Crystal form of heterocyclic compound as well as preparation method and application thereof

Abstract

The invention discloses a crystal form of a heterocyclic compound as well as a preparation method and application of the crystal form. The heterocyclic compound is a compound shown in the formula I, Cu-K alpha radiation is used for the crystal form of the heterocyclic compound, and diffraction peaks exist at the positions of 8.95 + / -0.20 degrees, 12.92 + / -0.20 degrees, 16.39 + / -0.20 degrees, 17.01 + / -0.20 degrees, 17.44 + / -0.20 degrees, 17.76 + / -0.20 degrees, 18.08 + / -0.20 degrees, 19.02 + / -0.20 degrees, 21.95 + / -0.20 degrees, 22.20 + / -0.20 degrees, 23.49 + / -0.20 degrees, 24.15 + / -0.20 degrees, 24.92 + / -0.20 degrees, 25.94 + / -0.20 degrees, 27.14 + / -0.20 degrees and 29.68 + / -0.20 degrees in an X- The crystal form of the heterocyclic compound has one or more of the following advantages: good chemical stability, good physical stability, good patent medicine prospect and good preparation process machinability.

Description

A crystal form of a heterocyclic compound, its preparation method and application

[0001] This application claims priority to Chinese patent application No. 202210938910.9, filed on August 5, 2022. This application incorporates the entire text of the aforementioned Chinese patent application. Technical Field

[0002] The present invention relates to a crystal form of a heterocyclic compound, a preparation method and application thereof. Background Art

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

[0004] The calcium influx caused by the activation of non-selective cation channels (such as TRPC5) also changes the intracellular free calcium concentration. Calcium is a ubiquitous second messenger molecule in cells, and the change of intracellular calcium levels has a profound impact on signal transduction and gene expression. Therefore, the activation of non-selective cation channels (such as TRPC5) can cause the change of gene expression and cell phenotype. Gene expression events include but are not limited to the generation of mRNA encoding cell surface receptors, ion channels and kinases. These changes in gene expression can cause the hyperexcitability in this cell.

[0005] Homomeric TRPC5 ion channels are signaling-gated, Ca-gated ion channels primarily expressed in neurons. 2+ Can pass through the channel. TRPC5 forms homomeric multi-subunit structures (such as tetramers (i.e., TRPC5 homo-multimers)) and heteromeric multi-subunit structures (such as tetramers (i.e., TRPC5-TRPC1 hetero-multimers)). Unless explicitly stated otherwise, when the term TRPC5 is used herein (e.g., when identifying a modulator of TRPC5, such as a TRPC5 antagonist), the term TRPC5 is used generally to include one or both of TRPC5 homo-multimers or hetero-multimers (e.g., TRPC5-TPRC1 or TRPC5-TRPC4 hetero-multimers).

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

[0007] Compounds that inhibit TRPC5 containing ion channels are useful, for example, for treating disorders by modulating the activity of transient receptor potential cation channel subfamily C, member 5 (TRPC5), which can exist in homomultimeric forms and in heteromultimeric forms 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., December 2, 2013; 123(12): 5298-5309, Zhou et al., Science 358, 1332-1336 (2017). Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome with clinical manifestations of massive proteinuria or nephrotic syndrome. The pathology is characterized by focal segmental glomerular sclerosis and podocyte degeneration leading to foot process fusion or disappearance. FSGS accounts for approximately 5% to 10% of adult nephrotic syndrome in my country, and patients are more common in young and middle-aged men. In patients with persistent nephrotic syndrome, more than 50% progress to end-stage renal disease within 5 to 10 years.

[0009] In healthy glomeruli, TRPC5 is sequestered in the cytoplasm, maintaining normal filtration barriers. When podocytes are damaged, podocyte damage activates RAC1, causing TRPC5 to transfer from the cytoplasm to the cell membrane, which promotes AT1 receptor-induced calcium ion influx through the TRPC5 channel, further promoting RAC1 activity. RAC1 activation induces actin reorganization and podocyte detachment from the glomerulus; the loss of podocytes destroys the filtration barrier, allowing serum proteins to leak into the urine.

[0010] Currently, the main FSGS treatment drugs used in clinical practice are 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, and are prone to relapse. Therefore, the development of new TRPC5 inhibitor drugs has positive significance for the treatment of the above-mentioned diseases. At the same time, developing pharmaceutical forms of these compounds suitable for drug production, such as forms with improved stability (e.g., storage stability), hygroscopicity, and / or efficacy (e.g., in vivo bioavailability), so as to achieve good results in the pharmaceutical and medication stages, has become a technical problem that needs to be solved urgently.

[0011] Summary of the Invention

[0012] The technical problem to be solved by the present invention is that existing TRPC5 inhibitors are limited in variety, have poor efficacy, and have a limited number of heterocyclic compound crystalline forms. Thus, a crystalline form of a heterocyclic compound, a preparation method, and its application are provided. The crystalline form of the heterocyclic compound of the present invention has one or more of the following advantages: good chemical stability, good physical stability, promising drug development prospects, and good processability in formulation processes.

[0013] The present invention provides a crystalline form B of a compound represented by formula I, which has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°;

[0014] In some embodiments, the crystalline form B of the compound represented by formula I uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has 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 crystalline form B of the compound of formula I has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 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. .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 There are diffraction peaks 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 crystalline form B of the compound represented by Formula I has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles having diffraction peaks as shown in Table 2.

[0017] In some embodiments, the crystalline form B of the compound represented by Formula I uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in FIG8 .

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

[0019] In some embodiments, the differential scanning calorimetry curve of Form B of the compound represented by Formula I is shown in FIG9 .

[0020] In some embodiments, the thermogravimetric analysis (TGA) curve of Form B of the compound of 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 Form B of the compound represented by Formula I is shown in FIG10 .

[0022] In some embodiments, the crystalline form B of the compound represented by formula I is a solvate-free form.

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

[0024] The present invention provides a solvate of the compound represented by formula I, which is a solvate represented by formula IA, a solvate represented by formula IR or a solvate represented by formula IT.

[0025] Among them, a is 0.50-1.50; r is 3.00-6.00; t is 1.00-5.00.

[0026] In some embodiments, in the solvate represented by Formula IA, a is 0.70, 0.75, 0.78, 0.79 or 0.80.

[0027] In some embodiments, a is 0.79, and the Form A of the solvate represented by Formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0028] In some embodiments, a is 0.79, and the crystalline form A of the solvate represented by the formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°, .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°.

[0029] In some embodiments, a is 0.79, and the crystalline form A of the solvate represented by the formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and 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. 0.20°, 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° , there are diffraction peaks at 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 Form A of the solvate represented by Formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles having diffraction peaks as shown in Table 1.

[0031] In some embodiments, a is 0.79. The X-ray powder diffraction (XRPD) pattern of Form A of the solvate represented by Formula IA using Cu-Kα radiation is shown in FIG1 .

[0032] In some embodiments, a is 0.79, and the differential scanning calorimetry (DSC) curve of 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.

[0033] In some embodiments, a is 0.79. The differential scanning calorimetry curve of Form A of the solvate represented by Formula IA is shown in FIG2 .

[0034] In some embodiments, a is 0.79, and the thermogravimetric analysis (TGA) curve of 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.

[0035] In some embodiments, a is 0.79. The thermogravimetric analysis curve of Form A of the solvate represented by Formula IA is shown in FIG3 .

[0036] In some embodiments, the crystalline form A of the solvate represented by Formula IA may be a crystalline form of a hydrate.

[0037] In some embodiments, a is 0.79, and the solvate represented by Formula IA is a crystalline form.

[0038] In some embodiments, in the solvate represented by Formula IR, r is 3.80, 4.00, 4.10, 4.20 or 4.30.

[0039] In some embodiments, r is 4.10, and the crystalline form R of the solvate represented by the formula IR has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0040] In some embodiments, r is 4.10, and the crystalline form R of the solvate represented by the formula IR uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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±0.2 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°.

[0041] In some embodiments, r is 4.10, and the crystalline form R of the solvate represented by the formula IR uses Cu-Kα radiation and an 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°, 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 There are diffraction peaks 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°.

[0042] In some embodiments, r is 4.10, and the crystalline form R of the solvate represented by the formula IR uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 60.

[0043] In some embodiments, r is 4.10, and the differential scanning calorimetry (DSC) curve of the crystalline form R of the solvate represented by Formula IR has endothermic peaks at 87.1°C±3°C and 182.4°C±3°C.

[0044] In some embodiments, r is 4.10, and the differential scanning calorimetry curve of Form R of the solvate represented by Formula IR is shown in Figure 61.

[0045] In some embodiments, r is 4.10, and the thermogravimetric analysis (TGA) curve of 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.

[0046] In some embodiments, r is 4.10, and the thermogravimetric analysis curve of Form R of the solvate represented by Formula IR is shown in Figure 62.

[0047] In some embodiments, the crystalline form R of the solvate represented by Formula IR may be a crystalline form of a hydrate.

[0048] In some embodiments, r is 4.10, and the solvate represented by Formula IR is a crystalline form.

[0049] In some embodiments, in the solvate represented by Formula IT, t is 2.00, 2.50, 2.80, 2.85 or 2.90.

[0050] In some embodiments, t is 2.85, and the crystalline form T of the solvate represented by the formula IT has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0051] In some embodiments, t is 2.85, and the crystalline form T of the solvate represented by the formula IT has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°.

[0052] In some embodiments, t is 2.85, and the crystalline form T of the solvate represented by the formula IT has an X-ray powder diffraction pattern using Cu-Kα radiation and 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°, 18.48 There are diffraction peaks at 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°.

[0053] In some embodiments, t is 2.85, and the crystalline form T of the solvate represented by Formula IT uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 68.

[0054] In some embodiments, t is 2.85, and the differential scanning calorimetry (DSC) curve of Form T of the solvate represented by Formula IT has endothermic peaks at 65.1°C±3°C and 181.5°C±3°C.

[0055] In some embodiments, t is 2.85. The differential scanning calorimetry curve of Form T of the solvate represented by Formula IT is shown in Figure 69.

[0056] In some embodiments, t is 2.85, and the thermogravimetric analysis (TGA) curve of Form T of the solvate represented by Formula IT shows a weight loss of 1.2% in the temperature range of 34°C±3°C to 140°C±3°C.

[0057] In some embodiments, t is 2.85, and the thermogravimetric analysis curve of Form T of the solvate represented by Formula IT is shown in Figure 70.

[0058] In some embodiments, the crystalline form T of the solvate represented by Formula IT is a hydrated crystalline form.

[0059] In some embodiments, t is 2.85, and the solvate represented by Formula IT is a crystalline form.

[0060] The present invention provides a solvate of the compound of formula I, which is a solvate of formula IC, a solvate of formula ID, a solvate of formula IE, a solvate of formula IF, a solvate of formula IG, a solvate of formula II, a solvate of formula IK, a solvate of formula IL, a solvate of formula IM, a solvate of formula IN, a solvate of formula IO, a solvate of formula IP, or a solvate of formula IS;

[0061] Among them, 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.

[0062] In some embodiments, in the solvate represented by Formula IC, c is 0.40, 0.45, 0.47, 0.50 or 0.80.

[0063] In some embodiments, in the crystalline form C of the solvate represented by Formula IC, c' is 1.00, 2.00, 2.50, 3.00 or 3.50.

[0064] In some embodiments, c is 0.47, c' is 2.50, and the Form C of the solvate represented by Formula IC has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0065] In some embodiments, c is 0.47, c' is 2.50, and the crystalline form C of the solvate represented by the formula IC uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°.

[0066] In some embodiments, c is 0.47, c' is 2.50, and the crystalline form C of the solvate represented by formula IC has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 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°, 20.10±0.20°, There are diffraction peaks at .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°.

[0067] In some embodiments, c is 0.47, c' is 2.50, and the X-ray powder diffraction (XRPD) pattern of Form C of the solvate represented by Formula IC using Cu-Kα radiation is shown in FIG. 14 .

[0068] In some embodiments, c is 0.47, c' is 2.50, and the differential scanning calorimetry (DSC) curve of Form C of the solvate represented by Formula IC has endothermic peaks at 69.2°C±3°C and 166.7°C±3°C.

[0069] In some embodiments, c is 0.47 and c′ is 2.50. The differential scanning calorimetry curve of Form C of the solvate represented by Formula IC is shown in FIG15 .

[0070] In some embodiments, c is 0.47, c' is 2.50, and the thermogravimetric analysis (TGA) curve of Form C of the solvate represented by Formula IC shows a weight loss of 3.7% in the temperature range of 34°C±3°C to 150°C±3°C, and a weight loss of 10.1% in the temperature range of 150°C±3°C to 200°C±3°C.

[0071] In some embodiments, c is 0.47 and c′ is 2.50. The thermogravimetric analysis curve of Form C of the solvate represented by Formula IC is shown in FIG16 .

[0072] In some embodiments, the crystalline form C of the solvate represented by Formula IC can be a crystalline form of a solvate of water and dimethyl sulfoxide.

[0073] In some embodiments, in the solvate represented by Formula ID, d is 0.50, 0.60, 0.69, 0.70 or 0.80.

[0074] In some embodiments, in the solvate represented by Formula ID, d' is 5.50, 5.80, 5.86, 5.90 or 6.00.

[0075] In some embodiments, in the solvate represented by Formula ID, d" is 6.00, 7.00, 7.08, 7.50 or 8.00.

[0076] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08, and the crystalline form D of the solvate represented by the formula ID has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0077] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08. The crystalline form D of the solvate represented by the formula ID uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles and further has diffraction peaks at one or more of the following positions: 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°, 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°.

[0078] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08. The X-ray powder diffraction pattern of the solvate of Formula ID using Cu-Kα radiation and expressed in 2θ angles is 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°, 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 There are diffraction peaks 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°.

[0079] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08. The X-ray powder diffraction (XRPD) pattern of Form D of the solvate represented by Formula ID using Cu-Kα radiation is shown in FIG18 .

[0080] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08, and the differential scanning calorimetry (DSC) curve of 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.

[0081] In some embodiments, d is 0.69, d′ is 5.86, and d″ is 7.08. The differential scanning calorimetry curve of Form D of the solvate represented by Formula ID is shown in FIG19 .

[0082] In some embodiments, d is 0.69, d' is 5.86, and d" is 7.08. The thermogravimetric analysis (TGA) curve of Form D of the solvate represented by Formula ID shows a weight loss of 5.3% in the temperature range of 34°C±3°C to 80°C±3°C, and a weight loss of 12.8% in the temperature range of 80°C±3°C to 140°C±3°C.

[0083] In some embodiments, d is 0.69, d′ is 5.86, and d″ is 7.08. The thermogravimetric analysis curve of Form D of the solvate represented by Formula ID is shown in FIG20 .

[0084] In some embodiments, d is 0.69, d′ is 5.86, and d″ is 7.08, and the solvate represented by Formula ID is a crystalline form.

[0085] In some embodiments, the crystalline form D of the solvate represented by Formula ID is a crystalline form of a solvate of 1,3-dimethyl-2-imidazolidinone, water and ethanol.

[0086] In some embodiments, in the solvate represented by Formula IE, e is 1.00, 1.21, 1.30, 1.40 or 1.50.

[0087] In some embodiments, in the solvate represented by Formula IE, e' is 5.50, 6.00, 6.20, 6.50 or 7.80.

[0088] In some embodiments, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by the formula IE has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0089] In some embodiments, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by the formula IE uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further presents diffraction peaks at one or more of the following positions: 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°.

[0090] In some embodiments, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by the formula IE uses Cu-Kα radiation and an 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 There are diffraction peaks at 0.20°, 14.38±0.20°, 14.94±0.20°, 17.46±0.20°, 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°.

[0091] In some embodiments, e is 1.21 and e' is 6.20. The X-ray powder diffraction (XRPD) pattern of Form E of the solvate represented by Formula IE using Cu-Kα radiation is shown in FIG. 22 .

[0092] In some embodiments, e is 1.21, e' is 6.20, and the differential scanning calorimetry (DSC) curve of 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.

[0093] In some embodiments, e is 1.21 and e′ is 6.20. The differential scanning calorimetry curve of Form E of the solvate represented by Formula IE is shown in FIG23 .

[0094] In some embodiments, e is 1.21, e' is 6.20, and the thermogravimetric analysis curve (TGA) of the crystalline form E of the solvate represented by Formula IE shows a weight loss of 2.7% in the temperature range of 33°C±3°C to 100°C±3°C, and a weight loss of 4.7% in the temperature range of 100°C±3°C to 170°C±3°C.

[0095] In some embodiments, e is 1.21, e' is 6.20, and the solvate represented by Formula IE is a crystalline form.

[0096] In some embodiments, e is 1.21 and e′ is 6.20. The thermogravimetric analysis curve of Form E of the solvate represented by Formula IE is shown in FIG. 24 .

[0097] In some embodiments, the crystalline form E of the solvate represented by Formula IE may be a crystalline form of a compound of water and N,N-dimethylformamide.

[0098] In some embodiments, in the solvate represented by Formula IF, f is 0.60, 0.70, 0.80, 0.88 or 0.90.

[0099] In some embodiments, in the solvate represented by Formula IF, f' is 0.50, 0.60, 0.64, 0.70 or 0.80.

