Salt and crystal form of KIF18A inhibitor compound as well as preparation method and application of salt and crystal form

Abstract

The invention relates to a salt and a crystal form of a KIF18A inhibitor compound as shown in a formula I, and a preparation method and application of the salt and the crystal form. Wherein the structure of formula I is as shown in the specification: # imgabs0 #

Description

[0001] This application claims priority to a prior application filed with the State Intellectual Property Office of China on October 13, 2023, with patent application number 202311331874.0 and invention name “Salts, crystal forms, preparation methods and uses of KIF18A inhibitor compounds”. The entire text of the application is incorporated into this application by reference. Technical Field

[0002] The present invention belongs to the field of medicine and relates to a salt, a crystal form, a preparation method and a use of a KIF18A inhibitor compound. Background Art

[0003] Cancer is one of the most prevalent diseases afflicting humans and is a leading cause of death worldwide. However, among the available cancer treatments and therapies, only a few have achieved a reasonable degree of success to date. Cancer is often characterized by unregulated cell proliferation. Damage to one or more genes responsible for cellular pathways that control proliferation progression through the cell cycle and centrosome cycle can lead to the loss of normal regulation of cell proliferation. These deregulated genes can encode various tumor suppressor proteins or oncogene proteins, which participate in a series of events leading to unchecked cell cycle progression and cell proliferation. Various kinases and kinesins have been identified that play key roles in cell cycle and mitosis regulation and progression in both normally dividing cells and cancer cells.

[0004] Kinesin is a molecular motor that plays an important role in cell division and intracellular vesicle and organelle transport. Mitotic kinesin plays a role in many aspects of spindle assembly, chromosome separation, centrosome separation and dynamics (O. Rath and F. Kozielski, Nature Review Cancer [Natural Cancer Review], 12: 527-39, 2012). Based on the sequence homology within the so-called "motor domain", human kinesin is classified into 14 subfamilies, and the ATPase activity of this domain drives unidirectional movement along microtubules (MT). The non-motor domains of these proteins are responsible for cargo attachment; "cargo" can include any of a variety of different membranous organelles, signal transduction scaffold systems and chromosomes. Kinesin uses ATP hydrolysis energy to move cargo along polarized microtubules. Therefore, kinesin is often referred to as a "plus end" or "minus end" directional motor.

[0005] The KIF18A gene belongs to the kinesin-8 subfamily and is a plus-end directed motor. KIF18A is believed to affect the dynamics of the plus end of the centromere microtubule to control correct chromosome positioning and spindle tension. Human KIF18A deletion leads to spindle elongation in HeLa cervical cancer cells, increased metaphase chromosome oscillation, and activation of the mitotic spindle assembly checkpoint. KIF18A appears to be a viable target for cancer therapy. KIF18A is overexpressed in many types of cancer, including but not limited to colon cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, bladder cancer, head cancer, neck cancer, cervical cancer and ovarian cancer. In addition, in cancer cell lines, KIF18A gene deletion or knockout or inhibition affects the mitotic spindle of cancer cell lines. In particular, it has been found that inhibition of KIF18A can induce mitotic cell arrest, which is a known weakness that can promote mitotic cell death by apoptosis, mitotic catastrophe or multiphase drive lethality or death after mitotic slippage in interphase. Therefore, there is a strong interest in finding inhibitors of the KIF18A protein.

[0006] Currently, there are no drugs on the market that inhibit the KIF18A pathway to treat many diseases, including cancer. Therefore, the development of new compounds that can inhibit the activity of KIF18A has positive significance for the treatment of diseases.

[0007] Chinese patent application CN202310400928.8 discloses the following compound of formula I:

[0008]

[0009] This compound can effectively inhibit the activity of KIF18A. Therefore, studying its salt form and crystal form will be helpful to further obtain drugs with clinical application value. Summary of the invention

[0010] In order to solve the problems existing in the prior art, on the one hand, the present invention provides a crystalline form of a compound of formula I, wherein the structure of the compound of formula I is as follows:

[0011]

[0012] In some embodiments, the present invention provides a free crystalline form A of the compound of formula I, wherein the free crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 3.8074, 11.3487, 15.1458, 15.4196, 16.2456, and 18.9612 having diffraction peaks; further, the free crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 3.8074, 9.8108, 10.3581 , 11.3487, 13.4688, 15.1458, 15.4196, 16.2456, 16.8635, 17.3003, 18.9612, 22.6628, and 30.5503; further, the X-ray powder diffraction spectrum of the free crystalline form A represented by a diffraction angle of 2θ±0.2° is 3.8074, 9.8108, 10.3581, 11.3487, 12.7984, 13.4688, 15 .1458, 15.4196, 16.2456, 16.8635, 17.3003, 18.9612, 20.7248, 22.6628, 23.6322, 30.5503, 26.6666, 27.4293, and 28.2276; further, the X-ray powder diffraction spectrum of the free crystalline form A represented by a diffraction angle of 2θ±0.2° is 3.8074, 9.8108, 10.3581, 11.3 487, 12.7984, 13.4688, 15.1458, 15.4196, 16.2456, 16.8635, 17.3003, 18.9612, 20.7248, 22.6628, 23.6322, 24.5787, 25.7207, 26.6666, 27.4293, 28.2276, 30.5503, 35.7206 have diffraction peaks; further, the free state crystalline form A has substantially Figure 1 XRPD spectrum shown.

[0013] In some embodiments, the free crystalline Form A has one, two or three of the following characteristics:

[0014] (1) The TGA curve of the free crystalline form A shows a weight loss of 0-2% at 150.0±3°C, preferably about 0-1% (e.g., 0.1%, 0.2%,

[0015] 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%);

[0016] (2) The DSC curve of free form A has two endothermic peaks at 167.9±3℃ and 180.3±3℃;

[0017] (3) The DSC curve of free form A has an exothermic peak at 170.5℃±3℃.

[0018] In some embodiments, the free crystalline Form A has one, two or three of the following characteristics:

[0019] (1) The TGA curve of free form A shows a weight loss of approximately 0.68% at 150.0±3°C;

[0020] (2) The DSC curve of free form A has two endothermic peaks at 167.9±3℃ and 180.3±3℃;

[0021] (3) The DSC curve of free form A has an exothermic peak at 170.5°C ± 3°C;

[0022] In some embodiments, the TGA / DSC graph of the free crystalline form A is substantially as follows Figure 2 As shown; the free state crystalline form A 1 The HNMR diagram is basically Figure 3a As shown;

[0023] In some embodiments, the free crystalline form is an anhydrate.

[0024] In some embodiments, the present invention provides a free crystalline form B of the compound of formula I, wherein the free crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.7812, 18.1668, 18.5510, 19.0431, 20.2387, and 21.1776 having diffraction peaks; further, the free crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.7812, 18.1668, 18.5510, 19.0431, 19.319 1, 19.7143, 20.2387, 21.1776 have diffraction peaks; further, the free state crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.7812, 9.9884, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, 21.1776; further, the free state crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.250 8, 9.7812, 9.9884, 15.0024, 15.2215, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, 21.1776, 22.0900, 27.6189, 28.2642; Still further, the X-ray powder diffraction spectrum of the free form B expressed at a diffraction angle of 2θ±0.2° is 9.2508, 9.7812, 9.9884, 10.8644, 13. There are diffraction peaks at 3822, 14.5151, 15.0024, 15.2215, 16.3081, 16.7223, 17.1474, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, 21.1776, 22.0900, 23.0450, 23.7619, 25.7395, 27.6189, 28.2642, and 30.0557; further, the free form B has substantially Figure 5 XRPD spectrum shown.

[0025] In some embodiments, the free crystalline Form B has one, two or three of the following characteristics:

[0026] (1) The TGA curve of the free crystalline form B shows a weight loss of 2-6% at 120.0±3°C, preferably about 3-5% (e.g., 3.0%, 3.5%,

[0027] 4.0%, 4.5%);

[0028] (2) The DSC curve of free form B has three endothermic peaks at 108.5±3℃, 165.8±3℃ and 180.2±3℃;

[0029] (3) The DSC curve of free form B has an exothermic peak at 167.7℃±3℃.

[0030] In some embodiments, the free crystalline Form B has one, two or three of the following characteristics:

[0031] (1) The TGA curve of free form B shows a weight loss of approximately 4.35% at 120.0±3°C;

[0032] (2) The DSC curve of free form B has three endothermic peaks at 108.5±3℃, 165.8±3℃ and 180.2±3℃;

[0033] (3) The DSC curve of free form B has an exothermic peak at 167.7℃±3℃;

[0034] In some embodiments, the TGA / DSC diagram of the free crystalline Form B is substantially as follows Figure 6 As shown; the free state crystalline form B 1 The HNMR diagram is basically Figure 7a As shown;

[0035] In some embodiments, the free crystalline Form B is a solvate;

[0036] In some embodiments, the free crystalline Form B is an EtOH solvate;

[0037] In some embodiments, the molar ratio of EtOH to the free state in the solvate is 0.10 (-0.8 wt %);

[0038] In some embodiments, the free crystalline Form B is a cosolvate of EtOH and water.

[0039] In some embodiments, the present invention provides a free crystalline form C of the compound of formula I, wherein the free crystalline form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5020, 16.1724, 16.5974, 21.5887, and 25.8930; further, the free crystalline form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5020, 15.3140, 16.1724, 16. 5974, 18.8700, 19.9398, 20.5180, 21.0065, 21.5887, 25.8930; further, the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° is 9.5020, 10.7612, 15.3140, 16.1724, 16.5974, 18.5313, 18.8700, 19.1799, 19.9398, 20. 5180, 21.0065, 21.5887, 25.8930, 28.4921 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° is 3.1461, 8.1061, 9.1126, 9.5020, 10.7612, 11.2726, 12.2849, 13.1097, 14.2058, 14.7763, 15.3140, 16.17 24, 16.5974, 17.5352, 18.5313, 18.8700, 19.1799, 19.9398, 20.5180, 21.0065, 21.2198, 21.5887, 22.1453, 22.7421, 23.2908, 24.1476, 24.6794, 25.4796, 25.8930, 27.4465, 28.4921, 29.8280, 30.7213,

[0040] There are diffraction peaks at 31.4381, 32.6390, 35.3421, 36.5656, and 38.4547; Still further, the free state crystalline form C has substantially Figure 8 XRPD spectrum shown.

[0041] In some embodiments, the free crystalline Form C has one or two of the following characteristics:

[0042] (1) The TGA curve of the free crystalline form C shows a weight loss of 1-6% at 150.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5%,

[0043] 2.0%, 2.5%, 3.0%, 3.5%, 4.0%);

[0044] (2) The DSC curve of free crystalline form C has two endothermic peaks at 53.0±3℃ and 182.3±3℃.

[0045] In some embodiments, the free crystalline Form C has one or two of the following characteristics:

[0046] (1) The TGA curve of free form C shows a weight loss of approximately 2.77% at 150.0±3°C;

[0047] (2) The DSC curve of free form C has two endothermic peaks at 53.0±3℃ and 182.3±3.

[0048] In some embodiments, the TGA / DSC graph of the free crystalline Form C is substantially as follows Fig. 9 As shown; the free state crystalline form C 1 The HNMR diagram is basically Fig.10 shown.

[0049] In some embodiments, the present invention provides a free crystalline form D of the compound of formula I, wherein the free crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 16.5793, 18.4363, 20.3590, 21.3940, 21.7745, and 26.5122 having diffraction peaks; further, the free crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 13.9909, 16.5793, 16.8857, 18.4363, 20.3590, 21.394 0, 21.7745, 26.5122 have diffraction peaks; further, the free state crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 13.9909, 14.9577, 16.5793, 16.8857, 18.4363, 20.1677, 20.3590, 21.3940, 21.7745, 26.5122 have diffraction peaks; further, the free state crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 11.8218, 13.99 09, 14.9577, 16.5793, 16.8857, 18.4363, 18.7513, 18.9436, 20.1677, 20.3590, 21.3940, 21.7745, 22.2999, 23.7694, 24.2605, 24.4938, 25.2628, 26.5122, 29.7635, 30.8099 have diffraction peaks; further, the free state crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.2985, 9.4241, 10.8461, 1 There are diffraction peaks at 1.8218, 12.5232, 13.2208, 13.9909, 14.9577, 16.5793, 16.8857, 18.4363, 18.7513, 18.9436, 20.1677, 20.3590, 21.3940, 21.7745, 22.2999, 23.7694, 24.2605, 24.4938, 25.2628, 26.5122, 29.2296, 29.7635, 30.8099, and 38.8753; further, the free state crystalline form D has substantially Fig.67 The XRPD spectrum shown;

[0050] In some embodiments, the free crystalline form D has one or more of the following characteristics:

[0051] (1) TGA curve at 120±3°C shows a weight loss of 3.0-8.0%, preferably about 4.0-7.0% (e.g., 5.0%, 5.5%, 6.0%,

[0052] 6.5%), more preferably, about 5.79%;

[0053] (2) The DSC curve has two endothermic peaks at 53.9±3℃ and 182.9±3℃;

[0054] In some embodiments, the TGA / DSC diagram of the free crystalline form D is substantially as follows Fig.68 As shown; the free state crystalline form D 1 The HNMR diagram is basically Fig.69 As shown;

[0055] In some embodiments, the free crystalline form D is a hydrate;

[0056] In some embodiments, the water content of the free crystalline form D is 2.0-3.5%, preferably 2.0-3.0%;

[0057] In some embodiments, the free crystalline form D is a monohydrate;

[0058] In some embodiments, the free crystalline Form D has the following crystal parameters:

[0059] Crystal Triclinic

[0060] Space group P-1

[0061] Unit cell parameters

[0062]

[0063] α=95.3240(10)°, β=97.7830(10)°, γ=100.4940(10)°

[0064] In some embodiments, the free crystalline Form D has the parameters listed in Table B3-1.

[0065] In some embodiments, the present invention provides a free crystalline form E of the compound of formula I, wherein the free crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 17.2384, 18.3327, 19.1326, 20.5505, 21.4769, and 24.8471 with diffraction peaks; further, the free crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 16.7268, 17.2384, 18.3327, 19.1326, 20.5505, 21.476 9, 21.8496, and 24.8471; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1459, 12.1780, 16.7268, 17.2384, 18.3327, 18.9674, 19.1326, 20.5505, 21.4769, 21.8496, and 24.8471; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.6847, 8.9272, 9.1459, 12.1780, 12.7789, 16.7268, 17.2384, 18.1543, 18.3327, 18.9674, 19.1326, 19.8795, 20.2931, 20.5505, 21.4769, 21.8496, 24.8471, 28.5466 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° is 8.6847, 8.9272, 9.1459, 9.4934, 12.1780, 12.7789, 15.3545, 16.7268, 17.2384, 18.1543, 18.3327, 18.9674, 19.1326, 19.8795, 20.2931, 20.5505, 21.4769, 21.8496, 22.1726, 23.0433, 24.8471, 25.6946, 26.8264, 28.5466, 29.5968 have diffraction peaks; further, the free state crystalline form E has substantially Fig.71 The XRPD spectrum shown;

[0066] In some embodiments, the free crystalline Form E has one or more of the following characteristics:

[0067] (1) TGA curve at 140±3°C shows a weight loss of 9-14%, preferably about 10-13% (e.g., 10.5%, 11.0%, 11.5%,

[0068] 12.0%, 12.5%); more preferably, about 11.97%;

[0069] (2) The DSC curve has two endothermic peaks at 123.0±3℃ and 182.9±3℃;

[0070] (3) The DSC curve has an exothermic peak at 148.0±3℃;

[0071] In some embodiments, the TGA / DSC graph of the free crystalline Form E is substantially as follows Fig.72 As shown; the free state crystalline form E 1 The HNMR diagram is basically Fig.73 As shown;

[0072] In some embodiments, the free crystalline Form E is a solvate;

[0073] In some embodiments, the free crystalline Form E is a THF solvate;

[0074] In some embodiments, in the THF solvate of the free crystalline Form E, the molar ratio of THF to the free state is 0.95:1.

