Polymorphic form of kinase inhibitor compound, pharmaceutical composition containing same, and preparation method therefor and use thereof

Abstract

Provided are a polymorphic form of a compound of formula I, a pharmaceutical composition containing same, and a preparation method therefor and a use thereof. The compound of formula I is as shown in formula I, having the crystal form of a crystal form 1, a crystal form 2, a crystal form 3, a crystal form 5, a crystal form 6 or a crystal form 7. Each crystal form of the compound of formula I has a good crystal form stability and chemical stability, and the main component, with respect to the chemical stability, has a purity reduction of less than 2%. The preparation method enables the preparation of various crystal forms of the compound of the formula I with a high purity, and the preparation method enables large scale production.

Description

Polymorphs of kinase inhibitor compounds, pharmaceutical compositions containing the same, preparation methods thereof and uses thereof Technical Field The present invention belongs to the field of pharmaceutical crystal forms, and particularly relates to polymorphs of a kinase inhibitor compound, a pharmaceutical composition containing the same, a preparation method thereof and uses thereof. Background Art Sunitinib is a potent multi-target kinase inhibitor, and this drug has significant curative effects on cancers, especially on renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Nevertheless, the application of sunitinib is limited due to its side effects. Among them, the most common and serious side effects clinically include neutropenia and fatigue toxicity. Such side effects greatly limit the use of sunitinib as a single drug or in combination with other treatments. For example, the results of a phase I clinical trial of a sunitinib and everolimus composition in patients with metastatic renal cell carcinoma showed poor tolerance to daily administration, and everolimus had to be converted to weekly administration (2011 Genitourinary cancer symposium, abst#311). However, if a dosing regimen of sunitinib administered for 4 weeks, rested for 2 weeks, and then everolimus administered for 5 weeks, rested for 1 week is adopted, although the tolerance is improved, the curative effect cannot meet the predetermined goal (2014 Genitourinary cancer symposium, abst#438). WO2008033562A2 and CN101553482A disclose a class of sunitinib derivatives in which the diethylaminoethyl side chain of sunitinib is replaced by a cyclic side chain, such as 5-[5-fluoro-2-oxo-1,2-dihydro-indole-(3Z)-ylidene methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ((S)-1-dimethylcarbamoyl-pyrrolidin-3-yl)-amide shown in formula I (molecular weight is 439.48, molecular formula is C 23 H 26 FN5O3), thereby having reduced inhibitory activity on AMPK, and thus alleviating side effects of sunitinib such as fatigue toxicity. In this compound, the basic diethylaminoethyl side chain in the sunitinib structure is replaced by a neutral dimethylcarbamoyl-pyrrolidin-3-yl. The basic side chain is beneficial to the solubility of sunitinib, but it will also cause extensive accumulation of the drug in human tissues, thus increasing its toxicity. Although replacing this basic side chain with a neutral group can reduce its accumulation in tissues to reduce toxicity, it also significantly reduces the water solubility, which becomes a problem that must be faced in drug development Challenges. Moreover, the existing preparation methods still cannot meet the requirements of large-scale production. Therefore, there is an urgent need to develop compound forms with good drug properties such as solubility, stability, bioavailability, or drug metabolism, their formulations, and suitable large-scale preparation methods, so as to obtain good drug efficacy. Summary of the Invention To improve the above problems in the prior art, the present invention provides a crystal form of the compound shown in Formula I: Wherein, the crystal form is selected from crystal form 1, crystal form 2, crystal form 3, crystal form 5, crystal form 6, crystal form 7, or a mixture of any two or more of them; The crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 8.6 ± 0.2°, and 12.9 ± 0.2° in the X-ray powder diffraction pattern; The crystal form 2 has characteristic peaks at diffraction angles 2θ of 8.8 ± 0.2°, 10.1 ± 0.2°, 23.8 ± 0.2°, and 26.7 ± 0.2° in the X-ray powder diffraction pattern; The crystal form 3 has a characteristic peak at a diffraction angle 2θ of 7.8 ± 0.2° in the X-ray powder diffraction pattern; The crystal form 5 has characteristic peaks at diffraction angles 2θ of 8.7 ± 0.2°, 17.0 ± 0.2°, and 17.4 ± 0.2° in the X-ray powder diffraction pattern; The crystal form 6 has characteristic peaks at diffraction angles 2θ of 7.9 ± 0.2°, 9.0 ± 0.2°, and 17.7 ± 0.2° in the X-ray powder diffraction pattern; The crystal form 7 has characteristic peaks at diffraction angles 2θ of 9.5 ± 0.2°, 10.6 ± 0.2°, and 16.0 ± 0.2° in the X-ray powder diffraction pattern; The X-ray powder diffraction patterns are all measured using the Kα line of the Cu target. Preferably, the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 8.6 ± 0.2°, 12.9 ± 0.2°, and 18.3 ± 0.2° in the X-ray powder diffraction pattern. Preferably, the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 12.9 ± 0.2°, and 18.3 ± 0.2° in the X-ray powder diffraction pattern. Preferably, the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 12.9 ± 0.2°, 17.2 ± 0.2°, and 18.3 ± 0.2° in the X-ray powder diffraction pattern. More preferably, the crystalline form 1 has characteristic peaks at diffraction angles 2θ of 4.3±0.2°, 7.6±0.2°, 8.6±0.2°, 9.0±0.2°, 12.4±0.2°, 12.9±0.2°, 17.2±0.2° and 18.3±0.2° in the X-ray powder diffraction pattern. As an example, the crystalline form 1 has characteristic peaks at diffraction angles 2θ selected from the following angles in the X-ray powder diffraction pattern: 4.3±0.2°, 6.7±0.2°, 7.6±0.2°, 8.6±0.2°, 9.0±0.2°, 12.4±0.2°, 12.9±0.2°, 14.3±0.2°, 15.5±0.2°, 16.7±0.2°, 17.2±0.2°, 18.3±0.2°, 19.6±0.2°, 20.3±0.2°, 21.2±0.2°, 21.5±0.2°, 22.4±0.2°, 23.1±0.2°, 24.2±0.2°, 25.1±0.2°, 25.9±0.2°, 27.0±0.2°, 27.4±0.2°, 28.8±0.2°, 30.8±0.2°, 33.4±0.2°, 39.2±0.2°. As an example, the crystalline form 1 has characteristic peaks at diffraction angles 2θ selected from the following angles in the X-ray powder diffraction pattern: 4.3±0.2°, 6.7±0.2°, 7.6±0.2°, 8.6±0.2°, 9.0±0.2°, 10.1±0.2°, 12.4±0.2°, 12.9±0.2°, 14.3±0.2°, 15.5±0.2°, 16.7±0.2°, 17.2±0.2°, 18.3±0.2°, 19.6±0.2°, 20.3±0.2°, 21.2±0.2°, 21.5±0.2°, 22.4±0.2°, 23.1±0.2°, 24.2±0.2°, 25.1±0.2°, 25.9±0.2°, 27.0±0.2°, 27.4±0.2°, 28.8±0.2°, 30.8±0.2°, 32.9±0.2°, 33.4±0.2°, 35.0±0.2°, 37.5±0.2°, 39.2±0.2°. Most preferably, the data of the X-ray powder diffraction pattern of the crystalline form 1 is as shown in Table 1 below: Table 1 Non-limitingly, a typical example of the crystalline form 1 has an X-ray powder diffraction pattern substantially as shown in Figure 1. Furthermore, the polarized light microscope photograph (PLM) of the crystalline form 1 is as shown in Figure 2. Among them, the crystalline form 1 is an elongated rod-shaped crystal. The solubility of the said polymorph 1 in common solvents at 25 °C is as follows: the solubility in methanol is 5 - 12.5 mg / mL; the solubility in ethanol is 1 - 2.5 mg / mL; the solubility in water is < 1 mg / mL; the solubility in acetone is 1 - 2.5 mg / mL; the solubility in ethyl acetate is < 1 mg / mL; the solubility in methyl tert-butyl ether is < 1 mg / mL; the solubility in tetrahydrofuran is 1 - 2.5 mg / mL; the solubility in acetonitrile is < 1 mg / mL; the solubility in toluene is < 1 mg / mL; the solubility in n-heptane is < 1 mg / mL. Furthermore, the polymorph 1 has a thermogravimetric analysis (TGA) pattern substantially as shown in Figure 3. Among them, the polymorph 1 has a weight loss of about 2.6% before 170 °C, which is the anhydrous form, and the decomposition temperature is about 320 °C. Furthermore, the polymorph 1 has a differential scanning calorimetry (DSC) pattern substantially as shown in Figure 4. Among them, the polymorph 1 has an exothermic peak at 150 - 170 °C, which is confirmed to be an exothermic polymorphic transition peak, and the polymorphic form after the transition is the polymorph 3. The melting point of the polymorph 1 is about 260 °C. Furthermore, the polymorph 1 has a dynamic vapor sorption (DVS) pattern substantially as shown in Figure 5. Among them, the weight change of the polymorph 1 in the range of 0% RH to 80% RH is about 2.8%. Preferably, the polymorph 2 has characteristic peaks at diffraction angles 2θ of 8.8 ± 0.2°, 10.1 ± 0.2°, 17.7 ± 0.2°, 19.9 ± 0.2°, 20.5 ± 0.2°, 23.8 ± 0.2° and 26.7 ± 0.2° in the X-ray powder diffraction pattern. More preferably, the polymorph 2 has characteristic peaks at diffraction angles 2θ of 5.1 ± 0.2°, 8.8 ± 0.2°, 10.1 ± 0.2°, 11.6 ± 0.2°, 14.6 ± 0.2°, 15.2 ± 0.2°, 16.5 ± 0.2°, 17.3 ± 0.2°, 17.7 ± 0.2°, 18.8 ± 0.2°, 19.9 ± 0.2°, 20.5 ± 0.2°, 21.7 ± 0.2°, 23.2 ± 0.2°, 23.8 ± 0.2° and 26.7 ± 0.2° in the X-ray powder diffraction pattern. As an example, the polymorph 2 has characteristic peaks at diffraction angles 2θ selected from the following angles in the X-ray powder diffraction pattern: 5.1 ± 0.2°, 7.8 ± 0.2°, 8.4 ± 0.2°, 8.8 ± 0.2°, 10.1 ± 0.2°, 11.6 ± 0.2°, 14.6 ± 0.2°, 15.2 ± 0.2°, Characteristic peaks are present at 15.5±0.2°, 16.1±0.2°, 16.5±0.2°, 17.3±0.2°, 17.7±0.2°, 18.8±0.2°, 19.0±0.2°, 19.4±0.2°, 19.9±0.2°, 20.5±0.2°, 21.7±0.2°, 22.1±0.2°, 23.2±0.2°, 23.8±0.2°, 24.7±0.2°, 25.9±0.2°, 26.7±0.2°, 27.5±0.2°, 28.7±0.2°, 29.7±0.2°, 30.3±0.2°, 31.6±0.2°, 32.5±0.2°, 33.1±0.2°, 36.8±0.2° and 38.9±0.2°. Preferably, the data of the X-ray powder diffraction pattern of the crystalline form 2 is as shown in Table 2 below: Table 2 Non-limitingly, a typical example of the crystalline form 2 has an X-ray powder diffraction pattern substantially as shown in Figure 7. Further, the polarized light microscope photograph (PLM) of the crystalline form 2 is as shown in Figure 8. Among them, the crystalline form 2 is a fine needle-like crystal. Further, the crystalline form 2 has a thermogravimetric analysis (TGA) spectrum substantially as shown in Figure 9. Among them, the crystalline form 2 has a weight loss of about 0.3% before 200 °C, which is an anhydrous substance, and the decomposition temperature is about 320 °C. Further, the crystalline form 2 has a differential scanning calorimetry (DSC) substantially as shown in Figure 10. Among them, the melting point of the crystalline form 2 is about 258 °C. Further, the crystalline form 2 has a dynamic vapor sorption (DVS) substantially as shown in Figure 11. Among them, the weight change of the crystalline form 2 in the range of 0% RH to 80% RH is about 0.05%. Preferably, the crystalline form 3 has characteristic peaks at diffraction angles 2θ of 7.8±0.2°, 9.3±0.2°, 13.7±0.2°, and 16.0±0.2° in the X-ray powder diffraction pattern. More preferably, the crystalline form 3 has characteristic peaks at diffraction angles 2θ of 3.9±0.2°, 7.8±0.2°, 9.3±0.2°, 13.7±0.2°, 16.0±0.2°, 18.2±0.2° and 27.2±0.2° in the X-ray powder diffraction pattern. As an example, the diffraction angles 2θ of the crystalline form 3 in the X-ray powder diffraction pattern are as shown in Table 3. Preferably, the data of the X-ray powder diffraction pattern of the crystalline form 3 is as shown in Table 3 below: Table 3 Non - restrictively, a typical example of the said Form 3 has an X - ray powder diffraction pattern substantially as shown in Figure 12. Further, the polarized light microscope photograph (PLM) of the said Form 3 is as shown in Figure 13. Among them, the said Form 3 is fine particles and there is partial aggregation. Further, the said Form 3 has a thermogravimetric analysis (TGA) spectrum substantially as shown in Figure 14. Among them, the said Form 3 has a weight loss of about 0.2% before 200 °C, which is an anhydrate, and the decomposition temperature is about 320 °C. Further, the said Form 3 has a differential scanning calorimetry (DSC) substantially as shown in Figure 15. Among them, the melting point of the said Form 3 is about 261 °C. Further, the said Form 3 has a dynamic vapor sorption (DVS) substantially as shown in Figure 16. Among them, the weight change of the said Form 3 in the range of 0% RH to 80% RH is about 0.08%. Preferably, the Form 5 has characteristic peaks at diffraction angles 2θ of 8.3 ± 0.2°, 8.7 ± 0.2°, 9.4 ± 0.2°, 17.0 ± 0.2°, 17.4 ± 0.2° and 18.1 ± 0.2° in the X - ray powder diffraction pattern. More preferably, the Form 5 has characteristic peaks at diffraction angles 2θ of 4.1 ± 0.2°, 8.3 ± 0.2°, 8.7 ± 0.2°, 9.4 ± 0.2°, 10.5 ± 0.2°, 13.4 ± 0.2°, 17.0 ± 0.2°, 17.4 ± 0.2° and 18.1 ± 0.2° in the X - ray powder diffraction pattern. As an example, the diffraction angles 2θ of the Form 5 in the X - ray powder diffraction pattern are as shown in Table 4. Most preferably, the data of the X - ray powder diffraction pattern of the Form 5 are as shown in Table 4 below: Table 4 Non - restrictively, a typical example of the said Form 5 has an X - ray powder diffraction pattern substantially as shown in Figure 17 Further, the polarized light microscope photograph (PLM) of the said Form 5 is as shown in Figure 18. Among them, the said Form 5 is fine particles and there is partial aggregation. Further, the said Form 5 has a thermogravimetric analysis (TGA) spectrum substantially as shown in Figure 19. Among them, the said Form 5 has a weight loss of about 1.2% before 200 °C, which is an anhydrate, and the decomposition temperature is about 319 °C. Furthermore, Form 5 has a differential scanning calorimetry (DSC) pattern substantially as shown in Figure 20. Among them, the melting point of Form 5 is about 258 °C, and the broad endothermic peak before 100 °C is due to the removal of surface solvent. Furthermore, Form 5 has a dynamic vapor sorption (DVS) pattern substantially as shown in Figure 21. Among them, the weight change of Form 5 in the range of 0% RH to 80% RH is about 2.5%. Preferably, Form 6 has characteristic peaks at diffraction angles 2θ of 7.9 ± 0.2°, 9.1 ± 0.2°, 9.6 ± 0.2°, 16.4 ± 0.2°, 17.7 ± 0.2° and 18.0 ± 0.2° in the X-ray powder diffraction pattern. More preferably, Form 6 has characteristic peaks at diffraction angles 2θ of 3.9 ± 0.2°, 7.9 ± 0.2°, 9.1 ± 0.2°, 9.6 ± 0.2°, 13.2 ± 0.2°, 16.4 ± 0.2°, 17.7 ± 0.2° and 18.0 ± 0.2° in the X-ray powder diffraction pattern. As an example, the diffraction angles 2θ of Form 6 in the X-ray powder diffraction pattern are shown in Table 5. Most preferably, the data of the X-ray powder diffraction pattern of Form 6 are as shown in Table 5 below: Table 5 Non-limitingly, a typical example of Form 6 has an X-ray powder diffraction pattern substantially as shown in Figure 22. Furthermore, the polarized light microscopy (PLM) photograph of Form 6 is shown in Figure 23. Among them, Form 6 is fine particles with some agglomeration. Furthermore, Form 6 has a thermogravimetric analysis (TGA) pattern substantially as shown in Figure 24. Among them, Form 6 has a weight loss of about 0.7% before 200 °C, which is the anhydrous form, and the decomposition temperature is about 320 °C. Furthermore, Form 6 has a differential scanning calorimetry (DSC) pattern substantially as shown in Figure 25. Among them, the melting point of Form 6 is about 259 °C. Furthermore, Form 6 has a dynamic vapor sorption (DVS) pattern as shown in Figure 26. Among them, the weight change of Form 6 in the range of 0% RH to 80% RH is about 0.26%. Preferably, Form 7 has characteristic peaks at diffraction angles 2θ of 9.5 ± 0.2°, 10.6 ± 0.2°, 13.8 ± 0.2°, 14.3 ± 0.2°, 16.0 ± 0.2°, 18.2 ± 0.2°, and 25.1 ± 0.2° in the X-ray powder diffraction pattern. More preferably, the crystal form 7 has characteristic peaks at diffraction angles 2θ of 4.8±0.2°, 9.5±0.2°, 10.6±0.2°, 13.8±0.2°, 14.3±0.2°, 16.0±0.2°, 18.2±0.2°, 25.1±0.2°, 27.8±0.2° and 28.9±0.2° in the X-ray powder diffraction pattern. As an example, the diffraction angles 2θ of the crystal form 7 in the X-ray powder diffraction pattern are shown in Table 6. Preferably, the data of the X-ray powder diffraction pattern of the crystal form 7 are shown in Table 6 below: Table 6 Non-limitingly, a typical example of the crystal form 7 has an X-ray powder diffraction pattern substantially as shown in Figure 27. Furthermore, the polarized light microscope photograph (PLM) of the crystal form 7 is shown in Figure 28. Among them, the crystal form 7 is fine particles and there is partial aggregation. Furthermore, the crystal form 7 has a thermogravimetric analysis (TGA) spectrum substantially as shown in Figure 29. Among them, the crystal form 7 has a weight loss of