A crystal form of a heterocyclic compound, a preparation method therefor, and applications thereof

Abstract

A heterocyclic compound, its preparation method, and its application are disclosed. The heterocyclic compound is the compound shown in Formula I. Its crystal form, when subjected to Cu-Kα radiation and expressed as a 2θ angle X-ray powder diffraction pattern, exhibits diffraction peaks at 8.95±0.20°, 12.92±0.20°, 16.39±0.20°, 17.01±0.20°, 17.44±0.20°, 17.76±0.20°, 18.08±0.20°, 19.02±0.20°, 21.95±0.20°, 22.20±0.20°, 23.49±0.20°, 24.15±0.20°, 24.92±0.20°, 25.94±0.20°, 27.14±0.20°, and 29.68±0.20°. The crystal form of this heterocyclic compound has one or more of the following advantages: good chemical stability, good physical stability, good drug development prospects, and good processability in formulation.

Description

[0001] This application claims priority to Chinese patent application 202210938910.9, filed on August 5, 2022. The entire contents of the aforementioned Chinese patent application are incorporated herein by reference. Technical Field

[0002] This invention relates to a crystal form of a heterocyclic compound, its preparation method, and its application. Background Technology

[0003] Cation channels (such as the transient receptor potential (TRP) cation channel subfamily C, member 5 (TRPC5)) regulate the flow of calcium and sodium ions across the cell membrane. The influx of sodium and calcium leads to cellular depolarization. This increases the likelihood that voltage-gated ion channels will reach the threshold required for activation. Therefore, activation of nonselective cation channels can increase electrical excitability and the frequency of voltage-dependent events. Voltage-dependent events include, but are not limited to, neuronal action potentials, cardiac action potentials, smooth muscle contraction, cardiac contraction, and skeletal muscle contraction.

[0004] Calcium influx induced by activation of nonselective cation channels (such as TRPC5) also alters intracellular free calcium concentration. Calcium is a ubiquitous second messenger molecule in cells, and changes in intracellular calcium levels have profound effects on signal transduction and gene expression. Therefore, activation of nonselective cation channels (such as TRPC5) can lead to changes in gene expression and cell phenotype. Gene expression events include, but are not limited to, the production of mRNAs encoding cell surface receptors, ion channels, and kinases. These changes in gene expression can lead to hyperexcitability in the cell.

[0005] The homopolymer TRPC5 ion channel is a signal transduction gating and Ca2+ ion channel primarily expressed in neurons. 2+ TRPC5 can be formed through channels. It can form homopolymeric multi-subunit structures (such as tetramers (i.e., TRPC5 homopolymers)) and heteropolymeric multi-subunit structures (such as tetramers (i.e., TRPC5-TRPC1 heteropolymers)). Unless explicitly stated otherwise, when the term TRPC5 is used herein (e.g., when identifying modulators of TRPC5, such as TRPC5 antagonists), the term TRPC5 is used generally to include one or both of the TRPC5 homopolymers or heteropolymers (e.g., TRPC5-TPRC1 or TRPC5-TRPC4 heteropolymers).

[0006] Modulating the function of TRPC5 protein provides a means of regulating calcium homeostasis, sodium homeostasis, membrane polarization and / or intracellular calcium levels, and compounds that can modulate TRPC5 function can be used in many ways, including but not limited to maintaining calcium homeostasis, regulating intracellular calcium levels, regulating membrane polarization, and treating or preventing diseases, symptoms or conditions related to calcium and / or sodium homeostasis or dyshomeostasis.

[0007] Compounds that inhibit TRPC5 containing ion channels are suitable for treating conditions by modulating the activity of transient receptor potential cation channel subfamily C, member 5 (TRPC5), which can exist in homomeric form and heteromeric form with other ion channels (such as TRPC1 or TRPC3) (i.e., TRPC5-TRPC1 and TRPC1-TRPC3-TRPC5).

[0008] TRPC5 is associated with diseases such as FSGS and diabetic nephropathy (J. Clin. Invest., 2 Dec 2, 2013; 123(12): 5298-5309, Zhou et al., Science 358, 1332-1336 (2017). Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome, clinically manifested as massive proteinuria or nephrotic syndrome, pathologically characterized by focal segmental glomerular sclerosis lesions and podocyte degeneration leading to fusion or disappearance of foot processes. FSGS accounts for approximately 5% to 10% of nephrotic syndrome in Chinese adults, and is more common in young and middle-aged men. More than 50% of patients with persistent nephrotic syndrome progress to end-stage renal disease within 5 to 10 years.

[0009] In a healthy glomerulus, TRPC5 is isolated in the cytoplasm, maintaining normal filtration. When podocytes are injured, the injury activates RAC1, causing TRPC5 to translocate from the cytoplasm to the cell membrane. This promotes AT1 receptor-induced calcium ion influx through the TRPC5 channel, further promoting RAC1 activity. RAC1 activation induces actin remodeling and detachment of podocytes from the glomerulus. The loss of podocytes disrupts the filtration barrier, allowing serum proteins to leak into the urine.

[0010] Currently used clinical treatments for FSGS mainly include hormones, immunosuppressants, CNIs, and alkylating agents, all of which have serious toxic side effects, and many require combination therapy with other drugs to be effective, leading to a high relapse rate. Therefore, developing new TRPC5 inhibitors is of great significance for the treatment of these diseases. Simultaneously, developing drug forms suitable for these compounds, such as those improving stability (e.g., storage stability), hygroscopicity, and / or efficacy (e.g., bioavailability), to achieve good results in both the manufacturing and administration stages, is a pressing technical challenge. Summary of the Invention

[0011] The technical problem this invention aims to solve is the shortcomings of existing TRPC5 inhibitors, namely, the limited variety of drugs, poor efficacy, and the scarcity of heterocyclic compound crystal forms. Therefore, this invention provides a heterocyclic compound crystal form, its preparation method, and its applications. The heterocyclic compound crystal form of this invention has one or more of the following advantages: good chemical stability, good physical stability, good drug development prospects, and good formulation processability.

[0012] This invention provides a crystal form B of the compound shown in Formula I, whose X-ray powder diffraction pattern, expressed as 2θ angle using Cu-Kα radiation, shows diffraction peaks at 8.95±0.20°, 12.92±0.20°, 16.39±0.20°, 17.01±0.20°, 17.44±0.20°, 17.76±0.20°, 18.08±0.20°, 19.02±0.20°, 21.95±0.20°, 22.20±0.20°, 23.49±0.20°, 24.15±0.20°, 24.92±0.20°, 25.94±0.20°, 27.14±0.20°, and 29.68±0.20°.

[0013] .

[0014] In some embodiments, the crystal form B of the compound shown in Formula I, when subjected to Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 10.63±0.20°, 11.69±0.20°, 13.52±0.20°, 14.49±0.20°, 14.74±0.20°, 15.83±0.20°, 18.81±0.20°, 19.72±0.20°, 21.27±0.20°, 22.62±0.20°, 22.99±0.20°, 25.41±0.20°, 25.74±0.20°, 26.18±0.20°, 26.58±0.20°, 27.85 ±0.20°, 28.23±0.20°, 28.70±0.20°, 29.16±0.20°, 30.17±0.20°, 30.51±0.20°, 31.20±0.20°, 32.16±0.20°, 32.52±0.20°, 32.74±0.20°, 32.89±0. 20°, 34.36±0.20°, 35.45±0.20°, 35.98±0.20°, 36.65±0.20°, 37.00±0.20°, 37.45±0.20°, 37.73±0.20°, 38.04±0.20°, 38.36±0.20° and 39.11±0.20°.

[0015] In some embodiments, the crystal form B of the compound shown in Formula I is analyzed using Cu-Kα radiation, and X-ray powder diffraction patterns expressed at 2θ angles at 8.95±0.20°, 10.63±0.20°, 11.69±0.20°, 12.92±0.20°, 13.52±0.20°, 14.49±0.20°, 14.74±0.20°, 15.83±0.20°, 16.39±0.20°, 17.01±0.20°, 17 0.44±0.20°, 17.76±0.20°, 18.08±0.20°, 18.81±0.20°, 19.02±0.20°, 19.72±0.20°, 21.27±0.20°, 21.95±0.20°, 22.20±0.20°, 22.62±0.20°, 22.99±0.20°, 23.49±0.20°, 24.15±0.20°, 24.92±0.20°, 25. 41±0.20°, 25.74±0.20°, 25.94±0.20°, 26.18±0.20°, 26.58±0.20°, 27.14±0.20°, 27.85±0.20°, 28.23±0.20°, 28.70±0.20°, 29.16±0.20°, 29.68±0.20°, 30.17±0.20°, 30.51±0.20°, 31.20±0.20°, 32.1 Diffraction peaks are observed at 6±0.20°, 32.52±0.20°, 32.74±0.20°, 32.89±0.20°, 34.36±0.20°, 35.45±0.20°, 35.98±0.20°, 36.65±0.20°, 37.00±0.20°, 37.45±0.20°, 37.73±0.20°, 38.04±0.20°, 38.36±0.20°, and 39.11±0.20°.

[0016] In some embodiments, the crystal form B of the compound shown in Formula I has the diffraction peaks shown in Table 2 in the X-ray powder diffraction pattern of Cu-Kα radiation, expressed in 2θ angle.

[0017] In some embodiments, the crystal form B of the compound represented by Formula I is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows: Figure 8 As shown.

[0018] In some embodiments, the differential scanning calorimetry (DSC) curve of crystal form B of the compound shown in Formula I has an endothermic peak at 247.7°C ± 3°C.

[0019] In some embodiments, the differential scanning calorimetry (DSC) curve of crystal form B of the compound represented by Formula I is as follows: Figure 9 As shown.

[0020] In some embodiments, the thermogravimetric analysis (TGA) curve of crystal form B of the compound shown in Formula I shows a weight loss of 1.0% in the temperature range of 35°C ± 3°C to 220°C ± 3°C.

[0021] In some embodiments, the thermogravimetric analysis curve of crystal form B of the compound represented by Formula I is as follows: Figure 10 As shown.

[0022] In some embodiments, the crystal form B of the compound represented by Formula I is a solvent-free compound.

[0023] In some embodiments, the crystal form B of the compound represented by Formula I is a solvent-free compound, wherein the solvent is, for example, water, trifluoroacetic acid, or dichloromethane.

[0024] This invention provides solvates of compounds represented by Formula I, which are solvates represented by Formula IA, Formula IR, or Formula IT.

[0025] or

[0026] Where a is 0.50-1.50; r is 3.00-6.00; and t is 1.00-5.00.

[0027] In some embodiments, in the solvate represented by formula IA, a is 0.70, 0.75, 0.78, 0.79, or 0.80.

[0028] In some embodiments, a is 0.79, and the crystal form A of the solvate represented by formula IA has diffraction peaks at 3.91±0.20°, 7.78±0.20°, 12.66±0.20°, 13.60±0.20°, 14.20±0.20°, 15.48±0.20°, 17.66±0.20°, 18.66±0.20°, 19.13±0.20°, 19.64±0.20°, 22.76±0.20°, 23.76±0.20°, 24.30±0.20°, 25.37±0.20°, and 27.78±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0029] In some embodiments, α is 0.79, and the crystal form A of the solvate represented by formula IA, when irradiated with Cu-Kα and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 4.18±0.20°, 8.36±0.20°, 11.67±0.20°, 13.83±0.20°, 14.57±0.20°, 15.05±0.20°, 16.39±0.20°, 17.51±0.20°, 18.16±0.20°, 21.06±0.20°, 22.23±0.20°, 23.45±0.20°, 24.52±0.20°, 25.08±0. 0.20°, 25.57±0.20°, 26.01±0.20°, 26.97±0.20°, 27.33±0.20°, 28.36±0.20°, 28.59±0.20°, 29.14±0.20°, 30.36±0.20°, 31.15±0.20°, 31.41±0.20°, 31.93±0.20°, 32.86±0.20°, 33.11±0.20°, 33.64±0.20°, 35.27±0.20°, 35.80±0.20°, 36.54±0.20°, 38.97±0.20° and 39.43±0.20°.

[0030] In some embodiments, a is 0.79, and the crystal form A of the solvate represented by formula IA is obtained using Cu-Kα radiation and X-ray powder diffraction patterns expressed at 2θ angles at 3.91±0.20°, 4.18±0.20°, 7.78±0.20°, 8.36±0.20°, 11.67±0.20°, 12.66±0.20°, 13.60±0.20°, 13.83±0.20°, and 14.20±0.20°. 0°, 14.57±0.20°, 15.05±0.20°, 15.48±0.20°, 16.39±0.20°, 17.51±0.20°, 17.66±0.20°, 18.16±0.20°, 18.66±0.20°, 19.13±0.20°, 19.64±0.20°, 21.06±0.20°, 22.23±0.20°, 22.76±0.20° 23.45±0.20°, 23.76±0.20°, 24.30±0.20°, 24.52±0.20°, 25.08±0.20°, 25.37±0.20°, 25.57±0.20°, 26.01±0.20°, 26.97±0.20°, 27.33±0.20°, 27.78±0.20°, 28.36±0.20°, 28.59±0.20°, 29 Diffraction peaks are observed at 0.14±0.20°, 30.36±0.20°, 31.15±0.20°, 31.41±0.20°, 31.93±0.20°, 32.86±0.20°, 33.11±0.20°, 33.64±0.20°, 35.27±0.20°, 35.80±0.20°, 36.54±0.20°, 38.97±0.20°, and 39.43±0.20°.

[0031] In some embodiments, a is 0.79, and the crystal form A of the solvate represented by formula IA has the diffraction peaks shown in Table 1 in the X-ray powder diffraction pattern expressed in 2θ angle using Cu-Kα radiation.

[0032] In some embodiments, a is 0.79, and the crystal form A of the solvate represented by formula IA is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 1 As shown.

[0033] In some embodiments, a is 0.79, and the differential scanning calorimetry (DSC) curve of crystal form A of the solvate represented by formula IA has endothermic peaks at 60.1°C ± 3°C, 189.7°C ± 3°C, and 204.5°C ± 3°C.

[0034] In some embodiments, a is 0.79, and the differential scanning calorimetry curve of crystal form A of the solvate represented by formula IA is as follows: Figure 2 As shown.

[0035] In some embodiments, a is 0.79, and the thermogravimetric analysis (TGA) curve of crystal form A of the solvate represented by formula IA shows a weight loss of 2.4% in the temperature range of 34°C ± 3°C to 180°C ± 3°C.

[0036] In some embodiments, a is 0.79, and the thermogravimetric analysis curve of crystal form A of the solvate represented by formula IA is as follows. Figure 3 As shown.

[0037] In some embodiments, the crystal form A of the solvate represented by formula IA may be the crystal form of the hydrate.

[0038] In some implementations, a is 0.79, and the solvate represented by formula IA is crystalline.

[0039] In some embodiments, in the solvate represented by formula IR, r is 3.80, 4.00, 4.10, 4.20, or 4.30.

[0040] In some embodiments, r is 4.10, and the crystal form R of the solvate represented by formula IR, when irradiated with Cu-Kα radiation, has diffraction peaks at 11.88±0.20°, 14.49±0.20°, 15.57±0.20°, 16.62±0.20°, 19.45±0.20°, 19.82±0.20°, 20.48±0.20°, 23.79±0.20°, 24.63±0.20°, 26.41±0.20°, 26.84±0.20°, 27.09±0.20°, 27.77±0.20°, and 29.86±0.20°.

[0041] In some embodiments, r is 4.10, and the crystal form R of the solvate represented by formula IR, when irradiated with Cu-Kα radiation and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 4.11±0.20°, 6.38±0.20°, 6.71±0.20°, 12.27±0.20°, 13.31±0.20°, 13.85±0.20°, 19.00±0.20°, 21.1±0.20°, 22.37±0.20°, 22.7±0.20°. 0°, 23.37±0.20°, 24.40±0.20°, 25.74±0.20°, 26.16±0.20°, 28.23±0.20°, 28.86±0.20°, 31.04±0.20°, 31.78±0.20°, 32.95±0.20°, 33.72±0.20°, 34.95±0.20°, 35.32±0.20°, 36.43±0.20°, 37.22±0.20° and 38.58±0.20°.

[0042] In some embodiments, r is 4.10, and the crystal form R of the solvate represented by formula IR is obtained by Cu-Kα radiation and X-ray powder diffraction patterns expressed in 2θ angles at 4.11±0.20°, 6.38±0.20°, 6.71±0.20°, 11.88±0.20°, 12.27±0.20°, 13.31±0.20°, and 13.85°. ±0.20°, 14.49±0.20°, 15.57±0.20°, 16.62±0.20°, 19.00±0.20°, 19.45±0.20°, 19.82±0.20°, 20.48±0.20°, 21.10±0.20°, 22.37±0.20°, 22.70±0.20°, 23.37 ±0.20°, 23.79±0.20°, 24.40±0.20°, 24.63±0.20°, 25.74±0.20°, 26.16±0.20°, 26.41±0.20°, 26.84±0.20°, 27.09±0.20°, 27.77±0.20°, 28.23±0.20°, 28.86 Diffraction peaks are observed at ±0.20°, 29.86±0.20°, 31.04±0.20°, 31.78±0.20°, 32.95±0.20°, 33.72±0.20°, 34.95±0.20°, 35.32±0.20°, 36.43±0.20°, 37.22±0.20°, and 38.58±0.20°.

[0043] In some embodiments, r is 4.10, and the crystal form R of the solvate represented by formula IR is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 60 As shown.

[0044] In some embodiments, r is 4.10, and the differential scanning calorimetry (DSC) curve of the crystal form R of the solvate represented by formula IR has endothermic peaks at 87.1°C ± 3°C and 182.4°C ± 3°C.

[0045] In some embodiments, r is 4.10, and the differential scanning calorimetry curve of the crystal form R of the solvate represented by formula IR is as follows: Figure 61 As shown.

[0046] In some embodiments, r is 4.10, and the thermogravimetric analysis (TGA) curve of the crystal form R of the solvate represented by formula IR shows a weight loss of 5.8% in the temperature range of 34°C ± 3°C to 140°C ± 3°C.

[0047] In some embodiments, r is 4.10, and the thermogravimetric analysis curve of the crystal form R of the solvate represented by formula IR is as follows. Figure 62 As shown.

[0048] In some embodiments, the crystal form R of the solvate represented by formula IR can be the crystal form of the hydrate.

[0049] In some embodiments, r is 4.10, and the solvate represented by formula IR is crystalline.

[0050] In some embodiments, in the solvate represented by formula IT, t is 2.00, 2.50, 2.80, 2.85, or 2.90.

[0051] In some embodiments, t is 2.85, and the crystal form T of the solvate represented by formula IT has diffraction peaks at 3.71±0.20°, 15.31±0.20°, 15.86±0.20°, 16.50±0.20°, 18.48±0.20°, 18.79±0.20°, 20.89±0.20°, 22.22±0.20°, 24.70±0.20°, 25.00±0.20°, and 25.52±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0052] In some embodiments, t is 2.85, and the crystal form T of the solvate represented by formula IT, when irradiated with Cu-Kα and expressed in 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 7.25±0.20°, 14.96±0.20°, 19.81±0.20°, 21.92±0.20°, 23.40±0.20°, and 34.92±0.20°.

[0053] In some embodiments, t is 2.85, and the crystal form T of the solvate represented by formula IT is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 3.71±0.20°, 7.25±0.20°, 14.96±0.20°, 15.31±0.20°, 15.86±0.20°, 16.50±0.20°, and 18.48°. Diffraction peaks are observed at ±0.20°, 18.79±0.20°, 19.81±0.20°, 20.89±0.20°, 21.92±0.20°, 22.22±0.20°, 23.40±0.20°, 24.70±0.20°, 25.00±0.20°, 25.52±0.20°, and 34.92±0.20°.

[0054] In some embodiments, t is 2.85, and the crystal form T of the solvate represented by formula IT is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 68 As shown.

[0055] In some embodiments, t is 2.85, and the differential scanning calorimetry (DSC) curve of the crystal form T of the solvate represented by formula IT has endothermic peaks at 65.1°C ± 3°C and 181.5°C ± 3°C.

[0056] In some embodiments, t is 2.85, and the differential scanning calorimetry curve of the crystal form T of the solvate represented by formula IT is as follows: Figure 69 As shown.

[0057] In some embodiments, t is 2.85, and the thermogravimetric analysis (TGA) curve of the crystal form T of the solvate represented by formula IT shows a weight loss of 1.2% in the temperature range of 34℃±3°C to 140℃±3°C.

[0058] In some embodiments, t is 2.85, and the thermogravimetric analysis curve of the crystal form T of the solvate represented by formula IT is as follows: Figure 70 As shown.

[0059] In some embodiments, the crystal form T of the solvate represented by formula IT is the crystal form of the hydrate.

[0060] In some implementations, t is 2.85, and the solvate represented by formula IT is crystalline.

[0061] The present invention provides solvates of compounds of Formula I, which are solvates of Formula I, Formula ID, Formula IE, Formula IF, Formula IG, Formula II, Formula IK, Formula IL, Formula IM, Formula IN, Formula IO, Formula IP, or Formula IS.

[0062] or ;

[0063] Where c is 0.30-1.50, c' is 1.00-4.00; d is 0.50-1.50, d' is 4.00-8.00, d'' is 6.00-9.00; e is 0.80-1.60, e' is 4.00-8.00; f is 0.50-1.20, f' is 0.30-1.00; g is 0.10-1.00, g' is... 0.40-1.00; i is 2.00-6.00; k is 0.80-2.00, k' is 0.20-1.00; l is 0.50-2.00, l' is 0.30-1.00; n is 2.00-5.00; o is 0.30-1.00; p is 0.30-1.00; m is 1.00-2.50; s is 1.00-3.00.

[0064] In some embodiments, in the solvate of formula IC, c is 0.40, 0.45, 0.47, 0.50, or 0.80.

[0065] In some embodiments, in the crystal form C of the solvate represented by formula IC, c' is 1.00, 2.00, 2.50, 3.00, or 3.50.

[0066] In some embodiments, c is 0.47 and c' is 2.50. The crystal form C of the solvate represented by formula IC has diffraction peaks at 7.42±0.20°, 12.37±0.20°, 15.60±0.20°, 16.60±0.20°, 17.19±0.20°, 19.67±0.20°, 22.31±0.20°, 22.96±0.20°, 23.95±0.20°, 24.48±0.20°, 24.84±0.20°, 28.42±0.20°, and 31.20±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0067] In some embodiments, c is 0.47 and c' is 2.50. The crystal form C of the solvate represented by formula IC, when irradiated with Cu-Kα and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 8.70±0.20°, 10.09±0.20°, 11.46±0.20°, 14.13±0.20°, 14.81±0.20°, 18.22±0.20°, 18. 87±0.20°, 20.10±0.20°, 20.77±0.20°, 26.19±0.20°, 27.70±0.20°, 29.44±0.20°, 32.39±0.20°, 33.52±0.20°, 36.41±0.20°, 36.68±0.20°, 37.45±0.20°, 38.31±0.20° and 38.51±0.20°.

[0068] In some embodiments, c is 0.47 and c' is 2.50. The crystal form C of the solvate represented by formula IC is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles at 7.42±0.20°, 8.70±0.20°, 10.09±0.20°, 11.46±0.20°, 12.37±0.20°, 14.13±0.20°, 14.81±0.20°, 15.60±0.20°, 16.60±0.20°, 17.19±0.20°, 18.22±0.20°, 18.87±0.20°, 19.67±0.20°, and 20.10±0. Diffraction peaks are observed at 0.20°, 20.77±0.20°, 22.31±0.20°, 22.96±0.20°, 23.95±0.20°, 24.48±0.20°, 24.84±0.20°, 26.19±0.20°, 27.70±0.20°, 28.42±0.20°, 29.44±0.20°, 31.20±0.20°, 32.39±0.20°, 33.52±0.20°, 36.41±0.20°, 36.68±0.20°, 37.45±0.20°, 38.31±0.20°, and 38.51±0.20°.

[0069] In some embodiments, c is 0.47 and c' is 2.50. The crystal form C of the solvate represented by formula IC is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 14 As shown.

[0070] In some embodiments, c is 0.47 and c' is 2.50, and the differential scanning calorimetry (DSC) curve of crystal form C of the solvate shown by formula IC has endothermic peaks at 69.2°C ± 3°C and 166.7°C ± 3°C.

[0071] In some embodiments, c is 0.47 and c' is 2.50, and the differential scanning calorimetry curve of crystal form C of the solvate represented by formula IC is as follows: Figure 15 As shown.

[0072] In some embodiments, c is 0.47 and c' is 2.50. The thermogravimetric analysis (TGA) curve of crystal form C of the solvate shown in Formula IC shows a weight loss of 3.7% in the temperature range of 34℃±3°C to 150℃±3°C and a weight loss of 10.1% in the temperature range of 150℃±3°C to 200℃±3°C.

[0073] In some embodiments, c is 0.47 and c' is 2.50, and the thermogravimetric analysis curve of crystal form C of the solvate represented by formula IC is as follows. Figure 16 As shown.

[0074] In some embodiments, the crystal form C of the solvate represented by formula IC can be the crystal form of a water-dimethyl sulfoxide compound.

[0075] In some embodiments, in the solvate represented by formula ID, d is 0.50, 0.60, 0.69, 0.70, or 0.80.

[0076] In some embodiments, in the solvate represented by formula ID, d' is 5.50, 5.80, 5.86, 5.90, or 6.00.

[0077] In some embodiments, in the solvate represented by formula ID, d'' is 6.00, 7.00, 7.08, 7.50, or 8.00.