[0075] In some embodiments, the present invention provides a free crystalline form F of the compound of formula I, wherein the free crystalline form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.9091, 14.5589, 15.7854, 18.2249, and 18.5345 with diffraction peaks; further, the free crystalline form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.7443, 10.9091, 14.5589, 15.7854, 17.1471, 18.224 9, 18.5345; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7443, 10.9091, 14.5589, 15.7854, 17.1471, 17.7727, 18.2249, 18.5345, and 20.2138; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.2680, 9.7443, 10.9091 , 13.5597, 14.5589, 15.7854, 17.1471, 17.7727, 18.2249, 18.5345, 20.2138, and 24.7687; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° is 7.2680, 9.7443, 10.9091, 12.6503, 13.5597, 14.5589, 15.0095, 15.7854, 17.1471, 17 .7727, 18.2249, 18.5345, 19.4299, 20.2138, 21.2140, 21.5620, 22.3451, 23.2974, 23.7177, 24.7687, 25.6111, 27.5720, 28.4674, 29.3309, 30.7039, 31.5840, 34.3936, 35.1042, 36.9389, 38.7357 have diffraction peaks; further, the free state crystalline form F has substantially Fig.76 The XRPD spectrum shown;

[0076] In some embodiments, the free crystalline Form F has one or more of the following characteristics:

[0077] (1) The TGA curve shows a weight loss of 0.5-2.5% at 150±3°C, preferably about 0.5-2.0% (e.g., 0.5%, 1.0%, 1.5%); more preferably, about 1.19%;

[0078] (2) The DSC curve has an endothermic peak at 181.1±3°C (peak temperature);

[0079] In some embodiments, the TGA / DSC graph of the free crystalline Form F is substantially as follows Fig.77 As shown; the free state crystalline form F 1 The HNMR diagram is basically Fig.78 As shown;

[0080] In some embodiments, the free crystalline Form F is an anhydrate.

[0081] In some embodiments, the present invention provides a free crystalline form G of the compound of formula I, wherein the free crystalline form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.1695, 12.2893, 18.5441, 19.4906, and 22.7762 having diffraction peaks; further, the free crystalline form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.1695, 10.5406, 12.2893, 14.5010, 18.5441, 19.4906, 22.7762; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1695, 9.2517, 9.4965, 10.5406, 12.2893, 14.5010, 18.5441, 18.8489, 19.4906, 22.7762; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6. 1695, 9.2517, 9.4965, 10.5406, 12.2893, 14.5010, 16.9986, 18.5441, 18.8489, 19.4906, 21.1520, 21.6669, 22.4742, 22.7762, and 24.7980; further, the X-ray powder diffraction spectrum of the free form G represented by a diffraction angle of 2θ±0.2° is 6.1695, 9.2517, 9.4965, 10 .2696, 10.5406, 10.9989, 12.2893, 14.5010, 16.5003, 16.9986, 18.5441, 18.8489, 19.4906, 20.6318, 21.1520, 21.6669, 22.4742, 22.7762, 24.7980, 25.3519, 26.0012, 26.8697, 28.1782 have diffraction peaks; further, the free state crystalline form G has substantially Fig.79 The XRPD spectrum shown;

[0082] In some embodiments, the free crystalline form G has one or more of the following characteristics:

[0083] (1) TGA curve at 110±3°C shows a weight loss of 8-13%, preferably about 9-11% (e.g., 9.5%, 10.0%, 10.5%,

[0084] 11.0%); more preferably, about 10.40%;

[0085] (2) The DSC curve has three endothermic peaks at 98.1±3℃, 154.8±3℃ and 180.8±3℃;

[0086] (3) The DSC curve has an exothermic peak at 157.8±3℃;

[0087] In some embodiments, the TGA / DSC graph of the free crystalline form G is substantially as follows Fig.80 As shown; the free state crystalline form G 1 The HNMR diagram is basically Fig.81 As shown;

[0088] In some embodiments, the free crystalline form G is a solvate;

[0089] In some embodiments, the free crystalline form G is a 1,4-dioxane solvate; in some embodiments, in the solvate, the molar ratio of 1,4-Dioxane to the free form is 0.04 (-0.6 wt%) or 0.02 (-0.3 wt%).

[0090] In some embodiments, the present invention provides a free crystalline form H of the compound of formula I, wherein the free crystalline form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.1382, 17.0866, 18.9850, 19.4851, 20.1891, and 21.3352 having diffraction peaks; further, the free crystalline form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.1382, 14.9595, 17.0866, 17.5191, 17.7454, 18.9850, 1 9.4851, 20.1891, 21.3352; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.1382, 14.9595, 17.0866, 17.5191, 17.7454, 18.9850, 19.4851, 20.1891, 21.3352, 21.5416, 24.7905; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5. 1382, 14.9595, 17.0866, 17.5191, 17.7454, 18.9850, 19.4851, 20.1891, 20.5085, 21.3352, 21.5416, 24.5735, 24.7905 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° is 5.1382, 8.6958, 10.2939, 11.0299, 11.5587, 12.1517, 13.0908, 14.5022, 14.9595, 15.2308, 16.5672, 17.0866, 17.5191, 17.7454, 18.4679, 18.9850, 19.4851, 20.1891, 20.5085, 21.3352, 21.5416, 22.2233, 22.7317, 24.2236, 24.5735, 24.7905, 25.0488, 26.0331, 28.5683 have diffraction peaks; further, the free state crystalline form H has substantially Figure 85b XRPD spectrum shown.

[0091] In some embodiments, the present invention provides a free crystalline form I of the compound of formula I, wherein the free crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5592, 17.8352, 19.3336, 19.8678, 20.1554, and 27.1065 having diffraction peaks; further, the free crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.55 92, 12.8988, 17.8352, 19.3336, 19.8678, 20.1554, and 27.1065; further, the X-ray powder diffraction spectrum of the free crystalline form I represented by a diffraction angle of 2θ±0.2° is 9.5592, 12.8988, 17.8352, 19.3336, 19.8678, 20.1554, 20.9976, 27.1065 Further, the free crystalline form I has a diffraction peak at 9.5592, 12.8988, 17.8352, 18.1790, 19.3336, 19.8678, 20.1554, 20.7214, 20.9976, 27.1065, and 28.0012 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; Still further, the free crystalline form I has a diffraction peak at 2θ±0.2°. The X-ray powder diffraction spectrum represented by a diffraction angle of 0.2° has diffraction peaks at 9.5592, 12.8988, 14.7994, 15.8059, 17.8352, 18.1790, 19.3336, 19.8678, 20.1554, 20.7214, 20.9976, 23.2310, 27.1065, and 28.0012; further, the free form I has substantially Fig.86 The XRPD spectrum shown;

[0092] In some embodiments, the free crystalline Form I has one or more of the following characteristics:

[0093] (1) The TGA curve shows a weight loss of 2-7% at 120±3°C, preferably about 3-6% (e.g., 3.5%, 4.0%, 4.5%);

[0094] (2) The DSC curve has three endothermic peaks at 54.6±3℃, 168.0±3℃ and 181.2±3℃;

[0095] (3) The DSC curve has an exothermic peak at 170.5±3℃;

[0096] In some embodiments, the TGA / DSC graph of the free crystalline Form I is substantially as follows Fig.87 As shown; the free state crystalline form I 1The HNMR diagram is basically Fig.88 As shown;

[0097] In some embodiments, the free crystalline Form I is a hydrate.

[0098] In some embodiments, the present invention provides a free crystalline form J of the compound of formula I, wherein the free crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 20.9755, 21.5744, and 25.8914 having diffraction peaks; further, the free crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 20.9755, 21.5744, and 25.8914 having diffraction peaks. , 20.5033, 20.9755, 21.5744, 25.8914 have diffraction peaks; further, the free state crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 18.5225, 18.8695, 19.9313, 20.5033, 20.9755, 21.5744, 25.8914 have diffraction peaks; further, the free state crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° There are diffraction peaks at 9.4887, 10.7503, 12.2600, 13.0965, 14.1913, 15.3049, 16.1644, 16.5855, 18.5225, 18.8695, 19.1552, 19.9313, 20.5033, 20.9755, 21.5744, 22.1570, 23.2764, 25.8914, and 28.4642; further, the X-ray powder diffraction spectrum of the free form J represented by a diffraction angle of 2θ±0.2° is 9.4887, 10.7503, 12 .2600, 13.0965, 14.1913, 15.3049, 16.1644, 16.5855, 17.5096, 18.5225, 18.8695, 19.1552, 19.9313, 20.5033, 20.9755, 21.5744, 22.1570, 23.2764, 24.1115, 24.6829, 25.8914, 27.1763, 28.4642, 29.7254, 30.7261, 32.6167 have diffraction peaks; further, the free state crystalline form J has substantially Fig.90 The XRPD spectrum shown;

[0099] In some embodiments, the free crystalline Form J has one or more of the following characteristics:

[0100] (1) The TGA curve shows a weight loss of 0.5-2.5% at 150±3°C, preferably about 0.5-1.5% (e.g., 0.5%, 1.0%, 1.5%); more preferably, about 1.09%;

[0101] (2) The DSC curve has an endothermic peak at 181.5±3℃;

[0102] In some embodiments, the TGA / DSC graph of the free crystalline Form J is substantially as follows Fig.91 As shown; the free state crystal form J 1 The HNMR diagram is basically Fig.92 As shown;

[0103] In some embodiments, the free crystalline Form J is an anhydrate.

[0104] In some embodiments, the present invention provides a free crystalline form K of the compound of formula I, wherein the free crystalline form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.0722, 18.7484, 19.0653, 19.7672, 20.4112, and 20.9312 having diffraction peaks; further, the free crystalline form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8469, 15.0722, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, and 20.9312. .9312, 21.1881; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is 9.8469, 10.1208, 15.0722, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1881, 21.6963, 28.3413; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is 9.8469, 10.1208 , 14.6920, 15.0722, 15.4155, 16.0745, 16.7829, 17.6356, 18.1386, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1881, 21.6963, 24.0591, 28.3413, 28.6573, 30.5394 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is 9.3256, 9.846 9, 10.1208, 13.0145, 14.6920, 15.0722, 15.4155, 16.0745, 16.7829, 17.6356, 18.1386, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1881, 21.6963, 24.0591, 26.2506, 28.3413, 28.6573, 30.5394, 33.0658 have diffraction peaks; further, the free state crystalline form K has substantially Fig.94 The XRPD spectrum shown;

[0105] In some embodiments, the free crystalline form K has one or more of the following characteristics:

[0106] (1) The TGA curve shows a weight loss of 6-11% at 150±3°C, preferably about 7-10% (e.g., 7.0%, 7.5%, 8.0%, 8.5%, 9.0%); more preferably, about 8.24%;

[0107] (2) The DSC curve has three endothermic peaks at 72.0±3℃, 165.2±3℃, and 180.2±3℃;

[0108] (3) The DSC curve has an exothermic peak at 167.1±3°;

[0109] In some embodiments, the TGA / DSC graph of the free crystalline form K is substantially as follows Fig.95 As shown; the free state crystal form K 1 The HNMR diagram is basically Fig.96 As shown;

[0110] In some embodiments, the free crystalline form K is a solvate;

[0111] In some embodiments, the free crystalline form K is an EtOH solvate or a cosolvate of EtOH and water;

[0112] In some embodiments, in the solvate, the molar ratio of EtOH to the free state is 0.27.

[0113] In some embodiments, the present invention provides a free crystalline form L of the compound of formula I, wherein the free crystalline form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.8304, 15.8341, 17.7145, 19.1795, 20.5748, and 25.5115 having diffraction peaks; further, the free crystalline form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.8304, 15.8341, 17.7145, 19.1795, 20.5748, and 25.5115. 9.1795, 20.0943, 20.5748, 25.5115 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8304, 15.8341, 17.7145, 19.1795, 20.0943, 20.5748, 22.4409, 25.5115 ... The final diffraction spectrum has diffraction peaks at 8.8304, 11.1727, 15.8341, 16.8550, 17.1190, 17.7145, 19.1795, 19.7076, 20.0943, 20.5748, 22.4409, and 25.5115; further, the X-ray powder diffraction spectrum of the free crystalline form L represented by a diffraction angle of 2θ±0.2° is 8.8304, 9.6805, 10.2446, 10.7612, There are diffraction peaks at 11.1727, 14.5973, 15.5971, 15.8341, 16.8550, 17.1190, 17.7145, 18.2884, 19.1795, 19.7076, 20.0943, 20.5748, 22.4409, 25.5115, 28.7935, 29.8794, 31.2614, 32.0233, and 35.9945; further, the free form L has substantially the following Fig.99b XRPD spectrum shown.

[0114] On the other hand, the present invention provides a pharmaceutically acceptable salt of the compound of formula I, which can be selected from the salt formed by the compound of formula I and an acid, and the acid can be selected from an inorganic acid or an organic acid. The pharmaceutically acceptable salt of the compound of formula I is selected from the hydrochloride, sulfate, maleate, phosphate, p-toluenesulfonate, methanesulfonate, ethanesulfonate, L-aspartate, fumarate, tartrate, 1,2-ethanedisulfonate of the compound of formula I.

[0115] According to a preferred embodiment of the present invention, the pharmaceutically acceptable salt of the compound of formula I is the hydrochloride, sulfate, maleate, phosphate, p-toluenesulfonate, methanesulfonate, ethanesulfonate, 1,2-ethanedisulfonate of the compound of formula I.

[0116] According to the embodiments of the present invention, those skilled in the art will appreciate that when the compound of formula I forms a salt with an acid, the molar ratio of the acid to the compound of formula I can be 5:1 to 1:5, for example 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5.

[0117] In other embodiments, the molar ratio of the acid to the compound of formula I is 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, 3.6:1, 3.7:1, 3.8:1, 3.9:1, 4.1:1, 4.2:1, 4.3:1, 4.4:1, 4.5:1, 4.6:1, 4.7:1, 4.8:1, 4.9:1.

[0118] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is the hydrochloride of the compound of formula I, in which the molar ratio of hydrochloric acid to the compound of formula I is 1:1, 1.1:1, 1.2:1, 1.3:1, or 2:1.

[0119] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a sulfate salt of the compound of formula I, wherein the molar ratio of sulfuric acid to the compound of formula I is 1:1, 1.1:1, 1.2:1, 1.5:1, 1.6:1, or 2:1.

