Salt of cyp11a1 inhibitor and crystal form thereof, preparation method therefor, and use thereof

Abstract

Provided are a salt of a compound of formula (I), a crystal form thereof, a preparation method therefor, and use thereof in preparing a related drug.

Description

A salt of a CYP11A1 inhibitor, its crystal form, preparation method, and application. Technical Field

[0001] This invention relates to multiple crystal forms of a salt of a compound, their preparation methods and applications, specifically to multiple crystal forms of a salt of a CYP11A1 inhibitor, their preparation methods and applications, belonging to the field of medicinal chemistry technology. Background Technology

[0002] Cytochrome P450 monooxygenase 11a1 (CYP11A1), also known as cholesterol side-chain lyase, is primarily involved in drug metabolism-related catalytic reactions and the synthesis of cholesterol, steroids, and other lipids. The CYP11A1 protein is located in the inner mitochondrial membrane and catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in steroid hormone synthesis. This reaction takes place in the mitochondria of the adrenal cortex and is catalyzed by cytochrome CYP11A1 (also called P450scc), along with Adx and AdR. CYP11A1, Adx, and AdR belong to the cholesterol hydroxylase / lyase system (CH / L), catalyzing the initiation step of steroid synthesis in mammals—the process of converting cholesterol into pregnenolone. Pregnenolone is an important precursor to steroid hormones. The reaction process involves three consecutive monooxygenation reactions: the formation of 22R-hydroxycholesterol (22HC), the formation of 20R,22R-dihydroxycholesterol, and the cleavage of the C20-C22 bond. Each monooxygenation reaction requires two electrons and one molecular oxygen. Electrons are provided by NADPH and transferred to P450scc via NADPH-AdR and Adx. Adx forms a complex with P450scc and can act as a mobile electron transporter.

[0003] CYP11A1 is primarily expressed in the placenta in response to the synthesis of placental hormones such as progesterone and testosterone, and is also highly expressed in the adrenal glands and testes, but is almost absent in other tissues. By inhibiting CYP11A1 (a key upstream enzyme in steroid biosynthesis of CYP17a1), complete blockade of the entire steroid biosynthesis can be achieved. Therefore, CYP11A1 inhibitors have great potential for treating steroid hormone-dependent cancers such as prostate cancer, even in advanced stages of the disease, particularly in patients exhibiting hormone resistance. Recently, compounds with CYP11A1 inhibitory activity have been shown to significantly inhibit tumor growth in vivo in a mouse CRPC xenograft model.

[0004] There is an urgent need to discover CYP11A1 inhibitors with good activity, high safety and few side effects, which have good clinical development prospects and can be used to treat cancer or other proliferative diseases or conditions.

[0005] PCT / CN2024 / 083998 discloses a compound of formula (I) that has good CYP11A1 inhibitory activity.

[0006] This invention describes multiple crystal forms of a salt of a compound of formula (I), which belongs to CYP11A1 inhibitors and is intended for the treatment or prevention of CYP11A1-mediated diseases. The preparation method of the compound is also disclosed. Summary of the Invention

[0007] This invention provides a pharmaceutically acceptable salt of the compound shown in formula (I) and its crystal form.

[0008] In some embodiments, the pharmaceutically acceptable salt is selected from maleate, 2-naphthalenesulfonate, 1,5-naphthalenedisulfonate, fumarate, hydrohalates (preferably hydrobromide and hydrochloride), sulfate, phosphate, L-tartrate, citrate, L-malate, hippurate, D-glucuronate, glycolate, mucilage, succinate, lactate, orotate, pamoate, glycine, alanine, arginine, cinnamate, benzoate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, valerate, triphenylacetate, L-proline, ferulic acid, 2-hydroxyethanesulfonate, mandelate, nitrate, methanesulfonate, malonate, gentianate, salicylate, oxalate, glutarate, ethanedisulfonate, sine, camphorsulfonate, dichloroacetate, ethanesulfonic acid, and trifluoroacetate.

[0009] In some embodiments, the pharmaceutically acceptable salt is selected from benzenesulfonate, L-malate, phosphate, sulfate, p-toluenesulfonate, hydrochloride, maleate, 2-naphthalenesulfonate, hydrobromide, methanesulfonate, citrate, mandelate, lactobionate, succinate, salicylate, 1,5-naphthalenedisulfonate, fumarate, nicotinate, hippurate, oxalate, 2-hydroxyethanesulfonate, ethanedisulfonate, sine, camphorsulfonate, dichloroacetate, ethanesulfonic acid, trifluoroacetate, and nitrate.

[0010] In some implementations, the pharmaceutically acceptable salt is selected from methanesulfonate, hydrochloride, and p-toluenesulfonate;

[0011] In some embodiments, the molar ratio of the compound represented by formula (I) to the anion of the pharmaceutically acceptable salt is 1:0.5 to 1:3.5;

[0012] In some embodiments, the molar ratio of the compound of formula (I) to the anion of the pharmaceutically acceptable salt is 1:1.

[0013] This invention provides a benzenesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 16.57°±0.2°, 18.77°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 13.35°±0.2°, 16.24°±0.2°, 16.57°±0.2°, 18.77°±0.2°. 0.77°±0.2°, 20.24°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 13.35°±0.2°, 16.24°±0.2°, 16.57°±0.2°, 17.83°±0.2°, 18.77°±0.2°, 19.78°±0.2°, 20.24°±0.2°, 20.52°±0.2°, 21.60°±0.2°, 22.32°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 1.

[0014] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 89.94℃, 224.66℃, and 258.27℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 2.380% before 150℃; and the isothermal adsorption curves show a weight gain of 1.923% in the 0-80%RH range, with slight hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 2-4.

[0015] This invention provides a phosphate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 18.74°±0.2°, 21.84°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 15.55°±0.2°, 17.29°±0.2°, 17.63°±0.2°, 18. 74°±0.2°, 21.84°±0.2°; in some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 15.55°±0.2°, 15.94°±0.2°, 17.29°±0.2°, 17.63°±0.2°, 18.74°±0.2°, 20.86°±0.2°, 21.84°±0.2°, 23.62°±0.2°, 24.29°±0.2°, 33.83°±0.2°; in some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 5.

[0016] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 57.13℃, 185.20℃, and 191.70℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 0.9135% before 100℃; and the isothermal adsorption curves show a weight gain of 1.602% in the 0-80%RH range, with slight hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 6-8.

[0017] This invention provides a phosphate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.76°±0.2°, 17.23°±0.2°, 17.60°±0.2°, 18.84°±0.2°, 19.25°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.76°±0.2°, 7.21°±0.2°, 9.59°±0.2°, 17.23°±0.2°, 17.60°±0.2°, 18.84°±0.2°, 19.25°±0.2°. 0.25°±0.2°, 21.69°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.33°±0.2°, 4.76°±0.2°, 7.21°±0.2°, 9.59°±0.2°, 11.51°±0.2°, 14.68°±0.2°, 17.23°±0.2°, 17.60°±0.2°, 18.48°±0.2°, 18.84°±0.2°, 19.25°±0.2°, 21.690°±0.2°, 32.67°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 9.

[0018] This invention provides a phosphate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 16.80°±0.2°, 17.25°±0.2°, 17.52°±0.2°, 20.53°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.92°±0.2°, 16.80°±0.2°, 17.04°±0.2°, 17.25°±0.2°, 17.52°±0.2°, 19. 67°±0.2°, 20.53°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.92°±0.2°, 15.37°±0.2°, 15.59°±0.2°, 16.80°±0.2°, 17.04°±0.2°, 17.25°±0.2°, 17.52°±0.2°, 19.67°±0.2°, 20.53°±0.2°, 21.41°±0.2°, 22.09°±0.2°, 25.85°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 10.

[0019] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 46.04℃, 103.90℃, 187.60℃, and 190.77℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 5.5069% before 140℃; and the isothermal adsorption curves show a weight gain of 5.709% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 11-13.

[0020] This invention provides a sulfate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.38°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°, 20.47°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.38°±0.2°, 6.14°±0.2°, 6.35°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°, 20.47°±0.2°. 47°±0.2°, 27.42°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.38°±0.2°, 6.14°±0.2°, 6.35°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°, 15.48±0.2°, 16.77°±0.2°, 17.02°±0.2°, 20.47°±0.2°, 21.66°±0.2°, 27.42°±0.2°, 27.71°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 14.

[0021] This invention provides a sulfate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.08°±0.2°, 3.65°±0.2°, 4.07°±0.2°, 6.24°±0.2°, 7.36°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern Characteristic diffraction peaks are observed at the following 2θ positions: 3.08°±0.2°, 3.65°±0.2°, 4.07°±0.2°, 6.24°±0.2°, 7.36°±0.2°, 15.25°±0.2°, 15.56°±0.2°, 15.77°±0.2°, and 20.42°±0.2°. In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 15.

[0022] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 52.81°C, 140.83°C, and 225.24°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.294% before 140°C; and the isothermal adsorption curves show a weight gain of 7.369% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 16-18.

[0023] This invention provides a sulfate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 18.15°±0.2°, 19.98°±0.2°, 20.55°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 18.15°±0.2°, 19.98°±0.2°, 20.55°±0.2°, 20.86°±0.2°, 21. 48°±0.2°, 23.56°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 15.19°±0.2°, 18.15°±0.2°, 18.49°±0.2°, 18.89°±0.2°, 19.98°±0.2°, 20.55°±0.2°, 20.86°±0.2°, 21.48°±0.2°, 23.14°±0.2°, 23.56°±0.2°, 24.35°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 19.

[0024] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 55.92°C, 114.56°C, and 135.50°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 5.91% before reaching 150°C; and the isothermal adsorption curves show a weight gain of 8.356% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 20-22.

[0025] This invention provides a p-toluenesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 20.72°±0.2°, 21.81°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 13.02°±0.2°, 17.40°±0.2°, 18.77°±0.2°, 20. 0.72°±0.2°, 21.81°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 13.02°±0.2°, 15.11°±0.2°, 16.20°±0.2°, 16.75°±0.2°, 17.40°±0.2°, 18.77°±0.2°, 20.72°±0.2°, 21.53°±0.2°, 21.81°±0.2°, 23.82°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 23.

[0026] In some implementations, the differential scanning calorimetry (DSC) curve shows a peak temperature of 263.85 °C; the thermogravimetric analysis (TGA) curve shows a weight loss of approximately 0.9256% before 120 °C; and the isothermal adsorption curve shows a weight gain of 2.571% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 24-26.

[0027] This invention provides a p-toluenesulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.70°±0.2°, 14.43°±0.2°, 18.49°±0.2°, 20.45°±0.2°, 22.81°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.70°±0.2°, 7.08°±0.2°, 7.36°±0.2°, 14.43°±0.2°, 16.74°±0.2°, 18.49°±0.2°, 2 0.45°±0.2°, 22.81°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.70°±0.2°, 7.08°±0.2°, 7.36°±0.2°, 11.04°±0.2°, 14.43°±0.2°, 16.74°±0.2°, 17.00°±0.2°, 18.49°±0.2°, 20.45°±0.2°, 20.97°±0.2°, 21.72°±0.2°, 21.97°±0.2°, 22.81°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 27.

[0028] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 81.00℃ and 265.58℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.0262% before 116.43℃; and the isothermal adsorption curves show a weight gain of 2.238% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 28-30, respectively.

[0029] This invention provides a p-toluenesulfonate crystal form 3 of compound (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.29°±0.2°, 6.43°±0.2°, 17.38°±0.2°, 21.21°±0.2°, 23.06°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.29°±0.2°, 6.43°±0.2°, 17.38°±0.2°, 18.22°±0.2°, 19.03°±0.2°, 19.69°±0.2°, 21. 21°±0.2°, 23.06°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.29°±0.2°, 6.43°±0.2°, 14.24°±0.2°, 16.23°±0.2°, 17.38°±0.2°, 18.22°±0.2°, 19.03°±0.2°, 19.69°±0.2°, 19.91°±0.2°, 21.21°±0.2°, 21.69°±0.2°, 23.06°±0.2°, 26.30°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 31.

[0030] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 53.79℃, 183.20℃, 211.42℃, and 260.50℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.0870% before 100℃; and the isothermal adsorption curves show a weight gain of 3.574% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 32-34, respectively.

[0031] This invention provides a disulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 16.38°±0.2°, 18.22°±0.2°, 19.69°±0.2°, 20.00°±0.2°, 21.29°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 12.13°±0.2°, 16.38°±0.2°, 18.22°±0.2°, 19.06°±0.2°, 19.69°±0.2°, 20.00°±0.2°, 2 1.29°±0.2°, 21.60°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 12.13°±0.2°, 15.33°±0.2°, 16.38°±0.2°, 17.90°±0.2°, 18.22°±0.2°, 19.06°±0.2°, 19.46°±0.2°, 19.69°±0.2°, 20.00°±0.2°, 21.29°±0.2°, 21.60°±0.2°, 21.88°±0.2°, 23.62°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 35.

[0032] This invention provides a disulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 21.20°±0.2°, 23.02°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.81°±0.2°, 17.07°±0.2°, 17.84°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 2 1.20°±0.2°, 23.02°±0.2°; In some embodiments, the X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 7.42°±0.2°, 14.81°±0.2°, 16.17°±0.2°, 17.07°±0.2°, 17.84°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 19.84°±0.2°, 21.20°±0.2°, 22.49°±0.2°, 23.02°±0.2°, 24.57°±0.2°; In some embodiments, Cu-Kα radiation is used, and the X-ray powder diffraction pattern is shown in Figure 36.

[0033] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 59.20°C and 185.03°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 4.735% before 50°C; and the isothermal adsorption curves show a weight gain of 6.162% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 37-39.

[0034] This invention provides a 2-hydroxyethanesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.80°±0.2°, 7.50°±0.2°, 18.99°±0.2°, 20.84°±0.2°, 21.73°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.80°±0.2°, 7.50°±0.2°, 16.38°±0.2°, 18.99°±0.2°, 20.41°±0.2°, 20.84°±0.2°, 2 1.73°±0.2°, 23.63°±0.2°; In some embodiments, the X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.80°±0.2°, 7.50°±0.2°, 16.38°±0.2°, 17.42°±0.2°, 17.92°±0.2°, 18.17°±0.2°, 18.99°±0.2°, 20.41°±0.2°, 20.84°±0.2°, 21.73°±0.2°, 22.09°±0.2°, 23.63°±0.2°, 25.33°±0.2°; In some embodiments, Cu-Kα radiation is used, and the X-ray powder diffraction pattern is shown in Figure 40.

[0035] This invention provides a 2-hydroxyethanesulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.25°±0.2°, 14.42°±0.2°, 20.32°±0.2°, 21.40°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.25°±0.2°, 14.42°±0.2°, 17.79°±0.2°, 20.32°±0.2°, 21.40°±0.2°, 23.12°±0.2°, 24.84°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 5.74°±0.2°, 7.25°±0.2°, 12.82°±0.2°, 14.42°±0.2°, 17.79°±0.2°, 18.70°±0.2°, 19.55°±0.2°, 20.32°±0.2°, 21.40°±0.2°, 21.57°±0.2°, 23.12°±0.2°, 24.84°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 41.