[0078] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08. The crystal form D of the solvate shown by formula ID has diffraction peaks at 5.04±0.20°, 10.07±0.20°, 13.40±0.20°, 13.68±0.20°, 14.79±0.20°, 18.21±0.20°, 22.12±0.20°, 23.12±0.20°, 23.45±0.20°, and 26.89±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0079] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08. The crystal form D of the solvate shown in formula ID, when irradiated with Cu-Kα radiation and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 6.48±0.20°, 9.07±0.20°, 11.01±0.20°, 14.18±0.20°, 15.21±0.20°, 17.04±0.20°, 17.86±0.20°, 18.57±0.20°, 19.30±0.20°, and 20.19±0.20°. 20.70±0.20°, 22.80±0.20°, 24.41±0.20°, 25.30±0.20°, 25.40±0.20°, 25.98±0.20°, 26.14±0.20°, 26.57±0.20°, 27.65±0.20°, 28.15±0.20°, 28.48±0.20°, 29.00±0.20°, 31.83±0.20°, 32.10±0.20°, 33.30±0.20°, 35.72±0.20°, and 36.84±0.20°.

[0080] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08. The crystal form D of the solvate shown by formula ID is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles of 5.04±0.20°, 6.48±0.20°, 9.07±0.20°, 10.07±0.20°, 11.01±0.20°, 13.40±0.20°, 13.68±0.20°, 14.18±0.20°, 14.79±0.20°, 15.21±0.20°, 17.04±0.20°, 17.86±0.20°, 18.21±0.20°, 18.57±0.20°, 19.30±0.20°, and 20.19±0.20°. 0°, 20.70±0.20°, 22.12±0.20°, 22.80±0.20°, 23.12±0.20°, 23.45±0.20°, 24.41±0.20°, 25.30±0.20°, 25.40±0.20°, 25.98±0.20°, 26.14±0.20°, 26.57±0 Diffraction peaks are observed at 0.20°, 26.89±0.20°, 27.65±0.20°, 28.15±0.20°, 28.48±0.20°, 29.00±0.20°, 31.83±0.20°, 32.10±0.20°, 33.30±0.20°, 35.72±0.20°, and 36.84±0.20°.

[0081] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08. The crystal form D of the solvate represented by formula ID is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 18 As shown.

[0082] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08, and the differential scanning calorimetry (DSC) curve of crystal form D of the solvate represented by formula ID has endothermic peaks at 49.5°C±3°C, 91.0°C±3°C, 121.0°C±3°C, and 178.9°C±3°C.

[0083] In some implementations, d is 0.69, d' is 5.86, and d'' is 7.08, and the differential scanning calorimetry curve of the crystal form D of the solvate represented by formula ID is as follows: Figure 19 As shown.

[0084] In some embodiments, d is 0.69, d' is 5.86, and d'' is 7.08. The thermogravimetric analysis (TGA) curve of crystal form D of the solvate shown by formula ID shows a weight loss of 5.3% in the temperature range of 34℃±3°C to 80℃±3°C and a weight loss of 12.8% in the temperature range of 80℃±3°C to 140℃±3°C.

[0085] In some implementations, d is 0.69, d' is 5.86, and d'' is 7.08, and the thermogravimetric analysis curve of crystal form D of the solvate represented by formula ID is as follows. Figure 20 As shown.

[0086] In some implementations, d is 0.69, d' is 5.86, and d'' is 7.08, and the solvate shown in Formula ID is crystalline.

[0087] In some embodiments, the crystal form D of the solvate represented by Formula ID is the crystal form of 1,3-dimethyl-2-imidazolium ketone, or the crystal form of a water-ethanol compound.

[0088] In some embodiments, in the solvate represented by Formula IE, e is 1.00, 1.21, 1.30, 1.40, or 1.50.

[0089] In some embodiments, in the solvate represented by Formula IE, e' is 5.50, 6.00, 6.20, 6.50, or 7.80.

[0090] In some embodiments, e is 1.21 and e' is 6.20. The crystal form E of the solvate represented by formula IE has diffraction peaks at 3.83±0.20°, 7.61±0.20°, 14.38±0.20°, 17.73±0.20°, 18.75±0.20°, 19.07±0.20°, 19.39±0.20°, 25.31±0.20°, 26.41±0.20°, and 32.85±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0091] In some embodiments, e is 1.21 and e' is 6.20. The crystal form E of the solvate represented by formula IE, when irradiated with Cu-Kα radiation and expressed in 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 11.47±0.20°, 12.59±0.20°, 12.82±0.20°, 13.10±0.20°, 13.68±0.20°, 14.94±0.20°, 17.46±0.20°, 22.57±0.20°, 23.56±0.20°, 24.51±0.20°, 25.46±0.20°, 29.33±0.20°, 29.63±0.20°, 30.83±0.20°, and 35.25±0.20°.

[0092] In some embodiments, e is 1.21 and e' is 6.20. The crystal form E of the solvate represented by formula IE is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 3.83±0.20°, 7.61±0.20°, 11.47±0.20°, 12.59±0.20°, 12.82±0.20°, 13.10±0.20°, 13.68±0.20°, 14.38±0.20°, 14.94±0.20°, 17.46±0.20°, 1 Diffraction peaks are observed at 7.73±0.20°, 18.75±0.20°, 19.07±0.20°, 19.39±0.20°, 22.57±0.20°, 23.56±0.20°, 24.51±0.20°, 25.31±0.20°, 25.46±0.20°, 26.41±0.20°, 29.33±0.20°, 29.63±0.20°, 30.83±0.20°, 32.85±0.20°, and 35.25±0.20°.

[0093] In some embodiments, e is 1.21 and e' is 6.20. The crystal form E of the solvate represented by formula IE is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows: Figure 22 As shown.

[0094] In some embodiments, e is 1.21 and e' is 6.20, and the differential scanning calorimetry (DSC) curve of the crystal form E of the solvate represented by formula IE has endothermic peaks at 81.2°C±3°C, 156.6°C±3°C and 181.4°C±3°C.

[0095] In some embodiments, e is 1.21 and e' is 6.20, and the differential scanning calorimetry curve of the crystal form E of the solvate represented by formula IE is as follows: Figure 23 As shown.

[0096] In some embodiments, e is 1.21 and e' is 6.20, and the thermogravimetric analysis (TGA) curve of crystal form E of the solvate shown by formula IE shows a weight loss of 2.7% in the temperature range of 33℃±3°C to 100℃±3°C and a weight loss of 4.7% in the temperature range of 100℃±3°C to 170℃±3°C.

[0097] In some implementations, e is 1.21 and e' is 6.20, and the solvate shown in Formula IE is crystalline.

[0098] In some embodiments, e is 1.21 and e' is 6.20, and the thermogravimetric analysis curve of crystal form E of the solvate represented by formula IE is as follows. Figure 24 As shown.

[0099] In some embodiments, the crystal form E of the solvate represented by formula IE can be the crystal form of a water-N,N-dimethylformamide compound.

[0100] In some embodiments, in the solvate represented by the formula IF, f is 0.60, 0.70, 0.80, 0.88, or 0.90.

[0101] In some embodiments, in the solvate represented by formula IF, f' is 0.50, 0.60, 0.64, 0.70, or 0.80.

[0102] In some embodiments, f is 0.88 and f' is 0.64. The crystal form F of the solvate represented by formula IF has diffraction peaks at 3.96±0.20°, 8.01±0.20°, 12.48±0.20°, 14.21±0.20°, 15.35±0.20°, 17.74±0.20°, 19.21±0.20°, 19.49±0.20°, 22.62±0.20°, 23.67±0.20°, 24.67±0.20°, and 26.82±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0103] In some embodiments, f is 0.88 and f' is 0.64, and the crystal form F of the solvate represented by formula IF, when irradiated with Cu-Kα and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 13.36±0.20°, 13.78±0.20°, 14.62±0.20°, 16.73±0.20°, 18.67±0.20°, 25.31±0.20°, 25.91±0.20°, 27.55±0.20°, 28.54±0.20°, 29.60±0.20°, 30.97±0.20°, 32.06±0.20°, and 35.33±0.20°.

[0104] In some embodiments, f is 0.88 and f' is 0.64. The crystal form F of the solvate represented by formula IF is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles at 3.96±0.20°, 8.01±0.20°, 12.48±0.20°, 13.36±0.20°, 13.78±0.20°, 14.21±0.20°, 14.62±0.20°, 15.35±0.20°, 16.73±0.20°, and 17.74±0.20°. °, 18.67±0.20°, 19.21±0.20°, 19.49±0.20°, 22.62±0.20°, 23.67±0.20°, 24.67±0.20°, 25.31±0.20°, 25.91±0.20°, 26.82±0.20°, 27.55±0.20°, 28.54±0.20°, 29.60±0.20°, 30.97±0.20°, 32.06±0.20° and 35.33±0.20°.

[0105] In some embodiments, f is 0.88 and f' is 0.64, and the crystal form F of the solvate represented by formula IF is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 26 As shown.

[0106] In some embodiments, f is 0.88 and f' is 0.64, and the differential scanning calorimetry (DSC) curve of crystal form F of the solvate represented by formula IF has endothermic peaks at 47.4°C±3°C, 117.2°C±3°C and 184.8°C±3°C.

[0107] In some implementations, f is 0.88 and f' is 0.64, and the differential scanning calorimetry curve of the crystal form F of the solvate represented by formula IF is as follows: Figure 27 As shown.

[0108] In some embodiments, f is 0.88 and f' is 0.64, and the thermogravimetric analysis (TGA) curve of crystal form F of the solvate represented by formula IF shows a weight loss of 2.5% in the temperature range of 34℃±3°C to 100℃±3°C and a weight loss of 0.4% in the temperature range of 100℃±3°C to 170℃±3°C.

[0109] In some implementations, f is 0.88 and f' is 0.64, and the thermogravimetric analysis curve of the crystal form F of the solvate represented by formula IF is as follows. Figure 28 As shown.

[0110] In some implementations, f is 0.88 and f' is 0.64, and the solvate represented by formula IF is crystalline.

[0111] In some embodiments, the crystal form of the solvate represented by Formula IF can be the crystal form of a water-isopropanol compound.

[0112] In some embodiments, in the solvate of formula IG, g is 0.10, 0.15, 0.25, 0.30, or 0.35.

[0113] In some embodiments, in the solvate represented by formula IG, g' is 0.50, 0.60, 0.70, 0.75, or 0.80.

[0114] In some embodiments, g is 0.25 and g' is 0.7. The crystal form G of the solvate represented by formula IG has diffraction peaks at 7.64±0.20°, 15.28±0.20°, 17.02±0.20°, 19.41±0.20°, 20.10±0.20°, 20.49±0.20°, 23.03±0.20°, 24.38±0.20°, 26.93±0.20°, and 27.94±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0115] In some embodiments, g is 0.25 and g' is 0.7, and the crystal form G of the solvate represented by formula IG, when irradiated with Cu-Kα and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 9.30±0.20°, 9.81±0.20°, 14.87±0.20°, 18.55±0.20°, 18.62±0.20°, 25.41±0.20°, 26.12±0.20°, 30.88±0.20°, and 37.98±0.20°.

[0116] In some embodiments, g is 0.25 and g' is 0.7. The crystal form G of the solvate represented by formula IG is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 7.64±0.20°, 9.30±0.20°, 9.81±0.20°, 14.87±0.20°, 15.28±0.20°, 17.02±0.20°, 18.55±0.20°, and 18... Diffraction peaks are observed at 0.62±0.20°, 19.41±0.20°, 20.10±0.20°, 20.49±0.20°, 23.03±0.20°, 24.38±0.20°, 25.41±0.20°, 26.12±0.20°, 26.93±0.20°, 27.94±0.20°, 30.88±0.20°, and 37.98±0.20°.

[0117] In some embodiments, g is 0.25 and g' is 0.7. The crystal form G of the solvate represented by formula IG is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 30 As shown.

[0118] In some embodiments, g is 0.25 and g' is 0.7, and the differential scanning calorimetry (DSC) curve of the crystal form G of the solvate represented by formula IG has endothermic peaks at 64.7°C ± 3°C and 209.3°C ± 3°C.

[0119] In some embodiments, g is 0.25 and g' is 0.7, and the differential scanning calorimetry curve of the crystal form G of the solvate represented by formula IG is as follows: Figure 31 As shown.

[0120] In some embodiments, g is 0.25 and g' is 0.7. The thermogravimetric analysis (TGA) curve of crystal form G of the solvate shown by formula IG shows a weight loss of 0.4% in the temperature range of 33℃±3°C to 100℃±3°C and a weight loss of 9.7% in the temperature range of 100℃±3°C to 210℃±3°C.

[0121] In some implementations, g is 0.25 and g' is 0.7, and the thermogravimetric analysis curve of the crystal form G of the solvate represented by formula IG is as follows. Figure 32 As shown.

[0122] In some implementations, g is 0.25 and g' is 0.7, and the solvate represented by formula IG is crystalline.

[0123] In some embodiments, the crystal form G of the solvate represented by formula IG can be the crystal form of a water-methyl tert-butyl ether compound.

[0124] In some embodiments, i in the solvate of Formula II is 3.50, 3.70, 3.80, 3.87, or 3.90.

[0125] In some embodiments, i is 3.87, and the crystal form I of the solvate shown in Formula II has diffraction peaks at 7.21±0.20°, 12.73±0.20°, 14.40±0.20°, 15.42±0.20°, 16.02±0.20°, 16.57±0.20°, 19.06±0.20°, 20.93±0.20°, 21.19±0.20°, 23.42±0.20°, 24.24±0.20°, 25.53±0.20°, 25.97±0.20°, 27.51±0.20°, 28.14±0.20°, and 32.97±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed in 2θ angle.

[0126] In some embodiments, i is 3.87, and the X-ray powder diffraction pattern of crystal form I of the solvate shown in Formula II, expressed as a 2θ angle using Cu-Kα radiation, also exhibits diffraction peaks at one or more of the following locations: 8.04±0.20°, 9.11±0.20°, 10.89±0.20°, 11.46±0.20°, 13.07±0.20°, 14.56... ±0.20°, 16.36±0.20°, 16.85±0.20°, 17.86±0.20°, 18.16±0.20°, 18.60±0.20°, 19.54±0.20°, 20.35±0.20°, 21.43±0.20°, 21.68±0.20°, 21.72±0.20°, 23.04±0 0.20°, 23.71±0.20°, 25.00±0.20°, 26.30±0.20°, 26.51±0.20°, 26.93±0.20°, 27.25±0.20°, 27.99±0.20°, 29.03±0.20°, 29.54±0.20°, 29.74±0.20°, 30.54±0.2 0°, 30.79±0.20°, 31.16±0.20°, 32.05±0.20°, 33.31±0.20°, 33.75±0.20°, 33.96±0.20°, 34.36±0.20°, 34.90±0.20°, 36.53±0.20°, 38.86±0.20° and 39.68±0.20°.

[0127] In some embodiments, i is 3.87, and the crystal form I of the solvate shown in Formula II is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 7.21±0.20°, 8.04±0.20°, 9.11±0.20°, 10.89±0.20°, 11.46±0.20°, 12.73±0.20°, 13.07±0.20°, 14.40±0.20°, 14.56±0.20°, 15.42±0.20°, and 16.02°. ±0.20°, 16.36±0.20°, 16.57±0.20°, 16.85±0.20°, 17.86±0.20°, 18.16±0.20°, 18.60±0.20°, 19.06±0.20°, 19.54±0.20°, 20.35±0.20°, 20.93±0.20°, 21.19±0.20°, 21.43±0.20°, 21.68±0.20°, 21.72±0.20°, 23.04 ±0.20°, 23.42±0.20°, 23.71±0.20°, 24.24±0.20°, 25.00±0.20°, 25.53±0.20°, 25.97±0.20°, 26.30±0.20°, 26.51±0.20°, 26.93±0.20°, 27.25±0.20°, 27.51±0.20°, 27.99±0.20°, 28.14±0.20°, 29.03±0.20°, 29.54 Diffraction peaks are observed at ±0.20°, 29.74±0.20°, 30.54±0.20°, 30.79±0.20°, 31.16±0.20°, 32.05±0.20°, 32.97±0.20°, 33.31±0.20°, 33.75±0.20°, 33.96±0.20°, 34.36±0.20°, 34.90±0.20°, 36.53±0.20°, 38.86±0.20°, and 39.68±0.20°.

[0128] In some embodiments, i is 3.87, and the crystal form I of the solvate shown in Formula II is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 34 As shown.

[0129] In some embodiments, i is 3.87, and the differential scanning calorimetry (DSC) curve of crystal form I of the solvate shown in Formula II has endothermic peaks at 44.8°C ± 3°C, 130.8°C ± 3°C, and 217.4°C ± 3°C.

[0130] In some embodiments, i is 3.87, and the differential scanning calorimetry curve of crystal form I of the solvate shown in Formula II is as follows: Figure 35 As shown.

[0131] In some embodiments, i is 3.87, and the thermogravimetric analysis (TGA) curve of crystal form I of the solvate shown in Formula II shows a weight loss of 0.2% in the temperature range of 34℃±3°C to 70℃±3°C and a weight loss of 20.4% in the temperature range of 70℃±3°C to 135℃±3°C.

[0132] In some embodiments, i is 3.87, and the thermogravimetric analysis curve of crystal form I of the solvate shown in Formula II is as follows: Figure 36 As shown.

[0133] In some embodiments, i is 3.87, and the solvate shown in Formula II is crystalline.

[0134] In some embodiments, the crystal form I of the solvate shown in Formula II can be the crystal form of an N-methylpyrrolidone compound.

[0135] In some embodiments, in the solvate represented by formula IK, k is 1.00, 1.20, 1.28, 1.30, or 1.50.

[0136] In some embodiments, in the solvate represented by formula IK, k' is 0.30, 0.35, 0.40, 0.45, or 0.50.

[0137] In some embodiments, k is 1.28 and k' is 0.40. The crystal form K of the solvate represented by formula IK has diffraction peaks at 8.01±0.20°, 9.19±0.20°, 13.87±0.20°, 16.22±0.20°, 17.78±0.20°, 20.63±0.20°, 22.24±0.20°, 22.66±0.20°, 23.40±0.20°, 25.09±0.20°, 29.12±0.20°, and 30.77±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0138] In some embodiments, k is 1.28 and k' is 0.40. The crystal form K of the solvate represented by formula IK, when subjected to Cu-Kα radiation and X-ray powder diffraction in 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 8.52±0.20°, 15.25±0.20°, 16.61±0.20°, 17.06±0.20°, and 18.64±0.20°. 0°, 19.10±0.20°, 20.04±0.20°, 21.27±0.20°, 24.07±0.20°, 27.08±0.20°, 27.67±0.20°, 28.26±0.20°, 33.93±0.20°, 34.48±0.20°, 35.19±0.20° and 38.23±0.20°.

[0139] In some embodiments, k is 1.28 and k' is 0.40. The crystal form K of the solvate represented by formula IK is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 8.01±0.20°, 8.52±0.20°, 9.19±0.20°, 13.87±0.20°, 15.25±0.20°, 16.22±0.20°, 16.61±0.20°, 17.06±0.20°, 17.78±0.20°, 18.64±0.20°, 19.10±0.20°, and 20.04±0. Diffraction peaks are observed at 0.20°, 20.63±0.20°, 21.27±0.20°, 22.24±0.20°, 22.66±0.20°, 23.40±0.20°, 24.07±0.20°, 25.09±0.20°, 27.08±0.20°, 27.67±0.20°, 28.26±0.20°, 29.12±0.20°, 30.77±0.20°, 33.93±0.20°, 34.48±0.20°, 35.19±0.20°, and 38.23±0.20°.

[0140] In some embodiments, k is 1.28 and k' is 0.40. The crystal form K of the solvate represented by formula IK is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 38 As shown.

[0141] In some embodiments, k is 1.28 and k' is 0.40, and the thermogravimetric analysis (TGA) curve of crystal form K of the solvate represented by formula IK shows a weight loss of 6.4% in the temperature range of 33℃±3°C to 180℃±3°C.

[0142] In some embodiments, k is 1.28 and k' is 0.40, and the thermogravimetric analysis curve of the crystal form K of the solvate represented by formula IK is as follows. Figure 39 As shown.

[0143] In some implementations, k is 1.28, k' is 0.40, and the solvate represented by formula IK is crystalline.

[0144] In some embodiments, the crystal form K of the solvate represented by formula IK can be the crystal form of a water-acetonitrile compound.

[0145] In some embodiments, in the solvate represented by formula IL, l is 0.80, 0.90, 1.01, 1.10, or 1.20.

[0146] In some embodiments, in the solvate represented by formula IL, l' is 0.60, 0.70, 0.74, 0.75, or 0.80.

[0147] In some embodiments, l is 1.01 and l' is 0.74. The crystal form L of the solvate represented by formula IL has diffraction peaks at 13.48±0.20°, 15.75±0.20°, 17.32±0.20°, 17.70±0.20°, 20.04±0.20°, 22.15±0.20°, 24.59±0.20°, 24.88±0.20°, 25.74±0.20°, 27.12±0.20°, 29.01±0.20°, and 30.81±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0148] In some embodiments, l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL, when irradiated with Cu-Kα and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 11.51±0.20°, 11.88±0.20°, 12.35±0.20°, 12.95±0.20°, 14.67±0.20°, 16.61±0.20°, 18.17±0.20°, 18.54±0.20°, 18.84±0.20°, 20.78±0.20°. 20°, 22.80±0.20°, 23.03±0.20°, 23.38±0.20°, 23.82±0.20°, 25.16±0.20°, 26.24±0.20°, 27.53±0.20°, 28.43±0.20°, 29.64±0.20°, 30.13±0.20°, 32.65±0.20°, 33.53±0.20°, 34.11±0.20°, 34.76±0.20°, 37.29±0.20° and 38.22±0.20°.

[0149] In some embodiments, l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 11.51±0.20°, 11.88±0.20°, 12.35±0.20°, 12.95±0.20°, 13.48±0.20°, and 14.67± 0.20°, 15.75±0.20°, 16.61±0.20°, 17.32±0.20°, 17.70±0.20°, 18.17±0.20°, 18.54±0.20°, 18.84±0.20°, 20.04±0.20°, 20.78±0.20°, 22.15±0.20°, 22.80± 0.20°, 23.03±0.20°, 23.38±0.20°, 23.82±0.20°, 24.59±0.20°, 24.88±0.20°, 25.16±0.20°, 25.74±0.20°, 26.24±0.20°, 27.12±0.20°, 27.53±0.20°, 28.43 Diffraction peaks are observed at ±0.20°, 29.01±0.20°, 29.64±0.20°, 30.13±0.20°, 30.81±0.20°, 32.65±0.20°, 33.53±0.20°, 34.11±0.20°, 34.76±0.20°, 37.29±0.20°, and 38.22±0.20°.

[0150] In some embodiments, l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL is obtained by Cu-Kα irradiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 41 As shown.

[0151] In some embodiments, l is 1.01 and l' is 0.74, and the differential scanning calorimetry (DSC) curve of the crystal form L of the solvate represented by formula IL has endothermic peaks at 57.2°C ± 3°C and 178.4°C ± 3°C.

[0152] In some embodiments, l is 1.01, l' is 0.74, and the differential scanning calorimetry curve of the crystal form L of the solvate represented by formula IL is as follows: Figure 42 As shown.

[0153] In some embodiments, l is 1.01, l' is 0.74, and the thermogravimetric analysis (TGA) curve of the crystal form L of the solvate represented by formula IL shows a weight loss of 2.5% in the temperature range of 35℃±3°C to 100℃±3°C and a weight loss of 6.9% in the temperature range of 100℃±3°C to 190℃±3°C.

[0154] In some implementations, l is 1.01 and l' is 0.74, and the thermogravimetric analysis curve of the crystal form L of the solvate represented by formula IL is as follows: Figure 43 As shown.

[0155] In some embodiments, l is 1.01, l' is 0.74, and the solvate represented by formula IL is crystalline.

[0156] In some embodiments, the crystal form L of the solvate represented by formula IL can be the crystal form of a water-anisole compound.

[0157] In some embodiments, in the solvate represented by the formula IN, n is 2.80, 3.20, 3.28, 3.30, or 3.50.

[0158] In some embodiments, n is 3.28, and the crystal form N of the solvate represented by formula IN has diffraction peaks at 7.82±0.20°, 8.56±0.20°, 14.55±0.20°, 15.58±0.20°, 17.37±0.20°, 18.46±0.20°, 19.66±0.20°, 22.61±0.20°, 22.87±0.20°, 25.08±0.20°, 26.07±0.20°, and 27.07±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angles.

[0159] In some embodiments, n is 3.28, and the crystal form N of the solvate represented by formula IN, when irradiated with Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 9.78±0.20°, 11.20±0.20°, 11.41±0.20°, 12.29±0.20°, 12.95±0.20°, 16.37±0.20°, 16.97±0.20°, 19.13±0.20°, 20.13±0.20°, 20.58±0.20°, 21.44±0.20°, 22.00±0.20°, 23.56±0.20°, 2 4.71±0.20°, 25.47±0.20°, 26.67±0.20°, 27.86±0.20°, 28.84±0.20°, 29.31±0.20°, 29.64±0.20°, 30.53±0.20°, 32.65±0.20°, 33.63±0.20°, 34.42±0.20°, 34.88±0.20°, 35.75±0.20°, 36.82±0.20°, 37.40±0.20°, 38.42±0.20°, 38.92±0.20°, 39.86±0.20° and 24.71±0.20°.