[0120] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a maleate salt of the compound of formula I, wherein the molar ratio of maleic acid to the compound of formula I is 1:1.

[0121] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a phosphate salt of the compound of formula I, wherein the molar ratio of phosphoric acid to the compound of formula I is 4:1, 4.3:1, 4.5:1, or 5:1.

[0122] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a p-toluenesulfonate salt of the compound of formula I, wherein the molar ratio of p-toluenesulfonic acid to the compound of formula I is 1:1.

[0123] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a methanesulfonate salt of the compound of formula I, wherein the molar ratio of methanesulfonic acid to the compound of formula I is 1:1 or 1.1:1.

[0124] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is an ethanesulfonate salt of the compound of formula I, wherein the molar ratio of ethanesulfonic acid to the compound of formula I is 1:1 or 1.1:1.

[0125] In some embodiments, the pharmaceutically acceptable salt of the compound of formula I is a 1,2-ethanedisulfonate salt of the compound of formula I, wherein the molar ratio of 1,2-ethanedisulfonic acid to the compound of formula I is 1:1, 1.1:1, or 1.2:1.

[0126] In another aspect, the present invention provides a crystalline form of a pharmaceutically acceptable salt of the compound of formula I.

[0127] In some embodiments, the present invention provides a hydrochloride salt form A of the compound of formula I, wherein the hydrochloride salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 18.8832, 19.5324, 20.1382, 21.3379, and 21.7432 having diffraction peaks; further, the hydrochloride salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 14.7835, 14.9893, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 21.3379, and 21.7432 having diffraction peaks; further, the hydrochloride salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 14.7835, 14.9893, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 21.3379, and 21.7432 having diffraction peaks; further, the hydrochloride salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 14.7835, 14.9893, 18.2960, 18.8832, 19.33 The diffraction spectrum has diffraction peaks at 10.1755, 14.7835, 14.9893, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 20.9418, 21.3379, 21.7432, 25.7379, 27.2284, and 29.8240; further The X-ray powder diffraction spectrum of the hydrochloride crystal form A represented by a diffraction angle of 2θ±0.2° is 6.6910, 9.4043, 10.1755, 11.3549, 12.0715, 12.7466, 13.3874, 14.1825, 14.7835, 14.9893, 17.2365, 18.2960,

[0128] 18.8832, 19.3310, 19.5324, 20.1382, 20.9418, 21.3379, 21.7432, 22.5426, 23.5259, 24.0002, 25.3951, 25.7379, 26.6858, 27.2284, 27.7725, 28.5839, 29.1003, 29.8240, 30.7557, 31.8138, 33.7066, 34.5682, 35.3206, 36.1697, 37.1954, 38.5831, 39.2520 have diffraction peaks; further, the hydrochloride form A has substantially Fig.12a or Figure 12b XRPD spectrum shown.

[0129] In some embodiments, the hydrochloride salt form A has one or two of the following characteristics:

[0130] (1) The TGA curve of hydrochloride crystal form A shows a weight loss of 4-12% at 160.0±3°C, preferably about 6-10% (e.g., 6.0%,

[0131] 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%);

[0132] (2) The DSC curve of hydrochloride form A has an endothermic peak at 165.8±3℃.

[0133] In some embodiments, the hydrochloride salt form A has one or two of the following characteristics:

[0134] (1) The TGA curve of hydrochloride form A shows a weight loss of 8.21% at 160.0±3°C;

[0135] (2) The DSC curve of hydrochloride form A has an endothermic peak at 165.8±3℃.

[0136] In some embodiments, the TGA / DSC diagram of the hydrochloride salt form A is substantially as follows Fig.13 As shown; the hydrochloride crystal form A 1 The HNMR diagram is basically Fig.14 shown.

[0137] In some embodiments, the present invention provides a hydrochloride salt form B of the compound of formula I, wherein the hydrochloride salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 5.8284, 12.9418, 15.8305, 17.4248, 17.7208, and 25.1539; further, the hydrochloride salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 5.8284, 12.9418, 15.8305, 16.6807, 17.4248, 17.7208, and 20. 3860, 21.1241, 24.6834, 25.1539 have diffraction peaks; further, the hydrochloride form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.8284, 12.9418, 15.6394, 15.8305, 16.6807, 17.4248, 17.7208, 20.3860, 21.1241, 24.6834, 25.1539; further, the hydrochloride form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at There are diffraction peaks at 5.8284, 12.0258, 12.9418, 14.5910, 15.6394, 15.8305, 16.6807, 17.4248, 17.7208, 18.9434, 19.3954, 19.8130, 20.3860, 21.1241, 24.6834, and 25.1539; further, the X-ray powder diffraction spectrum of the hydrochloride form B represented by a diffraction angle of 2θ±0.2° is 5.8284, 10.2084, 12.0258, 12.941 8, 14.5910, 15.6394, 15.8305, 16.6807, 17.0761, 17.4248, 17.7208, 18.9434, 19.3954, 19.8130, 20.3860, 21.1241, 23.0260, 23.5341, 24.6834, 25.1539, 26.7017, 27.1748, 28.3119, 29.2775, 30.8075, 34.0826 have diffraction peaks; further, the hydrochloride form B has substantially Fig.15 XRPD spectrum shown.

[0138] In some embodiments, the hydrochloride salt form B has one or two of the following characteristics:

[0139] (1) The TGA curve of the hydrochloride salt form B shows a weight loss of 10-20% at 180.0±3°C, preferably about 12-18% (e.g., 12.0%, 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, 15.0%, 15.5%, 16.0%, 16.5%, 17.0%, 17.5%, 18.0%);

[0140] (2) The DSC curve of hydrochloride form B has two endothermic peaks at 154.1±3℃ and 171.0±3℃.

[0141] In some embodiments, the hydrochloride salt form B has one or two of the following characteristics:

[0142] (1) The TGA curve of hydrochloride form B showed a weight loss of 16.61% at 180.0±3°C;

[0143] (2) The DSC curve of hydrochloride form B has two endothermic peaks at 154.1±3℃ and 171.0±3℃.

[0144] In some embodiments, the TGA / DSC diagram of the hydrochloride salt form B is substantially as follows Fig.16 As shown; the hydrochloride crystal form B 1 The HNMR diagram is basically Fig.17 shown.

[0145] In some embodiments, the present invention provides a hydrochloride salt form C of the compound of formula I, wherein the hydrochloride salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6027, 5.7758, 13.6699, 14.4660, 21.6765, 23.2062, and 27.1991; further, the hydrochloride salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6027, 5.7758, 13.6699, 14.4660, 17.1465, 18.7028, 21.6765, 23. 2062, 27.1991; further, the X-ray powder diffraction spectrum of the hydrochloride form C represented by a diffraction angle of 2θ±0.2° is 5.6027, 5.7758, 13.2815, 13.6699, 13.8622, 14.4660, 17.1465, 18.7028, 21.6765, 23.2062, 27.1991; further, the X-ray powder diffraction spectrum of the hydrochloride form C represented by a diffraction angle of 2θ±0.2° is 5.6027, 5.7758, 8.7367, 11.1522, 1 3.2815, 13.6699, 13.8622, 14.4660, 16.6600, 17.1465, 18.7028, 19.4828, 20.9473, 21.6765, 22.4844, 23.2062, 26.3673, and 27.1991 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form C represented by a diffraction angle of 2θ±0.2° is 5.6027, 5.7758, 8.7367, 9.2140, 11.1522, 11.8436, 13.2815, 13.6699, 13.8622, 14.4660, 15.2083, 16.1990, 16.6600, 17.1465, 17.9792, 18.7028, 19.4828, 20.0737, 20.3774, 20.9473, 21.6765, 22.0633, 22.4844, 23.2062, 24.0140, 24.9698, 25.8392, 26.3673, 27.1991, 28.0148, 29.1691, and 37.7780 have diffraction peaks; further, the hydrochloride crystal form C has substantially Fig.18 XRPD spectrum shown.

[0146] In some embodiments, the hydrochloride salt form C has one, two or three of the following characteristics:

[0147] (1) The TGA curve of hydrochloride form C shows a weight loss of 2-10% at 90.0±3°C, preferably about 3-6% (e.g., 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%);

[0148] (2) The TGA curve of the hydrochloride salt form C shows a weight loss of 2-10% at 170.0±3°C, preferably about 5-8% (e.g., 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%);

[0149] (3) The DSC curve of hydrochloride form C has two endothermic peaks at 77.8±3℃ and 174.6±3℃.

[0150] In some embodiments, the hydrochloride salt form C has one, two or three of the following characteristics:

[0151] (1) The TGA curve of hydrochloride form C shows a weight loss of 4.67% at 90.0±3°C;

[0152] (2) The TGA curve of hydrochloride form C shows a weight loss of 6.00% at 170.0±3°C;

[0153] (3) The DSC curve of hydrochloride form C has two endothermic peaks at 77.8±3℃ and 174.6±3℃.

[0154] In some embodiments, the TGA / DSC diagram of the hydrochloride salt form C is substantially as follows Fig.19 As shown; the hydrochloride crystal form C 1 The HNMR diagram is basically Fig. 20 shown.

[0155] In some embodiments, the present invention provides a hydrochloride salt form D of the compound of formula I, wherein the hydrochloride salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2274; further, the hydrochloride salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.578 2, 11.8655, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2274; further, the X-ray powder diffraction spectrum of the hydrochloride form D represented by a diffraction angle of 2θ±0.2° is 6.5782, 9.9619, 11.8655, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2274. .3323, 21.2274 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5782, 9.9619, 11.1481, 11.8655, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, 21.2274, 26.6683; further, the The hydrochloride crystal form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5782, 9.9619, 11.1481, 11.8655, 12.8040, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, 21.2274, 26.6683, and 29.0358. Further, the hydrochloride crystal form D has substantially Fig.107 XRPD spectrum shown.

[0156] In some embodiments, the present invention provides a hydrochloride salt form E of the compound of formula I, wherein the hydrochloride salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.9750, 12.8980, 15.2093, 15.6063, 17.9714, and 25.4838; further, the hydrochloride salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.9750, 12.8980, 15.2093, 15.60 63, 17.9714, 24.9674, 25.4838 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.9750, 12.8980, 15.0507, 15.2093, 15.6063, 17.8054, 17.9714, 24.9674, 25.4838 ... The diffraction spectrum has diffraction peaks at 5.9750, 12.8980, 15.0507, 15.2093, 15.6063, 16.0284, 17.8054, 17.9714, 19.8405, 20.5435, 22.5488, 24.9674, 25.4838, and 26.1257; further, the X-ray powder diffraction spectrum of the hydrochloride form E represented by a diffraction angle of 2θ±0.2° is 5.9750, 12.8980, 13.7 925, 15.0507, 15.2093, 15.6063, 16.0284, 17.8054, 17.9714, 18.9298, 19.8405, 20.5435, 21.0218, 21.9935, 22.5488, 24.9674, 25.4838, 26.1257, 27.4268, 29.8322, 30.4635, 31.7533 have diffraction peaks; further, the hydrochloride crystal form E has substantially Fig.110 XRPD spectrum shown.

[0157] In some embodiments, the present invention provides a hydrochloride salt form F of the compound of formula I, wherein the hydrochloride salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0385, 15.9019, 18.1478, 20.5749, and 25.4190 having diffraction peaks; further, the hydrochloride salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0385, 12.6362, 15.9019, 17.1363 .... The X-ray powder diffraction spectrum represented by a diffraction angle of 0.2° has diffraction peaks at 6.0385, 12.6362, 13.0399, 15.9019, 17.1363, 18.1478, 18.8427, 20.5749, 21.8092, and 25.4190; further, the X-ray powder diffraction spectrum of the hydrochloride salt form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0385, 12.6362, 13.0399, 15.9019, 16.8142, 17.1363, 18.1478, 18.4776, 18.8427, 19.3354,

[0158] There are diffraction peaks at 20.5749, 21.3694, 21.8092, 25.1076, and 25.4190; further, the X-ray powder diffraction spectrum of the hydrochloride form F represented by a diffraction angle of 2θ±0.2° is 6.0385, 12.0772, 12.6362, 13.0399, 13.5971, 14.9525, 15.9019, 16.8142, 17.1363, 18.1478, 18.477 6, 18.8427, 19.3354, 20.5749, 21.3694, 21.8092, 23.2223, 25.1076, 25.4190, 27.1737, 27.8200, 28.2136, 28.9299, 29.9049, 31.9291, 34.1705, 35.2232, 36.7164, 39.1368 have diffraction peaks; further, the hydrochloride form F has substantially Fig.111 XRPD spectrum shown.

[0159] In some embodiments, the present invention provides a hydrochloride crystalline form G of the compound of formula I, wherein the X-ray powder diffraction spectrum of the hydrochloride crystalline form G expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 9.4719, 18.6112, 19.0898, 20.7520, and 24.9637; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form G expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 6. 5684, 9.4719, 15.5605, 18.6112, 19.0898, 20.7520, and 24.9637; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form G represented by a diffraction angle of 2θ±0.2° is 6.5684, 7.0798, 9.4719, 15.5605, 18.6112, 19.0898, 20.752 0, 24.9637; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5684, 7.0798, 9.4719, 15.5605, 18.6112, 19.0898, 20.7520, 22.1933, 24.9637, and 28.7471; further, the hydrochloride crystal form G has diffraction peaks at 2θ±0.2°. The X-ray powder diffraction spectrum of the salt crystal form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5684, 7.0798, 9.4719, 13.6772, 14.4725, 15.5605, 18.6112, 19.0898, 20.7520, 22.1933, 24.9637, and 28.7471; further, the hydrochloride crystal form G has substantially Fig.106b XRPD spectrum shown.

[0160] In some embodiments, the present invention provides a hydrochloride salt form H of the compound of formula I, wherein the hydrochloride salt form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 12.9273, 15.1559, 15.5659, 17.6473, 18.2972, 19.4651, 19.7972, and 20.4603 having diffraction peaks; further, the hydrochloride salt form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 12.9273, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 19.4651, 19.7972, 20.4603, 20.7147 Further, the X-ray powder diffraction spectrum of the hydrochloride salt form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 12.4381, 12.9273, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147; further, the X-ray powder diffraction spectrum of the hydrochloride salt form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 8.4236, 10.0644, 10.4677, 12.0841, 12.4381, 12.9273, 13. 5430, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 18.7344, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147, 20.9217, 21.5046, 21.7941, 22.4391, 22.7460, 23.8221, 25.3590, 27.6629 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 8.4236, 10.0644, 10.4677, 12.0841, 12.4381, 12.9273, 13.5430, 15.1559, 15.5659, 16.2484, 16.8381, 17.6473, 18.2972, 18.7344, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147, 20.9217, 21.5046, 21.7941, 22.4391, 22.7460, 23.8221, 25.3590, 25.9795, 26.4453, 27.1720, 27.6629, 28.6111, 29.0095, 30.6017 have diffraction peaks; further, the hydrochloride form H has substantially Fig.106c The XRPD spectrum shown;

[0161] In some embodiments, the hydrochloride salt form H has one or more of the following characteristics:

[0162] (1) The TGA curve shows a weight loss of 5-10% at 170±3°C, preferably about 6-9% (e.g., 7.0%, 7.5%, 8.0%); more preferably, about 7.61%;

[0163] (2) The DSC curve has two endothermic peaks at 155.5°C and 191.5°C;

[0164] In some embodiments, the TGA / DSC diagram of the hydrochloride salt form H is substantially as follows Fig.108 As shown; the hydrochloride crystal form H 1 The HNMR diagram is basically Fig.109 shown.

