an MTBE solvate.

[0428] The terms "carrier" and "pharmaceutically acceptable carrier" refer to a diluent, adjuvant, excipient, or medium that is administered or formulated with a compound for administration. Non-limiting examples of such pharmaceutically acceptable carriers include liquids such as water, saline, and oils; and solids such as gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, urea, etc. Additionally, auxiliaries, stabilizers, thickeners, lubricants, flavoring agents, and coloring agents may be used. The corresponding stable isomers can be separated by known methods, such as extraction, filtration, or column chromatography.

[0429] The term "patient" or "subject" refers to a living organism that suffers from or is susceptible to a disease or symptom that can be treated by application of the drug or drug composition provided by the present invention, preferably a mouse, rat, other rodent, rabbit, dog, cat, pig, cattle, sheep, horse or primate, and most preferably a human.

[0430] The term "disease" or "symptom" refers to a state or health condition in which a patient or subject can be treated with the medicine, pharmaceutical composition, preparation or method provided by the present invention.

[0431] The term "prevention" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0432] The term "treatment" refers to preventing, halting, or slowing the progression of a subject's disease or ailment, or eliminating a subject's disease or ailment. In some embodiments, "treatment" means halting or slowing the progression of a subject's disease or ailment, or eliminating a subject's disease or ailment. In one embodiment, "treatment" means reducing at least one objective manifestation of a subject's disease or ailment.

[0433] The term "effective amount" refers to an amount sufficient to produce the desired biological effect.

[0434] The term “therapeutic effective amount” refers to an amount sufficient to produce the desired therapeutic effect, which includes one or more of the following: (1) prevention of disease: for example, prevention of disease, disorder or condition in an individual who is susceptible to disease, disorder or condition but has not yet experienced or developed the pathology or symptoms of the disease. (2) suppression of disease: for example, suppression of disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease (i.e., preventing the further development of the pathology and / or symptoms). (3) relief of disease: for example, relief of disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease (i.e., reversal of the pathology and / or symptoms).

[0435] The compounds described herein may include all stereoisomers of the compound. The term "stereoisomer" refers to isomers resulting from different spatial arrangements of atoms in a molecule, including enantiomers, diastereomers, cis-trans isomers, and conformational isomers. Unless otherwise specified, wedge-shaped solid lines are used. and wedge-shaped dashed key The absolute configuration representing the center of a solid.

[0436] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0437] Those skilled in the art can determine, using conventional methods, the appropriate amounts of salts, any one or a mixture of two salt crystal forms or free base crystal forms in a pharmaceutical composition, as well as various pharmaceutically acceptable carriers and / or other active ingredients.

[0438] The reagents and raw materials used in this invention are all commercially available.

[0439] The positive and progressive effects of this invention are as follows: the salt and its crystal form have stable physical and chemical properties, good processability in formulation, superior in vitro and in vivo biological performance, and broad application prospects. Attached Figure Description

[0440] Figure 1 shows the atomic thermal vibration ellipsoids of two crystallographically independent compound IR molecules in an asymmetric unit (Note: the atomic thermal vibration ellipsoids in the figure are drawn at a 50% probability level).

[0441] Figure 2 shows the atomic thermal vibration ellipsoids of two crystallographically independent compound IR molecules in an asymmetric unit (Note: the second conformational position of the disordered group on the second crystallographically independent compound IR molecule has been omitted).

[0442] Figure 3 shows the XRPD pattern of tartrate crystal form A;

[0443] Figure 4 shows the DSC-TGA spectrum of tartrate crystal form A;

[0444] Figure 5 shows tartrate crystal form A. 1 H-NMR spectrum;

[0445] Figure 6 shows the PLM diagram of tartrate crystal form A;

[0446] Figure 7 shows the XRPD pattern of succinate crystal form A;

[0447] Figure 8 shows the DSC-TGA spectrum of succinate crystal form A;

[0448] Figure 9 shows succinate crystal form A. 1 H-NMR spectrum;

[0449] Figure 10 shows the PLM diagram of succinate crystal form A;

[0450] Figure 11 shows the XRPD pattern of hydrochloride crystal form A;

[0451] Figure 12 shows the DSC-TGA spectrum of hydrochloride crystal form A;

[0452] Figure 13 shows the hydrochloride crystal form A. 1 H-NMR spectrum;

[0453] Figure 14 is the PLM diagram of hydrochloride crystal form A;

[0454] Figure 15 shows the XRPD pattern of hydrochloride crystal form B;

[0455] Figure 16 shows the DSC-TGA spectrum of hydrochloride crystal form B;

[0456] Figure 17 shows the hydrochloride crystal form B. 1 H-NMR spectrum;

[0457] Figure 18 shows the XRPD pattern of sodium salt crystal form A;

[0458] Figure 19 shows the DSC-TGA spectrum of sodium salt crystal form A;

[0459] Figure 20 shows sodium salt crystal form A. 1 H-NMR spectrum;

[0460] Figure 21 is the PLM diagram of sodium salt crystal form A;

[0461] Figure 22 shows the XRPD pattern of sodium salt crystal form B;

[0462] Figure 23 shows the DSC-TGA spectrum of sodium salt crystal form B;

[0463] Figure 24 shows sodium salt crystal form B. 1 H-NMR spectrum;

[0464] Figure 25 shows the PLM diagram of sodium salt crystal form B;

[0465] Figure 26 shows the XRPD pattern of sodium salt crystal form C;

[0466] Figure 27 shows the DSC-TGA spectrum of sodium salt crystal form C;

[0467] Figure 28 shows sodium salt crystal form C. 1 H-NMR spectrum;

[0468] Figure 29 shows the PLM diagram of sodium salt crystal form C;

[0469] Figure 30 shows the XRPD pattern of Tris salt crystal form A;

[0470] Figure 31 shows the DSC-TGA spectrum of Tris salt crystal form A;

[0471] Figure 32 shows the Tris salt crystal form A. 1 H-NMR spectrum;

[0472] Figure 33 shows the PLM diagram of Tris salt crystal form A;

[0473] Figure 34 shows the XRPD pattern of Tris salt crystal form B;

[0474] Figure 35 shows the DSC-TGA spectrum of Tris salt crystal form B;

[0475] Figure 36 shows the Tris salt crystal form B. 1 H-NMR spectrum;

[0476] Figure 37 shows the PLM diagram of Tris salt crystal form B;

[0477] Figure 38 shows the XRPD pattern of Tris salt crystal form C;

[0478] Figure 39 shows the DSC-TGA spectrum of Tris salt crystal form C;

[0479] Figure 40 shows the Tris salt crystal form C. 1 H-NMR spectrum;

[0480] Figure 41 shows the PLM diagram of Tris salt crystal form C;

[0481] Figure 42 shows the XRPD pattern of phosphate crystal form A;

[0482] Figure 43 shows the DSC-TGA spectrum of phosphate crystal form A;

[0483] Figure 44 shows the XRPD pattern of fumarate crystal form A;

[0484] Figure 45 shows the DSC-TGA spectrum of fumarate crystal form A;

[0485] Figure 46 shows the XRPD pattern of malate crystal form A;

[0486] Figure 47 shows the DSC-TGA spectrum of malate crystal form A;

[0487] Figure 48 shows the XRPD pattern of hydrobromide crystal form A;

[0488] Figure 49 shows the DSC-TGA spectrum of hydrobromide crystal form A;

[0489] Figure 50 shows the XRPD pattern of hydrobromide crystal form B;

[0490] Figure 51 shows the DSC-TGA spectrum of hydrobromide crystal form B;

[0491] Figure 52 shows the XRPD pattern of magnesium salt crystal form A;

[0492] Figure 53 shows the DSC-TGA spectrum of magnesium salt crystal form A;

[0493] Figure 54 shows the XRPD pattern of potassium salt crystal form A;

[0494] Figure 55 shows the DSC-TGA spectrum of potassium salt crystal form A;

[0495] Figure 56 shows the XRPD pattern of calcium salt crystal form A;

[0496] Figure 57 shows the DSC-TGA spectrum of calcium salt crystal form A;

[0497] Figure 58 shows the XRPD pattern of meglumine salt crystal form A;

[0498] Figure 59 shows the DSC-TGA spectrum of meglumine salt crystal form A;

[0499] Figure 60 shows the XRPD pattern of meglumine salt crystal form B;

[0500] Figure 61 shows the DSC-TGA spectrum of meglumine salt crystal form B;

[0501] Figure 62 shows the XRPD pattern of lysine salt crystal form A;

[0502] Figure 63 shows the DSC-TGA spectrum of lysine salt crystal form A;

[0503] Figure 64 shows the XRPD pattern of lysine salt crystal form B;

[0504] Figure 65 shows the DSC-TGA spectrum of lysine salt crystal form B;

[0505] Figure 66 shows the XRPD pattern of diethylamine salt crystal form A;

[0506] Figure 67 shows the DSC-TGA spectrum of diethylamine salt crystal form A;

[0507] Figure 68 shows the XRPD pattern of diethanolamine salt crystal form A;

[0508] Figure 69 shows the DSC-TGA spectrum of diethanolamine salt crystal form A;

[0509] Figure 70 shows the XRPD pattern of 1,2-ethylenedisulfonate crystal form A;

[0510] Figure 71 shows the DSC-TGA spectrum of 1,2-ethanedisulfonate crystal form A;

[0511] Figure 72 shows crystal form A of 1,2-ethanedisulfonate. 1 H-NMR spectrum. Detailed Implementation

[0512] The following detailed description, in conjunction with specific embodiments, illustrates the general formula compounds of the present invention, their preparation methods, and applications in further detail. The following embodiments are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0513] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0514] Abbreviations:

[0515] THF: Tetrahydrofuran; n-BuLi: n-Butyllithium; TBDMSCl: Tert-Butyldimethylchlorosilane; IPA: Isopropanol; IPAc: Isopropyl acetate; MTBE: Methyl tert-Butyl ether; ACN: Acetonitrile; DMSO: Dimethyl sulfoxide; Tris: Tris(hydroxymethyl)aminomethane; EtOAc: Ethyl acetate; DCM: Dichloromethane; EtOH: Ethanol; MSA: Methanesulfonic acid.

[0516] Instrumentation and Methods:

[0517] 1. X-ray powder diffraction (XRPD)

[0518] The XRPD test was performed using an X-ray powder diffractometer manufactured by PANalytical, and the test parameters are shown in the table below.

[0519] 2. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC)

[0520] The TGA analysis was performed using a Discovery TA5500 / TA550 thermogravimetric analyzer, and the DSC analysis was performed using a Discovery TA2500 / TA250 differential scanning calorimeter. The test parameters are shown in the table below:

[0521] 3. Dynamic Moisture Adsorption (DVS)

[0522] The DVS test used SMS (Surface Measurement Systems)'s DVS Intrinsic or Intrinsic Plus. The relative humidity at 25°C was corrected for using the deliquescence points of LiCl, Mg(NO3)2, and KCl. The test parameters are shown in the table below:

[0523] 4. Liquid NMR (Solution NMR)

[0524] 1H NMR (1H NMR) 1 H NMR was acquired on a Bruker 400M NMR spectrometer, using DMSO-d6 and deuterated methanol as solvents.

[0525] 5. Polarizing microscope (PLM)

[0526] PLM data were acquired at room temperature using an Axio Lab.A1 upright microscope.

[0527] 6. High-performance liquid chromatography (HPLC)

[0528] The purity of the samples was tested using an Agilent high-performance liquid chromatograph or a Waters ultra-high-performance liquid chromatograph, and the analytical conditions are shown in the table below:

[0529] ①High-performance liquid chromatography (HPLC) test conditions:

[0530] ②Ultra-high performance liquid chromatography test conditions:

[0531] 7. Ion chromatography (IC)

[0532] IC analysis was performed using either an ICS1100 or a Thermo Fisher Dionex Aquion ion chromatograph. The test conditions are shown in the table below:

[0533] ①Test conditions for the ICS1100 ion chromatograph:

[0534] ② Test conditions for the Thermo Fisher Dionex Aquion ion chromatograph:

[0535] 8. Single-crystal X-ray diffraction (SCXRD)

[0536] Single-crystal X-ray diffraction data were collected using a Rigaku XtaLAB Synergy R-type single-crystal X-ray diffractometer. Instrument parameters are as follows:

[0537] Example 1: Preparation of (R)-2-(1-((6-(5-(((((3,3-difluoropentan-2-yl)oxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)ethynyl)cyclopropyl)acetic acid (compound IR)

[0538] (1) Preparation of compound IN-01

[0539] Compound SM01 (60 g, 907.7 mmol) was dissolved in THF (240 mL), and the resulting solution was cooled to -78 °C (dry ice-ethyl acetate bath), followed by the dropwise addition of n-BuLi (399.4 mL, 998.5 mmol, 2.5 M n-hexane solution). After the addition was complete, the reaction mixture was stirred at -78 °C for 1 hour. Then, a THF (300 mL) solution of TBDMSCl (136.81 g, 907.7 mmol) was added dropwise, and the reaction mixture was stirred at -78 °C for 0.5 hours, followed by stirring at room temperature for 1 hour. The reaction mixture was cooled to 0 °C, and the reaction was quenched by adding saturated ammonium chloride solution (480 mL) and water (120 mL). The aqueous phase was extracted with ethyl acetate (300 mL × 2), the organic phases were combined, washed with saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 0) to give compound IN-01 (308 g), LC-MS: [M+H] + =181.36.

[0540] (2) Preparation of compound IN-02

[0541] IN-01 (150 g, 831.7 mmol) was dissolved in methyl tert-butyl ether (1500 mL). The resulting solution was cooled to -78 °C (dry ice-ethyl acetate bath), and then n-BuLi (366 mL, 914.8 mmol, 2.5 M hexane solution) was added dropwise. The reaction solution was stirred at -78 °C for 1 hour, and then stirred for another 3 hours after the solution naturally warmed to room temperature. The reaction solution was then cooled to 0 °C, and ethylene oxide (360.4 mL, 1.08 mol, 3 M diethyl ether solution) was added dropwise, maintaining this temperature while stirring for 1 hour. The reaction was quenched by adding saturated ammonium chloride solution (1200 mL) and water (300 mL). The aqueous phase was extracted with ethyl acetate (750 mL × 2), the organic phases were combined, washed with brine (500 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to give compound IN-02 (104 g), LC-MS: [M+H] + =225.1.

[0542] (3) Preparation of compound IN-03

[0543] IN-02 (84.0 g, 374.3 mmol) was dissolved in acetonitrile (840 mL) and water (840 mL). Sodium bicarbonate (94.34 g, 1122.9 mmol) and 2,2,6,6-tetramethylpiperidine oxide (11.7 g, 74.9 mmol) were added, followed by the addition of iodophenyldiacetic acid (301.4 g, 935.8 mmol) in portions. The reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched by adding saturated sodium sulfite solution (420 mL). The aqueous phase was extracted with ethyl acetate (600 mL × 3). The combined organic phases were washed with saturated brine (500 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound IN-03 (62 g). LC-MS: [M+H] + =239.40.

[0544] (4) Preparation of compound IN-04

[0545] IN-03 (67 g, 281.1 mmol) was dissolved in N,N-dimethylformamide (420 mL), and iodomethane (48.3 g, 340.1 mmol) was added. After cooling the reaction solution to 0–5 °C, potassium carbonate (42.7 g, 309.0 mmol) was added. The reaction solution was stirred at this temperature for 0.5 h, then heated to room temperature and stirred for another 2 h. The reaction solution was poured into water (1.1 L) and extracted with ethyl acetate (670 mL × 2). The combined organic phases were washed with water (670 mL × 2), washed with saturated brine (670 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 40) to give compound IN-04 (129 g). LC-MS: [M+H] + =253.42.

[0546] (5) Preparation of compound IN-05

[0547] Compound SM02 (50 g, 277.47 mmol) was dissolved in dichloromethane (500 mL), and dimethylhydroxylamine hydrochloride (32.48 g, 332.96 mmol), N,N-diisopropylethylamine (107.58 g, 832.41 mmol), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (158.25 g, 416.21 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched in water (500 mL) and extracted with dichloromethane (500 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to give compound IN-05 (60 g). LC-MS: [M+H] + =224.05.

[0548] (6) Preparation of compound IN-06

[0549] IN-05 (60 g, 268.73 mmol) was dissolved in THF (600 mL). The resulting solution was cooled to 0 °C, and ethyl magnesium bromide solution (201.55 mL, 403.10 mmol, 2 M THF solution) was added dropwise. The reaction mixture was heated to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution (500 mL) and extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give compound IN-06 (45 g). LC-MS: [M+H] + =193.25.

[0550] (7) Preparation of compound IN-07

[0551] IN-06 (55 g, 286.07 mmol) was dissolved in dichloromethane (550 mL). The resulting solution was cooled to 0 °C, and diethylaminotrifluoride (184.44 g, 1.14 mol) was added dropwise. The reaction mixture was heated to 30 °C and stirred for 48 hours. The reaction mixture was then quenched by slowly pouring in a saturated sodium bicarbonate aqueous solution (2000 mL), and extracted with dichloromethane (500 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound IN-07 (60 g crude). The crude compound was dissolved in THF (500 mL), activated carbon (5.5 g) was added, and the solution was heated to 50 °C and stirred for decolorization for 0.5 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain compound IN-07 (55 g). LC-MS: [M+H] + =215.25.