[0160] In some embodiments, n is 3.28, and the crystal form N of the solvate represented by formula IN is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 7.82±0.20°, 8.56±0.20°, 9.78±0.20°, 11.20±0.20°, 11.41±0.20°, 12.29±0.20°, 12.95±0.20°, and 14.55±0.20°. 20°, 15.58±0.20°, 16.37±0.20°, 16.97±0.20°, 17.37±0.20°, 18.46±0.20°, 19.13±0.20°, 19.66±0.20°, 20.13±0.20°, 20.58±0.20°, 21.44±0.20°, 22.00±0.20°, 22.61±0.20° 22.87±0.20°, 23.56±0.20°, 24.71±0.20°, 25.08±0.20°, 25.47±0.20°, 26.07±0.20°, 26.67±0.20°, 27.07±0.20°, 27.86±0.20°, 28.84±0.20°, 29.31±0.20°, 29.64±0.20°, 30 Diffraction peaks are observed at 0.53±0.20°, 32.65±0.20°, 33.63±0.20°, 34.42±0.20°, 34.88±0.20°, 35.75±0.20°, 36.82±0.20°, 37.40±0.20°, 38.42±0.20°, 38.92±0.20°, 39.86±0.20°, and 24.71±0.20°.

[0161] In some embodiments, n is 3.28, and the crystal form N of the solvate represented by formula IN is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 48 As shown.

[0162] In some embodiments, n is 3.28, and the differential scanning calorimetry (DSC) curve of the crystal form N of the solvate represented by formula IN has endothermic peaks at 56.0°C ± 3°C, 130.8°C ± 3°C, and 215.3°C ± 3°C.

[0163] In some embodiments, n is 3.28, and the differential scanning calorimetry curve of the crystal form N of the solvate represented by formula IN is as follows: Figure 49 As shown.

[0164] In some embodiments, n is 3.28, and the thermogravimetric analysis (TGA) curve of crystal form N of the solvate represented by formula IN shows a weight loss of 13.0% in the temperature range of 34℃±3°C to 90℃±3°C.

[0165] In some embodiments, n is 3.28, and the thermogravimetric analysis curve of crystal form N of the solvate represented by formula IN is as follows. Figure 50 As shown.

[0166] In some implementations, n is 3.28, and the solvate represented by formula IN is crystalline.

[0167] In some embodiments, the crystal form N of the solvate represented by formula IN can be the crystal form of an N-methylpyrrolidone compound.

[0168] In some embodiments, in the solvate of formula IO, o is 0.40, 0.50, 0.60, 0.65, or 0.70.

[0169] In some embodiments, o is 0.60, and the crystal form O of the solvate represented by formula IO has diffraction peaks at 7.77±0.20°, 14.94±0.20°, 16.97±0.20°, 20.12±0.20°, 20.81±0.20°, 21.08±0.20°, 23.38±0.20°, 23.78±0.20°, 24.50±0.20°, 26.03±0.20°, 27.32±0.20°, and 31.33±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at an angle of 2θ.

[0170] In some embodiments, o is 0.60, and the crystal form O of the solvate represented by formula IO, when irradiated with Cu-Kα and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, 13.77±0.20°, and 15.54±0. 20°, 18.11±0.20°, 18.66±0.20°, 19.55±0.20°, 24.89±0.20°, 25.28±0.20°, 25.59±0.20°, 28.30±0.20°, 30.24±0.20°, 33.23±0.20°, 34.66±0.20°, 38.12±0.20° and 39.45±0.20°.

[0171] In some embodiments, o is 0.60, and the crystal form O of the solvate represented by formula IO is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 7.77±0.20°, 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, 13.77±0.20°, 14.94±0.20°, 15.54±0.20°, 16.97±0.20°, 18.11±0.20°, 18.66±0.20°, 19.55±0.20°, 20.12± Diffraction peaks are observed at 0.20°, 20.81±0.20°, 21.08±0.20°, 23.38±0.20°, 23.78±0.20°, 24.50±0.20°, 24.89±0.20°, 25.28±0.20°, 25.59±0.20°, 26.03±0.20°, 27.32±0.20°, 28.30±0.20°, 30.24±0.20°, 31.33±0.20°, 33.23±0.20°, 34.66±0.20°, 38.12±0.20°, and 39.45±0.20°.

[0172] In some embodiments, o is 0.6, and the crystal form O of the solvate represented by formula IO is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 52 As shown.

[0173] In some embodiments, o is 0.6, and the differential scanning calorimetry (DSC) curve of crystal form O of the solvate represented by formula IO has endothermic peaks at 125.5°C ± 3°C and 209.6°C ± 3°C.

[0174] In some embodiments, o is 0.6, and the differential scanning calorimetry curve of crystal form O of the solvate represented by formula IO is as follows: Figure 53 As shown.

[0175] In some embodiments, o is 0.6, and the thermogravimetric analysis (TGA) curve of crystal form O of the solvate represented by formula IO shows a weight loss of 7.6% in the temperature range of 35°C ± 3°C to 170°C ± 3°C.

[0176] In some embodiments, o is 0.6, and the thermogravimetric analysis curve of the crystal form O of the solvate represented by formula IO is as follows: Figure 54 As shown.

[0177] In some embodiments, the crystal form O of the solvate represented by formula IO can be the crystal form of the ethyl acetate compound.

[0178] In some embodiments, in the solvate represented by formula IP, p is 0.40, 0.50, 0.56, 0.60, or 0.70.

[0179] In some embodiments, p is 0.56, and the crystal form P of the solvate shown by formula IP has diffraction peaks at 7.76±0.20°, 11.52±0.20°, 15.44±0.20°, 17.27±0.20°, 18.64±0.20°, 19.57±0.20°, 20.33±0.20°, 21.78±0.20°, 23.35±0.20°, 23.87±0.20°, 26.34±0.20°, 27.62±0.20°, and 31.26±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0180] In some embodiments, p is 0.56, and the crystal form P of the solvate shown in formula IP, when irradiated with Cu-Kα radiation and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 9.21±0.20°, 9.84±0.20°, 10.89±0.20°, 12.48±0.20°, 16.92±0.20°, 17.57±0.20°, 24.49±0.20°, 24.89±0.20°, 25.50±0.20°, 26.06±0.20°, 28.60±0.20°, 34.12±0.20°, 36.05±0.20°, 37.65±0.20°, and 39.42±0.20°.

[0181] In some embodiments, p is 0.56, and the crystal form P of the solvate represented by formula IP is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles at 7.76±0.20°, 9.21±0.20°, 9.84±0.20°, 10.89±0.20°, 11.52±0.20°, 12.48±0.20°, 15.44±0.20°, 16.92±0.20°, 17.27±0.20°, 17.57±0.20°, 18.64±0.20°, and 19.57±0.20°. Diffraction peaks are observed at 20.33±0.20°, 21.78±0.20°, 23.35±0.20°, 23.87±0.20°, 24.49±0.20°, 24.89±0.20°, 25.50±0.20°, 26.06±0.20°, 26.34±0.20°, 27.62±0.20°, 28.60±0.20°, 31.26±0.20°, 34.12±0.20°, 36.05±0.20°, 37.65±0.20°, and 39.42±0.20°.

[0182] In some embodiments, p is 0.56, and the crystal form P of the solvate represented by formula IP is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown below. Figure 56 As shown.

[0183] In some embodiments, p is 0.56, and the differential scanning calorimetry (DSC) curve of crystal form P of the solvate shown by formula IP has endothermic peaks at 157.4°C ± 3°C and 206.8°C ± 3°C.

[0184] In some embodiments, p is 0.56, and the differential scanning calorimetry (DSC) curve of crystal form P of the solvate represented by formula IP is as follows: Figure 57 As shown.

[0185] In some embodiments, p is 0.56, and the thermogravimetric analysis (TGA) curve of crystal form P of the solvate shown by formula IP shows a weight loss of 7.8% in the temperature range of 35°C to 180°C.

[0186] In some embodiments, p is 0.56, and the thermogravimetric analysis curve of crystal form P of the solvate represented by formula IP is as follows. Figure 58 As shown.

[0187] In some implementations, p is 0.56, and the solvate shown in formula IP is crystalline.

[0188] In some embodiments, the crystal form P of the solvate represented by formula IP can be the crystal form of the toluene compound.

[0189] In some embodiments, in the solvate represented by formula IM, m is 1.20, 1.30, 1.39, 1.40, or 1.50.

[0190] In some embodiments, m is 1.39, and the crystal form M of the solvate represented by formula IM has diffraction peaks at 8.38±0.20°, 16.03±0.20°, 16.80±0.20°, 17.98±0.20°, 18.50±0.20°, 19.28±0.20°, 22.47±0.20°, 24.00±0.20°, 26.46±0.20°, and 29.54±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angles.

[0191] In some embodiments, m is 1.39, and the crystal form M of the solvate represented by formula IM, when irradiated with Cu-Kα and expressed in 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 7.11±0.20°, 12.44±0.20°, 14.92±0.20°, 23.14±0.20°, 25.32±0.20°, and 30.82±0.20°.

[0192] In some embodiments, m is 1.39, and the crystal form M of the solvate represented by formula IM has diffraction peaks at 7.11±0.20°, 8.38±0.20°, 12.44±0.20°, 14.92±0.20°, 16.03±0.20°, 16.80±0.20°, 17.98±0.20°, 18.50±0.20°, 19.28±0.20°, 22.47±0.20°, 23.14±0.20°, 24.00±0.20°, 25.32±0.20°, 26.46±0.20°, 29.54±0.20°, and 30.82±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0193] In some embodiments, m is 1.39, and the crystal form M of the solvate represented by formula IM is obtained using Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 45 As shown.

[0194] In some embodiments, m is 1.39, and the thermogravimetric analysis (TGA) curve of crystal form M of the solvate represented by formula IM shows a weight loss of 16.7% in the temperature range of 36℃±3°C to 160℃±3°C.

[0195] In some embodiments, m is 1.39, and the thermogravimetric analysis curve of the crystal form M of the solvate represented by formula IM is as follows. Figure 46 As shown.

[0196] In some implementations, m is 1.39, and the solvate represented by formula IM is crystalline.

[0197] In some embodiments, the crystal form M of the solvate represented by formula IM can be the crystal form of a trifluoroethanol compound.

[0198] In some embodiments, in the solvate represented by formula IS, s is 2.00, 2.10, 2.20, 2.30, or 2.40.

[0199] In some embodiments, s is 2.20, and the crystal form S of the solvate represented by formula IS has diffraction peaks at 6.85±0.20°, 7.21±0.20°, 7.46±0.20°, 8.12±0.20°, 13.69±0.20°, 14.41±0.20°, 14.79±0.20°, 16.25±0.20°, 16.70±0.20°, 21.54±0.20°, 22.94±0.20°, and 25.55±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

[0200] In some embodiments, s is 2.20, and the crystal form S of the solvate represented by formula IS, when irradiated with Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 16.05±0.20°, and 19.10±0.20°. 19.57±0.20°, 19.98±0.20°, 20.25±0.20°, 20.55±0.20°, 20.91±0.20°, 24.49±0.20°, 25.01±0.20°, 26.01±0.20°, 27.51±0.20°, 28.19±0.20°, 28.52±0.20° and 29.07±0.20°.

[0201] In some embodiments, s is 2.20, and the crystal form S of the solvate represented by formula IS is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 6.85±0.20°, 7.21±0.20°, 7.46±0.20°, 8.12±0.20°, 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 13.69±0.20°, 14.41±0.20°, 14.79±0.20°, 16.05±0.20°, and 16.25±0.20°. Diffraction peaks are observed at 16.70±0.20°, 19.10±0.20°, 19.57±0.20°, 19.98±0.20°, 20.25±0.20°, 20.55±0.20°, 20.91±0.20°, 21.54±0.20°, 22.94±0.20°, 24.49±0.20°, 25.01±0.20°, 25.55±0.20°, 26.01±0.20°, 27.51±0.20°, 28.19±0.20°, 28.52±0.20°, and 29.07±0.20°.

[0202] In some embodiments, s is 2.20, and the crystal form S of the solvate represented by formula IS is obtained by Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is as follows. Figure 64 As shown.

[0203] In some embodiments, s is 2.20, and the differential scanning calorimetry (DSC) curve of the crystal form S of the solvate represented by formula IS has endothermic peaks at 107.1°C ± 3°C and 219.3°C ± 3°C.

[0204] In some embodiments, s is 2.20, and the differential scanning calorimetry curve of the crystal form S of the solvate represented by formula IS is as follows: Figure 65 As shown.

[0205] In some embodiments, s is 2.20, and the thermogravimetric analysis (TGA) curve of the crystal form S of the solvate shown by formula IS shows a weight loss of 9.8% in the temperature range of 36℃±3°C to 150℃±3°C.

[0206] In some embodiments, s is 2.20, and the thermogravimetric analysis curve of the crystal form S of the solvate represented by formula IS is as follows: Figure 66 As shown.

[0207] In some embodiments, s is 2.20, and the solvate represented by formula IS is crystalline.

[0208] In some embodiments, s is 2.20, and the crystal form S of the solvate represented by formula IS can be the crystal form of an N-methylpyrrolidone compound.

[0209] The present invention provides a method for preparing crystal form A of the solvate shown in formula IA, which includes the following steps: mixing the compound shown in formula I with acetonitrile, adding ethanol, and obtaining crystal form A of the solvate shown in formula IA.

[0210] In the method for preparing crystal form A of the solvate shown in Formula IA, the mass-to-volume ratio of the compound shown in Formula I to the acetonitrile can be 0.50~1.00 g / mL, for example 0.75 g / mL.

[0211] In the method for preparing crystal form A of the solvate shown in Formula IA, the mass-to-volume ratio of the compound shown in Formula I to the ethanol can be 0.05~0.15 g / mL, for example 0.09 g / mL.

[0212] In some embodiments, the method for preparing crystal form A of the solvate shown in Formula IA further includes a purification step, such as slurry purification using a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water may be 5:1.

[0213] In the purification step, the mass-to-volume ratio of the compound represented by Formula I to the mixed solvent can be 0.05~0.20 g / mL, preferably, the mass-to-volume ratio of the compound represented by Formula I to the mixed solvent is 0.12 g / mL.

[0214] In some embodiments, the preparation method of crystal form A of the solvate shown in Formula IA includes the following steps: mixing the compound shown in Formula I with acetonitrile, adding ethanol (e.g., slowly adding ethanol dropwise), filtering, and collecting the solid; purifying the obtained solid by slurrying with a mixed solvent of acetonitrile and water in a volume ratio of 5:1 to obtain crystal form A of the solvate shown in Formula IA.

[0215] The present invention provides a crystal form A of the solvate shown in Formula IA, which is obtained by the preparation method of crystal form A of the solvate shown in Formula IA.

[0216] This invention provides a method for preparing crystal form B of the compound shown in Formula I, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, or crystal form K of the solvate shown in Formula IK, comprising the following steps:

[0217] (1) Mix crystal form A of the solvate shown in the above formula IA with solvent C to obtain a mixture;

[0218] (2) The resulting mixture is stirred at a heating / cooling rate of 0.1°C / min in the range of 50°C to 5°C (e.g., heating the mixture from 5°C to 50°C or cooling it from 50°C to 5°C).

[0219] When the obtained compound is crystal form B as shown in Formula I, the solvent C is water;

[0220] When the resulting solvate is in crystal form F as shown in formula IF, the solvent propylene is isopropanol;

[0221] When the resulting solvate is of crystal form G as shown in formula IG, the solvent propyl is methyl tert-butyl ether;

[0222] When the resulting solvate is of crystal form I as shown in Formula II, the solvent propylene is N-methylpyrrolidone;

[0223] When the obtained solvate is of crystal form K as shown in formula IK, the solvent C is a mixed solvent of acetonitrile / water (1 / 1) (a mixed solvent of acetonitrile and water with a volume ratio of 1:1).

[0224] In the preparation methods of crystal form B of the compound shown in Formula I, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, or crystal form K of the solvate shown in Formula IK, the mass-volume ratio of crystal form A of the solvate shown in Formula IA to the solvent C can be 50~500g / L, for example 100g / L or 300g / L.

[0225] In some embodiments, in the preparation methods of crystal form B of the compound represented by formula I, crystal form F of the solvate represented by formula IF, crystal form G of the solvate represented by formula IG, crystal form I of the solvate represented by formula II, or crystal form K of the solvate represented by formula IK, step (2) may be repeated 6 to 10 times, for example 12 or 20 times.

[0226] In some embodiments, in the preparation methods of crystal form B of the compound represented by Formula I, crystal form F of the solvate represented by Formula IF, crystal form G of the solvate represented by Formula IG, crystal form I of the solvate represented by Formula II, or crystal form K of the solvate represented by Formula IK, before step (2), crystal form B of the compound represented by Formula I, crystal form F of the solvate represented by Formula IF, crystal form G of the solvate represented by Formula IG, crystal form I of the solvate represented by Formula II, or crystal form K of the solvate represented by Formula IK may be added. For example, crystal form B of the compound represented by Formula I, crystal form F of the solvate represented by Formula IF, and crystal form G of the solvate represented by Formula IK may be added in a mass ratio of (1~2):100 to crystal form A of the solvate represented by Formula IK. The crystal form G of the solvate shown in Formula G, the crystal form I of the solvate shown in Formula II, or the crystal form K of the solvate shown in Formula IK is preferably added in a mass ratio of 1:80 to the crystal form A of the solvate shown in Formula IA, the crystal form B of the compound shown in Formula I, the crystal form F of the solvate shown in Formula IF, the crystal form G of the solvate shown in Formula IG, the crystal form I of the solvate shown in Formula II, or the crystal form K of the solvate shown in Formula IK; the function of adding the corresponding crystal form B of the compound shown in Formula I, the crystal form F of the solvate shown in Formula IF, the crystal form G of the solvate shown in Formula IG, the crystal form I of the solvate shown in Formula II, or the crystal form K of the solvate shown in Formula IK is to act as a seed crystal to facilitate crystal formation.

[0227] In some embodiments, the preparation method of crystal form B of the compound represented by Formula I, crystal form F of the solvate represented by Formula IF, crystal form G of the solvate represented by Formula IG, crystal form I of the solvate represented by Formula II, or crystal form K of the solvate represented by Formula IK includes the following steps: mixing crystal form A of the solvate represented by Formula IA with solvent C (e.g., stirring at 50°C for 30 min), cooling the mixture from 50°C to 5°C at a rate of 0.1°C / min, and then heating it back up from 5°C to 50°C, repeating the heating and cooling cycles 12 or 20 times to obtain crystal form B of the compound represented by Formula I, crystal form F of the solvate represented by Formula IF, crystal form G of the solvate represented by Formula IG, crystal form I of the solvate represented by Formula II, or crystal form K of the solvate represented by Formula IK.

[0228] This invention provides a method for preparing crystal form C of a solvate represented by formula IC, crystal form D of a solvate represented by formula ID, or crystal form E of a solvate represented by formula IE, comprising the following steps:

[0229] (1) Dissolve crystal form A of the solvate shown in the above formula IA completely with solvent A;

[0230] (2) After adding solvent B to the obtained solution, crystallization is obtained to obtain the crystal form C of the solvate shown in formula IC, the crystal form D of the solvate shown in formula ID, or the crystal form E of the solvate shown in formula IE.

[0231] Wherein, when the obtained solvate is of crystal form C as shown in formula IC, solvent A is dimethyl sulfoxide and solvent B is acetonitrile;

[0232] When the resulting solvate is of crystal form D as shown in formula ID, solvent A is 1,3-dimethyl-2-imidazolium ketone and solvent B is ethanol;

[0233] When the resulting solvate is in crystal form E as shown in formula IE, solvent A is N,N-dimethylformamide and solvent B is acetone.

[0234] In the preparation methods of crystal form C of the solvate shown in formula IC, crystal form D of the solvate shown in formula ID, or crystal form E of the solvate shown in formula IE, the mass-volume ratio of crystal form A of the solvate shown in formula IA to solvent A can be 10~300g / L, preferably 15~150g / L, for example 15g / L, 50g / L or 150g / L.

[0235] In the preparation methods of crystal form C of the solvate shown in formula IC, crystal form D of the solvate shown in formula ID, or crystal form E of the solvate shown in formula IE, the volume ratio of solvent A to solvent B can be 1:1 to 1:3, for example 1:1 or 1:3, for example 1:3.

[0236] In some embodiments, the preparation method of crystal form C of the solvate of formula IC, crystal form D of the solvate of formula ID, or crystal form E of the solvate of formula IE includes the following steps: fully dissolving crystal form A of the solvate of formula IA with solvent A, adding solvent B to the resulting solution (for example, slowly adding solvent B to the mixture), filtering the resulting suspension to obtain crystal form C of the solvate of formula IC, crystal form D of the solvate of formula ID, or crystal form E of the solvate of formula IE.

[0237] This invention provides a method for preparing crystal form L of a solvate of formula IL, crystal form M of a solvate of formula IM, crystal form N of a solvate of formula IN, crystal form O of a solvate of formula IO, or crystal form P of a solvate of formula IP. The method comprises the following steps: mixing crystal form A of a solvate of formula IA with solvent D to obtain a mixture, and suspending the mixture to obtain crystal form L of a solvate of formula IL, crystal form M of a solvate of formula IM, crystal form N of a solvate of formula IN, crystal form O of a solvate of formula IO, or crystal form P of a solvate of formula IP.

[0238] Wherein, when the resulting solvate is of crystal form L as shown in formula IL, the solvent is anisole;

[0239] When the resulting solvate has crystal form M as shown in formula IM, the solvent T is trifluoroethanol;

[0240] When the resulting solvate is of crystal form N as shown in formula IN, the solvent is N-methylpyrrolidone;

[0241] When the resulting solvate is in crystal form O as shown in formula IO, the solvent is ethyl acetate;

[0242] When the resulting solvate is in crystal form P as shown in formula IP, the solvent T is toluene.

[0243] In the preparation methods of the solvate crystal form L of formula IL, the solvate crystal form M of formula IM, the solvate crystal form N of formula IN, the solvate crystal form O of formula IO, or the solvate crystal form P of formula IP, the mass-volume ratio of the solvate crystal form A of formula IA to the solvent T can be 50~300g / L, preferably 100g / L, 150g / L or 300g / L.

[0244] In the preparation methods of the solvate crystal form L of formula IL, the solvate crystal form M of formula IM, the solvate crystal form N of formula IN, the solvate crystal form O of formula IO, or the solvate crystal form P of formula IP, the suspension operation conditions may be: temperature of 25°C or 50°C, instrument rotation speed of 400 rpm, and time of 14 days or 7 days.

[0245] In some embodiments, the preparation method of the crystal form L of the solvate of formula IL, the crystal form M of the solvate of formula IM, the crystal form N of the solvate of formula IN, the crystal form O of the solvate of formula IO, or the crystal form P of the solvate of formula IP includes the following steps: mixing the crystal form A of the solvate of formula IA with solvent D to obtain a mixture, suspending the mixture at 25°C or 50°C and 400 rpm for 14 days or 7 days to obtain the crystal form L of the solvate of formula IL, the crystal form M of the solvate of formula IM, the crystal form N of the solvate of formula IN, the crystal form O of the solvate of formula IO, or the crystal form P of the solvate of formula IP.

[0246] The present invention provides a method for preparing crystal form S of the solvate shown in formula IS, comprising the following steps: at 50°C, fully dissolving crystal form A of the solvate shown in formula IA with N-methylpyrrolidone, adding acetone to the resulting solution and cooling it to obtain crystal form S of the solvate shown in formula IS.

[0247] In the method for preparing crystal form S of the solvate shown in formula IS, the mass-to-volume ratio of crystal form A of the solvate shown in formula IA to N-methylpyrrolidone can be 50~200 g / L, for example 75 g / L.

[0248] In the method for preparing the crystal form S of the solvate shown by formula IS, the volume ratio of acetone to N-methylpyrrolidone can be 1:1 to 8:1, for example 3:1.

[0249] In some embodiments, the method for preparing the crystal form S of the solvate of formula IS includes the following steps: at 50°C (e.g., at 50°C for 30 min), the crystal form A of the solvate of formula IA is fully dissolved in N-methylpyrrolidone, filtered, the filtrate is collected, the filtrate is cooled (e.g., placed in an environment of -20°C) and acetone is added, filtered, and the solid is collected to obtain the crystal form S of the solvate of formula IS.

[0250] This invention provides a method for preparing crystal form R of the solvate shown in formula IR, which includes the following steps:

[0251] (1) Mix the crystal form A of the solvate shown in the above formula IA, water and NaOH to obtain mixture A;

[0252] (2) Add hydrochloric acid aqueous solution to the obtained mixture A to obtain the crystal form R of the solvate of formula IR.

[0253] In the preparation method of the crystal form R of the solvate represented by formula IR, in step (1), the molar ratio of the crystal form A of the solvate represented by formula IA to NaOH can be 1:1 to 1:2, for example 1:1.7 or 1:2.

[0254] In the preparation method of the crystal form R of the solvate represented by formula IR, in step (2), the molar ratio of the crystal form A of the solvate represented by formula IA to hydrochloric acid can be 1:1 to 1:3, for example 1:2 or 1:3, or 2:2.

[0255] In some embodiments, in the method for preparing the crystal form R of the solvate represented by formula IR, in step (2), the crystal form R of the solvate represented by formula IR may be added to the mixture A, for example, the crystal form R of the solvate represented by formula IR is added at a mass ratio of (0.5~2):100 with the crystal form A of the solvate represented by formula IA, preferably the crystal form R of the solvate represented by formula IR is added at a mass ratio of 1:75 with the crystal form A of the solvate represented by formula IA; the function of adding the crystal form R of the solvate represented by formula IR is to act as a seed crystal to help crystal formation.