[0100] In some embodiments, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by the formula IF has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0101] In some embodiments, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by the formula IF uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further presents diffraction peaks at one or more of the following positions: 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°.

[0102] In some embodiments, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by the formula IF uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 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°, 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°.

[0103] In some embodiments, f is 0.88, f' is 0.64, and the X-ray powder diffraction (XRPD) pattern of Form F of the solvate represented by Formula IF using Cu-Kα radiation is shown in FIG. 26 .

[0104] In some embodiments, f is 0.88, f' is 0.64, and the differential scanning calorimetry (DSC) curve of 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.

[0105] In some embodiments, f is 0.88, f′ is 0.64, and the differential scanning calorimetry curve of Form F of the solvate represented by Formula IF is shown in FIG. 27 .

[0106] In some embodiments, f is 0.88, f' is 0.64, and the thermogravimetric analysis curve (TGA) of the crystalline form F of the solvate represented by Formula IF shows a weight loss of 2.5% in the temperature range of 34°C±3°C to 100°C±3°C, and a weight loss of 0.4% in the temperature range of 100°C±3°C to 170°C±3°C.

[0107] In some embodiments, f is 0.88, f′ is 0.64, and the thermogravimetric analysis curve of Form F of the solvate represented by Formula IF is shown in FIG28 .

[0108] In some embodiments, f is 0.88, f' is 0.64, and the solvate represented by Formula IF is a crystalline form.

[0109] In some embodiments, the crystalline form of the solvate represented by Formula IF can be a crystalline form of a solvate of water and isopropanol.

[0110] In some embodiments, in the solvate represented by formula IG, g is 0.10, 0.15, 0.25, 0.30 or 0.35.

[0111] In some embodiments, in the solvate represented by formula IG, g' is 0.50, 0.60, 0.70, 0.75 or 0.80.

[0112] In some embodiments, g is 0.25, g' is 0.7, and the crystalline form G of the solvate represented by the formula IG has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0113] In some embodiments, g is 0.25, g' is 0.7, and the crystalline form G of the solvate represented by the formula IG uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further presents diffraction peaks at one or more of the following positions: 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°.

[0114] In some embodiments, g is 0.25, g' is 0.7, and the crystalline form G of the solvate represented by the formula IG uses Cu-Kα radiation and an 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°, 18 There are diffraction peaks at .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°.

[0115] In some embodiments, g is 0.25, g' is 0.7, and the X-ray powder diffraction (XRPD) pattern of Form G of the solvate represented by Formula IG using Cu-Kα radiation is shown in FIG. 30 .

[0116] In some embodiments, g is 0.25, g' is 0.7, and the differential scanning calorimetry (DSC) curve of Form G of the solvate represented by Formula IG has endothermic peaks at 64.7°C±3°C and 209.3°C±3°C.

[0117] In some embodiments, g is 0.25 and g′ is 0.7. The differential scanning calorimetry curve of Form G of the solvate represented by Formula IG is shown in FIG31 .

[0118] In some embodiments, g is 0.25, g' is 0.7, and the thermogravimetric analysis curve (TGA) of Form G of the solvate represented by Formula IG shows a weight loss of 0.4% in the temperature range of 33°C±3°C to 100°C±3°C, and a weight loss of 9.7% in the temperature range of 100°C±3°C to 210°C±3°C.

[0119] In some embodiments, g is 0.25 and g′ is 0.7. The thermogravimetric analysis curve of Form G of the solvate represented by Formula IG is shown in FIG32 .

[0120] In some embodiments, g is 0.25, g' is 0.7, and the solvate represented by Formula IG is a crystalline form.

[0121] In some embodiments, the crystalline form G of the solvate represented by formula IG may be a crystalline form of water and methyl tert-butyl ether.

[0122] In some embodiments, in the solvate represented by formula II, i is 3.50, 3.70, 3.80, 3.87 or 3.90.

[0123] In some embodiments, i is 3.87, and the crystalline form I of the solvate represented by the formula II has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0124] In some embodiments, i is 3.87, and the crystalline form I of the solvate represented by formula II uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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 .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°.

[0125] In some embodiments, i is 3.87, and the crystalline form I of the solvate represented by formula II uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles is 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°, 16.02 ±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 There are diffraction peaks at 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°.

[0126] In some embodiments, i is 3.87, and the Form I of the solvate represented by Formula II uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 34.

[0127] In some embodiments, i is 3.87, and the differential scanning calorimetry (DSC) curve of the crystalline form I of the solvate represented by formula II has endothermic peaks at 44.8°C±3°C, 130.8°C±3°C, and 217.4°C±3°C.

[0128] In some embodiments, i is 3.87. The differential scanning calorimetry curve of Form I of the solvate represented by Formula II is shown in FIG35 .

[0129] In some embodiments, i is 3.87, and the thermogravimetric analysis (TGA) curve of Form I of the solvate represented by Formula II shows a weight loss of 0.2% in the temperature range of 34°C±3°C to 70°C±3°C, and a weight loss of 20.4% in the temperature range of 70°C±3°C to 135°C±3°C.

[0130] In some embodiments, i is 3.87, and the thermogravimetric analysis curve of Form I of the solvate represented by Formula II is shown in FIG36 .

[0131] In some embodiments, i is 3.87, and the solvate represented by Formula II is a crystalline form.

[0132] In some embodiments, the crystalline form I of the solvate represented by formula II can be a crystalline form of N-methylpyrrolidone solvate.

[0133] In some embodiments, in the solvate represented by Formula IK, k is 1.00, 1.20, 1.28, 1.30 or 1.50.

[0134] In some embodiments, in the solvate represented by Formula IK, k' is 0.30, 0.35, 0.40, 0.45 or 0.50.

[0135] In some embodiments, k is 1.28, k' is 0.40, and the Form K of the solvate represented by Formula IK has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0136] In some embodiments, k is 1.28, k' is 0.40, and the crystalline form K of the solvate represented by the formula IK uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles and further has diffraction peaks at one or more of the following positions: 8.52±0.20°, 15.25±0.20°, 16.61±0.20°, 17.06±0.20°, 18.64±0.2 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°.

[0137] In some embodiments, k is 1.28, k' is 0.40, and the crystalline form K of the solvate represented by formula IK has an X-ray powder diffraction pattern using Cu-Kα radiation and 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°, 20.04±0. There are diffraction peaks at .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°.

[0138] In some embodiments, k is 1.28, k' is 0.40, and the Form K of the solvate represented by Formula IK has an X-ray powder diffraction (XRPD) pattern as shown in FIG. 38 using Cu-Kα radiation.

[0139] In some embodiments, k is 1.28, k' is 0.40, and the thermogravimetric analysis (TGA) curve of Form K of the solvate represented by Formula IK shows a weight loss of 6.4% in the temperature range of 33°C±3°C to 180°C±3°C.

[0140] In some embodiments, k is 1.28, k' is 0.40, and the thermogravimetric analysis curve of Form K of the solvate represented by Formula IK is shown in FIG39 .

[0141] In some embodiments, k is 1.28, k' is 0.40, and the solvate represented by Formula IK is a crystalline form.

[0142] In some embodiments, the crystalline form K of the solvate represented by Formula IK can be a crystalline form of a solvate of water and acetonitrile.

[0143] In some embodiments, in the solvate represented by Formula IL, l is 0.80, 0.90, 1.01, 1.10 or 1.20.

[0144] In some embodiments, in the solvate represented by Formula IL, l' is 0.60, 0.70, 0.74, 0.75 or 0.80.

[0145] In some embodiments, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by the formula IL has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0146] In some embodiments, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by the formula IL uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles and further has diffraction peaks at one or more of the following positions: 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°.

[0147] In some embodiments, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by the formula IL uses Cu-Kα radiation and an 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°, 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°. 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±0.20°, 29.01±0.20°, 29.64±0.20°, 30.13±0.20°, 30.81±0.20°, 32.65 There are diffraction peaks at 33.53±0.20°, 34.11±0.20°, 34.76±0.20°, 37.29±0.20° and 38.22±0.20°.

[0148] In some embodiments, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by Formula IL uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 41.

[0149] In some embodiments, l is 1.01, l' is 0.74, and the differential scanning calorimetry (DSC) curve of the crystalline form L of the solvate represented by Formula IL has endothermic peaks at 57.2°C±3°C and 178.4°C±3°C.

[0150] In some embodiments, l is 1.01, l' is 0.74, and the differential scanning calorimetry curve of Form L of the solvate represented by Formula IL is shown in FIG42 .

[0151] In some embodiments, l is 1.01, l' is 0.74, and the thermogravimetric analysis (TGA) curve of Form L of the solvate represented by Formula IL shows a weight loss of 2.5% in the temperature range of 35°C±3°C to 100°C±3°C, and a weight loss of 6.9% in the temperature range of 100°C±3°C to 190°C±3°C.

[0152] In some embodiments, l is 1.01, l' is 0.74, and the thermogravimetric analysis curve of Form L of the solvate represented by Formula IL is shown in Figure 43.

[0153] In some embodiments, l is 1.01, l' is 0.74, and the solvate represented by Formula IL is a crystalline form.

[0154] In some embodiments, the crystalline form L of the solvate represented by Formula IL can be a crystalline form of a compound of water and anisole.

[0155] In some embodiments, in the solvate represented by formula IN, n is 2.80, 3.20, 3.28, 3.30 or 3.50.

[0156] In some embodiments, n is 3.28, and the crystalline form N of the solvate represented by the formula IN has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0157] In some embodiments, n is 3.28, and the crystalline form N of the solvate represented by the formula IN uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°.

[0158] In some embodiments, n is 3.28, and the crystalline form N of the solvate represented by the formula IN uses Cu-Kα radiation and an 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°, 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±0.20° , 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 There are diffraction peaks at .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°.

[0159] In some embodiments, n is 3.28, and the crystalline form N of the solvate represented by the formula IN uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 48.

[0160] In some embodiments, n is 3.28, and the differential scanning calorimetry (DSC) curve of 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.

[0161] In some embodiments, n is 3.28. The differential scanning calorimetry curve of Form N of the solvate represented by Formula IN is shown in FIG. 49 .

[0162] In some embodiments, n is 3.28, and the thermogravimetric analysis (TGA) curve of Form N of the solvate represented by Formula IN shows a weight loss of 13.0% in the temperature range of 34°C±3°C to 90°C±3°C.

[0163] In some embodiments, n is 3.28, and the thermogravimetric analysis curve of Form N of the solvate represented by Formula IN is shown in Figure 50.

[0164] In some embodiments, n is 3.28, and the solvate represented by Formula IN is a crystalline form.

[0165] In some embodiments, the crystalline form N of the solvate represented by formula IN can be a crystalline form of N-methylpyrrolidone solvate.

[0166] In some embodiments, in the solvate represented by Formula IO, o is 0.40, 0.50, 0.60, 0.65 or 0.70.

[0167] In some embodiments, o is 0.60, and the crystalline form O of the solvate represented by the formula IO has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0168] In some embodiments, o is 0.60, and the crystalline form O of the solvate represented by the formula IO uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, 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°.

[0169] In some embodiments, o is 0.60, and the Form O of the solvate represented by Formula IO has an X-ray powder diffraction pattern using Cu-Kα radiation and 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±0.20°, 21. There are diffraction peaks 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°.

[0170] In some embodiments, o is 0.6, and the Form O of the solvate represented by Formula IO uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 52.

[0171] In some embodiments, o is 0.6, and the differential scanning calorimetry (DSC) curve of the crystalline form O of the solvate represented by Formula IO has endothermic peaks at 125.5°C±3°C and 209.6°C±3°C.

[0172] In some embodiments, o is 0.6, and the differential scanning calorimetry curve of Form O of the solvate represented by Formula IO is shown in FIG. 53 .

[0173] In some embodiments, o is 0.6, and the thermogravimetric analysis (TGA) curve of the crystalline 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.

[0174] In some embodiments, o is 0.6, and the thermogravimetric analysis curve of Form O of the solvate represented by Formula IO is shown in Figure 54.

[0175] In some embodiments, the crystalline form O of the solvate represented by Formula IO can be a crystalline form of ethyl acetate.

[0176] In some embodiments, in the solvate represented by Formula IP, p is 0.40, 0.50, 0.56, 0.60 or 0.70.

[0177] In some embodiments, p is 0.56, and the crystalline form P of the solvate represented by the formula IP has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0178] In some embodiments, p is 0.56, and the crystalline form P of the solvate represented by the formula IP further exhibits an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles at one or more of the following diffraction peaks: 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°.

[0179] In some embodiments, p is 0.56, and the crystalline form P of the solvate represented by the formula IP has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 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°, 19.57±0.20°. , there are diffraction peaks 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°.

[0180] In some embodiments, p is 0.56, and the crystalline form P of the solvate represented by the formula IP uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 56.

[0181] In some embodiments, p is 0.56, and the differential scanning calorimetry (DSC) curve of the crystalline form P of the solvate represented by Formula IP has endothermic peaks at 157.4°C±3°C and 206.8°C±3°C.

[0182] In some embodiments, p is 0.56. The differential scanning calorimetry curve of the crystalline form P of the solvate represented by Formula IP is shown in Figure 57.

[0183] In some embodiments, p is 0.56, and the thermogravimetric analysis (TGA) curve of the crystalline form P of the solvate represented by Formula IP shows a weight loss of 7.8% in the temperature range of 35°C to 180°C.

[0184] In some embodiments, p is 0.56, and the thermogravimetric analysis curve of the crystalline form P of the solvate represented by Formula IP is shown in Figure 58.

[0185] In some embodiments, p is 0.56, and the solvate represented by Formula IP is a crystalline form.

[0186] In some embodiments, the crystalline form P of the solvate represented by Formula IP may be a crystalline form of a toluene solvate.

[0187] In some embodiments, in the solvate represented by formula IM, m is 1.20, 1.30, 1.39, 1.40 or 1.50.

[0188] In some embodiments, m is 1.39, and the crystalline form M of the solvate represented by the formula IM has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°.

[0189] In some embodiments, m is 1.39, and the crystalline form M of the solvate represented by the formula IM further exhibits an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, exhibiting diffraction peaks at one or more of the following positions: 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°.

[0190] In some embodiments, m is 1.39, and the crystalline form M of the solvate represented by the formula IM has an X-ray powder diffraction pattern expressed in 2θ angles using Cu-Kα radiation 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°.

[0191] In some embodiments, m is 1.39, and the crystalline form M of the solvate represented by Formula IM uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 45.

[0192] In some embodiments, m is 1.39, and the thermogravimetric analysis (TGA) curve of Form M of the solvate represented by Formula IM shows a weight loss of 16.7% in the temperature range of 36°C±3°C to 160°C±3°C.

[0193] In some embodiments, m is 1.39. The thermogravimetric analysis curve of Form M of the solvate represented by Formula IM is shown in FIG46 .

[0194] In some embodiments, m is 1.39, and the solvate represented by Formula IM is a crystalline form.

[0195] In some embodiments, the crystalline form M of the solvate represented by Formula IM can be a crystalline form of trifluoroethanol hydrate.

[0196] In some embodiments, in the solvate represented by Formula IS, s is 2.00, 2.10, 2.20, 2.30 or 2.40.

[0197] In some embodiments, the s is 2.20, and the Form S of the solvate represented by the formula IS has an X-ray powder diffraction pattern expressed in 2θ angles using Cu-Kα radiation 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°.

[0198] In some embodiments, the s is 2.20, and the crystalline form S of the solvate represented by the formula IS uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles and further has diffraction peaks at one or more of the following positions: 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 16.05±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°, 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°.

[0199] In some embodiments, the s is 2.20, and the crystalline form S of the solvate represented by the formula IS uses Cu-Kα radiation and an 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°, 16.25±0.20°. There are diffraction peaks 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°.

[0200] In some embodiments, the s is 2.20, and the crystalline form S of the solvate represented by the formula IS uses Cu-Kα radiation, and its X-ray powder diffraction (XRPD) pattern is shown in Figure 64.

[0201] In some embodiments, the s is 2.20, and the differential scanning calorimetry (DSC) curve of the crystalline form S of the solvate represented by the formula IS has endothermic peaks at 107.1°C±3°C and 219.3°C±3°C.

[0202] In some embodiments, the s is 2.20. The differential scanning calorimetry curve of the crystalline form S of the solvate represented by Formula IS is shown in Figure 65.

[0203] In some embodiments, the s is 2.20, and the thermogravimetric analysis (TGA) curve of the crystalline form S of the solvate represented by the formula IS shows a weight loss of 9.8% in the temperature range of 36°C±3°C to 150°C±3°C.

[0204] In some embodiments, the s is 2.20, and the thermogravimetric analysis curve of Form S of the solvate represented by Formula IS is shown in Figure 66.

[0205] In some embodiments, the s is 2.20, and the solvate represented by Formula IS is a crystalline form.

[0206] In some embodiments, the s is 2.20, and the crystalline form S of the solvate represented by Formula IS can be a crystalline form of N-methylpyrrolidone solvate.

[0207] The present invention provides a method for preparing the crystalline form A of the solvate represented by formula IA, comprising the following steps: mixing the compound represented by formula I with acetonitrile, and adding ethanol to obtain the crystalline form A of the solvate represented by formula IA.

