ALK inhibitors, their salts, solvates, crystalline forms, methods for producing the same, and their uses

Abstract

The present invention discloses crystalline forms of a compound represented by formula I or a salt thereof, which are crystalline form A of methanesulfonate of one equivalent of the compound represented by formula I, crystalline form D of the compound represented by formula I, crystalline form A of maleate of one equivalent of the compound represented by formula I, crystalline form C of tartrate of one equivalent of the compound represented by formula I, crystalline form B of citrate of one equivalent of the compound represented by formula I, or crystalline form D of succinate of one equivalent of the compound represented by formula I, and is characterized in that the above crystalline forms have one or more advantages such as high crystallinity, good stability, low hygroscopicity, high solubility, and high bioavailability. JPEG2026508811000144.jpg4191

Description

[Technical Field]

[0001] This application claims priority to Chinese patent application 2023100737229, filed on January 20, 2023, and Chinese patent application 2024100211025, filed on January 5, 2024. This application incorporates the full text of the aforementioned Chinese patent applications.

[0002] This invention belongs to the field of drug chemistry and, in particular, relates to the crystalline form of ALK inhibitors or their salts and solvates, as well as their methods of production and use. [Background technology]

[0003] The compound represented by formula I (APG-2449), disclosed in WO2018044767A1, is a potent triple kinase inhibitor of adhesion plaque kinase (FAK), ROS1, and anaplastic lymphoma kinase (ALK) with high-efficiency oral bioavailability for the treatment of cancer. APG-2449 exhibits antitumor activity in multiple xenograft tumor models. Preclinical tumor model studies have shown that APG-2449 can overcome drug resistance arising from first-generation ALK inhibitors and exhibits synergistic effects with EGFR inhibitors (particularly the newly approved third-generation AZD9291 / osimertinib) in an EGFRT790M mutant NSCLC xenograft tumor model. [Overview of the Initiative]

[0004] To overcome the disadvantages of amorphous compounds represented by formula I, such as low bioavailability, low stability, relatively high hygroscopicity, and low solubility, crystalline forms of ALK inhibitors or their salts and solvates are provided. These crystalline forms have one or more advantages, including high crystallinity, good stability, low hygroscopicity, high solubility, and high bioavailability.

[0005] This invention solves the above problems by the following technical solution.

[0006] The present invention provides a crystalline form A of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 5.494°±0.2°, 7.553°±0.2°, 8.711°±0.2°, 15.6°±0.2°, 17.183°±0.2°, 18.019°±0.2°, and 18.999°±0.2°. [ka]

[0007] In one embodiment, the above crystal form A, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 18.999°±0.2°, 5.494°±0.2°, 6.041°±0.2°, 6.451°±0.2°, 7.553°±0.2°, 8.711°±0.2°, 9.076°±0.2°, 10.588°±0.2°, 10.974°±0.2°, 11.195°±0.2°, 12.068°±0.2°, 12.252°±0.2°, 12.56°±0.2°, and 13.139°±0.2°. Diffraction peaks are found at the following positions: °, 13.795°±0.2°, 13.975°±0.2°, 14.895°±0.2°, 15.6°±0.2°, 15.794°±0.2°, 16.269°±0.2°, 16.46°±0.2°, 16.635°±0.2°, 17.183°±0.2°, 17.445°±0.2°, 18.019°±0.2°, 18.228°±0.2°, 18.525°±0.2°, 19.240°±0.2°, 19.438°±0.2°, and 19.659°±0.2°.

[0008] In one embodiment, the X-ray powder diffraction pattern analysis data for crystal form A is basically as shown in the table below.

[0009] [Table 1] .

[0010] In one embodiment, the thermogravimetric analysis curve (TGA) of the crystalline form A shows a weight loss of 0.08556% during the heating process from 37.52°C to 150.30°C.

[0011] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystalline form A has endothermic peaks with starting temperatures of 109.50°C and 154.49°C, respectively.

[0012] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystalline form A has endothermic peaks with peak temperatures of 117.55°C and 157.12°C, respectively. The present invention provides a crystalline form B of a compound represented by formula I, and its X-ray powder diffraction pattern (XRPD) has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.879° ± 0.2°, 15.66° ± 0.2°, 16.036° ± 0.2°, 17.28° ± 0.2°, 18.279° ± 0.2°, 19.905° ± 0.2° and 22.381° ± 0.2°,

Chemical formula

[0013] In one embodiment, the crystal form B has diffraction peaks at positions of 5.099 ± 0.2°, 5.677 ± 0.2°, 8.014 ± 0.2°, 8.616 ± 0.2°, 9.246 ± 0.2°, 9.660 ± 0.2°, 10.362 ± 0.2°, 10.879 ± 0.2°, 11.416 ± 0.2°, 11.652 ± 0.2°, 12.402 ± 0.2°, 12.923 ± 0.2°, 13.26 ± 0.2°, 13.779 ± 0.2°, 14.521 ± 0.2°, 15.24 ± 0.2°, 15.66 ± 0.2°, 16.036 ± 0.2°, 16.582 ± 0.2°, 17.042 ± 0.2°, 17.28 ± 0.2°, 18.279 ± 0.2°, 19.098 ± 0.2°, 19.402 ± 0.2°, 19.905 ± 0.2°, 20.558 ± 0.2°, 21.142 ± 0.2°, 21.686 ± 0.2°, 22.087 ± 0.2°, and 22.381 ± 0.2° in an X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0014] In one embodiment, the X-ray powder diffraction pattern analysis data of the crystal form B are basically as shown in the following table.

[0015]

Table 2

[0020] In one embodiment, the above crystalline form C, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ at 5.499°±0.2°, 8.914°±0.2°, 10.981°±0.2°, 11.997°±0.2°, 13.282°±0.2°, 13.526°±0.2°, 13.778°±0.2°, 14.294°±0.2°, 14.622°±0.2°, 15.38°±0.2°, 16.043°±0.2°, 16.236°±0.2°, 16.923°±0.2°, and 17.52°±0. Diffraction peaks are found at the following positions: 2°, 17.84°±0.2°, 18.299°±0.2°, 18.739°±0.2°, 19.601°±0.2°, 19.916°±0.2°, 20.038°±0.2°, 20.222°±0.2°, 20.777°±0.2°, 21.518°±0.2°, 21.743°±0.2°, 22.017°±0.2°, 22.362°±0.2°, 22.801°±0.2°, 22.962°±0.2°, 23.24°±0.2°, and 23.579°±0.2°.

[0021] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form C is basically as shown in the table below.

[0022] [Table 3-1] [Table 3-2] .

[0023] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form C shows a weight loss of 0.02699% during the heating process from 37.52°C to 150.30°C.

[0024] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form C has an endothermic peak with an onset temperature of 157.61°C.

[0025] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form C has an endothermic peak with a peak temperature of 158.64°C.

[0026] In one embodiment, the dynamic vapor adsorption curve (DVS) of the above crystalline form C shows that the weight increase due to moisture absorption is 0.31 ± 0.005% at 25°C and 80% RH.

[0027] The present invention provides a crystalline form D of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 11.539°±0.2°, 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2°, and 23.157°±0.2°. [ka]

[0028] In one embodiment, the crystal form D, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ with diffraction peaks at positions 18.081°±0.2°, 20.278°±0.2°, and 23.157°±0.2°.

[0029] In one embodiment, the crystal form D, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ with diffraction peaks at positions 13.558°±0.2°, 18.081°±0.2°, 20.278°±0.2°, and 23.157°±0.2°.

[0030] In one embodiment, the crystal form D, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ with diffraction peaks at positions 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2°, and 23.157°±0.2°.

[0031] In one embodiment, the crystal form D, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ with diffraction peaks at the following positions: 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2°, and 23.157°±0.2°.

[0032] In one embodiment, the crystal form D, when subjected to Cu-Kα radiation, has diffraction peaks at the following positions in its X-ray powder diffraction pattern, represented by 2θ: 11.539°±0.2°, 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2°, and 23.157°±0.2°.

[0033] In one embodiment, the above crystal form D, when analyzed using Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 6.297°±0.2°, 6.737°±0.2°, 11.097°±0.2°, 11.539°±0.2°, 12.381°±0.2°, 12.658°±0.2°, 12.837°±0.2°, 13.558°±0.2°, 14.102°±0.2°, 14.996°±0.2°, 15.66°±0.2°, 16.359°±0.2°, 16.522°±0.2°, and 17.04°±0. Diffraction peaks are found at the following positions: 0.2°, 17.2°±0.2°, 17.416°±0.2°, 18.081°±0.2°, 18.32°±0.2°, 18.515°±0.2°, 18.859°±0.2°, 19.501°±0.2°, 20.278°±0.2°, 20.541°±0.2°, 20.7°±0.2°, 20.937°±0.2°, 21.179°±0.2°, 21.801°±0.2°, 22.057°±0.2°, 22.543°±0.2°, and 23.157°±0.2°.

[0034] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form D is basically as shown in the table below.

[0035] [Table 4] .

[0036] In one embodiment, the X-ray powder diffraction pattern of crystal form D is basically as shown in Figure 1.

[0037] In one embodiment, the thermogravimetric analysis curve (TGA) of crystal form D shows a weight loss of 0.2139±0.005% during the heating process from 37.69±3℃ to 150.63±3℃.

[0038] In one embodiment, the thermogravimetric analysis curve (TGA) of crystal form D shows a weight loss of 0.2139% during the heating process from 37.69°C to 150.63°C.

[0039] In one embodiment, the thermogravimetric analysis curve of crystal form D is basically as shown in Figure 2.

[0040] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with an onset temperature of 165.58 ± 3°C.

[0041] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with an onset temperature of 165.58°C.

[0042] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a peak temperature of 167.41±3℃.

[0043] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a peak temperature of 167.41°C.

[0044] In one embodiment, the differential scanning calorimetry curve of crystal form D is basically as shown in Figure 3.

[0045] In one embodiment, the dynamic vapor adsorption curve (DVS) of the above crystalline form D shows that the weight increase due to moisture absorption is 0.14 ± 0.005% at 25°C and 80% RH.

[0046] In one embodiment, the dynamic vapor adsorption curve (DVS) of the above crystalline form D shows that the weight increase due to moisture absorption is 0.14% at 25°C and 80%RH.

[0047] In one embodiment, the dynamic vapor adsorption curve of the above-mentioned crystalline form D is basically as shown in Figure 4.

[0048] The present invention further provides a method for producing crystalline form D of the compound represented by formula I, preferably one of the following methods.

[0049] Method 1 comprises the following steps: stirring the amorphous form of the compound represented by formula I in a solvent to precipitate a solid to obtain the crystalline form D of the compound represented by formula I, wherein the solvent is an organic solvent or a mixed solvent of an organic solvent and water, and the organic solvent may be ethanol, isopropanol, acetonitrile, ethyl acetate, isopropyl acetate, methyl tert-butyl ether, toluene, n-heptane, dioxane, methyl acrylate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, butanone, or methyl isobutyl ketone, and if the organic solvent is ethanol, isopropanol, or dioxane, the stirring The stirring is carried out at 50°C, and if the organic solvent is methyl tert-butyl ether or toluene, the stirring is carried out at room temperature, for example, 25°C, and if the solvent is a mixed solvent of organic solvent and water, acetonitrile, ethyl acetate, isopropyl acetate, n-heptane, methyl acrylate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, butanone, or methyl isobutyl ketone, the stirring is preferably carried out at 25-50°C, the stirring time is preferably 2-4 days, and the mass-to-volume ratio of the amorphous compound represented by formula I to the solvent is preferably (50 mg-500 mg):1 mL. Method two comprises the following steps: an amorphous form of the compound represented by formula I is stirred in a good solvent to obtain a clarified solution, a poor solvent is added and stirred to precipitate a solid to obtain the crystalline form D of the compound represented by formula I, wherein the good solvent is tetrahydrofuran or dichloromethane, and if the good solvent is tetrahydrofuran, the poor solvent is acetonitrile or methyl tert-butyl ether, and if the good solvent is dichloromethane, the poor solvent is acetonitrile, methyl tert-butyl ether, ethyl acetate or n-heptane, the stirring is preferably carried out at room temperature, the stirring time is preferably 3 to 5 days, the mass-to-volume ratio of the compound represented by formula I to the good solvent is preferably (50 mg to 500 mg):1 mL, and the volume ratio of the good solvent to the poor solvent is preferably 1:(4 to 5). Method three comprises the following steps: stirring the amorphous form of the compound represented by formula I in a solvent until clarified, and then volatilizing to obtain the crystalline form D of the compound represented by formula I. The solvent may be a mixed solvent of acetone, ethyl acetate, acetonitrile, and dichloromethane, or a mixed solvent of isopropyl acetate and dichloromethane. Volatilization is preferably carried out at room temperature, for example, 25°C. The mass-to-volume ratio of the compound represented by formula I to the solvent is preferably (10 mg to 50 mg):1 mL, more preferably 20 mg:1 mL. The volume ratio of acetonitrile to dichloromethane is preferably 10:3, and the volume ratio of isopropyl acetate to dichloromethane is preferably 5:1. Method four comprises the following steps: stirring the amorphous form of the compound represented by formula I in a solvent at 50°C until clarified, and then cooling to obtain the crystalline form D of the compound represented by formula I, which is performed at 4°C. The solvent may be a mixed solvent of tetrahydrofuran, ethyl acetate, acetonitrile, and dichloromethane, or a mixed solvent of isopropyl acetate and dichloromethane. The mass-volume ratio of the compound represented by formula I to the solvent is preferably (50 mg to 500 mg):1 mL, more preferably 50 mg:1 mL. The volume ratio of acetonitrile to dichloromethane is preferably 1:1, and the volume ratio of isopropyl acetate to dichloromethane is preferably 1:1.

[0050] In one embodiment, in Method 1 above, if the solvent is a mixed solvent of an organic solvent and water, acetonitrile, ethyl acetate, isopropyl acetate, n-heptane, methyl acrylate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, butanone, or methyl isobutyl ketone, the stirring is preferably carried out at 25°C or 50°C, the stirring time is preferably 3 days, and the mass-volume ratio of the compound represented by Formula I to the organic solvent is preferably 83 mg:1 mL or 125 mg:1 mL.

[0051] In one embodiment, the stirring in method 2 is preferably carried out at 25°C. The stirring time is preferably 5 days, the mass-to-volume ratio of the compound represented by formula I to the dichloromethane is preferably 50 mg:1 mL, and the volume ratio of the good solvent to the poor solvent is preferably 1:4.

[0052] In one embodiment, the method for producing the above-mentioned crystalline form D further includes the steps of precipitation of the solid, followed by isolation and drying, thereby obtaining the above-mentioned crystalline form D.

[0053] The present invention provides a crystalline form E of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 7.193°±0.2°, 14.94°±0.2°, 17.818°±0.2°, 19.801°±0.2°, 21.478°±0.2°, 22.297°±0.2°, and 26.062°±0.2°. [ka]

[0054] In one embodiment, the above crystal form E, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 6.736°±0.2°, 7.193°±0.2°, 9.216°±0.2°, 9.799°±0.2°, 10.436°±0.2°, 12.396°±0.2°, 12.811°±0.2°, 13.459°±0.2°, 13.656°±0.2°, 14.438°±0.2°, 14.94°±0.2°, 15.098°±0.2°, 16.66°±0.2°, and 17.061°±0.2°. Diffraction peaks are found at the following positions: °, 17.818°±0.2°, 18.442°±0.2°, 18.621°±0.2°, 19.801°±0.2°, 20.021°±0.2°, 20.217°±0.2°, 20.717°±0.2°, 21.097°±0.2°, 21.478°±0.2°, 21.84°±0.2°, 22.297°±0.2°, 23.377°±0.2°, 24.256°±0.2°, 26.062°±0.2°, 26.361°±0.2°, and 27.14°±0.2°.

[0055] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form E is basically as shown in the table below.

[0056] [Table 5] .

[0057] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form E shows a weight loss of 0.1142% during the heating process from 36.80°C to 100.21°C.

[0058] In one embodiment, the differential scanning calorimetry (DSC) curve of crystal form E has endothermic peaks with starting temperatures of 105.44°C, 121.48°C, 155.87°C, and 166.05°C, respectively.

[0059] In one embodiment, the differential scanning calorimetry (DSC) curve of crystal form E has endothermic peaks with peak temperatures of 112.13°C, 126.80°C, 158.60°C, and 167.53°C, respectively.

[0060] The present invention provides a crystalline form F of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.976°±0.2°, 13.278°±0.2°, 17.622°±0.2°, 18.001°±0.2°, 19.982°±0.2°, 20.858°±0.2° and 21.12°±0.2°. [ka]

[0061] In one embodiment, the above crystal form F, when measured using Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 6.468°±0.2°, 8.976°±0.2°, 9.22°±0.2°, 9.917°±0.2°, 12.432°±0.2°, 13.006°±0.2°, 13.278°±0.2°, 13.794°±0.2°, 14.088°±0.2°, 14.639°±0.2°, 14.981°±0.2°, 15.257°±0.2°, 15.803°±0.2°, and 16.373°±0. Diffraction peaks are found at the following positions: 2°, 16.576°±0.2°, 17.622°±0.2°, 18.001°±0.2°, 18.505°±0.2°, 18.7°±0.2°, 19.661°±0.2°, 19.982°±0.2°, 20.581°±0.2°, 20.858°±0.2°, 21.12°±0.2°, 22.769°±0.2°, 23.077°±0.2°, 23.433°±0.2°, 24.399°±0.2°, 24.844°±0.2°, and 25.201°±0.2°.

[0062] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form F is basically as shown in the table below.

[0063] [Table 6-1] [Table 6-2] .

[0064] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form F shows a weight loss of 8.120% during the heating process from 36.87°C to 200.38°C.

[0065] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form F has endothermic peaks with starting temperatures of 93.99°C and 150.24°C, respectively.

[0066] In one embodiment, the differential scanning calorimetry (DSC) curve of the crystal form F has endothermic peaks with peak temperatures of 100.94°C and 155.50°C, respectively.

[0067] The present invention provides a crystalline form G of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 14.776°±0.2°, 17.837°±0.2°, 19.219°±0.2°, 20.317°±0.2°, 21.343°±0.2°, 21.898°±0.2° and 29.382°±0.2°. [ka]

[0068] In one embodiment, the above crystal form G, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 6.521°±0.2°, 7.294°±0.2°, 9.039°±0.2°, 9.237°±0.2°, 9.734°±0.2°, 10.459°±0.2°, 12.2°±0.2°, 12.681°±0.2°, 13.037°±0.2°, 13.778°±0.2°, 14.776°±0.2°, 15.095°±0.2°, 15.585°±0.2°, and 16.741°±0.2°. Diffraction peaks are found at the following positions: 17.093°±0.2°, 17.837°±0.2°, 18.499°±0.2°, 18.799°±0.2°, 19.219°±0.2°, 19.422°±0.2°, 19.581°±0.2°, 19.888°±0.2°, 20.317°±0.2°, 21.093°±0.2°, 21.343°±0.2°, 21.898°±0.2°, 22.374°±0.2°, 22.702°±0.2°, 23.075°±0.2°, and 29.382°±0.2°.

[0069] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form G is basically as shown in the table below.

[0070] [Table 7] .

[0071] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form G shows a weight loss of 0.1931% during the heating process from 37.20°C to 100.54°C.

[0072] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form G has an endothermic peak with an onset temperature of 113.63°C.

[0073] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form G has an endothermic peak with a peak temperature of 121.09°C.