about 0.5% before 200°C, it is an anhydrate, and the decomposition temperature is about 320°C. Furthermore, the crystal form 7 has a differential scanning calorimetry (DSC) substantially as shown in Figure 30. Among them, the melting point of the crystal form 7 is about 259°C. Furthermore, the crystal form 7 has a dynamic vapor sorption (DVS) substantially as shown in Figure 31. Among them, the weight change of the crystal form 7 in the range of 0% RH to 80% RH is about 0.27%. According to the present invention, the purities of the crystal forms 1, 2, 3, 5, 6, and 7 are preferably greater than 50%, such as more than 80%, more than 85%, more than 90%, more than 95%, such as more than 99%, more than 99.5% or more than 99.9%. The present invention also provides a preparation method of the crystal form, including one or more of the following methods: (1) The first preparation method of the crystal form 1, which includes the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, and volatilizing the solvent to obtain it; the solvent is methanol, a mixture of methanol and acetone, or an aqueous methanol solution; The second preparation method of the crystal form 1, which includes the following steps: mixing the compound of formula I with methanol to obtain a clear solution, adding a solvent to the clear solution under stirring to precipitate a solid, and obtaining it; the solvent is acetone, ethyl acetate, methyl tert-butyl ether, or acetonitrile; The third preparation method of polymorph 1 comprises the following steps: mixing the compound of formula I with methanol to obtain a clear solution, adding the clear solution into a solvent under stirring, and precipitating a solid to obtain the product; the solvent is water or methyl tert-butyl ether; The fourth preparation method of polymorph 1 comprises the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, cooling, and stirring for crystallization to obtain the product; the solvent is methanol, an aqueous methanol solution, a mixture of methanol and ethyl acetate, a mixture of methanol and methyl tert-butyl ether, or a mixture of methanol and acetonitrile. In the first preparation method of polymorph 1, the temperature for volatilizing the solvent is preferably 10-40°C. The mass-to-volume ratio of the compound of formula I to the solvent is preferably 10 mg / (0.5-2.2 mL), such as 10 mg / (0.5-2 mL), for example, it can be 5 mg / 1.0 mL, 10 mg / 0.6 mL, or 10 mg / 1.2 mL. When the solvent is a mixture of methanol and acetone, the volume ratio of methanol to acetone is preferably 1:1.5-2.5, for example, it can be 1:2; when the solvent is an aqueous methanol solution, the volume ratio of methanol to water is preferably 6:0.5-1.5, for example, it can be 6:1. In the second preparation method of polymorph 1, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of formula I. The temperature of the mixing is preferably 45-55°C, such as 50°C. According to common knowledge in the art, in order to ensure obtaining a clear solution, a hot filtration operation can be carried out after the compound of formula I is fully dissolved. The mass-to-volume ratio of the compound of formula I to methanol is preferably 20 mg / 1.2-1.6 mL, such as 20 mg / 1.4 mL. The mass-to-volume ratio of the compound of formula I to the solvent is preferably 20 mg / 2-4 mL, such as 20 mg / 3 mL. In the third preparation method of polymorph 1, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of formula I. The temperature of the mixing is preferably 45-55°C, such as 50°C. According to common knowledge in the art, in order to ensure obtaining a clear solution, a hot filtration operation can be carried out after the compound of formula I is fully dissolved. The mass-to-volume ratio of the compound of formula I to methanol is preferably 20 mg / 1.2-20 mg / 1.6 mL, such as 20 mg / 1.4 mL. The mass-to-volume ratio of the compound of formula I to the solvent is preferably 20 mg / 2.0-15 mL, such as 20 mg / 2.5-12.0 mL, such as 20 mg / 3.0 mL, 20 mg / 5.2 mL, 20 mg / 11.2 mL. In Preparation Method 4 of the crystalline form 1, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of Formula I, and usually a water bath heating method can be adopted; the temperature of the mixing is preferably 45-70 °C, such as 50 °C or the reflux temperature. According to the common knowledge in the art, to ensure obtaining a clear solution, a hot filtration operation can be carried out after the compound of Formula I is fully dissolved. Preferably, the compound of Formula I is mixed with a solvent and heated to reflux to obtain a clear solution. Preferably, Preparation Method 4 includes the following steps: mixing the compound of Formula I and methanol, heating to reflux to obtain a clear solution, cooling, stirring for crystallization, filtering, washing, and drying; Optionally, Preparation Method 4 further includes a concentration step, for example, concentrating to remove part of the solvent after obtaining the clear solution; Preferably, the concentration is carried out under reduced pressure conditions, and the vacuum degree of the reduced pressure conditions can be, for example, 200-1500 Pa, such as 500-1000 Pa; The concentration temperature can be 20-35 °C; Preferably, the reflux time is less than 4 hours, such as not exceeding 2 hours; Preferably, the water content of the methanol does not exceed 10%, such as not exceeding 6%, for example not exceeding 5%, preferably not exceeding 1%, such as anhydrous methanol. The target temperature for cooling can be 1-50 °C, for example 4-50 °C, such as 5-35 °C or 10-20 °C. The temperature for stirring and crystallization can be 1-50 °C, for example 4-50 °C, such as 5-35 °C or 10-20 °C. The solvent used for washing can be selected from the above-mentioned methanol for preparing the clear solution, methanol aqueous solution, mixture of methanol and ethyl acetate, mixture of methanol and methyl tert-butyl ether, or mixture of methanol and acetonitrile, preferably methanol. The mass-volume ratio of the compound of Formula I to the solvent is preferably 20 mg / (0.5-2.2 mL), for example, it can be 20 mg / 0.8 mL, 20 mg / 1.0 mL, 20 mg / 1.2 mL, 20 mg / 1.4 mL, 20 mg / 1.8 mL, 20 mg / 2.2 mL. When the solvent is methanol, the water content is preferably ≤10%; when the solvent is methanol aqueous solution, the volume ratio of methanol to water is preferably 7:1.5-2.5, such as 7:2; when the solvent is a mixture of methanol and ethyl acetate, the volume ratio of methanol to ethyl acetate is preferably 1:1.5-2.5, such as 1:2; when the solvent is a mixture of methanol and methyl tert-butyl ether, the volume ratio of methanol to methyl tert-butyl ether is preferably 4:6-8, such as 4:7; when the solvent is a mixture of methanol and acetonitrile, the volume ratio of methanol to acetonitrile is preferably 1:0.5-1.5, such as 1:1. (2) The preparation method of the crystal form 2 comprises the following steps: mixing and stirring the compound of formula I with a solvent for 2 to 6 days, separating the solid and liquid of the crystal slurry, and then drying to obtain the crystal form 2; the solvent is water, ethyl acetate, toluene, aqueous acetone solution, aqueous acetonitrile solution, a mixture of ethanol and toluene, or aqueous methanol solution. In the preparation method of the crystal form 2, the compound of formula I can be the crystal form 1 and / or the crystal form 6. The temperature of the stirring is preferably 4 to 50 °C. According to common knowledge in the art, during the stirring process, the temperature of the mixture can be adjusted. For example, stir at 50 °C for 2 h first, and then stir at room temperature for 2 days. The mass-volume ratio of the compound of formula I to the solvent is preferably (12.5 - 40.0 mg) / mL, and can be, for example, 10 mg / 0.5 mL, 10 mg / 0.6 mL, 10 mg / 0.8 mL, or 199 mg / 5 mL. When the solvent is an aqueous acetone solution, the volume ratio of acetone to water is preferably 2:1; when the solvent is an aqueous acetonitrile solution, the volume ratio of acetonitrile to water is preferably 2:1 to 5:1; when the solvent is a mixture of ethanol and toluene, the volume ratio of ethanol to toluene is preferably 1:1; when the solvent is an aqueous methanol solution, the volume ratio of methanol to water is preferably 1:1. The method and conditions for solid-liquid separation can be conventional methods and conditions in the art, and generally, filtration or filtration after centrifugation can be used; when only filtration is used for solid-liquid separation, the filtration is usually suction filtration. The method and conditions for drying can be conventional methods and conditions in the art, preferably vacuum drying, and more preferably vacuum drying at room temperature for 10 to 16 hours. (3) The first preparation method of the crystal form 3 comprises the following steps: mixing the compound of formula I with tetrahydrofuran to obtain a clear solution, and volatilizing the solvent to obtain the crystal form 3. The second preparation method of the crystal form 3 comprises the following steps: mixing the compound of formula I with ethanol to obtain a clear solution, and volatilizing the solvent at room temperature to obtain the crystal form 3. The third preparation method of the crystal form 3 comprises the following steps: mixing the compound of formula I with an aqueous ethanol solution to obtain a clear solution, and volatilizing the solvent at 60 °C to obtain the crystal form 3. The fourth preparation method of the crystal form 3 comprises the following steps: mixing and stirring the compound of formula I with a solvent, separating the solid and liquid of the crystal slurry, and then drying to obtain the crystal form 3; the solvent is ethanol, acetone, or an aqueous tetrahydrofuran solution. The fifth preparation method of the crystal form 3 comprises the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, cooling, and stirring for crystallization to obtain the crystal form 3; the solvent is tetrahydrofuran or a mixture of methanol and tetrahydrofuran. Preparation method VI of the crystalline form 3, which comprises the following steps: heating the crystalline form 1 to 180-190 °C and cooling to room temperature to obtain the crystalline form 3; or heating the crystalline form 7 to 258 °C and cooling to room temperature to obtain the crystalline form 3. In preparation method I of the crystalline form 3, the temperature of the volatile solvent is preferably 10-40 °C. The mass-to-volume ratio of the compound of formula I to tetrahydrofuran is preferably 1 mg / 0.5-1.5 mL, such as 1:1 mL. In preparation method II of the crystalline form 3, the mass-to-volume ratio of the compound of formula I to tetrahydrofuran is preferably 5 mg / 2-4 mL, such as 5 mg / 3 mL. In preparation method III of the crystalline form 3, the mass-to-volume ratio of the compound of formula I to tetrahydrofuran is preferably 10 mg / 1.0-1.4 mL, such as 10 mg / 1.2 mL. In the aqueous ethanol solution, the volume ratio of ethanol to water is preferably 5:0.5-1.5, such as 5:1. In preparation method IV of the crystalline form 3, the crystalline form of the compound of formula I is preferably the crystalline form 1. The stirring temperature is preferably 4-30 °C, and the stirring time is preferably 20 hours to 6 days. The mass-to-volume ratio of the compound of formula I to the solvent is preferably 10 mg / (0.4-0.8 mL), for example, it can be 10 mg / 0.5 mL, 10 mg / 0.8 mL, 200 mg / 8 mL, 200 mg / 10 mL or 201 mg / 15 mL. When the solvent is an aqueous solution of tetrahydrofuran, the volume ratio of tetrahydrofuran to water is preferably 1:0.5-1.5, such as 1:1. The method and conditions for solid-liquid separation can be conventional methods and conditions in the art, and generally, filtration or filtration after centrifugation can be used; when only filtration is used for solid-liquid separation, the filtration is usually suction filtration. The method and conditions for drying can be conventional methods and conditions in the art, preferably vacuum drying, and more preferably vacuum drying at room temperature for 10-16 hours. In a specific embodiment of preparation method IV of the crystalline form 3, 201.0 mg of the compound of formula I is mixed with 15 mL of ethanol to form a suspension, stirred at a speed of 800 rpm at room temperature for 20 hours, the crystal slurry is suction filtered to separate the solid, and dried at 60 °C for 1 hour to obtain the crystalline form 3. In Preparation Method 5 of the crystalline form 3, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of Formula I, and usually a water bath heating method can be adopted; the temperature of the mixing is preferably 45-55 °C, such as 50 °C. According to the common knowledge in the art, in order to ensure obtaining a clear solution, a hot filtration operation can be carried out after the compound of Formula I is fully dissolved. The target temperature for cooling is preferably 4-20 °C. The mass-to-volume ratio of the compound of Formula I to acetone is preferably 20 mg / (0.4-5 mL). When the solvent is a mixture of methanol and tetrahydrofuran, the volume ratio of methanol to tetrahydrofuran is preferably 1:0.8-1.2, such as 1:1. (4) Preparation Method 1 of the crystalline form 5, which comprises the following steps: mixing the compound of Formula I with acetone to obtain a clear solution, cooling, and stirring for crystallization to obtain the product. Preparation Method 2 of the crystalline form 5, which comprises the following steps: mixing and stirring the compound of Formula I with a solvent, separating the solid and liquid of the crystal slurry, and drying to obtain the product; or, after mixing the compound of Formula I with a solvent, adding seeds of the crystalline form 5, stirring, separating the solid and liquid of the crystal slurry, and drying to obtain the product; the solvent is methyl tert-butyl ether or acetone. In Preparation Method 1 of the crystalline form 5, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of Formula I, and usually a water bath heating method can be adopted; the temperature of the mixing is preferably 45-55 °C, such as 50 °C. According to the common knowledge in the art, in order to ensure obtaining a clear solution, a hot filtration operation can be carried out after the compound of Formula I is fully dissolved. The target temperature for cooling is preferably 4-20 °C. The mass-to-volume ratio of the compound of Formula I to acetone is preferably 20 mg / 4-6 mL, such as 20 mg / 5 mL. In Preparation Method 2 of the crystalline form 5, the crystalline form of the compound of Formula I is preferably the crystalline form 1. The seeds of the crystalline form 5 are added in an optional manner, and the seeds of the crystalline form 5 can be obtained by any preparation method of the crystalline form 5; the addition amount of the seeds of the crystalline form 5 is preferably not more than 2% of the total mass of the crystal slurry. The temperature of the stirring is preferably room temperature, and the stirring time is preferably 1-6 days. The mass-to-volume ratio of the compound of Formula I to the solvent is preferably (18-22 mg) / mL, such as (19.9-20 mg) / mL. The method and conditions for solid-liquid separation can be conventional methods and conditions in the art, and generally filtration or filtration after centrifugation can be adopted; when only filtration is used for solid-liquid separation, the filtration is usually suction filtration. The method and conditions for drying can be conventional methods and conditions in the art, preferably vacuum drying, and more preferably vacuum drying at room temperature for 10-16 hours. (5) The first preparation method of the crystal form 6 includes the following steps: mixing the compound of formula I with a mixture of toluene and methanol to obtain a clear solution, and volatilizing the solvent at room temperature to obtain the product; The second preparation method of the crystal form 6 includes the following steps: mixing the compound of formula I with methanol to obtain a clear solution, and mixing the clear solution and toluene under stirring to precipitate a solid, thus obtaining the product; The third preparation method of the crystal form 6 includes the following steps: mixing the compound of formula I with toluene and stirring for more than 16 hours, and drying the crystal slurry to obtain the product; alternatively, after mixing the compound of formula I with toluene, adding the crystal seeds of the crystal form 6, stirring, and drying the crystal slurry to obtain the product. In the first preparation method of the crystal form 6, the mass-volume ratio of the compound of formula I to the mixture of toluene and methanol is preferably 10 mg / 0.3 - 0.5 