[0036] This invention provides a 2-hydroxyethanesulfonate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.25°±0.2°, 4.43°±0.2°, 5.76°±0.2°, 11.55°±0.2°, 17.35°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder The diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.25°±0.2°, 4.43°±0.2°, 5.76°±0.2°, 7.48°±0.2°, 7.61°±0.2°, 11.55°±0.2°, 17.37°±0.2°, 20.72°±0.2°, and 21.07°±0.2°. In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 42.

[0037] In some implementations, the differential scanning calorimetry (DSC) curve shows a peak temperature of 142.15℃; the thermogravimetric analysis (TGA) curve shows a weight loss of approximately 3.798% before 140℃; and the isothermal adsorption curve shows a weight gain of 7.130% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 43-45.

[0038] This invention provides a maleate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 9.70°±0.2°, 18.60°±0.2°, 19.52°±0.2°, 24.45°±0.2°, 28.23°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 9.70°±0.2°, 14.60°±0.2°, 16.95°±0.2°, 18.60°±0.2°, 19.52°±0.2°, 24.45°±0.2°, 28.23°±0.2°. 45°±0.2°, 28.23°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 6.39°±0.2°, 9.70°±0.2°, 14.00°±0.2°, 14.60°±0.2°, 16.95°±0.2°, 17.48°±0.2°, 18.60°±0.2°, 19.52°±0.2°, 23.77°±0.2°, 24.45°±0.2°, 28.23°±0.2°, 37.73°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 46.

[0039] This invention provides a maleate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 16.72°±0.2°, 19.52°±0.2°, 21.56°±0.2°, 25.21°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 11.10°±0.2°, 16.72°±0.2°, 18.36°±0.2°, 19.52°±0.2°, 21.56°±0.2°, 25.21°±0.2°. 0.21°±0.2°, 28.07°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 9.40°±0.2°, 11.10°±0.2°, 16.72°±0.2°, 18.36°±0.2°, 19.52°±0.2°, 19.84°±0.2°, 21.12°±0.2°, 21.56°±0.2°, 22.38°±0.2°, 24.13°±0.2°, 25.21°±0.2°, 28.07°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 47.

[0040] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 109.06℃, 110.73℃, and 165.30℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 6.990% before 100℃; and the isothermal adsorption curves show a weight gain of 3.203% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 48-50.

[0041] This invention provides a maleate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.30°±0.2°, 8.85°±0.2°, 19.33°±0.2°, 23.75°±0.2°, 24.87°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.30°±0.2°, 8.85°±0.2°, 13.77°±0.2°, 16.57°±0.2°, 17.78°±0.2°, 19.33°±0.2°, 23. 0.75°±0.2°, 24.87°±0.2°; in some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.50°±0.2°, 7.40°±0.2°, 8.30°±0.2°, 8.85°±0.2°, 10.35°±0.2°, 13.77°±0.2°, 16.57°±0.2°, 17.78°±0.2°, 19.33°±0.2°, 23.75°±0.2°, 24.87°±0.2°, 26.80°±0.2°, 27.66°±0.2°; in some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 51.

[0042] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 106.00°C and 107.74°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 4.746% before 100°C; the differential scanning calorimetry and thermogravimetric analysis curves are shown in Figures 52-53.

[0043] This invention provides a 1,5-naphthalene disulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 9.38°±0.2°, 14.11°±0.2°, 18.32°±0.2°, 21.37°±0.2°, 22.83°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 9.38°±0.2°, 14.11°±0.2°, 16.58°±0.2°, 18.06°±0.2°, 18.32°±0.2°, 21.37°±0.2°, 22.52°±0.2°, 22.83°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 9.38°±0.2°, 14.11°±0.2°, 14.51°±0.2°, 16.58°±0.2°, 18.06°±0.2°, 18.32°±0.2°, 20.89°±0.2°, 21.37°±0.2°, 22.52°±0.2°, 22.83°±0.2°, 26.15°±0.2°, 28.81°±0.2°, 30.74°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 54.

[0044] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 281.04 °C and 284.30 °C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 0.3278% before 100 °C; and the isothermal adsorption curves show a weight gain of 0.8904% in the 0-80% RH range, with slight hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 55-57.

[0045] This invention provides a 1,5-naphthalene disulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 9.33°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.26°±0.2°, 20.87°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.54°±0.2°, 5.36°±0.2°, 9.33°±0.2°, 18.70°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.26°±0.2°, 20.87°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.54°±0.2°, 5.36°±0.2°, 9.33°±0.2°, 10.72°±0.2°, 14.51°±0.2°, 18.70°±0.2°, 19.02°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.26°±0.2°, 20.87°±0.2°, 24.93°±0.2°, 25.73°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 58.

[0046] This invention provides a 1,5-naphthalene disulfonate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.02°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 15.27°±0.2°, 19.04°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.02°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 11.42°±0.2°, 15.27°±0.2°, 19.04°±0.2° 19.94°±0.2°, 24.45°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.51°±0.2°, 5.02°±0.2°, 8.64°±0.2°, 8.95°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 11.42°±0.2°, 15.27°±0.2°, 17.41°±0.2°, 19.04°±0.2°, 19.94°±0.2°, 21.33°±0.2°, 24.45°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 59.

[0047] This invention provides a 2-naphthalenesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.63°±0.2°, 11.02°±0.2°, 14.74°±0.2°, 16.30°±0.2°, 20.13°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.63°±0.2°, 7.31°±0.2°, 11.02°±0.2°, 14.57°±0.2°, 14.74°±0.2°, 16.30°±0.2°, 1 7.92°±0.2°, 20.13°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.63°±0.2°, 7.31°±0.2°, 11.02°±0.2°, 14.57°±0.2°, 14.74°±0.2°, 16.30°±0.2°, 16.70°±0.2°, 17.92°±0.2°, 18.55°±0.2°, 20.13°±0.2°, 20.82°±0.2°, 21.06°±0.2°, 21.62°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 60.

[0048] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 58.87°C, 100.64°C, and 248.17°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 2.131% before 120°C; and the isothermal adsorption curves show a weight gain of 3.384% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 61-63.

[0049] This invention provides a 2-naphthalenesulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 22.00°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 16.79°±0.2°, 19.22°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 2 2.00°±0.2°, 23.56°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 15.27°±0.2°, 16.40°±0.2°, 16.79°±0.2°, 17.50°±0.2°, 19.22°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 21.18°±0.2°, 22.00°±0.2°, 22.59°±0.2°, 23.56°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 64.

[0050] This invention provides a 2-naphthalenesulfonate crystal form 3 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.19°±0.2°, 10.83°±0.2°, 14.47°±0.2°, 16.03°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.19°±0.2°, 10.83°±0.2°, 14.47°±0.2°, 16.03°±0.2°; The X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.19°±0.2°, 10.83°±0.2°, 12.78°±0.2°, 14.47°±0.2°, 16.03°±0.2°, 16.33°±0.2°, and 17.69°±0.2°. In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 65.

[0051] This invention provides a crystalline form 1 of the chloronaphthalate of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.93°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°, 18.00°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.98°±0.2°, 8.93°±0.2°, 11.52°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°, 18.00°±0.2°. 0.00°±0.2°, 22.19°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.98°±0.2°, 8.93°±0.2°, 10.68°±0.2°, 11.52°±0.2°, 14.05°±0.2°, 15.93°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°, 18.00°±0.2°, 21.69°±0.2°, 22.19°±0.2°, 26.04°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 66.

[0052] In some implementations, the differential scanning calorimetry (DSC) curve shows a peak temperature of 179.70 °C; the thermogravimetric analysis (TGA) curve shows a weight loss of approximately 0.2717% before 150 °C; and the isothermal adsorption curve shows a weight gain of 0.1477% in the 0-80% RH range with almost no hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 67-69.

[0053] This invention provides a camphor sulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.77°±0.2°, 9.25°±0.2°, 16.03°±0.2°, 16.72°±0.2°, 17.63°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.34°±0.2°, 8.77°±0.2°, 9.02°±0.2°, 9.25°±0.2°, 11.18°±0.2°, 16.03°±0.2°, 1 6.72°±0.2°, 17.63°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 6.85°±0.2°, 7.14°±0.2°, 8.34°±0.2°, 8.77°±0.2°, 9.02°±0.2°, 9.25°±0.2°, 11.18°±0.2°, 16.03°±0.2°, 16.72°±0.2°, 17.33°±0.2°, 17.63°±0.2°, 18.57°±0.2°, 25.67°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 70.

[0054] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 90.30°C and 182.45°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 2.358% before 70°C; and the isothermal adsorption curves show a weight gain of 0.7315% in the 0-80% RH range, with slight hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 71-73.

[0055] This invention provides a camphor sulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.78°±0.2°, 7.63°±0.2°, 11.50°±0.2°, 15.35°±0.2°, 17.94°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.78°±0.2°, 7.63°±0.2°, 11.50°±0.2°, 15.35°±0.2°, 17.94°±0.2°; The X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.78°±0.2°, 7.63°±0.2°, 9.76°±0.2°, 10.85°±0.2°, 11.50°±0.2°, 15.35°±0.2°, 17.94°±0.2°, and 20.64°±0.2°. In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 74.

[0056] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 56.60°C and 140.64°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.434% before 110°C; and the isothermal adsorption curves show a weight gain of 6.284% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 75-77.

[0057] This invention provides a dichloroacetate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 18.78°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°, 22 0.83°±0.2°, 23.02°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 16.07°±0.2°, 18.78°±0.2°, 19.08°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°, 22.83°±0.2°, 23.02°±0.2°, 24.25°±0.2°, 26.99°±0.2°, 27.75°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 78.

[0058] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 109.62°C and 151.46°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.958% before 80°C; and the isothermal adsorption curves show a weight gain of 3.287% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 79-81.

[0059] This invention provides an ethanesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 20.17°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 17.50°±0.2°, 17.79°±0.2°, 18 0.77°±0.2°, 20.17°±0.2°; in some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 17.50°±0.2°, 17.79°±0.2°, 18.36±0.2°, 18.77°±0.2°, 20.17°±0.2°, 20.72°±0.2°, 21.59°±0.2°, 21.75°±0.2°, 27.62°±0.2°; in some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 82.

[0060] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 151.43℃, 196.53℃, 199.40℃, and 219.01℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 1.578% before 150℃; and the isothermal adsorption curves show a weight gain of 4.414% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 83-85.

[0061] This invention provides an ethanesulfonate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 12.51°±0.2°, 15.14°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 10.47°±0.2°, 12.51°±0.2°, 13.69°±0.2°, 15. 14°±0.2°, 26.60°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 10.47°±0.2°, 12.51°±0.2°, 13.69°±0.2°, 15.14°±0.2°, 17.88±0.2°, 19.29°±0.2°, 20.69°±0.2°, 21.53°±0.2°, 22.31°±0.2°, 26.60°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 86.

[0062] In some implementations, the differential scanning calorimetry (DSC) curve shows a peak temperature of 212.87 °C; the thermogravimetric analysis (TGA) curve shows a weight loss of approximately 0.3714% before 175 °C; and the isothermal adsorption curve shows a weight gain of 1.254% in the 0-80% RH range, with slight hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 87-89.

[0063] This invention provides a hydrobromide crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.27°±0.2°, 3.95°±0.2°, 7.42°±0.2°, 19.96°±0.2°, 20.09°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.27°±0.2°, 3.95°±0.2°, 7.42°±0.2°, 19.96°±0.2°, 20.09°±0.2°; The θ position has characteristic diffraction peaks: 3.27°±0.2°, 3.95°±0.2°, 7.42°±0.2°, 7.54°±0.2°, 8.00°±0.2°, 8.11°±0.2°, 19.63°±0.2°, 19.96°±0.2°, 20.09°±0.2°, 20.42°±0.2°; in some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 90.

[0064] This invention provides a hydrobromide crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 6.20°±0.2°, 8.31°±0.2°, 10.39°±0.2°, 14.58°±0.2°, 20.89°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions. Diffraction peaks: 6.20°±0.2°, 8.31°±0.2°, 9.34°±0.2°, 10.39°±0.2°, 14.58°±0.2°, 20.89°±0.2°, 22.18°±0.2°, 22.51°±0.2°, 24.93°±0.2°, 25.22°±0.2°, 27.31°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 91.

[0065] This invention provides a methanesulfonate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.84°±0.2°, 7.76°±0.2°, 16.35°±0.2°, 17.43°±0.2°, 19.29°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions. The positions exhibit characteristic diffraction peaks: 3.84°±0.2°, 7.76°±0.2°, 16.35°±0.2°, 17.43°±0.2°, 19.29°±0.2°, 19.61°±0.2°, 20.41°±0.2°, 20.74°±0.2°, 20.89°±0.2°, 21.46°±0.2°; in some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 92.

[0066] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 74.73℃, 176.15℃, and 189.03℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 2.587% before 150℃; and the isothermal adsorption curves show a weight gain of 3.516% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 93-95.

[0067] This invention provides a nitrate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 3.76°±0.2°, 5.04°±0.2°, 6.11°±0.2°, 20.53°±0.2°, 20.88°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern The spectrum exhibits characteristic diffraction peaks at the following 2θ positions: 3.76°±0.2°, 4.59°±0.2°, 5.04°±0.2°, 6.11°±0.2°, 7.69°±0.2°, 20.53°±0.2°, 20.88°±0.2°, 21.25°±0.2°, and 36.44°±0.2°. In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 96.

[0068] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 83.06°C and 136.22°C, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 3.837% before 100°C; and the isothermal adsorption curves show a weight gain of 2.494% in the 0-80% RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 97-99.

[0069] This invention provides a trifluoroacetate crystal form 1 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 18.82°±0.2°, 20.70°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 10.75°±0.2°, 18.82°±0.2°, 20.70°±0.2°, 21.0°±0.2°. 8°±0.2°, 24.32°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 10.75°±0.2°, 18.82°±0.2°, 20.49°±0.2°, 20.70°±0.2°, 21.08°±0.2°, 21.52°±0.2°, 23.21°±0.2°, 24.32°±0.2°, 27.08°±0.2°, 29.88°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 100.

[0070] In some implementations, the differential scanning calorimetry (DSC) curves show peak temperatures of 112.35℃, 116.47℃, and 169.05℃, respectively; the thermogravimetric analysis (TGA) curves show a weight loss of approximately 0.5928% before 90℃; and the isothermal adsorption curves show a weight gain of 3.870% in the 0-80%RH range, indicating hygroscopicity. The differential scanning calorimetry, thermogravimetric analysis, and isothermal adsorption curves are shown in Figures 101-103.

[0071] This invention provides a trifluoroacetate crystal form 2 of the compound shown in formula (I); in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 8.96°±0.2°, 17.73°±0.2°, 19.05°±0.2°, 19.31°±0.2°, 22.51°±0.2°; in some embodiments, using Cu-Kα radiation, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 6.13°±0.2°, 8.96°±0.2°, 12.30°±0.2°, 17.73°±0.2°, 19.05°±0.2°, 19.31°±0.2°, 22.51°±0.2°. 0.51°±0.2°, 25.06°±0.2°; In some embodiments, its X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ positions: 6.13°±0.2°, 8.96°±0.2°, 12.30°±0.2°, 12.85±0.2°, 13.40°±0.2°, 14.62°±0.2°, 17.73°±0.2°, 19.05°±0.2°, 19.31°±0.2°, 20.51°±0.2°, 22.51°±0.2°, 24.36°±0.2°, 25.06°±0.2°; In some embodiments, Cu-Kα radiation is used, and its X-ray powder diffraction pattern is shown in Figure 104.