[0208] In the method for preparing the crystalline form A of the solvate represented by formula IA, the mass volume ratio of the compound represented by formula I to the acetonitrile can be 0.50 to 1.00 g / mL, for example, 0.75 g / mL.

[0209] In the method for preparing the crystalline form A of the solvate represented by formula IA, the mass volume ratio of the compound represented by formula I to the ethanol can be 0.05 to 0.15 g / mL, for example, 0.09 g / mL.

[0210] In some embodiments, the method for preparing Form A of the solvate represented by Formula IA further comprises a purification step, for example, slurry purification using a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water can be 5:1.

[0211] In the purification step, the mass volume ratio of the compound represented by formula I to the mixed solvent may be 0.05 to 0.20 g / mL. Preferably, the mass volume ratio of the compound represented by formula I to the mixed solvent is 0.12 g / mL.

[0212] In some embodiments, the preparation method of the crystalline form A of the solvate represented by formula IA comprises the following steps: mixing the compound represented by formula I with acetonitrile, adding ethanol (for example, slowly adding ethanol dropwise), filtering, and collecting the solid; and purifying the obtained solid by slurrying with a mixed solvent of acetonitrile and water in a volume ratio of 5:1 to obtain the crystalline form A of the solvate represented by formula IA.

[0213] The present invention provides a crystalline form A of a solvate represented by formula IA, which is prepared by the preparation method of the crystalline form A of the solvate represented by formula IA.

[0214] The present invention provides a method for preparing Form B of the compound represented by Formula I, Form F of the solvate represented by Formula IF, Form G of the solvate represented by Formula IG, Form I of the solvate represented by Formula II, or Form K of the solvate represented by Formula IK, comprising the following steps:

[0215] (1) mixing the crystalline form A of the solvate represented by the above formula IA with solvent C to obtain a mixture;

[0216] (2) stirring the resulting mixture in the range of 50°C to 5°C at a heating and cooling rate of 0.1°C / min (e.g., heating the mixture from 5°C to 50°C or cooling it from 50°C to 5°C);

[0217] When the obtained crystal form B of the compound represented by formula I is obtained, the solvent C is water;

[0218] When the obtained solvate is in Form F of Formula IF, the solvent C is isopropanol;

[0219] When the obtained solvate is in the form G of the formula IG, the solvent C is methyl tert-butyl ether;

[0220] When the obtained crystalline form I of the solvate represented by formula II is obtained, the solvent C is N-methylpyrrolidone;

[0221] When the obtained solvate is in the form K of formula IK, the solvent C is a mixed solution of acetonitrile / water (1 / 1) (a mixed solvent of acetonitrile and water in a volume ratio of 1:1).

[0222] In the preparation method of the crystalline form B of the compound represented by Formula I, the crystalline form F of the solvate represented by Formula IF, the crystalline form G of the solvate represented by Formula IG, the crystalline form I of the solvate represented by Formula II, or the crystalline form K of the solvate represented by Formula IK, the mass volume ratio of the crystalline form A of the solvate represented by Formula IA to the solvent C may be 50 to 500 g / L, for example, 100 g / L or 300 g / L.

[0223] In some embodiments, in the preparation method of the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK, step (2) can be repeated 6 to 10 times, for example, 12 times or 20 times.

[0224] In some embodiments, in the preparation method of the crystalline form B of the compound represented by Formula I, the crystalline form F of the solvate represented by Formula IF, the crystalline form G of the solvate represented by Formula IG, the crystalline form I of the solvate represented by Formula II, or the crystalline form K of the solvate represented by Formula IK, the crystalline form B of the compound represented by Formula I, the crystalline form F of the solvate represented by Formula IF, the crystalline form G of the solvate represented by Formula IG, the crystalline form I of the solvate represented by Formula II, or the crystalline form K of the solvate represented by Formula IK can be added before step (2), for example, the crystalline form B of the compound represented by Formula I is added at a mass ratio of (1 to 2):100 to the crystalline form A of the solvate represented by Formula IA. The crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK are preferably added with the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK at a mass ratio of 1:80 to the crystalline form A of the solvate represented by formula IA; the addition of the corresponding crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK serves as a seed crystal to facilitate crystal formation.

[0225] In some embodiments, the preparation method of the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA with solvent C (for example, stirring and mixing at 50°C for 30 minutes), 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, and repeating the heating and cooling 12 or 20 times to obtain the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK.

[0226] The present invention provides a method for preparing Form C of a solvate represented by Formula IC, Form D of a solvate represented by Formula ID, or Form E of a solvate represented by Formula IE, comprising the following steps:

[0227] (1) fully dissolving the crystalline form A of the solvate represented by the above formula IA with solvent A;

[0228] (2) adding solvent B to the resulting solution and crystallizing to obtain Form C of the solvate represented by Formula IC, Form D of the solvate represented by Formula ID, or Form E of the solvate represented by Formula IE;

[0229] When the obtained solvate is a crystalline form C represented by formula IC, solvent A is dimethyl sulfoxide and solvent B is acetonitrile;

[0230] When the obtained solvate is in Form D of Formula ID, Solvent A is 1,3-dimethyl-2-imidazolidinone and Solvent B is ethanol;

[0231] When the obtained solvate is in form E of formula IE, solvent A is N,N-dimethylformamide and solvent B is acetone.

[0232] In the preparation method of the crystalline form C of the solvate represented by Formula IC, the crystalline form D of the solvate represented by Formula ID, or the crystalline form E of the solvate represented by Formula IE, the mass volume ratio of the crystalline form A of the solvate represented by Formula IA to the solvent A may be 10 to 300 g / L, preferably 15 to 150 g / L, for example, 15 g / L, 50 g / L or 150 g / L.

[0233] In the preparation method of the crystalline form C of the solvate represented by Formula IC, the crystalline form D of the solvate represented by Formula ID, or the crystalline form E of the solvate represented by Formula IE, the volume ratio of the solvent A to the solvent B may be 1:1 to 1:3, for example, 1:1 or 1:3, for example, 1:3.

[0234] In some embodiments, the preparation method of the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, or the crystalline form E of the solvate represented by formula IE comprises the following steps: fully dissolving the crystalline form A of the solvate represented by formula IA with solvent A, adding solvent B to the obtained solution (for example, slowly adding solvent B to the mixture), and filtering the obtained suspension to obtain the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, or the crystalline form E of the solvate represented by formula IE.

[0235] The present invention provides a method for preparing Form L of a solvate represented by Formula IL, Form M of a solvate represented by Formula IM, Form N of a solvate represented by Formula IN, Form O of a solvate represented by Formula IO, or Form P of a solvate represented by Formula IP, comprising the steps of: mixing Form A of the solvate represented by Formula IA with a solvent D to obtain a mixture, and suspending the mixture to obtain Form L of the solvate represented by Formula IL, Form M of the solvate represented by Formula IM, Form N of the solvate represented by Formula IN, Form O of the solvate represented by Formula IO, or Form P of the solvate represented by Formula IP;

[0236] Wherein, when the obtained solvate is in the form L of the formula IL, the solvent D is anisole;

[0237] When the obtained solvate is in the form M of the formula IM, the solvent D is trifluoroethanol;

[0238] When the obtained crystalline form N of the solvate represented by formula IN is obtained, the solvent D is N-methylpyrrolidone;

[0239] When the obtained solvate is in Form O of Formula IO, the solvent D is ethyl acetate;

[0240] When the obtained crystal form P of the solvate represented by formula IP is obtained, the solvent is toluene.

[0241] In the preparation method of the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP, the mass volume ratio of the crystalline form A of the solvate represented by formula IA to the solvent D may be 50 to 300 g / L, preferably 100 g / L, 150 g / L or 300 g / L.

[0242] In the preparation method of the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP, the suspension operation conditions may be: temperature of 25°C or 50°C, instrument speed of 400 rpm, and time of 14 days or 7 days.

[0243] In some embodiments, the preparation method of the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA with solvent D to obtain a mixture, and suspending the mixture at 25°C or 50°C and 400 rpm for 14 days or 7 days to obtain the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP.

[0244] The present invention provides a method for preparing the crystalline form S of the solvate represented by formula IS, comprising the following steps: fully dissolving the crystalline form A of the solvate represented by formula IA in N-methylpyrrolidone at 50° C., adding acetone to the resulting solution and cooling the solution to obtain the crystalline form S of the solvate represented by formula IS.

[0245] In the method for preparing the crystalline form S of the solvate represented by Formula IS, the mass volume ratio of the crystalline form A of the solvate represented by Formula IA to N-methylpyrrolidone can be 50 to 200 g / L, for example, 75 g / L.

[0246] In the method for preparing the crystalline form S of the solvate represented by Formula IS, the volume ratio of acetone to N-methylpyrrolidone can be 1:1 to 8:1, for example, 3:1.

[0247] In some embodiments, the method for preparing the crystalline form S of the solvate represented by formula IS comprises the following steps: fully dissolving the crystalline form A of the solvate represented by formula IA in N-methylpyrrolidone at 50° C. (e.g., keeping warm at 50° C. for 30 minutes), filtering, collecting the filtrate, cooling the obtained filtrate (e.g., placing it in a −20° C. environment) and adding acetone, filtering, and collecting the solid to obtain the crystalline form S of the solvate represented by formula IS.

[0248] The present invention provides a method for preparing the crystalline form R of the solvate represented by formula IR, comprising the following steps:

[0249] (1) mixing Form A of the solvate represented by Formula IA, water, and NaOH to obtain a mixture A;

[0250] (2) adding aqueous hydrochloric acid to the obtained mixture A to obtain the crystalline form R of the solvate represented by formula IR.

[0251] In the method for preparing the crystalline form R of the solvate represented by formula IR, in step (1), the molar ratio of the crystalline 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.

[0252] In the method for preparing the crystalline form R of the solvate represented by formula IR, in step (2), the molar ratio of the crystalline 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, and also such as 2:2.

[0253] In some embodiments, in the preparation method of the crystalline form R of the solvate represented by formula IR, in the step (2), the crystalline form R of the solvate represented by formula IR can be added to the mixture A, for example, the crystalline form R of the solvate represented by formula IR is added in a mass ratio of (0.5 to 2):100 to the crystalline form A of the solvate represented by formula IA, preferably the crystalline form R of the solvate represented by formula IR is added in a mass ratio of 1:75 to the crystalline form A of the solvate represented by formula IA; the crystalline form R of the solvate represented by formula IR is added to serve as a seed crystal to facilitate crystal formation.

[0254] In some embodiments, the preparation method of the crystalline form R of the solvate represented by formula IR comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA with water to obtain a mixture, adding 2 times or 1.7 times the equivalent of NaOH to obtain mixture A, and mixing the mixture A with aqueous hydrochloric acid solution to obtain the crystalline form R of the solvate represented by formula IR.

[0255] The present invention provides a method for preparing the crystalline form T of the solvate represented by formula IT, comprising the following steps: drying the crystalline form R of the solvate represented by formula IR at 50° C. for 2 h to obtain the crystalline form T of the solvate represented by formula IT.

[0256] The present invention also provides a pharmaceutical composition comprising a substance X and a pharmaceutical excipient, wherein the substance X is selected from one or more of the crystalline form B of the compound represented by the above formula I, the crystalline form A of the solvate represented by the above formula IA, the crystalline form R of the solvate represented by the above formula IR, the crystalline form T of the solvate represented by the above formula IT, the crystalline form C of the solvate represented by the above formula IC, the crystalline form D of the solvate represented by the above formula ID, the crystalline form E of the solvate represented by the above formula IE, the crystalline form F of the solvate represented by the above formula IF, the crystalline form G of the solvate represented by the above formula IG, the crystalline form I of the solvate represented by the above formula II, the crystalline form K of the solvate represented by the above formula IK, the crystalline form L of the solvate represented by the above formula IL, the crystalline form M of the solvate represented by the above formula IM, the crystalline form N of the solvate represented by the above formula IN, the crystalline form O of the solvate represented by the above formula IO, the crystalline form P of the solvate represented by the above formula IP, and the crystalline form S of the solvate represented by the above formula IS.

[0257] In some embodiments, in the pharmaceutical composition, 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 solvate represented by IA, the solvate represented by IR, the solvate represented by IT, the solvate represented by IC, the solvate represented by ID, the solvate represented by IE, the solvate represented by IF, the solvate represented by IG, the solvate represented by II, the solvate represented by IK, the solvate represented by IL, the solvate represented by IM, the solvate represented by IN, the solvate represented by IO, the solvate represented by IP, and the solvate represented by IS.

[0258] The present invention also provides a use of a substance X in the preparation of a TRPC5 inhibitor, wherein the substance X is selected from one or more of the crystalline form B of the compound represented by formula I, the crystalline form A of the solvate represented by formula IA, the crystalline form R of the solvate represented by formula IR, the crystalline form T of the solvate represented by formula IT, the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, the crystalline form E of the solvate represented by formula IE, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, the crystalline form K of the solvate represented by formula IK, the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, the crystalline form P of the solvate represented by formula IP, and the crystalline form S of the solvate represented by formula IS, and the TRPC5 inhibitor is used in vivo or in vitro.

[0259] In some embodiments, in the use of the substance X in the preparation of a TRPC5 inhibitor, 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 solvate represented by IA, the solvate represented by IR, the solvate represented by IT, the solvate represented by IC, the solvate represented by ID, the solvate represented by IE, the solvate represented by IF, the solvate represented by IG, the solvate represented by II, the solvate represented by IK, the solvate represented by IL, the solvate represented by IM, the solvate represented by IN, the solvate represented by IO, the solvate represented by IP, and the solvate represented by IS.

[0260] The present invention also provides a use of a substance X in the preparation of a drug, wherein the substance X is selected from one or more of the crystalline form B of the compound represented by formula I, the crystalline form A of the solvate represented by formula IA, the crystalline form R of the solvate represented by formula IR, the crystalline form T of the solvate represented by formula IT, the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, the crystalline form E of the solvate represented by formula IE, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, the crystalline form K of the solvate represented by formula IK, the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, the crystalline form P of the solvate represented by formula IP, and the crystalline form S of the solvate represented by formula IS. The drug is a drug for treating and / or preventing TRPC5-mediated diseases.

[0261] In some embodiments, the use of the substance X in the preparation of a drug, wherein 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 solvate represented by IA, the solvate represented by IR, the solvate represented by IT, the solvate represented by IC, the solvate represented by ID, the solvate represented by IE, the solvate represented by IF, the solvate represented by IG, the solvate represented by II, the solvate represented by IK, the solvate represented by IL, the solvate represented by IM, the solvate represented by IN, the solvate represented by IO, the solvate represented by IP, and the solvate represented by IS.

[0262] In the application, the TRPC5-mediated disease can be a psychiatric disorder, a neurological disorder, a neurodegenerative disorder or a renal disease.

[0263] The psychiatric, neurological or neurodegenerative disorder can be selected from the group consisting of disorders associated with dysregulated emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, major depressive disorder, dysthymia, dysthymia and postpartum depression, and bipolar disorder), disorders associated with 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 tumors, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, Huntington's disease, learning disorders, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke and Weil-Cohen syndrome), disorders associated with impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and other brain disorders caused by trauma or other insults including aging.

[0264] The renal disease may be focal segmental glomerulosclerosis (FSGS), minimal change disease, diabetic nephropathy, Alport 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, mesangial proliferative glomerulonephritis, amyloidosis nephropathy (preferably primary amyloidosis nephropathy), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease (anti-glomerular basement membrane disease), C3 glomerulonephritis, hypertensive nephrosclerosis or primary glomerular disease (preferably IgA nephropathy).

[0265] The present invention also provides a use of a substance X in preparing a medicament, wherein the substance X is selected from one or more of the crystalline form B of the compound represented by formula I, the crystalline form A of the solvate represented by formula IA, the crystalline form R of the solvate represented by formula IR, the crystalline form T of the solvate represented by formula IT, the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, the crystalline form E of the solvate represented by formula IE, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, the crystalline form K of the solvate represented by formula IK, the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, the crystalline form P of the solvate represented by formula IP, and the crystalline form S of the solvate represented by formula IS. The medicament is for treating and / or preventing psychiatric disorders, neurological disorders, neurodegenerative disorders, or renal diseases.

[0266] In some embodiments, in the use of the substance X in the preparation of a drug, 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 solvate represented by IA, the solvate represented by IR, the solvate represented by IT, the solvate represented by IC, the solvate represented by ID, the solvate represented by IE, the solvate represented by IF, the solvate represented by IG, the solvate represented by II, the solvate represented by IK, the solvate represented by IL, the solvate represented by IM, the solvate represented by IN, the solvate represented by IO, the solvate represented by IP, and the solvate represented by IS.

[0267] In such applications, the psychiatric, neurological or neurodegenerative disorder may be selected from diseases associated with dysregulated emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, major depressive disorder, dysthymia, dysthymia and postpartum depression, and bipolar disorder), disorders associated with 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 disorders, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke and Weil-Cohen syndrome), disorders associated with impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and other brain disorders caused by trauma or other insults including aging.