[0074] The present invention provides a crystalline form H of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 5.444°±0.2°, 13.296°±0.2°, 10.885°±0.2°, 17.137°±0.2°, 17.512°±0.2°, 18.275°±0.2° and 19.998°±0.2°. [ka]

[0075] In one embodiment, the above crystalline form H, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ at 5.444°±0.2°, 8.528°±0.2°, 8.909°±0.2°, 9.669°±0.2°, 10.325°±0.2°, 10.885°±0.2°, 11.362°±0.2°, 11.994°±0.2°, 12.391°±0.2°, 13.296°±0.2°, 13.523°±0.2°, 14.24°±0.2°, 15.206°±0.2°, and 15.381°±0. Diffraction peaks are found at the following positions: 2°, 15.479°±0.2°, 15.972°±0.2°, 17.137°±0.2°, 17.512°±0.2°, 17.827°±0.2°, 18.275°±0.2°, 18.79°±0.2°, 19.003°±0.2°, 19.998°±0.2°, 20.774°±0.2°, 21.174°±0.2°, 21.483°±0.2°, 22.357°±0.2°, 22.901°±0.2°, 24.975°±0.2°, and 26.88°±0.2°.

[0076] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form H is basically as shown in the table below.

[0077] [Table 8] .

[0078] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystalline form H shows a weight loss of 1.110% during the heating process from 25.58°C to 150.63°C.

[0079] In one embodiment, the differential scanning calorimetry curve (DSC) of the above-mentioned crystalline form H has an endothermic peak with an onset temperature of 138.69°C.

[0080] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form H has an endothermic peak with a peak temperature of 150.32°C.

[0081] The present invention provides a crystalline form I of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 5.5058°±0.2°, 7.5176°±0.2°, 15.4455°±0.2°, 17.2025°±0.2°, 18.8815°±0.2°, 21.9424°±0.2°, and 23.5775°±0.2°. [ka]

[0082] In one embodiment, the above crystal form I, when measured using Cu-Kα radiation, has X-ray powder diffraction patterns represented by 2θ of 4.2926°±0.2°, 4.6616°±0.2°, 5.1103°±0.2°, 5.5058°±0.2°, 6.0446°±0.2°, 7.5176°±0.2°, 8.8154°±0.2°, 10.7679°±0.2°, 11.0145°±0.2°, 12.1007°±0.2°, 12.3584°±0.2°, 13.0245°±0.2°, 13.6613°±0.2°, 14.8321°±0.2°, Diffraction peaks are found at the following positions: 15.0219°±0.2°, 15.4455°±0.2°, 16.5217°±0.2°, 17.2025°±0.2°, 17.6832°±0.2°, 17.8573°±0.2°, 18.6876°±0.2°, 18.8815°±0.2°, 21.5792°±0.2°, 21.9424°±0.2°, 22.6197°±0.2°, 23.0634°±0.2°, 23.5775°±0.2°, 23.8621°±0.2°, 24.3147°±0.2°, and 24.7432°±0.2°.

[0083] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form I is basically as shown in the table below.

[0084] [Table 9] .

[0085] In one embodiment, the thermogravimetric analysis curve (TGA) of crystal form I shows a weight loss of 0.1408% during the heating process from 46.48°C to 100.54°C.

[0086] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form I has endothermic peaks with starting temperatures of 115.91°C and 155.71°C, respectively.

[0087] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form I has endothermic peaks with peak temperatures of 124.64°C and 157.93°C.

[0088] The present invention provides a crystalline form J of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.791°±0.2°, 12.203°±0.2°, 16.276°±0.2°, 17.338°±0.2°, 18.118°±0.2°, 18.942°±0.2° and 20.201°±0.2°. [ka]

[0089] In one embodiment, the above crystal form J, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 5.748°±0.2°, 8.791°±0.2°, 9.049°±0.2°, 9.42°±0.2°, 10.074°±0.2°, 10.882°±0.2°, 11.46°±0.2°, 11.826°±0.2°, 12.203°±0.2°, 13.259°±0.2°, 14.276°±0.2°, 14.694°±0.2°, 14.957°±0.2°, and 15.505°±0.2°. Diffraction peaks are found at the following positions: 16.276°±0.2°, 17.338°±0.2°, 18.118°±0.2°, 18.942°±0.2°, 19.742°±0.2°, 19.925°±0.2°, 20.201°±0.2°, 20.376°±0.2°, 21.222°±0.2°, 21.389°±0.2°, 21.762°±0.2°, 22.501°±0.2°, 22.863°±0.2°, 23.016°±0.2°, 23.376°±0.2°, and 23.759°±0.2°.

[0090] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form J is basically as shown in the table below.

[0091] [Table 10-1] [Table 10-2] .

[0092] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form J shows a weight loss of 0.2556% during the heating process from 35.20°C to 150.30°C.

[0093] In one embodiment, the differential scanning calorimetry (DSC) curve of the crystal form J has endothermic peaks with starting temperatures of 132.08°C and 152.97°C, respectively.

[0094] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form J has endothermic peaks with peak temperatures of 137.49°C and 155.43°C.

[0095] The present invention provides a crystalline form K of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 6.4564°±0.2°, 7.3943°±0.2°, 9.0755°±0.2°, 12.8967°±0.2°, 14.778°±0.2°, 19.2587°±0.2°, and 22.2392°±0.2°. [ka]

[0096] In one embodiment, the above crystal form K, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 6.4564°±0.2°, 7.3943°±0.2°, 9.0755°±0.2°, 10.5562°±0.2°, 11.1454°±0.2°, 11.3993°±0.2°, 12.2643°±0.2°, 12.8967°±0.2°, 14.778°±0.2°, 15.3086°±0.2°, 15.682°±0.2°, 16.3008°±0.2°, 17.4854°±0.2°, and 19.2587°±0.2°. Diffraction peaks are found at the following positions: °, 20.2788°±0.2°, 20.703°±0.2°, 21.2376°±0.2°, 21.5385°±0.2°, 21.688°±0.2°, 22.2392°±0.2°, 22.8603°±0.2°, 23.9619°±0.2°, 24.0585°±0.2°, 24.4456°±0.2°, 24.5831°±0.2°, 25.0787°±0.2°, 25.9017°±0.2°, 26.5371°±0.2°, 27.3914°±0.2°, and 28.2004°±0.2°.

[0097] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form K is basically as shown in the table below.

[0098] [Table 11-1] [Table 11-2] .

[0099] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form K shows a weight loss of 0.2766% during the heating process from 29.61°C to 100.11°C.

[0100] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form K has an endothermic peak with an onset temperature of 112.76°C.

[0101] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form K has an endothermic peak with a peak temperature of 116.84°C.

[0102] The present invention provides a crystalline form L of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 5.513°±0.2°, 13.504°±0.2°, 16.985°±0.2°, 18.045°±0.2°, 18.785°±0.2°, 20.219°±0.2°, and 21.844°±0.2°. [ka]

[0103] In one embodiment, the above crystal form L, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 5.513°±0.2°, 6.207°±0.2°, 8.909°±0.2°, 11.061°±0.2°, 11.427°±0.2°, 11.96°±0.2°, 12.5°±0.2°, 12.798°±0.2°, 13.28°±0.2°, 13.504°±0.2°, 14.081°±0.2°, 14.547°±0.2°, 15.64°±0.2°, and 16.404°±0.2°. Diffraction peaks are found at the following positions: 16.985°±0.2°, 17.159°±0.2°, 17.417°±0.2°, 18.045°±0.2°, 18.279°±0.2°, 18.489°±0.2°, 18.785°±0.2°, 19.323°±0.2°, 19.467°±0.2°, 20.219°±0.2°, 20.622°±0.2°, 21.46°±0.2°, 21.844°±0.2°, 22.006°±0.2°, 22.424°±0.2°, and 22.943°±0.2°.

[0104] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form L is basically as shown in the table below.

[0105] [Table 12] .

[0106] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form L shows a weight loss of 0.2308% during the heating process from 30.17°C to 150.15°C.

[0107] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form L has an endothermic peak with an onset temperature of 165.90°C.

[0108] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form L has an endothermic peak with a peak temperature of 171.33°C.

[0109] The present invention provides a crystalline form M of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 5.4969°±0.2°, 10.9723°±0.2°, 13.2767°±0.2°, 22°±0.2°, 23.5465°±0.2°, 27.5831°±0.2°, and 33.2405°±0.2°. [ka]

[0110] In one embodiment, the above crystal form M, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 4.9624°±0.2°, 5.4969°±0.2°, 5.8171°±0.2°, 5.9372°±0.2°, 8.8974°±0.2°, 10.9723°±0.2°, 11.9937°±0.2°, 13.2767°±0.2°, and 16.4617°±0. Diffraction peaks are found at the following positions: 2°, 22°±0.2°, 22.3562°±0.2°, 22.9591°±0.2°, 23.2262°±0.2°, 23.5465°±0.2°, 27.5831°±0.2°, 28.7603°±0.2°, 28.9834°±0.2°, 33.2405°±0.2°, 34.6165°±0.2°, and 38.9789°±0.2°.

[0111] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form M is basically as shown in the table below.

[0112] [Table 13] .

[0113] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form M shows a weight loss of 0.02364% during the heating process from 29.95°C to 150.15°C.

[0114] In one embodiment, the differential scanning calorimetry curve (DSC) of the above crystal form M has an endothermic peak with an onset temperature of 158.11°C.

[0115] In one embodiment, the differential scanning calorimetry curve (DSC) of the crystal form M has an endothermic peak with a peak temperature of 163.24°C.

[0116] The present invention provides a crystalline form N of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.402°±0.2°, 15.619°±0.2°, 17.4°±0.2°, 17.84°±0.2°, 18.404°±0.2°, 20.243°±0.2° and 22.6°±0.2°. [ka]

[0117] In one embodiment, the above crystalline form N, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ at 5.218°±0.2°, 6.643°±0.2°, 10.402°±0.2°, 10.874°±0.2°, 13.403°±0.2°, 13.583°±0.2°, 13.719°±0.2°, 14.031°±0.2°, 14.354°±0.2°, 14.742°±0.2°, 15.619°±0.2°, 15.96°±0.2°, 16.677°±0.2°, and 16.824°± Diffraction peaks are found at the following positions: 0.2°, 17.4°±0.2°, 17.84°±0.2°, 18.404°±0.2°, 18.945°±0.2°, 19.139°±0.2°, 19.477°±0.2°, 20.243°±0.2°, 21.798°±0.2°, 21.985°±0.2°, 22.179°±0.2°, 22.6°±0.2°, 22.844°±0.2°, 23.081°±0.2°, 23.272°±0.2°, 26.682°±0.2°, and 27.765°±0.2°.

[0118] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form N is basically as shown in the table below.

[0119] [Table 14] .

[0120] In one embodiment, the thermogravimetric analysis curve (TGA) of the above-mentioned crystalline form N shows a weight loss of 9.097% during the heating process from 29.97°C to 125.41°C.

[0121] In one embodiment, the differential scanning calorimetry (DSC) curve of the above-mentioned crystalline form N has endothermic peaks with starting temperatures of 64.45°C and 158.00°C, respectively.

[0122] In one embodiment, the differential scanning calorimetry (DSC) curve of the above-mentioned crystalline form N has endothermic peaks with peak temperatures of 72.35°C and 164.10°C, respectively.

[0123] The present invention provides a crystalline form O of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 6.2637°±0.2°, 12.5384°±0.2°, 15.377°±0.2°, 18.2659°±0.2°, 18.8011°±0.2°, 21.405°±0.2° and 24.3656°±0.2°. [ka]

[0124] In one embodiment, the above crystal form O, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 5.6701°±0.2°, 6.2637°±0.2°, 7.4001°±0.2°, 7.6972°±0.2°, 7.9176°±0.2°, 8.0144°±0.2°, 9.1172°±0.2°, 9.9174°±0.2°, 10.546°±0.2°, 11.1416°±0.2°, 12.5384°±0.2°, 13.8784°±0.2°, 14.0157°±0.2°, and 14.9304°±0.2°. Diffraction peaks are found at the following positions: 15.377°±0.2°, 15.6815°±0.2°, 16.1223°±0.2°, 16.7054°±0.2°, 18.2659°±0.2°, 18.8011°±0.2°, 19.8482°±0.2°, 20.2401°±0.2°, 20.735°±0.2°, 21.405°±0.2°, 22.2174°±0.2°, 22.4377°±0.2°, 22.8608°±0.2°, 22.9801°±0.2°, 23.621°±0.2°, and 24.3656°±0.2°.

[0125] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form O is basically as shown in the table below.

[0126] [Table 15-1] [Table 15-2] .

[0127] In one embodiment, the thermogravimetric analysis curve (TGA) of the above-mentioned crystalline form O shows a weight loss of 8.444% during the heating process from 29.88°C to 150.15°C.

[0128] In one embodiment, the differential scanning calorimetry (DSC) curve of the above-mentioned crystalline form O has endothermic peaks with starting temperatures of 117.33°C, 147.75°C, and 158.31°C, respectively.

[0129] In one embodiment, the differential scanning calorimetry (DSC) curve of the above-mentioned crystalline form O has endothermic peaks with peak temperatures of 122.88°C, 149.62°C, and 159.74°C, respectively.

[0130] The present invention provides a crystalline form P of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 5.516°±0.2°, 7.54°±0.2°, 11.012°±0.2°, 18.08°±0.2°, 18.962°±0.2°, 20.278°±0.2°, and 23.558°±0.2°. [ka]

[0131] In one embodiment, the above crystal form P, when measured using Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ at 5.516°±0.2°, 6.723°±0.2°, 7.54°±0.2°, 8.761°±0.2°, 11.012°±0.2°, 11.534°±0.2°, 12.657°±0.2°, 12.839°±0.2°, 13.459°±0.2°, 13.558°±0.2°, 14.102°±0.2°, 15.658°±0.2°, 16.359°±0.2°, and 16.519°± Diffraction peaks are found at the following positions: 0.2°, 17.04°±0.2°, 17.195°±0.2°, 17.404°±0.2°, 18.08°±0.2°, 18.322°±0.2°, 18.515°±0.2°, 18.962°±0.2°, 20.278°±0.2°, 21.66°±0.2°, 21.901°±0.2°, 22.06°±0.2°, 23.14°±0.2°, 23.558°±0.2°, 23.777°±0.2°, 24.283°±0.2°, and 24.98°±0.2°.

[0132] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form P is basically as shown in the table below.

[0133] [Table 16-1] [Table 16-2] .

[0134] In one embodiment, the thermogravimetric analysis curve (TGA) of the above-mentioned crystalline form P shows a weight loss of 0.4118% during the heating process from 30.74°C to 150.43°C.

[0135] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form P has endothermic peaks with starting temperatures of 106.68°C and 165.23°C, respectively.

[0136] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form P has endothermic peaks with peak temperatures of 120.91°C and 168.20°C, respectively.

[0137] The present invention provides a crystalline form Q of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 17.957°±0.2°, 18.421°±0.2°, 18.578°±0.2°, 19.22°±0.2°, 19.563°±0.2°, 21.58°±0.2° and 22.861°±0.2°. [ka]

[0138] In one embodiment, the above crystal form Q, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 7.481°±0.2°, 8.711°±0.2°, 9.357°±0.2°, 9.878°±0.2°, 10.03°±0.2°, 10.323°±0.2°, 10.685°±0.2°, 11.682°±0.2°, 12.365°±0.2°, 12.879°±0.2°, 13.262°±0.2°, 13.701°±0.2°, 14.221°±0.2°, and 15.008°±0. Diffraction peaks are found at the following positions: 2°, 15.307°±0.2°, 15.644°±0.2°, 15.981°±0.2°, 16.418°±0.2°, 17.483°±0.2°, 17.957°±0.2°, 18.421°±0.2°, 18.578°±0.2°, 19.102°±0.2°, 19.22°±0.2°, 19.563°±0.2°, 20.162°±0.2°, 20.453°±0.2°, 20.779°±0.2°, 21.58°±0.2°, and 22.861°±0.2°.

[0139] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form Q is basically as shown in the table below.

[0140] [Table 17] .

[0141] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form Q shows a weight loss of 1.609% during the heating process from 30.07°C to 150.15°C.

[0142] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form Q has endothermic peaks with starting temperatures of 73.53°C and 139.04°C, respectively.

[0143] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form Q has endothermic peaks with peak temperatures of 97.37°C and 142.10°C, respectively.

[0144] The present invention provides a crystalline form R of a compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 14.756°±0.2°, 17.758°±0.2°, 18.698°±0.2°, 20.377°±0.2°, 21.338°±0.2°, 21.979°±0.2°, and 25.521°±0.2°. [ka]

[0145] In one embodiment, the above crystal form R, when subjected to Cu-Kα radiation, exhibits an X-ray powder diffraction pattern represented by 2θ of 6.612°±0.2°, 7.2°±0.2°, 9.141°±0.2°, 10.376°±0.2°, 12.355°±0.2°, 13.183°±0.2°, 13.638°±0.2°, 14.756°±0.2°, 15.059°±0.2°, 16.62°±0.2°, 17.1°±0.2°, 17.758°±0.2°, 18.44°±0.2°, and 18.698°±0.2°. Diffraction peaks are found at the following positions: 19.397°±0.2°, 19.836°±0.2°, 20.121°±0.2°, 20.377°±0.2°, 21.142°±0.2°, 21.338°±0.2°, 21.979°±0.2°, 22.201°±0.2°, 23.019°±0.2°, 24.201°±0.2°, 24.898°±0.2°, 25.521°±0.2°, 26.581°±0.2°, 26.92°±0.2°, 27.243°±0.2°, and 29.38°±0.2°.

[0146] In one embodiment, the X-ray powder diffraction pattern analysis data for the above crystal form R is basically as shown in the table below.

[0147] [Table 18] .

[0148] In one embodiment, the thermogravimetric analysis curve (TGA) of the above crystal form R shows a weight loss of 4.375% during the heating process from 30.17°C to 150.72°C.

[0149] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form R has endothermic peaks with starting temperatures of 25.50°C, 103.97°C, 115.73°C, and 145.79°C, respectively.

[0150] In one embodiment, the differential scanning calorimetry (DSC) curve of the above crystal form R has endothermic peaks with peak temperatures of 33.23°C, 108.31°C, 120.82°C, and 156.29°C, respectively.

[0151] The present invention provides one equivalent of methanesulfonate crystal form A of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.2973°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2° and 20.7584°±0.2°. [ka]

[0152] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A has diffraction peaks at positions of 10.2973°±0.2°, 15.1407°±0.2°, and 17.8003°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0153] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A has diffraction peaks at positions of 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, and 20.6191°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0154] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A has diffraction peaks at the positions of 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, and 20.6191°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0155] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2°, and 20.7584°±0.2°.

[0156] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A has diffraction peaks at the following positions in its X-ray powder diffraction pattern, represented by 2θ, when Cu-Kα radiation is used: 10.2973°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2°, and 20.7584°±0.2°.

[0157] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ is 10.2973°±0.2°, 10.7003°±0.2°, 11.5381°±0.2°, 12.618°±0.2°, 12.918°±0.2°, 13.995°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 15.6419°±0.2°, 17.8003°±0.2°, 18.1003°±0.2°, 18.3418°±0.2°, 18.7198°±0.2°, 19.2 Diffraction peaks are found at the following positions: 81°±0.2°, 19.8025°±0.2°, 20.3791°±0.2°, 20.6191°±0.2°, 20.7584°±0.2°, 21.2626°±0.2°, 21.4387°±0.2°, 21.7211°±0.2°, 22.0791°±0.2°, 22.442°±0.2°, 22.8785°±0.2°, 23.1402°±0.2°, 23.4006°±0.2°, 23.739°±0.2°, 24.2791°±0.2°, 24.6595°±0.2°, and 25.2227°±0.2°.