mL, such as 10 mg / 0.4 mL. In the mixture of toluene and methanol, the volume ratio of toluene to methanol is preferably 1:0.7 - 1.3, such as 1:1. According to the common knowledge in the art, ultrasonic dispersion operation can be supplemented during the mixing process to obtain a clear solution; after ultrasonic dispersion, filtration can be further carried out to ensure obtaining a clear solution. In the second preparation method of the crystal form 6, the mixing can be carried out under heating conditions to facilitate the dissolution of the compound of formula I. The temperature of the mixing is preferably 45 - 55 °C. According to the common knowledge in the art, in order to ensure obtaining a clear solution, hot filtration operation can be carried out after the compound of formula I is fully dissolved. The mass-volume ratio of the compound of formula I to methanol is preferably 20 mg / 1.2 - 1.6 mL, such as 20 mg / 1.4 mL. The mass-volume ratio of the compound of formula I to toluene is preferably 20 mg / 2.5 - 12.0 mL, such as 20 mg / 3.0 - 11.2 mL. In the third preparation method of the crystal form 6, the crystal form of the compound of formula I is preferably the crystal form 1. The crystal seeds of the crystal form 6 are added in an optional manner, and the crystal seeds of the crystal form 6 can be obtained by any one of the preparation methods of the crystal form 6; the addition amount of the crystal seeds of the crystal form 6 is preferably not more than 2% of the total mass of the crystal slurry. The temperature of the stirring is preferably room temperature, and the stirring time is preferably 16 - 24 hours. The mass-volume ratio of the compound of formula I to the solvent is preferably 5 - 15 mg / mL, such as 10 mg / mL. The drying method and conditions can be the conventional methods and conditions in the art, preferably vacuum drying, more preferably vacuum drying at 50 - 60 °C for about 1 hour. (6) The first preparation method of the crystal form 7 includes the following steps: mixing the compound of formula I with ethyl acetate, stirring at 45 - 55 °C, such as 50 °C for about 30 minutes, separating the solid and liquid of the crystal slurry, and then drying to obtain the product; The second method for preparing the crystal form 7 comprises the following steps: mixing and stirring the compound of formula I with a mixture of N,N-dimethylacetamide and toluene, followed by solid-liquid separation and drying to obtain the product. The third method for preparing the crystal form 7 comprises the following steps: mixing and stirring the crystal form 1 and / or the crystal form 5 with water, followed by solid-liquid separation of the crystal slurry and drying to obtain the product. In the first method for preparing the crystal form 7, the crystal form of the compound of formula I is preferably the crystal form 1. The mass-volume ratio of the compound of formula I to the solvent is preferably (18 - 22 mg) / mL, such as (19.9 - 20 mg) / mL. The method and conditions for solid-liquid separation can be conventional methods and conditions in the art, generally by filtration or filtration after centrifugation; when only filtration is used for solid-liquid separation, the filtration is usually suction filtration. The method and conditions for drying can be conventional methods and conditions in the art, preferably vacuum drying, more preferably vacuum drying at 60 °C for about 1 hour. In the second method for preparing the crystal form 7, the stirring time is preferably about 1 hour. In the mixture of N,N-dimethylacetamide and toluene, the volume ratio of N,N-dimethylacetamide to toluene is preferably 1:8 - 10, such as 1:9. The method and conditions for solid-liquid separation can be conventional methods and conditions in the art, generally by filtration or filtration after centrifugation; when only filtration is used for solid-liquid separation, the filtration is usually suction filtration. The method and conditions for drying can be conventional methods and conditions in the art. In the third method for preparing the crystal form 7, the stirring temperature is preferably room temperature, and the stirring time is preferably about 24 hours. In the present invention, the method and conditions for volatilizing the solvent can be conventional methods and conditions in the art, generally natural volatilization to dryness, usually carried out in an open container. Unless otherwise specified, the preparation method of each crystal form may optionally include the step of drying the obtained crystal form. The drying includes atmospheric drying or vacuum drying. The temperature for vacuum drying can be above about 35 °C, such as above about 40 °C, above about 45 °C, above about 50 °C, for example about 40 - 60 °C. The vacuum degree for vacuum drying can be, for example, 200 - 1500 Pa, such as 500 - 1000 Pa. According to the preparation methods of each crystal form of the present invention, the compound of formula I as a raw material can be its pure product or a crude product prepared by a known method or the method of the present invention. When choosing its crude product as a raw material, an appropriate amount of activated carbon can be added when mixing the raw material with the solvent to improve the product purity. The present invention also provides a pharmaceutical composition, which comprises a therapeutically and / or prophylactically effective amount of the crystal form of the present invention or the crystal form prepared by the preparation method of the present invention, and at least one pharmaceutically acceptable excipient. Wherein, the crystal form can be selected from one or more of the crystal form 1, the crystal form 2, the crystal form 3, the crystal form 5, the crystal form 6, and the crystal form 7. Pharmaceutically acceptable excipients (such as carriers, excipients, etc.) that can be used in the pharmaceutical composition of the present invention include, but are not limited to, ion exchangers, aluminum, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS), such as d-α-tocopheryl polyethylene glycol 1000 succinate, surfactants used in pharmaceutical dosage forms, such as Tween or other similar polymeric delivery matrices, serum proteins, such as human serum albumin, buffering substances, such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polypropylene block polymers, polyethylene glycol, and lanolin. Cyclodextrins, such as α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, or chemically modified derivatives, such as hydroxyalkyl cyclodextrins, including 2-hydroxypropyl-β-cyclodextrin and 3-hydroxypropyl-β-cyclodextrin, or other solubilized derivatives, can also be advantageously used to enhance the delivery of the compounds of the chemical formula described in the present invention. In addition, the pharmaceutical composition may further contain or substantially not contain other forms of the compound of formula I, such as other crystal forms and / or amorphous forms. According to a preferred embodiment of the pharmaceutical composition of the present invention, the ratio of the total molar amount of crystal form 1, crystal form 2, crystal form 3, crystal form 5, crystal form 6, and crystal form 7 to the total molar amount of other forms of the compound of formula I can be greater than 50:50, for example, more than 60:40, more than 70:30, more than 80:20, more than 90:10, more than 95:5, more than 99:1, or 100:0. As an exemplary embodiment, in the pharmaceutical composition of the present invention, the ratio of the molar amount of crystal form 1 to the total molar amount of crystal form 2, crystal form 3, crystal form 5, crystal form 6, crystal form 7, and other forms of the compound of formula I can be greater than 50:50, for example, more than 60:40, more than 70:30, more than 80:20, more than 90:10, more than 95:5, more than 99:1, or 100:0. Alternatively, the ratio of the molar amount of crystal form 2 to the total molar amount of crystal form 1, crystal form 3, crystal form 5, crystal form 6, crystal form 7, and other forms of the compound of formula I can be greater than 50:50, for example, more than 80:20, more than 90:10, more than 95:5, more than 99:1, or 100:0. In the present invention, the pharmaceutical composition can be in solid or liquid form, for example, solid oral dosage forms including tablets, granules, powders, pills and capsules; liquid oral dosage forms including solutions, syrups, suspensions, dispersions and emulsions; injectable preparations including solutions, dispersions and lyophilized products. The preparations can be adapted for rapid release, delayed release or modified release of the active ingredient. They can be conventional, dispersible, chewable, orally dissolving or rapidly melting preparations. Routes of administration include oral, intravenous subcutaneous injection, injection into tissue, transdermal, rectal, intranasal administration, etc. For example, the pharmaceutical composition is a capsule, which contains a therapeutically and / or prophylactically effective amount of the crystalline form described in the present invention, Pearlitol 200SD, sodium bicarbonate, sodium lauryl sulfate and croscarmellose sodium; For example, the pharmaceutical composition is a tablet, the tablet core of which contains a therapeutically and / or prophylactically effective amount of the crystalline form described in the present invention, mannitol, microcrystalline cellulose, sodium bicarbonate powder, anhydrous citric acid, croscarmellose sodium, sodium lauryl sulfate, crospovidone, fumed silica, sodium stearyl fumarate, and water which may or may not be present; Preferably, one or more components in the pharmaceutical composition are ground and / or sieved. According to the present invention, the pharmaceutical composition may further contain one or more therapeutic or prophylactic active ingredients other than the above various forms of the compound of formula I. When the composition of the present invention contains such active ingredients, the above various forms of the compound of formula I and the additional active ingredients can be provided at a dose level of about 1% to 100%, more preferably about 5% to 95% of the doses that can be usually administered in a single treatment regimen. The additional active ingredient can be administered separately from the above various forms of the compound of formula I of the present invention as part of a multi-dose administration regimen. Optionally, the additional active ingredient can be part of a single dosage form and mixed with the above various forms of the compound of formula I of the present invention in a single composition. The pharmaceutical composition can be prepared by methods known to those skilled in the art. For example, one or more of the crystalline forms of the present invention can be mixed with one or more pharmaceutically acceptable excipients and optionally other components present. As an example, solid preparations can be prepared by processes such as direct mixing and granulation. The present invention also provides a method for treating or preventing a disease or disorder, which includes administering an effective amount of one of the crystalline forms or pharmaceutical compositions described in the present invention to a subject to be treated. The present invention also provides a method for modulating (such as inhibiting, antagonizing, activating) kinase activity, which includes contacting a kinase with the crystalline form or pharmaceutical composition described in the present invention. The present invention also provides the use of the crystalline form or pharmaceutical composition in the preparation of a drug. The drug can be used to modulate the kinase activity of a subject in need thereof. Alternatively, the drug can be used to treat or prevent a disease or disorder. Preferably, the disease or disorder can be any one of the diseases or disorders mediated by a kinase (such as one or more of VEGFR, PDGFR, Flt-3, KIT, RET or CSF1R). The disease or disorder can be cancer, including, for example, renal cell carcinoma and gastrointestinal stromal tumor, a tumor or a proliferative disorder. The present invention also provides a method for improving the efficacy of sunitinib or its derivative or reducing its side effects (such as neutropenia and / or fatigue toxicity), including administering an effective amount of a crystalline form or pharmaceutical composition of the present invention in place of sunitinib or its derivative to the subject. The present invention also provides a method for preparing a compound of formula I, including performing the following reaction: Wherein, HOBt represents hydroxybenzotriazole, and EDCI represents 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, Et3N represents triethylamine, and DMF represents N,N-dimethylformamide. The molar ratio of compound A to compound B can be 1:1 to 1:3, such as 1:1 to 1:1.5, for example 1:1.2; The molar ratio of compound A to triethylamine can be 1:1 to 1:10, for example 1:5; The molar ratio of compound A to EDCI can be 1:1 to 1:3, such as 1:1.2 to 1:1.8, for example 1:1.5; Preferably, the reaction is carried out under an inert atmosphere (such as a nitrogen atmosphere); Preferably, the reaction temperature can be 5 to 45 °C, such as 20 - 30 °C; Preferably, after the reaction is completed, an ether solvent, such as methyl tert-butyl ether, is added to the reaction mixture, stirred, filtered, and the filter cake is washed with methyl tert-butyl ether; Preferably, the product after being washed with methyl tert-butyl ether is mixed with methanol or its aqueous solution, such as anhydrous methanol, and heated to reflux; The reflux time is preferably not more than 2 hours, such as 0.5 - 1 hour; Preferably, after reflux, the reaction mixture is cooled to 10 - 20 °C, and stirred for 1 - 3 hours and then filtered; Preferably, the filter cake is washed with methanol, such as cold methanol, and dried to obtain the crude product of the compound of formula I. The drying includes atmospheric drying or vacuum drying. The temperature of vacuum drying can be above about 35 °C, such as above about 40 °C, above about 45 °C, above about 50 °C, for example about 40 - 60 °C. The degree of vacuum for vacuum drying can be, for example, 200 - 1500 Pa, such as 500 - 1000 Pa. Glossary of Terms and Definitions The term "subject" refers to an animal, such as a mammal, including but not limited to primates, such as humans, cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc. In an embodiment of the present invention, the "subject" refers to a human. The term "about" means that, according to the present invention, the described numerical value can include a range of ±20% of the specific numerical value, such as ±10%, such as ±5%, ±1%, ±0.5%, or ±0.1%, to implement the technical solution of the present invention. In the present invention, the term "crystal form" is not only understood as "crystal type" or "crystal structure"; in the technical solution, "crystal form" is more understood as "a substance with a specific crystal structure" or "a crystal of a specific crystal type". In the present invention, the "crystal form" is confirmed by the X-ray diffraction pattern shown. Those skilled in the art can understand that the experimental error therein depends on the instrument conditions, sample preparation, and sample purity. In particular, it is well known to those skilled in the art that the X-ray diffraction pattern usually changes with the instrument conditions. Additionally, the experimental error of the peak angle is usually 5% or less, and the errors of these angles should also be taken into account, usually allowing an error of ±0.2°. Additionally, due to the influence of experimental factors such as sample height, an overall shift of the peak angle will occur, and a certain shift is usually allowed. Therefore, those skilled in the art can understand that any crystal form having a pattern with the same or similar characteristic peaks as in the spectrum of the present invention falls within the scope of the present invention. The "anhydrate" means that the product contains no more than 3.0% by weight, such as no more than 1.5%, such as no more than 1% of water as measured by thermogravimetric analysis (TGA). In the present invention, "room temperature" is the conventional room temperature in the art, generally 10 - 30 °C. In the present invention, "crystal slurry" refers to "a supersaturated solution containing the compound of formula I" (i.e., there are undissolved solids in the solution). "Pharmaceutically acceptable" means present in a form or amount in a drug that has no adverse effects on the subject being administered. In the present invention, unless