[0268] In the application, the renal disease can be focal segmental glomerulosclerosis (FSGS), minimal change disease, diabetic nephropathy, Alport 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, mesangial proliferative glomerulonephritis, amyloidosis nephropathy (preferably primary amyloidosis nephropathy), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease (anti-glomerular basement membrane disease), C3 glomerulonephritis, hypertensive nephrosclerosis or primary glomerular disease (preferably IgA nephropathy).

[0269] Unless otherwise specified, the following terms appearing in the present specification and claims have the following meanings:

[0270] The term "treat" refers to therapeutic treatment. When referring to a specific condition, treatment means: (1) alleviating the disease or one or more biological manifestations of the condition, (2) interfering with (a) one or more points in the biological cascade that leads to or causes the condition or (b) one or more biological manifestations of the condition, (3) ameliorating 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 progression of the condition or one or more biological manifestations of the condition.

[0271] The term "prevent" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0272] The term "patient" refers to any animal, preferably a mammal, that is about to be or has been administered a compound or composition according to embodiments of the present 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., preferably humans.

[0273] The term "therapeutically effective amount" refers to an amount of a compound that, when administered to a patient, is sufficient to effectively treat a disease or condition described herein. The "therapeutically effective amount" will vary depending on the compound, the condition and its severity, and the age of the patient to be treated, and can be adjusted as needed by those skilled in the art.

[0274] The term "solvate" refers to a compound of the present invention combined with a stoichiometric or non-stoichiometric solvent. The solvent molecules in the solvate may be present in an ordered or non-ordered arrangement. Such solvents include, but are not limited to, water, methanol, and ethanol.

[0275] The term "pharmaceutical excipients" refers to excipients and additives used in the production of pharmaceuticals and the preparation of prescriptions. These are all substances contained in pharmaceutical preparations, in addition to the active ingredient. For a complete list, see Part IV of the Pharmacopoeia of the People's Republic of China (2020 edition) or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009, Sixth Edition).

[0276] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0277] The reagents and raw materials used in the present invention are commercially available.

[0278] The positive progress of the present invention is that the crystal form has good stability and good processability in preparation process, and has good efficacy and broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0279] FIG1 is an XRPD spectrum of Form A of the solvate represented by Formula IA.

[0280] FIG2 is a DSC spectrum of Form A of the solvate represented by Formula IA.

[0281] FIG3 is a TGA spectrum of Form A of the solvate represented by Formula IA.

[0282] Figure 4 is a diagram of Form A of the solvate of Formula IA 1 H-NMR spectrum (DMSO-d6).

[0283] Figure 5 is a diagram of Form A of the solvate of Formula IA1 H-NMR spectrum (D2O).

[0284] FIG6 is a PLM spectrum of Form A of the solvate represented by Formula IA.

[0285] FIG7 is an FT-IR spectrum of Form A of the solvate represented by Formula IA.

[0286] FIG8 is an XRPD spectrum of Form B of the compound represented by Formula I.

[0287] FIG9 is a DSC spectrum of Form B of the compound represented by Formula I.

[0288] FIG10 is a TGA spectrum of Form B of the compound represented by Formula I.

[0289] Figure 11 is a diagram of the crystalline form B of the compound represented by Formula I 1 H-NMR spectrum.

[0290] Figure 12 is a PLM spectrum of Form B of the compound represented by Formula I.

[0291] FIG13 is an FT-IR spectrum of Form B of the compound represented by Formula I.

[0292] FIG14 is an XRPD spectrum of Form C of the solvate represented by Formula IC.

[0293] FIG15 is a DSC spectrum of Form C of the solvate represented by Formula IC.

[0294] FIG16 is a TGA spectrum of Form C of the solvate represented by Formula IC.

[0295] Figure 17 is a diagram of Form C of the solvate represented by Formula IC 1 H-NMR spectrum.

[0296] FIG18 is an XRPD spectrum of Form D of the solvate represented by Formula ID.

[0297] FIG19 is a DSC spectrum of Form D of the solvate represented by Formula ID.

[0298] FIG20 is a TGA spectrum of Form D of the solvate represented by Formula ID.

[0299] Figure 21 is a diagram of Form D of the solvate represented by Formula ID 1 H-NMR spectrum.

[0300] Figure 22 is an XRPD spectrum of Form E of the solvate represented by Formula IE.

[0301] FIG23 is a DSC spectrum of Form E of the solvate represented by Formula IE.

[0302] FIG24 is a TGA spectrum of Form E of the solvate represented by Formula IE.

[0303] Figure 25 is a diagram of Form E of the solvate represented by Formula IE 1 H-NMR spectrum.

[0304] Figure 26 is an XRPD spectrum of Form F of the solvate represented by Formula IF.

[0305] Figure 27 is a DSC spectrum of Form F of the solvate represented by Formula IF.

[0306] Figure 28 is a TGA spectrum of Form F of the solvate represented by Formula IF.

[0307] Figure 29 is a diagram of Form F of the solvate represented by Formula IF 1 H-NMR spectrum.

[0308] Figure 30 is an XRPD spectrum of Form F of the solvate represented by Formula IG.

[0309] Figure 31 is a DSC spectrum of Form G of the solvate represented by Formula IG.

[0310] Figure 32 is a TGA spectrum of Form G of the solvate represented by Formula IG.

[0311] Figure 33 is a diagram of the crystalline form G of the solvate represented by formula IG 1 H-NMR spectrum.

[0312] Figure 34 is an XRPD spectrum of Form I of the solvate represented by Formula II.

[0313] Figure 35 is a DSC spectrum of Form I of the solvate represented by Formula II.

[0314] Figure 36 is a TGA spectrum of Form I of the solvate represented by Formula II.

[0315] Figure 37 is a diagram of the crystalline form I of the solvate represented by formula II 1 H-NMR spectrum.

[0316] FIG38 is an XRPD spectrum of Form K of the solvate represented by Formula IK.

[0317] FIG39 is a TGA spectrum of Form K of the solvate represented by Formula IK.

[0318] Figure 40 is a diagram of Form K of the solvate represented by Formula IK 1 H-NMR spectrum.

[0319] Figure 41 is an XRPD spectrum of Form L of the solvate represented by Formula IL.

[0320] Figure 42 is a DSC spectrum of Form L of the solvate represented by Formula IL.

[0321] Figure 43 is a TGA spectrum of Form L of the solvate represented by Formula IL.

[0322] Figure 44 is a diagram of the crystalline form L of the solvate represented by formula IL 1 H-NMR spectrum.

[0323] Figure 45 is an XRPD spectrum of Form M of the solvate represented by Formula IM.

[0324] Figure 46 is a TGA spectrum of Form M of the solvate represented by Formula IM.

[0325] Figure 47 is a diagram of the crystalline form M of the solvate represented by formula IM 1 H-NMR spectrum.

[0326] Figure 48 is an XRPD spectrum of Form N of the solvate represented by Formula IN.

[0327] Figure 49 is a DSC spectrum of Form N of the solvate represented by Formula IN.

[0328] Figure 50 is a TGA spectrum of Form N of the solvate represented by Formula IN.

[0329] Figure 51 is a diagram of the crystalline form N of the solvate represented by formula IN 1 H-NMR spectrum.

[0330] Figure 52 is an XRPD spectrum of Form O of the solvate represented by Formula IO.

[0331] Figure 53 is a DSC spectrum of Form O of the solvate represented by Formula IO.

[0332] Figure 54 is a TGA spectrum of Form O of the solvate represented by Formula IO.

[0333] Figure 55 is a diagram of the crystalline form O of the solvate represented by formula IO 1 H-NMR spectrum.

[0334] Figure 56 is an XRPD spectrum of Form P of the solvate represented by Formula IP.

[0335] Figure 57 is a DSC spectrum of Form P of the solvate represented by Formula IP.

[0336] Figure 58 is a TGA spectrum of Form P of the solvate represented by Formula IP.

[0337] Figure 59 is a diagram of the crystalline form P of the solvate represented by formula IP 1 H-NMR spectrum.

[0338] Figure 60 is the XRPD spectrum of Form R of the solvate represented by Formula IR.

[0339] Figure 61 is a DSC spectrum of Form R of the solvate represented by Formula IR.

[0340] Figure 62 is a TGA spectrum of Form R of the solvate represented by Formula IR.

[0341] Figure 63 is a diagram of the crystalline form R of the solvate represented by Formula IR 1 H-NMR spectrum.

[0342] Figure 64 is an XRPD spectrum of Form S of the solvate represented by Formula IS.

[0343] Figure 65 is a DSC spectrum of Form S of the solvate represented by Formula IS.

[0344] Figure 66 is a TGA spectrum of Form S of the solvate represented by Formula IS.

[0345] Figure 67 is a diagram of the crystalline form S of the solvate represented by Formula IS 1 H-NMR spectrum.

[0346] Figure 68 is an XRPD spectrum of Form T of the solvate represented by Formula IT.

[0347] Figure 69 is a DSC spectrum of Form T of the solvate represented by Formula IT.

[0348] Figure 70 is a TGA spectrum of Form T of the solvate represented by Formula IT.

[0349] Figure 71 is a diagram of Form T of the solvate represented by Formula IT 1 H-NMR spectrum.

[0350] FIG72 is an XRPD overlay of Form A of the solvate of Formula IA before and after a one-week stability experiment.

[0351] FIG73 is a TGA spectrum of Form A of the solvate represented by Formula IA obtained after being placed under sealed conditions at 60° C. for one week.

[0352] Figure 74 is a TGA spectrum of Form A of the solvate represented by Formula IA obtained after being placed under open conditions of 40°C / 75% RH for 1 week.

[0353] Figure 75 is a TGA spectrum of Form A of the solvate represented by Formula IA obtained after being placed under open conditions of 25°C / 92% RH for 1 week.

[0354] FIG76 is an XRPD overlay of Form B of the compound of Formula I before and after a one-week stability experiment.

[0355] Figure 77 is a TGA spectrum of Form B of the compound of Formula I obtained after being placed under sealed conditions at 60°C for one week.

[0356] Figure 78 is a TGA spectrum of Form B of the compound of Formula I obtained after being placed under open conditions of 40°C / 75% RH for 1 week.

[0357] Figure 79 is a TGA spectrum of Form B of the compound of Formula I obtained after being placed under open conditions of 25°C / 92% RH for 1 week.

[0358] Figure 80 is a DVS spectrum of Form A of the solvate represented by Formula IA at 25°C.

[0359] Figure 81 is an XRPD overlay of Form A of the solvate of Formula IA before and after DVS testing.

[0360] Figure 82 is a DVS diagram of Form B of the compound represented by Formula I at 25°C.

[0361] FIG83 is an XRPD overlay of Form B of the compound of Formula I before and after DVS testing.

[0362] Figure 84 is an XRPD overlay of Form B of the compound of Formula I before and after compression and grinding testing. DETAILED DESCRIPTION

[0363] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0364] Abbreviations:

[0365] ACN: acetonitrile; DMF: N,N-dimethylformamide; DMSO: dimethyl sulfoxide; DMI: 1,3-dimethyl-2-imidazolidinone; DSC: differential scanning calorimetry; DVS: dynamic water sorption; 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.

[0366] Instrumental method:

[0367] 1. X-ray diffraction (XRPD), test conditions are shown in the following table:

[0368] 2. Differential Scanning Calorimetry (DSC) analysis. The test conditions are shown in the following table:

[0369] 3. Thermogravimetric analysis (TGA), the test conditions are shown in the following table:

[0370] 4. Dynamic moisture sorption (DVS), test conditions are shown in the following table:

[0371] 5. High performance liquid chromatography (HPLC), test conditions are shown in the following table:

[0372] 6. Nuclear Magnetic Resonance ( 1 H-NMR), the test conditions are shown in the following table:

[0373] 7. Fourier transform infrared spectroscopy (FT-IR), the test conditions are shown in the following table:

[0374] 8.Karl Fisher, test conditions are shown in the following table:

[0375] 9. Polarized light microscopy (PLM), test conditions are as follows:

[0376] Preparation Example

[0377] Compound 1-1 was prepared according to the method described in WO2022 / 001767A1.

[0378] Example 1 Preparation of Form A of the Solvate Represented by Formula IA

[0379] Synthesis route:

[0380] 1.1 Preparation of Compound 1-2

[0381] Compound 1-1 (100 g, 0.23 mol), sodium iodide (37.3 g, 0.25 mmol) and tetrahydrofuran (1 L) were added to the reaction flask, stirred to dissolve, and cooled to about 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 warmed to room temperature (about 18°C) and reacted for 12 hours. The reaction solution was quenched with water and concentrated to remove tetrahydrofuran at a temperature below 25°C. Ethyl acetate (1 L × 2) was added to the concentrated system for extraction. 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.

[0382] 1.2 Preparation of Form A of the Solvate of Formula IA

[0383] Compound 1-2 (55 g, 83 mmol) was dissolved in dichloromethane (500 mL). Trifluoroacetic acid (100 mL) was added dropwise to the reaction mixture with stirring, and the mixture was stirred at 25°C for 1 hour. After completion of the reaction (LCMS indicated a purity of 80%), the mixture was concentrated under reduced pressure to obtain a crude oily compound of Formula I. Acetonitrile (50 mL) was added to the crude product for dispersion, resulting in solid precipitation. Ethanol (400 mL) was slowly added dropwise to the system, causing a large amount of solid precipitation. The mixture was stirred at room temperature (approximately 17°C) for 1 hour and filtered. The filter cake was slurried with 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 reached 98% or higher. The resulting solid was lyophilized to obtain Form A as a white solid. Its XRPD spectrum analysis data is shown in Table 1.

[0384] LC-MS[M+H] + =552.0; 1 H NMR (400MHz, DMSO-d6): δ8.14(s,1H),7.84(dd,J=9.2,2.8Hz,1H),7.79(dd,J=8.4,5.6Hz,1H),7.68(td,J=8 .4, 2.6Hz, 1H), 7.36 (s, 1H), 5.68 (d, J = 7.6Hz, 2H), 4.91 (s, 2H), 4.54 (t, J = 5.6Hz, 2H), 3.98 (t, J = 5.6Hz, 2H).

[0385] The characterization data of Form A are shown in the following table:

[0386] Table 1 XRPD pattern analysis data of Form A

[0387] Example 2 Preparation of Form B of the Compound of Formula I

[0388] Weigh approximately 30 mg of Form A and add 0.3 mL of water to ensure a suspension of appropriate concentration. Stir the suspension from 50°C to 5°C for 10 cycles at a heating and cooling rate of 0.1°C / min. After the cycles, centrifuge the resulting solid through a 0.45 μm filter at 5°C for 5 minutes. The resulting solid is used as seed crystals for the next step.

[0389] Weigh 400 mg of Form A into an 8 mL glass bottle. Add 4 mL of water and stir at 50°C for 30 minutes to obtain a suspension. Add approximately 5 mg of the seed crystals prepared above to the suspension. Place the sample on a temperature cycler and stir the suspension at 50°C to 5°C for 6 cycles at a temperature ramp rate of 0.1°C / min. Centrifuge and filter to collect the solid. After vacuum drying the solid at 50°C for 2 hours, 333.0 mg of Form B of the compound represented by Formula I was obtained, with a yield of 83.3%. The XRPD spectrum analysis data are shown in Table 2.

[0390] The characterization data of Form B are shown in the following table:

[0391] Table 2 XRPD pattern analysis data of Form B

[0392] Example 3 Preparation of Crystalline Forms C to E of the Solvate of the Compound Represented by Formula I

[0393] Forms C-E of the solvates of the compound represented by Formula I were prepared using an antisolvent crystallization method. Approximately 30 mg of Form A of the solvate represented by Formula IA was weighed and thoroughly dissolved in an appropriate volume of a good solvent (see the table below). The solution was then filtered through a 0.45 μm filter to obtain a clear solution. An antisolvent (1-3 times the volume of the good solvent) was slowly added to the clear solution. The resulting suspension was filtered, and the solid portion was characterized by XRPD. The good solvents and antisolvents used in the preparation of Forms C-E are shown in the table below, and the XRPD pattern analysis data are shown in Tables 3, 4, and 5.

[0394] The operating conditions are shown in the following table:

[0395] The characterization data of crystal forms C to E are shown in the following table:

[0396] Table 3 XRPD pattern analysis data of Form C

[0397] Table 4 XRPD pattern analysis data of Form D

[0398] Table 5 XRPD pattern analysis data of Form E

[0399] Example 4 Preparation of Forms F, G, I and K of the Solvate of the Compound of Formula I

[0400] Form F of the solvate represented by Formula IF, Form G of the solvate represented by Formula IG, Form I of the solvate represented by Formula II, and Form K of the solvate represented by Formula IK were prepared using a ramping cycle method. Approximately 30 mg of Form A of the solvate represented by Formula IA was weighed and added to the solvent according to the operating conditions shown in the table below to ensure a suspension of appropriate concentration. The suspension was stirred at 50°C to 5°C for 10 cycles at a ramp rate of 0.1°C / min. After the cycling, the resulting solid was centrifuged through a 0.45 μm filter at 5°C for 5 minutes and characterized by XRPD. The operating conditions for the preparation of Form F of the solvate represented by Formula IF, Form G of the solvate represented by Formula IG, Form I of the solvate represented by Formula II, and Form K of the solvate represented by Formula IK are shown in the table below, and the XRPD pattern analysis data are shown in Tables 6, 7, 8, and 9.