[0158] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of methanesulfonate crystal form A is basically as shown in the table below.

[0159] [Table 19] .

[0160] In one embodiment, the X-ray powder diffraction pattern of 1 equivalent of methanesulfonate crystal form A is basically as shown in Figure 5.

[0161] In one embodiment, the thermogravimetric analysis (TGA) curve of 1 equivalent of methanesulfonate crystalline form A shows a weight loss of 0.02143±0.005% during the heating process from 39.18±3°C to 150.63±3°C.

[0162] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of methanesulfonate crystalline form A shows a weight loss of 0.02143% during the heating process from 39.18°C to 150.63°C.

[0163] In one embodiment, the thermogravimetric analysis curve of the above 1 equivalent of methanesulfonate crystalline form A is basically as shown in Figure 6.

[0164] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form A has endothermic peaks with starting temperatures of 85.22±3°C and 220.46±3°C, respectively.

[0165] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form A has endothermic peaks with starting temperatures of 85.22°C and 220.46°C, respectively.

[0166] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form A has endothermic peaks with peak temperatures of 86.90±3°C and 222.22±3°C, respectively.

[0167] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form A has endothermic peaks with peak temperatures of 86.90°C and 222.22°C, respectively.

[0168] In one embodiment, the differential scanning calorimetry curve of one equivalent of methanesulfonate crystalline form A is basically as shown in Figure 7.

[0169] In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of methanesulfonate crystalline form A shows that the weight increase due to moisture absorption is 0.31 ± 0.005% at 25°C and 80% RH.

[0170] In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of methanesulfonate crystalline form A shows a weight increase due to moisture absorption of 0.31% at 25°C and 80%RH.

[0171] In one embodiment, the dynamic vapor adsorption curve of 1 equivalent of methanesulfonate crystalline form A is shown in Figure 9.

[0172] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form A 1 The 1H-NMR results indicate that the molar ratio of methanesulfonic acid to free base in the sample is 1:1.

[0173] In one embodiment, the proton nuclear magnetic resonance of the above 1 equivalent of methanesulfonate crystal form A is as shown in Figure 8.

[0174] The present invention further provides a method for producing one equivalent of methanesulfonate crystalline form A of the compound represented by formula I, comprising the step of stirring the amorphous form of the compound represented by formula I and methanesulfonic acid in tetrahydrofuran to precipitate a solid, thereby obtaining one equivalent of methanesulfonate crystalline form A of the compound represented by formula I, wherein the stirring is performed, for example, at room temperature of 25°C, the stirring time is preferably 2 to 7 days, more preferably 3 days, the molar ratio of amorphous form of the compound represented by formula I to methanesulfonic acid is preferably 1:1, and the mass-volume ratio of the compound represented by formula I to the solvent is preferably (10 mg to 100 mg):1 mL, more preferably 25 mg:1 mL.

[0175] In one embodiment, the method for producing 1 equivalent of methanesulfonate crystal form A further includes the steps of precipitation of the solid, isolation, and drying to obtain 1 equivalent of methanesulfonate crystal form A.

[0176] The present invention provides one equivalent of methanesulfonate crystalline form B of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 5.087°±0.2°, 9.975°±0.2°, 15.895°±0.2°, 19.013°±0.2°, 19.521°±0.2°, 24.658°±0.2° and 25.066°±0.2°. [ka]

[0177] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form B was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 5.087°±0.2°, 6.896°±0.2°, 9.975°±0.2°, 11.998°±0.2°, 13.18°±0.2°, 14.156°±0.2°, 14.733°±0.2°, 15.895°±0.2°, 16.663°±0.2°, 17.025°±0.2°, 17.456°±0.2°, 17.945°±0.2°, 19.013°±0.2°, 19. Diffraction peaks are found at the following positions: 521°±0.2°, 20.317°±0.2°, 21.079°±0.2°, 21.294°±0.2°, 21.911°±0.2°, 22.851°±0.2°, 22.964°±0.2°, 23.783°±0.2°, 24.254°±0.2°, 24.658°±0.2°, 25.066°±0.2°, 25.792°±0.2°, 26.82°±0.2°, 27.34°±0.2°, 27.821°±0.2°, 27.985°±0.2°, and 30.133°±0.2°.

[0178] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of methanesulfonate crystal form B is basically as shown in the table below.

[0179] [Table 20] .

[0180] In one embodiment, the thermogravimetric analysis (TGA) curve of 1 equivalent of methanesulfonate crystalline form B shows a weight loss of 4.876% during the heating process from 28.09°C to 90.26°C.

[0181] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form B has endothermic peaks with starting temperatures of 36.95°C, 93.93°C, 130.40°C, and 218.58°C, respectively.

[0182] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of methanesulfonate crystalline form B has endothermic peaks with peak temperatures of 57.12°C, 99.03°C, 136.18°C, and 219.99°C, respectively.

[0183] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form B 1 The 1H-NMR results indicate that the molar ratio of methanesulfonic acid to free base in the sample is 1:1.

[0184] The present invention provides one equivalent of methanesulfonate crystalline form C of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 15.133°±0.2°, 15.369°±0.2°, 18.155°±0.2°, 19.055°±0.2°, 22.54°±0.2°, 28.617°±0.2° and 33.447°±0.2°, [ka]

[0185] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form C is subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ are 10.424°±0.2°, 10.555°±0.2°, 12.919°±0.2°, 14.078°±0.2°, 14.292°±0.2°, 15.133°±0.2°, 15.369°±0.2°, 15.844°±0.2°, 17.882°±0.2°, 18.155°±0.2°, 18.323°±0.2°, 18.733°±0.2°, 19.055°±0.2°, 19 Diffraction peaks are found at the following positions: 0.674°±0.2°, 20.996°±0.2°, 21.605°±0.2°, 22.009°±0.2°, 22.54°±0.2°, 22.968°±0.2°, 23.277°±0.2°, 23.709°±0.2°, 24.975°±0.2°, 25.203°±0.2°, 25.406°±0.2°, 27.333°±0.2°, 28.078°±0.2°, 28.617°±0.2°, 28.764°±0.2°, 29.378°±0.2°, and 33.447°±0.2°.

[0186] In one embodiment, the X-ray powder diffraction pattern analysis data for the above 1 equivalent of methanesulfonate crystalline form C is basically as shown in the table below.

[0187] [Table 21-1] [Table 21-2] .

[0188] In one embodiment, the thermogravimetric analysis (TGA) curve of 1 equivalent of methanesulfonate crystalline form C shows a weight loss of 0.04218% during the heating process from 34.91°C to 250.03°C.

[0189] In one embodiment, the thermogravimetric analysis curve of the above 1 equivalent of methanesulfonate crystalline form C is basically as shown in Figure 65.

[0190] In one embodiment, the differential scanning calorimetry (DSC) curve of the above 1 equivalent of methanesulfonate crystalline form C has endothermic peaks with starting temperatures of 85.66°C and 220.56°C, respectively.

[0191] In one embodiment, the differential scanning calorimetry (DSC) curve of the above 1 equivalent of methanesulfonate crystalline form C has endothermic peaks with peak temperatures of 87.04°C and 222.69°C, respectively.

[0192] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form C 1 The 1H-NMR results indicate that the molar ratio of methanesulfonic acid to free base in the sample is 1:1.

[0193] The present invention provides one equivalent of methanesulfonate crystalline form D of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 13.335°±0.2°, 15.369°±0.2°, 18.019°±0.2°, 18.234°±0.2°, 18.62°±0.2°, 21.173°±0.2° and 25.632°±0.2°. [ka]

[0194] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form D is subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ is 10.328°±0.2°, 10.659°±0.2°, 11.775°±0.2°, 13.112°±0.2°, 13.335°±0.2°, 14.352°±0.2°, 14.898°±0.2°, 15.369°±0.2°, 15.873°±0.2°, 16.152°±0.2°, 17.848°±0.2°, 18.019°±0.2°, 18.234°±0.2°, 1 Diffraction peaks are found at the following positions: 8.62°±0.2°, 18.925°±0.2°, 21.173°±0.2°, 21.566°±0.2°, 21.757°±0.2°, 22.643°±0.2°, 22.892°±0.2°, 23.478°±0.2°, 23.771°±0.2°, 23.895°±0.2°, 24.14°±0.2°, 24.53°±0.2°, 25.069°±0.2°, 25.632°±0.2°, 26.022°±0.2°, 26.692°±0.2°, and 26.825°±0.2°.

[0195] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of methanesulfonate crystal form D is basically as shown in the table below.

[0196] [Table 22] .

[0197] In one embodiment, the thermogravimetric analysis (TGA) curve of 1 equivalent of methanesulfonate crystalline form D shows a weight loss of 0.006279% during the heating process from 22.75°C to 250.00°C.

[0198] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of methanesulfonate crystalline form D has endothermic peaks with starting temperatures of 84.66°C and 220.11°C, respectively.

[0199] In one embodiment, the differential scanning calorimetry (DSC) curve of the above 1 equivalent of methanesulfonate crystalline form D has endothermic peaks with peak temperatures of 86.50°C and 222.17°C, respectively.

[0200] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form D 1 The 1H-NMR results indicate that the molar ratio of methanesulfonic acid to free base in the sample is 1:1.

[0201] The present invention provides a methanesulfonate crystal form E of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.561°±0.2°, 18.089°±0.2°, 18.523°±0.2°, 19.026°±0.2°, 19.526°±0.2°, 22.768°±0.2° and 22.967°±0.2°. [ka]

[0202] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form E was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 5.047°±0.2°, 10.561°±0.2°, 12.766°±0.2°, 12.98°±0.2°, 14.213°±0.2°, 14.641°±0.2°, 15.055°±0.2°, 15.786°±0.2°, 16.053°±0.2°, 16.323°±0.2°, 17.037°±0.2°, 17.845°±0.2°, 18.089°±0.2°, 18. Diffraction peaks are found at the following positions: 523°±0.2°, 19.026°±0.2°, 19.526°±0.2°, 20.172°±0.2°, 20.653°±0.2°, 20.848°±0.2°, 21.072°±0.2°, 21.722°±0.2°, 22.144°±0.2°, 22.768°±0.2°, 22.967°±0.2°, 23.202°±0.2°, 23.417°±0.2°, 23.881°±0.2°, 24.427°±0.2°, 24.662°±0.2°, and 24.969°±0.2°.

[0203] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of methanesulfonate crystal form E is basically as shown in the table below.

[0204] [Table 23-1] [Table 23-2] .

[0205] In one embodiment, the thermogravimetric analysis (TGA) curve of the above 1 equivalent of methanesulfonate crystalline form E shows a weight loss of 1.181% during the heating process from 38.02°C to 150.14°C.

[0206] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of methanesulfonate crystalline form E has endothermic peaks with starting temperatures of 89.99°C, 101.61°C, and 219.49°C, respectively.

[0207] In one embodiment, the differential scanning calorimetry curve (DSC) of the above-mentioned 1 equivalent of methanesulfonate crystal form E has endothermic peaks with peak temperatures of 90.21 °C, 109.10 °C, and 221.65 °C, respectively.

[0208] In one embodiment, the above-mentioned 1 equivalent of methanesulfonate crystal form E 1 The results of 1H-NMR show that the molar ratio of methanesulfonic acid to free base in the sample is 1:1, the molar ratio of the residual amount of 1,4-dioxane solvent to free base is 0.12:1, and the weight ratio is 1.4%.

[0209] The present invention provides 1 equivalent of methanesulfonate crystal form F of the compound represented by formula I, and its X-ray powder diffraction pattern (XRPD) has at least 3, at least 4, at least 5, at least 6 or at least 7 characteristic peaks at 2θ angles of 10.219° ± 0.2°, 13.318° ± 0.2°, 16.777° ± 0.2°, 18.6° ± 0.2°, 18.802° ± 0.2°, 20.981° ± 0.2° and 22.621° ± 0.2°,

Chemical formula

[0210] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form F is subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ is 10.219°±0.2°, 10.535°±0.2°, 12.441°±0.2°, 13.318°±0.2°, 14.441°±0.2°, 14.978°±0.2°, 15.639°±0.2°, 16.14°±0.2°, 16.777°±0.2°, 17.697°±0.2°, 18.501°±0.2°, 18.6°±0.2°, 18.802°±0.2°, 1 Diffraction peaks are found at the following positions: 9.859°±0.2°, 19.995°±0.2°, 20.5°±0.2°, 20.66°±0.2°, 20.981°±0.2°, 21.162°±0.2°, 21.337°±0.2°, 21.78°±0.2°, 22.079°±0.2°, 22.198°±0.2°, 22.621°±0.2°, 22.941°±0.2°, 23.723°±0.2°, 23.984°±0.2°, 24.321°±0.2°, 24.76°±0.2°, and 28.78°±0.2°.

[0211] In one embodiment, the X-ray powder diffraction pattern analysis data for the above 1 equivalent of methanesulfonate crystal form F is basically as shown in Table 24.

[0212] [Table 24] .

[0213] In one embodiment, the thermogravimetric analysis (TGA) curve of the above 1 equivalent of methanesulfonate crystalline form F shows a weight loss of 4.840% during the heating process from 39.51°C to 150.96°C.

[0214] In one embodiment, the thermogravimetric analysis curve of the above 1 equivalent of methanesulfonate crystalline form F is basically as shown in Figure 77.

[0215] In one embodiment, the differential scanning calorimetry (DSC) curve of the above 1 equivalent of methanesulfonate crystalline form F has endothermic peaks with starting temperatures of 115.92°C and 213.19°C, respectively.

[0216] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of methanesulfonate crystalline form F has endothermic peaks with peak temperatures of 127.70°C and 217.04°C, respectively.

[0217] In one embodiment, the above 1 equivalent of methanesulfonate crystalline form F 1 The 1H-NMR results show that the molar ratio of methanesulfonic acid to free base in the sample is 1:1, the molar ratio of residual 1,4-dioxane solvent to free base is 0.43:1, and the weight ratio is 4.9%.

[0218] The present invention provides a maleate crystalline form A of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 5.2344°±0.2°, 10.8375°±0.2°, 12.9364°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2°, and 20.1186°±0.2°. [ka]

[0219] In one embodiment, the above 1 equivalent of maleate crystalline form A has diffraction peaks at positions of 17.781°±0.2°, 18.6613°±0.2°, and 20.1186°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0220] In one embodiment, the above 1 equivalent of maleate crystalline form A has diffraction peaks at positions of 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, and 20.1186°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0221] In one embodiment, the above 1 equivalent of maleate crystalline form A has diffraction peaks at the positions of 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2° and 20.1186°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0222] In one embodiment, the above 1 equivalent of maleate crystalline form A has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 5.2344°±0.2°, 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2°, and 20.1186°±0.2°.

[0223] In one embodiment, the above 1 equivalent of maleate crystalline form A has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 5.2344°±0.2°, 10.8375°±0.2°, 12.9364°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2°, and 20.1186°±0.2°.

[0224] In one embodiment, the above-mentioned 1 equivalent of maleate crystal form A has X-ray powder diffraction pattern peaks at positions of 5.2344° ± 0.2°, 8.0562° ± 0.2°, 9.3187° ± 0.2°, 9.981° ± 0.2°, 10.4404° ± 0.2°, 10.8375° ± 0.2°, 12.5202° ± 0.2°, 12.9364° ± 0.2°, 13.9614° ± 0.2°, 14.9983° ± 0.2°, 15.6783° ± 0.2°, 17.781° ± 0.2°, 18.3794° ± 0.2°, 18.6613° ± 0.2°, 18.9188° ± 0.2°, 19.4195° ± 0.2°, 19.701° ± 0.2°, 20.1186° ± 0.2°, 20.5991° ± 0.2°, 20.9388° ± 0.2°, 22.6192° ± 0.2°, 22.739° ± 0.2°, 23.3011° ± 0.2°, 24.6412° ± 0.2°, 25.1802° ± 0.2°, 26.1581° ± 0.2°, 28.061° ± 0.2°, 29.7621° ± 0.2°, 30.2013° ± 0.2° and 30.9209° ± 0.2° when using Cu-Kα radiation.

[0225] In one embodiment, the X-ray powder diffraction pattern analysis data of the above-mentioned 1 equivalent of maleate crystal form A is basically as shown in the following table.

[0226]

Table 25

[0227] In one embodiment, the X-ray powder diffraction pattern of the above-mentioned 1 equivalent of maleate crystal form A is basically as shown in Figure 10.

[0228] In one embodiment, the thermogravimetric analysis curve (TGA) of the above-mentioned 1 equivalent of maleate crystal form A shows a weight loss of 0.1441 ± 0.005% during the heating process from 30.24 ± 3°C to 150.15 ± 3°C.

[0229] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of maleate crystalline form A shows a weight loss of 0.1441% during the heating process from 30.24°C to 150.15°C.

[0230] In one embodiment, the thermogravimetric analysis curve of the above 1 equivalent of maleate crystalline form A is basically as shown in Figure 11.

[0231] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form A has an endothermic peak with an onset temperature of 212.82 ± 3°C.

[0232] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form A has an endothermic peak with an onset temperature of 212.82°C.

[0233] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form A has an endothermic peak with a peak temperature of 213.55 ± 3°C.

[0234] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form A has an endothermic peak with a peak temperature of 213.55°C.

[0235] In one embodiment, the differential scanning calorimetry curve of one equivalent of maleate crystalline form A is basically as shown in Figure 12.

[0236] In one embodiment, the dynamic vapor adsorption curve (DVS) of the above 1 equivalent of maleate crystalline form A shows that the weight increase due to moisture absorption is 0.11 ± 0.005% at 25°C and 80% RH.

[0237] In one embodiment, the dynamic vapor adsorption curve (DVS) of the above 1 equivalent of maleate crystalline form A shows that the weight increase due to moisture absorption is 0.11% at 25°C and 80%RH.

[0238] In one embodiment, the dynamic vapor adsorption curve of the above 1 equivalent of maleate crystalline form A is as shown in Figure 14.

[0239] In one embodiment, the above 1 equivalent of maleate crystalline form A 1 The 1H-NMR results indicate that the molar ratio of maleic acid to free base in the sample is 1:1.

[0240] In one embodiment, the proton nuclear magnetic resonance of one equivalent of maleate crystal form A is as shown in Figure 13.

[0241] The present invention further provides a method for producing one equivalent of maleate crystalline form A of the compound represented by formula I, comprising the steps of stirring amorphous form of the compound represented by formula I and maleic acid in ethanol at 50°C to obtain a suspension solution, continuing to stir the obtained suspension solution at room temperature to precipitate a solid, and obtaining one equivalent of maleate crystalline form A of the compound represented by formula I, wherein the continuing stirring of the suspension solution at room temperature is preferably carried out at 25°C, the duration of continuing stirring of the suspension solution at room temperature is preferably 6 to 8 days, more preferably 7 days, the mass ratio of amorphous form of the compound represented by formula I to maleic acid is preferably 5:1, and the mass-volume ratio of amorphous form of the compound represented by formula I to ethanol is preferably (50 to 500 mg):1 mL, more preferably 250 mg:1 mL.

[0242] In one embodiment, the method for producing 1 equivalent of maleate crystalline form A further includes the steps of precipitation of the solid, isolation, and drying to obtain 1 equivalent of maleate crystalline form A.