[0072] Its thermogravimetric analysis (TGA) curve shows a weight loss of approximately 0.1013% before 90℃; its thermogravimetric analysis curve is shown in Figure 105.

[0073] The crystal form of the salt of the compound of formula (I) of the present invention has advantages including, but not limited to, ease of processing and crystallization, convenient handling, easy purification, easy industrialization, low hygroscopicity, good flowability, easy micronization, high solubility, good pharmacokinetic characteristics and good stability, making it suitable for the preparation of pharmaceutical formulations.

[0074] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of any of the aforementioned salts or crystal forms, and a pharmaceutically acceptable carrier and / or excipient, preferably wherein the therapeutically effective amount is 1-1500 mg. The pharmaceutical composition may be in unit dosage form (unit dosage is also referred to as a “dosage strength”).

[0075] The present invention also provides the use of the salt or crystal form or composition described in any of the foregoing embodiments in the preparation of a medicament for treating CYP11A1-mediated diseases.

[0076] The present invention also provides a method for treating or preventing CYP11A1-mediated diseases, the method comprising administering to a subject a therapeutically effective amount of the salt or crystalline form or a combination thereof described in any of the foregoing embodiments, said therapeutically effective amount being 1-1500 mg. In some embodiments, the mammals described in the present invention include humans.

[0077] The term "effective amount" or "therapeutic effective amount" as used in this application means that administering a sufficient amount of the crystalline form disclosed in this application will alleviate, to some extent, one or more symptoms of the disease or condition being treated. In some embodiments, the result is a reduction and / or mitigation of the signs, symptoms, or causes of the disease, or any other desired alteration of the biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising the crystalline form disclosed in this application required to provide a clinically significant reduction in disease symptoms. Examples of therapeutically effective doses include, but are not limited to, 1-1500 mg, 1-1400 mg, 1-1300 mg, 1-1200 mg, 1-1000 mg, 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-250 mg, 1-200 mg, 1-150 mg, 1-125 mg, 1-100 mg, 1-80 mg, 1-60 mg, 1-50 mg, 1-40 mg, 1-25 mg, 1- 20mg, 5-1500mg, 5-1000mg, 5-900mg, 5-800mg, 5-700mg, 5-600mg, 5-500mg, 5-400mg, 5-300mg, 5-250mg, 5-200mg, 5 -150mg, 5-125mg, 5-100mg, 5-90mg, 5-70mg, 5-80mg, 5-60mg, 5-50mg, 5-40mg, 5-30mg, 5-25mg, 5-20mg, 10-1500mg, 10-1000mg, 10-900mg, 10-800mg, 10-700mg, 10-600mg, 10-500mg, 10-450mg, 10-400mg, 10-300mg, 10-250mg, 10-20 0mg, 10-150mg, 10-125mg, 10-100mg, 10-90mg, 10-80mg, 10-70mg, 10-60mg, 10-50mg, 10-40mg, 10-30mg, 10-20mg; 2 0-1500mg, 20-1000mg, 20-900mg, 20-800mg, 20-700mg, 20-600mg, 20-500mg, 20-400mg, 20-350mg, 20-300mg, 20-25 0mg, 20-200mg, 20-150mg, 20-125mg, 20-100mg, 20-90mg, 20-80mg, 20-70mg, 20-60mg, 20-50mg, 20-40mg, 20-30mg;50-1500mg, 50-1000mg, 50-900mg, 50-800mg, 50-700mg, 50-600mg, 50-500mg, 50-400mg, 50-300mg, 50-250mg, 50-200mg, 50-150mg, 50-125mg, 5 0-100mg; 100-1500mg, 100-1000mg, 100-900mg, 100-800mg, 100-700mg, 100-600mg, 100-500mg, 100-400mg, 100-300mg, 100-250mg, 100-200mg. ;

[0078] In some embodiments, the pharmaceutical composition or formulation of the present invention contains a therapeutically effective amount of the salt or crystal form of the present invention.

[0079] This invention relates to a pharmaceutical composition or formulation comprising a therapeutically effective amount of the salt or crystal form described herein, as well as a carrier and / or excipients. The pharmaceutical composition may be in unit dosage form (the amount of the active pharmaceutical ingredient in a unit dosage form is also referred to as a "dosage strength"). In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-1500 mg, 5-1500 mg, 5-1000 mg, 10-800 mg, 20-600 mg, 25-500 mg, 40-200 mg, 50-100 mg, 1 mg, 1.25 mg, 2.5 mg, 5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, etc. The salts or crystal forms of the present invention in g, 170mg, 180mg, 190mg, 200mg, 210mg, 220mg, 230mg, 240mg, 250mg, 275mg, 300mg, 325mg, 350mg, 375mg, 400mg, 425mg, 450mg, 475mg, 500mg, 525mg, 550mg, 575mg, 600mg, 625mg, 650mg, 675mg, 700mg, 725mg, 750mg, 775mg, 800mg, 850mg, 900mg, 950mg, 1000mg, 1100mg, 1200mg, 1300mg, 1400mg, and 1500mg.

[0080] A method for treating a disease in mammals, the method comprising administering to a subject a therapeutically effective amount of the crystalline form of the invention, and a pharmaceutically acceptable carrier and / or excipient, the therapeutically effective amount preferably being 1-1500 mg, wherein the disease is a CYP11A1-mediated disease, preferably prostate cancer.

[0081] A method for treating a disease in a mammal, the method comprising administering a salt or crystal form of the drug of the present invention, along with a pharmaceutically acceptable carrier and / or excipient, to a subject at a daily dose of 1-1500 mg / day, said daily dose being a single dose or multiple doses. In some embodiments, the daily dose includes, but is not limited to, 10-1500 mg / day, 20-1500 mg / day, 25-1500 mg / day, 50-1500 mg / day, 75-1500 mg / day, 100-1500 mg / day, 200-1500 mg / day, 10-1000 mg / day, 20-1000 mg / day, 25-1000 mg / day, 50-1000 mg / day, 75-1000 mg / day, and 100-1000 mg / day. / day, 200-1000mg / day, 25-800mg / day, 50-800mg / day, 100-800mg / day, 200-800mg / day, 25-400mg / day, 50-400mg / day, 100-400mg / day, 200-400mg / day. In some embodiments, the daily dose includes, but is not limited to, 1mg / day, 5mg / day, 10mg / day, 20mg / day, 25mg / day, 50mg / day, 75mg / day, 100mg / day, 125mg / day, 150mg / day, 200mg / day, 400mg / day, 600mg / day, 800mg / day, 1000mg / day, 1200mg / day, 1400mg / day, and 1500mg / day.

[0082] The present invention relates to a kit that may include a single-dose or multi-dose form of a crystal, the kit containing the crystal of the present invention in an amount identical to that in the above-described pharmaceutical composition.

[0083] In this invention, the amount of the crystal form of the invention is converted in the form of free alkali in each case.

[0084] "Product specification" refers to the weight of the active pharmaceutical ingredient contained in each vial, tablet, or other unit of preparation.

[0085] The crystalline form of the present invention is present in the form of about 5% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 10% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 15% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 20% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 25% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 30% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 35% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 40% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 45% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 50% by weight to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present in the form of about 55% by weight to about 100% by weight of the active pharmaceutical ingredient. In some embodiments, it is present at about 60% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 65% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 70% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 75% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 80% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 85% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 90% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 95% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 98% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, it is present at about 99% to about 100% by weight of the active pharmaceutical ingredient; in some embodiments, substantially all of the active pharmaceutical ingredient is substantially pure crystal.

[0086] The crystalline form of the present invention can be prepared by the following method:

[0087] 1. Volatilization experiment: Add the compound of formula I to the selected single solvent or binary solvent to form a clear solution of the sample, and volatilize it in an open container at different temperatures until the solvent is dry.

[0088] 2. Suspension method: Add the compound of formula I to the selected single solvent or binary solvent until a suspension is formed. After suspending and stirring at room temperature to 50°C for a certain period of time (e.g., 1h to 3 days, or 2h to 24h, or 2h to 12h, or 3 to 5h), centrifuge the suspension and dry it to obtain the product.

[0089] 3. Dissolution and crystallization method: Dissolve the compound of formula I in a good solvent, take a certain amount of the solution and add it dropwise to a poor solvent, or add the poor solvent dropwise to the solution, stir to precipitate the solid, separate and dry to obtain the product.

[0090] 4. Cooling method: Dissolve a certain amount of sample in the corresponding solvent at high temperature, transfer the solution to room temperature to cool, let it stand or stir to crystallize, separate, and dry to obtain the final product.

[0091] 5. Thermal method experiment: Take a certain amount of sample, place it on a glass slide and put it on a hot stage. Heat it to the target temperature at a certain rate (e.g., 5-20℃ / min, or 10-15℃ / min) and keep it at the temperature for a period of time (e.g., 0.5-5min, or 1-3min, or 1-2min). Then let it cool naturally to room temperature to obtain a solid.

[0092] 6. Gas-phase diffusion experiment: Add a certain amount of compound I at room temperature to a suitable amount of good solvent to completely dissolve the sample or prepare a saturated solution of good solvent; take a certain amount of solution, place the clear solution in a poor solvent atmosphere and let it stand at room temperature until a solid precipitates, then separate it to obtain the product. Alternatively, place the solid of compound I in a solvent atmosphere and let it stand at room temperature for 1 to 7 days to obtain the product.

[0093] The terms "good solvent" and "bad solvent" in this invention are relative. In a pair of solvents, the one with higher solubility is a good solvent, and the one with lower solubility is a bad solvent.

[0094] Unless otherwise specified, the solvent used in the above preparation method may be a single solvent or a combination of two or more solvents.

[0095] The X-ray powder diffraction or DSC pattern and TGA pattern disclosed in this invention, which are substantially the same, also fall within the scope of this invention.

[0096] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0097] IC 50 "Half-inhibition concentration" refers to the concentration at which half of the maximum inhibitory effect is achieved.

[0098] As used in this invention, "crystal of the present invention", "crystal form of the present invention", "crystal form of the present invention" and the like are interchangeable.

[0099] The "room temperature" mentioned in this invention generally refers to 4-30℃, and preferably to 20±5℃.

[0100] The crystal structure of the present invention can be analyzed using various analytical techniques known to those skilled in the art, including but not limited to X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and / or thermogravimetric analysis (TGA), also known as thermogravimetry (TG).

[0101] The "2θ or 2θ angle" mentioned in this invention refers to the peak position expressed in degrees (°) based on the setup in an X-ray diffraction experiment, and is typically the horizontal axis unit in a diffraction pattern. If the reflected beam is diffracted when the incident beam forms an angle θ with a certain lattice plane, the experimental setup needs to record the reflected beam at a 2θ angle. It should be understood that the specific 2θ value for a particular crystal form mentioned herein is intended to represent the 2θ value (expressed in degrees) measured using the X-ray diffraction experimental conditions described herein, and the error range of the 2θ may be ±0.3, ±0.2, or ±0.1.

[0102] It is understood that the numerical values ​​described and protected in this invention are approximate. Variations within these values ​​may be attributed to equipment calibration, equipment errors, crystal purity, crystal size, sample size, and other factors.

[0103] It is understood that the crystal forms of the present invention are not limited to those that are exactly the same as the characteristic spectra described in the accompanying drawings, such as XRD, DSC, TGA, and DVS. Any crystal form having a characteristic spectra that are substantially the same or essentially the same as those described in the accompanying drawings falls within the scope of the present invention.

[0104] It is understood that, as is well known in the field of differential scanning calorimetry (DSC), the melting peak height of a DSC curve depends on many factors related to sample preparation and instrument geometry, while the peak position is relatively insensitive to experimental details. Therefore, in some embodiments, the crystalline compounds of the present invention are characterized by DSC plots with characteristic peak positions, possessing substantially the same properties as the DSC plots provided in the accompanying drawings, with a measurement error tolerance of ±5°C, generally required to be ±3°C.

[0105] "Carrier" refers to a system that does not cause significant stimulation to the organism and does not eliminate the biological activity and properties of the given compound, and can change the way the drug enters the human body and its distribution in the body, control the release rate of the drug, and deliver the drug to the target organ. Non-limiting examples include microcapsules and microspheres, nanoparticles, liposomes, etc.

[0106] "Excipient" refers to an agent that is not itself a therapeutic agent but is used as a diluent, excipient, binder, and / or medium to be added to a pharmaceutical composition to improve its disposal or storage properties or to allow or promote the formation of a unit dosage form of the compound or pharmaceutical composition for administration. As is known to those skilled in the art, pharmaceutical excipients can provide a variety of functions and can be described as wetting agents, buffers, suspending agents, lubricants, emulsifiers, disintegrants, absorbents, preservatives, surfactants, colorants, flavoring agents, and sweeteners. Examples of pharmaceutical excipients include, but are not limited to: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, microcrystalline cellulose, and croscarmellose (e.g., sodium croscarmellose); (4) tragacanth gum powder; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter. (9) Oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) Diols, such as propylene glycol; (11) Polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) Esters, such as ethyl oleate and ethyl laurate; (13) Agar; (14) Buffers, such as magnesium hydroxide and aluminum hydroxide; (15) Alginate; (16) Atherless water; (17) Isotonic saline; (18) Ringer's solution; (19) Ethanol; (20) pH buffer solution; (21) Polyesters, polycarbonates and / or polyanhydrides; and (22) Other non-toxic compatible substances used in pharmaceutical preparations. Attached Figure Description

[0107] Figure 1 shows the X-ray powder diffraction pattern of the benzenesulfonate crystal form 1 of the compound shown in formula (I).

[0108] Figure 2 shows the differential scanning calorimetry (DSC) spectrum of the benzenesulfonate crystal form 1 of the compound shown in formula (I).

[0109] Figure 3 shows the thermogravimetric analysis curves of benzenesulfonate crystal form 1 of the compound shown in formula (I).

[0110] Figure 4 shows the isothermal adsorption curves of benzenesulfonate crystal form 1 of the compound shown in formula (I).

[0111] Figure 5 shows the X-ray powder diffraction pattern of the phosphate crystal form 1 of the compound shown in formula (I).

[0112] Figure 6 shows the differential scanning calorimetry (DSC) spectrum of the phosphate crystal form 1 of the compound shown in formula (I).

[0113] Figure 7 shows the thermogravimetric analysis curves of the phosphate crystal form 1 of the compound shown in formula (I).

[0114] Figure 8 shows the isothermal adsorption curves of phosphate crystal form 1 of the compound shown in formula (I).

[0115] Figure 9 shows the X-ray powder diffraction pattern of phosphate crystal form 2 of the compound shown in formula (I).

[0116] Figure 10 shows the X-ray powder diffraction pattern of phosphate crystal form 3 of the compound shown in formula (I).

[0117] Figure 11 shows the differential scanning calorimetry (DSC) spectrum of the phosphate crystal form 3 of the compound shown in formula (I).

[0118] Figure 12 shows the thermogravimetric analysis curves of phosphate crystal form 3 of the compound shown in formula (I).

[0119] Figure 13 shows the isothermal adsorption curves of phosphate crystal form 3 of the compound shown in formula (I).

[0120] Figure 14 shows the X-ray powder diffraction pattern of the sulfate crystal form 1 of the compound shown in formula (I).

[0121] Figure 15 shows the X-ray powder diffraction pattern of the sulfate crystal form 2 of the compound shown in formula (I).