otherwise specified, the information of each detection instrument and the parameters of the detection method are as follows: (1) X-ray powder diffractometer (XRD) & hot stage XRD, Bruker D8 Advance diffractometer; Technical specifications: Copper target wavelength is Kα irradiation (40Kv, 40mA), θ-2θ goniometer, Mo monochromator, Lynxeye detector; Standard substance: Al2O3; Acquisition software: Diffrac Plus XRD Commander; Analysis software: MDI Jade6; Method parameters: Detection angle, 3-40° 2θ / 3-30° 2θ (hot stage XRD); Step size, 0.02° 2θ; Speed, 0.15s.step -1 ; Detection sample amount > 2mg. (2) Differential scanning calorimeter (DSC), TA Instruments Q200 DSC; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Aluminum crucible; Detection sample amount: 0.5-5mg; Protective gas: Nitrogen; Gas flow rate: 40mL / min; Detection method: Heating rate 10°C / min, equilibrate at 20°C and then heat to 300°C. (3) Thermogravimetric analyzer (TGA), TA Instruments Q500 TGA; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Platinum crucible; Detection sample amount: 1-10mg; Protective gas: Nitrogen; Gas flow rate: 40mL / min; Detection method: High resolution 3.0 (Hi-Res sensitivity 3.0), heating rate 10°C / min, heat to 350°C; (4) Dynamic vapor sorption analyzer (DVS), TA Instruments Q5000 TGA; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Platinum crucible; Detection sample amount: 1-10mg; Protective gas: Nitrogen; Gas flow rate: 10mL / min; Detection method: Equilibrate at 25°C, humidity 0%, isothermal for 90min, test weight change in the range of 0% RH to 80% RH; Judgment criteria: Non-hygroscopic, not higher than 0.2%; Slightly hygroscopic, higher than 0.2% but not higher than 2.0%; Easily hygroscopic, higher than 2% but not higher than 15%; Extremely easily hygroscopic, higher than 15%. (5) Hot stage polarized light microscope (PLM), XP-500E; Shanghai Changfang Optical Instrument Co., Ltd. (6) Solubility determination, visual method; specific method: At 25°C, weigh a known amount of the sample, add the solvent to the sample in portions, stir or use ultrasonic assistance for dissolution until the sample is visually clear, and record the amount of solvent consumed. If the sample is still not clear at a specific concentration, its solubility is expressed as "<" the specific concentration; Judgment criteria: Very soluble, greater than 1 g / mL; Freely soluble, greater than 100 mg / mL but less than or equal to 1 g / mL; Soluble, greater than 33.3 mg / mL but less than or equal to 100 mg / mL; Sparingly soluble, greater than 10 mg / mL but less than or equal to 33.3 mg / mL; Slightly soluble, greater than 1 mg / mL but less than or equal to 10 mg / mL; Very slightly soluble, greater than 0.1 mg / mL but less than or equal to 1 mg / mL; Practically insoluble or insoluble, less than 0.1 mg / mL. Based on common knowledge in the art, the above preferred conditions can be combined arbitrarily to obtain various preferred examples of the present invention. The reagents and raw materials used in the present invention are all commercially available. The beneficial effects of the present invention are as follows: The crystal form of the present invention has good stability and chemical stability, and the reduction of the main component purity under the stability test conditions is less than 2%. Moreover, the pharmaceutical properties, pharmacokinetic characteristics, tissue accumulation and stability (such as grinding stability) of the crystal form of the present invention have all been improved, and it has good medicinal prospects. The inventor also surprisingly found that crystal form 2 has good stability and hygroscopicity, and crystal form 1 can achieve good comprehensive performance in other aspects on the premise of having sufficient stability and improved hygroscopicity, and has excellent drug-forming characteristics. Crystal form 1 and crystal form 2 have the highest solubility in methanol. And the preparation method of the crystal form of the present invention, for example, the preparation method of obtaining crystal form 1 from methanol, can obtain the crystal form of the compound of formula I with good yield and high purity, and the preparation method of the present invention is suitable for large-scale production. Brief Description of the Drawings Figure 1 is the X-ray powder diffraction pattern of crystal form 1. Figure 2 is the polarized light microscope photograph of crystal form 1. Figure 3 is the thermogravimetric analysis spectrum of crystal form 1. Figure 4 is the differential scanning calorimetry diagram of crystal form 1. Figure 5 is the dynamic moisture sorption diagram of crystal form 1. Figure 6 is of the compound of formula I of the present invention 1 1H-NMR spectrum, and the 1H-NMR spectra of crystal form 1, 2, 3, 5, 6 and 7 samples 1 are all consistent with Figure 6. Figure 7 is the X-ray powder diffraction pattern of crystal form 2. Figure 8 is the polarized light microscope photograph of crystal form 2. Figure 9 is the thermogravimetric analysis spectrum of Polymorph 2. Figure 10 is the differential scanning calorimetry chart of Polymorph 2. Figure 11 is the dynamic water adsorption graph of Polymorph 2. Figure 12 is the X-ray powder diffraction pattern of Polymorph 3. Figure 13 is the polarized light microscope photograph of Polymorph 3. Figure 14 is the thermogravimetric analysis spectrum of Polymorph 3. Figure 15 is the differential scanning calorimetry chart of Polymorph 3. Figure 16 is the dynamic water adsorption graph of Polymorph 3. Figure 17 is the X-ray powder diffraction pattern of Polymorph 5. Figure 18 is the polarized light microscope photograph of Polymorph 5. Figure 19 is the thermogravimetric analysis spectrum of Polymorph 5. Figure 20 is the differential scanning calorimetry chart of Polymorph 5. Figure 21 is the dynamic water adsorption graph of Polymorph 5. Figure 22 is the X-ray powder diffraction pattern of Polymorph 6. Figure 23 is the polarized light microscope photograph of Polymorph 6. Figure 24 is the thermogravimetric analysis spectrum of Polymorph 6. Figure 25 is the differential scanning calorimetry chart of Polymorph 6. Figure 26 is the dynamic water adsorption graph of Polymorph 6. Figure 27 is the X-ray powder diffraction pattern of Polymorph 7. Figure 28 is the polarized light microscope photograph of Polymorph 7. Figure 29 is the thermogravimetric analysis spectrum of Polymorph 7. Figure 30 is the differential scanning calorimetry chart of Polymorph 7. Figure 31 is the dynamic water adsorption graph of Polymorph 7. Figure 32 is the isothermal adsorption curve of Polymorph 1. Figure 33 is the isothermal adsorption curve of Polymorph 2. Figure 34 is the isothermal adsorption curve of Polymorph 3. Figure 35 is the isothermal adsorption curve of Polymorph 5. Figure 36 is the isothermal adsorption curve of Polymorph 6. Figure 37 is the isothermal adsorption curve of Polymorph 7. Figure 38 is the XRD pattern of the crystal form stability of Polymorph 1. Figure 39 is the DSC pattern of the crystal form stability of Polymorph 1. Figure 40 is the XRD pattern of the crystal form stability of Polymorph 2. Figure 41 is the DSC pattern of the crystal form stability of Polymorph 2. Figure 42 is the XRD pattern of the crystal form stability of Polymorph 3. Figure 43 is the DSC pattern of the crystal form stability of crystal form 3. Figure 44 is the XRD pattern of the crystal form stability of crystal form 5. Figure 45 is the DSC pattern of the crystal form stability of crystal form 5. Figure 46 is the XRD pattern of the crystal form stability of crystal form 6. Figure 47 is the DSC pattern of the crystal form stability of crystal form 6. Figure 48 is the XRD pattern of the crystal form stability of crystal form 7. Figure 49 shows the conversion of crystal forms 1, 2, 3, and 7 to crystal form 2 in acetone, ethyl acetate, methanol, or water. Figure 50 shows the conversion of crystal forms 1, 2, 3, and 7 to crystal form 3 in tetrahydrofuran (THF). Figure 51 shows the comparison of the XRD patterns of crystal forms 1 and 2, where the upper spectrum is for crystal form 1 and the lower spectrum is for crystal form 2. Figure 52 shows the relationship between the peak area at 2θ = 10.1° and the weight percentage content of crystal form 2 in crystal form 1. Figure 53 shows the comparison of the XRD patterns of crystal form 1 before and after grinding, where the upper spectrum is the XRD pattern before grinding and the lower spectrum is the XRD pattern after grinding. Detailed Embodiments The present invention will be further illustrated below by way of examples, but the present invention is not thereby limited to the scope of the described examples. For the experimental methods without specific conditions noted in the following examples, they are carried out according to conventional methods and conditions, or selected according to the product specifications. Unless otherwise specified, in the following examples and effect examples, the information of the detection instruments and the parameters of the detection methods used are as follows: (1) X-ray powder diffractometer (XRD) & hot stage XRD, Bruker D8 Advance diffractometer; Technical indicators: The wavelength of the copper target is Kα irradiation (40Kv, 40mA), θ-2θ goniometer, Mo monochromator, Lynxeye detector; Standard substance: Al2O3; Acquisition software: Diffrac Plus XRD Commander; Analysis software: MDI Jade 6; Method parameters: Detection angle, 3 - 40° 2θ / 3 - 30° 2θ (hot stage XRD); Step size, 0.02° 2θ; Speed, 0.15 s / step; Detection sample amount > 2 mg. (2) Differential Scanning Calorimeter (DSC), TA Instruments Q200 DSC; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Aluminum crucible; Test sample amount: 0.5 - 5 mg; Protective gas: Nitrogen; Gas flow rate: 40 mL / min; Detection method: Heating rate 10 °C / min, equilibrate at 20 °C and then heat to 300 °C. (3) Thermogravimetric Analyzer (TGA), TA Instruments Q500 TGA; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Platinum crucible; Test sample amount: 1 - 10 mg; Protective gas: Nitrogen; Gas flow rate: 40 mL / min; Detection method: High Resolution 3.0 (Hi-Res sensitivity 3.0), heating rate 10 °C / min, heat to 350 °C; (4) Dynamic Vapor Sorption (DVS), TA Instruments Q5000 TGA; Control software: Thermal Advantage; Analysis software: Universal Analysis; Sample pan: Platinum crucible; Test sample amount: 1 - 10 mg; Protective gas: Nitrogen; Gas flow rate: 10 mL / min; Detection method: Equilibrate at 25 °C, humidity 0%, isothermal for 90 min, test weight change in the range of 0% RH to 80% RH; Judgment criteria: Non-hygroscopic, not higher than 0.2%; Slightly hygroscopic, higher than 0.2% but not higher than 2.0%; Easily hygroscopic, higher than 2% but not higher than 15%; Extremely easily hygroscopic, higher than 15%. (5) Hot Stage Polarizing Light Microscope (PLM), XP-500E; Shanghai Changfang Optical Instrument Co., Ltd. (6) Solubility determination, visual method; Specific method: At 25 °C, weigh a known amount of sample, add solvent to the sample in portions, stir or use ultrasonic assistance for dissolution until the sample is visually clear, and record the amount of solvent consumed. If the sample is still not clear at a specific concentration, its solubility is expressed as "<" the specific concentration; Judgment criteria: Extremely soluble, greater than 1 g / mL; Freely soluble, greater than 100 mg / mL but less than or equal to 1 g / mL; Soluble, greater than 33.3 mg / mL but less than or equal to 100 mg / mL; Sparingly soluble, greater than 10 mg / mL but less than or equal to 33.3 mg / mL; Slightly soluble, greater than 1 mg / mL but less than or equal to 10 mg / mL; Very slightly soluble Soluble, greater than 0.1 mg / mL but less than or equal to 1 mg / mL; Sparingly soluble or insoluble, less than 0.1 mg / mL. (7) Nuclear magnetic resonance spectrometer (NMR), Bruker Ascend 500; Detection type: 1H NMR; Full-frequency excitation, spectral width 30 ppm single pulse, 30° angle excitation scanned 16 times, digital orthogonal detection, temperature controlled at 298K. (8) High performance liquid chromatography (HPLC), Ultimate 3000; Test purposes: Solubility test (area method), related substances (area normalization method). The method parameters are as follows: Chromatographic column: Shimadzu shim-pack VP-ODS (150L*4.6), Waters symmetry C18 (3.9*150mm 5μm); Column temperature: 25°C; Flow rate: 1.0 mL / min; Detection wavelength: 214 nm; Injection volume: 10 μL; Running time: 20 min; Sampling solvent: ACN; Injection concentration: 0.2 mg / mL; Mobile phase: Mobile phase A, H2O:CAN:H3PO4 = 90:10:0.1, Mobile phase B: H2O:CAN:H3PO4 = 10:90:0.1; Elution gradient is shown in Table 7 below: Table 7 In the following examples, "volatile solvent" means the solvent is naturally volatilized to dryness in an open container; "room temperature" is 10 - 30°C (30 - 70% RH); "crystal slurry" means a supersaturated solution containing the compound of formula I; "overnight" means the time spanning the night, usually 10 - 16 hours. In the following example tables, "NA" means "not applicable" or "not used". Preparation Example Under a nitrogen atmosphere and at 20 - 30°C, in a reactor, compound A (13.00 kg, 1 eq.) was added to DMF (97.8 kg). Subsequently, under a nitrogen atmosphere and at 20 - 30°C, triethylamine ("TEA", 21.88 kg, 5 eq.), hydroxybenzotriazole ("HOBt", 8.78 kg, 1.5 eq.), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide ("EDCI", 12.42 kg, 1.5 eq.) and compound B (10.1 kg, 1.2 eq.) were added to the reactor. Under a nitrogen atmosphere and at 20 - 30°C, the mixture was stirred for 22 hours. After the reaction was completed, the reaction mixture was transferred to a clean container and weighed (163.8 kg). Approximately 1 / 4 of the reaction mixture (40.90 kg) was added to the reactor, and then methyl tert-butyl ether ("MTBE", 62.8 kg) was added to the reaction mixture at 10 - 20°C. The resulting suspension was stirred at 10 - 20°C for 2 hours and then filtered. The remaining 3 / 4 of the reaction solution was treated similarly. The filter cakes were combined and washed with MTBE (46.2 kg). A portion of the combined solid (20.0 kg) was added to anhydrous methanol (74.2 kg), and the resulting mixture was heated to reflux for 45 minutes. Subsequently, the reaction mixture was cooled to 10 - 20°C within 1 - 2 hours and then stirred at 10 - 20°C for an additional 1.5 hours. The resulting suspension was filtered. The other substances washed with MTBE were treated similarly. The filter cakes were combined and washed with cold methanol (44.2 kg). The wet crude product was dried under reduced pressure (500 - 1000 Pa) at 50°C for 13 hours and then at 76°C for 23 hours to obtain approximately 12 kg of the crude product of the compound of formula I. Example 1 Method 1 for preparing polymorph 1 of the compound of formula I: 5 mg of the compound of formula I was mixed with a single solvent, or 10 mg of the compound of formula I was mixed with solvent 1 and solvent 2 to obtain a clear solution, which was left to evaporate to dryness at the corresponding temperature, and thus obtained. The specific preparation parameters are shown in Table 8 below. Table 8 Temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result Analysis Room temperature Methanol NA 1.0 Polymorph 1 40°C Methanol NA 1.0 Polymorph 1 Room temperature Methanol Acetone 0.2 / 0.4 Polymorph 1 40°C Methanol Water 1.2 / 0.2 Polymorph 1 Upon detection, the products prepared by the above preparation methods were all polymorph 1. The X-ray powder diffraction pattern of this polymorph 1 is shown in Figure 1, and the detailed data of its X-ray powder diffraction pattern are shown in Table 1 above. The polarized light microscope photograph of this polymorph 1 is shown in Figure 2, showing that it is an elongated rod-shaped crystal. This polymorph 1 has a thermogravimetric analysis spectrum as shown in Figure 3, showing that polymorph 1 has a weight loss of 2.6% before 170°C, which is the anhydrous form, and the decomposition temperature is 320°C; this polymorph 1 has a differential scanning calorimetry chart as shown in Figure 4, showing that it has an exothermic peak at 150 - 170°C, which was confirmed by XRD to be an exothermic polymorphic transition peak, and the polymorph after the transition is polymorph 3, and the melting point of this polymorph 1 is 260°C; this polymorph 1 has a dynamic moisture sorption chart as shown in Figure 5, showing that its weight change is 2.8% in the range of 0% RH to 80% RH. The 1 1H-NMR spectra of the compound of formula I and this polymorph 1 are both as shown in Figure 6, indicating that its chemical structure is as shown in formula I as follows: The solubility test results