[0401] The operating conditions are shown in the following table:

[0402] The characterization data of Forms F, G, I and K are shown in the following table: “ / / ”: indicates not performed.

[0403] Table 6 XRPD pattern analysis data of Form F

[0404] Table 7 XRPD pattern analysis data of Form G

[0405] Table 8 XRPD pattern analysis data of Form I

[0406] Table 9 XRPD pattern analysis data of Form K

[0407] Example 5 Preparation of Crystalline Forms L, N, O and P of the Solvate of the Compound Represented by Formula I

[0408] Form L of the solvate represented by Formula IL, Form N of the solvate represented by Formula IN, Form O of the solvate represented by Formula IO, and Form P of the solvate represented by Formula IP were prepared using a one-week suspension method at 50°C. Approximately 30 mg of Form A of the solvate represented by Formula IA was weighed and placed in a 2 mL glass vial. Solvent was added according to the operating conditions shown in the table below, and the suspension was stirred 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 pattern analysis data are shown in Tables 10, 11, 12, and 13.

[0409] The operating conditions are shown in the following table:

[0410] The characterization data are shown in the following table: “ / / ”: indicates not performed.

[0411] Table 10 XRPD pattern analysis data of Form L

[0412] Table 11 XRPD pattern analysis data of Form N

[0413] Table 12 XRPD pattern analysis data of Form O

[0414] Table 13 XRPD pattern analysis data of Form P

[0415] Example 6 Preparation of Form M of the Solvate Represented by Formula IM

[0416] Form M of the solvate represented by Formula IM was prepared through a 25°C suspension experiment. Approximately 30 mg of Form A of the solvate represented by Formula IA was weighed into a 2 mL glass vial, 0.2 mL of trifluoroethanol was added, and the suspension was stirred at 25°C and 400 rpm for two weeks. After two weeks, the resulting suspension was filtered, and the resulting solid fraction was characterized by XRPD. The XRPD pattern analysis data are shown in Table 14.

[0417] Characterization data are shown in the table below: “ / / ”: indicates not performed.

[0418] Table 14 XRPD pattern analysis data of Form M

[0419] Example 7 Preparation of Crystalline Form S of the Solvate Represented by Formula IS

[0420] Form S of the solvate represented by Formula IS was prepared by rapid cooling crystallization. Approximately 30 mg of Form A of the solvate represented by Formula IA was added to 0.4 mL of N-methylpyrrolidone and thoroughly dissolved at 50°C. The solution was then filtered hot through a 0.45 μm filter to obtain a clear solution. The resulting clear solution was incubated at 50°C for 30 minutes, then quickly cooled in a -20°C refrigerator, and the antisolvent acetone (1.2 mL) was added. The resulting solid was collected by filtration and characterized. Its XRPD pattern data are shown in Table 15.

[0421] Characterization data are shown in the table below: “ / / ”: indicates not performed.

[0422] Table 15 XRPD pattern analysis data of Form S

[0423] Example 8 Preparation of Crystalline Forms R and T of the Solvate of the Compound Represented by Formula I

[0424] 8.1 Preparation of Form R of the Solvate Represented by Formula IR

[0425] Approximately 20 mg of Form A of the solvate represented by Formula IA was weighed and suspended in 2 mL of water. 1.7 N of sodium hydroxide was added to clarify the suspension. The pH was measured to be 6.0. 1 mL of 100 mM aqueous hydrochloric acid was then added to adjust the pH to 2.5. Solids continued to precipitate. The resulting solids were collected by centrifugation and used as seed crystals for the following reaction.

[0426] Weigh 150 mg of Form A of the solvate represented by Formula IA and place it in 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, filter with a centrifuge tube to remove a small amount of insoluble flocculent at the bottom, and measure the pH value to be 11.0. Slowly add about 6 mL of 100 mM hydrochloric acid aqueous solution, and add about 2 mg of the seed crystals prepared above, continue stirring, and measure the pH value to be 2.5. Centrifuge and filter, collect the solid, and let it air in a fume hood for about 3 days. 116.2 mg of off-white Form R of the solvate represented by Formula IR was obtained, with a yield of 77.5%. Its XRPD spectrum analysis data are shown in Table 16.

[0427] 8.2 Preparation Method of Crystalline Form T of Solvate Represented by Formula IT

[0428] The crystalline form R of the solvate represented by Formula IR was dried under vacuum at 50° C. for 2 h to obtain the crystalline form T (hydrate) of the solvate represented by Formula IT. The XRPD pattern analysis data are shown in Table 17.

[0429] Characterization data are shown in the table below:

[0430] Table 16 XRPD pattern analysis data of Form R

[0431] Table 17 XRPD pattern analysis data of Form T

[0432] Evaluation of crystal form:

[0433] 1. Solid Stability Study of Form A and Form B

[0434] Form A of the solvate of Formula IA and Form B of the compound of Formula I were stored at 60°C sealed, 40°C / 75% RH open, and 25°C / 92% RH open for one week. The solids obtained after stability testing were analyzed by XRPD, TGA, and HPLC. As shown in Table 18, the results indicate that Form A and Form B showed no crystalline changes or significant chemical degradation during the stability testing (see Figures 72-79).

[0435] Table 18 Solid stability study of Forms A and B

[0436] 2. Hygroscopicity study of Form A and Form B

[0437] The hygroscopicity of Form A of the solvate of Formula IA and Form B of the compound of Formula I at 25°C was evaluated by dynamic moisture sorption testing. The DVS cycle for Form A was 40-95-0-95-40% RH, while the DVS cycle for Form B was 40-0-95-0-40% RH. The dm / dt ratio was 0.002, with the shortest equilibration time being 60 minutes and the longest equilibration time being 360 minutes. After DVS, XRPD analysis was performed to investigate any changes in the crystalline form.

[0438] The results show that Form A is hygroscopic. It absorbed 4.3% moisture from 40% to 95% RH at 25°C (see Figure 80), and there is a risk of crystal transformation at higher humidity. After the dynamic moisture sorption test, no crystal transformation occurred, and the crystallinity did not change significantly (see Figure 81). The results show that Form B is slightly hygroscopic. It absorbed 1.9% moisture from 0% to 95% RH at 25°C (see Figure 82). After the dynamic moisture sorption test, no crystal transformation occurred, and the crystallinity did not change significantly (see Figure 83).

[0439] 3. Feasibility Assessment of Form B Preparation

[0440] 3.1 Study on crystal transformation behavior under pressure

[0441] Approximately 10 mg of Form B of the compound of Formula I was weighed and compressed using a small tablet press at a pressure of 10 MPa for 5 minutes. XRPD characterization was performed to investigate the crystal transformation and changes in crystallinity. The results showed that Form B showed no significant change in crystallinity at this pressure (see Figure 84).

[0442] 3.2 Simulated dry grinding experiment

[0443] Approximately 10 mg of Form B of the compound of Formula I was weighed and ground in a mortar for 3 minutes. XRPD characterization was performed to investigate the crystal transformation and changes in crystallinity. The results showed that Form B showed no significant change in crystallinity in this experiment (see Figure 84).

[0444] 3.3 Simulated wet grinding experiment

[0445] Approximately 10 mg of Form B of the compound of Formula I was weighed, and 20 μL of water or ethanol was added, respectively. The mixture was then ground in a mortar for 3 minutes. XRPD characterization was performed to investigate the crystal transformation and changes in crystallinity. The results showed that the crystallinity of Form B did not change significantly when ground in water or ethanol, as shown in Figure 84.

[0446] Biological activity test

[0447] Effect Example 1

[0448] 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, and used Fluo-4AM fluorescent dye to detect the effects of compounds on Ca2+ in TRPC5-HEK 293 cells. 2+ The effect of the compound on TRPC5 channels can be used to indirectly reflect the effect of the compound on TRPC5 channels.

[0449] Pico145: MCE, lot number 31245;

[0450] DMEM high glucose: Gibco, lot number 2230805;

[0451] FBS: Gibco, lot number 1981614;

[0452] P / S: Gibco, lot number 2289326;

[0453] HEPES: Sigma, lot number WXBD0664V;

[0454] Blasticidin: Gibco, lot number 1737347;

[0455] Hygromycine: Yeasen, batch number H18010;

[0456] Doxycycline: Sigma, lot number BCBL6540V;

[0457] Fluo-4AM: Molecular Devices, lot number 1231041;

[0458] Poly-D-Lysine: Sigma, lot number SLBQ9797V.

[0459] 1. Cell Culture

[0460] 1.1 TRPC5-HEK 293 cell recovery

[0461] Recovery medium: 100% DMEM (Dulbecco's Modified Eagle Medium) high glucose

[0462] Selection medium: DMEM high glucose + 10% FBS (Phosphate Buffered Saline) + 1% P / S (Penicillin-Streptomycin Solution) + 1% HEPES (4-hydroxyethylpiperazineethanesulfonic acid) + Blastidicin (5 μg / mL) + Hygromycine (50 μg / mL)

[0463] Induction medium: DMEM high glucose + 10% FBS + 1% P / S + 1% HEPES + doxycycline (Doxycycline, 1 μg / mL)

[0464] Recovery process: Take out the cells from the liquid nitrogen tank, transfer them to a water bath in an ice box, and transfer the cryopreservative solution to the recovery solution when it dissolves in circles until it contains a small piece of ice. Centrifuge at 1000 rpm for 5 minutes, discard the supernatant, transfer to the selective culture medium, and expand the culture in a CO2 incubator (5% CO2, 95% humidity, 37°C).

[0465] 1.2 TRPC5-HEK 293 cell plating

[0466] 14 h before the real-time fluorescence experiment, cells were washed with PBS, digested with trypsin containing EDTA (TRYPSIN-EDTA), diluted with induction medium to 200,000 cells / mL, and plated into 96-well black-bottom transparent plates coated with poly-D-lysine (PDL) (stock solution 10 mg / mL, final concentration 10 μg / mL) at 100 μL / well, i.e. 20,000 cells / well.

[0467] 2. Buffer Preparation

[0468] 500 mL external solution for TRPC5 calcium signal detection: 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-hydroxyethylpiperazineethanesulfonic acid).

[0469] Calcium fluorescent dye: The external solution for TRPC5 calcium signal detection contains a final concentration of 4μM Fluo-4 (containing 0.5% BSA)

[0470] 3. Preparation of Compounds

[0471] Agonist: Englerin A (EA)

[0472] Agonist concentration: EC of EA for activation of TRPC5 50 About 0.35nM, use 0.3nM EA

[0473] Positive inhibitor: Pico145 (HC608)

[0474] Positive inhibitor concentration: 100 nM

[0475] Test compounds: Compound 1-1 and compound represented by formula I

[0476] Concentration of test compound: conventional preparation, prepared with DMSO, prepared to 8 times the final concentration of the test solution (the final concentrations of the test are: 1nM, 3nM, 10nM, 30nM, 100nM, 300nM and 1000nM), 60μL per bottom plate well.

[0477] 4. Data Processing

[0478] The fluorescence value of the Flipr test was subtracted from the value of the unstained cell well (i.e., the background fluorescence value). Graphpad Prism 6.0 software was used for statistics and data processing. The trajectory graph was normalized by removing the baseline and displayed as a ratio. The AUC (area under the curve formed by the calcium flux signal) was calculated for the dose-effect graph. The data were collected and the log value of the compound concentration was compared. The IC was calculated using the log[Inhibitor] vs. response—Variable slope. 50 value.

[0479] The results are shown in Table 19: The compound represented by Formula I has no inhibitory activity on TRPC5 channels.

[0480] Table 19

[0481] PK study of male SD rats after single oral administration of the compound of Example 2 (using 5% Solutol as solvent)

[0482] 1. Experimental purpose:

[0483] The time-blood concentration curves of the compound represented by formula I (125 mg / kg) and compound 1-1 (100 mg / kg) in the plasma of male rats after single oral administration were explored to obtain the PK parameters (C max , T max , AUC last , AUC inf , T 1 / 2 , MRT, etc.).

[0484] 2. Experimental Plan

[0485] 2.1 Experimental instruments

[0486] The experimental instruments are shown in Table 20:

[0487] Table 20

[0488] 2.2 Experimental Preparation

[0489] 2.2.1 Experimental Preparation of the Compound of Formula I of the Present Invention

[0490] Rats: 3 male SD rats, SPF grade, weighing 180–200 g (source: Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., certificate number: 110011201109106028);

[0491] Animals were kept in a standard animal room with free access to food and water, 3 animals per cage, a 12 / 12 hour light / dark cycle (7:00 am / 7:00 pm), and a temperature of 23 ± 1°C.

[0492] Dispensing: After accurately weighing the compound of PO group formula I, first add the required volume of 5% solutol (5% polyethylene glycol (15)-hydroxystearate, Beijing Fengli Jingqiu Pharmaceutical Co., Ltd., batch number 1760094G0), vortex mix for 2 minutes, ultrasonicate for 30 minutes, and stir for 2 hours until no obvious particles are visible to the naked eye. Administer the drug while stirring, and take the middle layer of the drug solution for administration.

[0493] Before administration, the drug solution needs to be sampled for analysis. Accurately sample 2 portions of 100 μL each from the upper, middle and lower parts of the suspension and send them for analysis and testing on the same day. The backup samples should be stored in a -75°C refrigerator for future use.

[0494] 2.2.2 Experimental preparation of compound 1-1

[0495] Rats: 3 male SD rats, SPF grade, weighing 220–300 g (source: Beijing Sibeifu Biotechnology Co., Ltd., certificate number: 110324200103216838);

[0496] Animals were kept in a standard animal room with free access to food and water, 3 animals per cage, a 12 / 12 hour light / dark cycle (7:00 am / 7:00 pm), and a temperature of 23 ± 1°C.

[0497] Preparation: After accurately weighing compound 1-1 for the PO group, add the required volume of 5% solutol, vortex mix for 2 minutes, sonicate for 30 minutes, and stir for 3 hours until no obvious particles are visible to the naked eye before oral administration;

[0498] Prepare for immediate use. Samples of the suspension must be retained for analysis. Take 2 portions of 100 μL each from the upper, middle, and lower portions of the suspension and send them for analysis and testing on the same day.

[0499] 2.3 Dosage regimen

[0500] Rats were randomly divided into 3 groups according to body weight. The specific grouping and dosing conditions are as follows (Table 21):

[0501] Table 21 Grouping and dosing information of the compounds represented by formula I of the present invention

[0502] 1. Animals in the PO group were fasted overnight but not watered before administration, and food was returned 4 hours after administration;

[0503] 2. Time of blood sampling: The time of blood sampling in the PO group was 0.167, 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 h.

[0504] Table 22 Grouping and dosing information of compound 1-1

[0505] 1. Animals in the PO group were fasted overnight but not watered before administration, and food was returned 4 hours after administration;

[0506] 2. Time of blood sampling: The time of blood sampling in the PO group was 0.167, 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 h.

[0507] 2.4 Sample collection and preparation

[0508] After administration to rats, blood was collected from the orbital venous plexus according to the sampling time point. Approximately 0.2-0.3 mL of blood was collected at each time point in an anticoagulant EP tube (containing 4 μL EDTA-K2, 375 mg / mL), which was slowly inverted up and down 3 times and stored in an ice box (no more than 30 minutes). The tube was centrifuged at 3500 × g for 10 minutes at 4°C, and the supernatant was transferred to a labeled EP tube. The plasma hemolysis was observed and recorded, and then sent for bioanalysis. If the test could not be performed on the same day, the sample should be stored at -80°C until testing (be careful not to perform multiple freezing / thawing processes).