[0256] In some embodiments, the method for preparing the crystal form R of the solvate represented by formula IR includes the following steps: mixing the crystal form A of the solvate represented by formula IA with water to obtain a mixture, adding 2 or 1.7 times the equivalent amount of NaOH to obtain mixture A, and mixing mixture A with an aqueous hydrochloric acid solution to obtain the crystal form R of the solvate represented by formula IR.

[0257] The present invention provides a method for preparing crystal form T of the solvate shown in formula IT, which includes the following steps: drying crystal form R of the solvate shown in formula IR at 50°C for 2 hours to obtain crystal form T of the solvate shown in formula IT.

[0258] The present invention also provides a pharmaceutical composition comprising substance X and a pharmaceutical excipient, wherein substance X is selected from one or more of the following: crystal form B of the compound represented by Formula I, crystal form A of the solvate represented by Formula IA, crystal form R of the solvate represented by Formula IR, crystal form T of the solvate represented by Formula IT, crystal form C of the solvate represented by Formula IC, crystal form D of the solvate represented by Formula ID, crystal form E of the solvate represented by Formula IE, crystal form F of the solvate represented by Formula IF, crystal form G of the solvate represented by Formula IG, crystal form I of the solvate represented by Formula II, crystal form K of the solvate represented by Formula IK, crystal form L of the solvate represented by Formula IL, crystal form M of the solvate represented by Formula IM, crystal form N of the solvate represented by Formula IN, crystal form O of the solvate represented by Formula IO, crystal form P of the solvate represented by Formula IP, and crystal form S of the solvate represented by Formula IS.

[0259] In some embodiments, in the pharmaceutical composition, substance X is a solvate of a compound of formula I. Specifically, the solvate of the compound of formula I is one or more of the following: the solvate of formula IA, the solvate of formula IR, the solvate of formula IT, the solvate of formula IC, the solvate of formula ID, the solvate of formula IE, the solvate of formula IF, the solvate of formula IG, the solvate of formula II, the solvate of formula IK, the solvate of formula IL, the solvate of formula IM, the solvate of formula IN, the solvate of formula IO, the solvate of formula IP, and the solvate of formula IS.

[0260] This invention also provides the use of substance X in the preparation of a TRPC5 inhibitor, wherein substance X is selected from one or more of the following: crystal form B of the compound shown in Formula I, crystal form A of the solvate shown in Formula IA, crystal form R of the solvate shown in Formula IR, crystal form T of the solvate shown in Formula IT, crystal form C of the solvate shown in Formula IC, crystal form D of the solvate shown in Formula ID, crystal form E of the solvate shown in Formula IE, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, crystal form K of the solvate shown in Formula IK, crystal form L of the solvate shown in Formula IL, crystal form M of the solvate shown in Formula IM, crystal form N of the solvate shown in Formula IN, crystal form O of the solvate shown in Formula IO, crystal form P of the solvate shown in Formula IP, and crystal form S of the solvate shown in Formula IS. The TRPC5 inhibitor is used in vivo or in vitro.

[0261] In some embodiments, in the application of substance X in the preparation of TRPC5 inhibitors, substance X is a solvate of the compound represented by formula I. Specifically, the solvate of the compound represented by formula I is one or more of the following: the solvate represented by formula IA, formula IR, formula IT, formula IC, formula ID, formula IE, formula IF, formula IG, formula II, formula IK, formula IL, formula IM, formula IN, formula IO, formula IP, and formula IS.

[0262] The present invention also provides the use of substance X in the preparation of a pharmaceutical product, wherein substance X is selected from one or more of the following: crystal form B of the compound shown in Formula I, crystal form A of the solvate shown in Formula IA, crystal form R of the solvate shown in Formula IR, crystal form T of the solvate shown in Formula IT, crystal form C of the solvate shown in Formula IC, crystal form D of the solvate shown in Formula ID, crystal form E of the solvate shown in Formula IE, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, crystal form K of the solvate shown in Formula IK, crystal form L of the solvate shown in Formula IL, crystal form M of the solvate shown in Formula IM, crystal form N of the solvate shown in Formula IN, crystal form O of the solvate shown in Formula IO, crystal form P of the solvate shown in Formula IP, and crystal form S of the solvate shown in Formula IS. The pharmaceutical product is a drug for treating and / or preventing TRPC5-mediated diseases.

[0263] In some embodiments, the use of substance X in the preparation of a pharmaceutical product, wherein substance X is a solvate of a compound represented by formula I, specifically, the solvate of the compound represented by formula I is one or more of the following: the solvate represented by formula IA, formula IR, formula IT, formula IC, formula ID, formula IE, formula IF, formula IG, formula II, formula IK, formula IL, formula IM, formula IN, formula IO, formula IP, and formula IS.

[0264] In the aforementioned applications, the TRPC5-mediated diseases may be mental illnesses, neurological disorders, neurodegenerative diseases, or kidney diseases.

[0265] The mental illnesses, neurological disorders, or neurodegenerative disorders mentioned may be selected from: disorders related to disordered emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, severe depressive disorder, psychotic depression, dysphoric mood and postpartum depression, and bipolar disorder); disorders related to anxiety and fear (e.g., post-traumatic stress disorder, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and separation anxiety); memory disorders (e.g., Alzheimer's disease, amnesia, aphasia, brain injury, brain tumor, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, Huntington's disease, learning disabilities, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke, and Wechsler-Colombian syndrome); disorders related to impaired impulse control and addiction; Parkinson's disease; amyotrophic lateral sclerosis (ALS); epilepsy; and other brain disorders caused by trauma or other damage including aging.

[0266] The kidney diseases mentioned may include focal segmental glomerulosclerosis (FSGS), minimal change disease, diabetic nephropathy, Allport syndrome, hypertensive nephropathy, nephrotic syndrome, steroid-resistant nephrotic syndrome, membranous nephropathy, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis (MPGN), immune complex-mediated MPGN, complement-mediated MPGN, lupus nephritis, post-infectious glomerulonephritis, thin basement membrane disease, glomerular membranoproliferative glomerulonephritis, amyloidosis (preferably primary amyloidosis), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease (anti-glomerular basement membrane disease), C3 glomerulonephritis, hypertensive nephrosclerosis, or primary glomerular disease (preferably IgA nephropathy).

[0267] The present invention also provides the application of substance X in the preparation of a pharmaceutical product, wherein substance X is selected from one or more of the following: crystal form B of the compound shown in Formula I, crystal form A of the solvate shown in Formula IA, crystal form R of the solvate shown in Formula IR, crystal form T of the solvate shown in Formula IT, crystal form C of the solvate shown in Formula IC, crystal form D of the solvate shown in Formula ID, crystal form E of the solvate shown in Formula IE, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, crystal form K of the solvate shown in Formula IK, crystal form L of the solvate shown in Formula IL, crystal form M of the solvate shown in Formula IM, crystal form N of the solvate shown in Formula IN, crystal form O of the solvate shown in Formula IO, crystal form P of the solvate shown in Formula IP, and crystal form S of the solvate shown in Formula IS. The pharmaceutical product is a drug for treating and / or preventing mental illnesses, neurological disorders, neurodegenerative diseases, or kidney diseases.

[0268] In some embodiments, when the substance X is used in the preparation of a pharmaceutical product, the substance X is a solvate of the compound represented by Formula I. Specifically, the solvate of the compound represented by Formula I is one or more of the following: the solvate represented by Formula IA, the solvate represented by Formula IR, the solvate represented by Formula IT, the solvate represented by Formula IC, the solvate represented by Formula ID, the solvate represented by Formula IE, the solvate represented by Formula IF, the solvate represented by Formula IG, the solvate represented by Formula II, the solvate represented by Formula IK, the solvate represented by Formula IL, the solvate represented by Formula IM, the solvate represented by Formula IN, the solvate represented by Formula IO, the solvate represented by Formula IP, and the solvate represented by Formula IS.

[0269] In the described application, the mental illness, neurological illness, or neurodegenerative illness may be selected from: illnesses related to disordered emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, severe depressive disorder, psychotic depression, dysphoric and postpartum depression, and bipolar disorder), illnesses related to anxiety and fear (e.g., post-traumatic stress disorder, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and separation anxiety), memory disorders (e.g., Alzheimer's disease, amnesia, aphasia, brain injury, brain tumor, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, Huntington's disease, learning disabilities, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke, and Wechsler-Colombian syndrome), illnesses related to impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and other brain illnesses caused by trauma or other damage including aging.

[0270] In the aforementioned applications, the kidney disease may be focal segmental glomerulosclerosis (FSGS), minimal change disease, diabetic nephropathy, Allport syndrome, hypertensive nephropathy, nephrotic syndrome, steroid-resistant nephrotic syndrome, membranous nephropathy, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis (MPGN), immune complex-mediated MPGN, complement-mediated MPGN, lupus nephritis, post-infectious glomerulonephritis, thin basement membrane disease, glomerular membranoproliferative glomerulonephritis, amyloidosis (preferably primary amyloidosis), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease (anti-glomerular basement membrane disease), C3 glomerulonephritis, hypertensive nephrosclerosis, or primary glomerular disease (preferably IgA nephropathy).

[0271] Unless otherwise stated, the following terms appearing in this specification and claims have the following meanings:

[0272] The term “treatment” refers to a therapeutic approach. When a specific condition is involved, treatment means: (1) alleviating one or more biological manifestations of the disease or condition; (2) interfering with (a) one or more points in a biological cascade that causes or precipitates the condition or (b) one or more biological manifestations of the condition; (3) improving one or more symptoms, effects or side effects associated with the condition, or one or more symptoms, effects or side effects associated with the condition or its treatment; or (4) slowing the development of the condition or one or more biological manifestations of the condition.

[0273] The term "prevention" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0274] The term "patient" refers to any animal, preferably a mammal, that is about to receive or has already received administration of the compound or composition according to embodiments of the invention. The term "mammal" includes any mammal. Examples of mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc., with humans being preferred.

[0275] The term "therapeutic effective amount" refers to the amount of a compound, when administered to a patient, sufficient to effectively treat the disease or condition described herein. The "therapeutic effective amount" will vary depending on the compound, the condition and its severity, and the age of the patient to be treated, and may be adjusted as needed by those skilled in the art.

[0276] The term "solvate" refers to a substance formed by the combination of the compound of this invention with a stoichiometric or non-stoichiometric solvent. Solvent molecules in a solvate can exist in an ordered or disordered arrangement. The solvents include, but are not limited to, water, methanol, and ethanol.

[0277] The term "pharmaceutical excipients" refers to excipients and additives used in the production of pharmaceuticals and the dispensing of prescriptions. It includes all substances contained in pharmaceutical preparations, excluding the active ingredient. See the Pharmacopoeia of the People's Republic of China (2020 Edition), Volume IV, or the Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009 Sixth Edition).

[0278] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0279] The reagents and raw materials used in this invention are all commercially available.

[0280] The positive and progressive effects of this invention are that the crystal form has good stability and good processability in formulation, and the efficacy is good with broad application prospects. Attached Figure Description

[0281] Figure 1 The image shows the XRPD spectrum of crystal form A of the solvate shown in formula IA.

[0282] Figure 2 The image shows the DSC spectrum of crystal form A of the solvate shown in formula IA.

[0283] Figure 3 The TGA spectrum is shown for crystal form A of the solvate represented by formula IA.

[0284] Figure 4 For the solvate shown in formula IA, the crystal form A is... 1 H-NMR spectrum (DMSO-d6).

[0285] Figure 5 For the solvate shown in formula IA, the crystal form A is... 1 H-NMR spectrum (D2O).

[0286] Figure 6 The PLM spectrum is shown for crystal form A of the solvate represented by formula IA.

[0287] Figure 7 The image shows the FT-IR spectrum of crystal form A of the solvate shown in formula IA.

[0288] Figure 8 The image shows the XRPD spectrum of crystal form B of the compound represented by Formula I.

[0289] Figure 9 The image shows the DSC spectrum of crystal form B of the compound represented by Formula I.

[0290] Figure 10 The TGA spectrum of crystal form B of the compound shown in Formula I is shown.

[0291] Figure 11 For the crystal form B of the compound shown in Formula I 1 H-NMR spectrum.

[0292] Figure 12 The PLM spectrum of crystal form B of the compound shown in Formula I is shown.

[0293] Figure 13 The image shows the FT-IR spectrum of crystal form B of the compound represented by Formula I.

[0294] Figure 14 The image shows the XRPD spectrum of crystal form C of the solvate shown in formula IC.

[0295] Figure 15 The image shows the DSC spectrum of crystal form C of the solvate shown in formula IC.

[0296] Figure 16 The TGA spectrum is shown for crystal form C of the solvate represented by formula IC.

[0297] Figure 17 For the crystal form C of the solvate shown in formula IC 1 H-NMR spectrum.

[0298] Figure 18 The image shows the XRPD spectrum of crystal form D of the solvate shown in formula ID.

[0299] Figure 19 The image shows the DSC spectrum of crystal form D of the solvate shown in formula ID.

[0300] Figure 20The TGA spectrum is shown for crystal form D of the solvate represented by formula ID.

[0301] Figure 21 For the crystal form D of the solvate shown in formula ID 1 H-NMR spectrum.

[0302] Figure 22 The image shows the XRPD spectrum of crystal form E of the solvate shown in formula IE.

[0303] Figure 23 The image shows the DSC spectrum of crystal form E of the solvate represented by formula IE.

[0304] Figure 24 The TGA spectrum is shown for crystal form E of the solvate represented by formula IE.

[0305] Figure 25 For the crystal form E of the solvate shown in formula IE 1 H-NMR spectrum.

[0306] Figure 26 The image shows the XRPD spectrum of crystal form F of the solvate represented by formula IF.

[0307] Figure 27 The image shows the DSC spectrum of crystal form F of the solvate represented by formula IF.

[0308] Figure 28 The TGA spectrum is shown for crystal form F of the solvate represented by formula IF.

[0309] Figure 29 For the crystal form F of the solvate shown by formula IF 1 H-NMR spectrum.

[0310] Figure 30 The image shows the XRPD spectrum of crystal form G of the solvate shown in formula IG.

[0311] Figure 31 The image shows the DSC spectrum of crystal form G of the solvate represented by formula IG.

[0312] Figure 32 The TGA spectrum is shown for crystal form G of the solvate represented by formula IG.

[0313] Figure 33 The crystal form G of the solvate shown in formula IG 1 H-NMR spectrum.

[0314] Figure 34 The image shows the XRPD spectrum of crystal form I of the solvate shown in Formula II.

[0315] Figure 35 The image shows the DSC spectrum of crystal form I of the solvate shown in Formula II.

[0316] Figure 36 The TGA spectrum is for crystal form I of the solvate shown in Formula II.

[0317] Figure 37 For the solvate shown in Formula II, crystal form I 1 H-NMR spectrum.

[0318] Figure 38 The image shows the XRPD spectrum of crystal form K of the solvate represented by formula IK.

[0319] Figure 39 The TGA spectrum is shown for crystal form K of the solvate represented by formula IK.

[0320] Figure 40 For the crystal form K of the solvate shown by formula IK 1 H-NMR spectrum.

[0321] Figure 41 The image shows the XRPD spectrum of crystal form L of the solvate represented by formula IL.

[0322] Figure 42 The image shows the DSC spectrum of crystal form L of the solvate represented by formula IL.

[0323] Figure 43 The TGA spectrum is shown for crystal form L of the solvate represented by formula IL.

[0324] Figure 44 For the solvate of formula IL, the crystal form L is 1 H-NMR spectrum.

[0325] Figure 45 The image shows the XRPD spectrum of crystal form M of the solvate represented by formula IM.

[0326] Figure 46 The TGA spectrum is shown for crystal form M of the solvate represented by formula IM.

[0327] Figure 47 For the crystal form M of the solvate shown in formula IM 1 H-NMR spectrum.

[0328] Figure 48 The image shows the XRPD spectrum of crystal form N of the solvate represented by formula IN.

[0329] Figure 49 The image shows the DSC spectrum of crystal form N of the solvate represented by formula IN.

[0330] Figure 50 The TGA spectrum is shown for crystal form N of the solvate represented by formula IN.

[0331] Figure 51 For the crystal form N of the solvate shown in formula IN 1 H-NMR spectrum.

[0332] Figure 52 The image shows the XRPD spectrum of crystal form O of the solvate shown in formula IO.

[0333] Figure 53 The image shows the DSC spectrum of crystal form O of the solvate shown in formula IO.

[0334] Figure 54 The TGA spectrum of crystal form O of the solvate shown in formula IO is shown.

[0335] Figure 55 For the solvate shown in formula IO, the crystal form O is 1 H-NMR spectrum.

[0336] Figure 56 The image shows the XRPD spectrum of crystal form P of the solvate shown in formula IP.

[0337] Figure 57 The image shows the DSC spectrum of crystal form P of the solvate represented by formula IP.

[0338] Figure 58 The TGA spectrum of crystal form P of the solvate shown in formula IP is shown.

[0339] Figure 59 The crystal form P of the solvate shown in formula IP 1 H-NMR spectrum.

[0340] Figure 60 The image shows the XRPD spectrum of the crystal form R of the solvate shown in formula IR.

[0341] Figure 61 The image shows the DSC spectrum of crystal form R of the solvate represented by formula IR.

[0342] Figure 62 The TGA spectrum of the crystal form R of the solvate shown in formula IR is shown.

[0343] Figure 63 The crystal form R of the solvate shown in formula IR 1 H-NMR spectrum.

[0344] Figure 64 The image shows the XRPD spectrum of crystal form S of the solvate shown by formula IS.

[0345] Figure 65 The image shows the DSC spectrum of crystal form S of the solvate shown by formula IS.

[0346] Figure 66The TGA spectrum is shown for crystal form S of the solvate represented by formula IS.

[0347] Figure 67 The crystal form S of the solvate shown by formula IS 1 H-NMR spectrum.

[0348] Figure 68 The image shows the XRPD spectrum of crystal form T of the solvate represented by formula IT.

[0349] Figure 69 The image shows the DSC spectrum of crystal form T of the solvate represented by formula IT.

[0350] Figure 70 The TGA spectrum is shown for crystal form T of the solvate represented by formula IT.

[0351] Figure 71 The crystal form T of the solvate shown by formula IT 1 H-NMR spectrum.

[0352] Figure 72 The image shows the XRPD overlays of the solvate crystal form A before and after a 1-week stability test, as shown in formula IA.

[0353] Figure 73 The TGA spectrum of crystal form A of the solvate of formula IA obtained after being placed in a sealed environment at 60°C for 1 week is shown.

[0354] Figure 74 The TGA spectrum of crystal form A of the solvate of formula IA obtained after being placed in an open environment at 40°C / 75%RH for 1 week is shown.

[0355] Figure 75 The TGA spectrum of crystal form A of the solvate of formula IA obtained after being placed in an open environment at 25°C / 92%RH for 1 week is shown.

[0356] Figure 76 XRPD overlay images of crystal form B of the compound shown in Formula I before and after a 1-week stability test.

[0357] Figure 77 The TGA spectrum of crystal form B of the compound of formula I obtained after being placed in a sealed environment at 60°C for 1 week.

[0358] Figure 78 The TGA spectrum of crystal form B of the compound of formula I obtained after being placed in an open environment at 40°C / 75%RH for 1 week.

[0359] Figure 79 The TGA spectrum of crystal form B of the compound of formula I obtained after being placed in an open environment at 25°C / 92%RH for 1 week.

[0360] Figure 80 The image shows the DVS spectrum of crystal form A of the solvate shown in formula IA at 25°C.

[0361] Figure 81 The image shows the XRPD overlay of crystal form A of the solvate shown in formula IA before and after the DVS test.

[0362] Figure 82 The image shows the DVS diagram of crystal form B of the compound shown in Formula I at 25°C.

[0363] Figure 83 XRPD overlay images of crystal form B of the compound shown in Formula I before and after DVS testing.

[0364] Figure 84 XRPD overlay images of crystal form B of the compound shown in Formula I before and after pressure and grinding tests. Detailed Implementation

[0365] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0366] Abbreviations:

[0367] ACN: Acetonitrile; DMF: N,N-dimethylformamide; DMSO: Dimethyl sulfoxide; DMI: 1,3-dimethyl-2-imidazolium ketone; DSC: Differential scanning calorimetry; DVS: Dynamic moisture adsorption; EA: Ethyl acetate; EtOH: Ethanol; eq.: Equivalent; FT-IR: Fourier transform infrared spectroscopy; HPLC: High performance liquid chromatography; IPA: Isopropanol; MTBE: Methyl tert-butyl ether; NMP: N-methylpyrrolidone; PLM: Polarizing microscope; RH: Relative humidity; TGA: Thermogravimetric analysis; T onset Initial temperature / starting temperature. TFE: trifluoroethanol; XRPD: X-ray powder diffraction.

[0368] Instrumentation and Methods:

[0369] 1. X-ray diffraction (XRPD), the test conditions are shown in the table below:

[0370]

[0371] 2. Differential scanning calorimetry (DSC) analysis, test conditions are shown in the table below:

[0372]

[0373] 3. Thermogravimetric analysis (TGA), the test conditions are shown in the table below:

[0374]

[0375] 4. Dynamic moisture adsorption (DVS), the test conditions are shown in the table below:

[0376]

[0377] 5. High-performance liquid chromatography (HPLC), the test conditions are shown in the table below:

[0378]

[0379] 6. Nuclear magnetic resonance (NMR) 1 H-NMR), the test conditions are shown in the table below:

[0380]

[0381] 7. Fourier transform infrared spectroscopy (FT-IR), the test conditions are shown in the table below:

[0382]

[0383] 8. Karl Fisher, test conditions are shown in the table below:

[0384]

[0385] 9. Polarizing microscope (PLM), test conditions are as follows:

[0386]

[0387] Preparation Examples

[0388] Compound 1-1 was prepared according to the method described in WO2022 / 001767A1.

[0389] Example 1: Preparation of crystal form A of the solvate shown in formula IA

[0390] Synthesis route:

[0391]

[0392] 1.1 Preparation of compounds 1-2

[0393] Compound 1-1 (100 g, 0.23 mol), sodium iodide (37.3 g, 0.25 mmol), and tetrahydrofuran (1 L) were added to a reaction flask and stirred to dissolve. The mixture was then cooled to approximately 0°C in an ice bath. Lithium tert-butoxide (1 M tetrahydrofuran solution, 271.6 mL, 0.28 mol) was added dropwise to the reaction solution. After the addition was complete, di-tert-butyl chloromethyl phosphate (87.8 g, 0.34 mol) was added to the reaction solution. The reaction solution was then heated to room temperature (approximately 18°C) and reacted for 12 hours. The reaction solution was quenched with water and concentrated below 25°C to remove tetrahydrofuran. The concentrated system was extracted with ethyl acetate (1 L × 2). The organic phase was washed with saturated brine (1 L), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain compound 1-2 (55 g). LC-MS [M+H] + =664.2.

[0394] 1.2 Preparation of crystal form A of the solvate shown in formula IA

[0395] Compounds 1-2 (55 g, 83 mmol) were dissolved in dichloromethane (500 mL). Trifluoroacetic acid (100 mL) was added dropwise to the reaction solution with stirring. The mixture was stirred at 25 °C for 1 hour. After the reaction was completed (LCMS showed a purity of 80%), the mixture was concentrated under reduced pressure to obtain a crude product of the oily compound I. Acetonitrile (50 mL) was added to the crude product for dispersion, and a solid precipitated. Ethanol (400 mL) was slowly added dropwise to the system, and a large amount of solid precipitated. The mixture was stirred at room temperature (approximately 17 °C) for 1 hour, filtered, and the filter cake was slurried using a mixed solvent of acetonitrile and water (300 mL, 5 / 1 (v / v)) at room temperature (approximately 17 °C). This operation was repeated several times until the purity of the compound was above 98%. The obtained solid was lyophilized to obtain crystal form A, a white solid. The XRPD spectral analysis data are shown in Table 1.

[0396] LC-MS [M+H] + =552.0; 1 H NMR (400 MHz, DMSO-d6): δ 8.14 (s, 1H), 7.84(dd, J = 9.2, 2.8 Hz, 1H), 7.79 (dd, J = 8.4, 5.6 Hz, 1H), 7.68 (td, J = 8.4,2.6 Hz, 1H), 7.36 (s, 1H), 5.68 (d, J = 7.6 Hz, 2H), 4.91 (s, 2H), 4.54 (t, J= 5.6 Hz, 2H), 3.98 (t, J = 5.6 Hz, 2H).

[0397] The characterization data for crystal form A are shown in the table below:

[0398]

[0399] Table 1. XRPD pattern analysis data for crystal form A

[0400]

[0401] Example 2: Preparation of crystal form B of the compound shown in Formula I

[0402] Weigh approximately 30 mg of crystal form A and add it to 0.3 mL of water to ensure a suspension of appropriate concentration. Stir the suspension at a temperature change rate of 0.1°C / min from 50°C to 5°C for 10 cycles. After the cycles are complete, filter the resulting solid through a 0.45 µm membrane and centrifuge at 5°C for 5 min. Use the resulting solid as seed crystals for the next step.

[0403] Weigh 400 mg of crystal form A into an 8 mL glass bottle. Add 4 mL of water and stir at 50°C for 30 min to obtain a suspension. Add approximately 5 mg of the seed crystals prepared above to the suspension. Place the sample on a temperature-regulating cycler and stir the suspension at a rate of 0.1°C / min from 50°C to 5°C for 6 cycles. Centrifuge and filter to collect the solid. After vacuum drying the solid at 50°C for 2 h, 333.0 mg of the off-white compound of formula I, crystal form B, was obtained, with a yield of 83.3%. Its XRPD spectral resolution data are shown in Table 2.

[0404] The characterization data for crystal form B are shown in the table below:

[0405]

[0406] Table 2. XRPD pattern analysis data for crystal form B

[0407] .