[0122] Figure 16 shows the differential scanning calorimetry (DSC) spectrum of the sulfate crystal form 2 of the compound shown in formula (I).

[0123] Figure 17 shows the thermogravimetric analysis curves of the sulfate crystal form 2 of the compound shown in formula (I).

[0124] Figure 18 shows the isothermal adsorption curves of the sulfate crystal form 2 of the compound shown in formula (I).

[0125] Figure 19 shows the X-ray powder diffraction pattern of the sulfate crystal form 3 of the compound shown in formula (I).

[0126] Figure 20 shows the differential scanning calorimetry (DSC) spectrum of the sulfate crystal form 3 of the compound shown in formula (I).

[0127] Figure 21 shows the thermogravimetric analysis curves of the sulfate crystal form 3 of the compound shown in formula (I).

[0128] Figure 22 shows the isothermal adsorption curves of the sulfate crystal form 3 of the compound shown in formula (I).

[0129] Figure 23 shows the X-ray powder diffraction pattern of p-toluenesulfonate crystal form 1 of the compound shown in formula (I).

[0130] Figure 24 shows the differential scanning calorimetry (DSC) spectrum of p-toluenesulfonate crystal form 1 of the compound shown in formula (I).

[0131] Figure 25 shows the thermogravimetric analysis curves of p-toluenesulfonate crystal form 1 of the compound shown in formula (I).

[0132] Figure 26 shows the isothermal adsorption curves of p-toluenesulfonate crystal form 1 of the compound shown in formula (I).

[0133] Figure 27 shows the X-ray powder diffraction pattern of p-toluenesulfonate crystal form 2 of the compound shown in formula (I).

[0134] Figure 28 shows the differential scanning calorimetry (DSC) spectrum of p-toluenesulfonate crystal form 2 of the compound shown in formula (I).

[0135] Figure 29 shows the thermogravimetric analysis curves of p-toluenesulfonate crystal form 2 of the compound shown in formula (I).

[0136] Figure 30 shows the isothermal adsorption curves of p-toluenesulfonate crystal form 2 of the compound shown in formula (I).

[0137] Figure 31 shows the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form 3 of the compound shown in formula (I).

[0138] Figure 32 shows the differential scanning calorimetry (DSC) spectrum of the p-toluenesulfonate crystal form 3 of the compound shown in formula (I).

[0139] Figure 33 shows the thermogravimetric analysis curves of the p-toluenesulfonate crystal form 3 of the compound shown in formula (I).

[0140] Figure 34 shows the isothermal adsorption curves of p-toluenesulfonate crystal form 3 of the compound shown in formula (I).

[0141] Figure 35 shows the X-ray powder diffraction pattern of the ethylene disulfonate crystal form 1 of the compound shown in formula (I).

[0142] Figure 36 shows the X-ray powder diffraction pattern of the ethylene disulfonate crystal form 2 of the compound shown in formula (I).

[0143] Figure 37 shows the differential scanning calorimetry (DSC) spectrum of the ethylene disulfonate crystal form 2 of the compound shown in formula (I).

[0144] Figure 38 shows the thermogravimetric analysis curves of the ethylene disulfonate crystal form 2 of the compound shown in formula (I).

[0145] Figure 39 shows the isothermal adsorption curves of the ethylene disulfonate crystal form 2 of the compound shown in formula (I).

[0146] Figure 40 shows the X-ray powder diffraction pattern of the 2-hydroxyethanesulfonate crystal form 1 of the compound shown in formula (I).

[0147] Figure 41 shows the X-ray powder diffraction pattern of the 2-hydroxyethanesulfonate crystal form 2 of the compound shown in formula (I).

[0148] Figure 42 shows the X-ray powder diffraction pattern of the 2-hydroxyethanesulfonate crystal form 3 of the compound shown in formula (I).

[0149] Figure 43 shows the differential scanning calorimetry (DSC) spectrum of the 2-hydroxyethanesulfonate crystal form 3 of the compound shown in formula (I).

[0150] Figure 44 shows the thermogravimetric analysis curves of the 2-hydroxyethanesulfonate crystal form 3 of the compound shown in formula (I).

[0151] Figure 45 shows the isothermal adsorption curves of the 2-hydroxyethanesulfonate crystal form 3 of the compound shown in formula (I).

[0152] Figure 46 shows the X-ray powder diffraction pattern of maleate crystal form 1 of the compound shown in formula (I).

[0153] Figure 47 shows the X-ray powder diffraction pattern of maleate crystal form 2 of the compound shown in formula (I).

[0154] Figure 48 shows the differential scanning calorimetry (DSC) spectrum of maleate crystal form 2 of the compound shown in formula (I).

[0155] Figure 49 shows the thermogravimetric analysis curves of maleate crystal form 2 of the compound shown in formula (I).

[0156] Figure 50 shows the isothermal adsorption curves of maleate crystal form 2 of the compound shown in formula (I).

[0157] Figure 51 shows the X-ray powder diffraction pattern of maleate crystal form 3 of the compound shown in formula (I).

[0158] Figure 52 shows the differential scanning calorimetry (DSC) spectrum of maleate crystal form 3 of the compound shown in formula (I).

[0159] Figure 53 shows the thermogravimetric analysis curves of maleate crystal form 3 of the compound shown in formula (I).

[0160] Figure 54 shows the X-ray powder diffraction pattern of crystal form 1 of the compound shown in formula (I).

[0161] Figure 55 shows the differential scanning calorimetry (DSC) spectrum of the 1,5-naphthalene disulfonate crystal form 1 of the compound shown in formula (I).

[0162] Figure 56 shows the thermogravimetric analysis curves of the 1,5-naphthalene disulfonate crystal form 1 of the compound shown in formula (I).

[0163] Figure 57 shows the isothermal adsorption curves of the 1,5-naphthalene disulfonate crystal form 1 of the compound shown in formula (I).

[0164] Figure 58 shows the X-ray powder diffraction pattern of crystal form 2 of the compound shown in formula (I).

[0165] Figure 59 shows the X-ray powder diffraction pattern of crystal form 3 of the compound shown in formula (I) 1,5-naphthalene disulfonate.

[0166] Figure 60 shows the X-ray powder diffraction pattern of crystal form 1 of the 2-naphthalenesulfonate of the compound shown in formula (I).

[0167] Figure 61 shows the differential scanning calorimetry (DSC) spectrum of the 2-naphthalenesulfonate crystal form 1 of the compound shown in formula (I).

[0168] Figure 62 shows the thermogravimetric analysis curves of the 2-naphthalenesulfonate crystal form 1 of the compound shown in formula (I).

[0169] Figure 63 shows the isothermal adsorption curves of the 2-naphthalenesulfonate crystal form 1 of the compound shown in formula (I).

[0170] Figure 64 shows the X-ray powder diffraction pattern of crystal form 2 of the compound shown in formula (I).

[0171] Figure 65 shows the X-ray powder diffraction pattern of the 2-naphthalenesulfonate crystal form 3 of the compound shown in formula (I).

[0172] Figure 66 shows the X-ray powder diffraction pattern of the sine naphthate crystal form 1 of the compound shown in formula (I).

[0173] Figure 67 shows the differential scanning calorimetry (DSC) spectrum of the chloronaphthalate crystal form 1 of the compound shown in formula (I).

[0174] Figure 68 shows the thermogravimetric analysis curves of the sine naphthate crystal form 1 of the compound shown in formula (I).

[0175] Figure 69 shows the isothermal adsorption curves of the naphthalene salt crystal form 1 of the compound shown in formula (I).

[0176] Figure 70 shows the X-ray powder diffraction pattern of camphor sulfonate crystal form 1 of the compound shown in formula (I).

[0177] Figure 71 shows the differential scanning calorimetry spectrum of camphor sulfonate crystal form 1 of the compound shown in formula (I).

[0178] Figure 72 shows the thermogravimetric analysis curves of camphor sulfonate crystal form 1 of the compound shown in formula (I).

[0179] Figure 73 shows the isothermal adsorption curves of camphor sulfonate crystal form 1 of the compound shown in formula (I).

[0180] Figure 74 shows the X-ray powder diffraction pattern of camphor sulfonate crystal form 2 of the compound shown in formula (I).

[0181] Figure 75 shows the differential scanning calorimetry (DSC) spectrum of camphor sulfonate crystal form 2 of the compound shown in formula (I).

[0182] Figure 76 shows the thermogravimetric analysis curves of camphor sulfonate crystal form 2 of the compound shown in formula (I).

[0183] Figure 77 shows the isothermal adsorption curves of camphor sulfonate crystal form 2 of the compound shown in formula (I).

[0184] Figure 78 shows the X-ray powder diffraction pattern of the dichloroacetate crystal form 1 of the compound shown in formula (I).

[0185] Figure 79 shows the differential scanning calorimetry (DSC) spectrum of the dichloroacetate crystal form 1 of the compound shown in formula (I).

[0186] Figure 80 shows the thermogravimetric analysis curves of dichloroacetate crystal form 1 of the compound shown in formula (I).

[0187] Figure 81 shows the isothermal adsorption curves of dichloroacetate crystal form 1 of the compound shown in formula (I).

[0188] Figure 82 shows the X-ray powder diffraction pattern of the ethanesulfonate crystal form 1 of the compound shown in formula (I).

[0189] Figure 83 shows the differential scanning calorimetry (DSC) spectrum of the ethanesulfonate crystal form 1 of the compound shown in formula (I).

[0190] Figure 84 shows the thermogravimetric analysis curves of the ethanesulfonate crystal form 1 of the compound shown in formula (I).

[0191] Figure 85 shows the isothermal adsorption curves of the ethanesulfonate crystal form 1 of the compound shown in formula (I).

[0192] Figure 86 shows the X-ray powder diffraction pattern of the ethanesulfonate crystal form 2 of the compound shown in formula (I).

[0193] Figure 87 shows the differential scanning calorimetry (DSC) spectrum of the ethanesulfonate crystal form 2 of the compound shown in formula (I).

[0194] Figure 88 shows the thermogravimetric analysis curves of the ethanesulfonate crystal form 2 of the compound shown in formula (I).

[0195] Figure 89 shows the isothermal adsorption curves of the ethanesulfonate crystal form 2 of the compound shown in formula (I).

[0196] Figure 90 shows the X-ray powder diffraction pattern of the hydrobromide crystal form 1 of the compound shown in formula (I).

[0197] Figure 91 shows the X-ray powder diffraction pattern of the hydrobromide crystal form 2 of the compound shown in formula (I).

[0198] Figure 92 shows the X-ray powder diffraction pattern of the methanesulfonate crystal form 1 of the compound shown in formula (I).

[0199] Figure 93 shows the differential scanning calorimetry (DSC) spectrum of the methanesulfonate crystal form 1 of the compound shown in formula (I).

[0200] Figure 94 shows the thermogravimetric analysis curves of the methanesulfonate crystal form 1 of the compound shown in formula (I).

[0201] Figure 95 shows the isothermal adsorption curves of the methanesulfonate crystal form 1 of the compound shown in formula (I).

[0202] Figure 96 shows the X-ray powder diffraction pattern of the nitrate crystal form 1 of the compound shown in formula (I).

[0203] Figure 97 shows the differential scanning calorimetry (DSC) spectrum of the nitrate crystal form 1 of the compound shown in formula (I).

[0204] Figure 98 shows the thermogravimetric analysis curves of the nitrate crystal form 1 of the compound shown in formula (I).

[0205] Figure 99 shows the isothermal adsorption curves of the nitrate crystal form 1 of the compound shown in formula (I).

[0206] Figure 100 shows the X-ray powder diffraction pattern of the trifluoroacetate crystal form 1 of the compound shown in formula (I).

[0207] Figure 101 shows the differential scanning calorimetry (DSC) spectrum of the trifluoroacetate crystal form 1 of the compound shown in formula (I).

[0208] Figure 102 shows the thermogravimetric analysis curves of the trifluoroacetate crystal form 1 of the compound shown in formula (I).

[0209] Figure 103 shows the isothermal adsorption curves of the trifluoroacetate crystal form 1 of the compound shown in formula (I).

[0210] Figure 104 shows the X-ray powder diffraction pattern of the trifluoroacetate crystal form 2 of the compound shown in formula (I).

[0211] Figure 105 shows the thermogravimetric analysis curves of the trifluoroacetate crystal form 2 of the compound shown in formula (I). Detailed Implementation

[0212] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but the scope of protection of the present invention includes, but is not limited to, these embodiments.

[0213] The structure of the compound was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) were expressed in 10⁻¹⁰ increments. -6The unit (ppm) is given. NMR measurements were performed using a Bruker Avance 111 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0214] MS was determined using (Agilent 6120B (ES1) and Aglent 6120B (APC1)).

[0215] The HPLC determination was performed using an Agilent 1260DAD high-performance liquid chromatograph (Ecl1pse Plus C18, 150×4.6mm).

[0216] The known starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as Titan Technology, Anaiji Chemical, Shanghai Demo, Chengdu Kelong Chemical, Shaoyuan Chemical Technology, and Bailingwei Technology.

[0217] The following detailed embodiments illustrate the implementation process and beneficial effects of the present invention, aiming to help readers better understand the essence and characteristics of the present invention, and are not intended to limit the scope of implementation of this case.

[0218] Example 1: Preparation of compound (I)

[0219] Step 1: Compound 61A (2.00 g, 8.96 mmol) was dissolved in dry toluene (60 mL), and pinacol borane (2.00 g, 15.61 mmol) was added dropwise, followed by bis(cyclopentadiene)zirconium hydride (0.46 g, 1.79 mmol). After the addition was complete, nitrogen gas was introduced, and the reaction was stirred at 65 °C for 18 h. TLC monitoring (petroleum ether: ethyl acetate = 2:1 (v / v)) showed that the reaction was complete. The reaction solution was concentrated to obtain compound 61B, which was used directly in the next step.

[0220] Step 2: Compounds 61B (3.14 g, 8.94 mmol) and 61a (3.96 g, 8.94 mmol) were dissolved in 1,4-dioxane (60 mL), followed by the addition of [1,1'-bis(diphenylphosphine)ferrocene]palladium(II) dichloride (0.65 g, 0.89 mmol), potassium carbonate (4.32 g, 31.29 mmol), and water (12 mL). After the addition was complete, the mixture was purged with nitrogen three times, and the reaction was stirred at 85 °C for 18 h. After the reaction was complete, water (50 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined and washed with saturated brine (40 mL × 1). After drying with anhydrous sodium sulfate, the mixture was filtered, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 2:1 (v / v)) to obtain compound 61C (1.4 g, yield: 30%).

[0221] LC-MS(ESI):m / z=463.10[M-56+H] + .

[0222] Step 3: Dissolve compound C (800 mg, 1.54 mmol) in dichloromethane (20 mL), add trifluoroacetic acid (5 mL), and react at room temperature for 2 h. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1 (v / v)) and the reaction was complete. The reaction solution was concentrated to obtain compound D (640 mg, crude product), which can be used directly in the next step without purification.

[0223] LC-MS (ESI): m / z = 419.10 [M+H] + .

[0224] Step 4: Compound 61D (640 mg, 1.53 mmol) was dissolved in dichloromethane (15 mL). Triethylamine (542 mg, 5.35 mmol) and cyclopropionyl chloride (240 mg, 2.30 mmol) were added sequentially under an ice-water bath. After the addition was complete, the reaction was continued under an ice-water bath for 2 h. The reaction was monitored by TLC (dichloromethane: methanol = 20:1 (v / v)) and found to be complete. The reaction solution was concentrated and the crude product was purified by column chromatography (eluent: dichloromethane: methanol = 65:1 (v / v)) to obtain compound (I) (87 mg, yield: 12%).