[0552] (8) Preparation of compound IN-08

[0553] IN-07 (50 g, 233.37 mmol) was dissolved in THF (500 mL), and wet palladium on carbon (5.0 g, 10%) and wet palladium hydroxide on carbon (2.0 g, 20%) were added. Under hydrogen protection, the reaction solution was heated to 50 °C and stirred for 24 hours. After cooling to room temperature, the reaction solution was filtered under reduced pressure. The filtrate was dried with molecular sieves, filtered again, and concentrated under reduced pressure to obtain a THF solution (186 g) of compound IN-08. LC-MS: [M+H] + =125.13.

[0554] (9) Preparation of compound IN-09

[0555] Compound SM03 (50 g, 199.27 mmol) and 2-(prop-2-yn-1-yloxy)tetrahydro-2H-pyran (41.9 g, 298.9 mmol) were dissolved in acetonitrile (500 mL), and bis(triphenylphosphine)palladium dichloride (7.0 g, 9.96 mmol), cuprous iodide (2.0 g, 9.96 mmol), and triethylamine (60.0 g, 597.8 mmol) were added. Under nitrogen protection, the reaction mixture was heated to 50 °C and stirred for 1.5 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give compound IN-09 (60.0 g). LC-MS: [M+H] + =311.95.

[0556] (10) Preparation of compound IN-10

[0557] IN-09 (60.0 g, 0.19 mol) and trimethylsilylmethyl azide (50 g, 0.38 mol) were dissolved in THF (600 mL). Pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium chloride (15 g, 0.019 mol), tetrabutylammonium iodide (7.0 g, 0.019 mol), and cuprous iodide (3.6 g, 0.019 mol) were added. Under nitrogen protection, the reaction mixture was heated to 40 °C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give compound IN-10 (68.0 g). LC-MS: [M+H] + =439.00.

[0558] (11) Preparation of compound IN-11

[0559] IN-10 (68.0 g, 155.21 mmol) was dissolved in THF (600 mL), and tetrabutylammonium fluoride (48.7 g, 186.26 mmol) was added in portions. The reaction mixture was stirred at room temperature for 1 hour. The solution was then concentrated under reduced pressure, and the residue was diluted with water (120 mL), extracted with ethyl acetate (60 mL), and the combined organic phases were washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to give compound IN-11 (42.2 g). LC-MS: [M+H] + =367.00.

[0560] (12) Preparation of compound IN-12

[0561] IN-11 (5 g, 13.6 mmol) and N,N'-dimethylethylenediamine (720 mg, 8.2 mmol) were dissolved in 1,4-dioxane (50 mL), and sodium iodide (10.3 g, 68.7 mmol) and cuprous iodide (260 mg, 1.4 mmol) were added. Under nitrogen protection, the reaction mixture was heated to 100 °C and stirred for 24 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give compound IN-12 (5.5 g). LC-MS: [M+H] + =415.00.

[0562] (13) Preparation of compound IN-13

[0563] IN-12 (5.5 g, 13.3 mmol) was dissolved in methanol (60 mL), and pyridine 4-methylbenzenesulfonic acid (3.3 g, 13.3 mmol) was added. The reaction mixture was heated to 60 °C and stirred for 16 hours. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to give compound IN-13 (4.5 g). LC-MS: [M+H] + =330.95.

[0564] (14) Preparation of compound IN-14

[0565] IN-13 (4.5 g, 13.6 mmol) was dissolved in acetonitrile (50 mL) and water (35 mL), and potassium permanganate (4.3 g, 27.2 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. Sodium hydroxide aqueous solution (2 M, 50 mL) was added to the reaction mixture, and the mixture was filtered under reduced pressure. The filtrate was extracted with ethyl acetate (50 mL), and the aqueous phases were combined. The pH was adjusted to 3 with dilute hydrochloric acid (1 M), and the mixture was filtered under reduced pressure. The filter cake was washed with pure water (30 mL) and dried under reduced pressure to give compound IN-14 (2.8 g). LC-MS: [M+H] + =344.95.

[0566] (15) Preparation of compound IN-15

[0567] IN-14 (16 g, 46.50 mmol), triethylamine (16.94 g, 167.39 mmol), and azidotrimethylsilane (10.71 g, 92.99 mmol) were dissolved in THF (160 mL). 1-Propylphosphine (44.38 g, 69.74 mmol, 50% ethyl acetate solution) was added dropwise with stirring. The reaction mixture was stirred at room temperature for 0.5 hours, and then a THF solution of compound IN-08 (74 g, 92.99 mmol) was added. The reaction mixture was heated to 80 °C and stirred for another 2 hours. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to obtain compound IN-15 (17 g). LC-MS: [M+H] + =466.20.

[0568] (16) Preparation of compound IN-16

[0569] IN-04 (16.28 g, 64.48 mmol) was dissolved in THF (170 mL), and a THF solution of tetrabutylammonium fluoride (1 M, 64.48 mL, 64.48 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 0.5 h. Anhydrous magnesium sulfate (30 g) was added to the reaction mixture and dried for 1 h. The mixture was filtered, and IN-15 (15 g, 32.24 mmol), bis(triphenylphosphine)palladium dichloride (2.26 g, 3.22 mmol), cuprous iodide (614 mg, 3.22 mmol), and triethylamine (9.79 g, 96.72 mmol) were added to the filtrate. The reaction mixture was stirred at room temperature for 16 h under nitrogen protection, then diluted with water (100 mL) and extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to obtain compound IN-16 (12 g, crude product), which was then preparatively separated by high performance liquid chromatography (0.1% trifluoroacetic acid) to obtain compound IN-16 (10 g). LC-MS: [M+H] + =476.20.

[0570] (17) Preparation of compound IR

[0571] IN-16 (3.00 g, 6.43 mmol) was dissolved in THF (45 mL), and a solution of lithium hydroxide monohydrate (0.80 g, 18.88 mmol) in water (15 mL) was added. The reaction mixture was stirred at room temperature. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, and water (15 mL) and dichloromethane (15 mL) were added. The mixture was then concentrated again under reduced pressure to further remove THF. The mixture was extracted and separated using dichloromethane (60 mL) and water (30 mL). After adjusting the pH of the aqueous phase to 1-2, the mixture was extracted once with dichloromethane (60 mL). The organic phases were combined, washed with saturated brine (350 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then dichloromethane (15 mL) was added. Heptane (30 mL) was slowly added dropwise at 10-15 °C, and the mixture was stirred for 1 hour. The mixture was filtered, and the filter cake was dried under vacuum at 45 °C to obtain compound IR (2.3 g, purity 96.18%). Its chirality was confirmed by single-crystal characterization. LC-MS: [M+H] + =462.15.

[0572] Single crystal characterization:

[0573] Approximately 20 mg of compound IR was weighed into a 3 mL glass bottle, and 0.5 mL of solvent 1,4-dioxane was added. If the solid was not completely dissolved, it was filtered using a 0.45 μm PTFE filter membrane. The 3 mL glass bottle containing the solution was placed openly into a 20 mL bottle containing 3 mL of the antisolvent cyclohexane. The 20 mL bottle was sealed with a cap and allowed to stand at room temperature for a certain period of time to allow the solvent vapor to interact with the solution and separate the precipitated solid. A single crystal of compound IR with a suitable size and high diffraction quality was selected from the obtained solid and characterized by room temperature single-crystal X-ray diffraction (SCXRD). The single-crystal structure analysis showed that the asymmetric unit of the crystal structure consisted of two compound IR molecules, and the structure did not contain any water of crystallization or other crystallizing solvent molecules, which confirmed that compound IR was amorphous. Based on the single-crystal structure data obtained from the analysis (as shown in Table 1, Figure 1, and Figure 2 below), the absolute configuration of the chiral center (C18) in the compound IR molecule was confirmed to be R configuration.

[0574] Table 1: Crystallographic data and structural refinement parameters of compound IR single crystals

[0575] 1 H NMR (400MHz, DMSO-d6) δ12.23(s,1H),9.89(s,1H),7.75(d,J=8.4Hz,1H),7.70(d,J=8.4Hz,1H),4.90-5.1 0(m,1H),3.90(s,3H),2.51(s,3H),2.46(s,2H),2.14-1.77(m,2H),1.52-1.13(m,3H),1.10-0.78(m,7H).

[0576] Example 2 Preparation of 2-(1-((6-(5-(((((3,3-difluoropentan-2-yl)oxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)ethynyl)cyclopropyl)acetic acid (compound I)

[0577] Compound I was prepared using the same method as Compound IR in Example 1, except that the starting material SM02 was replaced with SM04. LC-MS: [M+H] + =462.05.

[0578] 1H NMR (400MHz, DMSO-d6): δ7.74(d,J=8.2Hz,1H),7.65(d,J=8.2Hz,1H),5.04-4.91(m,1H), 3.85(s,3H),2.51(s,3H),2.26(s,2H),2.05-1.78(m,2H),1.23(s,3H),0.96-0.88(m,7H).

[0579] Example 3: Preparation of L-Tartrate

[0580] Compound IR (20 mg) and L-tartaric acid (6.5 mg, molar ratio of 1:1 to compound IR) were weighed and stirred for about 2 days in the solvent (0.5 mL) and temperature corresponding to those in Table 1-1. After centrifugation, the precipitate was dried under vacuum at 50 °C for 6 hours and characterized by XRPD. Specific information and results are summarized in Table 1-1.

[0581] Table 1-1 Preparation of L-Tartrate

[0582] This embodiment yielded a crystal form of L-tartrate of compound IR, named tartrate crystal form A. Tartrate crystal form A (group 2) was subjected to XRPD, TGA, DSC, and other methods. 1 The results of H NMR and PLM characterization are shown in Figures 3-6 and Tables 1-2-1-4.

[0583] TGA and DSC results (Figure 4) show that tartrate crystal form A loses 1.28% weight when heated to 140℃ and has an endothermic peak at 152.5℃ (peak temperature). 1 ¹H NMR results (Figure 5) show that the molar ratio of tartaric acid to compound IR in tartrate crystal form A is 1.3:1, and tartrate crystal form A does not contain IPAc. PLM results (Figure 6) show that tartrate crystal form A consists of crystal particles of varying sizes.

[0584] Table 1-2 Characterization results of tartrate crystal form A

[0585] Table 1-3 XRPD diffraction peak analysis data for tartrate crystal form A

[0586] Table 1-4 XRPD spectrum analysis data of tartrate crystal form A

[0587] Example 4 Preparation of Succinate

[0588] Compound IR (20 mg) and succinic acid (5.11 mg, molar ratio of IR to compound IR 1:1) were weighed and stirred for about 2 days in the solvent (0.5 mL) and temperature corresponding to those in Table 2-1. After centrifugation, the precipitate was dried under vacuum at 50 °C for 6 hours, and the resulting solid was characterized by XRPD. Specific information and results are summarized in Table 2-1.

[0589] Table 2-1 Preparation of Succinate

[0590] This embodiment yielded a succinate crystal form of compound IR, named succinate crystal form A. Succinate crystal form A (group 3) was subjected to XRPD, TGA, DSC, and other methods. 1 The results of H NMR and PLM characterization are shown in Figures 7-10 and Tables 2-2-2-4.

[0591] TGA and DSC results (Figure 8) show that succinate crystal form A loses 0.98% of its weight when heated to 140 °C, and has an endothermic peak at 151.5 °C (peak temperature). 1 ¹H NMR results (Figure 9) show that the molar ratio of succinic acid to compound IR in succinate crystal form A is 0.5:1, and succinate crystal form A does not contain MTBE. PLM results (Figure 10) show that succinate crystal form A consists of small crystal particles and rod-shaped crystals of varying lengths.

[0592] Table 2-2 Characterization results of succinate crystal form A

[0593] Table 2-3 XRPD diffraction peak analysis data for succinate crystal form A

[0594] Table 2-4 XRPD spectrum analysis data of succinate crystal form A

[0595] Example 5 Preparation of hydrochloride

[0596] (1) Preparation of hydrochloride crystal form A

[0597] Method 1:

[0598] Compound IR (20 mg) was weighed and mixed with hydrochloric acid (molar ratio of 1:1 to compound IR) in 0.5 mL of MTBE. The mixture was stirred at room temperature for 2 days, centrifuged, and the precipitate was vacuum dried at 50 °C for 6 hours to obtain a solid (characterized by XPPD as the crystalline form of compound IR). The supernatant from centrifugation was added to the obtained solid, followed by the addition of 0.2 mL of MTBE and 1.58 mg of hydrochloric acid (molar ratio of 1:1 to compound IR). The mixture was stirred at room temperature for 2 days, and the solid was separated from the liquid. The obtained solid was characterized by XRPD.

[0599] Method 2:

[0600] 20 mg of compound IR was weighed and mixed with hydrochloric acid (molar ratio of IR to compound IR was 1:1) in an EtOAc / n-heptane (0.5 mL, v / v = 1 / 3) system. The mixture was then suspended and stirred at room temperature for 1 day, followed by temperature cycling (50℃~5℃, 0.1℃ / min) and stirring for 1 day. The mixture was then centrifuged, and the precipitate was dried under vacuum at room temperature for 6 hours. The obtained solid was characterized by XRPD.

[0601] In this embodiment, methods 1 and 2 yielded a crystal form of the hydrochloride salt of compound IR, which was named hydrochloride crystal form A.

[0602] The hydrochloride crystal form A obtained by method 1 was subjected to XRPD, TGA, DSC, 1 Characterization was performed by 1H NMR, HPLC / IC and PLM. The results are shown in Figures 11-14 and Tables 3-1-3-3.

[0603] TGA and DSC results (Figure 12) show that hydrochloride crystal form A loses 7.02% of its weight when heated to 120 °C, and has an endothermic peak at 109.3 °C (peak temperature). 1 ¹H NMR results (Figure 13) show that MTBE is not present in hydrochloride crystal form A. HPLC / IC results show that the molar ratio of hydrochloric acid to compound IR in hydrochloride crystal form A is 1:1. PLM results (Figure 14) show that hydrochloride crystal form A consists of crystal particles of varying sizes.

[0604] Table 3-1 Characterization results of hydrochloride crystal form A

[0605] Table 3-2 XRPD diffraction peak analysis data for hydrochloride crystal form A

[0606] Table 3-3 XRPD spectrum analysis data of hydrochloride crystal form A

[0607] (2) Preparation of hydrochloride crystal form B

[0608] Method 1:

[0609] 20 mg of compound IR was weighed and mixed with hydrochloric acid (molar ratio of 1:1 to compound IR) in a THF / n-heptane (0.5 mL, v / v = 1 / 2) system. The mixture was then suspended and stirred at room temperature for 1 day. The mixture was then subjected to temperature cycling (50 °C to 5 °C, 0.1 °C / min) and stirred for 1 day. After centrifugation, the precipitate was dried under vacuum at room temperature for 6 hours. The obtained solid was characterized by XRPD.

[0610] Method 2:

[0611] 20 mg of compound IR was weighed and suspended in 0.5 mL of DCM at room temperature and stirred for 1 day. Then, the mixture was circulated at 50 °C to 5 °C at 0.1 °C / min and stirred for 1 day. Then, 1 mL of n-heptane was added and the mixture was circulated at 50 °C to 5 °C at 0.1 °C / min and stirred for 4 days. Finally, the mixture was circulated at -20 °C and stirred for 1 day. The mixture was then centrifuged and the precipitate was dried under vacuum at room temperature for 6 hours. The obtained solid was characterized by XRPD.

[0612] In this embodiment, methods 1 and 2 yielded a crystal form of the hydrochloride salt of compound IR, named hydrochloride crystal form B. Hydrochloride crystal form B (method 1) was subjected to XRPD, TGA, DSC, and... 1 Characterization by 1H NMR and HPLC / IC, the results are shown in Figures 15-17 and Tables 3-4-3-6.

[0613] The TGA results (Figure 16) show that hydrochloride crystal form B loses 7.27% of its weight when heated to 110 °C. The DSC results (Figure 16) show that hydrochloride crystal form B has an endothermic peak at 110.1 °C (peak temperature). 1 The 1H NMR spectrum (Figure 17) shows that there is no solvent residue in hydrochloride crystal form B. HPLC / IC results show that the molar ratio of hydrochloric acid to compound IR in hydrochloride crystal form B is 1:1.

[0614] Table 3-4 Characterization results of hydrochloride crystal form B

[0615] Table 3-5 XRPD diffraction peak analysis data for hydrochloride crystal form B

[0616] Table 3-6 XRPD spectrum analysis data of hydrochloride crystal form B

[0617] Example 6 Preparation of Sodium Salt

[0618] Compound IR (20 mg) and sodium hydroxide (1.73 mg, molar ratio of IR to compound IR 1:1) were weighed and placed in the corresponding solvents (0.5 mL) in Table 4-1. The mixture was stirred at room temperature for 2 days (except for group 2), centrifuged, and the precipitate was vacuum dried at room temperature for 16 hours. The resulting solid was characterized by XRPD. In group 2, the reaction solution became gelatinous after stirring at room temperature for 1 day. Stirring continued under temperature cycling (50℃~5℃, 0.1℃ / min, 2 cycles) until it became gelatinous again. Then, it was cooled to -20℃ and stirred for 5 days until it became gelatinous again. Finally, it was allowed to evaporate at room temperature to obtain a gelatinous sodium salt. Detailed information and results are summarized in 4-1.

[0619] Table 4-1 Preparation of Sodium Salts

[0620] This embodiment yielded two crystal forms of sodium salts of compound IR, named sodium salt crystal form A and sodium salt crystal form B, respectively. XRPD, TGA, and DSC were then performed on sodium salt crystal form A (group 1) and sodium salt crystal form B (group 3), respectively. 1 Characterization was performed by ¹H NMR, PLM, and HPLC / IC. The results are shown in Figures 18-25 and Tables 4-2-4-6.