[0408] Example 3 Preparation of crystal forms C~E of the solvate of the compound shown in Formula I

[0409] The solvates of the compounds shown in Formula I, in crystal forms C to E, were prepared using an antisolvent crystallization method. Approximately 30 mg of crystal form A of the solvate shown in Formula IA was weighed and dissolved thoroughly in an appropriate volume (see table below) of a good solvent. The solution was then filtered through a 0.45 µm filter membrane to obtain a clear solution. An antisolvent (1-3 times the volume of the good solvent) was slowly added to the resulting clear solution. The resulting suspension was filtered, and the resulting solid fraction was characterized by XRPD. The good solvents and antisolvents used in the preparation of crystal forms C to E are shown in the table below, and their XRPD spectral resolution data are shown in Tables 3, 4, and 5.

[0410] The operating conditions are shown in the table below:

[0411]

[0412] The C~E characterization data of the crystal form are shown in the table below:

[0413]

[0414] Table 3. XRPD pattern analysis data of crystal form C

[0415]

[0416] Table 4. XRPD pattern analysis data for crystal form D

[0417]

[0418] Table 5. XRPD pattern analysis data for crystal form E

[0419] .

[0420] Example 4 Preparation of crystal forms F, G, I and K of the solvates of the compounds shown in Formula I

[0421] The crystal forms F, G, I, and K of the solvate (Formula IF, IG, IG, II, and IK) were prepared using a temperature cycling method. Approximately 30 mg of crystal form A of the solvate (Formula IA) was weighed and added to the solvent under the conditions shown in the table below, ensuring a suspension of appropriate concentration. The suspension was stirred for 10 cycles from 50°C to 5°C at a temperature cycling rate of 0.1°C / min. After cycling, the resulting solid was centrifuged at 5°C for 5 min using a 0.45 µm filter membrane and characterized by XRPD. The operating conditions for preparing crystal forms F, G, I, and K of the solvate (Formula IF, IG, IG, II, and IK) are shown in the table below, and their XRPD spectral analysis data are shown in Tables 6, 7, 8, and 9.

[0422] The operating conditions are shown in the table below:

[0423]

[0424] The characterization data for crystal forms F, G, I, and K are shown in the table below:

[0425] " / / ": indicates that the action has not been taken.

[0426] Table 6. XRPD pattern analysis data for crystal form F.

[0427]

[0428] Table 7. XRPD pattern analysis data for crystal form G

[0429]

[0430] Table 8. XRPD pattern analysis data for crystal form I

[0431]

[0432] Table 9. XRPD pattern analysis data for crystal form K

[0433] .

[0434] Example 5 Preparation of crystal forms L, N, O and P of the solvates of the compounds shown in Formula I

[0435] The crystal forms L of the solvate represented by formula IL, N of the solvate represented by formula IN, O of the solvate represented by formula IO, and P of the solvate represented by formula IP were prepared using a one-week suspension method at 50°C. Approximately 30 mg of crystal form A of the solvate represented by formula IA was weighed and placed in a 2 mL glass bottle. Solvent was added under the operating conditions shown in the table below, and the mixture was suspended at 50°C and 400 rpm for one week. After one week, the resulting suspension was filtered, and the resulting solid fraction was characterized by XRPD. The XRPD spectral resolution data are shown in Tables 10, 11, 12, and 13.

[0436] The operating conditions are shown in the table below:

[0437]

[0438] The characterization data are shown in the table below:

[0439] " / / ": indicates that the action has not been taken.

[0440] Table 10 XRPD pattern analysis data of crystal form L

[0441]

[0442] Table 11 XRPD pattern analysis data of crystalline form N

[0443]

[0444] Table 12 XRPD spectrum analysis data of crystal form O

[0445]

[0446] Table 13 XRPD spectrum analysis data of crystal form P

[0447]

[0448] Example 6 Preparation of crystal form M of the solvate shown in formula IM

[0449] The crystal form M of the solvate shown in formula IM was prepared by a suspension experiment at 25°C. Approximately 30 mg of the crystal form A of the solvate shown in formula IA was weighed and placed in a 2 mL glass bottle, and 0.2 mL of trifluoroethanol was added. The mixture was suspended at 25°C and 400 rpm for 2 weeks. After 2 weeks, the resulting suspension was filtered, and the resulting solid fraction was characterized by XRPD. The XRPD spectrum analysis data are shown in Table 14.

[0450] The characterization data are shown in the table below:

[0451]

[0452] " / / ": indicates that the action has not been taken.

[0453] Table 14 XRPD spectrum analysis data for crystal form M

[0454]

[0455] Example 7 Preparation of crystal form S of the solvate shown by formula IS

[0456] Crystal form S of the solvate shown in Formula IS was prepared by rapid cooling crystallization. Approximately 30 mg of crystal form A of the solvate shown in Formula IA was weighed and added to 0.4 mL of N-methylpyrrolidone, dissolved completely at 50°C. The solution was then filtered hot through a 0.45 µm filter membrane to obtain a clear solution. The obtained clear solution was kept at 50°C for 30 min, and then rapidly cooled in a -20°C freezer, with the antisolvent acetone (1.2 mL) added. The resulting solid was collected by filtration and characterized; its XRPD spectral resolution data are shown in Table 15.

[0457] The characterization data are shown in the table below:

[0458] " / / ": indicates that the action has not been taken.

[0459] Table 15 XRPD pattern analysis data for crystal form S

[0460]

[0461] Example 8: Preparation of crystal forms R and T of the solvate of the compound shown in Formula I

[0462] 8.1 Preparation method of crystal form R of the solvate shown in formula IR

[0463] Weigh approximately 20 mg of solvate A (formula IA) and suspend it in 2 mL of water. Add 1.7 equivalents of sodium hydroxide to clarify the solution, and measure the pH to be 6.0. Then add 1 mL of 100 mM hydrochloric acid solution to adjust the pH to 2.5, and the solid continuously precipitates out. Collect the solid by centrifugation as seed crystals for the following reaction.

[0464] Weigh 150 mg of solvate A (formula IA) into a 20 mL glass bottle. Add 6 mL of water and stir to suspend at 25°C. Add 2 equivalents of sodium hydroxide, continue stirring, and filter through a centrifuge tube to remove a small amount of insoluble flocculent material at the bottom. The pH value is measured to be 11.0. Slowly add about 6 mL of 100 mM hydrochloric acid aqueous solution and about 2 mg of the seed crystals prepared above, continue stirring, and the pH value is measured to be 2.5. Centrifuge and filter, collect the solid, and air-dry in a fume hood for about 3 days. 116.2 mg of off-white solvate R (formula IR) was obtained, with a yield of 77.5%. Its XRPD spectral resolution data are shown in Table 16.

[0465] 8.2 Preparation method of crystal form T of the solvate shown in formula IT

[0466] The crystal form R of the solvate shown in formula IR was dried under vacuum at 50°C for 2 h to obtain the crystal form T (hydrate) of the solvate shown in formula IT. Its XRPD spectrum resolution data are shown in Table 17.

[0467] The characterization data are shown in the table below:

[0468]

[0469] Table 16 XRPD pattern analysis data for crystal form R

[0470]

[0471] Table 17 XRPD pattern analysis data for crystal form T

[0472]

[0473] Evaluation of crystal form:

[0474] 1. Solid stability studies of crystal form A and crystal form B

[0475] Crystal form A of the solvate shown in Formula IA and crystal form B of the compound shown in Formula I were placed under sealed conditions at 60°C, open conditions at 40°C / 75%RH, and open conditions at 25°C / 92%RH for one week. The solids obtained after the stability tests were analyzed by XRPD, TGA, and HPLC. As shown in Table 18, the results show that crystal form A and crystal form B did not exhibit any crystal form change or significant chemical degradation during the above stability tests. Figures 72-79 .

[0476] Table 18 Solid stability studies of crystal forms A and B

[0477]

[0478] 2. Hygroscopicity Study of Crystal Forms A and B

[0479] The hygroscopicity of solvate A (Formula IA) and solvate B (Formula I) at 25°C was evaluated using dynamic moisture adsorption (DVS) testing. The DVS cycle for solvate A was 40–95–0–95–40%RH, and for solvate B it was 40–0–95–0–40%RH. The dm / dt ratio was 0.002, the shortest equilibrium time was 60 min, and the longest equilibrium time was 360 min. After DVS testing, XRPD was used to investigate whether the crystal forms changed.

[0480] The results showed that crystal form A is hygroscopic. At 25°C, it absorbs 4.3% moisture from 40% to 95% RH. Figure 80 Furthermore, there is a risk of crystal transformation under high humidity. No crystal transformation was observed after dynamic moisture adsorption experiments, and the crystallinity did not change significantly. Figure 81 The results showed that crystal form B has slight hygroscopicity. It absorbs 1.9% moisture from 0% to 95% RH at 25°C. Figure 82 No crystallization phenomenon was observed after the dynamic moisture adsorption experiment, and the crystallinity did not change significantly. (See...) Figure 83 .

[0481] 3. Feasibility assessment of crystal form B formulation

[0482] 3.1 Study on crystal transformation behavior under pressure

[0483] Approximately 10 mg of crystal form B of the compound shown in Formula I was weighed and compressed into a tablet at 10 MPa for 5 minutes using a small tablet press. The crystal form transformation and changes in crystallinity were investigated by XRPD characterization. The results showed that the crystallinity of crystal form B did not change significantly under this pressure. Figure 84 .

[0484] 3.2 Simulated Dry Grinding Experiment

[0485] Approximately 10 mg of crystal form B of the compound shown in Formula I was weighed and ground in a mortar for 3 min. The crystal form transformation and changes in crystallinity were investigated by XRPD characterization. The results showed that the crystallinity of crystal form B did not change significantly in this experiment. Figure 84 .

[0486] 3.3 Simulated Wet Grinding Experiment

[0487] Approximately 10 mg of crystal form B of the compound shown in Formula I was weighed and added to 20 µL of water or ethanol, respectively. The mixture was then ground in a mortar for 3 min. XRPD characterization was used to investigate the crystal form transformation and changes in crystallinity. The results showed that grinding crystal form B in water or ethanol did not significantly change its crystallinity. (See below) Figure 84 .

[0488] Biological activity test

[0489] Example 1

[0490] TRPC5 is a non-selective cation channel that is permeable to calcium ions. Therefore, this experiment used the TRPC5 agonist Englerin A (EA) and the TRPC5 inhibitor Pico145 as positive controls. Fluo-4 AM fluorescent dye was used to detect the effects of these compounds on intracellular calcium ions in TRPC5-HEK 293 cells. 2+ The effect of the compound on the TRPC5 channel can be indirectly reflected by the influence of the compound.

[0491] Pico145: MCE, lot number 31245;

[0492] DMEM high sugar: Gibco, batch number 2230805;

[0493] FBS: Gibco, batch number 1981614;

[0494] P / S: Gibco, Lot No. 2289326;

[0495] HEPES: Sigma, batch number WXBD0664V;

[0496] Blasticidin: Gibco, batch number 1737347;

[0497] Hygromycine: Yeasen, batch number H18010;

[0498] Doxycycline: Sigma, batch number BCBL6540V;

[0499] Fluo-4 AM: Molecular Devices, Lot No. 1231041;

[0500] Poly-D-Lysine: Sigma, lot number SLBQ9797V.

[0501] 1. Cell Culture

[0502] 1.1 TRPC5-HEK 293 cell resuscitation

[0503] Resuscitation fluid: 100% DMEM (Dulbecco's Modified Eagle Medium), high sugar content.

[0504] Selective culture medium: DMEM high glucose + 10% FBS (Phosphate Buffered Saline) + 1% P / S (Penicillin-Streptomycin Solution) + 1% HEPES (4-hydroxyethylpiperazine ethanesulfonic acid) + Blasticidin (5 μg / mL) + Hygromycine (50 μg / mL)

[0505] Induction medium: DMEM high glucose + 10% FBS + 1% P / S + 1% HEPES + doxycycline (1 μg / mL)

[0506] Resuscitation process: Remove from liquid nitrogen tank, transfer to water bath in ice box, stir in a circular motion to dissolve until a small piece of ice is present, then transfer the cryopreservation solution to the resuscitation solution, centrifuge at 1000 rpm for 5 min, discard the supernatant, transfer to selective medium, and expand in a CO2 incubator (5% CO2, 95% humidity, 37℃).

[0507] 1.2 TRPC5-HEK 293 cell grafting plate

[0508] 14 h before the real-time fluorescence experiment, the cells were washed with PBS, digested with trypsin containing EDTA, and diluted with induction medium to 200,000 cells / mL. The cells were then inoculated into 96-well black-walled permeable plates coated with poly-D-Lysine (PDL) (stock solution 10 mg / mL, final concentration 10 μg / mL), 100 μL / well, which is 20,000 cells / well.

[0509] 2. Buffer solution preparation

[0510] 500 mL TRPC5 calcium signal detection external solution: 4.0908 g NaCl, 0.1864 g KCl, 0.111 g CaCl2, 0.0476 g MgCl2, 0.9 g Glucose, 1.1915 g HEPES (4-hydroxyethylpiperazine ethanesulfonic acid).

[0511] Calcium fluorescent dye: TRPC5 calcium signal detection external solution containing a final concentration of 4 μM Fluo-4 (containing 0.5% BSA).

[0512] 3. Preparation of compounds

[0513] Agonist: Englerin A (EA)

[0514] Agonist concentration: Due to EA activating TRPC5 EC 50 At approximately 0.35 nM, using 0.3 nM EA

[0515] Positive inhibitor: Pico145 (HC608)

[0516] Positive inhibitor concentration: 100 nM

[0517] Test compounds: Compound 1-1 and the compound shown in Formula I

[0518] Analytical compound concentration: Prepared using standard methods with DMSO, the solution is prepared to be 8 times the final detection concentration (final detection concentrations are 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM and 1000 nM respectively), 60 μL per well of the substrate.

[0519] 4. Data Processing

[0520] The fluorescence values ​​obtained by Flipr assay were subtracted from the values ​​of unstained cell wells (i.e., background fluorescence values). Statistical analysis and data processing were performed using Graphpad Prism 6.0 software. Normalization was performed by removing the baseline, and the results were displayed as ratios. The AUC (area under the curve of the calcium flow signal) was calculated. The data were collected and the logarithmic value of the compound concentration was used to calculate the IC using the log[Inhibitor] vs. response — Variable slope method. 50 value.

[0521] The results are shown in Table 19: The compound shown in Formula I has no inhibitory activity on the TRPC5 channel.

[0522] Table 19

[0523]

[0524] Example 2: PK study of male SD rats after single gavage administration of the compound (using 5% Solutol as solvent).

[0525] 1. Experimental objective:

[0526] The time-plasma concentration curves of the compound in the plasma of male rats after a single oral administration of the compound represented by Formula I (125 mg / kg) and compound 1-1 (100 mg / kg) were investigated to obtain the pharmacokinetic parameters (Cp) of the compound represented by Formula I and compound 1-1 in rats after a single oral administration. max T max AUC last AUC inf T 1 / 2 MRT, etc.

[0527] 2. Experimental Design

[0528] 2.1 Experimental Apparatus

[0529] The experimental instruments are shown in Table 20:

[0530] Table 20

[0531]

[0532] 2.2 Experimental Preparation

[0533] 2.2.1 Experimental preparation for the compound represented by Formula I of this invention

[0534] Rats: SD rats, SPF grade, 3 males, weighing between 180-200g (Source: Beijing Vital River Laboratory Animal Technology Co., Ltd., Certificate No.: 110011201109106028).

[0535] Householding conditions: Standard animal room, free access to food and water, 3 animals per cage, 12 / 12-hour light / dark cycle (7:00am / 7:00pm), temperature 23±1℃.

[0536] Preparation: After accurately weighing the compound shown in Formula I of PO, first add the required volume of 5% solubilol (5% polyethylene glycol (15)-hydroxystearate, Beijing Fengli Jingqiu Pharmaceutical Co., Ltd., batch number 1760094G0), vortex mix for 2 minutes, sonicate for 30 minutes, stir for 2 hours until no particles are visible to the naked eye, administer the drug while stirring, and take the middle layer of the drug solution for administration.

[0537] Before administration, the drug solution needs to be sampled for analysis. Two 100 μL samples of the suspension should be taken from the top, middle and bottom of the suspension and sent for analysis on the same day. Backup samples should be stored in a -75℃ refrigerator for later use.

[0538] 2.2.2 Experimental preparation for compound 1-1

[0539] Rats: SD rats, SPF grade, 3 males, weighing between 220-300g (Source: Beijing Speford Biotechnology Co., Ltd., Certificate No.: 110324200103216838).

[0540] Householding conditions: Standard animal room, free access to food and water, 3 animals per cage, 12 / 12-hour light / dark cycle (7:00am / 7:00pm), temperature 23±1℃.

[0541] Preparation: After accurately weighing compound 1-1 of group PO, add the required volume of 5% solubilol, vortex mix for 2 min, sonicate for 30 min, stir for 3 h until no particles are visible to the naked eye, and then administer by gavage.

[0542] Prepare and use immediately. Samples of the solution must be retained for analysis. Take two 100 μL portions (top, middle, and bottom) of the suspension and send them for analysis and testing on the same day.

[0543] 2.3 Dosing regimen

[0544] Rats were randomly divided into 3 groups according to their body weight. The specific grouping and drug administration are shown in Table 21 below:

[0545] Table 21 Information on grouped dosing of compounds represented by Formula I of this invention

[0546]

[0547] 1. Animals in the PO group were fasted overnight but allowed free water before administration, and were given food 4 hours after administration;

[0548] 2. Blood collection time points: Blood collection time points for the PO group were 0.167, 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours.

[0549] Table 22 Grouping and Dosing Information for Compound 1-1

[0550]

[0551] 1. Animals in the PO group were fasted overnight but allowed free water before administration, and were given food 4 hours after administration;

[0552] 2. Blood collection time points: Blood collection time points for the PO group were 0.167, 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours.

[0553] 2.4 Sample Collection and Preparation

[0554] After administration to rats, blood was collected from the orbital venous plexus at sampling time points. Approximately 0.2-0.3 mL of blood was collected at each time point into an anticoagulant EP tube (containing 4 μL EDTA-K2, 375 mg / mL). The tube was slowly inverted three times and stored in an ice box (for no more than 30 minutes). The tube was centrifuged at 3500×g for 10 minutes at 4°C. The supernatant was transferred to a labeled EP tube, and the plasma hemolysis was observed and recorded. The samples were then sent for bioanalytical analysis. If the samples could not be tested on the same day, they should be stored at -80°C until testing (note that repeated freezing / thawing processes should be avoided).

[0555] 2.5 Sample Analysis

[0556] 2.5.1 Sample analysis of the compound represented by Formula I of this invention

[0557] 2.5.1.1 Experimental Apparatus:

[0558] High-performance liquid chromatography pump: Exion LC AD Pump, Sciex Corporation

[0559] Autosampler (Exion LC AD Autosampler, Sciex Corporation)

[0560] Column Oven: Exion LC AD Column Oven, Sciex Corporation

[0561] Mass spectrometer: AB Sciex Qtrap 3500

[0562] High-speed refrigerated centrifuge: Thermo Fisher, ST16R, GG1206085-093

[0563] Analytical balance (Electronic balance): Mettler Toledo, MS-105DU, GG1206363

[0564] Miniature Vortex Analyzer: Shanghai Huxi Analytical Instrument Factory, WH-2, GG1206487

[0565] Experimental material: Rat plasma (EDTA-K2)

[0566] Analyte: Compound 1-1

[0567] Internal standard: Tolbutamide

[0568] Analytical method: Liquid chromatography-mass spectrometry (LC-MS)

[0569] 2.5.1.2 Mass spectrometry conditions:

[0570] Mass spectrometry parameters

[0571] Ion source: Ion Electrospray (ESI)

[0572] Ionization mode: Positive ion mode

[0573] Detection Mode: Multiple Response Monitoring (MRM)

[0574] Ion Spray Voltage: 5500

[0575] Turbo Ion Spray Temperature: 550℃

[0576] Curtain Gas: 35

[0577] Collision pool gas (CAD Gas): Medium

[0578] Nebulizing Gas (Gas 1): 55.00

[0579] Auxiliary Gas (Gas 2): 55.00

[0580] Detection of ion pairs (Table 23):

[0581] Table 23

[0582]

[0583] 2.5.1.3 Liquid phase method:

[0584] Column: Poroshell 120 EC-C18 (2.1 × 50 mm, 2.7 μm)

[0585] Mobile Phase A: 0.1% aqueous solution of formic acid

[0586] Mobile Phase B: A methanol solution of 0.1% formic acid

[0587] Rinse Port Wash Solution: Methanol: Water: Acetonitrile: Isopropanol = 1:1:1:1

[0588] Column temperature: 40℃

[0589] Flow rate: 0.65 mL / min

[0590] Automated sampler temperature (Sample Tray Temp): 15℃

[0591] Injection volume: 8 μL

[0592] Needle Stroke Lift: 49 mm

[0593] Rinse Pump Setting: Cleans only the inlet.

[0594] Rinse Mode: Pre-absorption cleaning for autosamplers

[0595] Rinse Volume for Autosampler: 500 μL

[0596] Rinse Dip Time during needle cleaning: 2 seconds

[0597] Elution gradient (Table 24):

[0598] Table 24

[0599]

[0600] 2.5.1.4 Pretreatment Method

[0601] Sample pretreatment: Take 3 μL of working solution and add 57 μL of blank matrix (rat blank plasma) to a 1.5 mL centrifuge tube. Add 240 μL of acetonitrile containing 200 ng / mL tolbutamide and 0.1% FA (formic acid) to precipitate the protein. Vortex for 1 minute. Centrifuge the sample at 13000 rpm for 15 minutes at 4˚C. Take 100 μL of the supernatant and add 100 μL of methanol:water (1:3, v:v) solution containing 0.1% FA. Vortex for 1 minute. Centrifuge the sample at 3500 rpm for 5 minutes in a 96-well plate centrifuge and inject directly.

[0602] 2.5.2 Sample Analysis of Compound 1-1

[0603] 2.5.2.1 Experimental Apparatus:

[0604] High-performance liquid chromatography pump: LC-30AD, Shimadzu Corporation

[0605] Autosampler: SIL-30AC, Prominence, Shimadzu

[0606] Column Oven: CTO-30A, Shimadzu Corporation

[0607] Mass spectrometer: AB Sciex Qtrap 3500

[0608] High-speed refrigerated centrifuge: Thermo Fisher, ST16R, GG1206085-093

[0609] Analytical balance (electronic balance): Mettler Toledo, MS-105D, GG1206363

[0610] Miniature Vortex Analyzer: Shanghai Huxi Analytical Instrument Factory, WH-2, GG1206487

[0611] Experimental material: Rat plasma (EDTA-K2)

[0612] Analyte: Compound 1-1

[0613] Internal standard: Tolbutamide

[0614] Analytical method: Liquid chromatography-mass spectrometry (LC-MS)

[0615] 2.5.2.2 Mass spectrometry conditions:

[0616] Mass spectrometry parameters

[0617] Ion source: Ion Electrospray (ESI)

[0618] Ionization mode: Positive ion mode

[0619] Detection Mode: Multiple Response Monitoring (MRM)

[0620] Ion Spray Voltage: 5500

[0621] Turbo Ion Spray Temperature: 550℃

[0622] Curtain Gas: 35

[0623] Collision pool gas (CAD Gas): Medium

[0624] Nebulizing Gas (Gas 1): 55.00

[0625] Auxiliary Gas (Gas 2): 55.00

[0626] Detection of ion pairs (Table 25):

[0627] Table 25

[0628]

[0629] 2.5.2.3 Liquid phase method:

[0630] Column: Poroshell 120 EC-C18 (4.6 × 50 mm, 2.7 μm)

[0631] Mobile Phase A: 0.1% aqueous solution of formic acid

[0632] Mobile Phase B: A methanol solution of 0.1% formic acid

[0633] Rinse Port Wash Solution: Methanol: Acetonitrile: Water: Isopropanol = 1:1:1:1

[0634] Flow rate: 0.8 mL / min

[0635] Automated sampler temperature (Sample Tray Temp): 15℃

[0636] Injection volume: 15 μL

[0637] Needle Stroke Lift: 49 mm

[0638] Rinse Pump Setting: Cleans only the inlet.

[0639] Rinse Mode: Pre-absorption cleaning for autosamplers

[0640] Rinse Volume for Autosampler: 500 μL

[0641] Rinse Dip Time during needle cleaning: 2 seconds

[0642] Elution gradient (Table 26):

[0643] Table 26

[0644]

[0645] 2.5.2.4 Pretreatment Method

[0646] Sample pretreatment: Take 30 μL of sample, add 120 μL of acetonitrile containing 0.1% FA and 200 ng / mL mixed standard solution to precipitate protein, vortex mix thoroughly, and centrifuge the sample at 13000 rpm for 10 minutes at 4˚C. Take 100 μL of the supernatant into another 96-well plate, add 100 μL of methanol:water (1:3, v:v) solution, and vortex mix for 10 minutes.

[0647] 2.6 Data Analysis

[0648] Data will be analyzed using WinNonlin (version 5.2.1, Pharsight, Mountain View, CA) via a non-compartmental model to obtain PK parameters (Cp selected according to different routes of administration). max T max AUC last AUC inf T 1 / 2 (Parameters such as MRT). Specific results are shown in Table 27 below. The analyte listed in the table is compound 1-1.

[0649] Table 27

[0650]

[0651] Note: 1.100* here means 125 mg / kg of the compound shown in Formula I, which is equivalent to 100 mg / kg of compound 1-1.