[0509] 2.5 Sample analysis

[0510] 2.5.1 Sample Analysis of the Compound of Formula I of the Present Invention

[0511] 2.5.1.1 Experimental instruments:

[0512] High-performance liquid chromatography pump (Pump): Exion LC AD Pump, Sciex

[0513] Autosampler (Exion LC AD Autosampler, Sciex

[0514] Column Oven: Exion LC AD Column Oven, Sciex

[0515] Mass spectrometer: AB Sciex Qtrap 3500

[0516] High-speed refrigerated centrifuge: Thermo Fisher, ST16R, GG1206085-093

[0517] Analytical balance (Electronic balance): Mettler Toledo, MS-105DU, GG1206363

[0518] Vortex: Shanghai Huxi Analytical Instrument Factory, WH-2, GG1206487

[0519] Experimental materials: Rat plasma (EDTA-K2)

[0520] Analyte: Compound 1-1

[0521] Internal standard: Tolbutamide

[0522] Analytical method: LC-MS / MS

[0523] 2.5.1.2 Mass spectrometry conditions:

[0524] Mass spectrometry parameters

[0525] Ion source: Ion Electrospray (ESI)

[0526] Ionization mode: Positive

[0527] Detection mode: Multiple reaction monitoring (MRM)

[0528] Electrospray voltage: 5500

[0529] Turbo Ion Spray Temp: 550°C

[0530] Curtain Gas: 35

[0531] Collision cell gas (CAD Gas): Medium

[0532] Nebulizing Gas (Gas 1): 55.00

[0533] Auxiliary Gas (Gas 2): 55.00

[0534] Detection ion pairs (Table 23):

[0535] Table 23

[0536] 2.5.1.3 Liquid Phase Method:

[0537] Chromatographic column: Poroshell 120EC-C18 (2.1×50mm, 2.7μm)

[0538] Mobile Phase A: 0.1% formic acid in water

[0539] Mobile Phase B: 0.1% formic acid in methanol

[0540] Rinse Port Wash Solution: Methanol: Water: Acetonitrile: Isopropanol = 1:1:1:1

[0541] Column Temperature: 40°C

[0542] Flow Rate: 0.65 mL / min

[0543] Sample Tray Temp: 15°C

[0544] Injection Volume: 8 μL

[0545] Needle Stroke: 49mm

[0546] Rinse Pump Setting: Rinse the injection port only

[0547] Rinse Mode: Rinse before aspiration

[0548] Rinse Volume of Autosampler: 500 μL

[0549] Rinse Dip Time: 2 seconds

[0550] Elution gradient (Table 24):

[0551] Table 24

[0552] 2.5.1.4 Pretreatment methods

[0553] Sample pretreatment: 3 μL of working solution was added to 57 μL of blank matrix (rat blank plasma) in a 1.5 mL centrifuge tube. Protein was precipitated by adding 240 μL of acetonitrile containing 200 ng / mL tolbutamide and 0.1% FA (formic acid). The sample was vortexed for 1 minute and centrifuged at 13,000 rpm for 15 minutes at 4°C. 100 μL of the supernatant was transferred to another 96-well plate and 100 μL of a methanol:water (1:3, v:v) solution containing 0.1% FA was added. The sample was vortexed for 1 minute and centrifuged at 3,500 rpm in a 96-well plate centrifuge for 5 minutes before direct injection.

[0554] 2.5.2 Sample analysis of compound 1-1

[0555] 2.5.2.1 Experimental instruments:

[0556] High performance liquid chromatography pump (Pump): LC-30AD, Shimadzu

[0557] Auto sampler: SIL-30AC, Prominence, Shimadzu

[0558] Column Oven: CTO-30A, Shimadzu

[0559] Mass spectrometer: AB Sciex Qtrap 3500

[0560] High-speed refrigerated centrifuge (Centrifuge): Thermo Fisher, ST16R, GG1206085-093

[0561] Analytical balance (Electronic balance): Mettler Toledo, MS-105D, GG1206363

[0562] Micro vortex analyzer (Vortex): Shanghai Huxi Analytical Instrument Factory, WH-2, GG1206487

[0563] Experimental materials: Rat plasma (EDTA-K2)

[0564] Analyte: Compound 1-1

[0565] Internal standard: Tolbutamide

[0566] Analytical method: LC-MS / MS

[0567] 2.5.2.2 Mass spectrometry conditions:

[0568] Mass spectrometry parameters

[0569] Ion source: Ion Electrospray (ESI)

[0570] Ionization mode: Positive

[0571] Detection mode: Multiple reaction monitoring (MRM)

[0572] Electrospray voltage: 5500

[0573] Turbo Ion Spray Temp: 550°C

[0574] Curtain Gas: 35

[0575] Collision cell gas (CAD Gas): Medium

[0576] Nebulizing Gas (Gas 1): 55.00

[0577] Auxiliary Gas (Gas 2): 55.00

[0578] Detection ion pairs (Table 25):

[0579] Table 25

[0580] 2.5.2.3 Liquid Phase Method:

[0581] Chromatographic column: Poroshell 120EC-C18 (4.6×50mm, 2.7μm)

[0582] Mobile Phase A: 0.1% formic acid in water

[0583] Mobile Phase B: 0.1% formic acid in methanol

[0584] Rinse Port Wash Solution: Methanol: Acetonitrile: Water: Isopropanol = 1:1:1:1

[0585] Flow Rate: 0.8mL / min

[0586] Sample Tray Temp: 15°C

[0587] Injection Volume: 15 μL

[0588] Needle Stroke: 49mm

[0589] Rinse Pump Setting: Rinse the injection port only

[0590] Rinse Mode: Rinse before aspiration

[0591] Rinse Volume of Autosampler: 500 μL

[0592] Rinse Dip Time: 2 seconds

[0593] Elution gradient (Table 26):

[0594] Table 26

[0595] 2.5.2.4 Pretreatment methods

[0596] Sample pretreatment: 30 μL of sample was added to 120 μL of acetonitrile containing 0.1% FA and 200 ng / mL standard solution to precipitate protein. The sample was vortexed and centrifuged at 13,000 rpm for 10 minutes at 4°C. 100 μL of the supernatant was transferred to another 96-deep-well plate, and 100 μL of a methanol:water (1:3, v:v) solution was added. The sample was shaken for 10 minutes.

[0597] 2.6 Data Analysis

[0598] The data will be analyzed by non-compartmental model using WinNonlin (version 5.2.1 Pharsight, Mountain View, CA) to obtain PK parameters (C max , T max , AUC last , AUC inf , T 1 / 2 , MRT and other parameters). Specific results are shown in Table 27 below. The analyte of the data listed in the table is compound 1-1.

[0599] Table 27 Note: 1. 100* here means that 125 mg / kg of the compound represented by Formula I is equivalent to 100 mg / kg of compound 1-1. 2. T 1 / 2 Middle Belt # The data are abnormal data in this experiment and have been eliminated when calculating the mean.

[0600] Experimental conclusion: The compound represented by formula I of the present invention has a better exposure amount compared with compound 1-1.

Claims

1. A crystalline form B of the compound represented by formula I, characterized in that: Its X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles has 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 crystalline form B of the compound of formula I according to claim 1, wherein The crystalline form B of the compound represented by the formula I has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°; Preferably, the crystalline form B of the compound represented by formula I uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 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°, 17.44 ±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°, 32.16 There are diffraction peaks at 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 crystalline form B of the compound of formula I according to claim 1, wherein The crystal form B satisfies one or more of the following conditions: (1) The X-ray powder diffraction pattern of the crystalline form B of the compound represented by Formula I using Cu-Kα radiation and expressed in 2θ angles has the diffraction peaks shown in Table 2; (2) Form B of the compound represented by Formula I was subjected to Cu-Kα radiation, and its X-ray powder diffraction pattern is shown in FIG8 ; (3) The differential scanning calorimetry curve of Form B of the compound represented by Formula I has an endothermic peak at 247.7°C ± 3°C; (4) The differential scanning calorimetry curve of Form B of the compound represented by Formula I is shown in FIG9 ; (5) The thermogravimetric analysis curve of Form B of the compound of Formula I shows a weight loss of 1.0% within the temperature range of 35°C ± 3°C to 220°C ± 3°C; (6) The thermogravimetric analysis curve of Form B of the compound represented by Formula I is shown in FIG10 ; (7) The crystalline form B of the compound represented by formula I is a solvent-free form.

4. A solvate of the compound of formula I, characterized in that: It is a solvate represented by formula IA, a solvate represented by formula IR, a solvate represented by formula IT, a solvate represented by formula IC, a solvate represented by formula ID, a solvate represented by formula IE, a solvate represented by formula IF, a solvate represented by formula IG, a solvate represented by formula II, a solvate represented by formula IK, a solvate represented by formula IL, a solvate represented by formula IM, a solvate represented by formula IN, a solvate represented by formula IO, a solvate represented by formula IP or a solvate represented by formula IS; Among them, a is 0.50-1.50; r is 3.00-6.00; t is 1.00-5.00; 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; Preferably, a is 0.70, 0.75, 0.78, 0.79 or 0.80; r is 3.80, 4.00, 4.10, 4.20 or 4.30; t is 2.00, 2.50, 2.80, 2.85 or 2.90; c is 0.40, 0.45, 0.47, 0.50 or 0.80, c' is 1.00, 2.00, 2.50, 3.00 or 3.50; d is 0.50, 0.60, 0.69, 0.70 or 0.8 0, d' is 5.50, 5.80, 5.86, 5.90 or 6.00, d" is 6.00, 7.00, 7.08, 7.50 or 8.00; e is 1.00, 1.21, 1.30, 1.40 or 1.50, e' is 5.50, 6.00, 6.20, 6.50 or 7.80; f is 0.60, 0.70, 0.80, 0.88 or 0.90, f' is 0.50, 0.60, 0.64, 0.70 or 0. 80; g is 0.10, 0.15, 0.25, 0.30 or 0.35, g' is 0.50, 0.60, 0.70, 0.75 or 0.80; i is 3.50, 3.70, 3.80, 3.87 or 3.90; k is 1.00, 1.20, 1.28, 1.30 or 1.50, k' is 0.30, 0.35, 0.40, 0.45 or 0.50; l is 0.80, 0.90, 1.01, 1.10 or 1.2 0, l' is 0.60, 0.70, 0.74, 0.75 or 0.80; n is 2.80, 3.20, 3.28, 3.30 or 3.50; o is 0.40, 0.50, 0.60, 0.65 or 0.70; p is 0.40, 0.50, 0.56, 0.60 or 0.70; m is 1.20, 1.30, 1.39, 1.40 or 1.50; s is 2.00, 2.10, 2.20, 2.30 or 2.

40.

5. The solvate of the compound of formula I according to claim 4, wherein The solvate satisfies one or more of the following conditions; (1) In the solvate represented by Formula IA, a is 0.79, and the crystalline form A of the solvate represented by Formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, a is 0.79, and the crystalline form A of the solvate represented by the formula IA uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; More preferably, a is 0.79, and the crystalline form A of the solvate represented by formula IA is irradiated with Cu-Kα and expressed in 2θ angles. The X-ray powder diffraction pattern was 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°, 14.20±0.20°, 14.57±0.20°, 15.05±0.20°, 15.48±0.2 0°、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°, 29.14±0.20°, 30 There are diffraction peaks at 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°; (2) In the solvate represented by Formula IA, a is 0.79, and the Form A of the solvate represented by Formula IA has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, as shown in Table 1; (3) In the solvate represented by Formula IA, a is 0.

79. The X-ray powder diffraction pattern of Form A of the solvate represented by Formula IA using Cu-Kα radiation is shown in FIG1 ; (4) In the solvate represented by Formula IA, a is 0.79, and the differential scanning calorimetry curve of 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; (5) In the solvate represented by Formula IA, a is 0.

79. The differential scanning calorimetry curve of Form A of the solvate represented by Formula IA is shown in FIG2 ; (6) In the solvate represented by Formula IA, a is 0.79, and the thermogravimetric analysis curve of 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; (7) In the solvate represented by Formula IA, a is 0.

79. The thermogravimetric analysis curve of Form A of the solvate represented by Formula IA is shown in FIG3 ; (8) The crystalline form A of the solvate represented by Formula IA is a hydrated crystalline form; (9) In the solvate represented by formula IR, r is 4.10, and the crystalline form R of the solvate represented by formula IR has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, r is 4.10, and the crystalline form R of the solvate represented by the formula IR uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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° , 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°; Further preferably, r is 4.10, and the crystalline form R of the solvate represented by the formula IR uses Cu-Kα radiation and an 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°, 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 There are diffraction peaks at 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°; (10) In the solvate represented by Formula IR, r is 4.

10. The X-ray powder diffraction pattern of Form R of the solvate represented by Formula IR using Cu-Kα radiation is shown in FIG60 ; (11) In the solvate represented by Formula IR, r is 4.10, and the differential scanning calorimetry curve of the crystalline form R of the solvate represented by Formula IR has endothermic peaks at 87.1°C±3°C and 182.4°C±3°C; (12) In the solvate represented by Formula IR, r is 4.

10. The differential scanning calorimetry curve of Form R of the solvate represented by Formula IR is shown in FIG61 ; (13) In the solvate represented by Formula IR, r is 4.10, and the thermogravimetric analysis curve of 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; (14) In the solvate represented by Formula IR, r is 4.

10. The thermogravimetric analysis curve of Form R of the solvate represented by Formula IR is shown in FIG62 ; (15) The crystalline form R of the solvate represented by formula IR is a hydrated crystalline form; (16) In the solvate represented by formula IT, t is 2.85, and the crystalline form T of the solvate represented by formula IT has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, t is 2.85, and the crystalline form T of the solvate represented by the formula IT has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°; Further preferably, t is 2.85, and the crystalline form T of the solvate represented by the formula IT uses Cu-Kα radiation and an 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°, 18.48± There are diffraction peaks 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°; (17) In the solvate represented by Formula IT, t is 2.

85. The X-ray powder diffraction pattern of Form T of the solvate represented by Formula IT using Cu-Kα radiation is shown in FIG68 ; (18) In the solvate represented by Formula IT, t is 2.85, and the differential scanning calorimetry curve of Form T of the solvate represented by Formula IT has endothermic peaks at 65.1°C±3°C and 181.5°C±3°C; (19) In the solvate represented by Formula IT, t is 2.

85. The differential scanning calorimetry curve of Form T of the solvate represented by Formula IT is shown in FIG69 ; (20) In the solvate represented by Formula IT, t is 2.85, and the thermogravimetric analysis curve of Form T of the solvate represented by Formula IT shows a weight loss of 1.2% in the temperature range of 34°C ± 3°C to 140°C ± 3°C; (21) In the solvate represented by Formula IT, t is 2.

85. The thermogravimetric analysis curve of Form T of the solvate represented by Formula IT is shown in FIG70 ; (22) The crystalline form T of the solvate represented by Formula IT is a hydrated crystalline form; (23) In the solvate represented by formula IC, c is 0.47, c' is 2.50, and the X-ray powder diffraction pattern of the solvate represented by formula IC in form C using Cu-Kα radiation and expressed in 2θ angles is 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 There are diffraction peaks at ±0.20°, 28.42±0.20°, and 31.20±0.20°; Preferably, c is 0.47, c' is 2.50, and the crystalline form C of the solvate represented by the formula IC uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; Further preferably, c is 0.47, c' is 2.50, and the X-ray powder diffraction pattern of the solvate represented by Formula IC using Cu-Kα radiation and expressed in 2θ angles is 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°, 20.10±0. There are diffraction peaks at 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°; (24) In the solvate represented by Formula IC, c is 0.47 and c' is 2.

50. The X-ray powder diffraction pattern of Form C of the solvate represented by Formula IC using Cu-Kα radiation is shown in FIG14 ; (25) In the solvate represented by Formula IC, c is 0.47 and c' is 2.

50. The differential scanning calorimetry curve of Form C of the solvate represented by Formula IC has endothermic peaks at 69.2°C ± 3°C and 166.7°C ± 3°C; (26) In the solvate represented by Formula IC, c is 0.47 and c' is 2.

50. The differential scanning calorimetry curve of Form C of the solvate represented by Formula IC is shown in FIG15 ; (27) In the solvate represented by formula IC, c is 0.47 and c' is 2.

50. The thermogravimetric analysis curve of the crystal form C of the solvate represented by formula IC shows a weight loss of 3.7% in the temperature range of 34°C ± 3°C to 150°C ± 3°C and a weight loss of 10.1% in the temperature range of 150°C ± 3°C to 200°C ± 3°C. (28) In the solvate represented by Formula IC, c is 0.47 and c' is 2.

50. The thermogravimetric analysis curve of Form C of the solvate represented by Formula IC is shown in FIG16 ; (29) The crystalline form C of the solvate represented by Formula IC is a crystalline form of a compound of water and dimethyl sulfoxide; (30) In the solvate represented by formula ID, d is 0.69, d' is 5.86, and d" is 7.

08. The X-ray powder diffraction pattern of the solvate represented by formula ID using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, d is 0.69, d' is 5.86, and d" is 7.

08. The X-ray powder diffraction pattern of the solvate represented by the formula ID using Cu-Kα radiation and expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°, 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°; Further preferably, d is 0.69, d' is 5.86, and d" is 7.08, and the X-ray powder diffraction pattern of the solvate represented by the formula ID using Cu-Kα radiation and expressed in 2θ angles is 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°, 20.19±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 There are diffraction peaks at .98±0.20°, 26.14±0.20°, 26.57±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°; (31) In the solvate represented by Formula ID, d is 0.69, d′ is 5.86, and d″ is 7.

08. The X-ray powder diffraction pattern of Form D of the solvate represented by Formula ID using Cu-Kα radiation is shown in FIG18 ; (32) 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 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; (33) 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 Form D of the solvate represented by Formula ID is shown in FIG19 ; (34) In the solvate represented by formula ID, d is 0.69, d' is 5.86, and d" is 7.

08. The thermogravimetric analysis curve of Form D of the solvate represented by formula ID shows a weight loss of 5.3% in the temperature range of 34°C ± 3°C to 80°C ± 3°C, and a weight loss of 12.8% in the temperature range of 80°C ± 3°C to 140°C ± 3°C. (35) In the solvate represented by Formula ID, d is 0.69, d′ is 5.86, and d″ is 7.

08. The thermogravimetric analysis curve of Form D of the solvate represented by Formula ID is shown in FIG20 ; (36) The crystalline form D of the solvate represented by formula ID is a crystalline form of a compound of 1,3-dimethyl-2-imidazolidinone, water and ethanol; (37) In the solvate represented by formula IE, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by formula IE has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by the formula IE uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; Further preferably, e is 1.21, e' is 6.20, and the crystalline form E of the solvate represented by the formula IE uses Cu-Kα radiation and an 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°, 17. There are diffraction peaks at .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°; (38) In the solvate represented by Formula IE, e is 1.21 and e′ is 6.