show that the solubility of this polymorph 1 in common solvents at 25 °C is as follows: the solubility in methanol is 5 - 12.5 mg / mL; the solubility in ethanol is 1 - 2.5 mg / mL; the solubility in water is < 1 mg / mL; the solubility in acetone is 1 - 2.5 mg / mL; the solubility in ethyl acetate is < 1 mg / mL; the solubility in methyl tert-butyl ether is < 1 mg / mL; the solubility in tetrahydrofuran is 1 - 2.5 mg / mL; the solubility in acetonitrile is < 1 mg / mL; the solubility in toluene is < 1 mg / mL; the solubility in n-heptane is < 1 mg / mL. Example 2 The second and third preparation methods of polymorph 1 of the compound of formula I: Take 20 mg of the compound of formula I and mix it with 1.4 mL of methanol. After heating to 50 °C until it dissolves clearly, filter while it is hot to obtain a clear solution. The operation of adding solvent 2 to the clear solution under stirring is denoted as forward addition (corresponding to the second preparation method), and the operation of adding the clear solution to solvent 2 under stirring is denoted as reverse addition (corresponding to the third preparation method). After solid starts to precipitate, continue stirring until the solid completely precipitates, and then it is obtained. The specific preparation parameters are shown in Table 9 below. Table 9 Addition method Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result analysis Forward addition Methanol Acetone 1.4 / 3.0 Polymorph 1 Forward addition Methanol Ethyl acetate 1.4 / 3.0 Polymorph 1 Forward addition Methanol Methyl tert-butyl ether 1.4 / 3.0 Polymorph 1 Forward addition Methanol Acetonitrile 1.4 / 3.0 Polymorph 1 Reverse addition Methanol Water 1.4 / 5.2 Polymorph 1 Reverse addition Methanol Methyl tert-butyl ether 1.4 / 11.2 Polymorph 1 After detection, the products obtained by the above preparation methods are all polymorph 1, and their XRD, PLM, TGA, DSC, DVS, 1 1H-NMR and solubility and other detection results are the same as those in Example 1. Example 3 The fourth preparation method of polymorph 1 of the compound of formula I: Take 20 mg of the compound of formula I, mix it with the corresponding solvent under a 50 °C water bath until it dissolves clearly, filter while it is hot to obtain a clear solution, and naturally cool it to 4 °C, then stir to crystallize and precipitate solids, and then it is obtained. The specific preparation parameters are shown in Table 10 below. Table 10 Crystallization temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result analysis 4 °C Methanol NA 1.4 Polymorph 1 4 °C Methanol Water 1.4 / 0.4 Polymorph 1 4 °C Methanol Ethyl acetate 0.4 / 0.8 Polymorph 1 4 °C Methanol Methyl tert-butyl ether 0.8 / 1.4 Polymorph 1 4 °C Methanol Acetonitrile 0.4 / 0.4 Polymorph 1 After testing, the products obtained by the above preparation methods are all crystal form 1, and the test results of XRD, PLM, TGA, DSC, DVS, 1 1H-NMR and solubility are the same as those in Example 1. Example 4 Preparation method 4 of crystal form 1 of the compound of formula I: Add the crude product (2.0 kg) of the compound of formula I, anhydrous methanol (72.0 kg) and activated carbon (0.20 kg) to the reactor, and heat under reflux for 1.5 hours. Filter the reaction solution, and heat the filtrate under reflux for 40 minutes. Filter the obtained solution hot into the reactor, and then concentrate under reduced pressure (500 - 1000 Pa) for about 4 hours to remove about 85 L of methanol. Cool the obtained suspension to 10 - 20 °C, then stir at 10 - 20 °C for about 45 minutes, and then filter. After washing the filter cake with methanol, the purity is detected by HPLC to be 99.9%. The obtained solid is dried under reduced pressure (500 - 1000 Pa) at 40 - 60 °C, and the obtained product is detected by XRD to be crystal form 1, and the yield exceeds 80%. Example 5 Preparation method of crystal form 2 of the compound of formula I. The crystal form of the compound of formula I used herein is crystal form 1. Preparation of samples numbered 1 - 9: Take 10 mg of the compound of formula I and mix it with the corresponding solvent to obtain a suspension, stir at the corresponding temperature for 5 - 6 days, centrifuge the crystal slurry, and dry the solid to obtain. Preparation of sample numbered 10: Take 199 mg of the compound of formula I and mix it with the corresponding solvent to obtain a suspension, stir at 50 °C for 2 hours, then stir at room temperature for 2 days, filter the crystal slurry, and dry the solid under vacuum at room temperature overnight to obtain. Preparation of sample numbered 11: Take 200 mg of the compound of formula I and mix it with the corresponding solvent to obtain a suspension, stir at 4 °C for 5 days, filter the crystal slurry, and dry the solid under vacuum at room temperature overnight to obtain. Preparation of sample numbered 12: Take 200 mg of the compound of formula I and mix it with the corresponding solvent to obtain a suspension, stir at room temperature for 3 days, filter the crystal slurry, and dry the solid under vacuum at room temperature overnight to obtain. Specific preparation parameters are shown in Table 11 below. Table 11 Serial number Temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result analysis 1 Room temperature Water NA 0.5 Crystal form 2 2 50 °C Ethyl acetate NA 0.5 Crystal form 2 3 50 °C Toluene NA 0.5 Crystal form 2 4 Room temperature Water Acetone 0.2 / 0.4 Crystal form 2 5 Room temperature water - acetonitrile 0.1 / 0.5 Crystal form 26 50℃ Ethanol - toluene 0.4 / 0.4 Crystal form 27 50℃ Water - acetonitrile 0.2 / 0.4 Crystal form 28 4℃ Water - methanol 0.4 / 0.4 Crystal form 29 - Ethyl acetate NA 5 Crystal form 210 4℃ Water - methanol 8 / 8 Crystal form 211 Room temperature water - acetonitrile 2 / 10 Crystal form 2 Upon detection, the products obtained by the above - mentioned preparation methods are all crystal form 2. The X - ray powder diffraction pattern of this crystal form 2 is shown in Figure 7, and the detailed data of its X - ray powder diffraction pattern are shown in Table 2 as mentioned above. The polarized light microscope photograph of this crystal form 2 is shown in Figure 8, showing that it is composed of fine needle - shaped crystals. This crystal form 2 has a thermogravimetric analysis spectrum as shown in Figure 9, showing that it has a weight loss of 0.3% before 200℃, it is an anhydrous substance, and the decomposition temperature is 320℃; this crystal form 2 has a differential scanning calorimetry chart as shown in Figure 10, showing that the melting point of this crystal form 2 is 258℃; this crystal form 2 has a dynamic water adsorption chart as shown in Figure 11, showing that its weight change is 0.05% in the range of 0% RH to 80% RH. The 1 1H - NMR spectrum is consistent with Figure 6. Example 6 Preparation methods one, two, and three for crystal form 3 of the compound of formula I: Take 5 mg of the compound of formula I and mix it with a single solvent, or take 10 mg of the compound of formula I and mix it with solvent 1 and solvent 2 to obtain a clear solution, and let it stand at the corresponding temperature and naturally evaporate to dryness to obtain the product. The specific preparation parameters are shown in Table 12 below. Table 12 Preparation method Temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result analysis Preparation method two Room temperature Ethanol NA 3.0 Crystal form 3 Preparation method one Room temperature Tetrahydrofuran NA 5.0 Crystal form 3 Preparation method one 40℃ Tetrahydrofuran NA 5.0 Crystal form 3 Preparation method three 60℃ Ethanol Water 1.0 / 0.2 Crystal form 3 Upon detection, the products obtained by the above - mentioned preparation methods are all crystal form 3. The X - ray powder diffraction pattern of this crystal form 3 is shown in Figure 12, and the detailed data of its X - ray powder diffraction pattern are shown in Table 3 as mentioned above. The polarized light microscope photograph of this crystal form 3 is shown in Figure 13, showing that it is composed of fine particles with some agglomeration. This crystal form 3 has a thermogravimetric analysis spectrum as shown in Figure 14, showing that it has a weight loss of 0.2% before 200℃, it is an anhydrous substance, and the decomposition temperature is 320℃; this crystal form 3 has a differential scanning calorimetry chart as shown in Figure 15, showing that the melting point of this crystal form 3 is 261℃; this crystal form 3 has a dynamic water adsorption chart as shown in Figure 16, showing that its weight change is 0.08% in the range of 0% RH to 80% RH. The 1 1H - NMR spectrum is consistent with Figure 6. Example 7 Method 4 for preparing polymorph 3 of the compound of Formula I. The polymorph of the compound of Formula I used herein is polymorph 1. Preparation of Samples No. 1 - 3: Take 10 mg of the compound of Formula I and mix it with the corresponding solvent to obtain a suspension, stir at the corresponding temperature for 5 - 6 days, centrifuge the crystal slurry, and dry the solid to obtain the product. Preparation of Samples No. 4 - 6: Take 200 mg of the compound of Formula I and mix it with the corresponding solvent to obtain a suspension, stir at the corresponding temperature for 5 days, filter the crystal slurry, and dry the solid under vacuum at room temperature overnight to obtain the product. Preparation of Sample No. 7: Mix 201.0 mg of the compound of Formula I with the corresponding solvent to obtain a suspension, stir at 800 rpm at the corresponding temperature for 20 hours, filter the crystal slurry to separate the solid, and dry it at 60 °C for 1 hour to obtain the product. For specific preparation parameters, see Table 13 below. Table 13 Table 13 Serial Number Temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result Analysis 1 Room temperature Ethanol NA 0.5 Polymorph 3 2 4 °C Acetone NA 0.5 Polymorph 3 3 Room temperature Water Tetrahydrofuran 0.4 / 0.4 Polymorph 3 4 Room temperature Ethanol NA 8 Polymorph 3 5 4 °C Acetone NA 8 Polymorph 3 6 Room temperature Water Tetrahydrofuran 5 / 5 Polymorph 3 7 Room temperature Ethanol NA 15 Polymorph 3 Upon detection, the products obtained by the above preparation methods are all polymorph 3, and their XRD, PLM, TGA, DSC, DVS, and 1 1H - NMR and other detection results are the same as those in Example 4. Example 8 Method 5 for preparing polymorph 3 of the compound of Formula I: Take 20 mg of the compound of Formula I, mix it with the corresponding solvent under a 50 °C water bath until it dissolves clearly, filter while it is hot to obtain a clear solution, naturally cool it to 4 °C, stir for crystallization, and precipitate the solid to obtain the product. For specific preparation parameters, see Table 14 below. Table 14 Crystallization Temperature Solvent 1 Solvent 2 Solvent 1 / Solvent 2 (mL) Result Analysis 4 °C Tetrahydrofuran NA 5 Polymorph 3 4 °C Methanol Tetrahydrofuran 0.2 / 0.2 Polymorph 3 Upon detection, the products obtained by the above preparation methods are all polymorph 3, and their XRD, PLM, TGA, DSC, DVS, and 1 1H - NMR and other detection results are the same as those in Example 4. Example 9 Method 6 for preparing polymorph 3 of the compound of Formula I: Heat polymorph 1 to 180 °C, and then cool it to room temperature to obtain the product. After testing, the products obtained by the above preparation methods are all crystal form 3, and their XRD, PLM, TGA, DSC, DVS and 1 1H-NMR and other test results are the same as those in Example 4. Example 10 A preparation method for crystal form 5 of the compound of formula I. Take 20 mg of the compound of formula I, mix it with 5 mL of acetone in a 50 °C water bath until dissolved clearly, then filter while it is hot to obtain a clear solution, cool it naturally to 4 °C, stir to crystallize, precipitate solids, and after centrifugation, take the solids and dry them in vacuo at room temperature to obtain the product. After testing, the product obtained by the above preparation method is crystal form 5. The X-ray powder diffraction pattern of this crystal form 5 is shown in Figure 17, and the detailed data of its X-ray powder diffraction pattern are shown in Table 4 above. The polarized light microscope photograph of this crystal form 5 is shown in Figure 18, showing that it is fine particles with some agglomeration. This crystal form 5 has a thermogravimetric analysis spectrum as shown in Figure 19, showing that it has a weight loss of 1.2% before 200 °C, and it is an anhydrous substance with a decomposition temperature of 319 °C; this crystal form 5 has a differential scanning calorimetry chart as shown in Figure 20, showing that the melting point of this crystal form 5 is 258 °C, and the broad endothermic peak before 100 °C is caused by the removal of surface solvent; this crystal form 5 has a dynamic water sorption graph as shown in Figure 21, showing that its weight change in the range of 0% RH to 80% RH is 2.5%. The 1 1H-NMR spectrum is consistent with Figure 6. Example 11 A preparation method for crystal form 5 of the compound of formula I. The crystal form of the compound of formula I used herein is crystal form 1. Preparation of sample No. 1: Take 199 mg of the compound of formula I and mix it with 10 mL of methyl tert-butyl ether to obtain a suspension, stir it at room temperature for 2 days, filter the crystal slurry, and dry the solid in vacuo at room temperature overnight to obtain the product. Preparation of sample No. 2: Take 600 mg of the compound of formula I and mix it with 30 mL of methyl tert-butyl ether, then add crystal seeds of crystal form 5 with a mass of 2% of the crystal slurry, stir it at room temperature for 1 day, filter the crystal slurry, and dry the solid in vacuo at room temperature overnight to obtain the product. Preparation of sample No. 3: The preparation method is the same as that of sample No. 1, except that acetone is used to replace methyl tert-butyl ether. After testing, the products obtained by the above preparation methods are all crystal form 5, and their XRD, PLM, TGA, DSC, DVS and 1 1H-NMR and other test results are the same as those in Example 9. Example 12 A preparation method for crystal form 6 of the compound of formula I: Mix 10 mg of the compound of Formula I with 0.4 mL of a mixture of toluene and methanol (volume ratio of toluene to methanol is 1:1), filter after ultrasonic dissolution to clarity to obtain a clear solution, and allow it to evaporate to dryness naturally at room temperature to obtain the product. Upon detection, the product prepared by the above preparation method is Crystal Form 6. The X-ray powder diffraction pattern of this Crystal Form 6 is shown in Figure 22, and the detailed data of its X-ray powder diffraction pattern are shown in Table 5 above. The polarized light microscope photograph of this Crystal Form 6 is shown in Figure 23, showing that it is composed of fine particles with some aggregation. This Crystal Form 6 has a thermogravimetric analysis spectrum as shown in Figure 24, showing a weight loss of 0.7% before 200 °C, being an anhydrous substance with a decomposition temperature of 320 °C; this Crystal Form 6 has a differential scanning calorimetry chart as shown in Figure 25, showing that the melting point of this Crystal Form 6 is 259 °C; this Crystal Form 6 has a dynamic vapor sorption chart as shown in Figure 26, showing a weight change of 0.26% in the range of 0% RH to 80% RH. The 1 1H-NMR spectrum is consistent with Figure 6. Example 13 The second preparation method of Crystal Form 6 of the compound of Formula I. Preparation of the sample of No. 1: Mix 20 mg of the compound of Formula I with 1.4 mL of methanol, heat to 50 °C until dissolved to clarity, filter while hot to obtain a clear solution, add 3.0 mL of toluene to the clear solution under stirring conditions, continue stirring after the solid starts to precipitate until the solid completely precipitates to obtain the product. Preparation of the sample of No. 2: Mix 20 mg of the compound of Formula I with 1.4 mL of methanol, heat to 50 °C until dissolved to clarity, filter while hot to obtain a clear solution, add the clear solution to 11.2 mL of toluene under stirring conditions, continue stirring after the solid starts to precipitate until the solid completely precipitates to obtain the product. Upon detection, the products prepared by the above preparation methods are all Crystal Form 6, and their XRD, PLM, TGA, DSC, DVS and 1 1H-NMR and other test results are the same as those in Example 12. Example 14 The third preparation method of Crystal Form 6 of the compound of Formula I. The crystal form of the compound of Formula I used herein is Crystal Form 1. Preparation of the sample of No. 1: Mix 200 mg of the compound of Formula I with 20 mL of