[0225] LCMS m / z = 487.7 [M+1] +

[0226] 1H NMR(400MHZ,DMSO-d6)δ8.30(s,1H),7.89(d,1H),7.62(s,1H),7.57(d,1H),7.47(d,1H),6.63(dd,1H),6.35(s,1H),6.11(d,1H ),4.03(s,4H),3.81(s,2H),3.49(s,1H),2.01(dd,1H),1.79(dd,4H),1.53-1.46(m,1H),1.26-1.15(m,4H),0.68-0.55(m,4H).

[0227] Example 2: Preparation of benzenesulfonate crystal form 1 of compound (I)

[0228] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; about 80 mg of benzenesulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain benzenesulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA, isothermal adsorption curve and DVS are shown in Figures 1-4 respectively.

[0229] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at 6.60 (d, J = 4.5Hz, 1H) is the -CH peak at position 23, and the peaks at 7.38-7.27 (m, 3H) are the -CH peaks of benzenesulfonic acid, with a ratio of 1:1. Therefore, the ratio of compound (I) to benzenesulfonic acid can be determined to be 1:1.

[0230] Example 3: Preparation of phosphate crystal form 1 of compound (I)

[0231] Take 200 mg of compound (I) sample, add 10 mL of acetonitrile to dissolve it, and obtain solution 1; about 52 mg of phosphoric acid, add 0.4 mL of acetonitrile to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain phosphate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 5-8.

[0232] Ion chromatography results showed that the free form reacted with phosphoric acid in a ratio of approximately 1:0.75 to form a salt.

[0233] Example 4: Preparation of phosphate crystal form 2 of compound (I)

[0234] Take 20 mg of compound (I) sample, add 0.5 mL of tetrahydrofuran and dissolve at 60 °C to obtain solution 1; take about 52 mg of phosphoric acid, add 0.2 mL of tetrahydrofuran and dissolve to obtain solution 2; at room temperature, add 0.02 mL of solution 2 dropwise to solution 1, and it precipitates immediately, sticking to the wall. After stirring for 5 min, it is basically dissolved. Stir at room temperature for 3 h and precipitate out in a gel-like state; add 2 mL of isopropyl ether, stir overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain phosphate crystal form 2 of compound (I), and its XRD pattern is shown in Figure 9.

[0235] Example 5: Preparation of phosphate crystal form 3 of compound (I)

[0236] Take 200 mg of compound (I) sample, add 5 mL of tetrahydrofuran to dissolve, to obtain solution 1; about 52 mg of phosphoric acid, add 0.4 mL of tetrahydrofuran to dissolve, to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, and it precipitates immediately. Stir for 10 min and it becomes transparent and sticks to the wall. Stir for 30 min and it becomes a suspension. Stir overnight at room temperature, centrifuge, and the obtained solid is vacuum dried overnight at 40 °C to obtain phosphate crystal form 3 of compound (I). Its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 10-13.

[0237] Ion chromatography results showed that the free form reacted with phosphoric acid in a ratio of approximately 1:1.31 to form a salt.

[0238] Example 6: Preparation of sulfate crystal form 1 of compound (I)

[0239] Take 20 mg of compound (I) sample, add 1 mL of ethanol and heat at 60 °C to dissolve it, to obtain solution 1; take about 45 mg of sulfuric acid, add 0.4 mL of ethanol to dissolve it, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, stir at 4 °C for 6 h and precipitate; stir at 4 °C overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain sulfate crystal form 1 of compound (I), and its XRD pattern is shown in Figure 14.

[0240] Example 7: Preparation of sulfate crystal form 2 of compound (I)

[0241] Take 200 mg of compound (I) sample and dissolve it in 5 mL of isopropanol to obtain solution 1; take about 45 mg of sulfuric acid and dissolve it in 0.4 mL of isopropanol to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, and a solid precipitates immediately, which is jelly-like. After stirring at room temperature for 2 h, add 10 mL of n-heptane; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain sulfate crystal form 2 of compound (I). Its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 15-18.

[0242] Ion chromatography results showed that the free form reacted with sulfuric acid at a ratio of approximately 1:0.84 to form a salt.

[0243] Example 8: Preparation of sulfate crystal form 3 of compound (I)

[0244] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 45 mg of sulfuric acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4 °C for 2 h to precipitate; stir at 4 °C overnight, centrifuge, and vacuum dry the obtained solid at 40 °C overnight to obtain sulfate crystal form 3 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 19-22.

[0245] Ion chromatography results showed that the free form reacted with sulfuric acid at a ratio of approximately 1:0.87 to form a salt.

[0246] Example 9: Preparation of p-toluenesulfonate crystal form 1 of compound (I)

[0247] Take 200 mg of compound (I) sample and dissolve it in 5 mL of ethanol to obtain solution 1; take about 78 mg of p-toluenesulfonic acid and dissolve it in 0.4 mL of ethanol to obtain solution 2; add solution 2 dropwise to solution 1 at room temperature, and it precipitates immediately; stir overnight at room temperature, centrifuge, and obtain p-toluenesulfonate crystal form 1 of compound (I), whose XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 23-26.

[0248] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at 6.58 (s, 1H) is the -CH peak at position 26, and the peak at 2.30 (d, J = 2.5Hz, 3H) is the -CH3 peak of p-toluenesulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to p-toluenesulfonic acid can be determined to be 1:1.

[0249] Example 10: Preparation of p-toluenesulfonate crystal form 2 of compound (I)

[0250] Take 20 mg of compound (I) sample, add 2 mL of isopropanol and heat at 60 °C to dissolve, to obtain solution 1; take about 78 mg of p-toluenesulfonic acid, add 0.4 mL of isopropanol to dissolve, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and vacuum dry the obtained solid at 40 °C overnight to obtain p-toluenesulfonate crystal form 2 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 27-30.

[0251] Example 11: Preparation of p-toluenesulfonate crystal form 3 of compound (I)

[0252] Take 20 mg of compound (I) sample, add 2 mL of water and heat at 60 °C to dissolve, to obtain solution 1; take about 78 mg of p-toluenesulfonic acid, add 0.4 mL of ethanol to dissolve, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and vacuum dry the obtained solid at 40 °C overnight to obtain p-toluenesulfonate crystal form 3 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 31-34.

[0253] Example 12: Preparation of ethylene disulfonate crystal form 1 of compound (I)

[0254] Take 20 mg of compound (I) sample, add 1 mL of ethanol and heat at 60 °C to dissolve it, to obtain solution 1; take about 86 mg of ethanedisulfonic acid, add 0.4 mL of ethanol to dissolve it, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, stir at 4 °C for 6 hours without precipitation, add 4 mL of n-heptane to precipitate; stir at 4 °C overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain ethanedisulfonate crystal form 1 of compound (I), the XRD pattern of which is shown in Figure 35.

[0255] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 26 (6.57 s, 1H) was the -CH peak, and the peak at position 2.63 (s, 4H) was the -CH2 peak of ethanedisulfonic acid. The ratio of these two peaks was 1:1. Therefore, the ratio of compound (I) to ethanedisulfonic acid was determined to be 1:1.

[0256] Example 13: Preparation of 2 crystal form of ethylene disulfonate of compound (I)

[0257] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 86 mg of ethanedisulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h and no precipitation occurs, then add 12 mL of n-heptane to precipitate; stir at 4℃ overnight, centrifuge, and the obtained solid is vacuum dried at 40℃ overnight to obtain ethanedisulfonate crystal form 2 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 36-39.

[0258] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 26 (6.57 s, 1H) was the -CH peak, and the peak at position 2.63 (s, 4H) was the -CH2 peak of ethanedisulfonic acid. The ratio of these two peaks was 1:1. Therefore, the ratio of compound (I) to ethanedisulfonic acid was determined to be 1:1.

[0259] Example 14: Preparation of 2-hydroxyethanesulfonic acid crystal form 1 of compound (I)

[0260] Take 20 mg of compound (I) sample, add 2 mL of acetonitrile and heat at 60 °C to dissolve, to obtain solution 1; take about 71 mg of 2-hydroxyethanesulfonic acid, add 0.4 mL of acetonitrile to dissolve, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, stir for 20 min and precipitate; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain 2-hydroxyethanesulfonic acid crystal form 1 of compound (I), and its XRD pattern is shown in Figure 40.

[0261] Example 15: Preparation of 2-hydroxyethanesulfonic acid crystal form 2 of compound (I)

[0262] Take 20 mg of compound (I) sample, add 1 mL of acetone and heat at 60 °C to dissolve it, to obtain solution 1; take about 71 mg of 2-hydroxyethanesulfonic acid, add 0.2 mL of acetone to dissolve it, to obtain solution 2; at room temperature, add 0.02 mL of solution 2 dropwise to solution 1, and it precipitates immediately. After stirring at room temperature for 3 h, it becomes jelly-like. Add 2 mL of isopropyl ether; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain 2-hydroxyethanesulfonic acid crystal form 2 of compound (I), and its XRD pattern is shown in Figure 41.

[0263] Example 16: Preparation of 2-hydroxyethanesulfonic acid crystal form 3 of compound (I)

[0264] Take 200 mg of compound (I) sample and dissolve it in 10 mL of acetonitrile to obtain solution 1; take about 71 mg of 2-hydroxyethanesulfonic acid and dissolve it in 0.4 mL of acetonitrile to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1 and stir for 10 min to precipitate; stir overnight at room temperature, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain 2-hydroxyethanesulfonic acid crystal form 3 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 42-45.

[0265] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.62 (d, J = 4.3Hz, 1H) is the -CH peak at position 23, and the peaks at positions 2.66-2.59 (m, 2H) are the -CH2 peaks of 2-hydroxyethanesulfonic acid. The ratio of these peaks is 1:1, thus the ratio of compound (I) to 2-hydroxyethanesulfonic acid can be determined to be 1:1.

[0266] Example 17: Preparation of maleate crystal form 1 of compound (I)

[0267] Take 20 mg of compound (I) sample, add 2 mL of acetonitrile and heat at 60 °C to dissolve, to obtain solution 1; take about 52 mg of maleic acid, add 0.2 mL of acetonitrile and 0.4 mL of ethanol to dissolve, to obtain solution 2; at room temperature, add 0.06 mL of solution 2 dropwise to solution 1, stir at 4 °C for 5 h and no precipitation occurs, add 12 mL of isopropyl ether to precipitate; stir at 4 °C overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain maleate crystal form 1 of compound (I), and its XRD pattern is shown in Figure 46.

[0268] Example 18: Preparation of maleate crystal form 2 of compound (I)

[0269] Take 200 mg of compound (I) sample, add 5 mL of acetone to dissolve it, and obtain solution 1; take about 52 mg of maleic acid, add 0.4 mL of acetone to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir for 10 min and precipitate; stir at room temperature overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain maleate crystal form 2 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 47-50.

[0270] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.42 (s, 1H) is the -CH peak at position 26, and the peak at position 6.25 (s, 2H) is the -CH peak of maleic acid, with a ratio of 1:1. Therefore, the ratio of compound (I) to maleic acid can be determined to be 1:1.

[0271] Example 19: Preparation of maleate crystal form 3 of compound (I)

[0272] Take 200 mg of compound (I) sample, add 10 mL of acetonitrile to dissolve, to obtain solution 1; take about 52 mg of maleic acid, add 0.4 mL of ethanol to dissolve, to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h, and precipitate; stir at 4℃ overnight, centrifuge, and the obtained solid is vacuum dried at 40℃ overnight to obtain maleate crystal form 3 of compound (I), whose XRD, DSC and TGA are shown in Figures 51-53.

[0273] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at 6.42 (s, 1H) is the -CH peak at position 26, and the peak at 6.25 (s, 3H) is the -CH peak of maleic acid, with a ratio of 1:1.5. Therefore, the ratio of compound (I) to maleic acid can be determined to be 1:1.5.

[0274] Example 20: Preparation of 1,5-naphthalenedisulfonate crystal form 1 of compound (I)

[0275] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 163 mg of 1,5-naphthalenedisulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir for 10 min to precipitate; stir at room temperature overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain 1,5-naphthalenedisulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 54-57.

[0276] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.61 (d, J = 5.6Hz, 1H) is the -CH peak at position 23, and the peak at position 7.41 (dt, J = 7.5, 4.6Hz, 2H) is the -CH peak of 1,5-naphthalenedisulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to 1,5-naphthalenedisulfonic acid can be determined to be 1:1.

[0277] Example 21: Preparation of 1,5-naphthalenedisulfonate crystal form 2 of compound (I)

[0278] Take 20 mg of compound (I) sample, add 0.5 mL of tetrahydrofuran and heat at 60 °C to dissolve it, to obtain solution 1; take about 163 mg of 1,5-naphthalenedisulfonic acid, add 0.4 mL of ethanol to dissolve it, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately in a gel-like state. After stirring for 3 h, it is suspended; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain 1,5-naphthalenedisulfonate crystal form 1 of compound (I), and its XRD pattern is shown in Figure 58.

[0279] Example 22: Preparation of 1,5-naphthalenedisulfonate crystal form 3 of compound (I)

[0280] Take 20 mg of compound (I) sample, add 1 mL of acetone and heat at 60 °C to dissolve it, to obtain solution 1; take about 163 mg of 1,5-naphthalenedisulfonic acid, add 0.4 mL of ethanol to dissolve it, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain 1,5-naphthalenedisulfonate crystal form 1 of compound (I), and its XRD pattern is shown in Figure 59.

[0281] Example 23: Preparation of 2-naphthalenesulfonate crystal form 1 of compound (I)

[0282] Take 200 mg of compound (I) sample, add 5 mL of isopropanol to dissolve, and obtain solution 1; take about 94 mg of 2-naphthalenesulfonic acid, add 0.4 mL of isopropanol to dissolve, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain 2-naphthalenesulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 60-63.

[0283] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at 6.15 (dd, J = 15.9, 3.0Hz, 1H) is the -CH peak at position 23, and the peaks at 7.82-7.99 (m, 6H) are the -CH peaks of 2-naphthalenesulfonic acid, with a ratio of 1:1.5. Therefore, the ratio of compound (I) to 2-naphthalenesulfonic acid can be determined to be 1:1.5.

[0284] Example 24: Preparation of 2-naphthalenesulfonate crystal form 2 of compound (I)

[0285] Take 20 mg of compound (I) sample, add 2 mL of isopropanol and heat at 60 °C to dissolve, to obtain solution 1; take about 94 mg of 2-naphthalenesulfonic acid, add 0.4 mL of isopropanol to dissolve, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and the obtained solid is vacuum dried at 40 °C overnight to obtain 2-naphthalenesulfonate crystal form 2 of compound (I), and its XRD pattern is shown in Figure 64.

[0286] Example 25: Preparation of 2-naphthalenesulfonate crystal form 3 of compound (I)

[0287] Take 20 mg of compound (I) sample, add 0.5 mL of tetrahydrofuran and heat at 60 °C to dissolve it, to obtain solution 1; take about 94 mg of 2-naphthalenesulfonic acid, add 0.4 mL of acetone to dissolve it, to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain 2-naphthalenesulfonate crystal form 3 of compound (I), and its XRD pattern is shown in Figure 65.