20. The X-ray powder diffraction pattern of Form E of the solvate represented by Formula IE using Cu-Kα radiation is shown in FIG22 ; (39) In the solvate represented by formula IE, e is 1.21 and e′ is 6.

20. The differential scanning calorimetry curve of the crystalline 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; (40) In the solvate represented by formula IE, e is 1.21 and e′ is 6.

20. The differential scanning calorimetry curve of Form E of the solvate represented by formula IE is shown in FIG23 ; (41) In the solvate represented by formula IE, e is 1.21 and e' is 6.

20. The thermogravimetric analysis curve of the crystalline form E of the solvate represented by formula IE shows a weight loss of 2.7% in the temperature range of 33°C ± 3°C to 100°C ± 3°C and a weight loss of 4.7% in the temperature range of 100°C ± 3°C to 170°C ± 3°C. (42) In the solvate represented by Formula IE, e is 1.21 and e′ is 6.

20. The thermogravimetric analysis curve of Form E of the solvate represented by Formula IE is shown in FIG24 ; (43) The crystalline form E of the solvate represented by formula IE is a crystalline form of a compound of water and N,N-dimethylformamide; (44) In the solvate represented by Formula IF, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by Formula IF has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by the formula IF uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; Further preferably, f is 0.88, f' is 0.64, and the crystalline form F of the solvate represented by the formula IF uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 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°, 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°; (45) In the solvate represented by Formula IF, f is 0.88 and f′ is 0.

64. The X-ray powder diffraction pattern of Form F of the solvate represented by Formula IF using Cu-Kα radiation is shown in FIG26 ; (46) In the solvate represented by Formula IF, f is 0.88 and f′ is 0.

64. The differential scanning calorimetry curve of 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; (47) In the solvate represented by Formula IF, f is 0.88 and f′ is 0.

64. The differential scanning calorimetry curve of Form F of the solvate represented by Formula IF is shown in FIG27 ; (48) In the solvate represented by Formula IF, f is 0.88 and f' is 0.

64. The thermogravimetric analysis curve of Form F of the solvate represented by Formula IF shows a weight loss of 2.5% in the temperature range of 34°C ± 3°C to 100°C ± 3°C and a weight loss of 0.4% in the temperature range of 100°C ± 3°C to 170°C ± 3°C. (49) In the solvate represented by Formula IF, f is 0.88 and f′ is 0.

64. The thermogravimetric analysis curve of Form F of the solvate represented by Formula IF is shown in FIG28 ; (50) The crystalline form F of the solvate represented by Formula IF is a crystalline form of a compound of water and isopropanol; (51) In the solvate represented by formula IG, g is 0.25 and g' is 0.

70. The X-ray powder diffraction pattern of the solvate represented by formula IG using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, g is 0.25, g' is 0.70, and the crystalline form G of the solvate represented by the formula IG is irradiated with Cu-Kα and measured at 2θ angles. The X-ray powder diffraction pattern shown also has diffraction peaks at one or more of the following positions: 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°; More preferably, g is 0.25, g' is 0.70, and the crystalline form G of the solvate represented by the formula IG uses Cu-Kα radiation and an 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°, 18 There are diffraction peaks at .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°; (52) In the solvate represented by Formula IG, g is 0.25 and g′ is 0.

70. The X-ray powder diffraction pattern of Form G of the solvate represented by Formula IG using Cu-Kα radiation is shown in FIG30 ; (53) In the solvate represented by formula IG, g is 0.25 and g′ is 0.

70. The differential scanning calorimetry curve of the crystalline form G of the solvate represented by formula IG has endothermic peaks at 64.7°C±3°C and 209.3°C±3°C; (54) In the solvate represented by Formula IG, g is 0.25 and g′ is 0.

70. The differential scanning calorimetry curve of Form G of the solvate represented by Formula IG is shown in FIG31 ; (55) In the solvate represented by formula IG, g is 0.25 and g' is 0.

70. The thermogravimetric analysis curve of the crystalline form G of the solvate represented by formula IG shows a weight loss of 0.4% in the temperature range of 33°C ± 3°C to 100°C ± 3°C and a weight loss of 9.7% in the temperature range of 100°C ± 3°C to 210°C ± 3°C. (56) In the solvate represented by Formula IG, g is 0.25 and g′ is 0.

70. The thermogravimetric analysis curve of Form G of the solvate represented by Formula IG is shown in FIG32 ; (57) The crystalline form G of the solvate represented by the formula IG is a crystalline form of water and methyl tert-butyl ether; (58) In the solvate represented by formula II, i is 3.87, and the crystalline form I of the solvate represented by formula II has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, i is 3.87, and the crystalline form I of the solvate represented by formula II uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 8.04±0.20°, 9.11±0.20°, 10.89±0.20°, 11.46±0.20°, 13.07±0.20°, 14.56±0.2 0°, 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°; Further preferably, i is 3.87, and the crystalline form I of the solvate represented by the formula II uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles is 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°, 16.02±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±0.20°, 29.74±0.20°, 30.54±0.20°, 30.79±0.20°, 31.16±0. There are diffraction peaks at 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°; (59) In the solvate represented by Formula II, i is 3.

87. The X-ray powder diffraction pattern of Form I of the solvate represented by Formula II using Cu-Kα radiation is shown in FIG34 ; (60) In the solvate represented by formula II, i is 3.87, and the differential scanning calorimetry curve of the crystalline form I of the solvate represented by formula II has endothermic peaks at 44.8°C±3°C, 130.8°C±3°C, and 217.4°C±3°C; (61) In the solvate represented by Formula II, i is 3.

87. The differential scanning calorimetry curve of Form I of the solvate represented by Formula II is shown in FIG35 ; (62) In the solvate represented by formula II, i is 3.

87. The thermogravimetric analysis curve of the crystalline form I of the solvate represented by formula II shows a weight loss of 0.2% in the temperature range of 34°C ± 3°C to 70°C ± 3°C, and a weight loss of 20.4% in the temperature range of 70°C ± 3°C to 135°C ± 3°C. (63) In the solvate represented by Formula II, i is 3.

87. The thermogravimetric analysis curve of Form I of the solvate represented by Formula II is shown in FIG36 ; (64) The crystalline form I of the solvate represented by formula II is a crystalline form of N-methylpyrrolidone compound; (65) In the solvate represented by formula IK, k is 1.28, k' is 0.40, and the crystalline form K of the solvate represented by formula IK has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, k is 1.28, k' is 0.40, and the crystalline form K of the solvate represented by the formula IK has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 8.52±0.20°, 15.25±0.20°, 16.61±0.20°, 17.06±0.20°, 18.64±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°; Further preferably, k is 1.28, k' is 0.40, and the X-ray powder diffraction pattern of the solvate represented by formula IK using Cu-Kα radiation and expressed in 2θ angles is 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°, 20.04±0. There are diffraction peaks at 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°; (66) In the solvate represented by Formula IK, k is 1.28 and k′ is 0.

40. The X-ray powder diffraction pattern of Form K of the solvate represented by Formula IK using Cu-Kα radiation is shown in FIG38 ; (67) In the solvate represented by formula IK, k is 1.28, k' is 0.40, and the thermogravimetric analysis curve of the crystalline form K of the solvate represented by formula IK loses 6.4% of weight in the temperature range of 33°C ± 3°C to 180°C ± 3°C; (68) In the solvate represented by Formula IK, k is 1.28 and k′ is 0.

40. The thermogravimetric analysis curve of Form K of the solvate represented by Formula IK is shown in FIG39 ; (69) The solvate represented by formula IK is a crystalline form of a compound of water and acetonitrile; (70) In the solvate represented by formula IL, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by formula IL has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by the formula IL uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; Further preferably, l is 1.01, l' is 0.74, and the crystalline form L of the solvate represented by the formula IL uses Cu-Kα radiation and an 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°, 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± There are diffraction peaks 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°; (71) In the solvate represented by Formula IL, l is 1.01, and l′ is 0.

74. The X-ray powder diffraction pattern of Form L of the solvate represented by Formula IL using Cu-Kα radiation is shown in FIG41 ; (72) In the solvate represented by formula IL, l is 1.01, l′ is 0.74, and the differential scanning calorimetry curve of the crystalline form L of the solvate represented by formula IL has endothermic peaks at 57.2°C ± 3°C and 178.4°C ± 3°C; (73) In the solvate represented by Formula IL, l is 1.01, and l′ is 0.

74. The differential scanning calorimetry curve of Form L of the solvate represented by Formula IL is shown in FIG42 ; (74) In the solvate represented by formula IL, l is 1.01, l' is 0.74, and the thermogravimetric analysis curve of the crystalline form L of the solvate represented by formula IL shows a weight loss of 2.5% in the temperature range of 35°C ± 3°C to 100°C ± 3°C, and a weight loss of 6.9% in the temperature range of 100°C ± 3°C to 190°C ± 3°C; (75) In the solvate represented by Formula IL, l is 1.01, and l′ is 0.

74. The thermogravimetric analysis curve of Form L of the solvate represented by Formula IL is shown in FIG43 ; (76) The crystalline form L of the solvate represented by formula IL is a crystalline form of a compound of water and anisole; (77) In the solvate represented by formula IN, n is 3.

28. The X-ray powder diffraction pattern of the solvate represented by formula IN, using Cu-Kα radiation and expressed in 2θ angles, 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°. Preferably, n is 3.28, and the crystalline form N of the solvate represented by the formula IN has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°; Further preferably, n is 3.28, and the crystalline form N of the solvate represented by the formula IN uses Cu-Kα radiation and an 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°, 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±0.20°, 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 There are diffraction peaks at .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°; (78) In the solvate represented by Formula IN, n is 3.

28. The X-ray powder diffraction pattern of Form N of the solvate represented by Formula IN using Cu-Kα radiation is shown in FIG48 ; (79) In the solvate represented by formula IN, n is 3.28, and the differential scanning calorimetry curve of the crystalline 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; (80) In the solvate represented by Formula IN, n is 3.

28. The differential scanning calorimetry curve of Form N of the solvate represented by Formula IN is shown in FIG49 ; (81) In the solvate represented by formula IN, n is 3.

28. The thermogravimetric analysis curve of Form N of the solvate represented by formula IN shows a weight loss of 13.0% in the temperature range of 34°C ± 3°C to 90°C ± 3°C. (82) In the solvate represented by Formula IN, n is 3.

28. The thermogravimetric analysis curve of Form N of the solvate represented by Formula IN is shown in FIG50 ; (83) The crystalline form N of the solvate represented by formula IN is a crystalline form of N-methylpyrrolidone compound; (84) In the solvate represented by formula IO, o is 0.60, and the crystalline form O of the solvate represented by formula IO has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, in the solvate represented by formula IO, o is 0.60, and the crystalline form O of the solvate represented by formula IO uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 2θ angles and further has diffraction peaks at one or more of the following positions: 8.47±0.20°, 9.42±0.20°, 9.79±0.20°, 11.05±0.20°, 11.49±0.20°, 13.77±0.20°, 15.5 4 ± 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°; Further preferably, in the solvate represented by formula IO, o is 0.60, and the X-ray powder diffraction pattern of the solvate represented by formula IO using Cu-Kα radiation and expressed in 2θ angles is 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°, There are diffraction peaks at 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°; (85) In the solvate represented by Formula IO, o is 0.

60. The X-ray powder diffraction pattern of Form O of the solvate represented by Formula IO using Cu-Kα radiation is shown in FIG52 ; (86) In the solvate represented by formula IO, o is 0.60, and the differential scanning calorimetry curve of the crystalline form O of the solvate represented by formula IO has endothermic peaks at 125.5°C±3°C and 209.6°C±3°C; (87) In the solvate represented by Formula IO, o is 0.

60. The differential scanning calorimetry curve of Form O of the solvate represented by Formula IO is shown in FIG53 ; (88) In the solvate represented by formula IO, o is 0.60, and the thermogravimetric analysis curve of the crystalline form O of the solvate represented by formula IO loses 7.6% of weight in the temperature range of 35°C ± 3°C to 170°C ± 3°C; (89) In the solvate represented by Formula IO, o is 0.

60. The thermogravimetric analysis curve of Form O of the solvate represented by Formula IO is shown in FIG54 ; (90) The crystalline form O of the solvate represented by formula IO is a crystalline form of ethyl acetate; (91) In the solvate represented by formula IP, p is 0.

56. The crystalline form P of the solvate represented by formula IP has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, in the solvate represented by formula IP, p is 0.56, and the crystalline form P of the solvate represented by formula IP uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 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°; Further preferably, in the solvate represented by formula IP, p is 0.56, and the crystalline form P of the solvate represented by formula IP uses Cu-Kα radiation and an X-ray powder diffraction pattern expressed in 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°, 19.57±0.20°, 11.70±0.20°, 12.91±0.20°, 13. There are diffraction peaks at 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°; (92) In the solvate represented by Formula IP, p is 0.

56. The X-ray powder diffraction pattern of Form P of the solvate represented by Formula IP using Cu-Kα radiation is shown in FIG56 ; (93) In the solvate represented by Formula IP, p is 0.56, and the differential scanning calorimetry curve of the crystalline form P of the solvate represented by Formula IP has endothermic peaks at 157.4°C ± 3°C and 206.8°C ± 3°C; (94) In the solvate represented by Formula IP, p is 0.

56. The differential scanning calorimetry curve of Form P of the solvate represented by Formula IP is shown in FIG57 ; (95) In the solvate represented by formula IP, p is 0.

56. The thermogravimetric analysis curve of the crystalline form P of the solvate represented by formula IP shows a weight loss of 7.8% in the temperature range of 35°C to 180°C. (96) In the solvate represented by Formula IP, p is 0.

56. The thermogravimetric analysis curve of Form P of the solvate represented by Formula IP is shown in FIG58 ; (97) The crystalline form P of the solvate represented by formula IP is a crystalline form of a toluene compound; (98) In the solvate represented by formula IM, m is 1.39, and the crystalline form M of the solvate represented by formula IM has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; Preferably, m is 1.39, and the crystalline form M of the solvate represented by the formula IM has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles, and further has diffraction peaks at one or more of the following positions: 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°; Further preferably, m is 1.39, and the crystalline form M of the solvate represented by the formula IM has an X-ray powder diffraction pattern using Cu-Kα radiation and expressed in 2θ angles 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°; (99) In the solvate represented by Formula IM, m is 1.

39. The X-ray powder diffraction pattern of Form M of the solvate represented by Formula IM using Cu-Kα radiation is shown in FIG45 ; (100) In the solvate represented by formula IM, m is 1.39, and the thermogravimetric analysis curve of the crystalline form M of the solvate represented by formula IM loses 16.7% of weight in the temperature range of 36°C ± 3°C to 160°C ± 3°C; (101) In the solvate represented by formula IM, m is 1.

39. The thermogravimetric analysis curve of the crystal form M of the solvate represented by formula IM is shown in FIG46 ; (102) The crystalline form M of the solvate represented by formula IM is a crystalline form of trifluoroethanol; (103) In the solvate represented by Formula IS, s is 2.

20. The X-ray powder diffraction pattern of the solvate represented by Formula IS using Cu-Kα radiation and expressed in 2θ angles 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°. Preferably, s is 2.20, and the crystalline form S of the solvate represented by the formula IS uses Cu-Kα radiation and the X-ray powder diffraction pattern expressed in 2θ angles further has diffraction peaks at one or more of the following positions: 10.43±0.20°, 11.47±0.20°, 11.90±0.20°, 12.77±0.20°, 16.05±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°, 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°; Further preferably, s is 2.20, and the X-ray powder diffraction pattern of the solvate represented by the formula IS using Cu-Kα radiation and expressed at 2θ angles is 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°, 16.25±0.20°, 1 Diffraction peaks are at 6.70±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°; (104) In the solvate represented by Formula IS, s is 2.

20. The X-ray powder diffraction pattern of Form S of the solvate represented by Formula IS using Cu-Kα radiation is shown in Figure 64; (105) In the solvate represented by Formula IS, s is 2.20, and the differential scanning calorimetry curve of the crystalline form S of the solvate represented by Formula IS has endothermic peaks at 107.1°C ± 3°C and 219.3°C ± 3°C; (106) In the solvate represented by Formula IS, s is 2.

20. The differential scanning calorimetry curve of Form S of the solvate represented by Formula IS is shown in Figure 65; (107) In the solvate represented by formula IS, s is 2.

20. The thermogravimetric analysis curve of the crystalline form S of the solvate represented by formula IS shows a weight loss of 9.8% in the temperature range of 36°C ± 3°C to 150°C ± 3°C; (108) In the solvate represented by Formula IS, s is 2.

20. The thermogravimetric analysis curve of Form S of the solvate represented by Formula IS is shown in Figure 66; (109) The solvate represented by Formula IS is a crystalline form of N-methylpyrrolidone compound.