toluene, stir at room temperature for 16 - 22 hours, and then vacuum dry the crystal slurry at 60 °C for 1 hour to obtain the product. Preparation of the sample of No. 2: Mix 600 mg of the compound of Formula I with 60 mL of toluene, then add crystal seeds of Crystal Form 6 accounting for 2% of the crystal slurry mass, stir at room temperature for 1 day, and then vacuum dry the crystal slurry at 50 °C for 1 hour to obtain the product. Upon detection, the products obtained by the above preparation methods are all crystal form 6, and the detection results of XRD, PLM, TGA, DSC, DVS and 1 1H-NMR, etc. are the same as those in Example 11. In addition, during the preparation of the sample No. 1, a sample was taken when stirring at room temperature for 6 hours. After suction filtration, caking was found, and the wet product was detected to contain crystal form 1. Example 15 Preparation method 1 of crystal form 7 of the compound of formula I. Preparation of sample No. 1: 199 mg of the compound of formula I was mixed with 10 mL of ethyl acetate, stirred at 50 °C for 30 minutes, and after filtration, the filter cake was dried in vacuo at 60 °C for 1 hour to obtain. Preparation of sample No. 2: 600 mg of the compound of formula I was mixed with 30 mL of ethyl acetate, stirred at 50 °C for 30 minutes, and after filtration, the filter cake was dried in vacuo at 60 °C for 1 hour to obtain. Upon detection, the products obtained by the above preparation methods are all crystal form 7. The X-ray powder diffraction pattern of this crystal form 7 is shown in Figure 27, and the detailed data of its X-ray powder diffraction pattern are shown in Table 7 above. The polarized light microscope photograph of this crystal form 7 is shown in Figure 28, showing that it is fine particles with partial aggregation. This crystal form 7 has a thermogravimetric analysis spectrum as shown in Figure 29, showing that it has a weight loss of 0.5% before 200 °C, it is an anhydrous substance, and the decomposition temperature is 320 °C; this crystal form 7 has a differential scanning calorimetry chart as shown in Figure 30, showing that the melting point of this crystal form 7 is 259 °C; This crystal form 7 has a dynamic moisture sorption diagram as shown in Figure 31, showing that its weight change is 0.27% in the range of 0% RH to 80% RH. The 1 1H-NMR spectrum is consistent with Figure 6. Example 16 Preparation method 2 of crystal form 7 of the compound of formula I (wherein the crystal form of the compound of formula I used is crystal form 1): The compound of formula I was mixed with a mixture of N,N-dimethylacetamide and toluene (the volume ratio of N,N-dimethylacetamide to toluene is 1:9). After stirring, the crystal slurry was filtered and dried to obtain. Upon detection, the products obtained by the above preparation methods are all crystal form 7, and the detection results of XRD, PLM, TGA, DSC, DVS and 1 1H-NMR, etc. are the same as those in Example 14. Effect Example 1 The isothermal adsorption curves of the samples of crystal forms 1, 2, 3, 5, 6 and 7 are shown in Figures 32 to 37. Effect Example 2 The crystal form stabilities of crystal forms 1, 2, 3, 5, 6 and 7 were investigated. The experimental conditions were as follows: sealed and placed at 80 °C for 24 hours, and placed open at 25 °C / 60% RH (relative humidity) and 40 °C / 75% RH for 7 days. The detection methods were: HPLC (only for the starting sample and the sample under the condition of 24 hours at 80 °C), XRD, and DSC. Investigation results: 1) XRD detection and DSC detection showed that the crystal forms and melting points of the samples of crystal forms 1, 2, 3, 5, 6, and 7 were basically unchanged and relatively stable; the specific detection results are shown in Figures 38 - 48, and the DSC pattern of the crystal form stability of crystal form 7 is shown in Figure 30; 2) HPLC detection showed that the main component purity of all crystal form samples under the condition of 24 hours at 80 °C decreased compared with the starting sample, but all were less than 2%; the specific data are shown in Table 15. Note: The impurity with a retention time of 4.73 minutes is the trans form of the compound, and the result is related to the degree of light avoidance during detection. Table 15 In addition, the long - term stability of crystal form 1 at 25 °C / 60% RH for 12 months, 24 months, 36 months, and 48 months was also investigated. The results showed that this crystal form was basically unchanged. Effect Example 3: Thermodynamic stability experiment Crystal forms 1, 2, 3, and 7 of the compound of formula I were respectively mixed with acetone, ethyl acetate, methanol, water, and tetrahydrofuran and kept at 60 °C for one day to study the thermodynamic stability of each crystal form. The insoluble solids were filtered and recovered for XRD analysis. Analysis conditions: Shimadzu XRD - 6000, CuK source 40 kV, 30 mA; detection angle: 5 - 50°, speed: 5° / min. The results showed that treating crystal forms 1, 2, 3, and 7 with acetone, ethyl acetate, methanol, or water could convert the said crystal forms into crystal form 2. However, according to the peak at about 13° of the 2θ angle in Figure 49, when using methanol, it was not completely converted into crystal form 2. Figure 50 showed that using THF could provide crystal form 3. Effect Example 4: Stability of crystal form 1 in methanol The stability results of crystal form 1 in methanol - containing water at different temperatures and times were as follows. The results showed that high temperature and moisture could accelerate the conversion of crystal form 1 to crystal form 2. Table 16 Effect Example 5: Quantitative Detection of Polymorph 2 in Polymorph 1 The content of polymorph 2 in polymorph 1 of formula I compound was analyzed by the XRD pattern obtained by Shimadzu XRD-6000, CuK source ( 40 kV, 30 mA). Detection angle: 9.6 - 10.4° 2θ; Step size: 0.02° 2θ; Counting time: 10 s. The XRD patterns of polymorphs 1 and 2 were compared in Figure 51. Among them, the peak of polymorph 1 at 2θ of 10.1° was very weak, while polymorph 2 had a strong characteristic peak. Therefore, the amount of polymorph 2 in polymorph 1 could be determined using the peak area of this peak. Polymorphs 1 and 2 were sieved through a 100-mesh sieve to ensure that the samples had similar particle sizes. The samples were prepared by mixing appropriate amounts (weight ratio) of polymorphs 1 and 2, as shown in Table 17. Determination was performed in parallel three times, and the average was taken as the peak intensity at 2θ of 10.1°. Table 17: Peak Areas of Samples with Different Contents (weight ratio) of Polymorph 2 in Polymorph 1 at 2θ of 10.1° As shown in Figure 52, the peak area at 2θ of 10.1° had a linear relationship with the weight percentage of polymorph 2 in polymorph 1. This indicated that when the content of polymorph 2 in polymorph 1 was 0.96% to 15.55%, its content could be accurately determined by this method. Samples with polymorph 2 contents of 4.75 wt% and 6.36 wt% were prepared respectively, and the peak areas at 2θ of 10.1° were measured. Moreover, the peak areas were also calculated through the linear relationship in Figure 52. As shown below, the deviation of the calculated values was within 10% of the measured values. Table 18 Effect Example 6: Solubility Determination The solubility detection method was as follows: An appropriate amount of the sample was taken to form a suspension in water, stirred in a water bath at 25 °C, and the solutions were taken at 0.5 h and 4 h respectively for HPLC concentration detection. Taking polymorph 1 as the standard, a solution with a concentration of 204.2 μg*mL -1 was prepared for HPLC detection. Assuming its content was 100%, it was detected 7 times, and the average peak area was 159.691 mAU*min (retention time 7.4 min). Result analysis: The solubility detection results of the polymorphs are shown in Table 19 below. The results showed that the solubility of polymorph 1 was much higher than that of the most stable polymorph 2. Table 19 Effect Example 7: Vapor Stress Crystallization Experiment of Crystal Form 1 Take about 10 mg of crystal form 1 and place it in the corresponding environment. The solid was characterized by XRD at different times, and the characterization results showed that only the known crystal form 1 appeared in this experiment. The specific experiments and results are shown in Table 20 below. The results show that crystal form 1 is stable under these conditions. Table 20 Effect Example 8: Pharmaceutical Property Experiments of Crystal Form 1 and Crystal Form 2 The water content, solubility, and dissolution rate of crystal forms 1 and 2 were measured using the above methods. The results are shown in Table 21, which shows that the solubility, dissolution rate, and water content (overall pharmaceutical properties) of crystal form 1 are higher than those of crystal form 2. Crystal forms 1 and 2 have the highest solubility in methanol. Table 21 Effect Example 9: Pharmacokinetic Experiment Twelve Sprague Dawley rats weighing 230 - 250 g were randomly divided into 2 groups, with each group including 3 males and 3 females. Crystal forms 1 and 2 were respectively formulated as suspensions in 0.5% carboxymethylcellulose (CMC). The rats were fasted for 12 hours with free access to water, and then orally administered at a dose of 10 mg / kg. Blood samples (0.2 - 0.3 ml) were collected in heparinized anticoagulant tubes before dosing and at 15, 30, 60, 120, 240, 360, 480, 720, and 1440 minutes after oral administration. Plasma was prepared by centrifugation and stored at -20 °C, and then analyzed using an API4000 MS combined with an HPLC unit. The pharmacokinetic parameters Cmax and AUC were calculated based on the measured plasma concentrations and summarized in Table 22. The results show that crystal form 1 has a Cmax approximately 4 times higher than that of crystal form 2 and an exposure (AUC) approximately 3 times higher than that of crystal form 2. Table 22 Effect Example 10: Tissue Accumulation Experiment of Crystal Form 1 Human colon cancer H-29 cells were implanted into the axilla of BALB / cA nude mice. Seven days after implanting H-29 cells, 8 female mice were administered crystal form 1 at 40 mg / kg (twice a day) or sunitinib at 40 mg / kg (once a day). Administration was continued for 21 days. Four hours after dosing on the morning of the 22nd day, plasma, tissue, and tumor samples were collected for analysis. The results are summarized in Table 23. The data show that the tissue accumulation of crystal form 1 in all tested tissues is significantly lower than that of sunitinib, while the content in plasma is comparable. Table 23 Sample Plasma Tumor Liver Kidney Heart Lung Muscle Brain Crystal Form 1 191.6 153.4 1,715.3 418.3 124.8 144.9 77.6 9.3 Sunitinib 261.3 27,137.2 14,816.6 14,852.0 3,881.2 15,713.5 1,483.2 333.9 Effect Example 11: Grinding Stability Experiment of Crystal Form 1 After grinding the crystal form 1, it was sieved, and the sieved samples with 200 - 300 mesh of American standard were collected and subjected to XRD analysis. Analysis conditions: Shimadzu XRD - 6000, CuK source 40 kV, 30 mA; Detection angle: 5 - 50°, Speed: 5° / min. Figure 53 shows that the XRD pattern basically did not change before and after grinding, indicating that crystal form 1 remained stable during the grinding process. Effect Example 12: Preparation of Capsules 1) Weighing, Grinding and Sieving Add about 1 / 4 volume of crystal form 1 to a mortar. Grind the crystal form 1 with a pestle to reduce the particle size. Sieve it through a 250 μm (#60) sieve into a sieve collection tray. Transfer the ground and sieved crystal form 1 to a container. Repeat the above steps until all the crystal form 1 is ground and sieved. Calculate the total amount of crystal form 1 available for preparing capsules. Sieve Pearlitol 200SD through a 500 μm (#35) sieve and collect it in a suitable container. 2) Mixing Transfer the content of 830.3 ± 0.1 g of the sieved Pearlitol in Container #1, 1,417.5 ± 0.1 g of sodium bicarbonate powder, 405.0 ± 0.1 g of sodium lauryl sulfate, and 405.0 ± 0.1 g of croscarmellose sodium to the formulation container containing crystal form 1 (162.0 ± 0.1 g). Use the sieved Pearlitol (830.3 ± 0.1 g) in Container #2 to dry - clean the container that once held the ground and sieved crystal form 1 three times, and transfer the substances obtained from dry - cleaning to the formulation container of crystal form 1. Subsequently, transfer the remaining sieved Pearlitol to the formulation container of crystal form 1. 3) Blending Install the Turbula Type T10B Shaker Mixer according to the manufacturer's guidelines and install the preparation container for Polymorph 1. Start the Turbula Type T10B Shaker Mixer and blend for 10 minutes. Screen the preparation of Polymorph 1 using a 500 μm sieve and blend the screened material for 2 minutes. Take 3 samples (each 900 - 2000 mg) from the top, middle, and bottom of the Polymorph 1 preparation container for content uniformity testing during the preparation process. 4) Capsule filling Determine the average self-weight of size 0 Swedish Orange Opaque Coni-Snap Capsules. Calculate the acceptable capsule filling weight limit. Prepare two Profill manual capsule fillers for filling. The preparation loading amount required for 100 capsules per tray is: 51.0 g (2% excess per tray). Weigh the amount of preparation required for each filling tray (51.0 ± 0.1 g). Fill the capsules evenly with the said preparation. Tap the Profill to completely and evenly fill all the preparation into the capsules. Adjust the Profill manual capsule filler to seal. Replace the capsule caps onto the capsule bodies filled with the preparation and press to close to ensure sealing. If necessary, repeat this step to ensure that all capsule caps are placed on the capsule bodies. Visually inspect the capsules and remove any capsules with physical defects (i.e., broken capsule caps). Conduct a weight check on each tray of capsules. Repeat the above steps until all available preparation is filled into the capsules. Dust all acceptable capsules. Effect Example 13: Preparation of tablets 1) The preparation formula is shown in the following table: Table 24 Component 100 mg strength tablets (kg / batch) 50 mg strength tablets (kg / batch) Batch size (number of tablets) 65,000 tablets 40,000 tablets Polymorph 1 6.5 7.5 4 1 2.0 2.3 2 1 Mannitol, USP 13.0000 9.0112 Microcrystalline cellulose 13.0000 9.0112 Sodium bicarbonate powder, USP 11.7000 7.2000 Anhydrous citric acid, BP, Ph Eur, USP 4.4590 2.7440 Croscarmellose sodium, NF 4.7450 2.9200 Sodium lauryl sulfate, NF 3.2500 2.0000 Crospovidone, USP 2.8600 1.7600 Fumed silica 1.8525 1.1400 Sodium stearyl fumarate, NF 0.3088 0.1900 Purified water 2QS (sufficient quantity) Total QS (tablet core) 61.7507 37.9996 Opadry II Orange 1.8525 1.1400 Total (coated tablets) 63.6032 39.1396 1 The unit content of polymorph 1 of the active pharmaceutical ingredient (API) has been adjusted for impurities and water content. 2 Removed during the processing The manufacturing process of the tablets is as follows: 1) API grinding / sieving Grind polymorph 1 and sieve it twice through a Comil sieve equipped with a 459 μm screen. 2) Excipient grinding / sieving Mix all excipients in a V-blender for 5 minutes, sieve through a Comil sieve, and remove lumps by passing through a 1 mm screen once. 3) Blending Transfer the ground and sieved materials to a V-blender and dry blend for 45 minutes. 4) Tableting On a high-speed rotary tablet press, compress the final blended product into oval (100 mg) or round (50 mg) tablet cores. Check the weight, thickness, and hardness of the tablets during the process, and then dust off, polish, and perform metal detection. 5) Coating Coat the tablet cores with film coating and dry them in a rotary pan coater. Separate and remove non-conforming tablets. Visually inspect the conforming tablets for defects and perform relevant quality tests. Place the loose tablets in a container lined with a double-layer polyethylene bag and desiccant and store them until the packaging process. 6) Final packaging Package the tablets in high-density polyethylene (HDPE) bottles sealed with induction-sealed polypropylene caps. Store the product at a controlled room temperature until the labeling process. 7) At the labeling and logistics center, label the product for standby. The above describes the exemplary embodiments of the present invention. However, the technical solutions of the present invention are not limited thereto. Those skilled in the art should understand that any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall fall within the protection scope of the present invention.