[0165] In some embodiments, the present invention provides a hydrochloride salt form I of the compound of formula I, wherein the hydrochloride salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.2065, 7.0236, 13.8915, 14.6038, 20.8063, 21.1874, and 24.9901 having diffraction peaks; further, the hydrochloride salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.2065 , 7.0236, 13.8915, 14.6038, 17.7770, 20.8063, 21.1874, 24.9901; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form I represented by a diffraction angle of 2θ±0.2° is 6.2065, 7.0236, 13.8915, 14.6038, 15.6403, 17.7770, 20.8063, 21.1874, 24. 9901, 25.4883 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2065, 7.0236, 11.6337, 13.8915, 14.6038, 15.6403, 17.7770, 19.2571, 20.8063, 21.1874, 24.9901, 25.4883; further, the The hydrochloride salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.2065, 7.0236, 11.6337, 13.8915, 14.6038, 15.6403, 17.0255, 17.7770, 19.2571, 20.8063, 21.1874, 23.6537, 24.9901, and 25.4883. Further, the hydrochloride salt form I has substantially Fig.106d XRPD spectrum shown.

[0166] In some embodiments, the present invention provides a hydrochloride salt form J of the compound of formula I, wherein the hydrochloride salt form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.3031, 15.0739, 18.8389, 19.8236, 20.0800, and 21.4914 having diffraction peaks; further, the hydrochloride salt form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.3031, 15.0739, 18.5121, 18.8389, 19.8236, 20.0800, 21.4914, and 22.0336 having diffraction peaks. Peak; further, the X-ray powder diffraction spectrum of the hydrochloride salt form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.3031, 12.9670, 15.0739, 18.5121, 18.8389, 19.8236, 20.0800, 21.4914, 21.7526, 22.0336, and 22.2164; further, the X-ray powder diffraction spectrum of the hydrochloride salt form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.7191, 9.4898, 10.3031, 11.5598, 12.9670, 13.7721, 14 .2248, 15.0739, 17.8940, 18.5121, 18.8389, 19.5450, 19.8236, 20.0800, 21.0834, 21.4914, 21.7526, 22.0336, 22.2164, 22.5454, 25.6500, 26.1804, 27.4986, and 30.2463 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form J represented by a diffraction angle of 2θ±0.2° is 6.7191, 9.4898, 10.3031, 11.5598, 12.9 670, 13.7721, 14.2248, 15.0739, 17.8940, 18.5121, 18.8389, 19.5450, 19.8236, 20.0800, 21.0834, 21.4914, 21.7526, 22.0336, 22.2164, 22.5454, 24.4676, 25.6500, 26.1804, 27.4986, 29.5851, 30.2463, 31.2643, 32.4691, 34.1280 have diffraction peaks; further, the hydrochloride crystal form J has substantially Fig.106e XRPD spectrum shown.

[0167] In some embodiments, the present invention provides a hydrochloride salt form K of the compound of formula I, wherein the hydrochloride salt form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.1719, 11.2365, 12.9493, 15.6381, 20.5819, and 25.3451 having diffraction peaks; further, the hydrochloride salt form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.1719, 11.2365, 12.94 93, 15.6381, 18.5078, 20.5819, 25.3451 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 11.2365, 12.9493, 15.6381, 17.8017, 18.5078, 20.5819, 25.3451, 26.0590, 26.3085; further, the salt The X-ray powder diffraction spectrum of the hydrochloride salt form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 7.6126, 11.2365, 12.9493, 13.9646, 15.6381, 17.8017, 18.5078, 19.8165, 20.5819, 25.3451, 26.0590, and 26.3085; further, the X-ray powder diffraction spectrum of the hydrochloride salt form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 7.6126, 11.2365, 12.9493, 13.9646, 15.6381, 17.8017, 18.5078, 19.8165, 20.5819, 25.3451, 26.0590, and 26.3085. The diffraction spectrum has diffraction peaks at 6.1719, 7.6126, 11.2365, 12.9493, 13.9646, 15.6381, 16.6189, 17.1911, 17.8017, 18.5078, 19.8165, 20.5819, 21.7916, 22.5977, 25.3451, 26.0590, 26.3085, and 30.7181; further, the hydrochloride crystal form K has substantially Fig.106f XRPD spectrum shown.

[0168] In some embodiments, the present invention provides a hydrochloride salt form L of the compound of formula I, wherein the hydrochloride salt form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.7752, 13.8951, 17.1547, 21.4837, and 24.0925; further, the hydrochloride salt form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.7752, 13.895 1, 15.3025, 17.1547, 17.8681, 21.4837, 24.0925, and 26.5641; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form L represented by a diffraction angle of 2θ±0.2° is 7.7752, 13.8951, 15.3025, 17.1547, 17.8681, 21.4837, 23.4738, 24.0925,

[0169] There is a diffraction peak at 26.5641; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form L represented by a diffraction angle of 2θ±0.2° is 7.7752, 10.4411, 13.8951, 15.3025, 16.3403, 17.1547, 17.8681, 19.2621, 21.4837, 23.4738,

[0170] The X-ray powder diffraction spectrum of the hydrochloride crystal form L expressed at a diffraction angle of 2θ±0.2° is 7.7752, 10.4411, 13.2333, 13.8951, 15.3025, 16.340 3, 17.1547, 17.8681, 19.2621, 19.9563, 21.4837, 22.4156, 23.4738, 24.0925, 25.5726, 26.5641, 28.1186, 30.8899, 38.4894 have diffraction peaks; further, the hydrochloride crystal form L has substantially Figure 106g The XRPD spectrum shown;

[0171] In some embodiments, the present invention provides a hydrochloride salt form M of the compound of formula I, wherein the hydrochloride salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8040, 14.8344, 18.8157, 19.2503, 20.6275, and 21.0461 having diffraction peaks; further, the hydrochloride salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5546, 9.8040, 14.8344 , 18.8157, 19.2503, 20.6275, 21.0461 have diffraction peaks; further, the hydrochloride crystal form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5546, 9.8040, 12.0038, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461; further, the hydrochloride crystal form M has diffraction peaks at 6.5546, 9.8040, 12.0038, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461; further, the hydrochloride crystal form M The X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5546, 9.8040, 10.8235, 12.0038, 13.1333, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461, 26.8393, and 28.6992; further, the ... hydrochloride form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°. The powder diffraction spectrum has diffraction peaks at 6.5546, 9.8040, 10.8235, 12.0038, 13.1333, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461, 22.8294, 24.8213, 26.8393, 28.6992, 29.5703, and 33.9685; further, the hydrochloride form M has substantially Figure 106h The XRPD spectrum shown;

[0172] In some embodiments, the present invention provides a sulfate salt crystalline form A of the compound of formula I, wherein the sulfate salt crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5297, 7.4156, 11.2590, 17.2920, and 19.5870 having diffraction peaks; further, the sulfate salt crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5297, 7.4156, 11.2590, 17.2920, 18.3831, 18.9056, 19.5870, 23.1076, and 25.1201 have diffraction peaks; further, the sulfate crystal form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5297, 7.4156, 11.2590, 17.2920, 18.3831, 18.9056, 19.5870, 19.8280, 23.1076, and 25.1201; further, the sulfate crystal form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° There are diffraction peaks at 6.5297, 7.4156, 11.2590, 14.8207, 15.0692, 17.2920, 17.5479, 18.3831, 18.9056, 19.5870, 19.8280, 21.1050, 23.1076, 23.6024, and 25.1201; further, the X-ray powder diffraction spectrum of the sulfate crystal form A represented by a diffraction angle of 2θ±0.2° is 6.5297, 7.4156, 9.8272, 11.2 590, 11.7996, 13.0075, 14.8207, 15.0692, 17.2920, 17.5479, 18.3831, 18.9056, 19.5870, 19.8280, 20.1191, 21.1050, 21.9720, 23.1076, 23.6024, 25.1201, 27.2805, 28.7070, 29.8446, 32.6299 have diffraction peaks; further, the sulfate crystal form A has substantially Fig. 22 XRPD spectrum shown.

[0173] In some embodiments, the sulfate salt crystalline form A has one or two of the following characteristics:

[0174] (1) The TGA curve of sulfate crystal form A shows a weight loss of 2-10% at 150.0±3°C, preferably about 4-7% (e.g., 4.0%, 4.5%,

[0175] 5.0%, 5.5%, 6.0%, 6.5%, 7.0%);

[0176] (2) The DSC curve of sulfate form A has two endothermic peaks at 52.9±3℃ and 167.1±3℃.

[0177] In some embodiments, the sulfate salt crystalline form A has one or two of the following characteristics:

[0178] (1) The TGA curve of sulfate form A shows a weight loss of 5.78% at 150.0±3°C;

[0179] (2) The DSC curve of sulfate form A has two endothermic peaks at 52.9±3℃ and 167.1±3℃.

[0180] In some embodiments, the TGA / DSC diagram of the sulfate salt form A is substantially as follows Fig.23 As shown; the sulfate crystal form A 1 The HNMR diagram is basically Fig.24 shown.

[0181] In some embodiments, the present invention provides a sulfate salt form B of the compound of formula I, wherein the sulfate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8491, 16.5561, 17.1270, 17.8255, and 19.6977 having diffraction peaks; further, the sulfate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8491, 1 6.5561, 17.1270, 17.8255, 18.1372, 19.6977, 19.0468, 22.6654, 26.1622; further, the X-ray powder diffraction spectrum of the sulfate crystal form B represented by a diffraction angle of 2θ±0.2° is 6.3375, 9.8491, 13.0250, 16.5561, 17.1270, 17.8255, 18.1372, 19.6977, 19.0468, 22.2378, 22.6654, 25.7586, 26.1622, 29.7168 have diffraction peaks; further, the sulfate crystal form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.3375, 8.6916, 9.1864, 9.8491, 11.7001, 12.1619 、13.0250、14.4700、15.1807、16.5561、17.1270、17.8255、18.1372、19.0468、19.6977、21.6775、22.2378、22.6654、23.4512、23.8100、24.8186、25.4720、25.7586、26.1622、27.1217、

[0182] There are diffraction peaks at 29.0464, 29.7168, 30.9706, 33.1687, and 34.5562; further, the sulfate crystal form B has substantially Fig.25 XRPD spectrum shown.

[0183] In some embodiments, the sulfate salt crystalline form B has one or two of the following characteristics:

[0184] (1) The TGA curve of sulfate salt form B shows a weight loss of 0-5% at 150.0±3°C, preferably about 1-3% (e.g., 1.0%, 1.5%, 2.0%, 2.5%, 3.0%);

[0185] (2) The DSC curve of sulfate form B has two endothermic peaks at 69.7±3℃ and 238.5±3℃.

[0186] In some embodiments, the sulfate salt crystalline form B has one or two of the following characteristics:

[0187] (1) The TGA curve of sulfate form B shows a weight loss of 1.16% at 150.0±3°C;

[0188] (2) The DSC curve of sulfate form B has two endothermic peaks at 69.7±3℃ and 238.5±3℃.

[0189] In some embodiments, the TGA / DSC diagram of the sulfate salt form B is substantially as follows Fig.26 As shown; the sulfate crystal form B 1 The HNMR diagram is basically Fig. 27 shown.

[0190] In some embodiments, the present invention provides a sulfate salt form C of the compound of formula I, wherein the sulfate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 8.9487, 17.5523, 17.9120, 19.9597, and 22.9905; further, the sulfate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 8.9487, 9.8314, 14.4549, 17.5523, 17.9120, 18.7584, 19.5850, 19.9597, 20.9974, 22.4850, 22.9905, 24.5952, and 29.4160; further, the sulfate salt form The X-ray powder diffraction spectrum of C expressed at a diffraction angle of 2θ±0.2° is 8.9487, 9.8314, 12.2693, 14.4549, 17.5523, 17.9120, 18.7584, 19.5850, 19.9597, 20.6152, 20.9974, 21.9335, 22.4850, 22.9 905, 23.6939, 23.9937, 24.5952, 26.7497, and 29.4160; further, the X-ray powder diffraction spectrum of the sulfate crystal form C represented by a diffraction angle of 2θ±0.2° is 7.4762, 8.0099, 8.9487, 9.8314, 11.7697, 12.2693,

[0191] 13.3788, 14.4549, 14.9774, 15.3199, 16.8293, 17.5523, 17.9120, 18.7584, 19.5850, 19.9597, 20.6152, 20.9974, 21.9335, 22.4850, 22.9905, 23.6939, 23.9937, 24.5952, 24.8904, 25.3759, 26.2847, 26.7497, 28.4461, 29.4160, 31.7091, 33.4595, 34.8478, 36.5099, 38.0959 have diffraction peaks; further, the sulfate crystal form C has substantially Fig.28 XRPD spectrum shown.

[0192] In some embodiments, the sulfate salt crystalline form C has one, two or three of the following characteristics:

[0193] (1) The TGA curve of sulfate crystal form C shows a weight loss of 1-5% at 100.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5%,

[0194] 2.0%, 2.5%, 3.0%, 3.5%, 4.0%);

[0195] (2) The DSC curve of sulfate form C has four endothermic peaks at 92.4±3℃, 159.3±3℃, 184.8±3℃ and 216.8±3℃;

[0196] (3) The DSC curve of sulfate crystal form C has an exothermic peak at 224.0±3℃.

[0197] In some embodiments, the sulfate salt crystalline form C has one, two or three of the following characteristics:

[0198] (1) The TGA curve of sulfate crystal form C shows a weight loss of 2.83% at 100.0±3℃;

[0199] (2) The DSC curve of sulfate form C has four endothermic peaks at 92.4±3℃, 159.3±3℃, 184.8±3℃ and 216.8±3℃;

[0200] (3) The DSC curve of sulfate crystal form C has an exothermic peak at 224.0±3℃.

[0201] In some embodiments, the TGA / DSC diagram of the sulfate salt form C is substantially as follows Fig.29 As shown; the sulfate crystal form C 1 HNMR images Fig.30 shown.

[0202] In some embodiments, the present invention provides a maleate salt form A of the compound of formula I, wherein the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 13.7865, 16.3294, 18.2795, 20.3336, and 20.8824 having diffraction peaks; further, the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 13.7865, 15.9646 , 16.3294, 18.2795, 20.3336, 20.8824, 21.3104, 21.5283, 23.1978, and 24.1136 have diffraction peaks; further, the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 10.4550, 13.7865, 15.9646, 16.3294, 17.7554, 18.2795, 20.333 6, 20.8824, 21.3104, 21.5283, 23.1978, 24.1136, and 24.7430; further, the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 8.1664, 10.4550, 11.4963, 13.7865, 14.9748, 15.6098, 15.9646, 16.3294, 17.23 88, 17.7554, 18.2795, 18.7232, 19.2252, 19.9626, 20.3336, 20.8824, 21.3104, 21.5283, 21.8250, 22.5862, 23.1978, 23.7175, 24.1136, 24.7430, 25.0797, 26.1594, 27.1361, 27.5054, 28.4773, 29.4248,

[0203] There are diffraction peaks at 30.0997, 30.4233, 31.3563, 32.1988, 32.8832, 34.8721, 36.2350, and 37.8027; further, the maleate salt form A has substantially Fig.31 XRPD spectrum shown.