[0243] The present invention provides one equivalent maleate crystalline form B of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 15.941°±0.2°, 16.504°±0.2°, 17.24°±0.2°, 18.257°±0.2°, 20.861°±0.2°, 22.819°±0.2° and 23.024°±0.2°. [ka]

[0244] In one embodiment, the above 1 equivalent of maleate crystalline form B was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 7.67°±0.2°, 7.965°±0.2°, 10.358°±0.2°, 11.077°±0.2°, 13.06°±0.2°, 14.716°±0.2°, 15.149°±0.2°, 15.572°±0.2°, 15.941°±0.2°, 16.301°±0.2°, 16.504°±0.2°, 17.24°±0.2°, 18.257°±0.2°, and 18.881°. Diffraction peaks are found at the following positions: °±0.2°, 20.012°±0.2°, 20.273°±0.2°, 20.861°±0.2°, 21.616°±0.2°, 22.044°±0.2°, 22.280°±0.2°, 22.558°±0.2°, 22.819°±0.2°, 23.024°±0.2°, 23.175°±0.2°, 23.599°±0.2°, 23.981°±0.2°, 25.755°±0.2°, 26.059°±0.2°, 26.532°±0.2°, and 26.983°±0.2°.

[0245] In one embodiment, the X-ray powder diffraction pattern analysis data for one equivalent of maleate crystal form B is basically as shown in the table below.

[0246] [Table 26] .

[0247] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of maleate crystalline form B shows a weight loss of 0.1454% during the heating process from 30.45°C to 150.43°C.

[0248] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form B has an endothermic peak with an onset temperature of 214.44°C.

[0249] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of maleate crystalline form B has an endothermic peak with a peak temperature of 215.00°C.

[0250] In one embodiment, the above 1 equivalent of maleate crystalline form B 1 The 1H-NMR results indicate that the molar ratio of maleic acid to free base in the sample is 1:1.

[0251] The present invention provides one equivalent of tartrate crystal form A of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.296°±0.2°, 11.744°±0.2°, 15.078°±0.2°, 18.321°±0.2°, 19.562°±0.2°, 20.32°±0.2° and 21.6°±0.2°. [ka]

[0252] In one embodiment, the above 1 equivalent of tartrate crystal form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ are 3.938°±0.2°, 9.562°±0.2°, 10.296°±0.2°, 10.836°±0.2°, 11.126°±0.2°, 11.744°±0.2°, 12.78°±0.2°, 13.908°±0.2°, 14.074°±0.2°, 15.078°±0.2°, 15.318°±0.2°, 15.714°±0.2°, 16.865°±0.2°, 17 Diffraction peaks are found at the following positions: 0.358°±0.2°, 18.321°±0.2°, 18.856°±0.2°, 19.562°±0.2°, 20.32°±0.2°, 21.6°±0.2°, 22.619°±0.2°, 23.802°±0.2°, 23.98°±0.2°, 25.046°±0.2°, 25.311°±0.2°, 25.998°±0.2°, 26.5°±0.2°, 27.1°±0.2°, 27.827°±0.2°, 28.286°±0.2°, and 28.917°±0.2°.

[0253] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form A is basically as shown in the table below.

[0254] [Table 27] .

[0255] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystal form A shows a weight loss of 2.467% during the heating process from 28.23°C to 150.30°C.

[0256] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of tartrate crystal form A has endothermic peaks with starting temperatures of 28.77°C, 118.07°C, and 214.88°C, respectively.

[0257] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of tartrate crystal form A has endothermic peaks with peak temperatures of 51.87°C, 130.04°C, and 223.29°C, respectively.

[0258] The present invention provides one equivalent of tartrate crystalline form B of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) of which has at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.817°±0.2°, 10.879°±0.2°, 16.161°±0.2°, 17.421°±0.2°, 17.657°±0.2°, 18.018°±0.2° and 19.182°±0.2°. [ka]

[0259] In one embodiment, the above 1 equivalent of tartrate crystal form B was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 8.423°±0.2°, 8.817°±0.2°, 9.406°±0.2°, 9.859°±0.2°, 10.331°±0.2°, 10.879°±0.2°, 11.359°±0.2°, 12.193°±0.2°, 12.52°±0.2°, 12.898°±0.2°, 13.036°±0.2°, 13.218°±0.2°, 13.36°±0.2°, and 14.283°. Diffraction peaks are found at the following positions: °±0.2°, 15.039°±0.2°, 15.579°±0.2°, 16.161°±0.2°, 16.321°±0.2°, 16.879°±0.2°, 17.002°±0.2°, 17.421°±0.2°, 17.657°±0.2°, 18.018°±0.2°, 19.062°±0.2°, 19.182°±0.2°, 19.422°±0.2°, 19.76°±0.2°, 20.076°±0.2°, 20.34°±0.2°, and 21.04°±0.2°.

[0260] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form B is basically as shown in the table below.

[0261]

Table 28-1

Table 28-2

[0262] In one embodiment, the thermogravimetric analysis curve (TGA) of the above 1 equivalent of tartrate crystal form B shows a weight loss of 7.235% during the heating process from 40.16 °C to 150.16 °C.

[0263] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form B has endothermic peaks with starting temperatures of 118.67 °C and 205.16 °C, respectively.

[0264] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form B has endothermic peaks with peak temperatures of 128.63 °C and 222.35 °C, respectively.

[0265] In one embodiment, the above 1 equivalent of tartrate crystal form B 1 The result of 1H-NMR shows that the molar ratio of tartaric acid to free base in the sample is 1:1, the molar ratio of the residual amount of tetrahydrofuran solvent to free base is 0.99:1, and the weight ratio is 8.3%.

[0266] The present invention provides 1 equivalent of tartrate crystal form C of the compound represented by formula I, and its X-ray powder diffraction pattern (XRPD) has at least 3, at least 4, at least 5, at least 6 or at least 7 characteristic peaks at 2θ angles of 10.196° ± 0.2°, 15.543° ± 0.2°, 15.757° ± 0.2°, 17.004° ± 0.2°, 18.196° ± 0.2°, 20.699° ± 0.2° and 21.665° ± 0.2°,

Chemical formula

[0267] In one embodiment, the above 1 equivalent of tartrate crystalline form C has diffraction peaks at positions of 10.196°±0.2°, 15.543°±0.2°, and 18.196°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0268] In one embodiment, the above 1 equivalent of tartrate crystalline form C has diffraction peaks at positions of 10.196°±0.2°, 15.543°±0.2°, 17.004°±0.2°, and 18.196°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0269] In one embodiment, the above 1 equivalent of tartrate crystalline form C has diffraction peaks at positions of 10.196°±0.2°, 15.543°±0.2°, 17.004°±0.2°, 18.196°±0.2°, and 20.699°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0270] In one embodiment, the above 1 equivalent of tartrate crystalline form C has diffraction peaks at the positions of 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2° and 20.699°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0271] In one embodiment, the above 1 equivalent of tartrate crystalline form C has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 20.699°±0.2°, and 21.665°±0.2°.

[0272] In one embodiment, the above 1 equivalent of tartrate crystal form C is subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ are 8.48°±0.2°, 10.196°±0.2°, 14.537°±0.2°, 15.052°±0.2°, 15.277°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 16.003°±0.2°, 16.377°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 18.782°±0.2°, 19.226°±0.2°, and 19.608°. Diffraction peaks are found at the following positions: °±0.2°, 20.001°±0.2°, 20.699°±0.2°, 21.665°±0.2°, 22.058°±0.2°, 22.545°±0.2°, 22.875°±0.2°, 23.097°±0.2°, 23.505°±0.2°, 23.819°±0.2°, 24.313°±0.2°, 24.642°±0.2°, 25.027°±0.2°, 25.699°±0.2°, 26.666°±0.2°, 26.867°±0.2°, and 27.857°±0.2°.

[0273] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form C is basically as shown in the table below.

[0274] [Table 29-1] [Table 29-2] .

[0275] In one embodiment, the X-ray powder diffraction pattern of 1 equivalent of tartrate crystal form C is basically as shown in Figure 15.

[0276] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystalline form C shows a weight loss of 0.04074±0.005% during the heating process from 29.99±3℃ to 150.15±3℃.

[0277] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystalline form C shows a weight loss of 0.04074% during the heating process from 29.99°C to 150.15°C.

[0278] In one embodiment, the thermogravimetric analysis curve of the above 1 equivalent of tartrate crystalline form C is basically as shown in Figure 16.

[0279] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystalline form C has an endothermic peak with an onset temperature of 188.73 ± 3°C.

[0280] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystalline form C has an endothermic peak with an onset temperature of 188.73°C.

[0281] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystalline form C has an endothermic peak with a peak temperature of 190.42 ± 3°C.

[0282] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystalline form C has an endothermic peak with a peak temperature of 190.42°C.

[0283] In one embodiment, the differential scanning calorimetry curve of the above 1 equivalent of tartrate crystalline form C is basically as shown in Figure 17.

[0284] In one embodiment, the above 1 equivalent of tartrate crystalline form C 1 The 1H-NMR results show that the molar ratio of tartaric acid to free base in the sample is 1:1, indicating that no solvent remains.

[0285] In one embodiment, the proton nuclear magnetic resonance of the above 1 equivalent of tartrate crystal form C is as shown in Figure 18.

[0286] The present invention further provides a method for producing one equivalent of tartrate crystalline form C of the compound represented by formula I, preferably one of the following methods.

[0287] Method 1 comprises the following steps: stirring 1 equivalent of tartrate crystal form B in a solvent to precipitate a solid, thereby obtaining 1 equivalent of tartrate crystal form C of the compound represented by formula I, wherein the solvent is acetonitrile, the stirring is preferably carried out at 35-45°C, the stirring time is preferably 2-7 days, and the mass-to-volume ratio of the compound represented by formula I to the solvent is preferably (50 mg-500 mg):1 mL. Method two includes the following steps: Stirring 1 equivalent of tartrate crystal form B in dichloromethane to obtain a clarified solution, add n-heptane and stir to precipitate a solid to obtain 1 equivalent of tartrate crystal form C of the compound represented by formula I, the stirring preferably being carried out at room temperature, the stirring time preferably being 3 to 5 days, the mass-to-volume ratio of 1 equivalent of tartrate crystal form B to the good solvent preferably being (50 mg to 500 mg):1 mL, and the volume ratio of the good solvent to the poor solvent preferably being 1:(4 to 5).

[0288] In one embodiment, in Method 1 described above, the stirring time is preferably 3 days, the stirring is preferably carried out at 40°C, and the mass-volume ratio of 1 equivalent of tartrate crystal form B to the solvent is preferably 250 mg:1 mL.

[0289] In one embodiment, in method 2 described above, the stirring is preferably carried out at 25°C, the stirring time is preferably 5 days, the mass-volume ratio of 1 equivalent of tartrate crystal form B to dichloromethane is preferably 50 mg:1 mL, and the volume ratio of dichloromethane to n-heptane is preferably 1:4.

[0290] In one embodiment, the method for producing 1 equivalent of tartrate crystal form C further includes the steps of precipitation of the solid, followed by isolation and drying, thereby obtaining 1 equivalent of tartrate crystal form C.

[0291] The present invention provides one equivalent of tartrate crystal form D of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 8.762°±0.2°, 15.257°±0.2°, 16.537°±0.2°, 17.539°±0.2°, 19.237°±0.2°, 20.401°±0.2° and 23.817°±0.2°. [ka]

[0292] In one embodiment, the above 1 equivalent of tartrate crystal form D was subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ was 8.762°±0.2°, 9.243°±0.2°, 11.323°±0.2°, 11.682°±0.2°, 13.705°±0.2°, 14.852°±0.2°, 15.257°±0.2°, 15.519°±0.2°, 16.065°±0.2°, 16.537°±0.2°, 17.539°±0.2°, 19.237°±0.2°, 19.698°±0.2°, 20.06 Diffraction peaks are found at the following positions: 6°±0.2°, 20.401°±0.2°, 21.144°±0.2°, 21.339°±0.2°, 21.856°±0.2°, 21.992°±0.2°, 22.977°±0.2°, 23.817°±0.2°, 24.081°±0.2°, 25.043°±0.2°, 26.068°±0.2°, 26.676°±0.2°, 27.702°±0.2°, 30.799°±0.2°, 31.764°±0.2°, 32.035°±0.2°, and 32.63°±0.2°.

[0293] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form D is basically as shown in the table below.

[0294] [Table 30] .

[0295] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystal form D shows a weight loss of 5.376% during the heating process from 30.04°C to 175.17°C.

[0296] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form D has endothermic peaks with starting temperatures of 123.48°C and 179.70°C, respectively.

[0297] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form D has endothermic peaks with peak temperatures of 130.10°C and 221.00°C.

[0298] In one embodiment, the above 1 equivalent of tartrate crystalline form D 1 The 1H-NMR results show that the molar ratio of tartaric acid to free base in the sample is 1:1, the molar ratio of residual ethyl acetate solvent to free base is 0.34:1, and the weight ratio is 3.69%.

[0299] The present invention provides one equivalent of tartrate crystal form E of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 11.677°±0.2°, 15.562°±0.2°, 18.562°±0.2°, 19.2°±0.2°, 19.461°±0.2°, 20.463°±0.2° and 23.421°±0.2°. [ka]

[0300] In one embodiment, the above 1 equivalent of tartrate crystal form E was subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ was 3.899°±0.2°, 10.198°±0.2°, 10.717°±0.2°, 11.12°±0.2°, 11.399°±0.2°, 11.677°±0.2°, 12.781°±0.2°, 13.06°±0.2°, 13.699°±0.2°, 14.901°±0.2°, 15.562°±0.2°, 16.401°±0.2°, 17.095°±0.2°, 17.3 Diffraction peaks are found at the following positions: 21°±0.2°, 17.76°±0.2°, 18.562°±0.2°, 18.972°±0.2°, 19.2°±0.2°, 19.461°±0.2°, 20.119°±0.2°, 20.463°±0.2°, 20.839°±0.2°, 21.24°±0.2°, 21.58°±0.2°, 22.518°±0.2°, 22.875°±0.2°, 23.421°±0.2°, 23.637°±0.2°, 24.143°±0.2°, and 24.318°±0.2°.

[0301] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form E is basically as shown in the table below.

[0302] [Table 31] .

[0303] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystal form E shows a weight loss of 7.196% during the heating process from 29.88°C to 175.45°C.

[0304] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form E has an endothermic peak with an onset temperature of 112.11°C.

[0305] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form E has an endothermic peak with a peak temperature of 122.45°C.

[0306] In one embodiment, the above 1 equivalent of tartrate crystalline form E 1 The 1H-NMR results show that the molar ratio of tartaric acid to free base in the sample is 1:1, the molar ratio of residual ethanol solvent to free base is 0.88:1, and the weight ratio is 4.85%.

[0307] The present invention provides one equivalent of tartrate crystal form F of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 10.098°±0.2°, 10.579°±0.2°, 18.341°±0.2°, 18.618°±0.2°, 19.36°±0.2°, 20.204°±0.2° and 20.563°±0.2°. [ka]

[0308] In one embodiment, the above 1 equivalent of tartrate crystal form F was subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ was 5.052°±0.2°, 8.502°±0.2°, 9.085°±0.2°, 10.098°±0.2°, 10.579°±0.2°, 11.483°±0.2°, 12.663°±0.2°, 13.13°±0.2°, 13.998°±0.2°, 14.102°±0.2°, 15.172°±0.2°, 15.6°±0.2°, 16.693°±0.2°, 17.076° Diffraction peaks are found at the following positions: °±0.2°, 17.762°±0.2°, 18.341°±0.2°, 18.618°±0.2°, 19.36°±0.2°, 20.204°±0.2°, 20.563°±0.2°, 20.977°±0.2°, 21.997°±0.2°, 22.508°±0.2°, 23.68°±0.2°, 25.14°±0.2°, 25.46°±0.2°, 25.675°±0.2°, 26.401°±0.2°, 28.005°±0.2°, and 28.201°±0.2°.

[0309] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of tartrate crystal form F is basically as shown in the table below.

[0310] [Table 32-1] [Table 32-2] .

[0311] In one embodiment, the thermogravimetric analysis (TGA) curve of the above 1 equivalent of tartrate crystalline form F shows a weight loss of 3.174% during the heating process from 30.17°C to 175.17°C.

[0312] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystalline form F has endothermic peaks with starting temperatures of 30.67°C, 89.32°C, and 142.85°C, respectively.

[0313] In one embodiment, the differential scanning calorimetry curve (DSC) of the above 1 equivalent of tartrate crystal form F has endothermic peaks with peak temperatures of 36.44°C, 118.40°C, and 150.31°C, respectively.

[0314] In one embodiment, the above 1 equivalent of tartrate crystalline form F 1 The 1H-NMR results show that the molar ratio of tartaric acid to free base in the sample is 1:1, the molar ratio of residual methanol solvent to free base is 0.74:1, and the weight ratio is 2.90%.

[0315] The present invention provides one equivalent of citrate crystalline form A of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.656°±0.2°, 13.455°±0.2°, 17.158°±0.2°, 18.093°±0.2°, 18.64°±0.2°, 21.819°±0.2° and 22.916°±0.2°. [ka]

[0316] In one embodiment, the above 1 equivalent of citrate crystal form A is subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ are 4.351°±0.2°, 7.501°±0.2°, 8.656°±0.2°, 9.991°±0.2°, 11.372°±0.2°, 11.663°±0.2°, 12.631°±0.2°, 13.065°±0.2°, 13.455°±0.2°, 13.703°±0.2°, 14.171°±0.2°, 15.113°±0.2°, 15.718°±0.2°, and 17.15 Diffraction peaks are found at the following positions: 8°±0.2°, 17.317°±0.2°, 17.715°±0.2°, 18.093°±0.2°, 18.64°±0.2°, 19.577°±0.2°, 19.77°±0.2°, 20.118°±0.2°, 20.403°±0.2°, 20.805°±0.2°, 21.122°±0.2°, 21.819°±0.2°, 22.916°±0.2°, 23.367°±0.2°, 23.637°±0.2°, 24.236°±0.2°, and 25.379°±0.2°.

[0317] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of citrate crystal form A is basically as shown in the table below.

[0318] [Table 33] .

[0319] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of citrate crystalline form A shows a weight loss of 0.7543% during the heating process from 29.61°C to 150.16°C.

[0320] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of citrate crystal form A has endothermic peaks with starting temperatures of 60.16°C, 151.22°C, 156.20°C, and 167.07°C, respectively.

[0321] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of citrate crystal form A has endothermic peaks with peak temperatures of 95.36°C, 152.85°C, 160.14°C, and 185.35°C, respectively.

[0322] In one embodiment, the above 1 equivalent of citrate crystalline form A 1 The 1H-NMR results indicate that the molar ratio of citrate to free base in the sample is 1:1, showing that no solvent remains.

[0323] The present invention provides one equivalent of citrate crystalline form B of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 15.0928°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.4798°±0.2°, 23.6411°±0.2° and 26.9181°±0.2°. [ka]

[0324] In one embodiment, the above 1 equivalent of citrate crystalline form B has diffraction peaks at positions of 16.8372°±0.2°, 21.4798°±0.2°, and 23.6411°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0325] In one embodiment, the above 1 equivalent of citrate crystalline form B has diffraction peaks at positions of 15.0928°±0.2°, 16.8372°±0.2°, 21.4798°±0.2°, and 23.6411°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0326] In one embodiment, the above 1 equivalent of citrate crystalline form B has diffraction peaks at the positions of 15.0928°±0.2°, 16.8372°±0.2°, 19.194°±0.2°, 21.4798°±0.2°, and 23.6411°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0327] In one embodiment, the above 1 equivalent of citrate crystalline form B has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 15.0928°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.4798°±0.2°, and 23.6411°±0.2°.