[0621] The TGA and DSC results of sodium salt crystal form A (Figure 19) show that the crystal form has a weight loss of 2.95% when heated to 130 °C and has an endothermic peak at 143.8 °C (peak temperature). 1 ¹H NMR results (Figure 20) show that sodium salt crystal form A does not contain IPA or n-heptane. HPLC / IC results show that the molar ratio of sodium ions to compound IR in sodium salt crystal form A is 0.9:1. PLM results (Figure 21) show that sodium salt crystal form A consists of crystal particles of varying sizes.

[0622] The TGA and DSC results (Figure 23) of sodium salt crystal form B showed a 2.39% weight loss when heated to 120 °C, with one endothermic peak at 142.6 °C and one exothermic peak at 178.1 °C. HPLC / IC results showed that the molar ratio of sodium ions to compound IR in sodium salt crystal form B was 0.6:1. 1 1H NMR results (Figure 24) show that sodium salt crystal form B does not contain IPAc or n-heptane. PLM results (Figure 25) show that sodium salt crystal form B consists of crystal particles of varying sizes.

[0623] Table 4-2 Characterization results of sodium salt crystal forms

[0624] Table 4-3 XRPD diffraction peak analysis data of sodium salt crystal form A

[0625] Table 4-4 XRPD spectrum analysis data of sodium salt crystal form A

[0626] Table 4-5 XRPD diffraction peak analysis data of sodium salt crystal form B

[0627] Table 4-6 XRPD spectrum analysis data of sodium salt crystal form B

[0628] Example 7 Preparation of sodium salt crystal form C

[0629] Compound IR (1005.5 mg) and sodium hydroxide (95.6 mg, molar ratio of IR to compound IR 1.1:1) were weighed and added to 20.0 mL of IPA / n-heptane (1 / 2, v / v). The mixture was suspended and stirred at room temperature for 4 days. The mixture was filtered and washed three times (20.0 mL total) with IPA / n-heptane (1 / 2, v / v). The filter cake was dried under vacuum at room temperature for 18.5 hours to obtain 955.0 mg of solid. XRPD, TGA, DSC, and other analytical methods were performed. 1 Characterization was performed by ¹H NMR, PLM, and HPLC / IC. The results are shown in Figures 26-29 and Tables 4-7-4-9.

[0630] This embodiment yielded a novel crystal form of the sodium salt of compound IR, named sodium salt crystal form C. TGA and DSC results (Figure 27) showed that sodium salt crystal form C exhibited a 3.61% weight loss upon heating to 130°C and a 5.59% weight loss upon further heating to 210°C, with two endothermic peaks at 137.7°C and 243.7°C (peak temperatures). HPLC / IC results indicated that the molar ratio of sodium ions to compound IR in sodium salt crystal form C was 1:1. 1 ¹H NMR results (Figure 28) show that sodium salt crystal form C does not contain n-heptane, but does contain IPA, and the molar ratio of IPA to compound IR is 0.01:1 (0.1 wt%). PLM results (Figure 29) show that sodium salt crystal form C consists of crystal particles of varying sizes.

[0631] Table 4-7 Characterization results of sodium salt crystal form C

[0632] Table 4-8 XRPD diffraction peak analysis data of sodium salt crystal form C

[0633] Table 4-9 XRPD spectrum analysis data of sodium salt crystal form C

[0634] Example 8 Preparation of Tris(hydroxymethyl)aminomethane (Tris) salt

[0635] At room temperature, 20 mg of compound IR and 5.24 mg of Tris (molar ratio of 1:1 to compound IR) were weighed and placed in the corresponding solvent (0.5 mL) in Table 5-1. The mixture was stirred for about 2 days, centrifuged, and the precipitate was vacuum dried at room temperature for 16 hours. The resulting solid was characterized by XRPD. Specific information and results are summarized in 5-1.

[0636] Table 5-1 Preparation of Tris Salts

[0637] In this embodiment, three Tris salt crystal forms of the IR compound were obtained and named Tris salt crystal form A, Tris salt crystal form B, and Tris salt crystal form C, respectively. XRPD, TGA, DSC, and other methods were used to analyze Tris salt crystal forms A (group 1), B (group 2), and C (group 3), respectively. 1 The results of H NMR and PLM characterization are shown in Figures 30-41 and Tables 5-2-5-8.

[0638] The TGA and DSC results of Tris salt crystal form A (Figure 31) show that the crystal form has a weight loss of 1.27% when heated to 130 °C and has an endothermic peak at 121.6 °C (peak temperature). 1 ¹H NMR results (Figure 32) show that the molar ratio of Tris to compound IR in Tris salt crystal form A is 1:1, and this crystal form does not contain IPA or n-heptane. PLM results (Figure 33) show that Tris salt crystal form A consists of crystal particles of varying sizes.

[0639] The TGA and DSC results (Figure 35) of Tris salt crystal form B show that the crystal form has a weight loss of 5.73% when heated to 120 °C, and has two endothermic peaks at 94.2 °C and 118.7 °C (peak temperature). 1 ¹H NMR results (Figure 36) show that the molar ratio of Tris to compound IR in Tris salt crystal form B is 1:1, and this crystal form does not contain acetone or n-heptane. PLM results (Figure 37) show that Tris salt crystal form B consists of rod-shaped crystal particles of varying sizes.

[0640] The TGA and DSC results of Tris salt crystal form C (Figure 39) show that the crystal form has a weight loss of 5.83% when heated to 130 °C, and has three endothermic peaks at 58.9 °C, 89.3 °C and 103.8 °C (peak temperature). 1¹H NMR results (Figure 40) show that the molar ratio of Tris to compound IR in Tris salt crystal form C is 1:1, and this crystal form does not contain IPAc or n-heptane. PLM results (Figure 41) show that Tris salt crystal form C consists of crystal particles of varying sizes.

[0641] Table 5-2 Characterization results of Tris salt crystal forms

[0642] Table 5-3 XRPD diffraction peak analysis data of Tris salt crystal form A

[0643] Table 5-4 XRPD spectrum analysis data of Tris salt crystal form A

[0644] Table 5-5 XRPD diffraction peak analysis data of Tris salt crystal form B

[0645] Table 5-6 XRPD spectrum analysis data of Tris salt crystal form B

[0646] Table 5-7 XRPD diffraction peak analysis data for Tris salt crystal form C

[0647] Table 5-8 XRPD spectrum analysis data of Tris salt crystal form C

[0648] Example 9

[0649] Following the methods described in Examples 3-6, salts of compounds IR (as shown in Table 6-1) were prepared. The specific steps were as follows: 20 mg of compound IR and the corresponding acid (molar ratio of acid to compound IR was 1:1) were weighed and stirred at room temperature for approximately 2 days in 0.5 mL of the solvent corresponding to Table 6-1. The mixture was then centrifuged, and the precipitate was vacuum-dried at 50°C for 6 hours. The resulting solid was characterized by XRPD. Specific information and results are summarized in Table 6-1.

[0650] Table 6-1 Preparation of salts of compound IR

[0651] In the table: X: Other crystal forms besides the corresponding salt crystal form, such as one, two or more crystal forms of compound IR, the corresponding acid crystal form, other crystal forms, etc.

[0652] a: After stirring the reaction solution at room temperature for 2 hours, the solution becomes clear. Then, the reaction solution is cooled to 5°C and stirred for 2 days.

[0653] b: The reaction solution was stirred at room temperature for 2 hours until it became clear. Then it was suspended at 5°C and stirred for 2 days until it became clear. 1.0 mL of n-heptane was added and the temperature was lowered to -20°C and stirred for 2 hours until it became gel. The reaction solution was placed under temperature cycling (50°C~5°C, 0.1°C / min) and stirred for 9 days until it became clear. The reaction solution was then left to evaporate at room temperature to obtain a gel.

[0654] c: The reaction solution becomes gelatinous after stirring at room temperature for 2 hours. After being cooled to 5°C and stirred for 2 days, it becomes gelatinous again. Then, after stirring for 9 days under temperature cycling (50°C~5°C, 0.1°C / min), the reaction solution becomes clear. The reaction solution is then left to evaporate at room temperature to obtain a gelatinous substance.

[0655] d: The reaction solution was stirred at room temperature for 2 hours until it became slightly gel-like, and then cooled to 5°C and stirred for 2 days.

[0656] e: Mix the supernatant after centrifugation, 0.2 mL of MTBE and the corresponding acid in Table 6-1 (the molar ratio of acid to compound IR is 1:1), dissolve and clarify, add to the solid obtained by vacuum drying, and stir at room temperature for 2 days.

[0657] *: Add 0.5 mL of n-heptane to the gel and stir at room temperature for 1 day to form a gel. Then stir under temperature cycling (50℃~5℃, 0.1℃ / min, 2 cycles) and then lower to -20℃ and stir for 1 day to precipitate a solid.

[0658] #: Add 0.5 mL of n-heptane to the gel and stir at room temperature for 1 day to form a gel. Then stir under temperature cycling (50℃~5℃, 0.1℃ / min, 2 cycles) and then lower to -20℃ and stir for 1 day to obtain the gel product.

[0659] The phosphate crystal form A (prepared in MTBE), fumarate crystal form A (prepared in MTBE), malate crystal form A (prepared in MTBE), hydrobromide crystal form A, and hydrobromide crystal form B obtained in Example 9 were subjected to XRPD, TGA, DSC, and other methods. 1 Characterization was performed by ¹H NMR, PLM, or HPLC / IC. The results are shown in Tables 6-2 to 6-12 and Figures 42 to 51.

[0660] Table 6-2 Characterization results of salt in Example 9

[0661] The TGA and DSC results of phosphate crystal form A (Figure 43) show that the crystal form has a weight loss of 2.26% when heated to 120 °C, and has three endothermic peaks at 75.6 °C, 139.4 °C and 146.3 °C (peak temperature). 1¹H NMR results showed that MTBE was not present in phosphate crystal form A. HPLC / IC results showed that the molar ratio of phosphoric acid to compound IR in phosphate crystal form A was 0.9:1. PLM results showed that phosphate crystal form A consisted of crystal particles of varying sizes (particle size <20 μm).

[0662] The TGA and DSC results of fumarate crystal form A (Figure 45) show that the crystal form has a weight loss of 2.25% when heated to 140 °C and has an endothermic peak at 157.7 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of fumaric acid to compound IR in fumarate crystal form A was 0.8:1, and fumarate crystal form A did not contain MTBE. PLM results showed that fumarate crystal form A consisted of rod-shaped crystals of varying sizes (particle size <20 μm).

[0663] The TGA and DSC results of malate crystal form A (Figure 47) show that the crystal form has a weight loss of 0.40% when heated to 140 °C and has an endothermic peak at 147.9 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of malic acid to compound IR in malate crystal form A was 0.5:1, and malate crystal form A did not contain MTBE. PLM results showed that malate crystal form A consisted of rod-shaped crystals of varying sizes (particle size <20 μm).

[0664] The TGA and DSC results of hydrobromide crystal form A (Figure 49) show that the crystal form has a weight loss of 3.28% when heated to 130 °C, and has two endothermic peaks at 55.5 °C and 112.0 °C (peak temperature). 1 ¹H NMR results showed that hydrobromide crystal form A contained IPAc, and the molar ratio of IPAc to compound IR was 0.03:1 (0.6 wt%). HPLC / IC results showed that the molar ratio of hydrobromic acid to compound IR in hydrobromide crystal form A was 0.9:1. PLM results showed that hydrobromide crystal form A consisted of irregular blocky crystal particles of varying sizes.

[0665] The TGA and DSC results of hydrobromide crystal form B (Figure 51) show that the crystal form loses 4.82% of its weight when heated to 90°C and 1.07% of its weight when heated to 130°C, and has two endothermic peaks at 93.0°C and 145.9°C (peak temperatures). 1 ¹H NMR results showed that hydrobromide crystal form B contained MTBE, and the molar ratio of MTBE to compound IR was 0.01:1 (0.2 wt%). HPLC / IC results showed that the molar ratio of hydrobromic acid to compound IR in hydrobromide crystal form B was 1.0:1. PLM results showed that hydrobromide crystal form B consisted of crystal particles of varying sizes (particle size <20 μm).

[0666] Table 6-3 XRPD diffraction peak analysis data for phosphate crystal form A

[0667] Table 6-4 XRPD spectrum analysis data of phosphate crystal form A

[0668] Table 6-5 XRPD diffraction peak analysis data of fumarate crystal form A

[0669] Table 6-6 XRPD spectrum analysis data of fumarate crystal form A

[0670] Table 6-7 XRPD diffraction peak analysis data for malate crystal form A

[0671] Table 6-8 XRPD spectrum analysis data of malate crystal form A

[0672] Table 6-9 XRPD diffraction peak analysis data for hydrobromide crystal form A

[0673] Table 6-10 XRPD spectrum analysis data of hydrobromide crystal form A

[0674] Table 6-11 XRPD diffraction peak analysis data for hydrobromide crystal form B

[0675] Table 6-12 XRPD spectrum analysis data of hydrobromide crystal form B

[0676] Example 10

[0677] Following the methods described in Examples 6-8, the salt forms of compounds IR in the table below were prepared. The specific steps included: weighing 20 mg of compound IR and the corresponding base (molar ratio of base to compound IR 1:1) in 0.5 mL of the solvent corresponding to Table 7-1, and stirring at room temperature for approximately 2 days. The mixture was then centrifuged, and the precipitate was vacuum-dried at room temperature for 16 hours. The resulting solid was characterized by XRPD. Specific information and results are summarized in Table 7-1.

[0678] Table 7-1 Preparation of salts of compound IR In the table: X: Other crystal forms besides the corresponding salt, such as one, two, or more of the crystal forms of compound IR, the corresponding acid, or other crystal forms. a: The reaction solution becomes gelatinous after stirring at room temperature for 1 day. It is then placed under temperature cycling (50℃~5℃, 0.1℃ / min, 2 cycles) and stirred until it becomes gelatinous again. It is then cooled to -20℃ and stirred for 5 days until it becomes gelatinous again. Finally, it is transferred to room temperature and allowed to evaporate in an open container to obtain a gelatinous product. b: The reaction solution becomes oily after stirring at room temperature for 1 day. It is then placed under temperature cycling (50℃~5℃, 0.1℃ / min, 2 cycles) and stirred until it becomes oily again. It is then cooled to -20℃ and stirred for 5 days until it becomes gelatinous again. Finally, it is transferred to room temperature and allowed to evaporate in an open container to obtain a gelatinous product. c: A small amount of precipitate forms after stirring the reaction solution at room temperature for 1 day. It is then cooled to 5℃ and stirred for another day.

[0679] The following crystal forms obtained in Example 10 were subjected to XRPD, TGA, DSC, and other analytical methods: magnesium salt crystal form A, potassium salt crystal form A (prepared in MTBE), calcium salt crystal form A (prepared in acetone / n-heptane), meglumine salt crystal form A (prepared in MTBE), meglumine salt crystal form B (prepared in IPAc / n-heptane), lysine salt crystal form A (prepared in acetone / n-heptane), lysine salt crystal form B (prepared in MTBE), diethylamine salt crystal form A (prepared in acetone / n-heptane), and diethanolamine salt crystal form A (prepared in MTBE). 1 Characterization was performed by ¹H NMR, PLM, or HPLC / IC. The results are shown in Tables 7-2 to 7-20 and Figures 52 to 69.

[0680] Table 7-2 Characterization results of salt in Example 10

[0681] The TGA and DSC results of magnesium salt crystal form A (Figure 53) show that the crystal form has a weight loss of 2.85% when heated to 100℃ and a weight loss of 1.94% when heated to 150℃, and has three endothermic peaks at 92.5℃, 128.6℃ and 166.5℃ (peak temperature). 1 ¹H NMR results showed that magnesium salt crystal form A did not contain acetone or n-heptane. HPLC / IC results showed that the molar ratio of magnesium ions to compound IR in magnesium salt crystal form A was 0.6:1. PLM results showed that magnesium salt crystal form A consisted of rod-shaped crystal particles of varying sizes (particle size <20 μm).

[0682] The TGA and DSC results (Figure 55) of potassium salt crystal form A show that the crystal form has a weight loss of 10.48% when heated to 110 °C, and has two endothermic peaks at 67.6 °C and 119.1 °C (peak temperature), and one exothermic peak at 160.2 °C (peak temperature). 1¹H NMR results showed that potassium salt crystal form A contained MTBE, and the molar ratio of MTBE to compound I was 0.02:1 (0.4 wt%). HPLC / IC results showed that the molar ratio of potassium ions to compound I in potassium salt crystal form A was 0.8:1. PLM results showed that potassium salt crystal form A consisted of crystal particles of varying sizes (particle size <20 μm).

[0683] The TGA and DSC results of calcium salt crystal form A (Figure 57) show that the crystal form has a weight loss of 4.21% when heated to 100 °C, and has two endothermic peaks at 55.0 °C and 137.3 °C (peak temperature). 1 ¹H NMR results showed that calcium salt crystal form A did not contain acetone or n-heptane. HPLC / IC results showed that the molar ratio of calcium ions to the compound in calcium salt crystal form A was 1.2:1. PLM results showed that calcium salt crystal form A consisted of crystal particles of varying sizes.