[0204] In some embodiments, the maleate salt form A has one or two of the following characteristics:

[0205] (1) The TGA curve of maleate crystalline form A shows a weight loss of 0-4% at 130.0±3°C, preferably about 0-3% (e.g., 0.5%,

[0206] 1.0%, 1.5%, 2.0%, 2.5%, 3.0%);

[0207] (2) The DSC curve of maleate salt form A has an endothermic peak at 142.1±3℃.

[0208] In some embodiments, the maleate salt form A has one or two of the following characteristics:

[0209] (1) The TGA curve of maleate form A shows a weight loss of 0.42% at 130.0±3°C;

[0210] (2) The DSC curve of maleate salt form A has an endothermic peak at 142.1±3℃.

[0211] In some embodiments, the TGA / DSC diagram of the maleate salt form A is substantially as follows Fig.32 As shown; the maleate crystalline form A 1 H NMR images Fig.33 shown.

[0212] In some embodiments, the present invention provides a phosphate crystal form A of the compound of formula I, wherein the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.3607, 17.8932, 19.3716, 19.8946, 20.5448, 21.1372, and 22.4294; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8. 8155, 9.3607, 17.8932, 18.4384, 19.3716, 19.8946, 20.5448, 21.1372, 22.4294, 24.5486 have diffraction peaks; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° is 8.8155, 9.3607, 11.1767, 16.4840, 17.8932, 18.43 84, 19.3716, 19.8946, 20.5448, 21.1372, 22.4294, 23.1105, 23.9976, 24.5486, 24.5486, 25.7922, and 26.3981; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° is 3.2059, 8.8155, 9.3607, 11.176 7, 13.9605, 16.4840, 17.8932, 18.4384, 19.3716, 19.8946, 20.5448, 21.1372, 22.4294, 23.1105, 23.9976, 24.5486, 25.7922, 26.3981, 26.9789, 28.2812, 30.2804 have diffraction peaks; further, the phosphate crystal form A has substantially Fig.34 XRPD spectrum shown.

[0213] In some embodiments, the phosphate crystal form A has one, two or three of the following characteristics:

[0214] (1) The TGA curve of the phosphate crystal form A shows a weight loss of 1-6% at 150.0±3°C, preferably about 2-5% (e.g., 2.0%, 2.5%,

[0215] 3.0%, 3.5%, 4.0%, 4.5%, 5.0%);

[0216] (2) The DSC curve of phosphate form A has two endothermic peaks at 41.5±3℃ and 169.6±3℃;

[0217] (3) The DSC curve of phosphate form A has an exothermic peak at 91.8℃±3℃.

[0218] In some embodiments, the phosphate crystal form A has one, two or three of the following characteristics:

[0219] (1) The TGA curve of phosphate form A shows a weight loss of 3.71% at 150.0±3°C;

[0220] (2) The DSC curve of phosphate form A has two endothermic peaks at 41.5±3℃ and 169.6±3℃;

[0221] (3) The DSC curve of phosphate form A has an exothermic peak at 91.8℃±3℃.

[0222] In some embodiments, the TGA / DSC graph of the phosphate crystal form A is substantially as follows Fig.35 As shown; the phosphate crystal form A 1 HNMR images Fig.36 shown.

[0223] In some embodiments, the present invention provides a p-toluenesulfonate crystalline form A of the compound of formula I, wherein the p-toluenesulfonate crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6569, 6.5865, 9.0105, 14.4962, 17.1789, and 19.7973 having diffraction peaks; further, the p-toluenesulfonate crystalline form A has substantially Fig.38 XRPD spectrum shown.

[0224] In some embodiments, the p-toluenesulfonate crystalline form A has one or two of the following characteristics:

[0225] (1) The TGA curve of p-toluenesulfonate Form A shows a weight loss of 2-8% at 150.0±3°C, preferably about 2-6% (e.g., 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%);

[0226] (2) The DSC curve of p-toluenesulfonate Form A has two endothermic peaks at 81.6±3℃ and 156.0±3℃;

[0227] In some embodiments, the p-toluenesulfonate crystalline form A has one or two of the following characteristics:

[0228] (1) The TGA curve of p-toluenesulfonate Form A shows a weight loss of 4.15% at 150.0±3°C;

[0229] (2) The DSC curve of p-toluenesulfonate Form A has two endothermic peaks at 81.6±3℃ and 156.0±3℃;

[0230] In some embodiments, the TGA / DSC diagram of the p-toluenesulfonate salt form A is substantially as follows Fig.39 As shown; the p-toluenesulfonate crystalline form A 1 H NMR images Fig.40 shown.

[0231] In some embodiments, the present invention provides a p-toluenesulfonate crystalline form B of the compound of formula I, wherein the p-toluenesulfonate crystalline form B has diffraction peaks at 7.6660, 16.2695, 17.6681, 19.5433, 20.3312, and 21.3520 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the p-toluenesulfonate crystalline form B has diffraction peaks at 7.6660, 11.1056, 14.5769, 16. 2695, 17.6681, 19.5433, 20.3312, 20.7694, 21.3520, and 26.0500; further, the X-ray powder diffraction spectrum of the p-toluenesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 7.6660, 11.1056, 14.5769, 14.9845, 16.2695, 17.6681, 19.5433, 20.3312, 20.7694, 21.3520, 22.8795,

[0232] 24.5060, 26.0500, and 28.2460; further, the X-ray powder diffraction spectrum of the p-toluenesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 6.8890, 7.6660, 9.9665, 11.1056, 11.8448, 12.6617, 13.1706, 13.6098, 13.8415, 14.5769, 14.9845, 16.2695, 17.6681, 18. 8718, 19.5433, 19.9700, 20.3312, 20.7694, 21.3520, 21.6902, 22.8795, 24.5060, 26.0500, 26.4583, 27.2822, 28.2460, 29.2107, 30.0879, 31.8132, 32.8460, 33.7653, 37.7617 have diffraction peaks; further, the p-toluenesulfonate salt form B has substantially Fig.41 XRPD spectrum shown.

[0233] In some embodiments, the p-toluenesulfonate crystalline Form B has one or two of the following characteristics:

[0234] (1) The TGA curve of the p-toluenesulfonate salt Form B shows a weight loss of 1-6% at 150.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%);

[0235] (2) The DSC curve of p-toluenesulfonate Form B has an endothermic peak at 204.3±3°C;

[0236] In some embodiments, the p-toluenesulfonate crystalline Form B has one or two of the following characteristics:

[0237] (1) The TGA curve of p-toluenesulfonate Form B shows a weight loss of 1.92% at 150.0±3°C;

[0238] (2) The DSC curve of p-toluenesulfonate Form B has an endothermic peak at 204.3±3°C;

[0239] In some embodiments, the TGA / DSC diagram of the p-toluenesulfonate salt Form B is substantially as follows Fig.42 As shown; the p-toluenesulfonate crystalline form B 1 The H NMR spectrum is basically Fig.43 shown.

[0240] In some embodiments, the present invention provides a mesylate salt form A of the compound of formula I, wherein the mesylate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.1654, 7.7112, 10.2242, 15.4030, 16.8120, and 19.2492 having diffraction peaks; further, the mesylate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.1654, 7.7112, 10.2242, 11.4305, 15.40 30, 16.8120, 17.7499, 18.3934, 18.9572, 19.2492, and 20.0359; further, the X-ray powder diffraction spectrum of the mesylate salt form A represented by a diffraction angle of 2θ±0.2° is 7.1654, 7.7112, 10.2242, 11.4305, 15.4030, 16.8120, 17.7499, 18.3934, 18.9572, 19.2492, 19.6796, 20.0359,

[0241] There are diffraction peaks at 21.4943, 23.1420, and 25.5679; further, the X-ray powder diffraction spectrum of the mesylate salt form A represented by a diffraction angle of 2θ±0.2° is 6.4245, 7.1654, 7.7112, 10.2242, 11.4305, 12.1973, 14.3852, 14.9410, 15.4030, 16.8120, 17.3257, 17.7499, 18.3934 , 18.9572, 19.2492, 19.6796, 20.0359, 20.7137, 21.0725, 21.4943, 22.4448, 23.1420, 23.6743, 24.4576, 25.1217, 25.5679, 27.3091, 28.2828, 30.2612, 31.6602, and 33.8876 have diffraction peaks; further, the mesylate salt form A has substantially Fig.45 XRPD spectrum shown.

[0242] In some embodiments, the mesylate salt form A has one or two of the following characteristics:

[0243] (1) The TGA curve of the mesylate salt form A shows a weight loss of 1-6% at 150.0±3°C, preferably about 2-5% (e.g., 2.0%,

[0244] 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%);

[0245] (2) The DSC curve of mesylate form A has an endothermic peak at 153.8±3°C;

[0246] In some embodiments, the mesylate salt form A has one or two of the following characteristics:

[0247] (1) The TGA curve of mesylate form A shows a weight loss of 3.08% at 150.0±3°C;

[0248] (2) The DSC curve of mesylate form A has an endothermic peak at 153.8±3°C;

[0249] In some embodiments, the TGA / DSC diagram of the mesylate salt form A is substantially as follows Fig.46 As shown; the mesylate crystal form A 1 H NMR images Fig.47 shown.

[0250] In some embodiments, the present invention provides a mesylate salt form B of the compound of formula I, wherein the mesylate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 7.9334, 17.1889, 17.9047, 19.4932, and 20.3844; further, the mesylate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 7.9334, 16.2948, 17.1889, 17.9047, 18.9481, 19.4932, 20.3844, 21.2069, 23.9181, and 26.8731; further, the mesylate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 2θ±0.2°. The X-ray powder diffraction spectrum shown has diffraction peaks at 7.9334, 12.4699, 13.8134, 14.2662, 16.2948, 17.1889, 17.9047, 18.9481, 19.4932, 20.3844, 21.2069, 22.9645, 23.9181, and 26.8731 Still further, the X-ray powder diffraction spectrum of the mesylate salt form B represented by a diffraction angle of 2θ±0.2° is 7.9334, 10.5237, 11.7673, 12.4699, 13.8134, 14.2662, 16.2948, 17.1889, 17.9047, 18.9481, 19.4932,

[0251] There are diffraction peaks at 20.3844, 21.2069, 22.3570, 22.9645, 23.9181, 25.0848, 26.8731, 28.8447, 30.5888, and 36.0120; further, the mesylate salt form B has substantially Fig.48 XRPD spectrum shown.

[0252] In some embodiments, the mesylate salt Form B has one or two of the following characteristics:

[0253] (1) The TGA curve of the mesylate salt form B shows a weight loss of 0-3% at 150.0±3°C, preferably about 0-2% (e.g., 0.5%,

[0254] 1.0%, 1.5%, 2.0%);

[0255] (2) The DSC curve of mesylate form B has three endothermic peaks at 161.8±3℃, 168.3±3℃ and 194.9±3℃.

[0256] In some embodiments, the mesylate salt Form B has one or two of the following characteristics:

[0257] (1) The TGA curve of mesylate Form B shows a weight loss of 0.67% at 150.0±3°C;

[0258] (2) The DSC curve of mesylate form B has three endothermic peaks at 61.8±3℃, 168.3±3℃ and 194.9±3℃.

[0259] In some embodiments, the TGA / DSC diagram of the mesylate salt form B is substantially as follows Fig.49 As shown; the mesylate crystal form B 1 The H NMR spectrum is basically Fig.50 shown.

[0260] In some embodiments, the present invention provides a mesylate salt form C of the compound of formula I, wherein the mesylate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6360, 9.3088, 15.7926, 17.1524, 17.5174, and 20.4316; further, the mesylate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6360, 9.3088, 15.7926, 17.1524, 17.5174, and 20.4316. The diffraction spectrum has diffraction peaks at 5.6360, 9.3088, 13.6745, 15.7926, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 25.2739, and 25.6773; further, the X-ray powder diffraction spectrum of the mesylate salt form C represented by a diffraction angle of 2θ±0.2° is 5.6360 , 9.3088, 12.6477, 13.6745, 15.7926, 16.1257, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 23.0206, 23.4450, 25.2739, 25.6773 have diffraction peaks; further, the mesylate salt form C has a diffraction peak at 2θ±0.2° The X-ray powder diffraction spectrum represented by the diffraction angle is 5.6360, 8.5661, 9.3088, 11.6453, 12.6477, 13.6745, 15.7926, 16.1257, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 23.0206, 23.4450, 25.2739,

[0261] There are diffraction peaks at 25.6773, 29.4554, and 32.4112; Still further, the mesylate salt form C has substantially Fig.51 XRPD spectrum shown.

[0262] In some embodiments, the mesylate salt form C has one or two of the following characteristics:

[0263] (1) The TGA curve of the mesylate salt form C shows a weight loss of 10-20% at 150.0±3°C, preferably about 12-16% (e.g., 12.0%,

[0264] 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, 15.0%, 15.5%, 16.0%);

[0265] (2) The DSC curve of mesylate form C has three endothermic peaks at 111.7±3℃, 135.8±3℃ and 139.6±3℃.

[0266] In some embodiments, the mesylate salt form C has one or two of the following characteristics:

[0267] (1) The TGA curve of mesylate form C shows a weight loss of 14.14% at 150.0±3°C;

[0268] (2) The DSC curve of mesylate form C has three endothermic peaks at 111.7±3℃, 135.8±3℃ and 139.6±3℃.

[0269] In some embodiments, the TGA / DSC diagram of the mesylate salt form C is substantially as follows Fig.52 As shown; the mesylate crystal form C 1 The H NMR spectrum is basically Fig.53 shown.

[0270] In some embodiments, the present invention provides a mesylate salt form D of the compound of formula I, wherein the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 17.0139, 17.2434, 17.5216, 19.2452, and 20.3331 having diffraction peaks; further, the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 19.2452, 19.8274, and 20.3331 having diffraction peaks; further, the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 19.2452, 19.8274, and 20.3331 having diffraction peaks. The X-ray powder diffraction spectrum represented by the diffraction angle of θ±0.2° has diffraction peaks at 7.3614, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 18.7631, 19.2452, 19.8274, 20.3331, and 25.3625; further, the mesylate crystal The X-ray powder diffraction spectrum of type D expressed at a diffraction angle of 2θ±0.2° is 7.3614, 8.5975, 11.1942, 12.9868, 13.4101, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 18.0167, 18.3980, 18.7631,

[0271] 19.2452, 19.8274, 20.3331, 21.8273, 22.4894, 23.0593, 25.3625; Still further, the X-ray powder diffraction spectrum of the mesylate salt form D represented by a diffraction angle of 2θ±0.2° is 6.3734, 7.3614, 8.5975, 9.8950, 11.1942, 12.9868, 13.4101, 14.7 295, 14.9968, 15.9124, 17.0139, 17.2434, 17.5216, 18.0167, 18.3980, 18.7631, 19.2452, 19.8274, 20.3331, 21.8273, 22.4894, 23.0593, 24.4152, 25.3625 have diffraction peaks; further, the mesylate salt form D has substantially Fig.102b The XRPD spectrum shown;

[0272] In some embodiments, the mesylate salt form D has one or more of the following characteristics:

[0273] (1) The TGA curve shows a weight loss of 1-4% at 150±3°C, preferably about 1.5-3% (e.g., 1.5%, 2.0%, 2.5%, 3.0%); more preferably, about 2.62%;

[0274] (2) The DSC curve has two endothermic peaks at 40.3±3℃ and 156.6±3℃;

[0275] In some embodiments, the TGA / DSC diagram of the mesylate salt form D is substantially as follows Fig.103 As shown; the mesylate crystal form D 1 The H NMR spectrum is basically Fig.104 shown.