[0328] In one embodiment, the above 1 equivalent of citrate crystalline form B has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 15.0928°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.4798°±0.2°, 23.6411°±0.2°, and 26.9181°±0.2°.

[0329] In one embodiment, the above 1 equivalent of citrate crystal form B is subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ is 7.5584°±0.2°, 9.2726°±0.2°, 10.6593°±0.2°, 11.3352°±0.2°, 12.54°±0.2°, 13.5438°±0.2°, 13.7735°±0.2°, 14.0152°±0.2°, 15.0928°±0.2°, 15.4425°±0.2°, 15.628°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°± Diffraction peaks are found at the following positions: 0.2°, 21.1607°±0.2°, 21.4798°±0.2°, 22.0822°±0.2°, 22.7152°±0.2°, 23.6411°±0.2°, 24.0169°±0.2°, 24.6133°±0.2°, 26.9181°±0.2°, 27.5774°±0.2°, 27.9026°±0.2°, 30.3368°±0.2°, 32.439°±0.2°, 33.9973°±0.2°, 34.2994°±0.2°, 34.7631°±0.2°, and 35.1435°±0.2°.

[0330] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of citrate crystal form B is basically as shown in the table below.

[0331] [Table 34] .

[0332] In one embodiment, the X-ray powder diffraction pattern of 1 equivalent of citrate crystal form B is basically as shown in Figure 19.

[0333] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of citrate crystalline form B shows a weight loss of 19.64±0.005% during the heating process from 35.86±3°C to 212.99±3°C.

[0334] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of citrate crystalline form B shows a weight loss of 19.64% during the heating process from 35.86°C to 212.99°C.

[0335] In one embodiment, the thermogravimetric analysis curve of one equivalent of citrate crystal form B is basically as shown in Figure 20.

[0336] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with an onset temperature of 178.23 ± 3°C.

[0337] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with an onset temperature of 178.23°C.

[0338] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with a peak temperature of 180.38 ± 3°C.

[0339] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with a peak temperature of 180.38°C.

[0340] In one embodiment, the differential scanning calorimetry curve of one equivalent of citrate crystal form B is basically as shown in Figure 21.

[0341] In one embodiment, the above 1 equivalent of citrate crystalline form B 1 The 1H-NMR results indicate that the molar ratio of citrate to free base in the sample is 1:1, showing that no solvent remains.

[0342] In one embodiment, the proton nuclear magnetic resonance of one equivalent of citrate crystal form B is as shown in Figure 22.

[0343] In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of citrate crystalline form B shows that the weight increase due to moisture absorption is 0.19% ± 0.005% at 25°C and 80% RH. In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of citrate crystalline form B shows a weight increase due to moisture absorption of 0.19% at 25°C and 80%RH.

[0344] In one embodiment, the dynamic vapor adsorption curve of 1 equivalent of citrate crystalline form B is basically as shown in Figure 23. The present invention further provides a method for producing one equivalent of citrate crystalline form B of the compound represented by formula I, comprising the steps of stirring amorphous form of the compound represented by formula I and citric acid in a solvent at 50°C to obtain a suspension solution, continuing to stir the obtained suspension solution at room temperature to precipitate a solid, and obtaining one equivalent of citrate crystalline form B of the compound represented by formula I, wherein the solvent is tetrahydrofuran, the mass-volume ratio of the solvent to the compound represented by formula I is preferably (10-100 mg):1 mL, more preferably 25 mg:1 mL, the molar ratio of the citric acid to the compound represented by formula I is preferably 1:1, the continuing stirring of the obtained suspension solution at room temperature is preferably carried out at 25°C, and the duration of continuing stirring of the obtained suspension solution at room temperature is preferably 3-5 days, more preferably 4 days.

[0345] In one embodiment, the method for producing 1 equivalent of citrate crystal form B further includes the steps of precipitation of the solid, followed by isolation and drying, thereby obtaining 1 equivalent of citrate crystal form B.

[0346] The present invention provides succinate crystal form A of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 4.499°±0.2°, 11.997°±0.2°, 15.099°±0.2°, 18.02°±0.2°, 20.297°±0.2°, 20.696°±0.2° and 23.059°±0.2°. [ka]

[0347] In one embodiment, the above 1 equivalent of succinate crystal form A was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 4.499°±0.2°, 6.876°±0.2°, 8.773°±0.2°, 8.959°±0.2°, 10.401°±0.2°, 11.997°±0.2°, 13.296°±0.2°, 13.616°±0.2°, 14.006°±0.2°, 14.337°±0.2°, 15.099°±0.2°, 15.944°±0.2°, 16.218°±0.2°, 16.6 Diffraction peaks are found at the following positions: 4°±0.2°, 17.316°±0.2°, 17.556°±0.2°, 18.02°±0.2°, 18.538°±0.2°, 19.117°±0.2°, 19.584°±0.2°, 20.297°±0.2°, 20.696°±0.2°, 20.859°±0.2°, 21.478°±0.2°, 22.08°±0.2°, 22.458°±0.2°, 23.059°±0.2°, 23.801°±0.2°, 24.066°±0.2°, and 24.3°±0.2°.

[0348] In one embodiment, the X-ray powder diffraction pattern analysis data for one equivalent of succinate crystal form A is basically as shown in the table below.

[0349] [Table 35] .

[0350] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form A shows a weight loss of 0.2518% during the heating process from 38.71°C to 150.16°C.

[0351] In one embodiment, the differential scanning calorimetry (DSC) curves of one equivalent of succinate crystal form A have endothermic peaks with starting temperatures of 167.37°C.

[0352] In one embodiment, the differential scanning calorimetry curve (DSC) of the succinate crystal form A in one equivalent has an endothermic peak with a peak temperature of 168.66°C.

[0353] In one embodiment, the above 1 equivalent of succinate crystalline form A 1 The 1H-NMR results indicate that the molar ratio of succinic acid to free base in the sample is 1:1, showing that no solvent remains.

[0354] The present invention provides succinate crystal form B of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.7986°±0.2°, 9.6353°±0.2°, 15.0967°±0.2°, 17.6804°±0.2°, 17.8403°±0.2°, 19.4381°±0.2° and 20.9405°±0.2°. [ka]

[0355] In one embodiment, the above 1 equivalent of succinate crystal form B was subjected to Cu-Kα radiation, and the X-ray powder diffraction pattern represented by 2θ was 4.413°±0.2°, 8.5426°±0.2°, 8.7986°±0.2°, 9.6353°±0.2°, 9.8769°±0.2°, 10.5788°±0.2°, 11.6749°±0.2°, 12.1356°±0.2°, 12.419°±0.2°, 12.731°±0.2°, 12.9957°±0.2°, 13.1995°±0.2°, 13.6583°±0.2°, 13.897°±0. Diffraction peaks are found at the following positions: 0.2°, 14.7617°±0.2°, 15.0967°±0.2°, 16.0212°±0.2°, 16.4598°±0.2°, 17.0656°±0.2°, 17.4649°±0.2°, 17.6804°±0.2°, 17.8403°±0.2°, 19.4381°±0.2°, 20.9405°±0.2°, 22.097°±0.2°, 24.5793°±0.2°, 25.176°±0.2°, 25.6151°±0.2°, 25.8172°±0.2°, and 26.6656°±0.2°.

[0356] In one embodiment, the X-ray powder diffraction pattern analysis data for one equivalent of succinate crystal form B is basically as shown in the table below.

[0357] [Table 36-1] [Table 36-2] .

[0358] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form B shows a weight loss of 4.942% during the heating process from 38.51°C to 137.03°C.

[0359] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of succinate crystal form B has endothermic peaks with starting temperatures of 93.69°C, 141.56°C, 176.96°C, and 188.31°C, respectively.

[0360] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of succinate crystal form B has endothermic peaks with peak temperatures of 114.14°C, 151.48°C, 179.76°C, and 219.49°C, respectively.

[0361] In one embodiment, the above 1 equivalent of succinate crystalline form B 1 The 1H-NMR results show that the molar ratio of succinic acid to free base in the sample is 1:1, the molar ratio of residual tetrahydrofuran solvent to free base is 0.75:1, and the weight ratio is 6.7%.

[0362] The present invention provides one equivalent of succinate crystal form C of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 8.8106°±0.2°, 9.8327°±0.2°, 10.5744°±0.2°, 17.6389°±0.2°, 17.8746°±0.2°, 19.5814°±0.2° and 21.1774°±0.2°. [ka]

[0363] In one embodiment, the above 1 equivalent of succinate crystalline form C was subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ were 4.4254°±0.2°, 8.1567°±0.2°, 8.8106°±0.2°, 9.8327°±0.2°, 10.5744°±0.2°, 10.9741°±0.2°, 12.0169°±0.2°, 12.7766°±0.2°, 13.2101°±0.2°, 14.5967°±0.2°, 14.9064°±0.2°, 15.475°±0.2°, 16.3197°±0.2°, and 17.6389°. Diffraction peaks are found at the following positions: ±0.2°, 17.8746°±0.2°, 18.541°±0.2°, 19.0788°±0.2°, 19.5814°±0.2°, 19.9794°±0.2°, 20.2206°±0.2°, 20.6426°±0.2°, 20.7938°±0.2°, 21.1774°±0.2°, 21.3595°±0.2°, 22.0773°±0.2°, 22.8039°±0.2°, 22.9977°±0.2°, 23.7612°±0.2°, 23.9994°±0.2°, and 24.1298°±0.2°.

[0364] In one embodiment, the X-ray powder diffraction pattern analysis data for one equivalent of succinate crystal form C is basically as shown in the table below.

[0365] [Table 37] .

[0366] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form C shows a weight loss of 5.472% during the heating process from 38.13°C to 125.09°C.

[0367] In one embodiment, the differential scanning calorimetry curve (DSC) of the succinate crystalline form C of one equivalent has endothermic peaks with starting temperatures of 98.60°C, 147.67°C, 162.11°C, and 181.14°C, respectively.

[0368] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of succinate crystalline form C has endothermic peaks with peak temperatures of 120.14°C, 150.58°C, 164.99°C, and 182.19°C, respectively.

[0369] In one embodiment, the above 1 equivalent of succinate crystalline form C 1 The 1H-NMR results show that the molar ratio of succinic acid to free base in the sample is 1:1, the molar ratio of residual 1,4-dioxane solvent to free base is 0.90:1, and the weight ratio is 9.5%.

[0370] The present invention provides succinate crystal form D of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 15.715°±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2° and 20.218°±0.2°. [ka]

[0371] In one embodiment, the succinate crystal form D of 1 equivalent has diffraction peaks at positions of 17.778°±0.2°, 18.698°±0.2°, and 20.079°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0372] In one embodiment, the succinate crystal form D of 1 equivalent has diffraction peaks at positions of 17.778°±0.2°, 18.698°±0.2°, 18.86°±0.2°, and 20.079°±0.2° in its X-ray powder diffraction pattern, represented by 2θ, using Cu-Kα radiation.

[0373] In one embodiment, the succinate crystal form D of 1 equivalent has diffraction peaks at positions of 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, and 20.079°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation.

[0374] In one embodiment, the succinate crystal form D of 1 equivalent has diffraction peaks at the following positions when the X-ray powder diffraction pattern, represented by 2θ, is measured using Cu-Kα radiation: 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2°, and 20.218°±0.2°.

[0375] In one embodiment, the succinate crystal form D of 1 equivalent has diffraction peaks at the following positions in the X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation: 15.715°±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2°, and 20.218°±0.2°.

[0376] In one embodiment, the above 1 equivalent of succinate crystal form D is subjected to Cu-Kα radiation, and the X-ray powder diffraction patterns represented by 2θ are 5.255°±0.2°, 8.059°±0.2°, 9.338°±0.2°, 9.941°±0.2°, 10.472°±0.2°, 11.401°±0.2°, 12.483°±0.2°, 12.86°±0.2°, 13.203°±0.2°, 13.901°±0.2°, 14.72°±0.2°, 15.038°±0.2°, 15.715°±0.2°, and 16.36°. Diffraction peaks are found at the following positions: ±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 19.421°±0.2°, 19.719°±0.2°, 20.079°±0.2°, 20.218°±0.2°, 20.542°±0.2°, 20.862°±0.2°, 20.997°±0.2°, 21.579°±0.2°, 22.461°±0.2°, 22.679°±0.2°, 22.899°±0.2°, and 23.222°±0.2°.

[0377] In one embodiment, the X-ray powder diffraction pattern analysis data for 1 equivalent of succinate crystal form D is basically as shown in the table below.

[0378] [Table 38] .

[0379] In one embodiment, the X-ray powder diffraction pattern of one equivalent of succinate crystal form D is basically as shown in Figure 24.

[0380] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form D shows a weight loss of 0.1218±0.005% during the heating process from 30.10±3℃ to 150.15±3℃.

[0381] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form D shows a weight loss of 0.1218% during the heating process from 30.10°C to 150.15°C.

[0382] In one embodiment, the thermogravimetric analysis curve of the succinate crystal form D in one equivalent is basically as shown in Figure 25.

[0383] In one embodiment, the differential scanning calorimetry (DSC) curves of one equivalent of succinate crystal form D have endothermic peaks with starting temperatures of 184.29 ± 3°C.

[0384] In one embodiment, the differential scanning calorimetry (DSC) curves of one equivalent of succinate crystal form D have endothermic peaks with starting temperatures of 184.29°C.

[0385] In one embodiment, the differential scanning calorimetry curve (DSC) of the succinate crystal form D of 1 equivalent has an endothermic peak with a peak temperature of 185.23 ± 3°C.

[0386] In one embodiment, the differential scanning calorimetry curve (DSC) of the succinate crystal form D of 1 equivalent has an endothermic peak with a peak temperature of 185.23°C.

[0387] In one embodiment, the differential scanning calorimetry curve of the succinate crystal form D of one equivalent is basically as shown in Figure 26.

[0388] In one embodiment, the above 1 equivalent of succinate crystalline form D 1 The 1H-NMR results indicate that the molar ratio of succinic acid to free base in the sample is 1:1, showing that no solvent remains.

[0389] In one embodiment, the proton nuclear magnetic resonance of the succinate crystal form D in one equivalent is basically as shown in Figure 27.

[0390] In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of succinate crystalline form D shows that the weight increase due to moisture absorption is 0.19 ± 0.005% at 25°C and 80% RH. In one embodiment, the dynamic vapor adsorption curve (DVS) of 1 equivalent of succinate crystalline form D shows a weight increase due to moisture absorption of 0.19% at 25°C and 80%RH.

[0391] In one embodiment, the dynamic vapor adsorption curve of the succinate crystalline form D in one equivalent is basically as shown in Figure 28.

[0392] The present invention further provides a method for producing one equivalent of succinate crystalline form D of the compound represented by formula I, comprising the steps of stirring amorphous and succinic acid of the compound represented by formula I in a solvent at 50°C to obtain a suspension solution, continuing to stir the obtained suspension solution at room temperature to precipitate a solid, thereby obtaining one equivalent of succinate crystalline form D of the compound represented by formula I, wherein the solvent is ethanol, the mass-volume ratio of the solvent to the compound represented by formula I is preferably (10-100 mg):1 mL, more preferably 25 mg:1 mL, the molar ratio of succinic acid to the compound represented by formula I is preferably 1:1, the continuing stirring of the obtained suspension solution at room temperature is preferably carried out at 25°C, and the duration of continuing stirring of the obtained suspension solution at room temperature is preferably 3-5 days, more preferably 4 days.

[0393] In one embodiment, the method for producing 1 equivalent of succinate crystalline form D further includes the steps of precipitation of the solid, isolation, and drying to obtain 1 equivalent of succinate crystalline form D.

[0394] The present invention provides a phosphate crystalline form E of one equivalent of the compound represented by formula I, the X-ray powder diffraction pattern (XRPD) thereof having at least three, at least four, at least five, at least six or at least seven characteristic peaks at 2θ angles of 6.558°±0.2°, 8.841°±0.2°, 13.524°±0.2°, 18.241°±0.2°, 18.86°±0.2°, 20.246°±0.2° and 28.756°±0.2°. [ka]

[0395] In one embodiment, the above 1 equivalent of phosphate crystal form E, when subjected to Cu-Kα radiation, exhibits X-ray powder diffraction patterns represented by 2θ of 4.241°±0.2°, 6.558°±0.2°, 8.563°±0.2°, 8.841°±0.2°, 9.236°±0.2°, 9.663°±0.2°, 11.539°±0.2°, 11.8°±0.2°, 12.262°±0.2°, 12.558°±0.2°, 13.06°±0.2°, 13.524°±0.2°, 14.943°±0.2°, and 17.18°. Diffraction peaks are found at the following positions: ±0.2°, 17.56°±0.2°, 18.084°±0.2°, 18.241°±0.2°, 18.86°±0.2°, 19.219°±0.2°, 19.484°±0.2°, 20.246°±0.2°, 23.124°±0.2°, 24.926°±0.2°, 25.221°±0.2°, 26.143°±0.2°, 28.756°±0.2°, 29.6°±0.2°, 30.543°±0.2°, 31.24°±0.2°, and 31.644°±0.2°.

[0396] In one embodiment, the X-ray powder diffraction pattern analysis data for the above 1 equivalent of phosphate crystal form E is basically as shown in the table below.

[0397] [Table 39] .

[0398] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of phosphate crystalline form E shows a weight loss of 0.6794% during the heating process from 30.15°C to 125.70°C.

[0399] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of phosphate crystal form E has endothermic peaks with starting temperatures of 160.90°C and 205.05°C, respectively.

[0400] In one embodiment, the differential scanning calorimetry (DSC) curve of one equivalent of phosphate crystal form E has endothermic peaks with peak temperatures of 167.60°C and 208.15°C, respectively.

[0401] In one embodiment, the above 1 equivalent of phosphate crystalline form E 1 The 1H-NMR results show that the molar ratio of residual ethanol solvent to free base is 0.14:1, and the weight ratio is 0.86%.

[0402] The present invention provides one equivalent of hydrochloride crystalline form A of the compound represented by formula I, and its X-ray powder diffraction pattern (XRPD), when using Cu-Kα radiation, is expressed as follows: 5.778°±0.2°, 8.463°±0.2°, 9.861°±0.2°, 10.416°±0.2°, 10.759°±0.2°, 12.215°±0.2°, 13.722°±0.2°, 14.12°±0.2°, 15.182°±0.2°, 15.539°±0.2°, 15.977°±0.2°, 16.326°±0.2°, 16.581° Diffraction peaks are found at the following positions: °±0.2°, 16.92°±0.2°, 17.297°±0.2°, 17.621°±0.2°, 17.859°±0.2°, 18.562°±0.2°, 19.157°±0.2°, 19.742°±0.2°, 20.382°±0.2°, 20.803°±0.2°, 21.355°±0.2°, 21.618°±0.2°, 22.161°±0.2°, 22.338°±0.2°, 22.915°±0.2°, 23.14°±0.2°, 23.361°±0.2°, and 23.638°±0.2°.

[0403] In one embodiment, the thermogravimetric analysis (TGA) curve of one equivalent of hydrochloride crystalline form A shows a weight loss of 0.2462% during the heating process from 20.93°C to 200.71°C.