[0684] The TGA and DSC results of meglumine salt crystal form A (Figure 59) show that the crystal form has a weight loss of 11.34% when heated to 120 °C, and has two endothermic peaks at 64.4 °C and 121.8 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of meglumine to compound IR in meglumine salt crystal form A was 1:1, and that meglumine salt crystal form A contained MTBE, with a molar ratio of MTBE to compound IR of 0.2:1 (3.4 wt%). PLM results showed that meglumine salt crystal form A consisted of crystal particles of varying sizes.

[0685] The TGA and DSC results of meglumine salt crystal form B (Figure 61) show that the crystal form has a weight loss of 5.44% when heated to 120 °C, and has three endothermic peaks at 49.2 °C, 68.1 °C and 95.0 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of meglumine to compound IR in meglumine salt crystal form B was 1:1, and this crystal form did not contain IPAc or n-heptane. PLM results showed that meglumine salt crystal form B consisted of crystal particles of varying sizes.

[0686] The TGA and DSC results of lysine salt crystal form A (Figure 63) show that the crystal form loses 8.00% weight when heated to 80℃ and 6.89% weight when heated to 150℃, and has three endothermic peaks at 77.5℃, 103.3℃ and 141.5℃ (peak temperature). 1 ¹H NMR results showed that the molar ratio of lysine to compound IR in lysine salt crystal form A was 1:1, and this crystal form did not contain acetone or n-heptane. PLM results showed that lysine salt crystal form A consisted of crystal particles of varying sizes.

[0687] The TGA and DSC results of lysine salt crystal form B (Figure 65) show that the crystal form has a weight loss of 7.17% when heated to 110 °C and has an endothermic peak at 131.0 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of lysine to compound IR in lysine salt crystal form B was 1:1. Lysine salt crystal form B contained MTBE, and the molar ratio of MTBE to compound IR was 0.07:1 (1.0 wt%). PLM results showed that lysine salt crystal form B consisted of irregular blocky crystal particles of varying sizes.

[0688] The TGA and DSC results of diethylamine salt crystal form A (Figure 67) show that the crystal form has an 8.01% weight loss when heated to 120 °C, and has two endothermic peaks at 119.7 °C and 152.0 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of diethylamine to compound IR in diethylamine salt crystal form A was 1:1, and diethylamine salt crystal form A did not contain acetone or n-heptane. PLM results showed that diethylamine salt crystal form A consisted of crystal particles of varying sizes.

[0689] The TGA and DSC results (Figure 69) of diethanolamine salt crystal form A show that the crystal form has a weight loss of 0.59% when heated to 110 °C and has an endothermic peak at 120.4 °C (peak temperature). 1 ¹H NMR results showed that the molar ratio of diethanolamine to compound IR in diethanolamine salt crystal form A was 1:1, and diethanolamine salt crystal form A did not contain MTBE. PLM results showed that diethanolamine salt crystal form A consisted of crystal particles of varying sizes.

[0690] Table 7-3 XRPD diffraction peak analysis data for magnesium salt crystal form A

[0691] Table 7-4 XRPD spectrum analysis data of magnesium salt crystal form A

[0692] Table 7-5 XRPD diffraction peak analysis data for potassium salt crystal form A

[0693] Table 7-6 XRPD spectrum analysis data of potassium salt crystal form A

[0694] Table 7-7 XRPD diffraction peak analysis data for calcium salt crystal form A

[0695] Table 7-8 XRPD spectrum analysis data of calcium salt crystal form A

[0696] Table 7-9 XRPD diffraction peak analysis data of meglumine salt crystal form A

[0697] Table 7-10 XRPD spectrum analysis data of meglumine salt crystal form A

[0698] Table 7-11 XRPD diffraction peak analysis data of meglumine salt crystal form B

[0699] Table 7-12 XRPD spectrum analysis data of meglumine salt crystal form B

[0700] Table 7-13 XRPD diffraction peak analysis data of lysine salt crystal form A

[0701] Table 7-14 XRPD spectrum analysis data of lysine salt crystal form A

[0702] Table 7-15 XRPD diffraction peak analysis data of lysine salt crystal form B

[0703] Table 7-16 XRPD spectrum analysis data of lysine salt crystal form B

[0704] Table 7-17 XRPD diffraction peak analysis data for diethylamine salt crystal form A

[0705] Table 7-18 XRPD spectrum analysis data of diethylamine salt crystal form A

[0706] Table 7-19 XRPD diffraction peak analysis data of diethanolamine salt crystal form A

[0707] Table 7-20 XRPD spectrum analysis data of diethanolamine salt crystal form A

[0708] Example 11 Preparation of 1,2-ethanedisulfonate

[0709] Compound IR (20 mg) was weighed and reacted with 1,2-ethanedisulfonic acid (molar ratio of 1:1 to compound IR) under the solvent (0.5 mL) and reaction conditions corresponding to those in Table 8-1. The mixture was centrifuged, and the precipitate was vacuum dried at 50 °C for 6 hours. The resulting solid was characterized by XRPD. Detailed information and results are summarized in Table 8-1.

[0710] Table 8-1 Preparation of 1,2-ethanedisulfonate In the table: the temperature cycle is "50℃~5℃, 0.1℃ / min".

[0711] This embodiment yielded a crystalline form of 1,2-ethanedisulfonate of compound IR, named 1,2-ethanedisulfonate crystalline form A. Crystalline form A (group 4) of 1,2-ethanedisulfonate was subjected to XRPD, TGA, DSC, and other assays. 1 The results of the 1H NMR characterization are shown in Figures 70-72 and Tables 8-2-8-4.

[0712] Table 8-2 Characterization results of 1,2-ethanedisulfonate crystal form A

[0713] The DSC results (Figure 71) show that 1,2-ethanedisulfonate crystal form A has three endothermic peaks at 60.8℃, 134.0℃, and 152.2℃ (peak temperature). The TGA results (Figure 71) show that 1,2-ethanedisulfonate crystal form A loses 8.15% of its weight when heated to 110℃. 1 The 1H NMR results (Figure 72) show that there is no solvent residue in 1,2-ethanedisulfonate crystal form A, and the molar ratio of 1,2-ethanedisulfonic acid to compound IR in 1,2-ethanedisulfonate crystal form A is 0.8:1.

[0714] Table 8-3 XRPD diffraction peak analysis data for 1,2-ethanedisulfonate crystal form A

[0715] Table 8-4 XRPD spectrum analysis data of 1,2-ethanedisulfonate crystal form A

[0716] Example 12 Performance Test

[0717] 1. Hygroscopicity test

[0718] The hygroscopicity of tartrate form A, succinate form A, sodium salt form C, and Tris salt form B was evaluated using a dynamic moisture adsorption (DVS) analyzer. Sodium salt form C was tested starting at 50% relative humidity (50% RH), while the other forms were tested starting at 0% relative humidity (0% RH). The percentage change in sample mass was collected under a constant temperature of 25°C as humidity varied (0% RH - 95% RH - 0% RH). The DVS evaluation results are summarized in Table 9-1.

[0719] Table 9-1 Results of Hygroscopicity Assessment

[0720] 2. Solid stability test

[0721] The solid stability of tartrate (form A), fumarate (form A), malate (form A), succinate (form A), sodium salt (form A), sodium salt (form C), diethanolamine salt (form A), Tris salt (form B), hydrochloride (form A), hydrochloride (form B), and 1,2-ethanedisulfonate (form A) was evaluated under the conditions specified in the table below. Their physical and chemical stability was tested by XRPD and HPLC, respectively. The results are summarized in Table 9-2.

[0722] Table 9-2 Results of Solid Stability Tests

[0723] 3. Dynamic solubility test

[0724] The dynamic solubility of tartrate form A, succinate form A, sodium salt form C, and Tris salt form B in pure water and three biosolvents was evaluated. The dynamic solubility of each crystal form in pure water, FaSSGF, FaSSIF, and FeSSIF was determined at 37°C using a rotary mixer (25 rpm) at a feed concentration of 5 mg / mL (calculated by compound IR) for 0.5, 2, 4, and 24 hours. Samples at each time point were centrifuged and filtered (using a 0.22 μm PTFE filter), and the HPLC concentration and pH of the filtrate were measured. The XRPD of the centrifuged solid samples was also tested. The solubility test results are summarized in Table 9-3.

[0725] Table 9-3 Results of Dynamic Solubility Test In the table: M: Crystal form of compound IR; *: The sample did not completely dissolve and clarify after being added to water. It dissolved and clarified after being mixed by rotation at 37°C for 30 min. The first spot (0.5 h) was taken, and then about 60 mg of sample was added. It dissolved and clarified, and no more sample was added.

[0726] Dynamic solubility results showed that sodium salt form C had the highest solubility in water, followed by Tris salt form B, while tartrate and succinate forms A had lower solubility. In FaSSGF, tartrate and succinate forms A had slightly higher solubility than sodium salt form C and Tris salt form B. In FaSSIF and FeSSIF, sodium salt form C and Tris salt form B had higher solubility than tartrate and succinate forms A. All salt forms converted to compounds during solubility tests, and the crystal forms of these compounds did not change in any of the systems.

[0727] 4. Mechanical stability test

[0728] The mechanical stability of succinate crystal form A and Tris salt crystal form B was evaluated by manual grinding. Approximately 20 mg of each crystal form was weighed into a mortar and manually ground for 3 minutes. The solid was then collected for XRPD testing. The results of the mechanical stability evaluation are summarized in Table 9-4.

[0729] Table 9-4 Mechanical Stability Assessment Results

[0730] The results showed that the crystal form of all salts did not change significantly after manual grinding.

[0731] Example 13 Biological Activity Test

[0732] 1. Evaluation of LPAR1 in vitro bioactivity

[0733] In this invention, the inhibitory properties of compounds, salts, and crystal forms of salts were determined using FLIPR (fluorescence imaging plate reader) in CHO-K1 cells (Chinese hamster ovary cells K1, ATCC) that highly expressed hLPAR1 (human lysophosphatidic acid receptor 1, accession number NM_001401.4).

[0734] CHO-K1 cells stably expressing hLPAR1 were placed in a cell culture incubator at 37°C and 5% CO2, and cultured in F-12 medium containing 10% FBS (fetal bovine serum, Gibco, 10099-141), 1% penicillin-streptomycin (Gibco, 15140-122), and 0.4 mg / mL Hygromycin B (Gibco, 10687010). 18–24 hours before the FLIPR assay, cells were seeded at a density of 250,000 cells / mL into 96-well plates and incubated overnight in a cell culture incubator. On the day of the experiment, the culture medium was discarded, and the cells were washed in FLIPR buffer (2.5 mM probenecid (Thermo, P36400), 1.3 mM CaCl2, 3.3 mM Na2CO3, 1 mM MgSO4, 20 mM HEPES (Invitrogen, 15630080), 1×HBSS (Invitrogen, 14065056), 0.1% BSA (BioSharp, 70080030)). 75 μL of 1 mM Fluo-4 AM fluorescent dye (Thermo, F14202) was added to each well, and the cells were incubated at 37°C for 1.0 h. Subsequently, the 96-well plate was washed once with buffer, and 50 μL of buffer containing the test sample or solvent was added to each well, and the cells were incubated at room temperature for 30 min. The cell plate was then placed in a FLIPR apparatus for baseline fluorescence measurement (excitation wavelength 485 nm, emission wavelength 525-535 nm). Subsequently, agonist (1 μM sodium oleoyl-L-α-lysophosphate (Sigma, L7260)) or solvent (ultrapure water) was added at 50 μL / well, and fluorescence values ​​were measured at 1-second intervals for 2 min. Finally, the output fluorescence counts were analyzed, and the IC50 was calculated using the log(inhibitor) vs. response-variable slope (four parameters) equation in GraphPad Prism 9.0 software. 50 value.

[0735] In vitro bioactivity evaluation results showed that compound IR exhibited excellent LPAR1 inhibitory activity, with an IC50 value for LPAR1 inhibition. 50 <25nM.

[0736] 2. Pharmacokinetic Study in Rats

[0737] Male SPF-grade SD rats (Beijing Vital River Laboratory Animal Technology Co., Ltd.), weighing 200-250g, were administered 1mg / kg (based on the compound) of the present invention or its salt or crystalline form of the salt via oral gavage (Po, fasting overnight but allowing free water, and food returned 4 hours after administration) and via tail vein bolus injection (Iv, fasting and allowing free water throughout the administration). The solvent for the Po group was 5% DMSO + 5% ethanol + 60% PEG400 + 30% physiological saline; the solvent for the Iv group was 10% ethanol + 20% purified water + 70% PEG400 solution. Blood was collected from the orbital venous plexus / jugular vein of rats at specific time points after drug administration (0.167, 0.5, 1, 2, 4, 6, 8, and 24 h for the Po group; and 0.033, 0.167, 1, 2, 4, 6, 8, and 24 h for the IV group). The concentration of compounds in plasma was detected by LC-MS / MS (AB SCIEX Qtrap4500). Data were analyzed using a non-compartmental model with WinNonlin (version 5.2.1 Pharsight, Mountain View, CA) to obtain pharmacokinetic parameters (including Cp). max C0, T max AUC last AUC inf T 1 / 2 (e.g., parameters).

[0738] Pharmacokinetic studies in rats showed that the compound of this invention, or its salt or crystal form, exhibited good pharmacokinetic properties in rats, achieving high in vivo exposure levels (5000 ng / mL*hr ≤ AUC) at relatively low doses. last <10000 ng / mL*hr) and high oral bioavailability (>120%), and long half-life (6h < T). 1 / 2 <12h).

[0739] 3. Pharmacokinetics in monkeys

[0740] Crab-eating macaques (Suzhou Xishan Zhongke Experimental Animal Co., Ltd.), aged 3-5 years and weighing 3-5 kg, were administered the compound of the present invention or its salt or a clear solution of its crystalline form via oral gavage (Po, fasting before administration but water allowed) and intravenous bolus injection (Iv, fasting and water allowed throughout the administration) after acclimatization. The solvent for the Po group was 5% DMSO + 5% ethanol + 60% PEG400 + 30% physiological saline, and the solvent for the IV group was 10% ethanol + 20% ultrapure water + 70% PEG400 solution. At specific time points after drug administration (0.167, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 32, and 48 h for the Po group; and 0.083, 0.25, 1, 2, 3, 4, 6, 9, 12, 24, 32, and 48 h for the IV group), approximately 1 mL of whole blood was collected from the peripheral blood vessels of the non-drug-treated limb of each cynomolgus monkey. The concentration of compounds in plasma was detected by LC-MS / MS (AB SCIEX Qtrap4500). Data were analyzed using a non-compartmental model with WinNonlin (version 5.2.1 Pharsight, Mountain View, CA) to obtain the pharmacokinetic parameters (including Cp) of the cynomolgus monkeys. max C0, T max AUC last AUC inf T 1 / 2 (e.g., parameters).

[0741] The pharmacokinetic studies in cynomolgus monkeys showed that the compound of the present invention or its salt or crystal form has superior pharmacokinetic properties in cynomolgus monkeys, achieving higher in vivo exposure at lower doses, higher bioavailability, longer half-life, higher clearance rate, and larger volume of distribution.

[0742] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the concept and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A salt of compound I or its stereoisomer, characterized in that, The salt is a salt formed by compound I or its stereoisomer with any of the following acids or bases: succinic acid, sodium hydroxide, hydrochloric acid, tartaric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid, lysine, 1,2-ethanedisulfonic acid, tris(hydroxymethyl)aminomethane, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, diethylamine, or diethanolamine.

2. The salt according to claim 1, characterized in that: It is selected from one or more of the following conditions: (1) The stereoisomer of compound I is compound IR: (2) In the salt, the molar ratio of acid or base to compound I or its stereoisomer is (0.3-2):1, preferably (0.5-1.3):1, for example 0.5:1, 0.6:1, 0.8:1, 0.9:1, 1:1, 1.1:1, 1.2:1 or 1.3:1; (3) The salt is a succinate, sodium salt, hydrochloride, tartrate, phosphate, fumarate, malate, hydrobromide, p-toluenesulfonate, benzenesulfonate, lysine salt, 1,2-ethanedisulfonate, tris(hydroxymethyl)aminomethane (Tris) salt, magnesium salt, potassium salt, calcium salt, choline salt, meglumine salt, diethylamine salt, or diethanolamine salt; (4) The salt is amorphous or crystalline; Preferably, the p-toluenesulfonate, benzenesulfonate, and choline salt are amorphous; Preferably, the crystal form is the succinate crystal form, sodium salt crystal form, hydrochloride crystal form, tartrate crystal form, phosphate crystal form, fumarate crystal form, malate crystal form, hydrobromide crystal form, lysine crystal form, 1,2-ethanedisulfonate crystal form, Tris salt crystal form, magnesium salt crystal form, potassium salt crystal form, calcium salt crystal form, meglumine salt crystal form, diethylamine salt crystal form, or diethanolamine salt crystal form of the compound I or its stereoisomers; Preferably, the crystal form may or may not contain a solvent, wherein the solvent is selected from organic solvents or water; Preferably, the organic solvent is selected from one, two or more of the following: isopropanol (IPA), isopropyl acetate (IPAc), methyl tert-butyl ether (MTBE), n-heptane, acetone, methanol, ethanol, 2-butanone, ethyl acetate, methyl acetate, 4-methyl-2-pentanone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, chloroform, n-hexane, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone. Preferably, the molar ratio of the organic solvent to compound I or its stereoisomer is (0.005-1):1, more preferably (0.01-0.2):1; for example, 0.2:1, 0.07:1, 0.03:1, 0.02:1 or 0.01:1; Preferably, the water is crystallized water or non-crystalline water.