Claims

1. Crystal forms of the compound represented by Formula I: Wherein, The crystalline form is selected from crystalline form 1, crystalline form 2, crystalline form 3, crystalline form 5, crystalline form 6, crystalline form 7, or a mixture of any two or more thereof; Crystalline form 1 has characteristic peaks at diffraction angles 2θ of 4.3±0.2°, 8.6±0.2°, and 12.9±0.2° in the X-ray powder diffraction pattern; Crystalline form 2 has characteristic peaks at diffraction angles 2θ of 8.8±0.2°, 10.1±0.2°, 23.8±0.2°, and 26.7±0.2° in the X-ray powder diffraction pattern; Crystalline form 3 has a characteristic peak at a diffraction angle 2θ of 7.8±0.2° in the X-ray powder diffraction pattern; Crystalline form 5 has characteristic peaks at diffraction angles 2θ of 8.7±0.2°, 17.0±0.2°, and 17.4±0.2° in the X-ray powder diffraction pattern; Crystalline form 6 has characteristic peaks at diffraction angles 2θ of 7.9±0.2°, 9.0±0.2°, and 17.7±0.2° in the X-ray powder diffraction pattern; Crystalline form 7 has characteristic peaks at diffraction angles 2θ of 9.5±0.2°, 10.6±0.2°, and 16.0±0.2° in the X-ray powder diffraction pattern; The X-ray powder diffraction patterns are all measured using the Kα line of a Cu target.

2. The crystal form according to claim 1, wherein: Crystalline form 1 has characteristic peaks at diffraction angles 2θ of 4.3±0.2°, 8.6±0.2°, 12.9±0.2°, and 18.3±0.2° in the X-ray powder diffraction pattern; Preferably, crystalline form 2 has characteristic peaks at diffraction angles 2θ of 8.8±0.2°, 10.1±0.2°, 17.7±0.2°, 19.9±0.2°, 20.5±0.2°, 23.8±0.2°, and 26.7±0.2° in the X-ray powder diffraction pattern; More preferably, crystalline form 2 has characteristic peaks at diffraction angles 2θ of 5.1±0.2°, 8.8±0.2°, 10.1±0.2°, 11.6±0.2°, 14.6±0.2°, 15.2±0.2°, 16.5±0.2°, 17.3±0.2°, 17.7±0.2°, 18.8±0.2°, 19.9±0.2°, 20.5±0.2°, 21.7±0.2°, 23.2±0.2°, 23.8±0.2°, and 26.7±0.2° in the X-ray powder diffraction pattern; Preferably, crystalline form 3 has characteristic peaks at diffraction angles 2θ of 7.8±0.2°, 9.3±0.2°, 13.7±0.2°, and 16.0±0.2° in the X-ray powder diffraction pattern; More preferably, crystalline form 3 has characteristic peaks at diffraction angles 2θ of 3.9±0.2°, 7.8±0.2°, 9.3±0.2°, 13.7±0.2°, 16.0±0.2°, 18.2±0.2°, and 27.2±0.2° in the X-ray powder diffraction pattern; Preferably, crystalline form 5 has characteristic peaks at diffraction angles 2θ of 8.3±0.2°, 8.7±0.2°, 9.4±0.2°, 17.0±0.2°, 17.4±0.2°, and 18.1±0.2° in the X-ray powder diffraction pattern; More preferably, the crystalline form 5 has characteristic peaks at diffraction angles 2θ of 4.1±0.2°, 8.3±0.2°, 8.7±0.2°, 9.4±0.2°, 10.5±0.2°, 13.4±0.2°, 17.0±0.2°, 17.4±0.2° and 18.1±0.2° in the X-ray powder diffraction pattern; Preferably, the crystalline form 6 has characteristic peaks at diffraction angles 2θ of 7.9±0.2°, 9.1±0.2°, 9.6±0.2°, 16.4±0.2°, 17.7±0.2° and 18.0±0.2° in the X-ray powder diffraction pattern; More preferably, the crystalline form 6 has characteristic peaks at diffraction angles 2θ of 3.9±0.2°, 7.9±0.2°, 9.1±0.2°, 9.6±0.2°, 13.2±0.2°, 16.4±0.2°, 17.7±0.2° and 18.0±0.2° in the X-ray powder diffraction pattern; Preferably, the crystalline form 7 has characteristic peaks at diffraction angles 2θ of 9.5±0.2°, 10.6±0.2°, 13.8±0.2°, 14.3±0.2°, 16.0±0.2°, 18.2±0.2°, and 25.1±0.2° in the X-ray powder diffraction pattern; More preferably, the crystalline form 7 has characteristic peaks at diffraction angles 2θ of 4.8±0.2°, 9.5±0.2°, 10.6±0.2°, 13.8±0.2°, 14.3±0.2°, 16.0±0.2°, 18.2±0.2°, 25.1±0.2°, 27.8±0.2° and 28.9±0.2° in the X-ray powder diffraction pattern.

3. The crystal form according to claim 1, wherein the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 12.9 ± 0.2° and 18.3 ± 0.2° in the X-ray powder diffraction pattern.

4. The crystal form according to claim 1, wherein the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 12.9 ± 0.2°, 17.2 ± 0.2° and 18.3 ± 0.2° in the X-ray powder diffraction pattern.

5. The crystal form according to claim 1, wherein the crystal form 1 has characteristic peaks at diffraction angles 2θ of 4.3 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 9.0 ± 0.2°, 12.4 ± 0.2°, 12.9 ± 0.2°, 17.2 ± 0.2° and 18.3 ± 0.2° in the X-ray powder diffraction pattern.