[0276] In some embodiments, the present invention provides a mesylate salt form E of the compound of formula I, wherein the mesylate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 7.6948, 13.5466, 18.9557, 19.4674, and 26.1850; further, the mesylate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 7.6948, 13.5466, 18.9557, 19.4674, 20.0144, 23.7738, and 26.1850; Further, the X-ray powder diffraction spectrum of the mesylate salt form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.6948, 13.5466, 18.9557, 19.4674, 20.0144, 22.3698, 23.7738, and 26.1850; further, the X-ray powder diffraction spectrum of the mesylate salt form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.6948, 13.5466, 14.5860, 16.1727, 17.5309, 17.8641, 18.9557, 19.467 4, 20.0144, 20.3406, 20.8237, 21.6960, 22.3698, 23.7738, 25.1077, 26.1850, and 29.2032 have diffraction peaks; further, the mesylate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6948, 11.0258, 12.4963, 13.5466, 14.2591, 14.5860, 15.3154, 16.1727, 16.8137, 17.0486, 17.5309, 1 7.8641, 18.9557, 19.4674, 20.0144, 20.3406, 20.8237, 21.6960, 22.3698, 22.8750, 23.1733, 23.7738, 25.1077, 25.3713, 25.7306, 26.1850, 26.8900, 27.6964, 28.4667, 29.2032, 30.5281, 31.4140, 33.7897, 35.9511 have diffraction peaks; further, the mesylate salt form E has substantially Fig.112b XRPD spectrum shown.

[0277] In some embodiments, the present invention provides a mesylate salt form F of the compound of formula I, wherein the mesylate salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 15.7726, 17.0258, 17.8165, 20.2728, and 23.7446 having diffraction peaks; further, the mesylate salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 15.7726,

[0278] There are diffraction peaks at 17.0258, 17.8165, 20.2728, 23.7446, and 25.3530; further, the X-ray powder diffraction spectrum of the mesylate salt form F represented by a diffraction angle of 2θ±0.2° is 7.8706, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207,

[0279] 23.7446, 25.3530; further, the X-ray powder diffraction spectrum of the mesylate salt form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.8706, 11.8701, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207, 23.7446, 25.3530, and 26.3257; further, the mesylate salt form F has diffraction peaks at 2θ±0.2°. The X-ray powder diffraction spectrum of the salt form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.0171, 7.8706, 11.8701, 13.4221, 14.3209, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207, 23.7446, 25.3530, and 26.3257; further, the mesylate salt form F has substantially the following properties: Fig.112c XRPD spectrum shown.

[0280] In some embodiments, the present invention provides a mesylate salt form G of the compound of formula I, wherein the mesylate salt form has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 16.1377, 17.7027, 18.1620, 19.1132, and 21.0530; further, the mesylate salt form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4837, 16.1377, 16.5841,

[0281] 17.7027, 18.1620, 19.1132, 21.0530, 24.3157; further, the mesylate salt form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 13.4333, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, 21.053 0, 24.3157, 24.8063, and 26.2930 have diffraction peaks; further, the X-ray powder diffraction spectrum of the mesylate salt form G represented by a diffraction angle of 2θ±0.2° is 8.6041, 10.1340, 12.6682, 13.4333, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132 , 21.0530, 22.0640, 24.3157, 24.8063, 25.5461, 26.2930, and 28.8940; further, the X-ray powder diffraction spectrum of the mesylate salt form G represented by a diffraction angle of 2θ±0.2° is 8.6041, 10.1340, 11.2069, 12.6682, 13.4333, 14.492 2, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, 21.0530, 22.0640, 24.3157, 24.8063, 25.5461, 26.2930, 26.9311, 27.7204, 28.8940 have diffraction peaks; further, the mesylate salt form G has substantially Fig.113b XRPD spectrum shown.

[0282] In some embodiments, the present invention provides a mesylate salt crystalline form H of the compound of formula I, wherein the mesylate salt crystalline form has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5858, 16.4833, 17.2040, 19.7648, and 22.2051 having diffraction peaks; further, the mesylate salt crystalline form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5858, 9.8551, 12 .8418, 16.4833, 17.2040, 19.7648, and 22.2051 have diffraction peaks; further, the mesylate salt form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5858, 9.8551, 12.8418, 16.4833, 17.2040, 19.7648, 22.2051, 25.4281, and 26.1391; further The X-ray powder diffraction spectrum of the mesylate salt form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5858, 9.8551, 12.8418, 16.4833, 17.2040, 17.7099, 18.5860, 19.7648, 21.8135, 22.2051, 25.4281, 26.1391, and 29.8198; further, the mesylate salt form H has a diffraction peak at 2θ±0.2°. The X-ray powder diffraction spectrum expressed by the diffraction angle of ±0.2° is 5.6472, 9.5858, 9.8551, 12.8418, 15.2067, 16.4833, 17.2040, 17.7099, 18.5860, 19.2029, 19.7648, 21.8135, 22.2051, 23.4137, 24.9851, 25.4281, 26.1391, 27.6138,

[0283] There are diffraction peaks at 29.8198, 30.9209, 32.0327, and 35.9179; Still further, the mesylate salt form H has substantially Fig.113c XRPD spectrum shown.

[0284] In some embodiments, the present invention provides a mesylate salt form I of the compound of formula I, wherein the mesylate salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 24.0274, and 25.6562; further, the mesylate salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 24.0274, and 25.6562; The X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 22.8525, 24.0274, and 25.6562; further, the X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° of the mesylate salt form I has diffraction peaks at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 22.8525, 24.0274, and 25.6562. The diffraction peaks are at 5.9556, 17.3872, 17.7652, 18.1048, 22.8525, 24.0274, and 25.6562; further, the X-ray powder diffraction spectrum of the mesylate salt form I represented by a diffraction angle of 2θ±0.2° is 7.9648, 11.3739, 15.1578, 15.9556, 16.6385, 17.38 72, 17.7652, 18.1048, 20.2628, 22.8525, 24.0274, and 25.6562; further, the X-ray powder diffraction spectrum of the mesylate salt form I represented by a diffraction angle of 2θ±0.2° is 7.9648, 11.3739, 15.1578, 15.9556, 16.6385, 17.3872,

[0285] There are diffraction peaks at 17.7652, 18.1048, 19.1430, 20.2628, 21.6954, 22.8525, 24.0274, 25.0167, and 25.6562; further, the mesylate salt form I has substantially Fig.113d XRPD spectrum shown.

[0286] In some embodiments, the present invention provides a mesylate salt form J of the compound of formula I, wherein the mesylate salt form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.6620, 13.5049, 16.1555, 18.1900, 21.9852, 22.2107, and 22.9624 having diffraction peaks; further, the mesylate salt form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° The figure has diffraction peaks at 8.6620, 10.0632, 11.4255, 13.5049, 16.1555, 18.1900, 21.9852, 22.2107, and 22.9624; further, the X-ray powder diffraction spectrum of the mesylate salt form J expressed at a diffraction angle of 2θ±0.2° is 8.6620, 10.0632, 11.4255, 13.5049, 16.1555, 17.56 47, 18.1900, 19.7621, 21.9852, 22.2107, and 22.9624; further, the X-ray powder diffraction spectrum of the mesylate salt form J expressed at a diffraction angle of 2θ±0.2° is 8.6620, 10.0632, 11.4255, 13.5049, 16.1555, 17.5647, 18.1900, 19.7621, 21.9852, 22. 2107, 22.9624, and 24.6246 have diffraction peaks; further, the X-ray powder diffraction spectrum of the mesylate salt form J represented by a diffraction angle of 2θ±0.2° is 8.6620, 10.0632, 11.4255, 13.5049, 14.5059, 15.1512, 16.1555, 17.5647, 18.1900, 19.7621, 20.5741, 21.9852,

[0287] There are diffraction peaks at 22.2107, 22.9624, 24.6246, and 30.6181; further, the mesylate salt form J has substantially Fig.113e XRPD spectrum shown.

[0288] In some embodiments, the present invention provides a mesylate salt form K of the compound of formula I, wherein the mesylate salt form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4362, 17.2898, 17.5619, 18.6931, 21.1887, and 25.1553; further, the mesylate salt form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4362, 17.2898, 17.5619, 18.6931, 21.1887, and 25.1553. The X-ray powder diffraction spectrum has diffraction peaks at 15.4362, 17.2898, 17.5619, 18.6931, 19.5256, 21.1887, and 25.1553; further, the X-ray powder diffraction spectrum of the mesylate salt form K represented by a diffraction angle of 2θ±0.2° is 15.4362, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256,

[0289] 21.1887, 21.9878, 25.1553; further, the mesylate salt form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.6859, 15.4362, 16.5219, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256, 21.1887, 21.9878, 22.9735, 25.1553, 26.0704, 28.8383, and 30.0689 ...2θ±0.2°. The X-ray powder diffraction spectrum represented by the diffraction angle has diffraction peaks at 8.6859, 9.9129, 12.6815, 13.4500, 14.0343, 15.4362, 16.5219, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256, 21.1887, 21.9878, 22.9735, 25.1553, 26.0704, 27.0875, 28.8383, 30.0689, 31.9147, and 33.0164; further, the mesylate salt form K has substantially Fig.113f XRPD spectrum shown.

[0290] In some embodiments, the present invention provides a mesylate salt crystalline form L of the compound of formula I, wherein the mesylate salt crystalline form L has diffraction peaks at 8.0867, 18.6275, 19.6478, and 21.1470 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the mesylate salt crystalline form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8. 0867, 11.8848, 18.6275, 19.6478, 21.1470, 21.6729, and 21.9361; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° is 8.0867, 11.8848, 18.6275, 19.6478, 21.1470, 21.67 29, 21.9361, and 29.6831; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° is 8.0867, 11.8848, 18.6275, 19.6478, 20.5586, 21.1470, 21.6729, 21.9361, 23.0719, 23.4214 , 27.7310, and 29.6831 have diffraction peaks; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° is 8.0867, 11.8848, 14.2858, 15.7466, 16.2087, 18.6275, 19.6478, 20.5586, 21.1470, 21.6729,

[0291] There are diffraction peaks at 21.9361, 22.3422, 23.0719, 23.4214, 23.9149, 27.7310, 28.6368, 29.6831, and 38.4394; further, the mesylate salt form L has substantially Figure 113g XRPD spectrum shown.

[0292] In some embodiments, the present invention provides a mesylate salt form M of the compound of formula I, wherein the mesylate salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 16.0880, 17.4084, 17.6442, 18.6200, 18.8984, and 20.6457; further, the mesylate salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and has diffraction peaks at 6.0854, 16.0880, 16.2048, 17. 4084, 17.6442, 18.6200, 18.8984, 20.6457 have diffraction peaks; further, the mesylate salt crystalline form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0854, 9.8088, 15.6545, 16.0880, 16.2048, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 20.6457 have diffraction peaks; further, the mesylate salt crystalline form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0854, 9.8088, 15.6545, 16.0880, 16.2048, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 20.6457 have diffraction peaks; further, the mesylate salt crystalline form The X-ray powder diffraction spectrum of the salt form M represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0854, 8.6714, 9.8088, 13.3246, 15.6545, 16.0880, 16.2048, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 19.7051, 20.6457, 21.0719, 22.1260, 24.4928, and 25.3051; further, The X-ray powder diffraction spectrum of the mesylate salt form M represented by a diffraction angle of 2θ±0.2° is 6.0854, 8.6714, 9.8088, 12.3906, 13.3246, 13.8974, 15.6545, 16.0880, 16.2048, 16.8014, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 19.7051, 20.6457, 21.0719, 22.1260,

[0293] There are diffraction peaks at 22.9780, 24.4928, 25.3051, 26.3685, and 28.9539; further, the mesylate salt form M has substantially Fig.114b XRPD spectrum shown.

[0294] In some embodiments, the present invention provides a mesylate salt form N of the compound of formula I, wherein the mesylate salt form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 17.4887, 17.7573, 18.3532, 19.4978, 19.7328, and 27.6786 having diffraction peaks; further, the mesylate salt form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.1585, 17.4887,

[0295] There are diffraction peaks at 17.7573, 18.3532, 19.4978, 19.7328, and 27.6786; further, the X-ray powder diffraction spectrum of the mesylate salt form N represented by a diffraction angle of 2θ±0.2° is 9.1585, 17.4887, 17.7573, 18.0588, 18.3532, 19.4978,

[0296] 19.7328, 20.2234, 21.1657, 25.2039, and 27.6786 have diffraction peaks; further, the mesylate salt form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.1585, 10.5913, 13.8291, 15.3223, 17.4887, 17.7573, 18.0588, 18.3532, 19.4978, 19.7328, 20.2234, 21.1657, 21.6656, 23.4530, 25.2039, 26.7244, 27.6786, and 30.5646. Still further, the mesylate salt form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.1585, 10.5913, 13.8291, 15.3223, 17.4887, 17.7573, 18.0588, 18.3532, 19.0631, 19.4978, 19.7328, 20.2234, 21.1657, 21.6656, 22.4118, 23.4530, 25.2039, 26.7244, 27.6786, 30.5646, and 34.8974. Still further, the mesylate salt form N has substantially Fig.114c XRPD spectrum shown.

[0297] In some embodiments, the present invention provides a mesylate salt form O of the compound of formula I, wherein the mesylate salt form O has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8632, 16.4454, 17.1724, 17.8526, 19.5652, and 19.7882 having diffraction peaks; further, the mesylate salt form O has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8632, 16.4454,

[0298] There are diffraction peaks at 17.1724, 17.8526, 19.1922, 19.5652, and 19.7882; further, the X-ray powder diffraction spectrum of the mesylate salt form O represented by a diffraction angle of 2θ±0.2° is 9.8632, 16.4454, 17.1724, 17.8526, 19.1922, 19.5652,

[0299] There are diffraction peaks at 19.7882, 21.5123, 22.6207, 25.3282, and 26.0079; further, the X-ray powder diffraction spectrum of the mesylate salt form O represented by a diffraction angle of 2θ±0.2° is 9.8632, 13.0102, 16.4454, 17.1724, 17.8526, 18.5219,

[0300] 19.1922, 19.5652, 19.7882, 20.7837, 21.5123, 22.1595, 22.6207, 23.3625, 25.3282, 26.0079, 29.5124 have diffraction peaks; further, the mesylate salt form O has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8632, 11.9975, 13.0102, 14.1723, 16.445 4, 17.1724, 17.8526, 18.5219, 19.1922, 19.5652, 19.7882, 20.7837, 21.5123, 22.1595, 22.6207, 23.3625, 24.6883, 25.3282, 26.0079, 29.5124, 30.2740, 31.3467, 32.7120 have diffraction peaks; further, the mesylate salt form O has substantially Fig.114d XRPD spectrum shown.