6. A method for preparing the crystalline form A of the solvate represented by formula IA as claimed in claim 5, characterized in that: The method comprises the following steps: mixing the compound represented by formula I with acetonitrile, and adding ethanol to obtain a crystalline form A of the solvate represented by formula IA; Preferably, the preparation method meets one or more of the following conditions: (1) The mass volume ratio of the compound represented by formula I to the acetonitrile is 0.50 to 1.00 g / mL, for example, 0.75 g / mL; (2) The mass volume ratio of the compound represented by Formula I to the ethanol is 0.05 to 0.15 g / mL, for example, 0.09 g / mL; (3) The method for preparing the crystalline form A of the solvate represented by Formula IA further comprises a purification step, for example, slurry purification using a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water is 5:1; (4) When the method for preparing the crystalline form A of the solvate represented by formula IA includes a purification step, the mass volume ratio of the compound represented by formula I to the mixed solvent is 0.05 to 0.20 g / mL, preferably, the mass volume ratio of the compound represented by formula I to the mixed solvent is 0.12 g / mL; (5) The method for preparing the crystalline form A of the solvate represented by formula IA comprises the following steps: mixing the compound represented by formula I with acetonitrile, adding ethanol, filtering, and collecting the solid; and purifying the obtained solid by slurrying with a mixed solvent of acetonitrile and water in a volume ratio of 5:1 to obtain the crystalline form A of the solvate represented by formula IA.

7. A method for preparing the crystalline form B of the compound of formula I according to any one of claims 1 to 3, the crystalline form F of the solvate of formula IF according to claim 5, the crystalline form G of the solvate of formula IG according to claim 5, the crystalline form I of the solvate of formula II according to claim 5, or the crystalline form K of the solvate of formula IK according to claim 5, characterized in that: It includes the following steps: (1) mixing Form A of the solvate represented by Formula IA according to claim 5 with solvent C to obtain a mixture; (2) stirring the resulting mixture in the range of 50°C to 5°C at a heating and cooling rate of 0.1°C / min; When the obtained crystal form B of the compound represented by formula I is obtained, the solvent C is water; When the obtained solvate is in Form F of Formula IF, the solvent C is isopropanol; When the obtained solvate is in the form G of the formula IG, the solvent C is methyl tert-butyl ether; When the obtained crystalline form I of the solvate represented by formula II is obtained, the solvent C is N-methylpyrrolidone; When the obtained solvate is a crystalline form K represented by formula IK, the solvent C is a mixed solution of acetonitrile and water in a ratio of 1:1; Preferably, the preparation method meets one or more of the following conditions: (1) The mass volume ratio of the crystalline form A of the solvate represented by Formula IA to the solvent C may be 50 to 500 g / L, for example, 100 g / L or 300 g / L; (2) step (2) is repeated 6 to 10 times, for example 12 times or 20 times; (3) Before the step (2) is performed, the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK is added, for example, the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the solvate represented by formula IK is added in a mass ratio of (1-2):100 to the crystalline form A of the solvate represented by formula IA. The crystalline form K of the solvate of the compound of formula I is preferably added with the crystalline form B of the compound of formula I, the crystalline form F of the solvate of formula IF, the crystalline form G of the solvate of formula IG, the crystalline form I of the solvate of formula II or the crystalline form K of the solvate of formula IK at a mass ratio of 1:80 to the crystalline form A of the solvate of formula IA; (4) The preparation method of the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK comprises the following steps: mixing the crystalline form A of the solvate represented by IA with solvent C, cooling the mixture from 50°C to 5°C at a rate of 0.1°C / min, and then heating the mixture from 5°C to 50°C, and repeating the heating and cooling steps 12 or 20 times to obtain the crystalline form B of the compound represented by formula I, the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG, the crystalline form I of the solvate represented by formula II, or the crystalline form K of the solvate represented by formula IK.

8. A method for preparing the crystalline form C of the solvate represented by formula IC according to claim 5, the crystalline form D of the solvate represented by formula ID according to claim 5, or the crystalline form E of the solvate represented by formula IE according to claim 5, characterized in that: It includes the following steps: (1) fully dissolving the crystalline form A of the solvate represented by formula IA according to claim 5 with solvent A; (2) adding solvent B to the resulting solution and crystallizing to obtain Form C of the solvate represented by Formula IC, Form D of the solvate represented by Formula ID, or Form E of the solvate represented by Formula IE; When the obtained solvate is a crystalline form C represented by formula IC, solvent A is dimethyl sulfoxide and solvent B is acetonitrile; When the obtained solvate is in Form D of Formula ID, Solvent A is 1,3-dimethyl-2-imidazolidinone and Solvent B is ethanol; When the obtained solvate is in Form E of Formula IE, Solvent A is N,N-dimethylformamide and Solvent B is acetone; Preferably, the preparation method meets one or more of the following conditions: (1) The mass volume ratio of Form A of the solvate represented by Formula IA to Solvent A is 10 to 300 g / L, preferably 15 to 150 g / L, for example 15 g / L, 50 g / L or 150 g / L; (2) The volume ratio of the solvent A to the solvent B is 1:1 to 1:3, for example 1:1, and further for example 1:3; (3) The preparation method of the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, or the crystalline form E of the solvate represented by formula IE comprises the following steps: fully dissolving the crystalline form A of the solvate represented by formula IA with solvent A, adding solvent B to the resulting solution, and filtering the resulting suspension to obtain the crystalline form C of the solvate represented by formula IC, the crystalline form D of the solvate represented by formula ID, or the crystalline form E of the solvate represented by formula IE.

9. A method for preparing the crystalline form L of the solvate represented by formula 1L according to claim 5, the crystalline form M of the solvate represented by formula 1M according to claim 5, the crystalline form N of the solvate represented by formula 10 according to claim 5, or the crystalline form P of the solvate represented by formula IP according to claim 5, characterized in that: The method comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA according to claim 5 with a solvent D to obtain a mixture, and suspending the mixture to obtain the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP; Wherein, when the obtained solvate is in the form L of the formula IL, the solvent D is anisole; When the obtained solvate is in the form M of the formula IM, the solvent D is trifluoroethanol; When the obtained crystalline form N of the solvate represented by formula IN is obtained, the solvent D is N-methylpyrrolidone; When the obtained solvate is in Form O of Formula IO, the solvent D is ethyl acetate; When the obtained solvate is in the form P of the formula IP, the solvent butyl is toluene; Preferably, the preparation method meets one or more of the following conditions: (1) The mass volume ratio of Form A of the solvate represented by Formula IA to Solvent D is 50 to 300 g / L, preferably 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; (3) The preparation method of the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA with the solvent D to obtain a mixture, and suspending the mixture at 25°C or 50°C and 400 rpm for 14 days or 7 days to obtain the crystalline form L of the solvate represented by formula IL, the crystalline form M of the solvate represented by formula IM, the crystalline form N of the solvate represented by formula IN, the crystalline form O of the solvate represented by formula IO, or the crystalline form P of the solvate represented by formula IP.

10. A method for preparing the crystalline form S of the solvate represented by formula IS according to claim 5, characterized in that: The method comprises the following steps: fully dissolving the crystalline form A of the solvate represented by formula IA according to claim 5 in N-methylpyrrolidone at 50° C., adding acetone to the resulting solution and cooling the solution to obtain the crystalline form S of the solvate represented by formula IS; Preferably, the preparation method meets one or more of the following conditions: (1) The mass volume ratio of the crystalline form A of the solvate represented by Formula IA to the N-methylpyrrolidone is 50 to 200 g / L, for example, 75 g / L; (2) the volume ratio of the acetone to the N-methylpyrrolidone is 1:1 to 8:1, for example, 3:1; (3) The preparation method of the crystalline form S of the solvate represented by the formula IS comprises the following steps: at 50° C., fully dissolving the crystalline form A of the solvate represented by the formula IA in N-methylpyrrolidone, filtering, collecting the filtrate, cooling the obtained filtrate and adding acetone, filtering, and collecting the solid to obtain the crystalline form S of the solvate represented by the formula IS.

11. A method for preparing the crystalline form R of the solvate represented by formula IR according to claim 5, characterized in that: It includes the following steps: (1) mixing Form A of the solvate represented by Formula IA according to claim 5, water, and NaOH to obtain a mixture A; (2) adding aqueous hydrochloric acid to the obtained mixture A to obtain a crystalline form R of the solvate represented by Formula IR; Preferably, the preparation method meets one or more of the following conditions: (1) In step (1), the molar ratio of the crystalline form A of the solvate represented by formula IA to NaOH is 1:1 to 1:2, for example, 1:1.7 or 1:2; (2) In step (2), the molar ratio of the crystalline form A of the solvate represented by formula IA to hydrochloric acid is 1:1 to 1:3, for example, 1:2 or 1:3, and further for example, 2:2; (3) In step (2), the crystalline form R of the solvate represented by formula IR is added to the mixture A, for example, the crystalline form R of the solvate represented by formula IR is added at a mass ratio of (0.5-2):100 to the crystalline form A of the solvate represented by formula IA, preferably the crystalline form R of the solvate represented by formula IR is added at a mass ratio of 1:75 to the crystalline form A of the solvate represented by formula IA; (4) The preparation method of the crystalline form R of the solvate represented by formula IR comprises the following steps: mixing the crystalline form A of the solvate represented by formula IA with water to obtain a mixture, adding 2 or 1.7 equivalents of NaOH to obtain mixture A, and mixing the mixture A with aqueous hydrochloric acid solution to obtain the crystalline form R of the solvate represented by formula IR.

12. A method for preparing the crystalline form T of the solvate represented by formula IT according to claim 5, characterized in that: The method comprises the following steps: drying the crystalline form R of the solvate represented by formula IR as claimed in claim 5 at 50° C. for 2 hours to obtain the crystalline form T of the solvate represented by formula IT.

13. A pharmaceutical composition, characterized in that It comprises a substance X and a pharmaceutical excipient, wherein the substance X is a solvate of the compound represented by formula I according to claim 4 or a crystalline form B of the compound represented by formula I according to any one of claims 1 to 3, a crystalline form A of the solvate represented by formula IA according to claim 5, a crystalline form R of the solvate represented by formula IR according to claim 5, a crystalline form T of the solvate represented by formula IT according to claim 5, a crystalline form C of the solvate represented by formula IC according to claim 5, a crystalline form D of the solvate represented by formula ID according to claim 5, a crystalline form E of the solvate represented by formula IE according to claim 5, a solvate represented by formula IF according to claim 5. The crystalline form F of the solvate, the crystalline form G of the solvate represented by formula IG as claimed in claim 5, the crystalline form I of the solvate represented by formula II as claimed in claim 5, the crystalline form K of the solvate represented by formula IK as claimed in claim 5, the crystalline form L of the solvate represented by formula IL as claimed in claim 5, the crystalline form M of the solvate represented by formula IM as claimed in claim 5, the crystalline form N of the solvate represented by formula IN as claimed in claim 5, the crystalline form O of the solvate represented by formula IO as claimed in claim 5, the crystalline form P of the solvate represented by formula IP as claimed in claim 5 and the crystalline form S of the solvate represented by formula IS as claimed in claim 5.

14. Use of a substance X in the preparation of a TRPC5 inhibitor, wherein the substance X is a solvate of the compound of formula I according to claim 4, or a crystalline form B of the compound of formula I according to any one of claims 1 to 3, a crystalline form A of the solvate of formula IA according to claim 5, a crystalline form R of the solvate of formula IR according to claim 5, a crystalline form T of the solvate of formula IT according to claim 5, a crystalline form C of the solvate of formula IC according to claim 5, a crystalline form D of the solvate of formula ID according to claim 5, a crystalline form E of the solvate of formula IE according to claim 5, or a crystalline form C of the solvate of formula IC according to claim 5. One or more of the crystalline form F of the solvate represented by formula IF, the crystalline form G of the solvate represented by formula IG as claimed in claim 5, the crystalline form I of the solvate represented by formula II as claimed in claim 5, the crystalline form K of the solvate represented by formula IK as claimed in claim 5, the crystalline form L of the solvate represented by formula IL as claimed in claim 5, the crystalline form M of the solvate represented by formula IM as claimed in claim 5, the crystalline form N of the solvate represented by formula IN as claimed in claim 5, the crystalline form O of the solvate represented by formula IO as claimed in claim 5, the crystalline form P of the solvate represented by formula IP as claimed in claim 5, and the crystalline form S of the solvate represented by formula IS as claimed in claim 5; The TRPC5 inhibitor is used in vivo or in vitro.

15. Use of a substance X in preparing a medicament, wherein the substance X is a solvate of the compound of formula I according to claim 4, or is the crystalline form B of the compound of formula I according to any one of claims 1 to 3, the crystalline form A of the solvate of formula IA according to claim 5, the crystalline form R of the solvate of formula IR according to claim 5, the crystalline form T of the solvate of formula IT according to claim 5, the crystalline form C of the solvate of formula IC according to claim 5, the crystalline form D of the solvate of formula ID according to claim 5, the crystalline form E of the solvate of formula IE according to claim 5, or the crystalline form F of the solvate of formula IF according to claim 5. One or more of the crystalline form F of the solvate represented by formula IG as claimed in claim 5, the crystalline form I of the solvate represented by formula II as claimed in claim 5, the crystalline form K of the solvate represented by formula IK as claimed in claim 5, the crystalline form L of the solvate represented by formula IL as claimed in claim 5, the crystalline form M of the solvate represented by formula IM as claimed in claim 5, the crystalline form N of the solvate represented by formula IN as claimed in claim 5, the crystalline form O of the solvate represented by formula IO as claimed in claim 5, the crystalline form P of the solvate represented by formula IP as claimed in claim 5 and the crystalline form S of the solvate represented by formula IS as claimed in claim 5; The medicine is a medicine for treating and / or preventing diseases mediated by TRPC5.

16. The use according to claim 15, characterized in that The TRPC5-mediated disease is a psychiatric disorder, a neurological disorder, a neurodegenerative disorder or a renal disease; Preferably, the psychiatric, neurological or neurodegenerative disorder is selected from the group consisting of disorders associated with dysregulated emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, major depressive disorder, dysthymia, dysthymia and postpartum depression, and bipolar disorder), disorders associated with 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 disorders, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke and Weil-Cohen syndrome), disorders associated with impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and other brain disorders caused by trauma or other insults including aging; Alternatively, the renal disease is focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy, Alport syndrome, hypertensive nephropathy, nephrotic syndrome, steroid-resistant nephrotic syndrome, membranous nephropathy, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis, immune complex-mediated MPGN, complement-mediated MPGN, lupus nephritis, post-infectious glomerulonephritis, thin basement membrane disease, mesangial proliferative glomerulonephritis, amyloidosis nephropathy (preferably primary amyloidosis nephropathy), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease, C3 glomerulonephritis, hypertensive nephrosclerosis or primary glomerular disease (preferably IgA nephropathy).

17. Use of a substance X in preparing a medicament, wherein the substance X is a solvate of the compound of formula I according to claim 4, or is the crystalline form B of the compound of formula I according to any one of claims 1 to 3, the crystalline form A of the solvate of formula IA according to claim 5, the crystalline form R of the solvate of formula IR according to claim 5, the crystalline form T of the solvate of formula IT according to claim 5, the crystalline form C of the solvate of formula IC according to claim 5, the crystalline form D of the solvate of formula ID according to claim 5, the crystalline form E of the solvate of formula IE according to claim 5, or the crystalline form F of the solvate of formula IF according to claim 5. One or more of the crystalline form F of the solvate represented by formula IG as claimed in claim 5, the crystalline form I of the solvate represented by formula II as claimed in claim 5, the crystalline form K of the solvate represented by formula IK as claimed in claim 5, the crystalline form L of the solvate represented by formula IL as claimed in claim 5, the crystalline form M of the solvate represented by formula IM as claimed in claim 5, the crystalline form N of the solvate represented by formula IN as claimed in claim 5, the crystalline form O of the solvate represented by formula IO as claimed in claim 5, the crystalline form P of the solvate represented by formula IP as claimed in claim 5 and the crystalline form S of the solvate represented by formula IS as claimed in claim 5; The drug is a drug for treating and / or preventing psychiatric disorders, neurological disorders, neurodegenerative disorders or kidney diseases, Preferably, the psychiatric disorder, neurological disorder or neurodegenerative disorder is selected from the group consisting of disorders associated with dysregulated emotional processing (e.g., borderline personality disorder or depression, such as major depressive disorder, major depressive disorder, dysthymia, dysthymia and postpartum depression, and bipolar disorder), disorders associated with 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 disorders, sleep disorders, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injuries, stroke and Weil-Cohen syndrome), disorders associated with impaired impulse control and addiction, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and other brain disorders caused by trauma or other insults including aging; Alternatively, the renal disease is focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy, Alport syndrome, hypertensive nephropathy, nephrotic syndrome, steroid-resistant nephrotic syndrome, membranous nephropathy, idiopathic membranous nephropathy, membranoproliferative glomerulonephropathy, The patient may have inflammation, immune complex-mediated MPGN, complement-mediated MPGN, lupus nephritis, postinfectious glomerulonephritis, thin basement membrane disease, mesangial proliferative glomerulonephritis, amyloidosis (preferably primary amyloidosis), C1q nephropathy, rapidly progressive glomerulonephritis, anti-GBM disease, C3 glomerulonephritis, hypertensive nephrosclerosis, or a primary glomerular disease (preferably IgA nephropathy).

Images