[0404] In one embodiment, the differential scanning calorimetry curve (DSC) of one equivalent of hydrochloride crystalline form A has endothermic peaks with starting temperatures of 267.00°C and 272.57°C.

[0405] In one embodiment, the dynamic vapor adsorption curve (DVS) of one equivalent of hydrochloride crystalline form A shows a weight increase of 0.15% due to moisture absorption at 25°C and 80%RH.

[0406] The present invention further provides a pharmaceutical composition comprising one equivalent of methanesulfonate crystal form A of the compound represented by formula I, crystal form D of the compound represented by formula I, one equivalent of maleate crystal form A of the compound represented by formula I, one equivalent of tartrate crystal form C of the compound represented by formula I, one equivalent of citrate crystal form B of the compound represented by formula I, one equivalent of succinate crystal form D of the compound represented by formula I, and one or more pharmaceutically acceptable excipients.

[0407] The present invention further provides the use of substance X in the production of an ALK inhibitor, wherein substance X is one equivalent of methanesulfonate crystal form A of the compound represented by formula I, crystal form D of the compound represented by formula I, one equivalent of maleate crystal form A of the compound represented by formula I, one equivalent of tartrate crystal form C of the compound represented by formula I, one equivalent of citrate crystal form B of the compound represented by formula I, one equivalent of succinate crystal form D of the compound represented by formula I, or the above pharmaceutical composition.

[0408] The present invention further provides the use of substance X in the treatment or prevention of cancer, wherein substance X is one equivalent of methanesulfonate crystalline form A of the compound represented by formula I, crystalline form D of the compound represented by formula I, one equivalent of maleate crystalline form A of the compound represented by formula I, one equivalent of tartrate crystalline form C of the compound represented by formula I, one equivalent of citrate crystalline form B of the compound represented by formula I, one equivalent of succinate crystalline form D of the compound represented by formula I, or the above pharmaceutical composition, wherein preferably the cancer is selected from the group consisting of anaplastic large cell lymphoma, non-small cell lung cancer, diffuse large B-cell lymphoma, inflammatory myofibroblastoma, neuroblastoma, anaplastic thyroid cancer, rhabdomyosarcoma, breast cancer, colorectal cancer, esophageal squamous cell carcinoma, and renal cell carcinoma.

[0409] By arbitrarily combining the above preferred conditions without deviating from the common sense of the field, relatively suitable examples of the present invention can be obtained.

[0410] The reagents and raw materials used in this invention are all commercially available.

[0411] A positive and progressive effect of the present invention is that it provides a crystalline form of an ALK inhibitor or its salt or solvate. The crystalline form has one or more advantages, such as high crystallinity, good stability, slight hygroscopicity, high solubility, and high bioavailability. [Brief explanation of the drawing]

[0412] [Figure 1] This is the XRPD pattern of crystalline form D of the compound represented by formula I. [Figure 2] This is the TGA pattern of crystalline form D of the compound represented by formula I. [Figure 3] This is the DSC pattern of crystalline form D of the compound represented by formula I. [Figure 4] This is the DVS pattern of crystalline form D of the compound represented by formula I. [Figure 5] This is the XRPD pattern of one equivalent of methanesulfonate crystal form A of the compound represented by formula I. [Figure 6] This is the TGA pattern of one equivalent of methanesulfonate crystal form A of the compound represented by formula I. [Figure 7] This is the DSC pattern of one equivalent of methanesulfonate crystal form A of the compound represented by formula I. [Figure 8] This is the 1H-NMR pattern of one equivalent of the methanesulfonate crystal form A of the compound represented by formula I. [Figure 9] This is the DVS pattern of one equivalent of methanesulfonate crystal form A of the compound represented by formula I. [Figure 10] This is the XRPD pattern of one equivalent of the maleate crystal form A of the compound represented by formula I. [Figure 11] This is the TGA pattern of one equivalent of maleate crystal form A of the compound represented by formula I. [Figure 12] This is the DSC pattern of one equivalent of the maleate crystalline form A of the compound represented by formula I. [Figure 13] This is the 1H-NMR pattern of one equivalent of the maleate crystal form A of the compound represented by formula I. [Figure 14] This is the DVS pattern of one equivalent of maleate crystal form A of the compound represented by formula I. [Figure 15] This is the XRPD pattern of one equivalent of the tartrate salt crystal form C of the compound represented by formula I. [Figure 16] This is the TGA pattern of one equivalent of the tartrate salt crystal form C of the compound represented by formula I. [Figure 17] This is the DSC pattern of one equivalent of the tartrate salt crystal form C of the compound represented by formula I. [Figure 18] This is the 1H-NMR pattern of one equivalent of the tartrate salt crystal form C of the compound represented by formula I. [Figure 19] This is the XRPD pattern of one equivalent of the citrate crystalline form B of the compound represented by formula I. [Figure 20] This is the TGA pattern of one equivalent of the citrate crystal form B of the compound represented by formula I. [Figure 21] This is the DSC pattern of one equivalent of the citrate crystalline form B of the compound represented by formula I. [Figure 22] This is the 1H-NMR pattern of one equivalent of the citrate crystal form B of the compound represented by formula I. [Figure 23] This is the DVS pattern of one equivalent of the citrate crystal form B of the compound represented by formula I. [Figure 24] This is the XRPD pattern of one equivalent of succinate crystal form D of the compound represented by formula I. [Figure 25] This is the TGA pattern of succinate crystal form D of one equivalent of the compound represented by formula I. [Figure 26] This is the DSC pattern of one equivalent of succinate crystal form D of the compound represented by formula I. [Figure 27] This is the 1H-NMR pattern of succinate crystal form D of one equivalent of the compound represented by formula I. [Figure 28] This is the DVS pattern of one equivalent of succinate crystal form D of the compound represented by formula I. [Modes for carrying out the invention]

[0413] In the following examples, the experimental methods described are carried out under conventional conditions or conventional measurement conditions, and the compounds used in the examples are obtained commercially or by homemade methods. In particular, the preparation of the amorphous form of the compound represented by formula I may refer to the method described in WO2018044767A1.

[0414] All solvents used in this invention are commercially available and can be used without further purification.

[0415] Unless otherwise specified, in the present invention, each example is carried out at room temperature, which is typically 20-30°C, preferably 25°C.

[0416] Unless otherwise specified, all acid salt crystal forms in the examples are 1 equivalent acid salt crystal forms.

[0417] The English abbreviations and their corresponding Japanese terms for the solvents selected in this invention are as follows:

[0418] [Table 40]

[0419] In this invention, the parameters for XRPD measurement were set as follows.

[0420] [Table 41]

[0421] In this invention, the parameters for DVS measurement were set as follows.

[0422] [Table 42]

[0423] TGA and DSC patterns were collected using a TA Q5500 thermogravimetric analyzer and a TA Q2500 differential scanning calorimetry analyzer, respectively, with the parameters set as follows.

[0424] [Table 43]

[0425] In this invention, the parameters for mDSC measurement were set as follows: amplitude: 1.0°C, modulation period: 120 seconds, heating rate: 2°C / min, and temperature range: 30°C to the set endpoint temperature.

[0426] In the present invention, 1 ¹H-NMR was measured using Qone-WNMR-I-AS400, with the following parameters: hydrogen spectrum, solvent: deuterated dimethyl sulfoxide, number of scans: 16, temperature: room temperature, magnetic field strength: 400 MHz.

[0427] In this invention, the parameters for HPLC (high-performance liquid chromatography) measurement were set as follows.

[0428] [Table 44-1] [Table 44-2]

[0429] Example 1 Preparation of crystalline form A of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of methanol was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0430] Example 2 Preparation of crystalline form B of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of ethanol was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0431] Example 3 Preparation of crystalline form C of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of isopropanol was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0432] Example 4 Preparation of crystalline form D of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.6 mL of acetonitrile was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Characterization of crystalline form D of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 1. 2) The results of the TGA characterization are shown in Figure 2. 3) The results of the DSC characterization are shown in Figure 3. 4) The results of the DVS characterization are shown in Figure 4.

[0433] Example 5 Preparation of crystalline form E of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of acetone was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0434] Example 6 Preparation of crystalline form F of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.1 mL of tetrahydrofuran was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0435] Example 7 Method for producing crystalline form G of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.2 mL of 1,4-dioxane was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0436] Example 8 Method for producing crystalline form H of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of pure water was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0437] Example 9 Method for producing crystalline form I of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of methanol was added, and the suspension was beaten at 50°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0438] Example 10 Method for producing crystalline form J of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of water was added, and the suspension was beaten at 50°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0439] Example 11 Method for producing crystalline form K of the compound represented by formula I: 20 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 1.2 mL of methanol / dichloromethane (5:1, v / v) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The supernatant was then taken and allowed to evaporate naturally at room temperature.

[0440] Example 12 Method for producing crystalline form L of the compound represented by formula I: 20 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 1.2 mL of ethanol / dichloromethane (5:1, v / v) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The supernatant was then taken and allowed to evaporate naturally at room temperature.

[0441] Example 13 Method for producing crystalline form M of the compound represented by formula I: 20 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 1.2 mL of isopropanol / dichloromethane (5:1, v / v) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The supernatant was then taken and allowed to evaporate naturally at room temperature.

[0442] Example 14 Method for producing crystalline form N of the compound represented by formula I: 20 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.5 mL of 1,4-dioxane was added, and the mixture was filtered through a 0.22 μm nylon filter head. The supernatant was then taken and allowed to evaporate naturally at room temperature.

[0443] Example 15 Method for producing crystalline form O of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.4 mL of methanol / dichloromethane (3:1, v / v) was added, the mixture was stirred at 50°C for 1 hour, filtered through a 0.22 μm nylon filter head to obtain a clarified solution, left in a refrigerator at 4°C until a solid precipitate formed, the supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0444] Example 16 Method for producing crystalline form P of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.3 mL of tetrahydrofuran was added, and the mixture was stirred at 25°C until the sample dissolved. The mixture was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, 1.2 mL of methanol was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0445] Example 17 Method for producing crystalline form Q of the compound represented by formula I: 50 mg of amorphous material of the compound represented by formula I was placed in a 2 mL glass bottle, 0.3 mL of tetrahydrofuran was added, and the mixture was stirred at 25°C until the sample dissolved. The mixture was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, 1.2 mL of n-heptane was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0446] Example 18 Method for producing crystalline form R of the compound represented by formula I: 50 mg of amorphous form of the compound represented by formula I was placed in a 2 mL glass bottle, 0.3 mL of tetrahydrofuran was added, and the mixture was stirred at 25°C until the sample dissolved. The mixture was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, 1.2 mL of pure water was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0447] Example 19: Screening test for free base polycrystalline form Suspension method Preparation method: 50 mg of amorphous compound represented by formula I was weighed, a fixed amount of the corresponding solvent (approximately 0.4 mL) was added to prepare a suspension, and the suspension was stirred for 3 days in the dark under conditions of 25°C (or 50°C). The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). The resulting solid was collected and subjected to XRPD measurement. The results are shown below.

[0448] [Table 45-1] [Table 45-2]

[0449] Volatilization method Manufacturing method: Approximately 20 mg of the amorphous form of the compound represented by formula I is weighed into each 2 mL vial, a fixed amount of the corresponding solvent (approximately 1 mL) is added, and the mixture is filtered through a 0.22 μm nylon filter head. The resulting filtrate is then processed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement. The results are shown below.

[0450] [Table 46]

[0451] Poor solvent method Preparation method: 50 mg of amorphous compound represented by formula I was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of poor solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). The resulting solid was collected and subjected to XRPD measurement. The results are shown below.

[0452] [Table 47]

[0453] heating cooling method Preparation method: Approximately 50 mg of amorphous compound represented by formula I was weighed into a glass bottle, a fixed amount of solvent (approximately 1 mL) was added, and the mixture was stirred at 50°C for 1 hour to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, and the mixture was left in a refrigerator at 4°C until a solid precipitate formed. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). The resulting solid was collected and subjected to XRPD measurement. The results are shown below.

[0454] [Table 48-1] [Table 48-2]

[0455] Example 20 Method for producing one equivalent of methanesulfonate crystalline form A of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I and methanesulfonic acid (acid-base molar ratio of 1:1) were stirred in 4 mL of tetrahydrofuran at room temperature for 3 days to obtain the product. Characterization of one equivalent of methanesulfonate crystalline form A of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 5. 2) The results of the TGA characterization are shown in Figure 6. 3) The results of the DSC characterization are shown in Figure 7. 4) That 1 The results of the 1H-NMR characterization are shown in Figure 8, indicating that the molar ratio of methanesulfonic acid to free base in the sample is 1:1. 5) The results of the DVS characterization are shown in Figure 9.

[0456] Example 21 Method for producing one equivalent of methanesulfonate crystal form B of the compound shown in formula I: 50 mg of one equivalent of methanesulfonate crystal form A was placed in a 2 mL glass bottle, 0.2 mL of methanol / water (50:50, v / v) was added, and the suspension was beaten at 25°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0457] Example 22 Method for producing one equivalent of methanesulfonate crystal form C of the compound shown in formula I: 50 mg of one equivalent of methanesulfonate crystal form A was placed in a 2 mL glass bottle, 0.2 mL of acetonitrile was added, and the suspension was beaten at 50°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0458] Example 23 Method for producing one equivalent of methanesulfonate crystal form D of the compound shown in formula I: 50 mg of one equivalent of methanesulfonate crystal form A was placed in a 2 mL glass bottle, 0.2 mL of acetone was added, and the suspension was beaten at 50°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0459] Example 24 Method for producing one equivalent of methanesulfonate crystal form E of the compound shown in formula I: 50 mg of one equivalent of methanesulfonate crystal form A was placed in a 2 mL glass bottle, 0.2 mL of 1,4-dioxane was added, and the suspension was beaten at 50°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0460] Example 25 Method for producing one equivalent of methanesulfonate crystalline form F of the compound represented by formula I: Approximately 100 mg of amorphous methanesulfonate of the compound represented by formula I was weighed into a glass bottle, a fixed amount (approximately 4 mL) of 1,4-dioxane was added at 50°C, and methanesulfonic acid was added (the molar ratio of acid to base was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0461] Example 26 Screening test for polycrystalline methanesulfonates Unless otherwise specified, all crystalline forms mentioned in Example 26 were 1 equivalent methanesulfonate crystalline forms. Suspension method Approximately 50 mg of methanesulfonate crystalline form A of the compound represented by formula I was weighed, and a fixed amount of the corresponding solvent (approximately 0.2 mL) was added to prepare a suspension. The suspension was stirred for 3 days in the dark under conditions of 25°C (or 50°C / 80°C), the supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). See the table below for the results.

[0462] [Table 49-1] [Table 49-2]

[0463] Volatilization method A total of 15 slow volatilization tests were set up using different solvent systems. Approximately 20 mg of one equivalent of methanesulfonate crystalline form A of the compound represented by formula I was weighed into 2 mL vials, a fixed amount (approximately 1 mL) of the corresponding solvent was added, and the mixture was filtered through a 0.22 μm nylon filter head. The resulting filtrate was then analyzed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement; see the table below for the results.

[0464] [Table 50]

[0465] Inverse solvent method Approximately 50 mg of methanesulfonate crystalline form A of the compound represented by formula I was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of reverse solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0466] [Table 51]

[0467] heating cooling method Approximately 50 mg of methanesulfonate crystalline form A of the compound represented by formula I was weighed into a glass bottle, a fixed amount of solvent (approximately 1 mL) was added, and the mixture was stirred at 50°C for 1 hour to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, and the mixture was left in a refrigerator at 4°C until a solid precipitate formed. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0468] [Table 52]

[0469] Diffusion method Approximately 50 mg of methanesulfonate crystalline form A of the compound represented by formula I was weighed into a glass bottle, a fixed amount of solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. The vial containing the clarified solution was placed in a large bottle containing four times the amount of reverse solvent (which has a certain degree of volatility and can volatilize into a good solvent). The large bottle was sealed and left to stand at room temperature. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0470] [Table 53]

[0471] Screening tests of polycrystalline methanesulfonates showed that, in the suspension method, one equivalent of methanesulfonate crystalline form A exhibited better stability in ethanol, isopropanol, ethyl acetate, isopropyl acetate, methyl tert-butyl ether, tetrahydrofuran, N-methylpyrrolidone, methyl acetate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, toluene, or n-heptane. At 25-85°C, one equivalent of methanesulfonate crystalline form A was stirred in toluene or n-heptane and remained stable. At 25-50°C, one equivalent of methanesulfonate crystalline form A was stirred in ethanol, isopropanol, ethyl acetate, isopropyl acetate, methyl tert-butyl ether, tetrahydrofuran, N-methylpyrrolidone, methyl acetate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, toluene, or n-heptane and remained stable.

[0472] Example 27 Method for producing one equivalent of maleate crystalline form A of the compound represented by formula I: Approximately 955.9 mg of maleic acid was weighed into a 12 mL glass bottle, and 7.5 mL of ethanol was added to obtain a clarified solution, which was prepared for use. Approximately 5 g of amorphous form of the compound represented by formula I was weighed into a 20 mL glass bottle. 12.5 mL of ethanol and maleic acid ethanol solution were added at 50°C. The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 7 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Characterization of one equivalent of maleate crystal form A of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 10. 2) The results of the TGA characterization are shown in Figure 11. 3) The results of the DSC characterization are shown in Figure 12. 4) That 1 The results of the 1H-NMR characterization are shown in Figure 13, indicating that the molar ratio of maleic acid to free base in the sample is 1:1, and that no solvent remains. 5) The results of the DVS characterization are shown in Figure 14. The DVS results indicate that the sample showed a weight increase of 0.11% due to moisture absorption at 80% RH, indicating that it was not hygroscopic and that the crystal shape did not change before and after moisture absorption.

[0473] Example 28 Method for producing one equivalent of maleate crystalline form B of the compound shown in formula I: 50 mg of one equivalent of maleate crystalline form A was placed in an 8 mL glass bottle, 1 mL of dichloromethane was added, and the mixture was stirred at 25°C until the sample dissolved. The mixture was filtered through a 0.22 μm nylon filter head to obtain a clarified solution, 4 mL of acetone was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0474] Example 29: Screening test of polycrystalline maleate salts Unless otherwise specified, all crystalline forms mentioned in Example 29 were maleate crystalline forms at 1 equivalent. Suspension method Approximately 50 mg of one equivalent of maleate crystalline form A of the compound represented by formula I was weighed, and a fixed amount of the corresponding solvent (approximately 0.2 mL) was added to prepare a suspension. The suspension was stirred for 3 days in the dark under conditions of 25°C (or 50°C), the supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). See the table below for the results.

[0475] Table 86 Screening test results for maleate polycrystalline salts - suspension method [Table 54-1] [Table 54-2]

[0476] Volatilization method A total of 10 slow volatilization tests were set up using different solvent systems. Approximately 20 mg of one equivalent of the compound represented by formula I, maleate crystalline form A, was weighed into a 2 mL vial, a fixed amount of the corresponding solvent (approximately 1 mL) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The resulting filtrate was then processed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement; see the table below for the results.