3. The salt according to claim 2, characterized in that: It is selected from one or more of the following conditions: (1) The succinate crystal form is succinate crystal form A of compound IR; the succinate crystal form A has characteristic peaks at 7.2±0.2°, 11.3±0.2°, 14.8±0.2° and 20.2±0.2° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle; (2) The Tris salt crystal form of the compound IR is Tris salt crystal form A, Tris salt crystal form B or Tris salt crystal form C; The Tris salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 17.2±0.2°, and 19.8±0.2° in 2θ angles. The Tris salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 14.5±0.2°, 20.1±0.2°, 20.7±0.2°, and 21.8±0.2° when expressed in 2θ angles. The Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 10.3±0.2°, 13.7±0.2°, and 17.2±0.2° when expressed in 2θ angles. (3) The tartrate crystal form is tartrate crystal form A of compound IR; The tartrate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 14.7±0.2°, 15.0±0.2°, and 20.8±0.2° in 2θ angles. (4) The sodium salt crystal form is sodium salt crystal form A, sodium salt crystal form B or sodium salt crystal form C of compound IR; The sodium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 13.1±0.2°, 13.3±0.2°, 21.1±0.2°, and 23.2±0.2° in 2θ angles. The sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, and 15.5±0.2° when expressed in 2θ angles. The sodium salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 13.1±0.2°, 13.3±0.2°, 17.4±0.2°, 17.9±0.2°, 21.1±0.2°, and 23.2±0.2°, expressed in 2θ angles. (5) The hydrochloride crystal form is either hydrochloride crystal form A or hydrochloride crystal form B of compound IR; The hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, and 12.9±0.2° in 2θ angles. The hydrochloride crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 10.0±0.2°, 11.0±0.2°, 11.8±0.2°, and 13.8±0.2° in 2θ angles. (6) The phosphate crystal form is phosphate crystal form A of compound IR; The phosphate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.1±0.2°, 14.5±0.2°, 14.8±0.2°, and 16.7±0.2° in 2θ angles. (7) The fumarate crystal form is fumarate crystal form A of compound IR; The fumarate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 11.3±0.2°, 14.7±0.2°, and 14.9±0.2° in 2θ angles. (8) The malate crystal form is malate crystal form A of compound IR; The malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks at 6.8±0.2°, 14.3±0.2°, and 15.2±0.2° in X-ray powder diffraction at 2θ angles. (9) The hydrobromide crystal form is either hydrobromide crystal form A or hydrobromide crystal form B of compound IR; The hydrobromide crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 10.0±0.2°, 15.0±0.2°, and 26.1±0.2° in 2θ angles. The hydrobromide crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.6±0.2°, 8.8±0.2°, 19.9±0.2°, 20.7±0.2°, and 26.1±0.2° in 2θ angles. (10) The crystal form of the 1,2-ethanedisulfonate is the crystal form A of the 1,2-ethanedisulfonate of compound IR; The 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.4±0.2°, 8.2±0.2°, 11.0±0.2°, and 11.2±0.2° when expressed in 2θ angles. (11) The magnesium salt crystal form is magnesium salt crystal form A of compound IR; The magnesium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.4±0.2°, 8.7±0.2°, 9.8±0.2°, 11.5±0.2°, 13.1±0.2°, and 18.6±0.2° in 2θ angles. (12) The potassium salt crystal form is potassium salt crystal form A of compound IR; The potassium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 8.2±0.2°, and 9.5±0.2° when expressed in 2θ angles. (13) The calcium salt crystal form is calcium salt crystal form A of compound IR; The calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, and 12.0±0.2°, expressed in 2θ angles. (14) The crystal form of the meglumine salt is either crystal form A or crystal form B of the meglumine salt of compound IR; The meglumine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks at 9.8±0.2°, 13.2±0.2°, and 17.2±0.2° in X-ray powder diffraction at 2θ angles. The meglumine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.6±0.2°, 6.1±0.2°, 9.7±0.2°, and 13.8±0.2° in 2θ angles. (15) The lysine salt crystal forms are lysine salt crystal form A and lysine salt crystal form B of compound IR; The lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, and 14.0±0.2° in 2θ angles. The lysine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks at 10.3±0.2° and 19.9±0.2° in X-ray powder diffraction at 2θ angles. (16) The diethylamine salt crystal form is the diethylamine salt crystal form A of compound IR; The diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 13.3±0.2°, 15.4±0.2°, 16.2±0.2°, 18.1±0.2°, and 21.7±0.2° in 2θ angles. (17) The diethanolamine salt crystal form is the diethanolamine salt crystal form A of compound IR; The diethanolamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 10.5±0.2°, 13.1±0.2°, 16.9±0.2°, 19.7±0.2°, and 22.2±0.2° when expressed in 2θ angles.

4. The salt according to claim 3, characterized in that: It is selected from one or more of the following conditions: (1) In the succinate crystal form A, the molar ratio of succinic acid to compound IR is (0.4-0.7):1; (2) The succinate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 14.8±0.2°, 17.0±0.2°, 18.6±0.2°, 19.6±0.2°, 20.2±0.2°, 20.8±0.2°, 22.7±0.2°, 23.8±0.2°, and 30.6±0.2° in terms of 2θ angles. (3) The differential scanning calorimetry curve of the succinate crystal form A has an endothermic peak at a peak temperature of about 150.0℃±5℃; (4) The thermogravimetric analysis curve of the succinate crystal form A shows a weight loss of 0.98% ± 0.4% in the temperature range of 29.2℃ ± 3℃ to 140.0℃ ± 3℃; (5) In the Tris salt crystal form A, the molar ratio of Tris to compound IR is (0.9-1.2):1; (6) The Tris salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 11.1±0.2°, 11.7±0.2°, 12.4±0.2°, 13.2±0.2°, 14.0±0.2°, 17.2±0.2°, 18.8±0.2°, and 19.8±0.2° in 2θ angles. (7) The differential scanning calorimetry curve of the Tris salt crystal form A has an endothermic peak at a peak temperature of about 121.6℃±3℃; (8) The thermogravimetric analysis curve of the Tris salt crystal form A shows a weight loss of 1.27% ± 0.5% in the temperature range of 28.4℃ ± 3℃ to 130.0℃ ± 3℃; (9) In the Tris salt crystal form B, the molar ratio of Tris to compound IR is (0.9-1.2):1; (10) The Tris salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.3±0.2°, 9.8±0.2°, 10.9±0.2°, 14.5±0.2°, 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, and 21.8±0.2° in 2θ angles. (11) The differential scanning calorimetry curve of the Tris salt crystal form B has an endothermic peak at a peak temperature of approximately 94.2℃±5℃ and / or 118.7℃±3℃. (12) The thermogravimetric analysis curve of the Tris salt crystal form B shows a weight loss of 5.73% ± 4.5% in the temperature range of 29.0℃ ± 3℃ to 120.0℃ ± 10℃; (13) In the Tris salt crystal form C, the molar ratio of Tris to compound IR is (0.9-1.2):1; (14) The Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 6.9±0.2°, 10.3±0.2°, 13.7±0.2°, 17.2±0.2° and 20.2±0.2° in 2θ angles. (15) The differential scanning calorimetry curve of the Tris salt crystal form C has endothermic peaks at peak temperatures of approximately 58.9±3℃, 89.3±3℃ and 103.8±3℃; (16) The thermogravimetric analysis curve of the Tris salt crystal form C shows a weight loss of 5.83% ± 1.0% in the temperature range of 29.0℃ ± 3℃ to 130.0℃ ± 3℃; (17) In the tartrate crystal form A, the molar ratio of tartaric acid to compound IR is (1.0-1.5):1; (18) The tartrate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 7.3±0.2°, 8.3±0.2°, 11.3±0.2°, 14.7±0.2°, 15.0±0.2°, 17.2±0.2°, 19.7±0.2°, 20.2±0.2°, 20.8±0.2°, and 29.8±0.2° in terms of 2θ angles. (19) The differential scanning calorimetry curve of the tartrate crystal form A has an endothermic peak at a peak temperature of approximately 152.5 ± 3 °C; (20) The thermogravimetric analysis curve of the tartrate crystal form A shows a weight loss of 1.28% ± 1.0% in the temperature range of 28.6℃ ± 5℃ to 140.0℃ ± 10℃; (21) In the sodium salt crystal form A, the molar ratio of sodium ions to compound IR is (0.7-1.2):1; (22) The sodium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, 14.9±0.2°, 21.1±0.2°, and 23.2±0.2° in 2θ angles. (23) The differential scanning calorimetry curve of the sodium salt crystal form A has an endothermic peak at a peak temperature of approximately 143.8 ± 3 °C; (24) The thermogravimetric analysis curve of the sodium salt crystal form A shows a weight loss of 2.95% ± 1.0% in the temperature range of 28.6℃ ± 3℃ to 130.0℃ ± 3℃; (25) In the sodium salt crystal form B, the molar ratio of sodium ions to compound IR is (0.4-0.8):1; (26) The sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, 15.5±0.2°, 18.9±0.2°, 19.8±0.2°, 20.4±0.2°, 21.2±0.2°, 24.5±0.2°, and 25.0±0.2° in 2θ angles. (27) The differential scanning calorimetry curve of the sodium salt crystal form B has an endothermic peak at a peak temperature of about 142.6±3℃; (28) The differential scanning calorimetry curve of the sodium salt crystal form B has an exothermic peak at a peak temperature of about 178.1±3℃; (29) The thermogravimetric analysis curve of the sodium salt crystal form B shows a weight loss of 2.39% ± 1.0% in the temperature range of 25.9℃ ± 3℃ to 120.0℃ ± 3℃; (30) In the sodium salt crystal form C, the molar ratio of sodium ions to compound IR is (0.9-1.2):1; (31) The sodium salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 11.2±0.2°, 11.9±0.2°, 13.1±0.2°, 13.3±0.2°, 14.0±0.2°, 17.4±0.2°, 17.9±0.2°, 18.4±0.2°, 19.6±0.2°, 20.6±0.2°, 21.1±0.2°, 22.7±0.2°, 23.2±0.2°, 25.0±0.2°, and 27.9±0.2° in terms of angle 2θ. (32) The differential scanning calorimetry curve of the sodium salt crystal form C has endothermic peaks at peak temperatures of approximately 137.7±3℃ and 243.7±3℃; (33) The thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 3.61% ± 1.0% in the temperature range of 26.4℃ ± 3℃ to 130.0℃ ± 3℃; (34) The thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 5.59% ± 1.0% in the temperature range of 130.0℃ ± 3℃ to 210.0℃ ± 3℃; (35) The sodium salt crystal form C contains an organic solvent; (36) The sodium salt crystal form C is a solvate; (37) In the hydrochloride crystal form A, the molar ratio of hydrochloric acid to compound IR is (0.9-1.2):1; (38) The hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, 11.5±0.2°, 11.9±0.2°, 12.9±0.2°, 15.5±0.2°, 20.7±0.2°, 23.1±0.2°, 24.4±0.2°, and 28.0±0.2° in 2θ angles. (39) The differential scanning calorimetry curve of the hydrochloride crystal form A has an endothermic peak at a peak temperature of about 109.3±3℃; (40) The thermogravimetric analysis curve of the hydrochloride crystal form A shows a weight loss of 7.02% ± 1.0% in the temperature range of 29.0℃ ± 3℃ to 120.0℃ ± 3℃; (41) In the hydrochloride crystal form B, the molar ratio of hydrochloric acid to compound IR is (0.9-1.2):1; (42) The hydrochloride crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.8±0.2°, 10.0±0.2°, 11.0±0.2°, 11.8±0.2°, 13.8±0.2°, 14.5±0.2°, 15.4±0.2°, 15.7±0.2°, 20.9±0.2°, and 25.1±0.2° in 2θ angles. (43) The differential scanning calorimetry curve of the hydrochloride crystal form B has an endothermic peak at a peak temperature of about 110.1±3℃; (44) The thermogravimetric analysis curve of the hydrochloride crystal form B shows a weight loss of 7.27% ± 2.0% in the temperature range of 25.5℃ ± 3℃ to 110.0℃ ± 3℃; (45) In the phosphate crystal form A, the molar ratio of phosphoric acid to compound IR is (0.7-1.1):1; (46) The phosphate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.2±0.2°, 7.1±0.2°, 14.5±0.2°, 14.8±0.2°, 16.7±0.2°, 19.2±0.2°, 22.3±0.2°, 24.8±0.2°, 29.2±0.2°, and 30.2±0.2° in 2θ angles. (47) The differential scanning calorimetry curve of the phosphate crystal form A has endothermic peaks at peak temperatures of approximately 75.6±3℃, 139.4±3℃ and 146.3±3℃; (48) The thermogravimetric analysis curve of the phosphate crystal form A shows a weight loss of 2.26% ± 1.0% in the temperature range of 23.8℃ ± 3℃ to 120.0℃ ± 3℃; (49) In the fumarate crystal form A, the molar ratio of fumaric acid to compound IR is (0.6-1.0):1; (50) Fumarate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 14.7±0.2°, 14.9±0.2°, 18.7±0.2°, 19.6±0.2°, 20.1±0.2°, 22.8±0.2°, and 28.8±0.2° in 2θ angles. (51) The differential scanning calorimetry curve of the fumarate crystal form A has an endothermic peak at a peak temperature of about 157.7±3℃; (52) The thermogravimetric analysis curve of the fumarate crystal form A shows a weight loss of 2.25% ± 1.0% in the temperature range of 28.9℃ ± 3℃ to 140.0℃ ± 3℃; (53) In the malate crystal form A, the molar ratio of malic acid to compound IR is (0.3-0.7):1; (54) The malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.8±0.2°, 11.4±0.2°, 14.3±0.2°, 15.2±0.2°, 16.5±0.2°, 19.4±0.2° and 24.4±0.2° in 2θ angles. (55) The differential scanning calorimetry curve of the malate crystal form A has an endothermic peak at a peak temperature of about 147.9±3℃; (56) The thermogravimetric analysis curve of the malate crystal form A shows a weight loss of 0.40% ± 0.1% in the temperature range of 29.0℃ ± 3℃ to 140.0℃ ± 3℃; (57) In the hydrobromide crystal form A, the molar ratio of hydrobromic acid to compound IR is (0.7-1.1):1; (58) The hydrobromide crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.0±0.2°, 7.7±0.2°, 10.0±0.2°, 10.9±0.2°, 11.7±0.2°, 15.0±0.2°, 18.4±0.2°, 20.0±0.2°, 20.4±0.2°, 21.9±0.2°, 22.6±0.2°, 25.0±0.2°, 26.1±0.2°±0.2°, 29.7±0.2°, and 31.2±0.2° in terms of angle 2θ. (59) The differential scanning calorimetry curve of the hydrobromide crystal form A has endothermic peaks at peak temperatures of approximately 55.5±3℃ and 112.0±3℃. (60) The thermogravimetric analysis curve of the hydrobromide crystal form A shows a weight loss of 3.28% ± 1.0% in the temperature range of 29.2℃ ± 3℃ to 130.0℃ ± 3℃; (61) The hydrobromide crystal form A contains an organic solvent; (62) The hydrobromide crystal form A is a solvate; (63) In the hydrobromide crystal form B, the molar ratio of hydrobromic acid to compound IR is (0.8-1.2):1; (64) The hydrobromide crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.6±0.2°, 8.8±0.2°, 12.5±0.2°, 12.6±0.2°, 13.9±0.2°, 14.3±0.2°, 15.2±0.2°, 15.4±0.2°, 19.2±0.2°, 19.6±0.2°, 19.9±0.2°, 20.7±0.2°, 21.1±0.2°, 23.3±0.2°, and 26.1±0.2° in terms of angle 2θ. (65) The differential scanning calorimetry curve of the hydrobromide crystal form B has endothermic peaks at peak temperatures of approximately 93.0±3℃ and 145.9±3℃. (66) The thermogravimetric analysis curve of the hydrobromide crystal form B shows a weight loss of 4.82% ± 1.0% in the temperature range of 29.2℃ ± 3℃ to 90.0℃ ± 3℃; (67) The thermogravimetric analysis curve of the hydrobromide crystal form B shows a weight loss of 1.07% ± 0.5% in the temperature range of 90.0℃ ± 3℃ to 130.0℃ ± 3℃; (68) The hydrobromide crystal form B contains an organic solvent; (69) The hydrobromide crystal form B is a solvate; (70) In the 1,2-ethanedisulfonate crystal form A, the molar ratio of 1,2-ethanedisulfonic acid to compound IR is (0.6-1.0):1; (71) The 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.9±0.2°, 6.4±0.2°, 7.8±0.2°, 8.2±0.2°, 11.0±0.2°, 11.2±0.2°, 12.9±0.2°, 16.0±0.2°, 17.1±0.2°, 17.7±0.2°, 21.5±0.2°, 23.0±0.2°, and 24.2±0.2° in terms of angle 2θ. (72) The differential scanning calorimetry curve of the 1,2-ethanedisulfonate crystal form A has endothermic peaks at peak temperatures of approximately 60.8±3℃, 134.0±3℃ and 152.2±3℃; (73) The thermogravimetric analysis curve of the 1,2-ethanedisulfonate crystal form A shows a weight loss of 8.15% ± 2.0% in the temperature range of 23.8℃ ± 3℃ to 110.0℃ ± 3℃; (74) In the magnesium salt crystal form A, the molar ratio of magnesium ions to compound IR is (0.4-0.8):1; (75) The magnesium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, 15.0±0.2°, 17.2±0.2°, 17.4±0.2°, 18.2±0.2°, 18.6±0.2°, and 19.5±0.2° in 2θ angles. (76) The differential scanning calorimetry curve of the magnesium salt crystal form A has endothermic peaks at peak temperatures of approximately 92.5±3℃, 128.6±3℃ and 166.5±3℃; (77) The thermogravimetric analysis curve of the magnesium salt crystal form A shows a weight loss of 2.85% ± 1.0% in the temperature range of 28.4℃ ± 3℃ to 100.0℃ ± 3℃; (78) The thermogravimetric analysis curve of the magnesium salt crystal form A shows a weight loss of 1.94% ± 0.5% in the temperature range of 100.0℃ ± 3℃ to 150.0℃ ± 3℃; (79) In the potassium salt crystal form A, the molar ratio of potassium ions to compound IR is (0.6-1.0):1; (80) The potassium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 4.4±0.2°, 8.2±0.2°, 9.5±0.2°, 11.5±0.2°, 12.7±0.2°, 14.6±0.2°, 17.9±0.2°, and 25.2±0.2° in 2θ angles. (81) The differential scanning calorimetry curve of the potassium salt crystal form A has endothermic peaks at peak temperatures of approximately 67.6±3℃ and 119.1±3℃; (82) The differential scanning calorimetry curve of the potassium salt crystal form A has an exothermic peak at a peak temperature of about 160.2±3℃; (83) The thermogravimetric analysis curve of the potassium salt crystal form A shows a weight loss of 10.48% ± 1.0% in the temperature range of 21.2℃ ± 3℃ to 110.0℃ ± 3℃; (84) The potassium salt crystal form A contains an organic solvent; (85) The potassium salt crystal form A is a solvate; (86) In the calcium salt crystal form A, the molar ratio of calcium ions to compound IR is (1.0-1.4):1; (87) The calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, 12.0±0.2°, 14.8±0.2°, 15.9±0.2° and 18.1±0.2° in 2θ angles. (88) The differential scanning calorimetry curve of the calcium salt crystal form A has endothermic peaks at peak temperatures of approximately 55.0±3℃ and 137.3±3℃; (89) The thermogravimetric analysis curve of the calcium salt crystal form A shows a weight loss of 4.21% ± 1.0% in the temperature range of 28.5℃ ± 3℃ to 100.0℃ ± 3℃; (90) In the meglumine salt crystal form A, the molar ratio of meglumine to compound IR is (0.8-1.2):1; (91) The methylglucamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.1±0.2°, 9.8±0.2°, 13.2±0.2°, 17.2±0.2° and 20.8±0.2° in 2θ angles. (92) The differential scanning calorimetry curve of the meglumine salt crystal form A has endothermic peaks at peak temperatures of approximately 64.4±3℃ and 121.8±3℃; (93) The thermogravimetric analysis curve of the meglumine salt crystal form A shows a weight loss of 11.34% ± 1.0% in the temperature range of 23.4℃ ± 3℃ to 120.0℃ ± 3℃; (94) The meglumine salt crystal form A contains an organic solvent; (95) The meglumine salt crystal form A is a solvate; (96) In the meglumine salt crystal form B, the molar ratio of meglumine to compound IR is (0.8-1.2):1; (97) The methylglucamine salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.6±0.2°, 6.1±0.2°, 9.7±0.2°, 11.9±0.2°, 13.8±0.2°, 14.5±0.2°, 18.2±0.2° and 21.0±0.2° in 2θ angles. (98) The differential scanning calorimetry (DSC) curve of the meglumine salt crystal form B has endothermic peaks at peak temperatures of approximately 49.2±3℃, 68.1±3℃ and 95.0±3℃. (99) The thermogravimetric analysis curve of the meglumine salt crystal form B shows a weight loss of 5.44% ± 1.0% in the temperature range of 28.5℃ ± 3℃ to 120.0℃ ± 3℃; (100) In the lysine salt crystal form A, the molar ratio of lysine to compound IR is (0.8-1.2):1; (101) The lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, 14.0±0.2°, 15.0±0.2°, 17.6±0.2°, 19.8±0.2° and 22.1±0.2° in 2θ angles. (102) The differential scanning calorimetry curve of the lysine salt crystal form A has endothermic peaks at peak temperatures of approximately 77.5±3℃, 103.3±3℃ and 141.5±3℃; (103) The thermogravimetric analysis curve of the lysine salt crystal form A shows a weight loss of 8.00% ± 1.0% in the temperature range of 28.4℃ ± 3℃ to 80.0℃ ± 3℃; (104) The thermogravimetric analysis curve of the lysine salt crystal form A shows a weight loss of 6.89% ± 1.0% in the temperature range of 80.0℃ ± 3℃ to 150.0℃ ± 3℃; (105) In the lysine salt crystal form B, the molar ratio of lysine to compound IR is (0.8-1.2):1; (106) The lysine salt crystal form B has diffraction peaks as shown in Table 7-15 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (107) The differential scanning calorimetry curve of the lysine salt crystal form B has an endothermic peak at a peak temperature of about 131.0±3℃; (108) The thermogravimetric analysis curve of the lysine salt crystal form B shows a weight loss of 7.17% ± 1.0% in the temperature range of 23.9℃ ± 3℃ to 110.0℃ ± 3℃; (109) The lysine salt crystal form B contains an organic solvent; (110) The lysine salt crystal form B is a solvate; (111) In the diethylamine salt crystal form A, the molar ratio of diethylamine to compound IR is (0.8-1.2):1; (112) The diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 5.9±0.2°, 9.8±0.2°, 11.0±0.2°, 11.7±0.2°, 12.5±0.2°, 13.3±0.2°, 15.1±0.2°, 15.4±0.2°, 16.2±0.2°, 18.1±0.2°, 21.7±0.2°, 22.8±0.2°, and 23.6±0.2° in 2θ angles. (113) The differential scanning calorimetry curve of the diethylamine salt crystal form A has endothermic peaks at peak temperatures of approximately 119.7±3℃ and 152.0±3℃; (114) The thermogravimetric analysis curve of the diethylamine salt crystal form A shows a weight loss of 8.01% ± 1.0% in the temperature range of 24.9℃ ± 3℃ to 120.0℃ ± 3℃; (115) In the diethanolamine salt crystal form A, the molar ratio of diethanolamine to compound IR is (0.8-1.2):1; (116) The diethanolamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 8.9±0.2°, 10.5±0.2°, 13.1±0.2°, 16.9±0.2°, 17.8±0.2°, 19.0±0.2°, 19.7±0.2°, 22.2±0.2°, 23.6±0.2°, 24.5±0.2°, and 24.9±0.2° in 2θ angles. (117) The differential scanning calorimetry curve of the diethanolamine salt crystal form A has an endothermic peak at a peak temperature of about 120.4±3℃; (118) The thermogravimetric analysis curve of the diethanolamine salt crystal form A shows a weight loss of 0.59% ± 0.1% in the temperature range of 25.6℃ ± 3℃ to 110.0℃ ± 3℃.