[0301] In some embodiments, the present invention provides an ethanesulfonate salt form A of the compound of formula I, wherein the ethanesulfonate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4322, 14.8852, 16.6572, 17.5439, and 20.0726 having diffraction peaks; further, the ethanesulfonate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4322, 10.3920, 13.3770, 14.4406, 14.8852, 16.6572, 17.5439, 20.0726, and 22.0062 having diffraction peaks; further, the ethanesulfonate salt form A has substantially Fig.55 XRPD spectrum shown.

[0302] In some embodiments, the ethanesulfonate salt form A has one or two of the following characteristics:

[0303] (1) The TGA curve of ethanesulfonate crystal form A shows a weight loss of 5-12% at 150.0±3°C, preferably about 6-10% (e.g., 6.0%,

[0304] 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10.0%);

[0305] (2) The DSC curve of ethanesulfonate form A has two endothermic peaks at 36.3±3℃ and 141.5±3℃.

[0306] In some embodiments, the ethanesulfonate salt form A has one or two of the following characteristics:

[0307] (1) The TGA curve of ethanesulfonate Form A shows a weight loss of 8.29% at 150.0±3°C;

[0308] (2) The DSC curve of ethanesulfonate form A has two endothermic peaks at 36.3±3℃ and 141.5±3℃.

[0309] In some embodiments, the TGA / DSC diagram of the ethanesulfonate salt form A is substantially as follows Fig.56 As shown; the ethanesulfonate crystal form A 1 The H NMR spectrum is basically Fig.57 shown.

[0310] In some embodiments, the present invention provides an ethanesulfonate salt form B of the compound of formula I, wherein the ethanesulfonate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 15.3679, 17.7077, 18.9091, 19.5992, and 20.7324 having diffraction peaks; further, the ethanesulfonate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 11.9022, 15.3679, 17.7077, 18.9091, 19.5992, 19.9469, 20.7324, 22.2822, and 24.6012 having diffraction peaks; further, the ethanesulfonate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 11.9022, 15.3679, 17.7077, 18.9091, 19.5992, 19.9469, 20.7324, 22.2822, and 24.6012 having diffraction peaks; further, the ethanesulfonate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 11.9022, The X-ray powder diffraction spectrum expressed at a diffraction angle of ±0.2° is 4.9173, 11.9022, 14.8131, 15.3679, 17.7077, 18.9091, 19.5992, 19.9469, 20.7324, 22.2822, 23.7415, 24.6012, 25.4858, 27.0 042; Still further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 4.9173, 10.3467, 11.9022, 13.3498, 13.9472, 14.8131, 15.3679, 16.5326, 17.7077, 18.9091,

[0311] There are diffraction peaks at 19.5992, 19.9469, 20.7324, 21.2340, 22.2822, 23.7415, 24.6012, 25.4858, 27.0042, 27.7863, 29.2924, 29.9997, and 31.9631; further, the ethanesulfonate salt form B has substantially Fig.58a Or the XRPD spectrum shown in 58b.

[0312] In some embodiments, the ethanesulfonate salt Form B has one or two of the following characteristics:

[0313] (1) The TGA curve of ethanesulfonate crystal form B shows a weight loss of 3-10% at 150.0±3°C, preferably about 4-8% (e.g., 4.0%,

[0314] 4.5%, 5.0%, 5.5%, 6.0%, 6.5%7.0%, 7.5%, 8.0%);

[0315] (2) The DSC curve of ethanesulfonate form B has two endothermic peaks at 107.1±3℃ and 145.3±3℃.

[0316] In some embodiments, the ethanesulfonate salt Form B has one or two of the following characteristics:

[0317] (1) The TGA curve of ethanesulfonate Form B shows a weight loss of 6.30% at 150.0±3°C;

[0318] (2) The DSC curve of ethanesulfonate form B has two endothermic peaks at 107.1±3℃ and 145.3±3℃.

[0319] In some embodiments, the TGA / DSC diagram of the ethanesulfonate salt form B is substantially Fig.59 As shown; the ethanesulfonate crystal form B 1 The H NMR spectrum is basically Fig.60 shown.

[0320] In some embodiments, the present invention provides an ethanesulfonate salt form C of the compound of formula I, wherein the ethanesulfonate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.3040, 10.4226, 13.6779, 15.9618, 20.3279, and 20.9348 having diffraction peaks; further, the ethanesulfonate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° There are diffraction peaks at 6.3040, 8.7771, 10.4226, 13.6779, 15.9618, 19.0549, 20.3279, and 20.9348; further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form C represented by a diffraction angle of 2θ±0.2° is 6.3040, 8.7771, 10.4226, 13.6779, 15.9618, 17.6528, 1 9.0549, 19.8646, 20.3279, 20.9348, 21.7435, 23.4169, 26.2647 have diffraction peaks; further, the ethanesulfonate salt form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.3040, 8.7771, 10.4226, 12.0274, 12.5635, 13.6779, 14.9315 , 15.9618, 17.6528, 18.0467, 19.0549, 19.8646, 20.3279, 20.9348, 21.7435, 23.4169, 24.3601, 26.2647, 26.8633, 28.5527, 29.9377, 32.4837, 35.6194 have diffraction peaks; further, the ethanesulfonate salt form C has substantially Fig.121b XRPD spectrum shown.

[0321] In some embodiments, the present invention provides an ethanesulfonate salt form D of the compound of formula I, wherein the ethanesulfonate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9081, 15.7893, 17.4668, 17.7671, 19.9837, 20.9514, and 23.8046 having diffraction peaks; further, the ethanesulfonate salt form D has substantially Fig.121c XRPD spectrum shown.

[0322] In some embodiments, the ethanesulfonate salt form D has one or more of the following characteristics:

[0323] (1) The TGA curve shows a weight loss of 0.5-3% at 150±3°C, preferably about 0.5-2% (e.g., 0.5%, 1.0%, 1.5%, 2.0%); more preferably, about 1.70%;

[0324] (2) The DSC curve has three endothermic peaks at 55.5±3℃, 142.4±3℃ and 184.2±3℃;

[0325] (3) The DSC curve has an exothermic peak at 91.6±3℃.

[0326] In some embodiments, the TGA / DSC diagram of the ethanesulfonate salt form D is substantially as follows Fig.122 As shown; the ethanesulfonate crystal form D 1 The H NMR spectrum is basically Fig.123 shown.

[0327] In some embodiments, the present invention provides an ethanesulfonate salt form E of the compound of formula I, wherein the ethanesulfonate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, 13.6740, 15.4870, 18.9455, 20.0718, 21.4317, and 23.2933 having diffraction peaks; further, the ethanesulfonate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, 10.9010, 13.6740, 15.4870, 16.1908, 18.9455, 20.0718, 21.4317, and 23.2933 having diffraction peaks; further, the ethanesulfonate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, 10.9010, 13.6740, 15.4870, 16.1908, 18.9455, 20.0718, 21.4317, and 23.2933 having diffraction peaks; further, the ethanesulfonate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, The X-ray powder diffraction spectrum represented by the diffraction angle of θ±0.2° has diffraction at 6.4770, 9.3320, 10.9010, 12.3962, 13.6740, 15.4870, 16.1908, 17.8603, 18.9455, 19.6221, 20.0718, 21.4317, 23.2933 Peak; Still further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form E represented by a diffraction angle of 2θ±0.2° is 6.4770, 9.3320, 10.9010, 12.3962, 13.6740, 14.7088, 15.4870, 16.1908, 17.8603, 18.9455, 19.6221,

[0328] There are diffraction peaks at 20.0718, 20.4917, 21.4317, 23.2933, 24.8830, and 27.4600; further, the ethanesulfonate crystal form E has substantially Fig.121d XRPD spectrum shown.

[0329] In some embodiments, the ethanesulfonate salt form E has one or more of the following characteristics:

[0330] (1) The TGA curve shows a weight loss of 2-7% at 110±3°C, preferably about 3-6% (e.g., 4.0%, 4.5%, 5.0%, 5.5%); more preferably, about 4.64%;

[0331] (2) The DSC curve has three endothermic peaks at 48.4±3℃, 104.0±3℃ and 188.3±3℃;

[0332] In some embodiments, the TGA / DSC diagram of the ethanesulfonate salt form E is substantially as follows Fig.124 As shown; the ethanesulfonate crystal form E 1 The H NMR spectrum is basically Fig.125 shown.

[0333] In some embodiments, the present invention provides an ethanesulfonate salt form F of the compound of formula I, wherein the ethanesulfonate salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.7081, 9.3273, and 18.7028; further, the ethanesulfonate salt form F has substantially Fig.121e XRPD spectrum shown.

[0334] In some embodiments, the present invention provides a 1,2-ethanedisulfonate salt form A of the compound of formula I, wherein the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5776, 9.7934, 16.5380, 17.6744, 19.6187, 20.1184, and 20.7238; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5776, 9.7934, 12.9489, 16.5380, 16.9718, 17.6744, 19.6187, 20.1184, 20.7238 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° is 9.5776, 9.7934, 12.9489, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.219 ... -X-ray powder diffraction spectrum has diffraction peaks at 9.5776, 9.7934, 12.9489, 13.3845, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198, 23.1294, 25.3534, 26.0706, 26.5387, and 27.8458; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° is 9.5776, 9.7934 , 11.0447, 12.1309, 12.9489, 13.3845, 14.5687, 15.5203, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198, 23.1294, 24.1339, 25.3534, 26.0706, 26.5387, 27.8458, 30.3527, 31.4653 have diffraction peaks; further, the 1,2-ethanedisulfonate salt form A has substantially Fig.126b XRPD spectrum shown.

[0335] In some embodiments, the present invention provides a 1,2-ethanedisulfonate salt form B of the compound of formula I, wherein the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5593, 16.2913, 16.5067, 17.0648, 17.7815, and 20.1011; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6887, 9.5593, 12.9139, 16.2913, 16.5067 , 17.0648, 17.7815, and 20.1011 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6887, 9.5593, 10.0235, 12.9139, 16.2913, 16.5067, 17.0648, 17.7815, 18.6648, 20.1011, and 22.2426; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks. The spectrum has diffraction peaks at 5.6887, 9.5593, 10.0235, 12.9139, 14.9480, 16.2913, 16.5067, 17.0648, 17.7815, 18.6648, 20.1011, 21.5441, 22.2426, 22.8020, 25.8424, 26.4853, 29.8463, and 30.3500; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 5.6887, 7.536 1, 9.5593, 10.0235, 12.9139, 14.9480, 16.2913, 16.5067, 17.0648, 17.7815, 18.6648, 20.1011, 21.5441, 21.9422, 22.2426, 22.8020, 23.3535, 23.8750, 25.8424, 26.4853, 27.9265, 29.8463, 30.3500, 32.6082 have diffraction peaks; further, the 1,2-ethanedisulfonate salt form B has substantially Fig.126c XRPD spectrum shown.

[0336] In some embodiments, the present invention provides a 1,2-ethanedisulfonate salt form C of the compound of formula I, wherein the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 17.8877, 19.3330, 19.8489, 20.7131, and 21.1631; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 13.3305, 16.7417, 17.887 7, 19.3330, 19.8489, 20.7131, and 21.1631 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.9129, 13.3305, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, and 23.0842; further, the 1,2-ethanedisulfonate salt form C has diffraction peaks at 10.9129, 13.3305, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, and 23.0842; further, The X-ray powder diffraction spectrum of the crystal form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.9129, 12.0262, 13.3305, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, 22.3700, 23.0842, 24.1491, and 27.8056; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystal form C represented by a diffraction angle of 2θ±0.2° The diffraction spectrum has diffraction peaks at 7.9970, 9.8985, 10.9129, 12.0262, 13.3305, 15.5409, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, 22.3700, 23.0842, 24.1491, 25.2521, 27.8056, and 31.2456; further, the 1,2-ethanedisulfonate salt form C has substantially Fig.126d XRPD spectrum shown.

[0337] On the other hand, the present invention provides a method for preparing the free crystalline form A of the compound of formula I, comprising the following steps: placing the compound of formula I in an organic solvent and stirring, concentrating and drying, then adding water and heating under reflux; stirring at room temperature overnight, filtering, and drying. The organic solvent is selected from acetonitrile.

[0338] On the other hand, the present invention provides a method for preparing the free crystalline form B of the compound of formula I, comprising the steps of: slurrying the compound of formula I in an organic solvent for 1-5 days, centrifuging and separating the solid and drying. The organic solvent is selected from alcohols, preferably ethanol. The drying is selected from vacuum drying, and the drying temperature is 40-60°C, preferably 50°C.

[0339] On the other hand, the present invention provides a method for preparing the free crystalline form C of the compound of formula I, comprising the steps of: slurrying the compound of formula I in an organic solvent, centrifuging and separating the solid and drying. The organic solvent is selected from MTBE. The drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C. The slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days.

[0340] According to an embodiment of the present invention, the compound of formula I can be prepared by referring to the synthesis method disclosed in Chinese patent application CN202310400928.8.

[0341] On the other hand, the present invention provides a method for preparing the free crystalline form D of the compound of formula I, comprising the following steps:

[0342] Step 1:

[0343]

[0344] Add compound I-8, THF, and anhydrous ethanol, stir to dissolve, add anhydrous calcium chloride, stir to dissolve, cool to 0°C, add sodium borohydride, react at room temperature overnight, pour the reaction solution into water, add ethyl acetate, let stand to separate, pour out the supernatant, add ethyl acetate to wash the bottom solid, concentrate the organic phase and purify it through a silica gel column to obtain a compound of formula I, add acetonitrile to dissolve, concentrate until no liquid drops, add water and heat to 90-120°C, beat for 4-6h, filter, wash the filter cake, add water and heat to 90-120°C to beat for 4-6h, beat at room temperature overnight, filter, and freeze-dry the solid to obtain a mixed crystal of the compound of formula I;

[0345] Step 2: After the mixed crystals of the compound of formula I are slurried in IPA / H2O (volume ratio of 982:18) at room temperature for about 5 days, the solids are separated by centrifugation and air-dried at room temperature to obtain Form D.

[0346] On the other hand, the present invention provides a method for preparing the free crystalline form E of the compound of formula I, comprising the following steps:

[0347] The mixed crystal of the compound of formula I is placed in THF atmosphere for gas-solid infiltration and then air-dried at room temperature to obtain the mixed crystal.

[0348] On the other hand, the present invention provides a method for preparing the free crystalline form F of the compound of formula I, comprising the following steps:

[0349] The mixed crystal of the compound of formula I is heated to 160-180° C. and cooled to room temperature and humidity to obtain.

[0350] On the other hand, the present invention provides a method for preparing the free crystalline form G of the compound of formula I, comprising the following steps:

[0351] The mixed crystal of the compound of formula I is first dissolved in 1,4-Dioxane, placed in a H2O atmosphere for gas-liquid diffusion to precipitate a solid, and then placed in the air to dry to obtain a solid.