[0288] Example 26: Preparation of 1 crystal form of sine naphthate of compound (I)

[0289] Take 200 mg of compound (I) sample, add 10 mL of acetonitrile to dissolve, to obtain solution 1; take about 85 mg of sine and add 0.4 mL of ethanol to dissolve, to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir for 10 min to precipitate; stir overnight at room temperature, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain sine naphthate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 66-69.

[0290] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.38 (d, J = 2.0Hz, 1H) is the -CH peak at position 23, and the peak at position 8.30 (dd, J = 8.4, 2.8Hz, 1H) is the -CH peak of sinoacid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to sinoacid can be determined to be 1:1.

[0291] Example 27: Preparation of camphor sulfonate crystal form 1 of compound (I)

[0292] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 105 mg of camphor sulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h without precipitation, add 30 mL of n-heptane to precipitate; stir at 4℃ overnight, centrifuge, and the obtained solid is vacuum dried at 40℃ overnight to obtain camphor sulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 71-73.

[0293] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.15 (d, J = 16.0Hz, 1H) is the -CH peak at position 23, and the peak at position 1.05 (d, J = 2.5Hz, 4H) is the -CH peak of camphor sulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to camphor sulfonic acid can be determined to be 1:1.

[0294] Example 28: Preparation of camphor sulfonate crystal form 2 of compound (I)

[0295] Take 200 mg of compound (I) sample, add 10 mL of acetonitrile to dissolve, to obtain solution 1; take about 105 mg of camphor sulfonic acid, add 0.4 mL of ethanol to dissolve, to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4 °C for 2 h to precipitate; stir at 4 °C overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain camphor sulfonate crystal form 2 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 74-77.

[0296] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.15 (d, J = 16.0Hz, 1H) is the -CH peak at position 23, and the peak at position 1.05 (d, J = 2.5Hz, 7H) is the -CH peak of camphor sulfonic acid. The ratio of these two peaks is 1:2. Therefore, the ratio of compound (I) to camphor sulfonic acid can be determined to be 1:2.

[0297] Example 29: Preparation of dichloroacetate crystal form 1 of compound (I)

[0298] Take 200 mg of compound (I) sample and dissolve it in 5 mL of dichloromethane to obtain solution 1; take about 60 mg of dichloroacetic acid and dissolve it in 0.4 mL of dichloromethane to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1 and stir at 4 °C for 2 h to precipitate; stir at 4 °C overnight, centrifuge, and vacuum dry the obtained solid at 40 °C overnight to obtain dichloroacetic acid salt crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 78-81.

[0299] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.39 (s, 1H) is the -CH peak at position 26, and the peaks at positions 1.11-1.03 (m, 1H) are the -CH peaks of dichloroacetic acid, with a ratio of 1:1. Therefore, the ratio of compound (I) to dichloroacetic acid can be determined to be 1:1.

[0300] Example 30: Preparation of ethanesulfonate crystal form 1 of compound (I)

[0301] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 50 mg of ethanesulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h without precipitation, add 15 mL of n-heptane to precipitate; stir at 4℃ overnight, centrifuge, and the obtained solid is vacuum dried at 40℃ overnight to obtain ethanesulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 82-85.

[0302] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.15 (dd, J = 16.1, 2.8Hz, 1H) is the -CH peak at position 23, and the peak at position 1.06 (t, J = 7.4Hz, 4H) is the -CH2 peak of ethanesulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to ethanesulfonic acid can be determined to be 1:1.

[0303] Example 31: Preparation of ethanesulfonate crystal form 2 of compound (I)

[0304] Take 200 mg of compound (I) sample, add 10 mL of acetonitrile to dissolve, to obtain solution 1; take about 50 mg of ethanesulfonic acid, add 0.4 mL of acetonitrile to dissolve, to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h to precipitate; stir at 4℃ overnight, centrifuge, and vacuum dry the obtained solid at 40℃ overnight to obtain ethanesulfonate crystal form 2 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 86-89.

[0305] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.15 (dd, J = 16.1, 2.8Hz, 1H) is the -CH peak at position 23, and the peak at position 1.06 (t, J = 7.4Hz, 4H) is the -CH2 peak of ethanesulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to ethanesulfonic acid can be determined to be 1:1.

[0306] Example 32: Preparation of hydrobromide crystal form 1 of compound (I)

[0307] Take 20 mg of compound (I) sample, add 1 mL of ethanol and dissolve at 60 °C to obtain solution 1; take about 92 mg of hydrobromic acid, add 0.4 mL of ethanol and dissolve to obtain solution 2; at room temperature, add 0.04 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature overnight, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain hydrobromide crystal form 1 of compound (I), and its XRD pattern is shown in Figure 90.

[0308] Example 33: Preparation of hydrobromide crystal form 2 of compound (I)

[0309] Take 20 mg of compound (I) sample and dissolve it in 0.5 mL of dichloromethane to obtain solution 1; take about 92 mg of hydrobromic acid and dissolve it in 0.2 mL of dichloromethane to obtain solution 2; at room temperature, add 0.02 mL of solution 2 dropwise to solution 1, and it precipitates immediately; stir at room temperature for 3 h, add 1 mL of isopropyl ether, stir overnight at room temperature, centrifuge, and the resulting solid is vacuum dried overnight at 40 °C to obtain hydrobromide crystal form 2 of compound (I), and its XRD pattern is shown in Figure 91.

[0310] Example 34: Preparation of methanesulfonate crystal form 1 of compound (I)

[0311] Take 200 mg of compound (I) sample, add 5 mL of ethanol to dissolve it, and obtain solution 1; take about 55 mg of methanesulfonic acid, add 0.4 mL of ethanol to dissolve it, and obtain solution 2; at room temperature, add solution 2 dropwise to solution 1, stir at 4℃ for 2 h to precipitate; stir at 4℃ overnight, dry, add 1 mL of ethanol, crystallize at room temperature for 3 days, centrifuge, and the obtained solid is vacuum dried at 40℃ overnight to obtain methanesulfonate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 92-95.

[0312] Peak shift analysis by 1H NMR (400MHz, DMSO-d6) revealed that the chemical shift of compound (I) at position 6.58 (s, 1H) is the -CH peak at position 26, and the peak at position 2.32 (s, 4H) is the -CH3 peak of methanesulfonic acid. The ratio of these two peaks is 1:1. Therefore, the ratio of compound (I) to methanesulfonic acid can be determined to be 1:1.

[0313] Example 35: Preparation of nitrate crystal form 1 of compound (I)

[0314] Take 200 mg of compound (I) sample and dissolve it in 5 mL of dichloromethane to obtain solution 1; take about 43 mg of nitric acid and dissolve it in 0.4 mL of dichloromethane to obtain solution 2; add solution 2 dropwise to solution 1 at room temperature, and it precipitates immediately. Stir at room temperature for 2 h to form a gel, and add 10 mL of n-heptane; stir at room temperature overnight, centrifuge, and the resulting solid is vacuum dried at 40 °C overnight to obtain nitrate crystal form 1 of compound (I). Its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 96-99.

[0315] Ion chromatography results showed that the free form reacted with nitric acid in a ratio of approximately 1:0.69 to form a salt.

[0316] Example 36: Preparation of the trifluoroacetate crystal form 1 of compound (I)

[0317] Take 200 mg of compound (I) sample and dissolve it in 10 mL of acetonitrile to obtain solution 1; take about 44 mg of trifluoroacetic acid and dissolve it in 0.4 mL of acetonitrile to obtain solution 2; at room temperature, add solution 2 dropwise to solution 1 and stir at 4 °C for 2 h to precipitate; stir at 4 °C overnight, centrifuge, and vacuum dry the obtained solid at 40 °C overnight to obtain trifluoroacetate crystal form 1 of compound (I), and its XRD, DSC, TGA and isothermal adsorption curves are shown in Figures 100-103.

[0318] Ion chromatography results showed that the free state formed a salt with trifluoroacetic acid at a ratio of approximately 1:0.71.

[0319] Example 37: Preparation of the trifluoroacetate crystal form 2 of compound (I)

[0320] Take 200 mg of compound (I) sample and dissolve it in 5 mL of acetonitrile to obtain solution 1; take about 44 mg of trifluoroacetic acid and dissolve it in 0.2 mL of acetonitrile to obtain solution 2; add solution 2 dropwise to solution 1 at room temperature, and it precipitates immediately; stir overnight at room temperature, centrifuge, and dry the obtained solid under vacuum at 40 °C overnight to obtain the trifluoroacetate crystal form 2 of compound (I), whose XRD and TGA are shown in Figures 104-105.

[0321] X-ray powder diffraction (XRD) / DSC / TGA / DVS / ICC testing

[0322] Detailed XRD / DSC / TGA / DVS test parameters are shown in Table 1, and XRD data for each crystal form are shown in Tables 2 to 8.

[0323] Table 1 Test Instruments and Parameters

[0324] Table 2: List of XRD peaks for benzenesulfonate crystal form 1 of compound (I)

[0325] Table 3: List of XRD peaks for phosphate crystal form 1 of compound (I)

[0326] Table 4: List of XRD peaks for phosphate crystal form 2 of compound (I)

[0327] Table 5: List of XRD peaks for phosphate crystal form 3 of compound (I)

[0328] Table 6: List of XRD peaks for sulfate crystal form 1 of compound (I)

[0329] Table 7: List of XRD peaks for sulfate crystal form 2 of compound (I)

[0330] Table 8: List of XRD peaks for sulfate crystal form 3 of compound (I)

[0331] Table 9: List of XRD peaks for p-toluenesulfonate crystal form 1 of compound (I)

[0332] Table 10: List of XRD peaks for p-toluenesulfonate crystal form 2 of compound (I)

[0333] Table 11: List of XRD peaks for p-toluenesulfonate crystal form 3 of compound (I)

[0334] Table 12: List of XRD peaks for ethylene disulfonate crystal form 1 of compound (I)

[0335] Table 13: List of XRD peaks for ethylene disulfonate crystal form 2 of compound (I)

[0336] Table 14: List of XRD peaks for 2-hydroxyethanesulfonate crystal form 1 of compound (I)

[0337] Table 15: List of XRD peaks for 2-hydroxyethanesulfonate crystal form 2 of compound (I)

[0338] Table 16: List of XRD peaks for 2-hydroxyethanesulfonate crystal form 3 of compound (I)

[0339] Table 17: List of XRD peaks for maleate crystal form 1 of compound (I)

[0340] Table 18: List of XRD peaks for maleate crystal form 2 of compound (I)

[0341] Table 19: List of XRD peaks for maleate crystal form 3 of compound (I)

[0342] Table 20: List of XRD peaks for 1,5-naphthalenedisulfonate crystal form 1 of compound (I)

[0343] Table 21: XRD peak list of 1,5-naphthalenedisulfonate crystal form 2 of compound (I)

[0344] Table 22: List of XRD peaks for 1,5-naphthalenedisulfonate crystal form 3 of compound (I)

[0345] Table 23: List of XRD peaks for 2-naphthalenesulfonate crystal form 1 of compound (I)

[0346] Table 24: List of XRD peaks for 2-naphthalenesulfonate crystal form 2 of compound (I)

[0347] Table 25: List of XRD peaks for 2-naphthalenesulfonate crystal form 3 of compound (I)

[0348] Table 26: List of XRD peaks for chloronaphthalate crystal form 1 of compound (I)

[0349] Table 27: List of XRD peaks for camphor sulfonate crystal form 1 of compound (I)

[0350] Table 28: List of XRD peaks for camphor sulfonate crystal form 2 of compound (I)

[0351] Table 29: List of XRD peaks for dichloroacetate crystal form 1 of compound (I)

[0352] Table 30: List of XRD peaks for ethanesulfonate crystal form 1 of compound (I)

[0353] Table 31: List of XRD peaks for ethanesulfonate crystal form 2 of compound (I)

[0354] Table 32: List of XRD peaks for hydrobromide crystal form 1 of compound (I)

[0355] Table 33: List of XRD peaks for hydrobromide crystal form 2 of compound (I)

[0356] Table 34: List of XRD peaks for methanesulfonate crystal form 1 of compound (I)

[0357] Table 35: List of XRD peaks for nitrate crystal form 1 of compound (I)

[0358] Table 36: List of XRD peaks for the trifluoroacetate crystal form 1 of compound (I)

[0359] Table 37: List of XRD peaks for the trifluoroacetate crystal form 2 of compound (I)

[0360] Stability Study

[0361] Table 38. Solid-state stability experiment information table

[0362] Table 39. Results of Solid-State Stability Test

[0363] Conclusion: The crystal form of the salt of formula (I) of this invention has good stability.

[0364] Biological testing:

[0365] 1. Inhibitory effect of the compound on testosterone levels in NCI-H295R cells

[0366] The purpose of this study was to use enzyme-linked immunosorbent assay (ELISA) to detect the level of Testosterone in NCI-H295R cells, thereby evaluating the inhibitory effect of the compound on the level of Testosterone in NCI-H295R cells.

[0367] H295R cells were purchased from ATCC and cultured in DMEM (F12 + 10% FBS + 0.00625 mg / ml insulin + 0.00625 mg / ml transferrin + 6.25 ng / ml selenium + 1.25 mg / ml BSA + 0.00535 mg / ml linoleic acid) at 37°C in a 5% CO2 incubator. Cells in the exponential growth phase were collected and cultured for 3 days in hormone-deprived medium (phenol red-free 1640 + 1% PS + 10% CSS FBS + 1.25 mg / ml BSA + 0.00625 mg / ml insulin + 0.00625 mg / ml transferrin + 6.25 ng / ml selenium + 0.00535 mg / ml linoleic acid). On the third day, cells in the exponential growth phase were collected and plated with hormone-deprived medium to a concentration of 60,000 cells / well at a volume of 90 μL per well. Then, 10 μL of different concentrations of the compound were added, and the plates were incubated in a CO2 incubator for another 3 days. After incubation, following the instructions of the testosterone detection ELISA kit (Beyotime, PT872), 50 μL of cell culture supernatant was collected from each well and centrifuged at 500g for 5 min at room temperature. The supernatant was then collected. 25 μL of the sample was added to each well, followed by 75 μL of prepared horseradish peroxidase-labeled testosterone. The mixture was thoroughly mixed for 10 seconds, and the wells were sealed with white sealing film. The plates were incubated at room temperature in the dark for 120 min. The plate was then washed three times with 300 μl of liquid per well, and after the last wash, it was patted dry on thick absorbent paper. 100 μl of TMB solution was added per well, and the wells were sealed with white sealing film. The plate was incubated at room temperature in the dark for 15-20 min. Then, 50 μl of stop solution was added per well, and the OD450 absorbance was measured immediately after mixing. Absorbance readings were analyzed using Graphpad Prim 8.0 software, and an S-shaped concentration curve was plotted using a four-parameter nonlinear regression model to calculate the IC50. 50 The results were processed according to equation (1), and the inhibition rate of each concentration of the compound was calculated. Then, using Graphpad Prim 8.0 software, the IC50 concentration of the compound at an inhibition rate of 50% was calculated. 50 Value. Where RLU compound is the reading of the drug-treated group, and RLU control is the average value of the solvent control group. Inhibition rate % = 100 - RLU compound / RLU control × 100 Equation (1)

[0368] Table 40 Inhibitory effects of compounds on testosterone levels in NCI-H295R cells

[0369] NA: Not tested.