5. The salt according to claim 3, characterized in that: It is selected from one or more of the following conditions: (1) In the succinate crystal form A, the molar ratio of succinic acid to compound IR is (0.5-0.6):1; (2) The succinate crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 4.2±0.2°, 7.2±0.2°, 8.4±0.2°, 11.3±0.2°, 12.6±0.2°, 14.8±0.2°, 17.0±0.2°, 18.0±0.2°, 18.6±0.2°, and 19.6± Characteristic peaks are present at 0.2°, 20.2±0.2°, 20.8±0.2°, 22.2±0.2°, 22.7±0.2°, 23.8±0.2°, 24.5±0.2°, 25.2±0.2°, 26.2±0.2°, 26.8±0.2°, 27.4±0.2°, 29.5±0.2°, and 30.6±0.2°. (3) The differential scanning calorimetry curve of the succinate crystal form A has an endothermic peak at a peak temperature of about 151.5℃±3℃; (4) The thermogravimetric analysis curve of the succinate crystal form A shows a weight loss of 0.98% in the temperature range of 29.2℃ to 140.0℃; (5) The succinate crystal form A contains no organic solvent or contains an organic solvent; (6) In the Tris salt crystal form A, the molar ratio of Tris to compound IR is 1:1; (7) The Tris salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.2±0.2°, 7.4±0.2°, 11.1±0.2°, 11.7±0.2°, 12.4±0.2°, 13.2±0.2°, 14.0±0.2°, 15.1±0.2°, 17.2±0.2°, 18.8±0.2°, 19.8±0.2°, 20.2±0.2°, 21.4±0.2°, 22.0±0.2°, 23.6±0.2°, 24.9±0.2°, 26.1±0.2°, 27.5±0.2°, 28.6±0.2°, and 29.0±0.2° in terms of angle 2θ. (8) In the Tris salt crystal form B, the molar ratio of Tris to compound IR is 1:1; (9) The Tris salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 7.3±0.2°, 9.2±0.2°, 9.8±0.2°, 10.9±0.2°, 11.9±0.2°, 14.5±0.2°, 17.5±0.2°, 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, 21.8±0.2°, 26.9±0.2°, and 27.9±0.2° in terms of angle 2θ. (10) In the Tris salt crystal form C, the molar ratio of Tris to compound IR is 1:1; (11) The Tris salt crystal form C, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.5±0.2°, 5.4±0.2°, 6.9±0.2°, 10.3±0.2°, 13.7±0.2°, 17.2±0.2°, 20.2±0.2° and 24.0±0.2° in 2θ angles. (12) In the tartrate crystal form A, the molar ratio of tartaric acid to compound IR is 1.3:1; (13) The tartrate crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 4.1±0.2°, 7.3±0.2°, 8.3±0.2°, 11.3±0.2°, 14.7±0.2°, 15.0±0.2°, 17.2±0.2°, 17.9±0.2°, 18.6±0.2°, 19.7±0.2°, and 20.2°. Characteristic peaks are observed at ±0.2°, 20.8±0.2°, 22.4±0.2°, 23.1±0.2°, 24.2±0.2°, 25.1±0.2°, 26.2±0.2°, 29.2±0.2°, 29.8±0.2°, 32.1±0.2°, 33.4±0.2°, 35.9±0.2°, 36.8±0.2°, and 37.5±0.2°. (14) In the sodium salt crystal form A, the molar ratio of sodium ions to compound IR is 0.9:1; (15) The sodium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 11.2±0.2°, 11.8±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, 14.9±0.2°, 15.6±0.2°, 17.8±0.2°, 18.6±0.2°, 19.5±0.2°, 21.1±0.2°, 23.2±0.2°, and 25.1±0.2° in terms of angle 2θ. (16) In the sodium salt crystal form B, the molar ratio of sodium ions to compound IR is 0.6:1; (17) The sodium salt crystal form B, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.2±0.2°, 8.9±0.2°, 10.1±0.2°, 11.7±0.2°, 13.5±0.2°, 14.8±0.2°, 15.5±0.2°, 17.9±0.2°, 18.9±0.2°, 19.8±0.2°, 20.4±0.2°, 21.2±0.2°, 22.1±0.2°, 23.9±0.2°, 24.5±0.2°, 25.0±0.2°, and 26.4±0.2° in terms of angle 2θ. (18) In the sodium salt crystal form C, the molar ratio of sodium ions to compound IR is 1:1; (19) The sodium salt crystal form C was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 6.2±0.2°, 10.2±0.2°, 10.8±0.2°, 11.2±0.2°, 11.9±0.2°, 12.4±0.2°, 13.1±0.2°, 13.3±0.2°, 14.0±0.2°, 17.4±0.2°, 17.9±0.2°, and 18.4°. Characteristic peaks are observed at ±0.2°, 19.3±0.2°, 19.6±0.2°, 20.6±0.2°, 21.1±0.2°, 22.3±0.2°, 22.7±0.2°, 23.2±0.2°, 23.8±0.2°, 25.0±0.2°, 25.7±0.2°, 27.9±0.2°, 28.9±0.2°, 31.1±0.2°, and 33.4±0.2°. (20) The differential scanning calorimetry curve of the sodium salt crystal form C has endothermic peaks at peak temperatures of approximately 137.7℃ and 243.7℃; (21) The thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 3.61% in the temperature range of 26.4℃ to 130.0℃; (22) The thermogravimetric analysis curve of the sodium salt crystal form C shows a weight loss of 5.59% in the temperature range of 130.0℃ to 210.0℃; (23) The sodium salt crystal form C contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, acetone or MTBE; (24) The sodium salt crystal form C contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (25) The sodium salt crystal form C is an organic solvate, wherein the molar ratio of the organic solvent to compound IR in the organic solvate is (0.01-0.2):1; (26) In the hydrochloride crystal form A, the molar ratio of hydrochloric acid to compound IR is 1:1 or 1.1:1; (27) The hydrochloride crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 5.0±0.2°, 7.7±0.2°, 9.9±0.2°, 10.8±0.2°, 11.5±0.2°, 11.9±0.2°, 12.9±0.2°, 14.8±0.2°, 15.5±0.2°, 18.4±0.2°, 19.1±0.2°, 19.8±0.2°, 20.7±0.2°, 23.1±0.2°, 24.4±0.2°, 24.9±0.2°, 26.1±0.2°, 28.0±0.2°, and 30.2±0.2°. (28) The differential scanning calorimetry curve of the hydrochloride crystal form A has an endothermic peak at a peak temperature of about 109.3℃; (29) The thermogravimetric analysis curve of the hydrochloride crystal form A shows a weight loss of 7.02% in the temperature range of 29.0℃ to 120.0℃; (30) In the hydrochloride crystal form B, the molar ratio of hydrochloric acid to compound IR is 1:1; (31) The hydrochloride crystal form B was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 5.0±0.2°, 6.9±0.2°, 7.8±0.2°, 10.0±0.2°, 10.2±0.2°, 11.0±0.2°, 11.8±0.2°, 12.2±0.2°, 12.9±0.2°, and 13.8±0.2°. Characteristic peaks are present at 14.1±0.2°, 14.5±0.2°, 15.4±0.2°, 15.7±0.2°, 18.1±0.2°, 18.5±0.2°, 20.6±0.2°, 20.9±0.2°, 21.2±0.2°, 22.7±0.2°, 24.2±0.2°, 25.1±0.2°, and 25.8±0.2°. (32) In the phosphate crystal form A, the molar ratio of phosphoric acid to compound IR is 0.9:1; (33) The phosphate crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 4.2±0.2°, 7.1±0.2°, 8.3±0.2°, 11.1±0.2°, 14.5±0.2°, 14.8±0.2°, 16.7±0.2°, 18.0±0.2°, 18.9±0.2°, 19.2±0.2°, and 20.1± Characteristic peaks are present at 0.2°, 21.9±0.2°, 22.3±0.2°, 23.0±0.2°, 23.9±0.2°, 24.8±0.2°, 25.2±0.2°, 25.7±0.2°, 27.7±0.2°, 29.2±0.2°, 30.2±0.2°, 31.7±0.2°, 33.2±0.2°, and 33.7±0.2°. (34) In the fumarate crystal form A, the molar ratio of fumaric acid to compound IR is 0.8:1; (35) The fumarate crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.2±0.2°, 7.2±0.2°, 8.1±0.2°, 8.4±0.2°, 11.3±0.2°, 12.6±0.2°, 14.7±0.2°, 14.9±0.2°, 15.1±0.2°, 17.0±0.2°, 18.0±0.2°, 18.7±0.2°, and 19.6±0.2°. Characteristic peaks are observed at 20.1±0.2°, 21.0±0.2°, 21.7±0.2°, 22.2±0.2°, 22.8±0.2°, 23.9±0.2°, 24.5±0.2°, 25.4±0.2°, 26.2±0.2°, 26.8±0.2°, 27.5±0.2°, 28.8±0.2°, 29.4±0.2°, 30.5±0.2°, 32.5±0.2°, and 34.4±0.2°. (36) In the malate crystal form A, the molar ratio of malic acid to compound IR is 0.5:1; (37) The malate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.5±0.2°, 6.8±0.2°, 8.9±0.2°, 11.4±0.2°, 14.3±0.2°, 15.2±0.2°, 16.5±0.2°, 18.0±0.2°, 19.0±0.2°, 19.4±0.2°, 20.6±0.2°, 21.8±0.2°, 22.3±0.2°, 23.7±0.2°, 24.4±0.2°, 26.2±0.2°, 26.6±0.2°, 27.8±0.2°, and 29.1±0.2°. (38) In the hydrobromide crystal form A, the molar ratio of hydrobromic acid to compound IR is 0.9:1; (39) The hydrobromide crystal form A has diffraction peaks as shown in Table 6-9 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (40) The hydrobromide crystal form A contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; (41) The hydrobromide crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (42) The hydrobromide crystal form A is an organic solvate; (43) The hydrobromide crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (44) In the hydrobromide crystal form B, the molar ratio of hydrobromic acid to compound IR is 1:1; (45) The hydrobromide crystal form B was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 6.6±0.2°, 8.8±0.2°, 10.2±0.2°, 11.7±0.2°, 12.5±0.2°, 12.6±0.2°, 13.9±0.2°, 14.3±0.2°, 15.2±0.2°, 15.4±0.2°, 15.9±0.2°, and 16.5°. Characteristic peaks are observed at ±0.2°, 17.7±0.2°, 18.5±0.2°, 19.2±0.2°, 19.6±0.2°, 19.9±0.2°, 20.7±0.2°, 21.1±0.2°, 22.0±0.2°, 23.3±0.2°, 24.3±0.2°, 26.1±0.2°, 29.9±0.2°, 27.4±0.2°, and 29.9±0.2°. (46) The hydrobromide crystal form B contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; (47) The hydrobromide crystal form B contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (48) The hydrobromide crystal form B is an organic solvate; (49) The hydrobromide crystal form B is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (50) In the 1,2-ethanedisulfonate crystal form A, the molar ratio of 1,2-ethanedisulfonic acid to compound IR is 0.8:1; (51) The 1,2-ethanedisulfonate crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 3.9±0.2°, 6.4±0.2°, 7.8±0.2°, 8.2±0.2°, 11.0±0.2°, 11.2±0.2°, 12.3±0.2°, 12.9±0.2°, 14.2±0.2°, 16.0±0.2°, 17.1±0.2°, 17.7±0.2°, 18.3±0.2°, 19.0±0.2°, 19.9±0.2°, 21.5±0.2°, 23.0±0.2°, 24.2±0.2°, 24.7±0.2°, and 28.9±0.2° in terms of angle 2θ. (52) In the magnesium salt crystal form A, the molar ratio of magnesium ions to compound IR is 0.6:1; (53) The magnesium salt crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.1±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, and 14.7±0. Characteristic peaks are present at 0.2°, 15.0±0.2°, 15.3±0.2°, 17.2±0.2°, 17.4±0.2°, 18.2±0.2°, 18.6±0.2°, 19.0±0.2°, 19.5±0.2°, 20.1±0.2°, 25.6±0.2°, 33.0±0.2°, and 38.0±0.2°. (54) In the potassium salt crystal form A, the molar ratio of potassium ions to compound IR is 0.8:1; (55) The potassium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.1±0.2°, 4.4±0.2°, 5.8±0.2°, 8.2±0.2°, 8.7±0.2°, 9.5±0.2°, 10.0±0.2°, 10.3±0.2°, 11.5±0.2°, 12.7±0.2°, 13.1±0.2°, 14.6±0.2°, 15.4±0.2°, 17.4±0.2°, 17.9±0.2°, 22.1±0.2°, 24.5±0.2°, and 25.2±0.2° in terms of angle 2θ. (56) The potassium salt crystal form A contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone and MTBE; (57) The potassium salt crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (58) The potassium salt crystal form A is an organic solvate; (59) The potassium salt crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (60) In the calcium salt crystal form A, the molar ratio of calcium ions to compound IR is 1.2:1; (61) The calcium salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 4.0±0.2°, 6.1±0.2°, 9.5±0.2°, 12.0±0.2°, 12.7±0.2°, 14.1±0.2°, 14.8±0.2°, 15.9±0.2°, 16.8±0.2°, 18.1±0.2°, 20.9±0.2°, 24.5±0.2°, 25.7±0.2°, 26.5±0.2°, and 34.2±0.2° in terms of 2θ angles. (62) In the meglumine salt crystal form A, the molar ratio of meglumine to compound IR is 1:1; (63) The crystal form A of the meglumine salt has diffraction peaks as shown in Table 7-9 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (64) The meglumine salt crystal form A contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; (65) The meglumine salt crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (66) The meglumine salt crystal form A is an organic solvate; (67) The meglumine salt crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (68) In the meglumine salt crystal form B, the molar ratio of meglumine to compound IR is 1:1; (69) The crystal form B of the meglumine salt has diffraction peaks as shown in Table 7-11 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (70) In the lysine salt crystal form A, the molar ratio of lysine to compound IR is 1:1; (71) The lysine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at 6.0±0.2°, 8.9±0.2°, 10.6±0.2°, 12.6±0.2°, 14.0±0.2°, 15.0±0.2°, 17.6±0.2°, 19.8±0.2°, 22.1±0.2°, 24.0±0.2°, and 30.7±0.2° in 2θ angles. (72) In the lysine salt crystal form B, the molar ratio of lysine to compound IR is 1:1; (73) The lysine salt crystal form B has diffraction peaks as shown in Table 7-16 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (74) The lysine salt crystal form B contains an organic solvent; the organic solvent is one, two or more of IPA, IPAc, n-heptane, acetone or MTBE; (75) The lysine salt crystal form B contains an organic solvent; the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; for example, 0.07:1; (76) The lysine salt crystal form B is an organic solvate; (77) The lysine salt crystal form B is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is (0.01-0.2):1; (78) In the diethylamine salt crystal form A, the molar ratio of diethylamine to compound IR is 1:1; (79) The diethylamine salt crystal form A, when subjected to Cu-Kα radiation, exhibits characteristic peaks in X-ray powder diffraction at angles of 2θ at 5.9±0.2°, 9.8±0.2°, 11.0±0.2°, 11.7±0.2°, 12.5±0.2°, 13.3±0.2°, 15.1±0.2°, 15.4±0.2°, 16.2±0.2°, 17.6±0.2°, 18.1±0.2°, 19.2±0.2°, 20.9±0.2°, 21.7±0.2°, 22.8±0.2°, 23.6±0.2°, 24.0±0.2°, 25.7±0.2°, 26.5±0.2°, 27.9±0.2°, and 29.6±0.2°. (80) In the diethanolamine salt crystal form A, the molar ratio of diethanolamine to compound IR is 1:1; (81) The diethanolamine salt crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 7.7±0.2°, 8.9±0.2°, 10.5±0.2°, 13.1±0.2°, 14.0±0.2°, 15.5±0.2°, 15.8±0.2°, 16.9±0.2°, 17.8±0.2°, 19.0±0.2°, 19.7±0.2°, 20.1±0.2°, 20.5±0.2°, 21.1±0.2°, 21.4±0.2°, and 21. Characteristic peaks are present at 9±0.2°, 22.2±0.2°, 22.6±0.2°, 23.0±0.2°, 23.6±0.2°, 24.3±0.2°, 24.5±0.2°, 24.9±0.2°, 25.8±0.2°, 26.4±0.2°, 26.8±0.2°, 27.3±0.2°, 28.1±0.2°, 28.5±0.2°, 29.4±0.2°, 30.0±0.2°, 33.1±0.2°, 34.2±0.2°, and 38.0±0.2°.