[0477] [Table 55]

[0478] Inverse solvent method Approximately 50 mg of maleate crystalline form A was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of reverse solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0479] [Table 56]

[0480] Screening tests of the polycrystalline maleate salts showed that, in a suspension method, one equivalent of maleate crystalline form A exhibited better stability in ethanol, isopropanol, acetone, ethyl acetate, isopropyl acetate, methyl tert-butyl ether, dichloromethane, tetrahydrofuran, toluene, n-heptane, dioxane, methyl acetate, 2-methyltetrahydrofuran, cyclohexane, n-hexane, methyl ethyl ketone, or methyl isobutyl ketone. At 25-50°C, one equivalent of maleate crystalline form A was stirred in the above solvents and remained stable.

[0481] Example 30 Method for producing 1 equivalent of tartrate crystalline form A of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of ethanol was added at 50°C, and tartaric acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0482] Example 31 Method for producing 1 equivalent of tartrate crystalline form B of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of tetrahydrofuran was added at 50°C, and tartaric acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0483] Example 32 Method for producing one equivalent of tartrate crystal form C of the compound shown in formula I: 50 mg of one equivalent of tartrate crystal form B was placed in a 2 mL glass bottle, 0.2 mL of acetonitrile was added, and the suspension was beaten at 40°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Characterization of one equivalent of tartrate crystal form C of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 15. 2) The results of the TGA characterization are shown in Figure 16. 3) The results of the DSC characterization are shown in Figure 17. 4) That 1 The results of the 1H-NMR characterization are shown in Figure 18, indicating that the molar ratio of tartaric acid to free base in the sample was 1:1, and that no solvent remained.

[0484] Example 33 Method for producing one equivalent of tartrate crystal form D of the compound shown in formula I: 50 mg of one equivalent of tartrate crystal form B was placed in a 2 mL glass bottle, 0.2 mL of ethyl acetate was added, and the suspension was beaten at 40°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0485] Example 34 Method for producing one equivalent of tartrate crystal form E of the compound shown in formula I: 50 mg of one equivalent of tartrate crystal form B was placed in a 2 mL glass bottle, 0.2 mL of ethanol was added, and the suspension was beaten at 40°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0486] Example 35 Method for producing one equivalent of tartrate crystal form F of the compound shown in formula I: 50 mg of one equivalent of tartrate crystal form B was placed in a 2 mL glass bottle, 0.2 mL of methanol was added, and the suspension was beaten at 40°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0487] Example 36: Screening of polycrystalline tartrates Unless otherwise specified, all crystalline forms mentioned in Example 36 were 1 equivalent tartrate crystalline forms. Suspension method Approximately 50 mg of 1 equivalent of tartrate crystalline form B of the compound represented by formula I was weighed, and 0.2 mL of the corresponding solvent was added to prepare a suspension. The suspension was stirred for 3 days under light protection at 40°C, the supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). See the table below for the results.

[0488] [Table 57-1] [Table 57-2]

[0489] Volatilization method Three slow volatilization tests were conducted using different solvent systems. Approximately 20 mg of one equivalent of the compound represented by formula I, tartrate crystalline form B, was weighed into each 2 mL vial. A fixed amount of the corresponding solvent (approximately 1 mL) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The resulting filtrate was then processed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement; see the table below for the results.

[0490] [Table 58]

[0491] Inverse solvent method Approximately 50 mg of one equivalent of tartrate crystalline form B of the compound represented by formula I was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of reverse solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0492] [Table 59]

[0493] Screening tests of one equivalent of polycrystalline tartrate showed that, in suspension, one equivalent of crystalline tartrate B exhibited better stability in acetone, tetrahydrofuran, n-heptane, or dioxane. At 40°C, one equivalent of crystalline tartrate B was stirred in the above crystalline forms, and crystalline tartrate B remained stable.

[0494] Example 37 Method for producing one equivalent of citrate crystalline form A of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of ethanol was added at 50°C, and citric acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0495] Example 38 Method for producing one equivalent of citrate crystalline form B of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of tetrahydrofuran was added at 50°C, and citric acid was added (acid-base molar ratio 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Characterization of one equivalent of the citrate crystalline form B of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 19. 2) The results of the TGA characterization are shown in Figure 20. 3) The results of the DSC characterization are shown in Figure 21. 4) That 1 The results of the 1H-NMR characterization are shown in Figure 22, indicating that the molar ratio of citrate to free base in the sample is 1:1, and that no solvent remains. 5) The results of the DVS characterization are shown in Figure 23.

[0496] Example 39: Screening of polycrystalline citrates Unless otherwise specified, all crystalline forms mentioned in Example 39 were 1 equivalent citrate crystalline forms. Suspension method Approximately 50 mg of one equivalent of citrate crystalline form B of the compound represented by formula I was weighed, and 0.2 mL of the corresponding solvent was added to prepare a suspension. The suspension was stirred for 3 days under light protection at 40°C, the supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). See the table below for the results.

[0497] [Table 60]

[0498] Volatilization method Three slow volatilization tests were conducted using different solvent systems. Approximately 20 mg of one equivalent of the compound represented by formula I, citrate crystalline form B, was weighed into each 2 mL vial. A fixed amount of the corresponding solvent (approximately 1 mL) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The resulting filtrate was then processed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement; see the table below for the results.

[0499] [Table 61]

[0500] Inverse solvent method Approximately 50 mg of one equivalent of the citrate crystalline form B of the compound represented by formula I was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of reverse solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0501] [Table 62]

[0502] Screening tests of one equivalent of polycrystalline citrate showed that one equivalent of citrate crystalline form B exhibited better stability in the solvent. For example, in the suspension method, when the solvent was methanol, ethanol, acetonitrile, acetone, ethyl acetate, dichloromethane, tetrahydrofuran, n-heptane, or dioxane, or when it was a mixed solvent of methanol, acetonitrile, or acetone with water, one equivalent of citrate crystalline form B remained stable after stirring at 40°C.

[0503] Example 40 Method for producing one equivalent of succinate crystalline form A of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of ethanol was added at 50°C, and succinic acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0504] Example 41 Method for producing succinate crystalline form B of one equivalent of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of tetrahydrofuran was added at 50°C, and succinic acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0505] Example 42 Method for producing one equivalent of succinate crystalline form C of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (4 mL) of 1,4-dioxane was added at 50°C, and succinic acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0506] Example 43 Method for producing one equivalent of succinate crystalline form D of the compound represented by formula I: Approximately 1.5 g of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (approximately 60 mL) of ethanol was added at 50°C, and succinic acid was added (acid-base molar ratio was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Characterization of succinate crystal form D of one equivalent of the compound represented by formula I: 1) The results of the XRPD characterization are shown in Figure 24. 2) The results of the TGA characterization are shown in Figure 25. 3) The results of the DSC characterization are shown in Figure 26. 4) That 1 The results of the 1H-NMR characterization are shown in Figure 27, indicating that the molar ratio of succinic acid to free base in the sample is 1:1, and that no solvent remains. 5) The results of the DVS characterization are shown in Figure 28.

[0507] Example 44 Screening of polycrystalline succinates Unless otherwise specified, all crystalline forms mentioned in Example 44 were 1 equivalent succinate crystalline forms. Suspension method Approximately 50 mg of succinate crystalline form D of the compound represented by formula I was weighed, and 0.2 mL of the corresponding solvent was added to prepare a suspension. The suspension was stirred for 3 days under 40°C in the dark, and the supernatant was removed by centrifugation. The resulting precipitate was dried under vacuum (25°C, -0.1 MPa). See the table below for the results.

[0508] [Table 63]

[0509] Volatilization method Three slow volatilization tests were conducted using different solvent systems. Approximately 20 mg of one equivalent of succinate crystalline form D of the compound represented by formula I was weighed into a 2 mL vial, a fixed amount of the corresponding solvent (approximately 1 mL) was added, and the mixture was filtered through a 0.22 μm nylon filter head. The resulting filtrate was then processed using Parafilm. (登録商標) The vial was sealed with sealing film, a pinhole was punctured through it, and the mixture was slowly evaporated at room temperature. The resulting solid was collected and subjected to XRPD measurement; see the table below for the results.

[0510] [Table 64]

[0511] Inverse solvent method Approximately 50 mg of succinate crystalline form D of the compound represented by formula I was weighed into a glass bottle, a fixed amount of good solvent (approximately 1 mL) was added, and the mixture was stirred at 25°C until the sample dissolved to obtain a clarified solution. If the sample was not completely dissolved, the solution was filtered through a 0.22 μm nylon filter head to obtain a clarified solution. Under conditions of stirring at room temperature, four times the amount of reverse solvent was slowly added dropwise, and the mixture was stirred for 5 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0512] [Table 65]

[0513] Screening tests of one equivalent of succinate polycrystalline form showed that succinate crystalline form D exhibited better stability in the solvent. For example, in the suspension method, when the solvent was methanol, ethanol, acetonitrile, acetone, ethyl acetate, dichloromethane, water, n-heptane, or dioxane, or a mixed solvent of methanol, acetonitrile, acetone, and water, one equivalent of succinate crystalline form D remained stable after stirring at 40°C.

[0514] Example 45 Method for producing crystalline form A of phosphate by 1 equivalent of the compound represented by formula I: Approximately 100 mg of amorphous form of the compound represented by formula I was weighed into a glass bottle, a fixed amount (approximately 4 mL) of ethanol was added at 50°C, and phosphoric acid was added (the molar ratio of acid to base was 1:1). The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 4 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa). Method for producing one equivalent of phosphate crystal form E of the compound shown in formula I: 50 mg of one equivalent of phosphate crystal form A was placed in a 2 mL glass bottle, 0.2 mL of ethyl acetate was added, and the suspension was beaten at 40°C for 3 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0515] Example 46 Method for producing crystalline form A of the hydrochloride salt of one equivalent of the compound represented by formula I: Approximately 2 g of amorphous form of the compound represented by formula I was weighed into a 20 mL glass bottle, and 5 mL of ethanol and approximately 3.12 mL of diluted 1 M hydrochloric acid ethanol solution were added at 50°C. The resulting suspension was stirred at 50°C for about 1 hour, then left to stand at 25°C and stirred for 2 days. The supernatant was removed by centrifugation, and the resulting precipitate was dried under vacuum (25°C, -0.1 MPa).

[0516] Example 47 Stability of crystalline form D of the compound represented by formula I Approximately 30 mg of each crystalline form D of the compound represented by formula I was weighed into a 4 mL clear glass bottle. Each sample was placed under the stability conditions shown in the table below, and samples were taken at the appropriate time points, and their appearance and XRPD measurements were performed. 5 mg of stability test samples were weighed out at different time points, dissolved in 10 mL of diluent, and the resulting clarified solutions were subjected to HPLC analysis. The obtained stability results are recorded in the table below.

[0517] [Table 66]

[0518] Example 48 Stability of methanesulfonate crystalline form A Approximately 30 mg of methanesulfonate crystalline form A was weighed into 4 mL clear glass bottles. Each sample was placed under the stability measurement conditions shown in the table below, sampled at different time points, and XRPD measurements were performed.

[0519] [Table 67-1] [Table 67-2]

[0520] Example 49: Stability of maleate crystalline form A and hydrochloride crystalline form A Approximately 30 mg each of two different samples (hydrochloride and maleate) were weighed into 4 mL clear glass vials. The vials were placed open under stability test conditions of 40°C / 75%RH and 90%RH, and closed at 60°C and in an illuminated box (the light-shielded test samples were left standing and treated to protect them from light in the same way as the light-irradiated test samples). Samples were taken at different time points, and XRPD measurements were performed for each sample. 5.28 mg of hydrochloride and 5.91 mg of maleate (corresponding to 5 mg of free base) were weighed and placed under different stability measurement conditions simultaneously with the above sample. Samples were taken at different time points, dissolved in 10 mL of diluent, and the resulting clarified solutions were subjected to HPLC analysis. [Table 68-1] [Table 68-2]

[0521] Example 50: Stability of phosphate crystal form E, tartrate crystal form C, citrate crystal form B, and succinate crystal form D Approximately 30 mg each of phosphate crystalline form E, tartrate crystalline form C, citrate crystalline form B, and succinate crystalline form D were weighed into 4 mL clear glass bottles. Each was placed under the stability conditions shown in the table below, and samples were taken at the appropriate time points, with visual inspection and XRPD measurement performed. A certain amount of stability sample (corresponding to 5 mg of free base mass) was then weighed, dissolved in 10 mL of diluent, and the resulting clarified solution was subjected to HPLC measurement. The obtained stability results are recorded in the table below.

[0522] [Table 69] [Table 70] [Table 71] [Table 72]

[0523] Example 51 Solubility of methanesulfonate crystalline form A 30 mg of methanesulfonate crystalline form A was weighed, and three portions were weighed for each medium and each time point. These were added to 15 mL centrifuge tubes, and 5 mL of a different pH buffer was added to each. The resulting suspensions were shaken at 37°C (100 rpm), and the pH was measured and recorded. If the pH change was ΔpH > 0.1, the pH was adjusted to the initial value with 1 M NaOH. After equilibration for 1 hour, solubility tests were performed three times in parallel for each test at 15 min, 2 h, 4 h, and 24 h. The state of the suspensions at 15 min, 2 h, 4 h, and 24 h was recorded. Different sample solutions were collected in 1.5 mL centrifuge tubes at 15 min, 2 h, 4 h, and 24 h, and the supernatant was obtained by centrifugation at 12000 rpm for 2 minutes. After 2-fold dilution, the sample solution (diluted 10-fold if all was dissolved) was used, and after centrifugation of the residual substrate, XRPD measurement was performed.

[0524] [Table 73-1] [Table 73-2]

[0525] Example 52 Solubility of methanesulfonate crystalline form A, maleate crystalline form A, and hydrochloride crystalline form A in biological media Approximately 20 mg of each sample (methanesulfonate, hydrochloride, and maleate) was weighed into a glass bottle, 10 mL of a different medium was added to each, and the resulting suspensions were stirred at 37°C. After 2 hours, approximately 3 mL of each sample solution was taken (ensuring that a certain amount of sample suspension remained in the glass bottle), and the filtrate was passed through a 0.22 μm filter membrane to be used as the sample solution. The filtrate was diluted to a certain ratio and measured by HPLC (the phenomenon may be recorded if it dissolves completely, or if the amount of dissolved sample is small, dilute it 2-fold before testing). After 24 hours, sampling was performed according to the same steps, and pH and HPLC measurements were taken. Undissolved solids in the bottles were subjected to XRPD measurement.

[0526] Solubility measurement results (37°C, mg / mL) of methanesulfonate crystalline form A, maleate crystalline form A, and hydrochloride crystalline form A in biological media. [Table 74]

[0527] Solubility measurement of methanesulfonate crystalline form A, maleate crystalline form A, and hydrochloride crystalline form A in biological media: Residual solid XRPD results [Table 75]

[0528] The crystalline form provided in this invention has the advantages of high crystallinity, good stability, slight hygroscopicity, high solubility, and high bioavailability.

Claims

1. The crystalline form of the compound represented by formula I or a salt thereof is one equivalent of methanesulfonate crystalline form A of the compound represented by formula I, one equivalent of methanesulfonate crystalline form D of the compound represented by formula I, one equivalent of maleate crystalline form A of the compound represented by formula I, one equivalent of tartrate crystalline form C of the compound represented by formula I, one equivalent of citrate crystalline form B of the compound represented by formula I, or one equivalent of succinate crystalline form D of the compound represented by formula I. 【Chemistry 1】 Of these, one equivalent of methanesulfonate crystalline form A of the compound represented by formula I exhibits an X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, which has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 10.2973°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2°, and 20.7584°±0.2°. Crystal form D of the compound represented by formula I has an X-ray powder diffraction pattern represented by 2θ that, when using Cu-Kα radiation, has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 11.539°±0.2°, 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2°, and 23.157°±0.2°. One equivalent of the maleate crystalline form A of the compound represented by formula I exhibits an X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, with at least three, at least four, at least five, at least six, or at least seven characteristic peaks at the 2θ angles of 5.2344°±0.2°, 10.8375°±0.2°, 12.9364°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2°, and 20.1186°±0.2°. One equivalent of the tartrate crystalline form C of the compound represented by formula I exhibits an X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, with at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 20.699°±0.2°, and 21.665°±0.2°. One equivalent of the citrate crystalline form B of the compound represented by formula I exhibits an X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, with at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 20.699°±0.2°, and 21.665°±0.2°. The succinate crystal form D of one equivalent of the compound represented by formula I is characterized in that, when Cu-Kα radiation is used, the X-ray powder diffraction pattern represented by 2θ has at least three, at least four, at least five, at least six, or at least seven characteristic peaks at 2θ angles of 15.715°±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2°, and 20.218°±0.2°. Crystal form.