[0370] Conclusion: The compound of formula (I) of this invention has a significant inhibitory effect on the level of Testosterone in NCI-H295R cells.

[0371] 2. The purpose of this study is to use enzyme-linked immunosorbent assay (ELISA) to detect the level of pregnenolone in NCI-H295R cells, and to evaluate the inhibitory effect of the compound on the level of pregnenolone in NCI-H295R cells.

[0372] H295R cells were purchased from ATCC (CRL-2128) and cultured in DMEM (F12 + 10% FBS + 0.00625 mg / mL insulin + 0.00625 mg / mL transferrin + 6.25 ng / mL selenium + 1.25 mg / mL BSA + 0.00535 mg / mL linoleic acid) at 37°C in a 5% CO2 incubator. Cells in the exponential growth phase were collected and cultured for 3 days in hormone-deprived medium (phenol red 1640 + 1% PS + 10% CSS FBS + 1.25 mg / mL BSA + 0.00625 mg / mL insulin + 0.00625 mg / mL transferrin + 6.25 ng / mL selenium + 0.00535 mg / mL linoleic acid). On the third day, cells in the exponential growth phase were collected and plated with hormone-deprived medium to an appropriate concentration, resulting in 60,000 cells / well and a volume of 90 μL per well. Then, 10 μL of different concentrations of the compound were added, and the plates were incubated in a CO2 incubator for another 3 days. After incubation, the cell culture supernatant was collected and centrifuged at 800 × g for 10 min at 2-8℃. The supernatant was then analyzed according to the instructions of the pregnenolone detection ELISA kit (Antibodies-A73791), and the OD450 signal was read.

[0373] Data processing:

[0374] 2.1 Plot the standard curve. Plot the concentration of the standard on the x-axis and the OD450 value on the y-axis. Connect the coordinate points of each standard with a smooth line and fit the curve according to the 4-PL (four parameter logistic) method.

[0375] 2.2 Sample Quantification: The corresponding concentrations (CONC) of testosterone / pregnenolone in the sample were calculated using the absorbance value of the sample and the standard curve. The inhibition rates of each compound concentration were calculated according to equation (2). An S-shaped concentration curve was plotted using a three-parameter nonlinear regression model in Graphpad Prim 8.0 software, and the IC50 was calculated. 50The value is the concentration of the compound when the inhibition rate is 50%. Where CONC cpd is the concentration of the drug-treated group, and CONC ctrl is the average concentration of the solvent control group. Inhibition rate % = 100% - CONC cpd / CONC ctrl × 100% Equation (2)

[0376] Table 41 Inhibitory effects of compounds on Pregnenolone levels in NCI-H295R cells NA: Not tested.

[0377] Conclusion: The compound of formula (I) of this invention has a significant inhibitory effect on the level of Pregnenolone in NCI-H295R cells.

[0378] 3. Rat pharmacokinetic test

[0379] 3.1 Experimental animals: Male SD rats, approximately 220g, 6-8 weeks old, 6 rats / compound. Purchased from Chengdu Dashuo Experimental Animal Co., Ltd.

[0380] 3.2 Experimental Design: On the day of the experiment, SD rats were randomly divided into groups according to their body weight. They were fasted for 12-14 hours before drug administration but allowed free access to water. They were fed 4 hours after drug administration.

[0381] Table 42 Drug Administration Information

[0382] Intravenous administration solvent: 5% DMA + 5% HS-15 + 90% NS; Gavage administration solvent: 0.5% MC

[0383] Blood samples of 0.1 ml were collected via the orbital cavity before and after isoflurane anesthesia, placed in EDTAK2 centrifuge tubes, and centrifuged at 5000 rpm for 10 min at 4°C to collect plasma. Blood collection time points for the intravenous group: 0, 5, 15, 30 min, 1, 2, 4, 6, 8, 24 h; blood collection time points for the gavage group: 0, 5, 15, 30 min, 1, 2, 4, 6, 8, 24 h. All samples were stored at -80°C before analysis.

[0384] Table 43 Pharmacokinetic parameters of the tested compounds in rat plasma

[0385] Conclusion: The compound of formula (I) of this invention has good bioavailability and pharmacokinetic characteristics.

[0386] 4. Pharmacokinetic assays in mice

[0387] 4.1 Experimental animals: Male ICR mice, 20-25g, 6 mice / compound. Purchased from Chengdu Dashuo Experimental Animal Co., Ltd.

[0388] 4.2 Experimental Design: On the day of the experiment, ICR mice were randomly divided into groups according to their body weight. They were fasted for 12–14 hours before administration but allowed free access to water, and were fed 4 hours after administration.

[0389] Table 44 Drug Administration Information

[0390] Intravenous administration solvent: 5% DMA + 5% HS-15 + 90% NS; Gavage administration solvent: 0.5% MC

[0391] Blood samples of 0.06 mL were collected via the orbital cavity before and after isoflurane anesthesia, placed in EDTAK2 centrifuge tubes, and centrifuged at 5000 rpm for 10 min at 4°C to collect plasma. Blood collection time points for both the intravenous and gavage groups were 0, 5, 15, 30 min, 1, 2, 4, 7, and 24 h. All samples were stored at -80°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0392] Table 45 Pharmacokinetic parameters of the tested compounds in mouse plasma

[0393] Drug delivery solvent: 0.5% MC

[0394] Conclusion: The compound of formula (I) of this invention has good pharmacokinetic characteristics in mice.

Claims

1. A pharmaceutically acceptable salt of the compound shown in formula (I), 2. The pharmaceutically acceptable salt according to claim 1, wherein the salt is selected from maleate, 2-naphthalenesulfonate, 1,5-naphthalenedisulfonate, fumarate, hydrohalate, sulfate, phosphate, L-tartrate, citrate, L-malate, hippurate, D-glucuronate, glycolate, mucilage, succinate, lactate, orotate, pamoate, glycinate, alanine, arginine, cinnamate, benzoate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, valerate, triphenylacetate, L-proline, ferulic acid salt, 2-hydroxyethanesulfonate, mandelate, nitrate, and methanesulfonate. Malonate, gentianate, salicylate, oxalate, glutarate, ethanedisulfonate, sine, camphor sulfonate, dichloroacetate, ethanesulfonic acid, trifluoroacetate; preferably benzenesulfonate, L-malate, phosphate, sulfate, p-toluenesulfonate, hydrochloride, maleate, 2-naphthalenesulfonate, hydrobromide, methanesulfonate, citrate, mandelate, lactobionate, succinate, salicylate, 1,5-naphthalenedisulfonate, fumarate, nicotinate, hippurate, oxalate, 2-hydroxyethanesulfonate, ethanedisulfonate, sine, camphor sulfonate, dichloroacetate, ethanesulfonic acid, trifluoroacetate, nitrate.

3. The pharmaceutically acceptable salt according to claim 2, wherein the molar ratio of the compound shown in formula (I) to the acid anion of the pharmaceutically acceptable salt is 1:0.5 to 1:3.5, preferably 1:1, 1:2 or 1:

3.

4. The pharmaceutically usable salt according to claim 2, which is the benzenesulfonate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 16.57°±0.2°, 18.77°±0.2°; or has characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 13.35°±0.2°, 16.24°±0.2°, 16.57°±0.2°. 2°, 18.77°±0.2°, 20.24°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.74°±0.2°, 7.55°±0.2°, 11.38°±0.2°, 13.35°±0.2°, 16.24°±0.2°, 16.57°±0.2°, 17.83±0.2°, 18.77°±0.2°, 19.78°±0.2°, 20.24°±0.2°; 20.52°±0.2°, 21.60°±0.2°, 22.32°±0.2°; or their X-ray powder diffraction patterns are basically as shown in Figure 1.

5. The pharmaceutically usable salt according to claim 2, which is the phosphate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα radiation: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 18.74°±0.2°, 21.84°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 15.55°±0.2°, 17.29°±0.2°, 17.63°±0.2°. 18.74°±0.2°, 21.84°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.10°±0.2°, 6.20°±0.2°, 12.41°±0.2°, 15.55°±0.2°, 15.94±0.2°, 17.29°±0.2°, 17.63°±0.2°, 18.74°±0.2°, 20.86°±0.2°, 21.84°±0.2°, 23.62°±0.2°, 24.29°±0.2°, 33.83°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 5; Alternatively, it may be the phosphate crystal form 3 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 16.80°±0.2°, 17.25°±0.2°, 17.52°±0.2°, 20.53°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.92°±0.2°, 16.80°±0.2°, 17.04°±0.2°, 17.25°±0.2°, 17.52°±0.2°, 19.67°±0.2°. 2θ ± 0.2°, 20.53° ± 0.2°; or characteristic diffraction peaks at the following 2θ positions: 4.83° ± 0.2°, 14.92° ± 0.2°, 15.37° ± 0.2°, 15.59° ± 0.2°, 16.80° ± 0.2°, 17.04° ± 0.2°, 17.25° ± 0.2°, 17.52° ± 0.2°, 19.67° ± 0.2°, 20.53° ± 0.2°, 21.41° ± 0.2°, 22.09° ± 0.2°, 25.85° ± 0.2°; or their X-ray powder diffraction patterns are basically as shown in Figure 10.

6. The pharmaceutically usable salt according to claim 2, which is the sulfate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα radiation: 3.38°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°, 20.47°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 3.38°±0.2°, 6.14°±0.2°, 6.35°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°. 20.47°±0.2°, 27.42°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.38°±0.2°, 6.14°±0.2°, 6.35°±0.2°, 6.75°±0.2°, 10.18°±0.2°, 13.63°±0.2°, 15.48±0.2°, 16.77°±0.2°, 17.02°±0.2°, 20.47°±0.2°, 21.66°±0.2°, 27.42°±0.2°, 27.71°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 14; Alternatively, it may be the sulfate crystal form 3 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 18.15°±0.2°, 19.98°±0.2°, 20.55°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 18.15°±0.2°, 19.98°±0.2°, 20.55°±0.2°, 20.86°±0.2°, 21.48°. ±0.2°, 23.56°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.94°±0.2°, 9.92°±0.2°, 15.19°±0.2°, 18.15°±0.2°, 18.49°±0.2°, 18.89°±0.2°, 19.98°±0.2°, 20.55°±0.2°, 20.86°±0.2°, 21.48°±0.2°, 23.14°±0.2°, 23.56°±0.2°, 24.35°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 19.

7. The pharmaceutically usable salt according to claim 2, which is the p-toluenesulfonate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 20.72°±0.2°, 21.81°±0.2°; or has characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 13.02°±0.2°, 17.40°±0.2°, 18.77°±0.2°. 2°, 20.72°±0.2°, 21.81°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 3.75°±0.2°, 7.33°±0.2°, 10.96°±0.2°, 13.02°±0.2°, 15.11°±0.2°, 16.20°±0.2°, 16.75°±0.2°, 17.40°±0.2°, 18.77°±0.2°, 20.72°±0.2°, 21.53°±0.2°, 21.81°±0.2°, 23.82°±0.2°; or their X-ray powder diffraction patterns are basically as shown in Figure 23; Alternatively, it may be the p-toluenesulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 3.70°±0.2°, 14.43°±0.2°, 18.49°±0.2°, 20.45°±0.2°, 22.81°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 3.70°±0.2°, 7.08°±0.2°, 7.36°±0.2°, 14.43°±0.2°, 16.74°±0.2°, 18.49°±0.2°, 20.45°±0.2°, 22.81°±0.2°; or its X-ray powder diffraction pattern is essentially as shown in Figure 27. Alternatively, it may be the p-toluenesulfonate crystal form 3 of compound (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 4.29°±0.2°, 6.43°±0.2°, 17.38°±0.2°, 21.21°±0.2°, 23.06°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.29°±0.2°, 6.43°±0.2°, 17.38°±0.2°, 18.22°±0.2°, 19.03°±0.2°, 19.69°±0.2°, 21.21°±0.2°, 23.06°±0.2°; or its X-ray powder diffraction pattern is basically as shown in Figure 31.

8. The pharmaceutically usable salt according to claim 2, which is the ethylene disulfonate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 16.38°±0.2°, 18.22°±0.2°, 19.69°±0.2°, 20.00°±0.2°, 21.29°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 12.13°±0.2°, 16.38°±0.2°, 18.22°±0.2°, 19.06°±0.2°, 19.69°±0.2°, 20.00°±0.2°. 0.2°, 21.29°±0.2°, 21.60°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 12.13°±0.2°, 15.33±0.2°, 16.38°±0.2°, 17.90°±0.2°, 18.22°±0.2°, 19.06°±0.2°, 19.46°±0.2°, 19.69°±0.2°, 20.00°±0.2°, 21.29°±0.2°, 21.60°±0.2°, 21.88°±0.2°, 23.62°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 35; Alternatively, it may be the ethylene disulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 21.20°±0.2°, 23.02°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.81°±0.2°, 17.07°±0.2°, 17.84°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 21.20°±0.2°, 23.02°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 14.81°±0.2°, 17.07°±0.2°, 17.84°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 21.20°±0.2°, 23.02°±0.2°. 0°±0.2°, 23.02°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 7.42±0.2°, 14.81°±0.2°, 16.17°±0.2°, 17.07°±0.2°, 17.84°±0.2°, 19.12°±0.2°, 19.46°±0.2°, 19.84°±0.2°, 21.20°±0.2°, 22.49°±0.2°, 23.02°±0.2°, 24.57°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 36.

9. The pharmaceutically acceptable salt according to claim 2, which is the 2-hydroxyethanesulfonate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 3.80°±0.2°, 7.50°±0.2°, 18.99°±0.2°, 20.84°±0.2°, 21.73°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 3.80°±0.2°, 7.50°±0.2°, 16.38°±0.2°, 18.99°±0.2°, 20.41°±0.2°, 20.84°±0.2°. 0.2°, 21.73°±0.2°, 23.63°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.80°±0.2°, 7.50°±0.2°, 16.38°±0.2°, 17.42±0.2°, 17.92°±0.2°, 18.17°±0.2°, 18.99°±0.2°, 20.41°±0.2°, 20.84°±0.2°, 21.73°±0.2°, 23.63°±0.2°, 22.09°±0.2°, 25.33°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 40; Alternatively, it may be the 2-hydroxyethanesulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.25°±0.2°, 14.42°±0.2°, 20.32°±0.2°, 21.40°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.25°±0.2°, 14.42°±0.2°, 17.79°±0.2°, 20.32°±0.2°, 21.40°±0.2°, 23. 12°±0.2°, 24.84°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 5.74±0.2°, 7.25°±0.2°, 12.82°±0.2°, 14.42°±0.2°, 17.79°±0.2°, 18.70°±0.2°, 19.55°±0.2°, 20.32°±0.2°, 21.40°±0.2°, 21.57°±0.2°, 23.12°±0.2°, 24.84°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 41.