[0652] 2.T 1 / 2 middle belt # The data in question are outliers from the experiment and have been removed when calculating the mean.

[0653] Experimental conclusion: The compound shown in Formula I of this invention has a better exposure level compared with compound 1-1.

Claims

1. A crystal form B of the compound shown in Formula I, characterized in that, Its X-ray powder diffraction pattern, expressed as 2θ angle using Cu-Kα radiation, shows diffraction peaks at 8.95±0.20°, 12.92±0.20°, 16.39±0.20°, 17.01±0.20°, 17.44±0.20°, 17.76±0.20°, 18.08±0.20°, 19.02±0.20°, 21.95±0.20°, 22.20±0.20°, 23.49±0.20°, 24.15±0.20°, 24.92±0.20°, 25.94±0.20°, 27.14±0.20°, and 29.68±0.20°. 。 2. The crystal form B of the compound of formula I as described in claim 1, characterized in that, The crystal form B of the compound shown in Formula I, when subjected to Cu-Kα radiation and expressed at a 2θ angle, exhibits diffraction peaks at one or more of the following locations in its X-ray powder diffraction pattern: 10.63±0.20°, 11.69±0.20°, 13.52±0.20°, 14.49±0.20°, 14.74±0.20°, 15.83±0.20°, 18.81±0.20°, 19.72±0.20°, 21.27±0.20°, 22.62±0.20°, 22.99±0.20°, 25.41±0.20°, 25.74±0.20°, 26.18±0.20°, 26.58±0.20°, and 27.85±0.20°. °, 28.23±0.20°, 28.70±0.20°, 29.16±0.20°, 30.17±0.20°, 30.51±0.20°, 31.20±0.20°, 32.16±0.20°, 32.52±0.20°, 32.74±0.20°, 32.89±0.20°, 34.36±0.20°, 35.45±0.20°, 35.98±0.20°, 36.65±0.20°, 37.00±0.20°, 37.45±0.20°, 37.73±0.20°, 38.04±0.20°, 38.36±0.20° and 39.11±0.20°.

3. The crystal form B of the compound of formula I as described in claim 1, characterized in that, The crystal form B of the compound shown in Formula I has an X-ray powder diffraction pattern expressed as a 2θ angle using Cu-Kα radiation at 8.95±0.20°, 10.63±0.20°, 11.69±0.20°, 12.92±0.20°, 13.52±0.20°, 14.49±0.20°, 14.74±0.20°, 15.83±0.20°, 16.39±0.20°, 17.01±0.20°, and 17.44±0.20°. 20°, 17.76±0.20°, 18.08±0.20°, 18.81±0.20°, 19.02±0.20°, 19.72±0.20°, 21.27±0.20°, 21.95±0.20°, 22.20±0.20°, 22.62±0.20°, 22.99±0.20°, 23.49±0.20°, 24.15±0.20°, 24.92±0.20°, 25.41±0 0.20°, 25.74±0.20°, 25.94±0.20°, 26.18±0.20°, 26.58±0.20°, 27.14±0.20°, 27.85±0.20°, 28.23±0.20°, 28.70±0.20°, 29.16±0.20°, 29.68±0.20°, 30.17±0.20°, 30.51±0.20°, 31.20±0.20°, 32.16± Diffraction peaks are observed at 0.20°, 32.52±0.20°, 32.74±0.20°, 32.89±0.20°, 34.36±0.20°, 35.45±0.20°, 35.98±0.20°, 36.65±0.20°, 37.00±0.20°, 37.45±0.20°, 37.73±0.20°, 38.04±0.20°, 38.36±0.20°, and 39.11±0.20°.

4. The crystal form B of the compound of formula I as described in claim 1, characterized in that, The crystal form B satisfies the following condition: The crystal form B of the compound shown in Formula I was subjected to Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 8.

5. Crystal form B of the compound of formula I as described in claim 1, characterized in that, The crystal form B satisfies the following condition: The differential scanning calorimetry curve of crystal form B of the compound shown in Formula I has an endothermic peak at 247.7°C ± 3°C.

6. The crystalline Form B of the compound of Formula I according to claim 1, characterized in that, The crystal form B satisfies the following condition: The differential scanning calorimetry curve of crystal form B of the compound represented by Formula I is shown in Figure 9.

7. The crystalline Form B of the compound of Formula I according to claim 1, characterized in that, The crystal form B satisfies the following condition: The thermogravimetric analysis curve of crystal form B of the compound shown in Formula I shows a weight loss of 1.0% in the temperature range of 35℃±3°C to 220℃±3°C.

8. The crystalline Form B of the compound of Formula I according to claim 1, characterized in that, The crystal form B satisfies the following condition: The thermogravimetric analysis curve of crystal form B of the compound represented by Formula I is shown in Figure 10.

9. The crystalline Form B of the compound of Formula I according to claim 1, characterized in that, The crystal form B satisfies the following condition: The crystal form B of the compound shown in Formula I is a solvent-free compound.

10. A solvate of the compound shown in Formula I, characterized in that, It is a solvate of formula IA, formula IR, formula IT, formula IC, formula ID, formula IE, formula IF, formula IG, formula II, formula IK, formula IL, formula IM, formula IN, formula IO, formula IP, or formula IS. or ； Where a is 0.79; r is 4.10; t is 2.85; c is 0.47, c' is 2.50; d is 0.69, d' is 5.86, d'' is 7.08; e is 1.21, e' is 6.20; f is 0.88, f' is 0.64; g is 0.25, g' is 0.70; i is 3.87; k is 1.28, k' is 0.40; l is 1.01, l' is 0.74; n is 3.28; o is 0.60; p is 0.56; m is 1.39; s is 2.

20.

11. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate of formula IA, a is 0.79, and the crystal form A of the solvate of formula IA, when irradiated with Cu-Kα and expressed at an angle of 2θ, exhibits diffraction peaks at 3.91±0.20°, 7.78±0.20°, 12.66±0.20°, 13.60±0.20°, 14.20±0.20°, 15.48±0.20°, 17.66±0.20°, 18.66±0.20°, 19.13±0.20°, 19.64±0.20°, 22.76±0.20°, 23.76±0.20°, 24.30±0.20°, 25.37±0.20°, and 27.78±0.20°.

12. A solvate of a compound of formula I according to claim 11, wherein The solvate satisfies the following condition: a is 0.79, and the crystal form A of the solvate shown in formula IA, when subjected to Cu-Kα radiation and expressed at a 2θ angle, exhibits one or more diffraction peaks at the following locations: 4.18±0.20°, 8.36±0.20°, 11.67±0.20°, 13.83±0.20°, 14.57±0.20°, 15.05±0.20°, 16.39±0.20°, 17.51±0.20°, 18.16±0.20°, 21.06±0.20°, 22.23±0.20°, 23.45±0.20°, 24.52±0.20°, 25.08 ±0.20°, 25.57±0.20°, 26.01±0.20°, 26.97±0.20°, 27.33±0.20°, 28.36±0.20°, 28.59±0.20°, 29.14±0.20°, 30.36±0.20°, 31.15±0.20°, 31.41±0.20°, 31.93±0.20°, 32.86±0.20°, 33.11±0.20°, 33.64±0.20°, 35.27±0.20°, 35.80±0.20°, 36.54±0.20°, 38.97±0.20°, and 39.43±0.20°.

13. The solvate of the compound of formula I as described in claim 11, characterized in that, The solvate satisfies the following conditions: a is 0.79, and the crystal form A of the solvate shown in formula IA is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 3.91±0.20°, 4.18±0.20°, 7.78±0.20°, 8.36±0.20°, 11.67±0.20°, 12.66±0.20°, 13.60±0.20°, 13.83±0.20°, and 14.20± 0.20°, 14.57±0.20°, 15.05±0.20°, 15.48±0.20°, 16.39±0.20°, 17.51±0.20°, 17.66±0.20°, 18.16±0.20°, 18.66±0.20°, 19.13±0.20°, 19.64±0.20°, 21.06±0.20°, 22.23±0.20°, 22.76±0.20° °, 23.45±0.20°, 23.76±0.20°, 24.30±0.20°, 24.52±0.20°, 25.08±0.20°, 25.37±0.20°, 25.57±0.20°, 26.01±0.20°, 26.97±0.20°, 27.33±0.20°, 27.78±0.20°, 28.36±0.20°, 28.59±0.20°, 2 Diffraction peaks are observed at 9.14±0.20°, 30.36±0.20°, 31.15±0.20°, 31.41±0.20°, 31.93±0.20°, 32.86±0.20°, 33.11±0.20°, 33.64±0.20°, 35.27±0.20°, 35.80±0.20°, 36.54±0.20°, 38.97±0.20°, and 39.43±0.20°.

14. A solvate of a compound of formula I according to claim 11, wherein The solvate satisfies the following conditions: in the solvate shown by formula IA, a is 0.79, and the crystal form A of the solvate shown by formula IA is X-ray powder diffraction pattern as shown in Figure 1 using Cu-Kα radiation.

15. A solvate of the compound of formula I according to claim 11, wherein The solvate satisfies the following conditions: in the solvate of formula IA, a is 0.79, and the differential scanning calorimetry curve of crystal form A of the solvate of formula IA has endothermic peaks at 60.1°C±3°C, 189.7°C±3°C and 204.5°C±3°C.

16. The solvate of the compound of formula I as described in claim 11, characterized in that, The solvate satisfies the following condition: in the solvate shown by formula IA, a is 0.79, and the differential scanning calorimetry curve of crystal form A of the solvate shown by formula IA is shown in Figure 2.

17. A solvate of the compound of formula I according to claim 11, wherein The solvate satisfies the following conditions: in the solvate of formula IA, a is 0.79, and the thermogravimetric analysis curve of crystal form A of the solvate of formula IA shows a weight loss of 2.4% in the temperature range of 34℃±3°C to 180℃±3°C.

18. The solvate of the compound of formula I as described in claim 11, characterized in that, The solvate satisfies the following condition: in the solvate shown by formula IA, a is 0.79, and the thermogravimetric analysis curve of crystal form A of the solvate shown by formula IA is shown in Figure 3.

19. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate represented by formula IR, r is 4.10, and the crystal form R of the solvate represented by formula IR has diffraction peaks at 11.88±0.20°, 14.49±0.20°, 15.57±0.20°, 16.62±0.20°, 19.45±0.20°, 19.82±0.20°, 20.48±0.20°, 23.79±0.20°, 24.63±0.20°, 26.41±0.20°, 26.84±0.20°, 27.09±0.20°, 27.77±0.20°, and 29.86±0.20° in the X-ray powder diffraction pattern expressed in 2θ angle using Cu-Kα radiation.

20. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following conditions: r is 4.10, and the crystal form R of the solvate shown in formula IR, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 4.11±0.20°, 6.38±0.20°, 6.71±0.20°, 12.27±0.20°, 13.31±0.20°, 13.85±0.20°, 19.00±0.20°, 21.1±0.20°, 22.37±0.20°, 22.7±0. 0.20°, 23.37±0.20°, 24.40±0.20°, 25.74±0.20°, 26.16±0.20°, 28.23±0.20°, 28.86±0.20°, 31.04±0.20°, 31.78±0.20°, 32.95±0.20°, 33.72±0.20°, 34.95±0.20°, 35.32±0.20°, 36.43±0.20°, 37.22±0.20° and 38.58±0.20°.

21. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following conditions: r is 4.10, and the crystal form R of the solvate shown in formula IR is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 4.11±0.20°, 6.38±0.20°, 6.71±0.20°, 11.88±0.20°, 12.27±0.20°, 13.31±0.20°, and 13... 0.85±0.20°, 14.49±0.20°, 15.57±0.20°, 16.62±0.20°, 19.00±0.20°, 19.45±0.20°, 19.82±0.20°, 20.48±0.20°, 21.10±0.20°, 22.37±0.20°, 22.70±0.20°, 23. 37±0.20°, 23.79±0.20°, 24.40±0.20°, 24.63±0.20°, 25.74±0.20°, 26.16±0.20°, 26.41±0.20°, 26.84±0.20°, 27.09±0.20°, 27.77±0.20°, 28.23±0.20°, 28.8 Diffraction peaks are observed at 6±0.20°, 29.86±0.20°, 31.04±0.20°, 31.78±0.20°, 32.95±0.20°, 33.72±0.20°, 34.95±0.20°, 35.32±0.20°, 36.43±0.20°, 37.22±0.20°, and 38.58±0.20°.

22. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following conditions: in the solvate represented by formula IR, r is 4.10, and the crystal form R of the solvate represented by formula IR is obtained by Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 60.

23. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following conditions: in the solvate represented by formula IR, r is 4.10, and the differential scanning calorimetry curve of the crystal form R of the solvate represented by formula IR has endothermic peaks at 87.1°C±3°C and 182.4°C±3°C.

24. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following condition: in the solvate represented by formula IR, r is 4.10, and the differential scanning calorimetry curve of the crystal form R of the solvate represented by formula IR is shown in Figure 61.

25. A solvate of a compound of formula I according to claim 19, wherein The solvate satisfies the following conditions: in the solvate represented by formula IR, r is 4.10, and the thermogravimetric analysis curve of the crystal form R of the solvate represented by formula IR shows a weight loss of 5.8% in the temperature range of 34℃±3°C to 140℃±3°C.

26. The solvate of the compound of formula I as described in claim 19, characterized in that, The solvate satisfies the following condition: in the solvate represented by formula IR, r is 4.10, and the thermogravimetric analysis curve of the crystal form R of the solvate represented by formula IR is shown in Figure 62.

27. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate represented by formula IT, t is 2.85, and the crystal form T of the solvate represented by formula IT has diffraction peaks at 3.71±0.20°, 15.31±0.20°, 15.86±0.20°, 16.50±0.20°, 18.48±0.20°, 18.79±0.20°, 20.89±0.20°, 22.22±0.20°, 24.70±0.20°, 25.00±0.20°, and 25.52±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at an angle of 2θ.

28. A solvate of a compound of formula I according to claim 27, wherein The solvate satisfies the following conditions: t is 2.85, and the crystal form T of the solvate represented by formula IT, when irradiated with Cu-Kα and expressed in 2θ angles, also exhibits diffraction peaks at one or more of the following locations: 7.25±0.20°, 14.96±0.20°, 19.81±0.20°, 21.92±0.20°, 23.40±0.20°, and 34.92±0.20°.

29. A solvate of a compound of formula I according to claim 27, wherein The solvate satisfies the following conditions: t is 2.85, and the crystal form T of the solvate represented by formula IT is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 3.71±0.20°, 7.25±0.20°, 14.96±0.20°, 15.31±0.20°, 15.86±0.20°, 16.50±0.20°, and 18. Diffraction peaks are observed at 48±0.20°, 18.79±0.20°, 19.81±0.20°, 20.89±0.20°, 21.92±0.20°, 22.22±0.20°, 23.40±0.20°, 24.70±0.20°, 25.00±0.20°, 25.52±0.20°, and 34.92±0.20°.

30. The solvate of the compound of formula I as described in claim 27, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IT, t is 2.85, and the crystal form T of the solvate represented by formula IT is X-ray powder diffraction pattern as shown in Figure 68 using Cu-Kα radiation.

31. A solvate of a compound of formula I according to claim 27, wherein The solvate satisfies the following conditions: in the solvate represented by formula IT, t is 2.85, and the differential scanning calorimetry curve of the crystal form T of the solvate represented by formula IT has endothermic peaks at 65.1°C±3°C and 181.5°C±3°C.

32. A solvate of a compound of formula I according to claim 27, wherein The solvate satisfies the following condition: in the solvate represented by formula IT, t is 2.85, and the differential scanning calorimetry curve of the crystal form T of the solvate represented by formula IT is shown in Figure 69.

33. A solvate of a compound of formula I according to claim 27, wherein The solvate satisfies the following conditions: in the solvate represented by formula IT, t is 2.85, and the thermogravimetric analysis curve of crystal form T of the solvate represented by formula IT shows a weight loss of 1.2% in the temperature range of 34℃±3°C to 140℃±3°C.

34. The solvate of the compound of formula I as described in claim 27, characterized in that, The solvate satisfies the following condition: in the solvate represented by formula IT, t is 2.85, and the thermogravimetric analysis curve of crystal form T of the solvate represented by formula IT is shown in Figure 70.

35. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate of formula IC, c is 0.47 and c' is 2.50; the crystal form C of the solvate of formula IC, when irradiated with Cu-Kα and expressed at an angle of 2θ, exhibits diffraction peaks at 7.42±0.20°, 12.37±0.20°, 15.60±0.20°, 16.60±0.20°, 17.19±0.20°, 19.67±0.20°, 22.31±0.20°, 22.96±0.20°, 23.95±0.20°, 24.48±0.20°, 24.84±0.20°, 28.42±0.20°, and 31.20±0.20°.

36. A solvate of a compound of formula I according to claim 35, wherein The solvate satisfies the following conditions: c is 0.47, c' is 2.50, and the crystal form C of the solvate shown in formula IC, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 8.70±0.20°, 10.09±0.20°, 11.46±0.20°, 14.13±0.20°, 14.81±0.20°, 18.22±0.20°, 1 8.87±0.20°, 20.10±0.20°, 20.77±0.20°, 26.19±0.20°, 27.70±0.20°, 29.44±0.20°, 32.39±0.20°, 33.52±0.20°, 36.41±0.20°, 36.68±0.20°, 37.45±0.20°, 38.31±0.20° and 38.51±0.20°.

37. A solvate of a compound of formula I according to claim 35, wherein The solvate satisfies the following conditions: c is 0.47, c' is 2.50, and the crystal form C of the solvate shown in formula IC is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles at 7.42±0.20°, 8.70±0.20°, 10.09±0.20°, 11.46±0.20°, 12.37±0.20°, 14.13±0.20°, 14.81±0.20°, 15.60±0.20°, 16.60±0.20°, 17.19±0.20°, 18.22±0.20°, 18.87±0.20°, 19.67±0.20°, and 20.10°. Diffraction peaks are observed at ±0.20°, 20.77±0.20°, 22.31±0.20°, 22.96±0.20°, 23.95±0.20°, 24.48±0.20°, 24.84±0.20°, 26.19±0.20°, 27.70±0.20°, 28.42±0.20°, 29.44±0.20°, 31.20±0.20°, 32.39±0.20°, 33.52±0.20°, 36.41±0.20°, 36.68±0.20°, 37.45±0.20°, 38.31±0.20°, and 38.51±0.20°.

38. A solvate of a compound of formula I according to claim 35, wherein The solvate satisfies the following conditions: in the solvate shown by formula IC, c is 0.47 and c' is 2.

50. The crystal form C of the solvate shown by formula IC is X-ray powder diffraction pattern as shown in Figure 14 using Cu-Kα radiation.

39. The solvate of the compound of formula I as described in claim 35, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula IC, c is 0.47 and c' is 2.50, and the differential scanning calorimetry curve of crystal form C of the solvate shown by formula IC has endothermic peaks at 69.2°C±3°C and 166.7°C±3°C.

40. The solvate of the compound of formula I as described in claim 35, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula IC, c is 0.47 and c' is 2.

50. The differential scanning calorimetry curve of crystal form C of the solvate shown by formula IC is shown in Figure 15.

41. The solvate of the compound of formula I as described in claim 35, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula IC, c is 0.47 and c' is 2.50; the thermogravimetric analysis curve of crystal form C of the solvate shown by formula IC shows a weight loss of 3.7% in the temperature range of 34℃±3°C to 150℃±3°C and a weight loss of 10.1% in the temperature range of 150℃±3°C to 200℃±3°C.

42. A solvate of a compound of formula I according to claim 35, wherein The solvate satisfies the following conditions: in the solvate represented by formula IC, c is 0.47 and c' is 2.

50. The thermogravimetric analysis curve of crystal form C of the solvate represented by formula IC is shown in Figure 16.

43. The solvate of the compound of formula I as described in claim 10, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula ID, d is 0.69, d' is 5.86, and d'' is 7.08; the crystal form D of the solvate shown by formula ID, when irradiated with Cu-Kα and expressed at an angle of 2θ, exhibits diffraction peaks at 5.04±0.20°, 10.07±0.20°, 13.40±0.20°, 13.68±0.20°, 14.79±0.20°, 18.21±0.20°, 22.12±0.20°, 23.12±0.20°, 23.45±0.20°, and 26.89±0.20°.

44. A solvate of a compound of formula I according to claim 43, wherein The solvate satisfies the following conditions: d = 0.69, d' = 5.86, and d'' = 7.

08. The crystal form D of the solvate shown in formula ID, when subjected to Cu-Kα radiation and expressed at a 2θ angle, exhibits one or more diffraction peaks at the following locations: 6.48±0.20°, 9.07±0.20°, 11.01±0.20°, 14.18±0.20°, 15.21±0.20°, 17.04±0.20°, 17.86±0.20°, 18.57±0.20°, 19.30±0.20°, and 20.19±0.20°. 0°, 20.70±0.20°, 22.80±0.20°, 24.41±0.20°, 25.30±0.20°, 25.40±0.20°, 25.98±0.20°, 26.14±0.20°, 26.57±0.20°, 27.65±0.20°, 28.15±0.20°, 28.48±0.20°, 29.00±0.20°, 31.83±0.20°, 32.10±0.20°, 33.30±0.20°, 35.72±0.20° and 36.84±0.20°.

45. The solvate of the compound of formula I as described in claim 43, characterized in that, The solvate satisfies the following conditions: d = 0.69, d' = 5.86, and d'' = 7.

08. The crystal form D of the solvate shown in formula ID is obtained using Cu-Kα radiation and X-ray powder diffraction patterns expressed at 2θ angles of 5.04±0.20°, 6.48±0.20°, 9.07±0.20°, 10.07±0.20°, 11.01±0.20°, 13.40±0.20°, 13.68±0.20°, 14.18±0.20°, 14.79±0.20°, 15.21±0.20°, 17.04±0.20°, 17.86±0.20°, 18.21±0.20°, 18.57±0.20°, 19.30±0.20°, and 20.19±0.20°. 0.20°, 20.70±0.20°, 22.12±0.20°, 22.80±0.20°, 23.12±0.20°, 23.45±0.20°, 24.41±0.20°, 25.30±0.20°, 25.40±0.20°, 25.98±0.20°, 26.14±0.20°, 26.57± Diffraction peaks are observed at 0.20°, 26.89±0.20°, 27.65±0.20°, 28.15±0.20°, 28.48±0.20°, 29.00±0.20°, 31.83±0.20°, 32.10±0.20°, 33.30±0.20°, 35.72±0.20°, and 36.84±0.20°.

46. ​​The solvate of the compound of formula I as described in claim 43, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula ID, d is 0.69, d' is 5.86, and d'' is 7.

08. The crystal form D of the solvate shown by formula ID is obtained by Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 18.

47. The solvate of the compound of formula I as described in claim 43, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula ID, d is 0.69, d' is 5.86, and d'' is 7.08; the differential scanning calorimetry curve of crystal form D of the solvate shown by formula ID has endothermic peaks at 49.5°C±3°C, 91.0°C±3°C, 121.0°C±3°C, and 178.9°C±3°C.

48. A solvate of a compound of formula I according to claim 43, wherein The solvate satisfies the following conditions: in the solvate represented by formula ID, d is 0.69, d' is 5.86, and d'' is 7.

08. The differential scanning calorimetry curve of the crystal form D of the solvate represented by formula ID is shown in Figure 19.

49. The solvate of the compound of formula I as described in claim 43, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula ID, d is 0.69, d' is 5.86, and d'' is 7.08; the thermogravimetric analysis curve of crystal form D of the solvate shown by formula ID shows a weight loss of 5.3% in the temperature range of 34℃±3°C to 80℃±3°C, and a weight loss of 12.8% in the temperature range of 80℃±3°C to 140℃±3°C.

50. The solvate of the compound of formula I as described in claim 43, characterized in that, The solvate satisfies the following conditions: in the solvate shown by formula ID, d is 0.69, d' is 5.86, and d'' is 7.

08. The thermogravimetric analysis curve of crystal form D of the solvate shown by formula ID is shown in Figure 20.

51. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.20; the crystal form E of the solvate represented by formula IE has diffraction peaks at 3.83±0.20°, 7.61±0.20°, 14.38±0.20°, 17.73±0.20°, 18.75±0.20°, 19.07±0.20°, 19.39±0.20°, 25.31±0.20°, 26.41±0.20°, and 32.85±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at an angle of 2θ.

52. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: e is 1.21, e' is 6.20, and the crystal form E of the solvate shown in formula IE, when irradiated with Cu-Kα radiation and expressed in 2θ angle X-ray powder diffraction pattern, also exhibits diffraction peaks at one or more of the following locations: 11.47±0.20°, 12.59±0.20°, 12.82±0.20°, 13.10±0.20°, 13.68±0.20°, 14.94±0.20°, 17.46±0.20°, 22.57±0.20°, 23.56±0.20°, 24.51±0.20°, 25.46±0.20°, 29.33±0.20°, 29.63±0.20°, 30.83±0.20°, and 35.25±0.20°.

53. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: e is 1.21, e' is 6.20, and the crystal form E of the solvate shown in formula IE is obtained by Cu-Kα radiation and X-ray powder diffraction at angles of 2θ at 3.83±0.20°, 7.61±0.20°, 11.47±0.20°, 12.59±0.20°, 12.82±0.20°, 13.10±0.20°, 13.68±0.20°, 14.38±0.20°, 14.94±0.20°, and 17.46±0.20°. Diffraction peaks are observed at 17.73±0.20°, 18.75±0.20°, 19.07±0.20°, 19.39±0.20°, 22.57±0.20°, 23.56±0.20°, 24.51±0.20°, 25.31±0.20°, 25.46±0.20°, 26.41±0.20°, 29.33±0.20°, 29.63±0.20°, 30.83±0.20°, 32.85±0.20°, and 35.25±0.20°.

54. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.

20. The crystal form E of the solvate represented by formula IE is X-ray powder diffraction pattern as shown in Figure 22 using Cu-Kα radiation.

55. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.20, and the differential scanning calorimetry curve of crystal form E of the solvate represented by formula IE has endothermic peaks at 81.2°C±3°C, 156.6°C±3°C and 181.4°C±3°C.

56. The solvate of the compound of formula I as described in claim 51, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.

20. The differential scanning calorimetry curve of the crystal form E of the solvate represented by formula IE is shown in Figure 23.

57. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.20; the thermogravimetric analysis curve of crystal form E of the solvate represented by formula IE shows a weight loss of 2.7% in the temperature range of 33℃±3°C to 100℃±3°C and a weight loss of 4.7% in the temperature range of 100℃±3°C to 170℃±3°C.

58. A solvate of a compound of formula I according to claim 51, wherein The solvate satisfies the following conditions: in the solvate represented by formula IE, e is 1.21 and e' is 6.

20. The thermogravimetric analysis curve of crystal form E of the solvate represented by formula IE is shown in Figure 24.

59. A solvate of a compound of formula I according to claim 10, wherein The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.64; the crystal form F of the solvate represented by formula IF, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, exhibits diffraction peaks at 3.96±0.20°, 8.01±0.20°, 12.48±0.20°, 14.21±0.20°, 15.35±0.20°, 17.74±0.20°, 19.21±0.20°, 19.49±0.20°, 22.62±0.20°, 23.67±0.20°, 24.67±0.20°, and 26.82±0.20°.

60. The solvate of the compound of formula I as described in claim 59, characterized in that, The solvate satisfies the following conditions: f is 0.88, f' is 0.64, and the crystal form F of the solvate shown by formula IF, when irradiated with Cu-Kα and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 13.36±0.20°, 13.78±0.20°, 14.62±0.20°, 16.73±0.20°, 18.67±0.20°, 25.31±0.20°, 25.91±0.20°, 27.55±0.20°, 28.54±0.20°, 29.60±0.20°, 30.97±0.20°, 32.06±0.20°, and 35.33±0.20°.

61. The solvate of the compound of formula I as described in claim 59, characterized in that, The solvate satisfies the following conditions: f is 0.88, f' is 0.64, and the crystal form F of the solvate represented by formula IF, when subjected to Cu-Kα radiation and X-ray powder diffraction at an angle of 2θ, is at 3.96±0.20°, 8.01±0.20°, 12.48±0.20°, 13.36±0.20°, 13.78±0.20°, 14.21±0.20°, 14.62±0.20°, 15.35±0.20°, 16.73±0.20°, and 17.74±0. 20°, 18.67±0.20°, 19.21±0.20°, 19.49±0.20°, 22.62±0.20°, 23.67±0.20°, 24.67±0.20°, 25.31±0.20°, 25.91±0.20°, 26.82±0.20°, 27.55±0.20°, 28.54±0.20°, 29.60±0.20°, 30.97±0.20°, 32.06±0.20° and 35.33±0.20°.

62. The solvate of the compound of formula I as described in claim 59, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.

64. The crystal form F of the solvate represented by formula IF is X-ray powder diffraction pattern as shown in Figure 26 using Cu-Kα radiation.

63. The solvate of a compound of formula I according to claim 59, wherein The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.64, and the differential scanning calorimetry curve of crystal form F of the solvate represented by formula IF has endothermic peaks at 47.4°C±3°C, 117.2°C±3°C and 184.8°C±3°C.

64. The solvate of a compound of formula I according to claim 59, wherein The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.

64. The differential scanning calorimetry curve of the crystal form F of the solvate represented by formula IF is shown in Figure 27.

65. The solvate of the compound of formula I as described in claim 59, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.64; the thermogravimetric analysis curve of crystal form F of the solvate represented by formula IF shows a weight loss of 2.5% in the temperature range of 34℃±3°C to 100℃±3°C, and a weight loss of 0.4% in the temperature range of 100℃±3°C to 170℃±3°C.

66. A solvate of a compound of formula I according to claim 59, wherein The solvate satisfies the following conditions: in the solvate represented by formula IF, f is 0.88 and f' is 0.

64. The thermogravimetric analysis curve of crystal form F of the solvate represented by formula IF is shown in Figure 28.

67. The solvate of the compound of formula I as described in claim 10, characterized in that, The solvate satisfies the following conditions: in the solvate of formula IG, g is 0.25 and g' is 0.70; the crystal form G of the solvate of formula IG, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, exhibits diffraction peaks at 7.64±0.20°, 15.28±0.20°, 17.02±0.20°, 19.41±0.20°, 20.10±0.20°, 20.49±0.20°, 23.03±0.20°, 24.38±0.20°, 26.93±0.20°, and 27.94±0.20°.

68. A solvate of a compound of formula I according to claim 67, wherein The solvate satisfies the following conditions: g is 0.25, g' is 0.70, and the crystal form G of the solvate shown in formula IG, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 9.30±0.20°, 9.81±0.20°, 14.87±0.20°, 18.55±0.20°, 18.62±0.20°, 25.41±0.20°, 26.12±0.20°, 30.88±0.20°, and 37.98±0.20°.

69. The solvate of the compound of formula I as described in claim 67, characterized in that, The solvate satisfies the following conditions: g is 0.25, g' is 0.70, and the crystal form G of the solvate shown in formula IG is obtained by Cu-Kα radiation and X-ray powder diffraction at angles of 2θ at 7.64±0.20°, 9.30±0.20°, 9.81±0.20°, 14.87±0.20°, 15.28±0.20°, 17.02±0.20°, and 18.55±0.20°. Diffraction peaks are observed at 18.62±0.20°, 19.41±0.20°, 20.10±0.20°, 20.49±0.20°, 23.03±0.20°, 24.38±0.20°, 25.41±0.20°, 26.12±0.20°, 26.93±0.20°, 27.94±0.20°, 30.88±0.20°, and 37.98±0.20°.

70. The solvate of a compound of formula I according to claim 67, wherein The solvate satisfies the following conditions: in the solvate represented by formula IG, g is 0.25 and g' is 0.

70. The crystal form G of the solvate represented by formula IG is X-ray powder diffraction pattern as shown in Figure 30 using Cu-Kα radiation.

71. A solvate of a compound of formula I as claimed in claim 67, wherein, The solvate satisfies the following conditions: in the solvate of formula IG, g is 0.25 and g' is 0.70, and the differential scanning calorimetry curve of crystal form G of the solvate of formula IG has endothermic peaks at 64.7°C±3°C and 209.3°C±3°C.

72. A solvate of a compound of formula I according to claim 67, wherein The solvate satisfies the following conditions: in the solvate represented by formula IG, g is 0.25 and g' is 0.

70. The differential scanning calorimetry curve of crystal form G of the solvate represented by formula IG is shown in Figure 31.

73. A solvate of a compound of formula I according to claim 67, wherein The solvate satisfies the following conditions: in the solvate represented by formula IG, g is 0.25 and g' is 0.70; the thermogravimetric analysis curve of crystal form G of the solvate represented by formula IG shows a weight loss of 0.4% in the temperature range of 33℃±3°C to 100℃±3°C, and a weight loss of 9.7% in the temperature range of 100℃±3°C to 210℃±3°C.

74. The solvate of the compound of formula I as described in claim 67, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IG, g is 0.25 and g' is 0.

70. The thermogravimetric analysis curve of crystal form G of the solvate represented by formula IG is shown in Figure 32.

75. The solvate of the compound of formula I as described in claim 10, characterized in that, The solvate satisfies the following conditions: in the solvate of Formula II, i is 3.87; the crystal form I of the solvate of Formula II, when subjected to Cu-Kα radiation and X-ray powder diffraction patterns expressed in 2θ angles, is at 7.21±0.20°, 12.73±0.20°, 14.40±0.20°, 15.42±0.20°, 16.02±0.20°, and 16... Diffraction peaks are observed at 0.57±0.20°, 19.06±0.20°, 20.93±0.20°, 21.19±0.20°, 23.42±0.20°, 24.24±0.20°, 25.53±0.20°, 25.97±0.20°, 27.51±0.20°, 28.14±0.20°, and 32.97±0.20°.

76. The solvate of the compound of formula I as described in claim 75, characterized in that, The solvate satisfies the following condition: i is 3.87, and the crystal form I of the solvate shown in Formula II, when subjected to Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 8.04±0.20°, 9.11±0.20°, 10.89±0.20°, 11.46±0.20°, 13.07±0.20°, 14... 0.56±0.20°, 16.36±0.20°, 16.85±0.20°, 17.86±0.20°, 18.16±0.20°, 18.60±0.20°, 19.54±0.20°, 20.35±0.20°, 21.43±0.20°, 21.68±0.20°, 21.72±0.20°, 23.04 ±0.20°, 23.71±0.20°, 25.00±0.20°, 26.30±0.20°, 26.51±0.20°, 26.93±0.20°, 27.25±0.20°, 27.99±0.20°, 29.03±0.20°, 29.54±0.20°, 29.74±0.20°, 30.54±0. 20°, 30.79±0.20°, 31.16±0.20°, 32.05±0.20°, 33.31±0.20°, 33.75±0.20°, 33.96±0.20°, 34.36±0.20°, 34.90±0.20°, 36.53±0.20°, 38.86±0.20° and 39.68±0.20°.

77. The solvate of the compound of formula I as described in claim 75, characterized in that, The solvate satisfies the following conditions: i is 3.87, and the crystal form I of the solvate shown in Formula II is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 7.21±0.20°, 8.04±0.20°, 9.11±0.20°, 10.89±0.20°, 11.46±0.20°, 12.73±0.20°, 13.07±0.20°, 14.40±0.20°, 14.56±0.20°, 15.42±0.20°, 16 0.02±0.20°, 16.36±0.20°, 16.57±0.20°, 16.85±0.20°, 17.86±0.20°, 18.16±0.20°, 18.60±0.20°, 19.06±0.20°, 19.54±0.20°, 20.35±0.20°, 20.93±0.20°, 21.19±0.20°, 21.43±0.20°, 21.68±0.20°, 21.72±0.20°, 23. 04±0.20°, 23.42±0.20°, 23.71±0.20°, 24.24±0.20°, 25.00±0.20°, 25.53±0.20°, 25.97±0.20°, 26.30±0.20°, 26.51±0.20°, 26.93±0.20°, 27.25±0.20°, 27.51±0.20°, 27.99±0.20°, 28.14±0.20°, 29.03±0.20°, 29.5 Diffraction peaks are observed at 4±0.20°, 29.74±0.20°, 30.54±0.20°, 30.79±0.20°, 31.16±0.20°, 32.05±0.20°, 32.97±0.20°, 33.31±0.20°, 33.75±0.20°, 33.96±0.20°, 34.36±0.20°, 34.90±0.20°, 36.53±0.20°, 38.86±0.20°, and 39.68±0.20°.

78. The solvate of the compound of formula I as described in claim 75, characterized in that, The solvate satisfies the following conditions: in the solvate of Formula II, i is 3.87, and the crystal form I of the solvate of Formula II is X-ray powder diffraction pattern as shown in Figure 34 using Cu-Kα radiation.

79. A solvate of a compound of formula I according to claim 75, wherein The solvate satisfies the following conditions: in the solvate of Formula II, i is 3.87, and the differential scanning calorimetry curve of crystal form I of the solvate of Formula II has endothermic peaks at 44.8°C±3°C, 130.8°C±3°C and 217.4°C±3°C.

80. A solvate of a compound of formula I according to claim 75, wherein The solvate satisfies the following condition: in the solvate shown in Formula II, i is 3.87, and the differential scanning calorimetry curve of crystal form I of the solvate shown in Formula II is shown in Figure 35.

81. A solvate of a compound of formula I according to claim 75, wherein The solvate satisfies the following conditions: in the solvate of Formula II, i is 3.87, and the thermogravimetric analysis curve of crystal form I of the solvate of Formula II shows a weight loss of 0.2% in the temperature range of 34℃±3°C to 70℃±3°C, and a weight loss of 20.4% in the temperature range of 70℃±3°C to 135℃±3°C.

82. A solvate of a compound of formula I according to claim 75, wherein The solvate satisfies the following condition: in the solvate shown in Formula II, i is 3.87, and the thermogravimetric analysis curve of crystal form I of the solvate shown in Formula II is shown in Figure 36.

83. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate of formula IK, k is 1.28, k' is 0.40, and the crystal form K of the solvate of formula IK has diffraction peaks at 8.01±0.20°, 9.19±0.20°, 13.87±0.20°, 16.22±0.20°, 17.78±0.20°, 20.63±0.20°, 22.24±0.20°, 22.66±0.20°, 23.40±0.20°, 25.09±0.20°, 29.12±0.20°, and 30.77±0.20° using Cu-Kα radiation and X-ray powder diffraction patterns expressed at 2θ angles.

84. A solvate of a compound of formula I according to claim 83, wherein The solvate satisfies the following conditions: k is 1.28, k' is 0.40, and the crystal form K of the solvate shown by formula IK, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 8.52±0.20°, 15.25±0.20°, 16.61±0.20°, 17.06±0.20°, 18.64±0.20°. 0.20°, 19.10±0.20°, 20.04±0.20°, 21.27±0.20°, 24.07±0.20°, 27.08±0.20°, 27.67±0.20°, 28.26±0.20°, 33.93±0.20°, 34.48±0.20°, 35.19±0.20° and 38.23±0.20°.

85. A solvate of a compound of formula I according to claim 83, wherein The solvate satisfies the following conditions: k is 1.28, k' is 0.40, and the crystal form K of the solvate shown by formula IK is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 8.01±0.20°, 8.52±0.20°, 9.19±0.20°, 13.87±0.20°, 15.25±0.20°, 16.22±0.20°, 16.61±0.20°, 17.06±0.20°, 17.78±0.20°, 18.64±0.20°, 19.10±0.20°, and 20.04°. Diffraction peaks are observed at ±0.20°, 20.63±0.20°, 21.27±0.20°, 22.24±0.20°, 22.66±0.20°, 23.40±0.20°, 24.07±0.20°, 25.09±0.20°, 27.08±0.20°, 27.67±0.20°, 28.26±0.20°, 29.12±0.20°, 30.77±0.20°, 33.93±0.20°, 34.48±0.20°, 35.19±0.20°, and 38.23±0.20°.

86. The solvate of the compound of formula I as described in claim 83, characterized in that, The solvate satisfies the following conditions: in the solvate of formula IK, k is 1.28 and k' is 0.

40. The crystal form K of the solvate of formula IK is obtained by Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 38.

87. The solvate of the compound of formula I as described in claim 83, characterized in that, The solvate satisfies the following conditions: in the solvate of formula IK, k is 1.28, k' is 0.40, and the thermogravimetric analysis curve of crystal form K of the solvate of formula IK shows a weight loss of 6.4% in the temperature range of 33℃±3°C to 180℃±3°C.

88. A solvate of a compound of formula I according to claim 83, wherein The solvate satisfies the following conditions: in the solvate represented by formula IK, k is 1.28 and k' is 0.

40. The thermogravimetric analysis curve of crystal form K of the solvate represented by formula IK is shown in Figure 39.

89. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL has diffraction peaks at 13.48±0.20°, 15.75±0.20°, 17.32±0.20°, 17.70±0.20°, 20.04±0.20°, 22.15±0.20°, 24.59±0.20°, 24.88±0.20°, 25.74±0.20°, 27.12±0.20°, 29.01±0.20°, and 30.81±0.20° using Cu-Kα radiation and 2θ angle X-ray powder diffraction patterns.

90. A solvate of a compound of formula I according to claim 89, wherein The solvate satisfies the following conditions: l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL, when subjected to Cu-Kα radiation and expressed at a 2θ angle, also exhibits diffraction peaks at one or more of the following locations: 11.51±0.20°, 11.88±0.20°, 12.35±0.20°, 12.95±0.20°, 14.67±0.20°, 16.61±0.20°, 18.17±0.20°, 18.54±0.20°, 18.84±0.20°, 20.78± 0.20°, 22.80±0.20°, 23.03±0.20°, 23.38±0.20°, 23.82±0.20°, 25.16±0.20°, 26.24±0.20°, 27.53±0.20°, 28.43±0.20°, 29.64±0.20°, 30.13±0.20°, 32.65±0.20°, 33.53±0.20°, 34.11±0.20°, 34.76±0.20°, 37.29±0.20° and 38.22±0.20°.

91. A solvate of a compound of formula I according to claim 89, wherein The solvate satisfies the following conditions: l is 1.01, l' is 0.74, and the crystal form L of the solvate represented by formula IL is obtained by Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angles at 11.51±0.20°, 11.88±0.20°, 12.35±0.20°, 12.95±0.20°, 13.48±0.20°, and 14. 67±0.20°, 15.75±0.20°, 16.61±0.20°, 17.32±0.20°, 17.70±0.20°, 18.17±0.20°, 18.54±0.20°, 18.84±0.20°, 20.04±0.20°, 20.78±0.20°, 22.15±0.20°, 22.8 0±0.20°, 23.03±0.20°, 23.38±0.20°, 23.82±0.20°, 24.59±0.20°, 24.88±0.20°, 25.16±0.20°, 25.74±0.20°, 26.24±0.20°, 27.12±0.20°, 27.53±0.20°, 28.4 Diffraction peaks are observed at 3±0.20°, 29.01±0.20°, 29.64±0.20°, 30.13±0.20°, 30.81±0.20°, 32.65±0.20°, 33.53±0.20°, 34.11±0.20°, 34.76±0.20°, 37.29±0.20°, and 38.22±0.20°.

92. A solvate of a compound of formula I according to claim 89, wherein The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01 and l' is 0.

74. The crystal form L of the solvate represented by formula IL is X-ray powder diffraction pattern as shown in Figure 41 using Cu-Kα radiation.

93. The solvate of the compound of formula I as described in claim 89, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01 and l' is 0.74, and the differential scanning calorimetry curve of crystal form L of the solvate represented by formula IL has endothermic peaks at 57.2°C±3°C and 178.4°C±3°C.

94. The solvate of the compound of formula I as described in claim 89, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01 and l' is 0.

74. The differential scanning calorimetry curve of the crystal form L of the solvate represented by formula IL is shown in Figure 42.

95. The solvate of the compound of formula I as described in claim 89, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01 and l' is 0.74; the thermogravimetric analysis curve of crystal form L of the solvate represented by formula IL shows a weight loss of 2.5% in the temperature range of 35℃±3°C to 100℃±3°C and a weight loss of 6.9% in the temperature range of 100℃±3°C to 190℃±3°C.

96. A solvate of a compound of formula I according to claim 89, wherein The solvate satisfies the following conditions: in the solvate represented by formula IL, l is 1.01 and l' is 0.

74. The thermogravimetric analysis curve of crystal form L of the solvate represented by formula IL is shown in Figure 43.

97. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IN, n is 3.28, and the crystal form N of the solvate represented by formula IN has diffraction peaks at 7.82±0.20°, 8.56±0.20°, 14.55±0.20°, 15.58±0.20°, 17.37±0.20°, 18.46±0.20°, 19.66±0.20°, 22.61±0.20°, 22.87±0.20°, 25.08±0.20°, 26.07±0.20°, and 27.07±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at an angle of 2θ.

98. A solvate of a compound of formula I according to claim 97, wherein The solvate satisfies the following conditions: n is 3.28, and the crystal form N of the solvate represented by formula IN, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, exhibits one or more diffraction peaks at the following locations: 9.78±0.20°, 11.20±0.20°, 11.41±0.20°, 12.29±0.20°, 12.95±0.20°, 16.37±0.20°, 16.97±0.20°, 19.13±0.20°, 20.13±0.20°, 20.58±0.20°, 21.44±0.20°, 22.00±0.20°, 23.56±0.20°. 24.71±0.20°, 25.47±0.20°, 26.67±0.20°, 27.86±0.20°, 28.84±0.20°, 29.31±0.20°, 29.64±0.20°, 30.53±0.20°, 32.65±0.20°, 33.63±0.20°, 34.42±0.20°, 34.88±0.20°, 35.75±0.20°, 36.82±0.20°, 37.40±0.20°, 38.42±0.20°, 38.92±0.20°, 39.86±0.20° and 24.71±0.20°.

99. The solvate of the compound of formula I as described in claim 97, characterized in that, The solvate satisfies the following conditions: n is 3.28, and the crystal form N of the solvate represented by formula IN is obtained by Cu-Kα radiation and X-ray powder diffraction at angles of 2θ at 7.82±0.20°, 8.56±0.20°, 9.78±0.20°, 11.20±0.20°, 11.41±0.20°, 12.29±0.20°, 12.95±0.20°, and 14.55°. ±0.20°, 15.58±0.20°, 16.37±0.20°, 16.97±0.20°, 17.37±0.20°, 18.46±0.20°, 19.13±0.20°, 19.66±0.20°, 20.13±0.20°, 20.58±0.20°, 21.44±0.20°, 22.00±0.20°, 22.61±0.2 0°, 22.87±0.20°, 23.56±0.20°, 24.71±0.20°, 25.08±0.20°, 25.47±0.20°, 26.07±0.20°, 26.67±0.20°, 27.07±0.20°, 27.86±0.20°, 28.84±0.20°, 29.31±0.20°, 29.64±0.20°, 3 Diffraction peaks are observed at 0.53±0.20°, 32.65±0.20°, 33.63±0.20°, 34.42±0.20°, 34.88±0.20°, 35.75±0.20°, 36.82±0.20°, 37.40±0.20°, 38.42±0.20°, 38.92±0.20°, 39.86±0.20°, and 24.71±0.20°.

100. The solvate of the compound of formula I as described in claim 97, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IN, n is 3.28, and the crystal form N of the solvate represented by formula IN is X-ray powder diffraction pattern as shown in Figure 48 using Cu-Kα radiation.

101. A solvate of a compound of formula I according to claim 97, wherein The solvate satisfies the following conditions: in the solvate represented by formula IN, n is 3.28, and the differential scanning calorimetry curve of crystal form N of the solvate represented by formula IN has endothermic peaks at 56.0°C±3°C, 130.8°C±3°C, and 215.3°C±3°C.

102. A solvate of a compound of formula I according to claim 97, wherein The solvate satisfies the following condition: in the solvate represented by formula IN, n is 3.28, and the differential scanning calorimetry curve of the crystal form N of the solvate represented by formula IN is shown in Figure 49.

103. A solvate of a compound of formula I as claimed in claim 97, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IN, n is 3.28, and the thermogravimetric analysis curve of crystal form N of the solvate represented by formula IN shows a weight loss of 13.0% in the temperature range of 34℃±3°C to 90℃±3°C.

104. The solvate of the compound of formula I as described in claim 97, characterized in that, The solvate satisfies the following condition: in the solvate represented by formula IN, n is 3.28, and the thermogravimetric analysis curve of crystal form N of the solvate represented by formula IN is shown in Figure 50.

105. The solvate of the compound of formula I as described in claim 10, characterized in that, The solvate satisfies the following conditions: in the solvate of formula 10, o is 0.60, and the crystal form O of the solvate of formula 10, when subjected to Cu-Kα radiation and X-ray powder diffraction pattern expressed in 2θ angle, exhibits diffraction peaks at 7.77±0.20°, 14.94±0.20°, 16.97±0.20°, 20.12±0.20°, 20.81±0.20°, 21.08±0.20°, 23.38±0.20°, 23.78±0.20°, 24.50±0.20°, 26.03±0.20°, 27.32±0.20°, and 31.33±0.20°.

106. The solvate of the compound of formula I as described in claim 105, characterized in that, The solvate satisfies the following conditions: in the solvate of formula 10, o is 0.60, and the crystal form O of the solvate of formula 10, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, exhibits one or more diffraction peaks at the following locations: 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, and 13.77±0.20°. 15.54±0.20°, 18.11±0.20°, 18.66±0.20°, 19.55±0.20°, 24.89±0.20°, 25.28±0.20°, 25.59±0.20°, 28.30±0.20°, 30.24±0.20°, 33.23±0.20°, 34.66±0.20°, 38.12±0.20° and 39.45±0.20°.

107. A solvate of a compound of formula I according to claim 105, wherein The solvate satisfies the following conditions: in the solvate of formula IO, o is 0.60, and the crystal form O of the solvate of formula IO, when subjected to Cu-Kα radiation and X-ray powder diffraction pattern expressed at 2θ angles, is within the ranges of 7.77±0.20°, 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, 13.77±0.20°, 14.94±0.20°, 15.54±0.20°, 16.97±0.20°, 18.11±0.20°, 18.66±0.20°, and 19.55±0.20°. Diffraction peaks are observed at 0°, 20.12±0.20°, 20.81±0.20°, 21.08±0.20°, 23.38±0.20°, 23.78±0.20°, 24.50±0.20°, 24.89±0.20°, 25.28±0.20°, 25.59±0.20°, 26.03±0.20°, 27.32±0.20°, 28.30±0.20°, 30.24±0.20°, 31.33±0.20°, 33.23±0.20°, 34.66±0.20°, 38.12±0.20°, and 39.45±0.20°.

108. A solvate of a compound of formula I as claimed in claim 105, wherein, The solvate satisfies the following conditions: in the solvate of formula 10, o is 0.60, and the crystal form O of the solvate of formula 10 is X-ray powder diffraction pattern as shown in Figure 52 using Cu-Kα radiation.