6. The salt according to claim 3, characterized in that: It is selected from one or more of the following conditions: (1) In the succinate crystal form A, the molar ratio of succinic acid to compound IR is 0.5:1 or 0.6:1; (2) The X-ray powder diffraction of the succinate crystal form A is selected from one of the following conditions: (i) The succinate crystal form A exhibits diffraction peaks as shown in Table 2-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The succinate crystal form A exhibits diffraction peaks as shown in Table 2-4 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The succinate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 7; (3) The succinate crystal form A has an endothermic peak at a peak temperature of approximately 151.5℃; (4) The succinate crystal form A has a basic DSC-TGA spectrum as shown in Figure 8; (5) The succinate crystal form A has a basic polarized microstructure as shown in Figure 10; (6) The succinate crystal form A has the basic characteristics shown in Figure 9. 1 H-NMR spectrum; (7) The succinate crystal form A does not contain organic solvents; (8) The X-ray powder diffraction of the Tris salt crystal form A is selected from one of the following conditions: (i) The Tris salt crystal form A exhibits diffraction peaks as shown in Table 5-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The Tris salt crystal form A exhibits diffraction peaks as shown in Table 5-4 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The Tris salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 30; (9) The Tris salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 31; (10) The Tris salt crystal type A has a basic polarized microstructure as shown in Figure 33; (11) The Tris salt crystal form A has the basic structure shown in Figure 32. 1 H-NMR spectrum; (12) The Tris salt crystal form A does not contain organic solvents; (13) The X-ray powder diffraction of the Tris salt crystal form B is selected from one of the following conditions: (i) The Tris salt crystal form B was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 3.7±0.2°, 7.3±0.2°, 9.2±0.2°, 9.8±0.2°, 10.0±0.2°, 10.9±0.2°, 11.9±0.2°, 14.0±0.2°, 14.5±0.2°, 15.4±0.2°, 16.9±0.2°, and 17.5±0.2°. Characteristic peaks are observed at 18.1±0.2°, 18.5±0.2°, 20.1±0.2°, 20.7±0.2°, 21.8±0.2°, 23.2±0.2°, 24.0±0.2°, 25.5±0.2°, 26.9±0.2°, 27.5±0.2°, 27.9±0.2°, 29.2±0.2°, 33.0±0.2°, 34.3±0.2°, and 36.4±0.2°. (ii) The Tris salt crystal form B exhibits diffraction peaks as shown in Table 5-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The Tris salt crystal form B exhibits diffraction peaks as shown in Table 5-6 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iv) The Tris salt crystal form B has a basic X-ray powder diffraction pattern as shown in Figure 34. (14) The Tris salt crystal form B has a basic DSC-TGA pattern as shown in Figure 35; (15) The Tris salt crystal type B has a basic polarized microstructure as shown in Figure 37; (16) The Tris salt crystal form B has the basic structure shown in Figure 36. 1 H-NMR spectrum; (17) The Tris salt crystal form B does not contain organic solvents; (18) The X-ray powder diffraction of the Tris salt crystal form C is selected from one of the following conditions: (i) The Tris salt crystal form C exhibits diffraction peaks as shown in Table 5-7 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The Tris salt crystal form C exhibits diffraction peaks as shown in Table 5-8 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The Tris salt crystal form C has a basic X-ray powder diffraction pattern as shown in Figure 38; (19) The Tris salt crystal form C has a basic DSC-TGA pattern as shown in Figure 39; (20) The Tris salt crystal form C has a basic polarized microstructure as shown in Figure 41; (21) The Tris salt crystal form C has the basic structure shown in Figure 40. 1 H-NMR spectrum; (22) The Tris salt crystal form C does not contain organic solvents; (23) The X-ray powder diffraction of the tartrate crystal form A is selected from one of the following conditions: (i) The tartrate crystal form A exhibits diffraction peaks as shown in Table 1-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The tartrate crystal form A exhibits diffraction peaks as shown in Table 1-4 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The tartrate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 3; (24) The tartrate crystal form A has a basic DSC-TGA spectrum as shown in Figure 4; (25) The tartrate crystal form A has a basic polarized microstructure as shown in Figure 6; (26) The tartrate crystal form A has the basic structure shown in Figure 5. 1 H-NMR spectrum; (27) The tartrate crystal form A does not contain organic solvents; (28) The X-ray powder diffraction of the sodium salt crystal form A is selected from one of the following conditions: (i) The sodium salt crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 3.4±0.2°, 6.2±0.2°, 9.0±0.2°, 10.2±0.2°, 11.2±0.2°, 11.8±0.2°, 13.1±0.2°, 13.3±0.2°, 13.6±0.2°, and 14.9±0. Characteristic peaks are present at 0.2°, 15.6±0.2°, 17.8±0.2°, 18.6±0.2°, 19.5±0.2°, 20.5±0.2°, 21.1±0.2°, 22.4±0.2°, 23.2±0.2°, 25.1±0.2°, 25.6±0.2°, 28.9±0.2°, and 31.1±0.2°. (ii) The sodium salt crystal form A exhibits diffraction peaks as shown in Table 4-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The sodium salt crystal form A has diffraction peaks as shown in Table 4-4 when subjected to Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iv) The sodium salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 18; (29) The sodium salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 19; (30) The sodium salt crystal form A has a basic polarized light microstructure as shown in Figure 21; (31) The sodium salt crystal form A has the basic structure shown in Figure 20. 1 H-NMR spectrum; (32) The sodium salt crystal form A does not contain organic solvents; (33) The X-ray powder diffraction of the sodium salt crystal form B is selected from one of the following conditions: (i) The sodium salt crystal form B exhibits diffraction peaks as shown in Table 4-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The sodium salt crystal form B exhibits diffraction peaks as shown in Table 4-6 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The sodium salt crystal form B has a basic X-ray powder diffraction pattern as shown in Figure 22; (34) The sodium salt crystal form B has a basic DSC-TGA spectrum as shown in Figure 23; (35) The sodium salt crystal form B has a basic polarized microstructure as shown in Figure 25; (36) The sodium salt crystal form B has the basic structure shown in Figure 24. 1 H-NMR spectrum; (37) The sodium salt crystal form B does not contain organic solvents; (38) The X-ray powder diffraction of the sodium salt crystal form C is selected from one of the following conditions: (i) The sodium salt crystal form C exhibits diffraction peaks as shown in Table 4-8 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The sodium salt crystal form C exhibits diffraction peaks as shown in Table 4-9 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The sodium salt crystal form C has a basic X-ray powder diffraction pattern as shown in Figure 26; (39) The sodium salt crystal form C has a basic DSC-TGA spectrum as shown in Figure 27; (40) The sodium salt crystal form C has a basic polarized light microstructure as shown in Figure 29; (41) The sodium salt crystal form C has the basic structure shown in Figure 28. 1 H-NMR spectrum; (42) The sodium salt crystal form C contains an organic solvent; the organic solvent is IPA; (43) The sodium salt crystal form C contains an organic solvent; the molar ratio of the organic solvent to compound IR is 0.01:1; (45) The sodium salt crystal form C is an IPA solvate, IPAc solvate, acetone solvate or MTBE solvate; (46) The sodium salt crystal form C is an organic solvate, wherein the molar ratio of the organic solvent to compound IR in the organic solvate is 0.01:1; (47) In the hydrochloride crystal form A, the molar ratio of hydrochloric acid to compound IR is 1:1; (48) The X-ray powder diffraction of the hydrochloride crystal form A is selected from one of the following conditions: (i) The hydrochloride crystal form A has diffraction peaks as shown in Table 3-2 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (ii) The hydrochloride crystal form A exhibits diffraction peaks as shown in Table 3-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The hydrochloride crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 11; (49) The hydrochloride crystal form A has a basic DSC-TGA spectrum as shown in Figure 12; (50) The hydrochloride crystal form A has a basic polarized microstructure as shown in Figure 14; (51) The hydrochloride crystal form A has the basic structure shown in Figure 13. 1 H-NMR spectrum; (52) The hydrochloride crystal form A does not contain organic solvents; (53) The X-ray powder diffraction of the hydrochloride crystal form B is selected from one of the following conditions: (i) The hydrochloride crystal form B was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 5.0±0.2°, 6.9±0.2°, 7.8±0.2°, 10.0±0.2°, 10.2±0.2°, 11.0±0.2°, 11.8±0.2°, 12.2±0.2°, 12.9±0.2°, 13.8±0.2°, 14.1±0.2°, 14.5±0.2°, 15.4±0.2°, 15.7±0.2°, Characteristic peaks are present at 18.1±0.2°, 18.5±0.2°, 19.5±0.2°, 20.6±0.2°, 20.9±0.2°, 21.2±0.2°, 22.7±0.2°, 23.4±0.2°, 24.2±0.2°, 24.5±0.2°, 25.1±0.2°, 25.8±0.2°, 27.4±0.2°, 27.9±0.2°, 29.7±0.2°, 31.2±0.2°, and 32.3±0.2°. (ii) The hydrochloride crystal form B exhibits diffraction peaks as shown in Table 3-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The hydrochloride crystal form B has diffraction peaks as shown in Table 3-6 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (iv) The hydrochloride crystal form B has a basic X-ray powder diffraction pattern as shown in Figure 15; (54) The hydrochloride crystal form B has a basic DSC-TGA spectrum as shown in Figure 16; (55) The hydrochloride crystal form B has the basic structure shown in Figure 17. 1 H-NMR spectrum; (56) The hydrochloride crystal form B does not contain organic solvents; (57) The X-ray powder diffraction of the phosphate crystal form A is selected from one of the following conditions: (i) The phosphate crystal form A exhibits diffraction peaks as shown in Table 6-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The phosphate crystal form A exhibits diffraction peaks as shown in Table 6-4 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The phosphate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 42; (58) The phosphate crystal form A has a basic DSC-TGA spectrum as shown in Figure 43; (59) The phosphate crystal form A does not contain organic solvents; (60) The X-ray powder diffraction of the fumarate crystal form A is selected from one of the following conditions: (i) The fumarate crystal form A exhibits diffraction peaks as shown in Table 6-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The fumarate crystal form A exhibits diffraction peaks as shown in Table 6-6 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The fumarate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 44; (61) The fumarate crystal form A has a basic DSC-TGA spectrum as shown in Figure 45; (62) The fumarate crystal form A does not contain organic solvents; (63) The X-ray powder diffraction of the malate crystal form A is selected from one of the following conditions: (i) The malate crystal form A has diffraction peaks as shown in Table 6-7 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The malate crystal form A has diffraction peaks as shown in Table 6-8 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°. (iii) The malate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 46; (64) The malate crystal form A has a basic DSC-TGA spectrum as shown in Figure 47; (65) The malate crystal form A does not contain organic solvents; (66) The X-ray powder diffraction of the hydrobromide crystal form A is selected from one of the following conditions: (i) The hydrobromide crystal form A has diffraction peaks as shown in Table 6-10 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (ii) The hydrobromide crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 48; (67) The hydrobromide crystal form A has a basic DSC-TGA spectrum as shown in Figure 49; (68) The hydrobromide crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is 0.03:1; (69) The hydrobromide crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is 0.03:1; (70) The hydrobromide crystal form A is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate or MTBE solvate; (71) The X-ray powder diffraction of the hydrobromide crystal form B is selected from one of the following conditions: (i) The hydrobromide crystal form B has diffraction peaks as shown in Table 6-11 when subjected to Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The hydrobromide crystal form B exhibits diffraction peaks as shown in Table 6-12 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The hydrobromide crystal form B has a basic X-ray powder diffraction pattern as shown in Figure 50. (72) The hydrobromide crystal form B has a basic DSC-TGA spectrum as shown in Figure 51; (73) The hydrobromide crystal form B contains an organic solvent; the molar ratio of the organic solvent to compound I or its stereoisomer is 0.01:1; (74) The hydrobromide crystal form B is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate or MTBE solvate; (75) The hydrobromide crystal form B is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound I or its stereoisomer is 0.01:1; (76) The X-ray powder diffraction of the 1,2-ethanedisulfonate crystal form A is selected from one of the following conditions: (i) The 1,2-ethanedisulfonate crystal form A exhibits diffraction peaks as shown in Table 8-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The 1,2-ethanedisulfonate crystal form A exhibits diffraction peaks as shown in Table 8-4 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The 1,2-ethanedisulfonate crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 70; (77) The 1,2-ethanedisulfonate crystal form A has a basic DSC-TGA spectrum as shown in Figure 71; (78) The 1,2-ethylenedisulfonate crystal form A has the basic characteristics shown in Figure 72. 1 H-NMR spectrum; (79) The 1,2-ethanedisulfonate crystal form A does not contain organic solvents; (80) The X-ray powder diffraction of the magnesium salt crystal form A is selected from one of the following conditions: (i) The magnesium salt crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, at 4.4±0.2°, 5.8±0.2°, 7.7±0.2°, 8.7±0.2°, 9.8±0.2°, 11.1±0.2°, 11.5±0.2°, 13.1±0.2°, 13.5±0.2°, 14.1±0.2°, 14.7±0.2°, 15.0±0.2°, 15.3±0.2°, 17.2±0.2°, and 17.4±0.2°. Characteristic peaks are present at 2°, 18.2±0.2°, 18.6±0.2°, 19.0±0.2°, 19.5±0.2°, 20.1±0.2°, 21.8±0.2°, 23.1±0.2°, 23.5±0.2°, 24.0±0.2°, 25.0±0.2°, 25.6±0.2°, 26.2±0.2°, 28.2±0.2°, 29.8±0.2°, 33.0±0.2°, 34.6±0.2°, and 38.0±0.2°. (ii) The magnesium salt crystal form A exhibits diffraction peaks as shown in Table 7-3 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The magnesium salt crystal form A has diffraction peaks as shown in Table 7-4 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (iv) The magnesium salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 52; (81) The magnesium salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 53; (82) The magnesium salt crystal form A does not contain organic solvents; (83) The X-ray powder diffraction of the potassium salt crystal form A is selected from one of the following conditions: (i) The potassium salt crystal form A was subjected to Cu-Kα radiation, and X-ray powder diffraction, expressed in 2θ angles, was performed at 4.1±0.2°, 4.4±0.2°, 5.1±0.2°, 5.8±0.2°, 7.0±0.2°, 8.2±0.2°, 8.7±0.2°, 9.5±0.2°, 10.0±0.2°, 10.3±0.2°, 11.5±0.2°, 12.2±0.2°, 12.7±0.2°, 13.1±0.2°, 13.9±0.2°, and 14.6±0.2°. Characteristic peaks are observed at 15.4±0.2°, 16.5±0.2°, 17.4±0.2°, 17.9±0.2°, 18.9±0.2°, 19.5±0.2°, 21.1±0.2°, 22.1±0.2°, 23.5±0.2°, 24.5±0.2°, 24.7±0.2°, 25.2±0.2°, 26.5±0.2°, 27.1±0.2°, 27.9±0.2°, 30.6±0.2°, 32.4±0.2°, and 35.5±0.2°. (ii) The potassium salt crystal form A exhibits diffraction peaks as shown in Table 7-5 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The potassium salt crystal form A exhibits diffraction peaks as shown in Table 7-6 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iv) The potassium salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 54. (84) The potassium salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 55; (85) The potassium salt crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is 0.02:1; (86) The potassium salt crystal form A is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate or MTBE solvate; (87) The potassium salt crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is 0.02:1; (88) The X-ray powder diffraction of the calcium salt crystal form A is selected from one of the following conditions: (i) The calcium salt crystal form A has diffraction peaks as shown in Table 7-7 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (ii) The calcium salt crystal form A has diffraction peaks as shown in Table 7-8 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (iii) The calcium salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 56; (89) The calcium salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 57; (90) The calcium salt crystal form A does not contain organic solvents; (91) The X-ray powder diffraction of the meglumine salt crystal form A is selected from one of the following conditions: (i) The crystal form A of the meglumine salt has diffraction peaks as shown in Table 7-10 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (ii) The crystal form A of the meglumine salt has a basic X-ray powder diffraction pattern as shown in Figure 58; (92) The meglumine salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 59; (93) The meglumine salt crystal form A contains an organic solvent; the molar ratio of the organic solvent to compound IR is 0.2:1; (94) The crystal form A of the meglumine salt is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate or MTBE solvate; (95) The meglumine salt crystal form A is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is 0.2:1; (96) The X-ray powder diffraction of the meglumine salt crystal form B is selected from one of the following conditions: (i) The crystal form B of the meglumine salt exhibits diffraction peaks as shown in Table 7-12 using Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The crystal form B of the meglumine salt has a basic X-ray powder diffraction pattern as shown in Figure 60. (97) The meglumine salt crystal form B has a basic DSC-TGA spectrum as shown in Figure 61. (98) The meglumine salt crystal form B does not contain organic solvents; (99) The X-ray powder diffraction of the lysine salt crystal form A is selected from one of the following conditions: (i) The lysine salt crystal form A has diffraction peaks as shown in Table 7-13 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle, with an error range of ±0.2°. (ii) The lysine salt crystal form A has diffraction peaks as shown in Table 7-14 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (iii) The lysine salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 62; (100) The lysine salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 63; (101) The lysine salt crystal form A does not contain organic solvents; (102) The lysine salt crystal form B has a basic X-ray powder diffraction pattern as shown in Figure 64. (103) The lysine salt crystal form B has a basic DSC-TGA spectrum as shown in Figure 65. (104) The lysine salt crystal form B is an IPA solvate, IPAc solvate, n-heptane solvate, acetone solvate or MTBE solvate; (105) The lysine salt crystal form B is an organic solvate; in the organic solvate, the molar ratio of the organic solvent to compound IR is 0.07:1; (106) The X-ray powder diffraction of the diethylamine salt crystal form A is selected from one of the following conditions: (i) The diethylamine salt crystal form A has diffraction peaks as shown in Table 7-17 when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in terms of 2θ angle, with an error range of ±0.2°. (ii) The diethylamine salt crystal form A has diffraction peaks as shown in Table 7-18 when subjected to Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The diethylamine salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 66; (107) The diethylamine salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 67; (108) The diethylamine salt crystal form A does not contain organic solvents; (109) The X-ray powder diffraction of the diethanolamine salt crystal form A is selected from one of the following conditions: (i) The diethanolamine salt crystal form A has diffraction peaks as shown in Table 7-19 when subjected to Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (ii) The diethanolamine salt crystal form A has diffraction peaks as shown in Table 7-20 when subjected to Cu-Kα radiation and X-ray powder diffraction with an angle of 2θ, with an error range of ±0.2°. (iii) The diethanolamine salt crystal form A has a basic X-ray powder diffraction pattern as shown in Figure 68; (110) The diethanolamine salt crystal form A has a basic DSC-TGA spectrum as shown in Figure 69; (111) The diethanolamine salt crystal form A does not contain organic solvents.