6. The crystalline form according to claim 1, wherein the crystalline form 1 has characteristic peaks at diffraction angles 2θ in the X-ray powder diffraction pattern selected from the following angles: 4.3 ± 0.2°, 6.7 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 9.0 ± 0.2°, 12.4 ± 0.2°, 12.9 ± 0.2°, 14.3 ± 0.2°, 15.5 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°, 18.3 ± 0.2°, 19.6 ± 0.2°, 20.3 ± 0.2°, 21.2 ± 0.2°, 21.5 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 24.2 ± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 27.0 ± 0.2°, 27.4 ± 0.2°, 28.8 ± 0.2°, 30.8 ± 0.2°, 33.4 ± 0.2°, 39.2 ± 0.2°.

7. The crystalline form according to claim 1, wherein the crystalline form 1 has characteristic peaks at diffraction angles 2θ in the X-ray powder diffraction pattern selected from the following angles: 4.3 ± 0.2°, 6.7 ± 0.2°, 7.6 ± 0.2°, 8.6 ± 0.2°, 9.0 ± 0.2°, 10.1 ± 0.2°, 12.4 ± 0.2°, 12.9 ± 0.2°, 14.3 ± 0.2°, 15.5 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°, 18.3 ± 0.2°, 19.6 ± 0.2°, 20.3 ± 0.2°, 21.2 ± 0.2°, 21.5 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 24.2 ± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 27.0 ± 0.2°, 27.4 ± 0.2°, 28.8 ± 0.2°, 30.8 ± 0.2°, 32.9 ± 0.2°, 33.4 ± 0.2°, 35.0 ± 0.2°, 37.5 ± 0.2°, 39.2 ± 0.2°.

8. The crystalline form according to claim 1, wherein: The X-ray powder diffraction pattern of the crystalline form 1 is shown in Figure 1; The X-ray powder diffraction pattern of the crystalline form 2 is shown in Figure 7; The X-ray powder diffraction pattern of the crystalline form 3 is shown in Figure 12; The X-ray powder diffraction pattern of the crystalline form 5 is shown in Figure 17; The X-ray powder diffraction pattern of the crystalline form 6 is shown in Figure 22; The X-ray powder diffraction pattern of the crystalline form 7 is shown in Figure 27.

9. The method for preparing the crystalline form according to any one of claims 1-8, comprising one or more of the following methods: 1) The first preparation method of polymorph 1 includes the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, and volatilizing the solvent to obtain it; the solvent is methanol, a mixture of methanol and acetone, or an aqueous methanol solution; The second preparation method of polymorph 1 includes the following steps: mixing the compound of formula I with methanol to obtain a clear solution, adding a solvent to the clear solution under stirring, and precipitating a solid to obtain it; the solvent is acetone, ethyl acetate, methyl tert-butyl ether, or acetonitrile; The third preparation method of polymorph 1 includes the following steps: mixing the compound of formula I with methanol to obtain a clear solution, adding the clear solution to a solvent under stirring, and precipitating a solid to obtain it; the solvent is water or methyl tert-butyl ether; The fourth preparation method of polymorph 1 includes the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, cooling, and stirring to crystallize to obtain it; the solvent is methanol, an aqueous methanol solution, a mixture of methanol and ethyl acetate, a mixture of methanol and methyl tert-butyl ether, or a mixture of methanol and acetonitrile; 2) The preparation method of polymorph 2 includes the following steps: mixing and stirring the compound of formula I with a solvent for 2 to 6 days, separating the crystal slurry into solid and liquid, and drying to obtain it; the solvent is water, ethyl acetate, toluene, an aqueous acetone solution, an aqueous acetonitrile solution, a mixture of ethanol and toluene, or an aqueous methanol solution; 3) The first preparation method of polymorph 3 includes the following steps: mixing the compound of formula I with tetrahydrofuran to obtain a clear solution, and volatilizing the solvent to obtain it; The second preparation method of polymorph 3 includes the following steps: mixing the compound of formula I with ethanol to obtain a clear solution, and volatilizing the solvent at room temperature to obtain it; The third preparation method of polymorph 3 includes the following steps: mixing the compound of formula I with an aqueous ethanol solution to obtain a clear solution, and volatilizing the solvent to obtain it; The fourth preparation method of polymorph 3 includes the following steps: mixing and stirring the compound of formula I with a solvent, separating the crystal slurry into solid and liquid, and drying to obtain it; the solvent is ethanol, acetone, or an aqueous tetrahydrofuran solution; The fifth preparation method of polymorph 3 includes the following steps: mixing the compound of formula I with a solvent to obtain a clear solution, cooling, and stirring to crystallize to obtain it; the solvent is tetrahydrofuran or a mixture of methanol and tetrahydrofuran; The sixth preparation method of polymorph 3 includes the following steps: heating polymorph 1 to 180 - 190 °C, and cooling to room temperature to obtain it; or heating polymorph 7 to 258 °C, and cooling to room temperature to obtain it; 4) The first preparation method of polymorph 5 includes the following steps: mixing the compound of formula I with acetone to obtain a clear solution, cooling, and stirring to crystallize to obtain it; The second preparation method of the crystal form 5 includes the following steps: mixing and stirring the compound of formula I with a solvent, separating the solid and liquid of the crystal slurry, and then drying to obtain the product; or, after mixing the compound of formula I with a solvent, adding the crystal seeds of the crystal form 5, stirring, separating the solid and liquid of the crystal slurry, and then drying to obtain the product; the solvent is methyl tert-butyl ether or acetone; 5) The first preparation method of the crystal form 6 includes the following steps: mixing the compound of formula I with a mixture of toluene and methanol to obtain a clear solution, and volatilizing the solvent at room temperature to obtain the product; The second preparation method of the crystal form 6 includes the following steps: mixing the compound of formula I with methanol to obtain a clear solution, mixing the clear solution and toluene under stirring to precipitate a solid, and then obtaining the product; The third preparation method of the crystal form 6 includes the following steps: mixing and stirring the compound of formula I with toluene for more than 16 hours, and drying the crystal slurry to obtain the product; or, after mixing the compound of formula I with toluene, adding the crystal seeds of the crystal form 6, stirring, and drying the crystal slurry to obtain the product; 6) The first preparation method of the crystal form 7 includes the following steps: mixing the compound of formula I with ethyl acetate, stirring, separating the solid and liquid of the crystal slurry, and then drying to obtain the product; The second preparation method of the crystal form 7 includes the following steps: mixing and stirring the compound of formula I with a mixture of N,N-dimethylacetamide and toluene, separating the solid and liquid, and then drying to obtain the product; The third preparation method of the crystal form 7 includes the following steps: mixing and stirring the crystal form 1 and / or the crystal form 5 with water, separating the solid and liquid of the crystal slurry, and then drying to obtain the product.

10. The preparation method according to claim 9, wherein: In Preparation Method 1 of the crystalline form 1, the temperature for volatilizing the solvent is 10-40°C; Preferably, the mass-to-volume ratio of the compound of Formula I to the solvent is 10 mg / 0.5-2.2 mL, such as 10 mg / 0.5-2 mL; When the solvent is a mixture of methanol and acetone, the volume ratio of methanol to acetone is 1:1.5-2.5; When the solvent is an aqueous methanol solution, the volume ratio of methanol to water is preferably 6:0.5-1.5; In Preparation Method 2 of the crystalline form 1, the temperature for mixing is 45-55°C; Preferably, the mass-to-volume ratio of the compound of Formula I to methanol is 20 mg / 1.2-1.6 mL; the mass-to-volume ratio of the compound of Formula I to the solvent is about 20 mg / 2-4 mL; In Preparation Method 3 of the crystalline form 1, the temperature for mixing is 45-55°C; Preferably, the mass-to-volume ratio of the compound of formula I to methanol is 20 mg / 1.2 - 20 mg / 1.6 mL; the mass-to-volume ratio of the compound of formula I to the solvent is 20 mg / 2.0 - 15 mL, such as 20 mg / 2.5 - 12.0 mL, such as 20 mg / 3.0 mL, 20 mg / 5.2 mL, 20 mg / 11.2 mL; In Preparation Method 4 of the crystalline form 1, the temperature of the mixing is 45 - 70 °C, such as 50 °C or the reflux temperature; Preferably, the mass-to-volume ratio of the compound of formula I to the solvent is 20 mg / 0.5 - 2.2 mL; When the solvent is an aqueous methanol solution, the volume ratio of methanol to water is 7:1.5 - 2.5; When the solvent is a mixture of methanol and ethyl acetate, the volume ratio of methanol to ethyl acetate is 1:1.5 - 2.5; When the solvent is a mixture of methanol and methyl tert-butyl ether, the volume ratio of methanol to methyl tert-butyl ether is 4:6 - 8; When the solvent is a mixture of methanol and acetonitrile, the volume ratio of methanol to acetonitrile is 1:0.5 - 1.

5.

11. The preparation method according to claim 9 or 10, wherein in the fourth preparation method of Form 1, the compound of formula I is mixed with a solvent and heated to reflux to obtain a clear solution; Preferably, the fourth preparation method comprises the following steps: Mix the compound of formula I and methanol, heat to reflux to obtain a clear solution, cool down, stir to crystallize, filter, wash, and dry; 12. The preparation method according to any one of claims 9-11, wherein the fourth preparation method of Form 1 comprises a concentration step, for example, after obtaining the clear solution, part of the solvent is removed by concentration; Preferably, the concentration is carried out under reduced pressure, and the degree of vacuum under the reduced pressure conditions can be, for example, 200-1500 Pa, such as 500-1000 Pa; Preferably, the concentration temperature can be 20-35 °C.

13. The preparation method according to claim 11 or 12, wherein in the fourth preparation method of Form 1, the reflux time is less than 4 hours, such as not exceeding 2 hours.

14. The preparation method according to any one of claims 9-13, wherein in the fourth preparation method of Form 1, the target temperature for cooling can be 1-50 °C, for example 4-50 °C, such as 5-35 °C or 10-20 °C.

15. The preparation method according to any one of claims 9-14, wherein in the fourth preparation method of Form 1, the temperature for stirring and crystallization can be 1-50 °C, for example 4-50 °C, such as 5-35 °C or 10-20 °C.

16. The preparation method according to any one of claims 9-15, wherein when the solvent is methanol, the water content of the methanol does not exceed 10%, such as not exceeding 6%, for example not exceeding 5%, preferably not exceeding 1%, such as anhydrous methanol.

17. The preparation method according to claim 9, wherein in the preparation method of Form 2, the compound of formula I can be Form 1 and / or Form 6; The temperature for stirring is preferably 4-50 °C; The mass-to-volume ratio of the compound of formula I to the solvent is preferably 12.5-40.0 mg / mL.

18. A pharmaceutical composition, which comprises a therapeutically and / or prophylactically effective amount of the crystal form according to any one of claims 1-8, and at least one pharmaceutically acceptable excipient; Preferably, the pharmaceutical composition may further contain or substantially not contain other forms of the compound of formula I, such as other crystal forms and / or amorphous forms; Preferably, one or more components in the pharmaceutical composition are ground and / or sieved.

19. The pharmaceutical composition according to claim 18, wherein the pharmaceutical composition is a capsule, which comprises a therapeutically and / or prophylactically effective amount of the crystalline form according to any one of claims 1-8, Pearlitol 200 SD, sodium bicarbonate, sodium lauryl sulfate and croscarmellose sodium.

20. The pharmaceutical composition according to claim 18, wherein the pharmaceutical composition is a tablet, and the tablet core comprises a therapeutically and / or prophylactically effective amount of the crystalline form according to any one of claims 1-8, mannitol, microcrystalline cellulose, sodium bicarbonate powder, anhydrous citric acid, croscarmellose sodium, sodium lauryl sulfate, crospovidone, fumed silica, sodium stearyl fumarate, and water which is optionally present or absent.

21. A method for treating or preventing a disease or disorder, comprising administering to a subject in need thereof an effective amount of the crystalline form according to any one of claims 1-8 or the pharmaceutical composition according to any one of claims 18-20.

22. The method according to claim 21, wherein the disease or disorder is any one of the diseases or disorders mediated by a kinase (such as one or more of VEGFR, PDGFR, Flt-3, KIT, RET or CSF1R).

23. The method according to claim 21, wherein the disease or disorder is cancer, including, for example, renal cell carcinoma and gastrointestinal stromal tumor, a tumor or a proliferative disorder.

24. A method for modulating kinase activity, the method comprising contacting a kinase (such as one or more of VEGFR, PDGFR, Flt-3, KIT, RET or CSF1R) with the crystalline form according to any one of claims 1-8 or the pharmaceutical composition according to any one of claims 18-20.

25. A method for preparing a compound of formula I, comprising carrying out the following reaction: wherein, HOBt represents hydroxybenzotriazole, EDCI represents 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, Et3N represents triethylamine, and DMF represents N,N-dimethylformamide; The molar ratio of compounds A and B can be 1:1 - 1:3, such as 1:1 - 1:1.5, such as 1:1.2; The molar ratio of compound A to triethylamine can be 1:1 - 1:10, such as 1:5; The molar ratio of compound A to EDCI can be 1:1 - 1:3, such as 1:1.2 - 1:1.8, such as 1:1.5; Preferably, the reaction is carried out under an inert atmosphere (such as a nitrogen atmosphere); Preferably, the reaction temperature can be 5 - 45 °C, such as 20 - 30 °C; Preferably, after the reaction is completed, an ether solvent, such as methyl tert-butyl ether, is added to the reaction mixture, stirred, filtered, and the filter cake is washed with methyl tert-butyl ether; Preferably, the product washed with methyl tert-butyl ether is mixed with methanol or its aqueous solution, such as anhydrous methanol, and heated to reflux; The reflux time is preferably not more than 2 hours, such as 0.5 - 1 hour; Preferably, after reflux, the reaction mixture is cooled to 10 - 20 °C, and stirring is continued for 1 - 3 hours before filtration; Preferably, the filter cake is washed with methanol, such as cold methanol, dried, to obtain a crude product of the compound of formula I; The drying includes atmospheric drying or vacuum drying. The temperature of vacuum drying can be above about 35 °C, such as above about 40 °C, above about 45 °C, above about 50 °C, such as about 40 - 60 °C. The vacuum degree of vacuum drying can be, for example, 200 - 1500 Pa, such as 500 - 1000 Pa.