109. A solvate of a compound of formula I as claimed in claim 105, wherein, The solvate satisfies the following conditions: in the solvate of formula 10, o is 0.60, and the differential scanning calorimetry curve of crystal form O of the solvate of formula 10 has endothermic peaks at 125.5°C±3°C and 209.6°C±3°C.

110. The solvate of the compound of formula I as described in claim 105, characterized in that, The solvate satisfies the following condition: in the solvate shown by formula 10, o is 0.60, and the differential scanning calorimetry curve of crystal form O of the solvate shown by formula 10 is shown in Figure 53.

111. The solvate of the compound of formula I as described in claim 105, characterized in that, The solvate satisfies the following conditions: in the solvate of formula 10, o is 0.60, and the thermogravimetric analysis curve of crystal form O of the solvate of formula 10 shows a weight loss of 7.6% in the temperature range of 35℃±3°C to 170℃±3°C.

112. The solvate of the compound of formula I as described in claim 105, characterized in that, The solvate satisfies the following condition: in the solvate shown by formula 10, o is 0.60, and the thermogravimetric analysis curve of crystal form O of the solvate shown by formula 10 is shown in Figure 54.

113. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate shown by formula IP, p is 0.56, and the crystal form P of the solvate shown by formula IP has diffraction peaks at 7.76±0.20°, 11.52±0.20°, 15.44±0.20°, 17.27±0.20°, 18.64±0.20°, 19.57±0.20°, 20.33±0.20°, 21.78±0.20°, 23.35±0.20°, 23.87±0.20°, 26.34±0.20°, 27.62±0.20°, and 31.26±0.20° using Cu-Kα radiation and X-ray powder diffraction patterns expressed at 2θ angles.

114. The solvate of the compound of formula I as described in claim 113, characterized in that, The solvate satisfies the following conditions: in the solvate of formula IP, p is 0.56, and the crystal form P of the solvate of formula IP, when irradiated with Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 9.21±0.20°, 9.84±0.20°, 10.89±0.20°, 12.48±0.20°, 16.92±0.20°, 17.57±0.20°, 24.49±0.20°, 24.89±0.20°, 25.50±0.20°, 26.06±0.20°, 28.60±0.20°, 34.12±0.20°, 36.05±0.20°, 37.65±0.20°, and 39.42±0.20°.

115. The solvate of a compound of formula I according to claim 113, wherein The solvate satisfies the following conditions: in the solvate represented by formula IP, p is 0.56, and the crystal form P of the solvate represented by formula IP has an X-ray powder diffraction pattern expressed as 2θ angle using Cu-Kα radiation at 7.76±0.20°, 9.21±0.20°, 9.84±0.20°, 10.89±0.20°, 11.52±0.20°, 12.48±0.20°, 15.44±0.20°, 16.92±0.20°, 17.27±0.20°, 17.57±0.20°, 18.64±0.20°, and 19. Diffraction peaks are observed at 57±0.20°, 20.33±0.20°, 21.78±0.20°, 23.35±0.20°, 23.87±0.20°, 24.49±0.20°, 24.89±0.20°, 25.50±0.20°, 26.06±0.20°, 26.34±0.20°, 27.62±0.20°, 28.60±0.20°, 31.26±0.20°, 34.12±0.20°, 36.05±0.20°, 37.65±0.20°, and 39.42±0.20°.

116. A solvate of a compound of formula I as claimed in claim 113, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IP, p is 0.56, and the crystal form P of the solvate represented by formula IP is X-ray powder diffraction pattern as shown in Figure 56 using Cu-Kα radiation.

117. The solvate of the compound of formula I as described in claim 113, characterized in that, The solvate satisfies the following conditions: in the solvate represented by formula IP, p is 0.56, and the differential scanning calorimetry curve of crystal form P of the solvate represented by formula IP has endothermic peaks at 157.4°C±3°C and 206.8°C±3°C.

118. A solvate of a compound of formula I as claimed in claim 113, wherein, The solvate satisfies the following condition: in the solvate represented by formula IP, p is 0.56, and the differential scanning calorimetry curve of crystal form P of the solvate represented by formula IP is shown in Figure 57.

119. A solvate of a compound of formula I as claimed in claim 113, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IP, p is 0.56, and the thermogravimetric analysis curve of crystal form P of the solvate represented by formula IP shows a weight loss of 7.8% in the temperature range of 35℃ to 180℃.

120. A solvate of a compound of formula I as claimed in claim 113, wherein, The solvate satisfies the following condition: in the solvate represented by formula IP, p is 0.56, and the thermogravimetric analysis curve of crystal form P of the solvate represented by formula IP is shown in Figure 58.

121. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IM, m is 1.39, and the crystal form M of the solvate represented by formula IM has diffraction peaks at 8.38±0.20°, 16.03±0.20°, 16.80±0.20°, 17.98±0.20°, 18.50±0.20°, 19.28±0.20°, 22.47±0.20°, 24.00±0.20°, 26.46±0.20°, and 29.54±0.20° when X-ray powder diffraction is performed using Cu-Kα radiation and expressed at 2θ angle.

122. A solvate of a compound of formula I according to claim 121, wherein The solvate satisfies the following conditions: m is 1.39, and the crystal form M of the solvate shown by formula IM, when irradiated with Cu-Kα and expressed in 2θ angles, also exhibits one or more diffraction peaks at the following locations: 7.11±0.20°, 12.44±0.20°, 14.92±0.20°, 23.14±0.20°, 25.32±0.20°, and 30.82±0.20°.

123. A solvate of a compound of formula I as claimed in claim 121, wherein, The solvate satisfies the following conditions: m is 1.39, and the crystal form M of the solvate shown by formula IM has diffraction peaks at 7.11±0.20°, 8.38±0.20°, 12.44±0.20°, 14.92±0.20°, 16.03±0.20°, 16.80±0.20°, 17.98±0.20°, 18.50±0.20°, 19.28±0.20°, 22.47±0.20°, 23.14±0.20°, 24.00±0.20°, 25.32±0.20°, 26.46±0.20°, 29.54±0.20°, and 30.82±0.20° when analyzed by Cu-Kα radiation and expressed at an angle of 2θ.

124. The solvate of a compound of formula I according to claim 121, wherein The solvate satisfies the following conditions: in the solvate represented by formula IM, m is 1.39, and the crystal form M of the solvate represented by formula IM is obtained by Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 45.

125. A solvate of a compound of formula I as claimed in claim 121, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IM, m is 1.39, and the thermogravimetric analysis curve of crystal form M of the solvate represented by formula IM shows a weight loss of 16.7% in the temperature range of 36℃±3°C to 160℃±3°C.

126. A solvate of a compound of formula I as claimed in claim 121, wherein, The solvate satisfies the following condition: in the solvate represented by formula IM, m is 1.39, and the thermogravimetric analysis curve of crystal form M of the solvate represented by formula IM is shown in Figure 46.

127. A solvate of a compound of formula I as claimed in claim 10, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IS, s is 2.20, and the crystal form S of the solvate represented by formula IS has diffraction peaks at 6.85±0.20°, 7.21±0.20°, 7.46±0.20°, 8.12±0.20°, 13.69±0.20°, 14.41±0.20°, 14.79±0.20°, 16.25±0.20°, 16.70±0.20°, 21.54±0.20°, 22.94±0.20°, and 25.55±0.20° using Cu-Kα radiation and X-ray powder diffraction at 2θ angle.

128. The solvate of the compound of formula I as described in claim 127, characterized in that, The solvate satisfies the following condition: s is 2.20, and the crystal form S of the solvate shown by formula IS, when subjected to Cu-Kα radiation and expressed at an angle of 2θ, also exhibits diffraction peaks at one or more of the following locations: 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 16.05±0.20°, and 19.10±0.20°. °, 19.57±0.20°, 19.98±0.20°, 20.25±0.20°, 20.55±0.20°, 20.91±0.20°, 24.49±0.20°, 25.01±0.20°, 26.01±0.20°, 27.51±0.20°, 28.19±0.20°, 28.52±0.20° and 29.07±0.20°.

129. The solvate of the compound of formula I as described in claim 127, characterized in that, The solvate satisfies the following conditions: s is 2.20, and the crystal form S of the solvate shown by formula IS is obtained by Cu-Kα radiation and X-ray powder diffraction at angles of 2θ at 6.85±0.20°, 7.21±0.20°, 7.46±0.20°, 8.12±0.20°, 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 13.69±0.20°, 14.41±0.20°, 14.79±0.20°, 16.05±0.20°, and 16.25±0.20°. Diffraction peaks are observed at 16.70±0.20°, 19.10±0.20°, 19.57±0.20°, 19.98±0.20°, 20.25±0.20°, 20.55±0.20°, 20.91±0.20°, 21.54±0.20°, 22.94±0.20°, 24.49±0.20°, 25.01±0.20°, 25.55±0.20°, 26.01±0.20°, 27.51±0.20°, 28.19±0.20°, 28.52±0.20°, and 29.07±0.20°.

130. The solvate of a compound of formula I according to claim 127, wherein The solvate satisfies the following conditions: in the solvate represented by formula IS, s is 2.20, and the crystal form S of the solvate represented by formula IS is obtained by Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in Figure 64.

131. A solvate of a compound of formula I as claimed in claim 127, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IS, s is 2.20, and the differential scanning calorimetry curve of the crystal form S of the solvate represented by formula IS has endothermic peaks at 107.1°C±3°C and 219.3°C±3°C.

132. A solvate of a compound of formula I as claimed in claim 127, wherein, The solvate satisfies the following condition: in the solvate represented by formula IS, s is 2.20, and the differential scanning calorimetry curve of the crystal form S of the solvate represented by formula IS is shown in Figure 65.

133. A solvate of a compound of formula I as claimed in claim 127, wherein, The solvate satisfies the following conditions: in the solvate represented by formula IS, s is 2.20, and the thermogravimetric analysis curve of crystal form S of the solvate represented by formula IS shows a weight loss of 9.8% in the temperature range of 36℃±3°C to 150℃±3°C.

134. The solvate of a compound of formula I according to claim 127, wherein The solvate satisfies the following condition: in the solvate represented by formula IS, s is 2.20, and the thermogravimetric analysis curve of the crystal form S of the solvate represented by formula IS is shown in Figure 66.

135. A method for preparing crystal form A of the solvate of formula IA as described in any one of claims 11 to 18, characterized in that, It includes the following steps: mixing the compound shown in Formula I with acetonitrile, adding ethanol, to obtain crystal form A of the solvate shown in Formula IA; The preparation method satisfies the following conditions: (1) The mass-to-volume ratio of the compound shown in Formula I to the acetonitrile is 0.75 g / mL; (2) The mass-to-volume ratio of the compound shown in Formula I to the ethanol is 0.09 g / mL; (3) The method for preparing crystal form A of the solvate shown in formula IA further includes a purification step, wherein the solvate is purified by pulping with a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water is 5:1; (4) When the preparation method of the crystal form A of the solvate shown in Formula IA includes a purification step, the mass-volume ratio of the compound shown in Formula I to the mixed solvent is 0.12 g / mL.

136. The method for preparing crystal form A of the solvate of formula IA as described in claim 135, characterized in that, It includes the following steps: The compound shown in Formula I was mixed with acetonitrile, ethanol was added, the mixture was filtered, and the solid was collected. The solid was purified by slurrying with a mixed solvent of acetonitrile and water in a volume ratio of 5:1 to obtain crystal form A of the solvate shown in Formula IA.

137. A method for preparing crystal form B of the compound of formula I as claimed in any one of claims 1 to 9, crystal form F of the solvate of formula IF as claimed in any one of claims 59 to 66, crystal form G of the solvate of formula IG as claimed in any one of claims 67 to 74, crystal form I of the solvate of formula II as claimed in any one of claims 75 to 82, or crystal form K of the solvate of formula IK as claimed in any one of claims 83 to 88, characterized in that, It includes the following steps: (1) A mixture is obtained by mixing crystal form A of the solvate of formula IA as described in any one of claims 11 to 18 with solvent C; (2) The resulting mixture is stirred at a heating / cooling rate of 0.1°C / min within the range of 50°C to 5°C; When the obtained compound is crystal form B as shown in Formula I, the solvent C is water; When the resulting solvate is in crystal form F as shown in formula IF, the solvent propylene is isopropanol; When the resulting solvate is of crystal form G as shown in formula IG, the solvent propyl is methyl tert-butyl ether; When the resulting solvate is of crystal form I as shown in Formula II, the solvent propylene is N-methylpyrrolidone; When the obtained solvate has crystal form K as shown in formula IK, the solvent propylene is a mixed solvent of acetonitrile / water = 1 / 1; The preparation method satisfies the following conditions: (1) The mass-to-volume ratio of crystal form A of the solvate shown in formula IA to solvent C is 100 g / L or 300 g / L; (2) Step (2) is performed 12 or 20 times; (3) Before step (2), add crystal form B of the compound shown in formula I, crystal form F of the solvate shown in formula IF, crystal form G of the solvate shown in formula IG, crystal form I of the solvate shown in formula II, or crystal form K of the solvate shown in formula IK, in a mass ratio of 1:80 with crystal form A of the solvate shown in formula IA.

138. The method for preparing crystal form B of the compound represented by formula I, crystal form F of the solvate represented by formula IF, crystal form G of the solvate represented by formula IG, crystal form I of the solvate represented by formula II, or crystal form K of the solvate represented by formula IK, as described in claim 137, is characterized in that, It includes the following steps: mixing crystal form A of the solvate shown in IA with solvent C, cooling the mixture from 50°C to 5°C at a rate of 0.1°C / min, and then heating it from 5°C to 50°C, repeating the heating and cooling cycles 12 or 20 times to obtain crystal form B of the compound shown in Formula I, crystal form F of the solvate shown in Formula IF, crystal form G of the solvate shown in Formula IG, crystal form I of the solvate shown in Formula II, or crystal form K of the solvate shown in Formula IK.

139. A method for preparing crystal form C of the solvate of formula IC as described in any one of claims 35 to 42, crystal form D of the solvate of formula ID as described in any one of claims 43 to 50, or crystal form E of the solvate of formula IE as described in any one of claims 51 to 58, characterized in that, It includes the following steps: (1) The crystal form A of the solvate of formula IA as described in any one of claims 11 to 18 is fully dissolved in solvent A; (2) After adding solvent B to the obtained solution, crystallization is obtained to obtain the crystal form C of the solvate shown in formula IC, the crystal form D of the solvate shown in formula ID, or the crystal form E of the solvate shown in formula IE. Wherein, when the obtained solvate is of crystal form C as shown in formula IC, solvent A is dimethyl sulfoxide and solvent B is acetonitrile; When the resulting solvate is of crystal form D as shown in formula ID, solvent A is 1,3-dimethyl-2-imidazolium ketone and solvent B is ethanol; When the resulting solvate is in crystal form E as shown in formula IE, solvent A is N,N-dimethylformamide and solvent B is acetone; The preparation method satisfies the following conditions: (1) The mass-to-volume ratio of crystal form A of the solvate shown in formula IA to solvent A is 15 g / L, 50 g / L or 150 g / L; (2) The volume ratio of solvent A to solvent B is 1:1 or 1:

3.

140. The method for preparing crystal form C of the solvate of formula IC, crystal form D of the solvate of formula ID, or crystal form E of the solvate of formula IE as described in claim 139, characterized in that, It includes the following steps: fully dissolving crystal form A of the solvate shown in formula IA with solvent A, adding solvent B to the resulting solution, filtering the resulting suspension to obtain crystal form C of the solvate shown in formula IC, crystal form D of the solvate shown in formula ID, or crystal form E of the solvate shown in formula IE.

141. A method for preparing a solvate of formula IL as described in any one of claims 89 to 96, a solvate of formula IM as described in any one of claims 121 to 126, a solvate of formula IN as described in any one of claims 97 to 104, a solvate of formula IO as described in any one of claims 105 to 112, or a solvate of formula IP as described in any one of claims 113 to 120, characterized in that, It comprises the following steps: mixing the crystal form A of the solvate of formula IA as described in any one of claims 11 to 18 with solvent D to obtain a mixture, and suspending it to obtain the crystal form L of the solvate of formula IL, the crystal form M of the solvate of formula IM, the crystal form N of the solvate of formula IN, the crystal form O of the solvate of formula IO, or the crystal form P of the solvate of formula IP. Wherein, when the resulting solvate is of crystal form L as shown in formula IL, the solvent is anisole; When the resulting solvate has crystal form M as shown in formula IM, the solvent T is trifluoroethanol; When the resulting solvate is of crystal form N as shown in formula IN, the solvent is N-methylpyrrolidone; When the resulting solvate is in crystal form O as shown in formula IO, the solvent is ethyl acetate; When the resulting solvate is in crystal form P as shown in formula IP, the solvent is toluene; The preparation method satisfies the following conditions: (1) The mass-volume ratio of crystal form A to solvent D of the solvate shown in formula IA is 100 g / L, 150 g / L or 300 g / L; (2) The suspension operation conditions are: temperature of 25°C or 50°C, instrument speed of 400 rpm, and time of 14 days or 7 days.

142. A method for preparing crystal form S of the solvate of formula IS as described in any one of claims 127 to 134, characterized in that, It comprises the following steps: at 50°C, fully dissolving crystal form A of the solvate of formula IA according to any one of claims 11 to 18 with N-methylpyrrolidone, adding acetone to the resulting solution and cooling it to obtain crystal form S of the solvate of formula IS; The preparation method satisfies the following conditions: (1) The mass-to-volume ratio of crystal form A of the solvate shown in formula IA to that of N-methylpyrrolidone is 75 g / L; (2) The volume ratio of the acetone to the N-methylpyrrolidone is 3:

1.

143. The method for preparing crystal form S of the solvate of formula IS as described in claim 142, characterized in that, It includes the following steps: at 50°C, the crystal form A of the solvate shown in formula IA is fully dissolved in N-methylpyrrolidone, filtered, the filtrate is collected, the filtrate is cooled and acetone is added, filtered, and the solid is collected to obtain the crystal form S of the solvate shown in formula IS.

144. A method of preparing a crystalline Form R of the solvate of Formula I-R as claimed in any one of claims 19 to 26, comprising: It includes the following steps: (1) Mixing crystal form A of the solvate of formula IA as described in any one of claims 11 to 18, water, and NaOH to obtain mixture A; (2) Add hydrochloric acid aqueous solution to the obtained mixture A to obtain the crystal form R of the solvate shown in formula IR; The preparation method satisfies the following conditions: (1) In step (1), the molar ratio of crystal form A of the solvate shown in formula IA to NaOH is 1:1.7 or 1:2; (2) In step (2), the molar ratio of crystal form A of the solvate shown in formula IA to hydrochloric acid is 1:2, 1:3 or 2:2; (3) In step (2), the crystal form R of the solvate shown in formula IR is added to the mixture A in a mass ratio of 1:75 with the crystal form A of the solvate shown in formula IA.

145. The method for preparing the crystal form R of the solvate of formula IR as described in claim 144, characterized in that, It includes the following steps: mixing crystal form A of the solvate shown in formula IA with water to obtain a mixture, adding 2 or 1.7 times the equivalent amount of NaOH to obtain mixture A, and mixing mixture A with hydrochloric acid aqueous solution to obtain crystal form R of the solvate shown in formula IR.

146. A method for preparing crystal form T of the solvate of formula IT as described in any one of claims 27 to 34, characterized in that, It comprises the following steps: drying the crystal form R of the solvate of formula IR as described in any one of claims 19 to 26 at 50°C for 2 hours to obtain the crystal form T of the solvate of formula IT.

147. A pharmaceutical composition comprising, It comprises substance X and pharmaceutical excipients, wherein substance X is a solvate of the compound of formula I as claimed in claim 10, or crystal form B of the compound of formula I as claimed in any one of claims 1 to 9, crystal form A of the solvate of formula IA as claimed in any one of claims 11 to 18, crystal form R of the solvate of formula IR as claimed in any one of claims 19 to 26, crystal form T of the solvate of formula IT as claimed in any one of claims 27 to 34, crystal form C of the solvate of formula IC as claimed in any one of claims 35 to 42, crystal form D of the solvate of formula ID as claimed in any one of claims 43 to 50, crystal form E of the solvate of formula IE as claimed in any one of claims 51 to 58, crystal form F of the solvate of formula IF as claimed in any one of claims 59 to 66, and so on. Seek one or more of the following: crystal form G of the solvate of formula IG as described in any one of claims 67 to 74; crystal form I of the solvate of formula II as described in any one of claims 75 to 82; crystal form K of the solvate of formula IK as described in any one of claims 83 to 88; crystal form L of the solvate of formula IL as described in any one of claims 89 to 96; crystal form M of the solvate of formula IM as described in any one of claims 121 to 126; crystal form N of the solvate of formula IN as described in any one of claims 97 to 104; crystal form O of the solvate of formula IO as described in any one of claims 105 to 112; crystal form P of the solvate of formula IP as described in any one of claims 113 to 120; and crystal form S of the solvate of formula IS as described in any one of claims 127 to 134.

148. The use of a substance X in the preparation of a TRPC5 inhibitor, said substance X being a solvate of the compound of formula I as claimed in claim 10, or crystal form B of the compound of formula I as claimed in any one of claims 1 to 9, crystal form A of the solvate of formula IA as claimed in any one of claims 11 to 18, crystal form R of the solvate of formula IR as claimed in any one of claims 19 to 26, crystal form T of the solvate of formula IT as claimed in any one of claims 27 to 34, crystal form C of the solvate of formula IC as claimed in any one of claims 35 to 42, crystal form D of the solvate of formula ID as claimed in any one of claims 43 to 50, crystal form E of the solvate of formula IE as claimed in any one of claims 51 to 58, and crystal form IF of the solvate as claimed in any one of claims 59 to 66. F, one or more of the following: crystal form G of the solvate of formula IG as claimed in any one of claims 67 to 74; crystal form I of the solvate of formula II as claimed in any one of claims 75 to 82; crystal form K of the solvate of formula IK as claimed in any one of claims 83 to 88; crystal form L of the solvate of formula IL as claimed in any one of claims 89 to 96; crystal form M of the solvate of formula IM as claimed in any one of claims 121 to 126; crystal form N of the solvate of formula IN as claimed in any one of claims 97 to 104; crystal form O of the solvate of formula IO as claimed in any one of claims 105 to 112; crystal form P of the solvate of formula IP as claimed in any one of claims 113 to 120; and crystal form S of the solvate of formula IS as claimed in any one of claims 127 to 134. The TRPC5 inhibitor is used in vivo or in vitro.

149. The use of a substance X in the preparation of a pharmaceutical product, said substance X being a solvate of the compound of formula I as claimed in claim 10, or crystal form B of the compound of formula I as claimed in any one of claims 1 to 9, crystal form A of the solvate of formula IA as claimed in any one of claims 11 to 18, crystal form R of the solvate of formula IR as claimed in any one of claims 19 to 26, crystal form T of the solvate of formula IT as claimed in any one of claims 27 to 34, crystal form C of the solvate of formula IC as claimed in any one of claims 35 to 42, crystal form D of the solvate of formula ID as claimed in any one of claims 43 to 50, crystal form E of the solvate of formula IE as claimed in any one of claims 51 to 58, crystal form F of the solvate of formula IF as claimed in any one of claims 59 to 66, or as... Crystal form G of the solvate of formula IG as claimed in any one of claims 67 to 74, crystal form I of the solvate of formula II as claimed in any one of claims 75 to 82, crystal form K of the solvate of formula IK as claimed in any one of claims 83 to 88, crystal form L of the solvate of formula IL as claimed in any one of claims 89 to 96, crystal form M of the solvate of formula IM as claimed in any one of claims 121 to 126, crystal form N of the solvate of formula IN as claimed in any one of claims 97 to 104, crystal form O of the solvate of formula IO as claimed in any one of claims 105 to 112, crystal form P of the solvate of formula IP as claimed in any one of claims 113 to 120, and crystal form S of the solvate of formula IS as claimed in any one of claims 127 to 134; The drug is used to treat and / or prevent TRPC5-mediated diseases.

150. The use of claim 149, wherein the compound is administered in combination with a second compound. The TRPC5-mediated diseases mentioned above are mental illnesses, neurological disorders, or kidney diseases; The mental or neurological disorders mentioned are selected from: disorders related to disordered emotional processing, disorders related to anxiety and fear, memory impairment, disorders related to impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, or epilepsy. The kidney diseases mentioned include focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy, Allport syndrome, hypertensive nephropathy, nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, post-infectious glomerulonephritis, thin basement membrane disease, amyloidosis nephropathy, C1q nephropathy, rapidly progressive glomerulonephritis, anti-glomerular basement membrane disease, C3 glomerulonephritis, or primary glomerular diseases.

151. The use of claim 150, wherein the compound is of formula (Ia) ###0010### (Ia). The mental or neurological disorders mentioned are neurodegenerative disorders; The kidney diseases mentioned are steroid-resistant nephrotic syndrome, idiopathic membranous nephropathy, immune complex-mediated membranoproliferative glomerulonephritis, complement-mediated membranoproliferative glomerulonephritis, glomerular membranoproliferative glomerulonephritis, or hypertensive nephrosclerosis.

152. The application as described in claim 150, characterized in that, The mental or neurological disorders mentioned are selected from: borderline personality disorder or depression, post-traumatic stress disorder, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, obsessive-compulsive disorder, separation anxiety, Alzheimer's disease, amnesia, aphasia, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, Huntington's disease, learning disabilities, sleep disorders, multiple personality disorder, schizophrenia, or Wechsler syndrome; The kidney disease mentioned is primary amyloid nephropathy or IgA nephropathy.

153. The application as described in claim 150, characterized in that, The mental or neurological disorders mentioned are selected from: major depressive disorder, dysphoric disorder, postpartum depression, or bipolar disorder.

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