2. The crystal form according to claim 1, (1) The crystalline form A of 1 equivalent of methanesulfonate has diffraction peaks at positions 10.2973°±0.2°, 15.1407°±0.2° and 17.8003°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, for example, it has diffraction peaks at 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2° and 20.6191°±0.2°, and also for example, at 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2° and 18.3418°±0.2°. It has diffraction peaks at 20.6191°±0.2°, and also, for example, diffraction peaks at 10.2973°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2° and 20.7584°±0.2°, and also, for example, diffraction peaks at 10.2973°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 17.8003°±0.2°, 18.3418°±0.2°, 20.6191°±0.2° and 20.7584°±0.2°, and also, for example For example, 10.2973°±0.2°, 10.7003°±0.2°, 11.5381°±0.2°, 12.618°±0.2°, 12.918°±0.2°, 13.995°±0.2°, 14.7185°±0.2°, 15.1407°±0.2°, 15.6419°±0.2°, 17.8003°±0.2°, 18.1003°±0.2°, 18.3418°±0.2°, 18.7198°±0.2°, 19.281°±0.2°, 19.8025°±0.2°, 20.3791°±0.2°, 20.6191°±0.2°, 20.7584 The diffraction peaks are located at 21.2626°±0.2°, 21.4387°±0.2°, 21.7211°±0.2°, 22.0791°±0.2°, 22.442°±0.2°, 22.8785°±0.2°, 23.1402°±0.2°, 23.4006°±0.2°, 23.739°±0.2°, 24.2791°±0.2°, 24.6595°±0.2°, and 25.2227°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for one equivalent of methanesulfonate crystal form A is basically as shown in the table below. Table 1 、 (2) The thermogravimetric analysis curve of one equivalent of methanesulfonate crystalline form A showed a weight loss of 0.02143 ± 0.005% during the heating process from 39.18 ± 3°C to 150.63 ± 3°C. For example, the thermogravimetric analysis curve of one equivalent of methanesulfonate crystalline form A shows a weight loss of 0.02143% during the heating process from 39.18°C to 150.63°C. (3) The differential scanning calorimetry curve (DSC) of one equivalent of methanesulfonate crystalline form A has endothermic peaks with starting temperatures of 85.22 ± 3°C and 220.46 ± 3°C, respectively. For example, the differential scanning calorimetry curve (DSC) of one equivalent of methanesulfonate crystalline form A has endothermic peaks with starting temperatures of 85.22°C and 220.46°C, respectively. (4) The differential scanning calorimetry curve (DSC) of one equivalent of methanesulfonate crystalline form A has endothermic peaks with peak temperatures of 86.90 ± 3°C and 222.22 ± 3°C, respectively. For example, the differential scanning calorimetry curve (DSC) of one equivalent of methanesulfonate crystalline form A has endothermic peaks with peak temperatures of 86.90°C and 222.22°C, respectively. (5) The dynamic vapor adsorption curve (DVS) of one equivalent of methanesulfonate crystalline form A shows that the weight increase due to moisture absorption is 0.31 ± 0.005% at 25°C and 80% RH. For example, the dynamic vapor adsorption curve (DVS) of one equivalent of methanesulfonate crystalline form A shows that the weight increase due to moisture absorption is 0.31% at 25°C and 80% RH. (6) The crystal form D, when subjected to Cu-Kα radiation, has diffraction peaks in the X-ray powder diffraction pattern represented by 2θ at positions 18.081°±0.2°, 20.278°±0.2° and 23.157°±0.2°, for example, diffraction peaks at 18.081°±0.2°, 20.278°±0.2° and 23.157°±0.2°, and also for example, diffraction peaks at 13.558°±0.2°, 18.081°±0.2°, 20.278°±0.2° and 23.157°±0.2°, and also for example, 13.558°±0.2°, It has diffraction peaks at 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2° and 23.157°±0.2°, and also has diffraction peaks at, for example, 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, 20.278°±0.2° and 23.157°±0.2°, and also has diffraction peaks at, for example, 11.539°±0.2°, 12.658°±0.2°, 13.558°±0.2°, 18.081°±0.2°, 18.859°±0.2°, and 20.278°± It has diffraction peaks at 0.2° and 23.157°±0.2°, and also, for example, 6.297°±0.2°, 6.737°±0.2°, 11.097°±0.2°, 11.539°±0.2°, 12.381°±0.2°, 12.658°±0.2°, 12.837°±0.2°, 13.558°±0.2°, 14.102°±0.2°, 14.996°±0.2°, 15.66°±0.2°, 16.359°±0.2°, 16.522°±0.2°, 17.04°±0.2°, 17.2°±0.2°, 17.416°±0.2°, Diffraction peaks are present at 18.081°±0.2°, 18.32°±0.2°, 18.515°±0.2°, 18.859°±0.2°, 19.501°±0.2°, 20.278°±0.2°, 20.541°±0.2°, 20.7°±0.2°, 20.937°±0.2°, 21.179°±0.2°, 21.801°±0.2°, 22.057°±0.2°, 22.543°±0.2°, and 23.157°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for the crystal form D is basically as shown in the table below. Table 2 、 (7) The thermogravimetric analysis (TGA) curve of crystal form D showed a weight loss of 0.2139 ± 0.005% during the heating process from 37.69 ± 3°C to 150.63 ± 3°C. For example, the thermogravimetric analysis (TGA) curve of crystal form D shows a weight loss of 0.2139% during the heating process from 37.69°C to 150.63°C. (8) The differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a starting temperature of 165.58 ± 3°C, For example, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a starting temperature of 165.58°C. (9) The differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a peak temperature of 167.41 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of the crystal form D has an endothermic peak with a peak temperature of 167.41°C. (10) The dynamic vapor adsorption curve (DVS) of the crystalline form D shows that the weight increase due to moisture absorption is 0.14 ± 0.005% at 25°C and 80% RH. For example, the dynamic vapor adsorption curve (DVS) of the crystalline form D shows that the weight increase due to moisture absorption is 0.14% at 25°C and 80% RH. (11) The maleate crystal form A of one equivalent has diffraction peaks at positions 17.781°±0.2°, 18.6613°±0.2° and 20.1186°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, for example, it has diffraction peaks at 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2° and 20.1186°±0.2°, and also for example, 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2° and It has diffraction peaks at 20.1186°±0.2°, and also, for example, diffraction peaks at 5.2344°±0.2°, 10.8375°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2° and 20.1186°±0.2°, and also, for example, diffraction peaks at 5.2344°±0.2°, 10.8375°±0.2°, 12.9364°±0.2°, 17.781°±0.2°, 18.6613°±0.2°, 18.9188°±0.2° and 20.1186°±0.2°, and also, for example 5.2344°±0.2°, 8.0562°±0.2°, 9.3187°±0.2°, 9.981°±0.2°, 10.4404°±0.2°, 10.8375°±0.2°, 12.5202°±0.2°, 12.9364°±0.2°, 13.9614°±0.2°, 14.9983°±0.2°, 15.6783°±0.2°, 17.781°±0.2°, 18.3794°±0.2°, 18.6613°±0.2°, 18.9188°±0.2°, 19.4195°±0.2°, 19.701°±0.2°, 20.1186° Diffraction peaks are present at ±0.2°, 20.5991°±0.2°, 20.9388°±0.2°, 22.6192°±0.2°, 22.739°±0.2°, 23.3011°±0.2°, 24.6412°±0.2°, 25.1802°±0.2°, 26.1581°±0.2°, 28.061°±0.2°, 29.7621°±0.2°, 30.013°±0.2°, and 30.9209°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for one equivalent of maleate crystal form A is basically as shown in the table below. Table 3 、 (12) The thermogravimetric analysis (TGA) curve of one equivalent of maleate crystalline form A showed a weight loss of 0.1441 ± 0.005% during the heating process from 30.24 ± 3°C to 150.15 ± 3°C. For example, the thermogravimetric analysis (TGA) curve of one equivalent of maleate crystalline form A shows a weight loss of 0.1441% during the heating process from 30.24°C to 150.15°C. (13) The differential scanning calorimetry curve (DSC) of one equivalent of maleate crystalline form A has an endothermic peak with an onset temperature of 212.82 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of maleate crystalline form A has an endothermic peak with a starting temperature of 212.82°C. (14) The differential scanning calorimetry curve (DSC) of one equivalent of maleate crystalline form A has an endothermic peak with a peak temperature of 213.55 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of maleate crystal form A has an endothermic peak with a peak temperature of 213.55°C. (15) The dynamic vapor adsorption curve (DVS) of one equivalent of maleate crystalline form A shows that the weight increase due to moisture absorption is 0.11 ± 0.005% at 25°C and 80% RH. For example, the dynamic vapor adsorption curve (DVS) of one equivalent of maleate crystalline form A shows that the weight increase due to moisture absorption is 0.11% at 25°C and 80% RH. (16) The 1 equivalent of tartrate crystalline form C, when subjected to Cu-Kα radiation, has diffraction peaks in the X-ray powder diffraction pattern represented by 2θ at positions 17.781°±0.2°, 18.6613°±0.2° and 20.1186°±0.2°, for example, having diffraction peaks at 10.196°±0.2°, 15.543°±0.2°, 17.004°±0.2° and 18.196°±0.2°, and also for example, 10.196°±0.2°, 15.543°±0.2°, 17.004°±0.2°, and 18.196°±0.2°. It has diffraction peaks at ° and 20.699°±0.2°, and for example, it has diffraction peaks at 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2° and 20.699°±0.2°, and for example, it has diffraction peaks at 10.196°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 20.699°±0.2° and 21.665°±0.2°, and For example, 8.48°±0.2°, 10.196°±0.2°, 14.537°±0.2°, 15.052°±0.2°, 15.277°±0.2°, 15.543°±0.2°, 15.757°±0.2°, 16.003°±0.2°, 16.377°±0.2°, 17.004°±0.2°, 18.196°±0.2°, 18.782°±0.2°, 19.226°±0.2°, 19.608°±0.2°, 20.001°±0.2°, 20.699°±0.2°, 21.665°±0.2°, 22.058 Diffraction peaks are present at 22.545°±0.2°, 22.875°±0.2°, 23.097°±0.2°, 23.505°±0.2°, 23.819°±0.2°, 24.313°±0.2°, 24.642°±0.2°, 25.027°±0.2°, 25.699°±0.2°, 26.666°±0.2°, 26.867°±0.2°, and 27.857°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for one equivalent of tartrate crystal form C is basically as shown in the table below. Table 4 、 (17) The thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystalline form C showed a weight loss of 0.04074 ± 0.005% during the heating process from 29.99 ± 3°C to 150.15 ± 3°C. For example, the thermogravimetric analysis (TGA) curve of one equivalent of tartrate crystalline form C shows a weight loss of 0.04074% during the heating process from 29.99°C to 150.15°C. (18) The differential scanning calorimetry curve (DSC) of one equivalent of tartrate crystalline form C has an endothermic peak with an onset temperature of 188.73 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of tartrate crystalline form C has an endothermic peak with a starting temperature of 188.73°C. (19) The differential scanning calorimetry curve (DSC) of one equivalent of tartrate crystalline form C has an endothermic peak with a peak temperature of 190.42 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of tartrate crystalline form C has an endothermic peak with a peak temperature of 190.42°C. (20) The tartrate crystalline form C of 1 equivalent １ The H-NMR results showed that the molar ratio of tartaric acid to free base in the sample was 1:1, indicating that no solvent remained. (21) The 1 equivalent of citrate crystalline form B, when subjected to Cu-Kα radiation, has diffraction peaks in the X-ray powder diffraction pattern represented by 2θ at positions 16.8372°±0.2°, 21.4798°±0.2° and 23.6411°±0.2°, for example, 15.0928°±0.2°, 16.8372°±0.2°, 21.4798°±0.2° and 23.6411°±0.2°, and also for example, 15.0928°±0.2°, 16.8372°±0.2°, 19.194°±0.2°, 21.4798°±0.2° and It has diffraction peaks at 23.6411°±0.2°, and also, for example, diffraction peaks at 15.0928°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.4798°±0.2° and 23.6411°±0.2°, and also, for example, diffraction peaks at 15.0928°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.4798°±0.2°, 23.6411°±0.2° and 26.9181°±0.2°, and also, for example 7.5584°±0.2°, 9.2726°±0.2°, 10.6593°±0.2°, 11.3352°±0.2°, 12.54°±0.2°, 13.5438°±0.2°, 13.7735°±0.2°, 14.0152°±0.2°, 15.0928°±0.2°, 15.4425°±0.2°, 15.628°±0.2°, 16.8372°±0.2°, 18.5382°±0.2°, 19.194°±0.2°, 21.1607°±0.2°, 21.4798°±0.2°, 22.0822°±0.2°, 22.7152 Diffraction peaks are present at °±0.2°, 23.6411°±0.2°, 24.0169°±0.2°, 24.6133°±0.2°, 26.9181°±0.2°, 27.5774°±0.2°, 27.9026°±0.2°, 30.3368°±0.2°, 32.439°±0.2°, 33.9973°±0.2°, 34.2994°±0.2°, 34.7631°±0.2°, and 35.1435°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for one equivalent of citrate crystal form B is basically as shown in the table below. Table 5 、 (22) The thermogravimetric analysis (TGA) curve of one equivalent of citrate crystalline form B showed a weight loss of 19.64 ± 0.005% during the heating process from 35.86 ± 3°C to 212.99 ± 3°C. For example, the thermogravimetric analysis (TGA) curve of one equivalent of citrate crystalline form B shows a weight loss of 19.64% during the heating process from 35.86°C to 212.99°C. (23) The differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with an onset temperature of 178.23 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystal form B has an endothermic peak with a starting temperature of 178.23°C. (24) The differential scanning calorimetry curve (DSC) of one equivalent of citrate crystalline form B has an endothermic peak with a peak temperature of 180.38 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of citrate crystalline form B has an endothermic peak with a peak temperature of 180.38°C. (25) The 1 equivalent of the citrate crystalline form B １ The H-NMR results showed that the molar ratio of citrate to free base in the sample was 1:1, indicating that no solvent remained. (26) The dynamic vapor adsorption curve (DVS) of one equivalent of citrate crystalline form B shows that the weight increase due to moisture absorption is 0.19 ± 0.005% at 25°C and 80% RH. For example, the dynamic vapor adsorption curve (DVS) of one equivalent of citrate crystalline form B shows that the weight increase due to moisture absorption is 0.19% at 25°C and 80% RH. (27) The succinate crystal form D of one equivalent has diffraction peaks at positions 17.778°±0.2°, 18.698°±0.2° and 20.079°±0.2° in its X-ray powder diffraction pattern represented by 2θ using Cu-Kα radiation, for example, 17.778°±0.2°, 18.698°±0.2°, 18.86°±0.2° and 20.079°±0.2°, and also for example, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2° and 18.86°±0.2°. It also has diffraction peaks at 20.079°±0.2°, and for example, diffraction peaks at 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2° and 20.218°±0.2°, and for example, diffraction peaks at 15.715°±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0.2°, 20.079°±0.2° and 20.218°±0.2°, and For example, 5.255°±0.2°, 8.059°±0.2°, 9.338°±0.2°, 9.941°±0.2°, 10.472°±0.2°, 11.401°±0.2°, 12.483°±0.2°, 12.86°±0.2°, 13.203°±0.2°, 13.901°±0.2°, 14.72°±0.2°, 15.038°±0.2°, 15.715°±0.2°, 16.36°±0.2°, 17.778°±0.2°, 18.44°±0.2°, 18.698°±0.2°, 18.86°±0. Diffraction peaks are present at 2°, 19.421°±0.2°, 19.719°±0.2°, 20.079°±0.2°, 20.218°±0.2°, 20.542°±0.2°, 20.862°±0.2°, 20.997°±0.2°, 21.579°±0.2°, 22.461°±0.2°, 22.679°±0.2°, 22.899°±0.2°, and 23.222°±0.2°. Preferably, the X-ray powder diffraction pattern analysis data for 1 equivalent of succinate crystal form D is basically as shown in the table below. Table 6 、 (28) The thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form D showed a weight loss of 0.1218 ± 0.005% during the heating process from 30.10 ± 3°C to 150.15 ± 3°C. For example, the thermogravimetric analysis (TGA) curve of one equivalent of succinate crystalline form D shows a weight loss of 0.1218% during the heating process from 30.10°C to 150.15°C. (29) The differential scanning calorimetry curve (DSC) of one equivalent of succinate crystalline form D has an endothermic peak with a starting temperature of 184.29 ± 3°C, For example, the differential scanning calorimetry curve (DSC) of one equivalent of succinate crystal form D has endothermic peaks with starting temperatures of 184.29°C. (30) The differential scanning calorimetry curve (DSC) of one equivalent of succinate crystalline form D has an endothermic peak with a peak temperature of 185.23 ± 3°C. For example, the differential scanning calorimetry curve (DSC) of one equivalent of succinate crystal form D has an endothermic peak with a peak temperature of 185.23°C. (31) The succinate crystalline form D of 1 equivalent １ The H-NMR results showed that the molar ratio of succinic acid to free base in the sample was 1:1, indicating that no solvent remained. (32) The dynamic vapor adsorption curve (DVS) of one equivalent of succinate crystalline form D shows that the weight increase due to moisture absorption is 0.19 ± 0.005% at 25°C and 80% RH. For example, the dynamic vapor adsorption curve (DVS) of one equivalent of succinate crystalline form D shows that the weight increase due to moisture absorption is 0.19% at 25°C and 80% RH. It is characterized by satisfying one or more of the following conditions: The crystal form described in claim 1.

3. The crystal form according to claim 1, (1) The X-ray powder diffraction pattern of one equivalent of methanesulfonate crystal form A is basically as shown in Figure 5. (2) The thermogravimetric analysis curve of one equivalent of methanesulfonate crystalline form A is basically as shown in Figure 6. (3) The differential scanning calorimetry curve of one equivalent of methanesulfonate crystalline form A is basically as shown in Figure 7. (4) The proton nuclear magnetic resonance of one equivalent of methanesulfonate crystal form A is basically as shown in Figure 8. (5) The dynamic vapor adsorption curve of one equivalent of methanesulfonate crystalline form A is as shown in Figure 9. (6) The X-ray powder diffraction pattern of the crystal form D is basically as shown in Figure 1, (7) The thermogravimetric analysis curve of the crystal form D is basically as shown in Figure 2, (8) The differential scanning calorimetry curve of the crystal form D is basically as shown in Figure 3, (9) The dynamic vapor adsorption curve of the crystalline form D is as shown in Figure 4, (10) The X-ray powder diffraction pattern of one equivalent of maleate crystal form A is basically as shown in Figure 10. (11) The thermogravimetric analysis curve of one equivalent of maleate crystalline form A is basically as shown in Figure 11, (12) The differential scanning calorimetry curve of one equivalent of maleate crystalline form A is basically as shown in Figure 12. (13) The proton nuclear magnetic resonance of one equivalent of maleate crystal form A is basically as shown in Figure 13, (14) The dynamic vapor adsorption curve of one equivalent of maleate crystalline form A is as shown in Figure 14. (15) The X-ray powder diffraction pattern of one equivalent of tartrate crystal form C is basically as shown in Figure 15. (16) The thermogravimetric analysis curve of one equivalent of tartrate crystalline form C is basically as shown in Figure 16. (17) The differential scanning calorimetry curve of one equivalent of tartrate crystalline form C is basically as shown in Figure 17. (18) The proton nuclear magnetic resonance of one equivalent of tartrate crystal form C is basically as shown in Figure 18. (19) The X-ray powder diffraction pattern of one equivalent of citrate crystal form B is basically as shown in Figure 19. (20) The thermogravimetric analysis curve of one equivalent of citrate crystalline form B is basically as shown in Figure 20. (21) The differential scanning calorimetry curve of one equivalent of citrate crystal form B is basically as shown in Figure 21. (22) The proton nuclear magnetic resonance of one equivalent of citrate crystal form B is basically as shown in Figure 22, (23) The dynamic vapor adsorption curve of 1 equivalent of citrate crystalline form B is as shown in Figure 23. (24) The X-ray powder diffraction pattern of one equivalent of succinate crystal form D is basically as shown in Figure 24. (25) The thermogravimetric analysis curve of the succinate crystal form D of one equivalent is basically as shown in Figure 25. (26) The differential scanning calorimetry curve of one equivalent of succinate crystal form D is basically as shown in Figure 26. (27) The proton nuclear magnetic resonance of one equivalent of succinate crystal form D is basically as shown in Figure 27, (28) The dynamic vapor adsorption curve of one equivalent of succinate crystalline form D is as shown in Figure 28. It is characterized by satisfying one or more of the following conditions: The crystal form described in claim 1.

4. A pharmaceutical composition comprising one equivalent of methanesulfonate crystal form A of the compound represented by formula I as described in any one of claims 1 to 3, crystal form D of the compound represented by formula I, crystal form A of the compound represented by formula I, crystal form C of the compound represented by formula I, crystal form B of the compound represented by formula I, or crystal form D of the compound represented by formula I, and one or more pharmaceutically acceptable excipients. Pharmaceutical composition.

5. The use of substance X in the manufacture of an ALK inhibitor, wherein substance X is one equivalent of methanesulfonate crystal form A of the compound represented by formula I as described in any one of claims 1 to 3, crystal form D of the compound represented by formula I, one equivalent of maleate crystal form A of the compound represented by formula I, one equivalent of tartrate crystal form C of the compound represented by formula I, one equivalent of citrate crystal form B of the compound represented by formula I, one equivalent of succinate crystal form D of the compound represented by formula I, or the pharmaceutical composition described in claim 4. use.

6. The use of substance X in the treatment or prevention of cancer, wherein substance X is one equivalent of methanesulfonate crystalline form A of the compound represented by formula I as described in any one of claims 1 to 3, crystalline form D of the compound represented by formula I, crystalline form A of the compound represented by formula I as an equivalent, crystalline form C of the compound represented by formula I as an equivalent, crystalline form B of the compound represented by formula I as an equivalent, crystalline form D of the compound represented by formula I as an equivalent, or the pharmaceutical composition as described in claim 4, wherein preferably the cancer is selected from the group consisting of anaplastic large cell lymphoma, non-small cell lung cancer, diffuse large B-cell lymphoma, inflammatory myofibroblastoma, neuroblastoma, anaplastic thyroid cancer, rhabdomyosarcoma, breast cancer, colorectal cancer, esophageal squamous cell carcinoma, and renal cell carcinoma. use.

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