7. The method for preparing the salt according to any one of claims 1-6, characterized in that, The preparation method includes the following steps: mixing compound I or its stereoisomer with an acid or base and reacting the mixture in a solvent to obtain a salt of compound I or its stereoisomer.

8. The method for preparing salt according to claim 7, characterized in that, It is selected from one or more of the following conditions: (1) The acid is succinic acid, hydrochloric acid, tartaric acid, phosphoric acid, fumaric acid, malic acid, hydrobromic acid, p-toluenesulfonic acid, benzenesulfonic acid or 1,2-ethanedisulfonic acid; (2) The base is sodium hydroxide, tris(hydroxymethyl)aminomethane, magnesium hydroxide, potassium hydroxide, calcium hydroxide, choline, meglumine, lysine, diethylamine or diethanolamine; (3) The molar ratio of the acid or base to compound I or its stereoisomer is (0.5-2.5):1; for example, 0.65:1, 0.75:1, 1:1, 1.1:1 or 2:1; (4) The solvent is an organic solvent or water; preferably, the organic solvent is one, two or more of IPA, IPAc, MTBE, n-heptane, acetone, methanol, ethanol, 2-butanone, ethyl acetate, methyl acetate, 4-methyl-2-pentanone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, chloroform, n-hexane, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide or N-methylpyrrolidone, or a mixture of any one or two of the above solvents with n-heptane; For example, the solvent used to prepare succinates and crystal forms of compound I or its stereoisomers is IPA, IPAc or MTBE; For example, the solvent used to prepare the tartrate salt and crystal form of compound I or its stereoisomer is IPA, IPAc or MTBE; For example, the solvent for preparing the trihydroxymethylaminomethane salt of compound I or its stereoisomer and its crystal form is selected from a mixed solvent of IPA and n-heptane (the volume ratio of IPA to n-heptane is 1:2), a mixed solvent of IPAc and n-heptane (the volume ratio of IPAc to n-heptane is 1:2), a mixed solvent of acetone and n-heptane (the volume ratio of acetone to n-heptane is 1:4), or MTBE. For example, the solvent for preparing the sodium salt of compound I or its stereoisomer and its crystal form is selected from a mixed solvent of IPA and n-heptane (the volume ratio of IPA to n-heptane is 1:2), a mixed solvent of IPAc and n-heptane (the volume ratio of IPAc to n-heptane is 1:2), or MTBE. (5) The volume ratio of the solvent to the mass of compound I or its stereoisomer is (20-100) mL:1g, for example, 20mL:1g, 25mL:1g, 35mL:1g, 50mL:1g or 75mL:1g; (6) The reaction temperature is -20 to 50°C, preferably 5 to 50°C; for example, -20°C, 5°C or 20 to 30°C.

9. The method for preparing salt according to claim 7, characterized in that, It is selected from one or more of the following conditions: (1) When the solvent is IPAc, the tartrate crystal form A, succinate crystal form A, phosphate crystal form A, fumarate crystal form A, malate crystal form A or hydrobromide crystal form A is obtained; (2) When the solvent is MTBE, the following crystal forms are obtained: tartrate crystal form A, succinate crystal form A, hydrochloride crystal form A, sodium salt crystal form B, Tris salt crystal form B, phosphate crystal form A, fumarate crystal form A, malate crystal form A, hydrobromide crystal form B, potassium salt crystal form A, meglumine salt crystal form A, low-crystallinity lysine salt crystal form B, diethylamine salt crystal form A, or diethanolamine salt crystal form A; (3) When the solvent is a mixed solvent of ethyl acetate and n-heptane, preferably, when the solvent is a mixed solvent of ethyl acetate and n-heptane in a volume ratio of 1:3, the hydrochloride crystal form A or the 1,2-ethanedisulfonate crystal form A is obtained; (4) When the solvent is a mixed solvent of tetrahydrofuran and n-heptane, preferably, when the solvent is a mixed solvent of tetrahydrofuran and n-heptane in a volume ratio of 1:2, the hydrochloride crystal form B or the 1,2-ethanedisulfonate crystal form A is obtained. (5) When the solvent is a mixture of dichloromethane and n-heptane, preferably, when the solvent is a mixture of dichloromethane and n-heptane in a volume ratio of 1:2, the hydrochloride crystal form B is obtained; (6) When the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, the sodium salt crystal form A, sodium salt crystal form C, Tris salt crystal form A, low crystallinity potassium salt crystal form A, calcium salt crystal form A, meglumine salt crystal form A, lysine salt crystal form A, diethylamine salt crystal form A or diethanolamine salt crystal form A are obtained; (7) When the solvent is a mixed solvent of IPAc and n-heptane, preferably, when the solvent is a mixed solvent of IPAc and n-heptane in a volume ratio of 1:2, the sodium salt crystal form B, Tris salt crystal form C, potassium salt crystal form A, meglumine salt crystal form B, diethylamine salt crystal form A or diethanolamine salt crystal form A are obtained. (8) When the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, and the molar ratio of the base (e.g., NaOH) to compound IR is 1:1, the sodium salt crystal form A is obtained; (9) When the solvent is a mixed solvent of IPA and n-heptane, preferably, when the solvent is a mixed solvent of IPA and n-heptane in a volume ratio of 1:2, and the molar ratio of the base (e.g., NaOH) to compound IR is 1.1:1, the sodium salt crystal form C is obtained; (10) When the solvent is a mixed solvent of acetone and n-heptane, preferably, when the solvent is a mixed solvent of acetone and n-heptane in a volume ratio of 1:4, Tris salt crystal form B, magnesium salt crystal form A, calcium salt crystal form A, meglumine salt crystal form B, lysine salt crystal form A or diethylamine salt crystal form A is obtained. (11) When the solvent is IPA, the tartrate crystal form A, succinate crystal form A, fumarate crystal form B or malate crystal form A is obtained; (12) When the solvent is ACN or dichloromethane, 1,2-ethanedisulfonate crystal form A is obtained.

10. A pharmaceutical composition, characterized in that, The pharmaceutical composition contains the salt according to any one of claims 1-6.

11. The pharmaceutical composition of claim 10, characterized in that, It is selected from one or more of the following conditions: (1) The pharmaceutical composition further contains a pharmaceutically acceptable carrier; (2) The pharmaceutical composition further contains a second active ingredient, such as one, two or more of the following: other LPAR1 inhibitors, LPAR2 inhibitors, LPAR3 inhibitors, ROCK inhibitors, FAAH inhibitors, TGF-β inhibitors, ACC inhibitors, ASK-1 inhibitors, FXR agonists, GLP-1 agonists, PPARα agonists, VEGFR inhibitors, FGFR inhibitors, PDGFR inhibitors, ATX inhibitors, GPR84 agonists, PASK inhibitors, CFTR agonists, JAK1 inhibitors, ADAMTS5 inhibitors, TOL2 / 3 inhibitors, CTGF inhibitors, αv-β6 / αv-β1 antagonists, JNK1 inhibitors, mineralocorticoid receptor antagonists, Nrf2 activators, chymotrypsin inhibitors, PDE inhibitors, NOX1 / 4 inhibitors, leukotriene receptor antagonists, thromboxane receptor antagonists, SLC22A12 inhibitors, sGC inhibitors, xanthine oxidase inhibitors, or TGFP antagonists.

12. A formulation, characterized in that, The formulation contains the salt according to any one of claims 1-6 or the pharmaceutical composition according to any one of claims 10-11; Preferably, the formulation is an LPAR1 inhibitor.

13. The use of the salt according to any one of claims 1-6, the pharmaceutical composition according to any one of claims 10-11, and the formulation according to claim 12 in the preparation of a medicament for the prevention and / or treatment of LPAR1-mediated diseases or conditions; Preferably, the drug is an LPAR1 inhibitor; Preferably, the disease or symptom is a fibrotic disease, a respiratory disease, pain, a nervous system disease, a cardiovascular disease, an inflammatory disease, a kidney disease, a liver disease, an eye disease, cancer, a gastrointestinal disease, a urinary system disease, a metabolic disease, or transplant rejection; Preferably, the disease or condition is pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, progressive pulmonary fibrosis), renal fibrosis, liver fibrosis, skin fibrosis, intestinal fibrosis, ocular fibrosis, cardiac fibrosis, pancreatic fibrosis, interstitial lung disease, idiopathic interstitial pneumonia, asthma, chronic obstructive pulmonary disease, bronchospasm, cough, chronic cough, respiratory failure, silicosis, acute lung injury, acute respiratory distress syndrome, acute kidney injury, chronic kidney disease, diabetic nephropathy, alcoholic steatohepatitis, non-alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis), acute hepatitis, chronic hepatitis, cirrhosis, impaired liver function, primary biliary cirrhosis, autoimmune diseases, inflammation, arthritis, rheumatoid arthritis, scleroderma, Raynaud's phenomenon, chronic pruritus, lupus, cryptogenic fibrotic alveolitis, psoriasis, systemic sclerosis, collagen vascular disease, Alzheimer's disease, Parkinson's disease, etc. Neurodegenerative diseases, traumatic brain injury, epilepsy, mental illness, sleep disorders, collagen vascular diseases, myocardial infarction, stroke, thrombosis, atherosclerosis, heart failure, hypertension, colitis, inflammatory bowel disease, digestive tract diseases, gastrointestinal dysfunction, cancer pain, neuropathic pain, inflammatory pain, surgical pain, visceral pain, toothache, premenstrual pain, central pain, pain caused by burns, migraine, cluster headache, chronic pain, urinary incontinence, dysuria, cystitis, benign prostatic hyperplasia, urinary disorders associated with benign prostatic hyperplasia, bladder neck sclerosis, hypoactive bladder, macular degeneration, diabetic retinopathy, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, intestinal cancer, liver cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, tumor metastasis or osteoporosis; More preferably, the disease or condition is interstitial lung disease, pulmonary fibrosis (especially idiopathic pulmonary fibrosis), liver fibrosis, kidney fibrosis, non-alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis), psoriasis, or scleroderma.

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