10. The pharmaceutically acceptable salt according to claim 2, which is the maleate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 9.70°±0.2°, 18.60°±0.2°, 19.52°±0.2°, 24.45°±0.2°, 28.23°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 9.70°±0.2°, 14.60°±0.2°, 16.95°±0.2°, 18.60°±0.2°, 19.52°±0.2°. 0.2°, 24.45°±0.2°, 28.23°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.83°±0.2°, 6.39±0.2°, 9.70°±0.2°, 14.00°±0.2°, 14.60°±0.2°, 16.95°±0.2°, 17.48°±0.2°, 18.60°±0.2°, 19.52°±0.2°, 23.77°±0.2°, 24.45°±0.2°, 28.23°±0.2°, 37.73°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 46; Alternatively, it may be the maleate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 16.72°±0.2°, 19.52°±0.2°, 21.56°±0.2°, 25.21°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 11.10°±0.2°, 16.72°±0.2°, 18.36°±0.2°, 19.52°±0.2°, 21.56°±0.2°, 25.21°±0.2°. 1°±0.2°, 28.07°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 8.32°±0.2°, 9.40±0.2°, 11.10°±0.2°, 16.72°±0.2°, 18.36°±0.2°, 19.52°±0.2°, 19.84°±0.2°, 21.12°±0.2°, 21.56°±0.2°, 22.38°±0.2°, 24.13°±0.2°, 25.21°±0.2°, 28.07°±0.2°; or their X-ray powder diffraction patterns are basically as shown in Figure 47; Alternatively, it may be the maleate crystal form 3 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 8.30°±0.2°, 8.85°±0.2°, 19.33°±0.2°, 23.75°±0.2°, 24.87°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 8.30°±0.2°, 8.85°±0.2°, 13.77°±0.2°, 16.57°±0.2°, 17.78°±0.2°, 19.33°±0.2°, 23.77°±0.2°. 5°±0.2°, 24.87°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 5.50±0.2°, 7.40°±0.2°, 8.30°±0.2°, 8.85°±0.2°, 10.35°±0.2°, 13.77°±0.2°, 16.57°±0.2°, 17.78°±0.2°, 19.33°±0.2°, 23.75°±0.2°, 24.87°±0.2°, 26.80°±0.2°, 27.66°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 51.

11. The pharmaceutically acceptable salt according to claim 2, which is the 1,5-naphthalenedisulfonate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 9.38°±0.2°, 14.11°±0.2°, 18.32°±0.2°, 21.37°±0.2°, 22.83°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 9.38°±0.2°, 14.11°±0.2°, 16.58°±0.2°, 18.06°±0.2°, 18.32°±0.2°, 21.37° ±0.2°, 22.52°±0.2°, 22.83°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 9.38°±0.2°, 14.11°±0.2°, 14.51°±0.2°, 16.58°±0.2°, 18.06°±0.2°, 18.32°±0.2°, 20.89°±0.2°, 21.37°±0.2°, 22.52°±0.2°, 22.83°±0.2°, 26.15°±0.2°, 28.81°±0.2°, 30.74°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 54; Alternatively, it may be the 1,5-naphthalenedisulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 9.33°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.26°±0.2°, 20.87°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.54°±0.2°, 5.36°±0.2°, 9.33°±0.2°, 18.70°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.87°±0.2°. 0.26°±0.2°, 20.87°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.54°±0.2°, 5.36°±0.2°, 9.33°±0.2°, 10.72±0.2°, 14.51°±0.2°, 18.70°±0.2°, 19.02°±0.2°, 19.77°±0.2°, 20.06°±0.2°, 20.26°±0.2°, 20.87°±0.2°, 24.93°±0.2°, 25.73°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 58; Alternatively, it may be the 1,5-naphthalenedisulfonate crystal form 3 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 5.02°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 15.27°±0.2°, 19.04°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 5.02°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 11.42°±0.2°, 15.27°±0.2°, 19.04°±0.2°, 1 9.94°±0.2°, 24.45°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.51±0.2°, 5.02°±0.2°, 8.64°±0.2°, 8.95°±0.2°, 9.19°±0.2°, 10.09°±0.2°, 11.42°±0.2°, 15.27°±0.2°, 17.41°±0.2°, 19.04°±0.2°, 19.94°±0.2°, 21.33°±0.2°, 24.45°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 59.

12. The pharmaceutically usable salt according to claim 2, which is the 2-naphthalenesulfonate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 3.63°±0.2°, 11.02°±0.2°, 14.74°±0.2°, 16.30°±0.2°, 20.13°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 3.63°±0.2°, 7.31°±0.2°, 11.02°±0.2°, 14.57°±0.2°, 14.74°±0.2°, 16.30°±0.2°. 0.2°, 17.92°±0.2°, 20.13°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.63°±0.2°, 7.31°±0.2°, 11.02°±0.2°, 14.57°±0.2°, 14.74°±0.2°, 16.30°±0.2°, 16.70±0.2°, 17.92°±0.2°, 18.55°±0.2°, 20.13°±0.2°, 20.82°±0.2°, 21.06°±0.2°, 21.62°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 60; Alternatively, it may be the 2-naphthalenesulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 22.00°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 16.79°±0.2°, 19.22°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 22.00°±0.2°. 0°±0.2°, 23.56°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 3.87°±0.2°, 13.35°±0.2°, 15.27°±0.2°, 16.40°±0.2°, 16.79°±0.2°, 17.50°±0.2°, 19.22°±0.2°, 20.28°±0.2°, 20.93°±0.2°, 21.18°±0.2°, 22.00°±0.2°, 22.59°±0.2°, 23.56°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 64; Alternatively, it may be the 2-naphthalenesulfonate crystal form 3 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.19°±0.2°, 10.83°±0.2°, 14.47°±0.2°, 16.03°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 3.59°±0.2°, 7.19°±0.2°, 10.83°±0.2°, 12.78°±0.2°, 14.47°±0.2°, 16.03°±0.2°, 16.33°±0.2°, 17.69°±0.2°; or its X-ray powder diffraction pattern is basically as shown in Figure 65.

13. The pharmaceutically usable salt according to claim 2, which is the chloronaphthalate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 8.93°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°, 18.00°±0.2°; or has characteristic diffraction peaks at the following 2θ positions: 4.98°±0.2°, 8.93°±0.2°, 11.52°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°. 2°, 18.00°±0.2°, 22.19°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.98°±0.2°, 8.93°±0.2°, 10.68°±0.2°, 11.52°±0.2°, 14.05°±0.2°, 15.93°±0.2°, 16.75°±0.2°, 17.18°±0.2°, 17.38°±0.2°, 18.00°±0.2°, 21.69°±0.2°, 22.19°±0.2°, 26.04°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 66.

14. The pharmaceutically usable salt according to claim 2, which is camphor sulfonate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα radiation: 8.77°±0.2°, 9.25°±0.2°, 16.03°±0.2°, 16.72°±0.2°, 17.63°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 8.34°±0.2°, 8.77°±0.2°, 9.02°±0.2°, 9.25°±0.2°, 11.18°±0.2°, 16.03°±0.2°. 0.2°, 16.72°±0.2°, 17.63°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 6.85±0.2°, 7.14°±0.2°, 8.34°±0.2°, 8.77°±0.2°, 9.02°±0.2°, 9.25°±0.2°, 11.18°±0.2°, 16.03°±0.2°, 16.72°±0.2°, 17.33°±0.2°, 17.63°±0.2°, 18.57°±0.2°, 25.67°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 70; Alternatively, it may be camphor sulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 3.78°±0.2°, 7.63°±0.2°, 11.50°±0.2°, 15.35°±0.2°, 17.94°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 3.78°±0.2°, 7.63°±0.2°, 9.76°±0.2°, 10.85°±0.2°, 11.50°±0.2°, 15.35°±0.2°, 17.94°±0.2°, 20.64°±0.2°; or its X-ray powder diffraction pattern is basically as shown in Figure 74.

15. The pharmaceutically usable salt according to claim 2, which is the dichloroacetate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°; or has characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 18.78°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°. 2°, 22.83°±0.2°, 23.02°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 7.99°±0.2°, 9.46°±0.2°, 16.07±0.2°, 18.78°±0.2°, 19.08°±0.2°, 20.21°±0.2°, 20.47°±0.2°, 20.93°±0.2°, 22.83°±0.2°, 23.02°±0.2°, 24.25°±0.2°, 26.99°±0.2°, 27.75°±0.2°; or have an X-ray powder diffraction pattern as shown in Figure 78.

16. The pharmaceutically usable salt according to claim 2, which is the ethanesulfonate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 20.17°±0.2°; or has characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 17.50°±0.2°, 17.79°±0.2°. 2°, 18.77°±0.2°, 20.17°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 4.01°±0.2°, 8.09°±0.2°, 12.39°±0.2°, 15.92°±0.2°, 17.50°±0.2°, 17.79°±0.2°, 18.36°±0.2°, 18.77°±0.2°, 20.17°±0.2°, 20.72°±0.2°, 21.59°±0.2°, 21.75°±0.2°, 27.62°±0.2°; or their X-ray powder diffraction patterns are basically as shown in Figure 83; Alternatively, it may be the ethanesulfonate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 12.51°±0.2°, 15.14°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 10.47°±0.2°, 12.51°±0.2°, 13.69°±0.2°, 15.14°. ±0.2°, 26.60°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 4.45°±0.2°, 7.46°±0.2°, 8.97°±0.2°, 10.47°±0.2°, 12.51°±0.2°, 13.69°±0.2°, 15.14°±0.2°, 17.88±0.2°, 19.29°±0.2°, 20.69°±0.2°, 21.53°±0.2°, 22.31°±0.2°, 26.60°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 86.

17. The pharmaceutically usable salt according to claim 2, which is the hydrobromide crystal form 2 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 6.20°±0.2°, 8.31°±0.2°, 10.39°±0.2°, 14.58°±0.2°, 20.89°±0.2°; or exhibits characteristic diffraction peaks at the following 2θ positions: 6.20°±0.2°, 8.31°±0.2°, 9.34°±0.2°, 10.39°±0.2°, 14.58°±0.2°, 20.89°±0.2°, 22.18°±0.2°, 22.51°±0.2°, 24.93±0.2°, 25.22°±0.2°, 27.31°±0.2°; or their X-ray powder diffraction patterns are basically shown in Figure 91.

18. The pharmaceutically usable salt according to claim 2, which is the methanesulfonate crystal form 1 of the compound shown in formula (I), and whose X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, has characteristic diffraction peaks at the following 2θ positions: 3.84°±0.2°, 7.76°±0.2°, 16.35°±0.2°, 17.43°±0.2°, 19.29°±0.2°; or has characteristic diffraction peaks at the following 2θ positions. Characteristic diffraction peaks: 3.84°±0.2°, 7.76°±0.2°, 16.35°±0.2°, 17.43°±0.2°, 19.29°±0.2°, 19.61°±0.2°, 20.41°±0.2°, 20.74°±0.2°, 20.89°±0.2°, 21.46°±0.2°; or their X-ray powder diffraction patterns are basically shown in Figure 92.

19. The pharmaceutically usable salt according to claim 2, which is the trifluoroacetate crystal form 1 of the compound shown in formula (I), exhibits characteristic diffraction peaks at the following 2θ positions in its X-ray powder diffraction pattern under Cu-Kα irradiation: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 18.82°±0.2°, 20.70°±0.2°; or characteristic diffraction peaks at the following 2θ positions: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 10.75°±0.2°, 18.82°±0.2°, 20.70°±0.2°. 21.08°±0.2°, 21.08°±0.2°, 24.32°±0.2°; or have characteristic diffraction peaks at the following 2θ positions: 5.32°±0.2°, 8.01°±0.2°, 9.71°±0.2°, 10.75°±0.2°, 18.82°±0.2°, 20.49°±0.2°, 20.70°±0.2°, 21.08°±0.2°, 21.52°±0.2°, 23.21°±0.2°, 24.32°±0.2°, 27.08°±0.2°, 29.88°±0.2°; or have an X-ray powder diffraction pattern basically as shown in Figure 100; Alternatively, it may be the trifluoroacetate crystal form 2 of the compound shown in formula (I), and its X-ray powder diffraction pattern, when subjected to Cu-Kα radiation, exhibits characteristic diffraction peaks at the following 2θ positions: 8.96°±0.2°, 17.73°±0.2°, 19.05°±0.2°, 19.31°±0.2°, 22.51°±0.2°; or it may exhibit characteristic diffraction peaks at the following 2θ positions: 6.13°±0.2°, 8.96°±0.2°, 12.30°±0.2°, 17.73°±0.2°, 19.05°±0.2°, 19.31°±0.2°, 22.51°±0.2°. 2θ ± 0.2°, 25.06° ± 0.2°; or have characteristic diffraction peaks at the following 2θ positions: 6.13° ± 0.2°, 8.96° ± 0.2°, 12.30° ± 0.2°, 12.85° ± 0.2°, 13.40° ± 0.2°, 14.62° ± 0.2°, 17.73° ± 0.2°, 19.05° ± 0.2°, 19.31° ± 0.2°, 20.51° ± 0.2°, 22.51° ± 0.2°, 24.36° ± 0.2°, 25.06° ± 0.2°; or have an X-ray powder diffraction pattern as shown in Figure 104.

20. A method for preparing a pharmaceutically acceptable salt of a compound of formula (I), comprising the step of forming a salt with an acid and the compound of formula (I); wherein the pharmaceutically acceptable salt is selected from maleate, 2-naphthalenesulfonate, 1,5-naphthalenedisulfonate, fumarate, hydrohalate, sulfate, phosphate, L-tartrate, citrate, L-malate, hippurate, D-glucuronate, glycolate, mucilage, succinate, lactate, orotate, pamoate, glycinate, alanine, arginine, cinnamate, benzoate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, valerate, triphenylacetate, L-proline, ferulic acid, 2-hydroxyethanesulfonate, Mandelates, nitrates, methanesulfonates, malonates, gentianates, salicylates, oxalates, glutarates, ethanedisulfonates, sine, camphor sulfonates, dichloroacetate, ethanesulfonic acid, trifluoroacetate; preferably from benzenesulfonates, L-malates, phosphates, sulfates, p-toluenesulfonates, hydrochlorides, maleates, 2-naphthalenesulfonates, hydrobromide, methanesulfonates, citrates, mandelates, lactobionates, succinates, salicylates, 1,5-naphthalenedisulfonates, fumarates, nicotinates, hippurates, oxalates, 2-hydroxyethanesulfonates, ethanedisulfonates, sine, camphor sulfonates, dichloroacetate, ethanesulfonic acid, trifluoroacetate, nitrates; more preferably from hydrochlorides; 21. The preparation method according to claim 20, wherein, The crystallization solvent used for crystallizing the pharmaceutically acceptable salt is selected from C. 1-6 Halogenated alkane solvents, C 2-6 Ester solvents, C 2-6 Ether solvents, C 1-6 One or more of alcohols or water.

22. The preparation method according to claim 21, wherein, The crystallization solvent is selected from one or more of dichloromethane, 1,2-dichloroethane, ethyl acetate, methanol, ethanol, isopropanol, propanol, diethyl ether, tetrahydrofuran, and water.

23. A pharmaceutical composition comprising a therapeutically effective amount of any one of claims 1-19, a salt or crystal form, and a pharmaceutically acceptable carrier and / or excipient, wherein the therapeutically effective amount is preferably 1-1500 mg.

24. Use of the salt or crystal form of any one of claims 1-19, or the pharmaceutical composition of claim 23, in the preparation of a medicament for treating or preventing CYP11A1-mediated diseases.

25. A method for treating or preventing CYP11A1-mediated diseases, the method comprising administering to a subject a therapeutically effective amount of the salt or crystal form of any one of claims 1-19, or the pharmaceutical composition of claim 23, wherein the therapeutically effective amount is preferably 1-1500 mg.

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