[0352] On the other hand, the present invention provides a method for preparing the free crystalline form H of the compound of formula I, comprising the following steps:

[0353] The mixed crystal of the compound of formula I is placed in a DMSO atmosphere and then subjected to gas-solid diffusion to obtain the mixed crystal.

[0354] On the other hand, the present invention provides a method for preparing the free crystalline form I of the compound of formula I, comprising the following steps:

[0355] The mixed crystals of the compound of formula I are slurried in MeOH at room temperature for about 5 days, and then air-dried at room temperature to obtain a precipitate.

[0356] On the other hand, the present invention provides a method for preparing the free crystalline form J of the compound of formula I, comprising the following steps:

[0357] The mixed crystal of the compound of formula I is heated to 100° C. and cooled to room temperature with humidity to obtain.

[0358] On the other hand, the present invention provides a method for preparing the free crystalline form K of the compound of formula I, comprising the following steps:

[0359] The mixed crystals of the compound of formula I were slurried in EtOH at room temperature for about 2 days, and the solids were separated by centrifugation and dried in vacuo at room temperature to obtain the product.

[0360] On the other hand, the present invention provides a method for preparing the free crystalline form L of the compound of formula I, comprising the following steps:

[0361] The compound of formula I was obtained after slurrying in MeOH at room temperature for about 3 days.

[0362] On the other hand, the present invention also provides a method for preparing a pharmaceutically acceptable salt of the compound of formula I (including a crystalline form of a pharmaceutically acceptable salt of the compound of formula I), which comprises the following methods:

[0363] Method 1 comprises the following steps: slurrying the compound of formula I or the mixed crystal of the compound of formula I and the salt-forming agent (e.g., the corresponding acid) in solvent A, centrifuging and separating the solid and drying. The solvent A is selected from one or more mixtures of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water. The alcohol is selected from methanol and ethanol. The drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C. The slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days.

[0364] Method 2 comprises the following steps: slurrying the compound of formula I or the mixed crystal of the compound of formula I and the salt-forming agent (e.g., the corresponding acid) in solvent A, adding solvent B to crystallize into gel, circulating at a temperature of 50°C to 5°C to obtain a suspension, centrifuging and separating the solid and drying. The solvent A is selected from one or more mixtures of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water. The alcohol is selected from methanol and ethanol. The solvent B is selected from n-heptane. The drying is selected from vacuum drying, and the drying temperature is 40-60°C, preferably 50°C. The slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days.

[0365] Method three comprises the following steps: circulating the compound of formula I or the mixed crystal of the compound of formula I with a salt-forming agent (e.g., the corresponding acid) in solvent A at a temperature of 50°C to 5°C to obtain a solid, centrifuging and drying the solid. The solvent A is selected from one or more mixtures of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water. The alcohol is selected from methanol and ethanol. The drying is selected from vacuum drying, and the drying temperature is 40-60°C, preferably 50°C. The beating time is 1-5 days, for example, 1, 2, 3, 4, 5 days.

[0366] In another aspect, the present invention provides a pharmaceutical composition comprising one or more of the free crystalline forms of the compound of formula I (e.g., free crystalline forms A to free crystalline forms L) and pharmaceutically acceptable salts of the compound of formula I (including crystalline forms thereof).

[0367] In another aspect, the present invention provides a use of a free crystalline form of the compound of formula I (e.g., free crystalline form A to free crystalline form L), a pharmaceutically acceptable salt of the compound of formula I (including its crystalline form), or the pharmaceutical composition in the preparation of a drug, wherein the drug can inhibit KIF18A; and / or, prevent and / or treat KIF18A-related diseases; the drug is expected to be used to prevent and / or treat proliferative disorders of cancer, psoriasis, atopic dermatitis, autoimmune diseases, or inflammatory bowel disease.

[0368] Cancers that should be mentioned include mesothelioma, neuroblastoma, rectal cancer, colon cancer, the familiar adenomatous polyposis and hereditary nonpolyposis colorectal cancer, esophageal cancer, lip cancer, laryngeal cancer, hypopharyngeal cancer, tongue cancer, salivary gland cancer, stomach cancer, adenocarcinoma, medullary thyroid cancer, papillary thyroid cancer, kidney cancer, renal parenchymal cancer, ovarian cancer, cervical cancer, uterine corpus cancer, endometrial cancer, choriocarcinoma, pancreatic cancer, prostate cancer, bladder cancer, testicular cancer, breast cancer, urinary cancer, melanoma Pigmented tumors, brain tumors, lymphomas, head and neck cancers, acute lymphatic leukemia, chronic lymphatic leukemia, acute myeloid leukemia, chronic myeloid leukemia, hepatocellular carcinoma, gallbladder cancer, bronchial carcinoma, small cell lung cancer, non-small cell lung cancer, multiple myeloma, basal sarcoma, teratoma, retinoblastoma, choroidal melanoma, seminoma, rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myoma, liposarcoma, fibrosarcoma, Ewing sarcoma and plasmacytoma.

[0369] Autoimmune diseases that should be mentioned include rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, mixed connective tissue disease, dermatomyositis, polymyositis, Reiter's syndrome, autoimmune lymphoproliferative syndrome, multiple sclerosis, myasthenia gravis, and encephalomyelitis.

[0370] Inflammatory bowel diseases that should be mentioned include ulcerative colitis or Crohn's disease.

[0371] According to an embodiment of the present invention, the free crystalline form of the compound of Formula I (e.g., free crystalline form A to free crystalline form L) and the pharmaceutically acceptable salt of the compound of Formula I (including its crystalline form) can be used in combination with a second active therapeutic drug.

[0372] The present invention also relates to a method for preventing and / or treating a disease related to KIF18A, comprising administering to a patient a therapeutically effective amount of a free crystalline form of the compound of formula I (e.g., free crystalline form A to free crystalline form L), a pharmaceutically acceptable salt of the compound of formula I (including its crystalline form), or the pharmaceutical composition.

[0373] Definitions and Explanations of Terms

[0374] Unless otherwise specified, the definitions of groups and terms recorded in the specification and claims of this application, including their definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific compounds in examples, etc., can be arbitrarily combined and combined with each other. The group definitions and compound structures after such combinations and combinations shall fall within the scope of the description of this application.

[0375] Unless otherwise specified, the numerical ranges recorded in this specification and claims are equivalent to recording at least each specific integer value therein. For example, when certain numerical ranges are defined or understood as "numbers", it should be understood to record the two endpoints of the range, each integer within the range, and each decimal within the range. For example, "a number from 0 to 10" should be understood to record not only each integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, but also at least the sum of each integer therein and 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, respectively.

[0376] When the description and claims record "about" a certain value, it includes the value itself, as well as the values ​​within the range of the value acceptable in the art, such as the values ​​within the range of ±15% of the value, the values ​​within the range of ±10%, the values ​​within the range of ±5%, etc. For example, about 10 represents: values ​​within the range of 10±1.5, that is, values ​​within the range of 8.5 to 11.5; values ​​within the range of 10±1.0, that is, values ​​within the range of 9.0 to 11.0; and values ​​within the range of 10±0.5, that is, values ​​within the range of 9.5 to 10.5.

[0377] The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans.

[0378] The term "therapeutically effective amount" refers to the amount of an active compound or drug that elicits the biological or medical response that a researcher, veterinarian, physician or other clinician is seeking in a tissue, system, animal, individual or human, and includes one or more of the following: (1) preventing disease: for example, preventing a disease, disorder or condition in an individual who is susceptible to the disease, disorder or condition but has not yet experienced or developed the pathology or symptoms of the disease; (2) inhibiting disease: for example, inhibiting the disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease, disorder or condition (i.e., preventing further development of the pathology and / or symptoms); (3) alleviating disease: for example, alleviating the disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease, disorder or condition (i.e., reversing the pathology and / or symptoms).

[0379] The term "pharmaceutically acceptable" means that the formulation components or active ingredients have no undue adverse effect on health for the general purpose of treatment.

[0380] The term "crystalline form" refers to forms of a crystal having the same chemical composition but having different spatial arrangements of the molecules and / or ions that form the crystal.

[0381] The term "X-ray powder diffraction pattern substantially as shown" means that at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%, or at least 95%, or at least 99% of the main peaks shown in the X-ray powder diffraction pattern appear in the X-ray powder diffraction pattern; the main peak refers to a peak with a relative intensity greater than 10%, preferably greater than 20%, and more preferably greater than 30%, with the highest peak as a reference (the relative intensity of the highest peak is designated as 100%).

[0382] Those skilled in the art can determine the appropriate amount of the salt, any one of the crystalline forms of the salt or the free crystalline form, a mixture of the two in any ratio, and various pharmaceutically acceptable carriers and / or other active ingredients in the pharmaceutical composition according to conventional methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0383] Figure 1 XRPD pattern of free form A

[0384] Figure 2 TGA / DSC diagram of the free starting sample (form A)

[0385] Figure 3a The free starting sample (Form A) 1 H NMR spectra

[0386] Figure 3b XRPD overlay of the free starting sample (form A) before and after the heating experiment

[0387] Figure 4 XRPD overlay of different crystalline samples in free state

[0388] Figure 5 XRPD pattern of free form B

[0389] Figure 6 TGA / DSC diagram of free form B

[0390] Figure 7a Free form B 1 H NMR spectra

[0391] Figure 7b After heating (60℃) experiment of free crystal form B 1 H NMR spectra Figure 7c After heating (120℃) of free crystal form B1 H NMR spectra

[0392] Figure 8 XRPD pattern of free crystal form C

[0393] Fig. 9 TGA / DSC diagram of free crystal form C

[0394] Fig.10 Free form C 1 H NMR spectra

[0395] Fig.11 XRPD overlay of different crystalline forms of hydrochloride

[0396] Fig.12a XRPD pattern of hydrochloride form A

[0397] Figure 12b XRPD pattern of the hydrochloride salt form A prepared repeatedly

[0398] Fig.13 TGA / DSC diagram of hydrochloride form A

[0399] Fig.14 Hydrochloride Form A 1 H NMR spectra

[0400] Fig.15 XRPD pattern of hydrochloride form B

[0401] Fig.16 TGA / DSC diagram of hydrochloride form B

[0402] Fig.17 Hydrochloride Form B 1 H NMR spectra

[0403] Fig.18 XRPD pattern of hydrochloride form C

[0404] Fig.19 TGA / DSC diagram of hydrochloride crystal form C

[0405] Fig. 20 Hydrochloride Form C 1 H NMR spectra

[0406] Fig.21 XRPD overlay of different crystalline forms of sulfate

[0407] Fig. 22 XRPD pattern of sulfate form A

[0408] Fig.23 TGA / DSC diagram of sulfate crystal form A

[0409] Fig.24 Sulfate Form A 1 H NMR spectra

[0410] Fig.25 XRPD pattern of sulfate form B

[0411] Fig.26 TGA / DSC diagram of sulfate crystal form B

[0412] Fig. 27 Sulfate Form B 1 H NMR spectra

[0413] Fig.28 XRPD pattern of sulfate crystal form C

[0414] Fig.29 TGA / DSC diagram of sulfate crystal form C

[0415] Fig.30 Sulfate Form C 1 H NMR spectra

[0416] Fig.31 XRPD pattern of maleate salt form A

[0417] Fig.32 TGA / DSC diagram of maleate crystal form A

[0418] Fig.33 Maleate Form A 1 H NMR spectra

[0419] Fig.34 XRPD pattern of phosphate crystal form A

[0420] Fig.35 TGA / DSC graph of phosphate crystal form A

[0421] Fig.36 Phosphate Form A 1 H NMR spectra

[0422] Fig.37 XRPD overlay of different crystalline forms of p-toluenesulfonate

[0423] Fig.38 XRPD pattern of p-toluenesulfonate Form A

[0424] Fig.39 TGA / DSC diagram of p-toluenesulfonate form A

[0425] Fig.40 p-Toluenesulfonate Form A 1 H NMR spectra

[0426] Fig.41XRPD pattern of p-toluenesulfonate Form B

[0427] Fig.42 TGA / DSC diagram of p-toluenesulfonate crystal form B

[0428] Fig.43 p-Toluenesulfonate Form B 1 H NMR spectra

[0429] Fig.44 XRPD overlay of different crystalline forms of mesylate

[0430] Fig.45 XRPD pattern of mesylate salt form A

[0431] Fig.46 TGA / DSC diagram of mesylate form A

[0432] Fig.47 Methanesulfonate Form A 1 H NMR spectra

[0433] Fig.48 XRPD pattern of mesylate salt form B

[0434] Fig.49 TGA / DSC diagram of mesylate form B

[0435] Fig.50 Methanesulfonate Form B 1 H NMR spectra

[0436] Fig.51 XRPD pattern of mesylate salt form C

[0437] Fig.52 TGA / DSC diagram of mesylate form C

[0438] Fig.53 Methanesulfonate Form C 1 H NMR spectra

[0439] Fig.54 XRPD overlay of different crystalline forms of ethanesulfonate

[0440] Fig.55 XRPD pattern of ethanesulfonate form A

[0441] Fig.56 TGA / DSC diagram of ethanesulfonate form A

[0442] Fig.57 Ethysulfonate Form A 1 H NMR spectra

[0443] Fig.58a XRPD pattern of ethanesulfonate form B

[0444] Figure 58b XRPD overlay of repeated preparation of ethanesulfonate salt Form B

[0445] Fig.59 TGA / DSC diagram of ethanesulfonate form B

[0446] Fig.60 Ethysulfonate Form B 1 H NMR spectra

[0447] Fig.61 Room temperature solubility curve of the crystal form in water

[0448] Fig.62 Room temperature solubility curve of the crystal form in SGF

[0449] Fig.63 Room temperature solubility curve of the crystal form in FaSSIF

[0450] Fig.64 XRPD pattern of free starting sample 2 (mixed crystal)

[0451] Fig.65 TGA / DSC graph of free starting sample 2 (mixed crystal)

[0452] Fig.66 The free starting sample 2 (mixed crystal) 1 H NMR spectra

[0453] Fig.67 XRPD pattern of free crystal form D

[0454] Fig.68 TGA / DSC diagram of free crystal form D

[0455] Fig.69 Free form D 1 H NMR spectra

[0456] Fig.70 VT-XRPD superimposed image of free form D

[0457] Fig.71 XRPD pattern of free crystal form E sample

[0458] Fig.72 TGA / DSC diagram of free crystal form E

[0459] Fig.73 Free form E 1 H NMR spectra

[0460] Fig.74 XRPD overlay of free crystal form E before and after heating experiment

[0461] Fig.75 Free crystal form E after heating experiment 1 H NMR spectra

[0462] Fig.76 XRPD pattern of free form F sample

[0463] Fig.77 TGA / DSC graph of free form F

[0464] Fig.78 Free Form F 1 H NMR spectra

[0465] Fig.79 XRPD pattern of free crystal form G sample

[0466] Fig.80 TGA / DSC diagram of free crystal form G

[0467] Fig.81 Free form G 1 H NMR spectra

[0468] Fig.82 XRPD overlay of free crystal form G before and after heating experiment

[0469] Fig.83 After heating test (120℃) of free crystal form G 1 H NMR spectra Fig.84 After heating test (160℃) of free crystal form G 1 H NMR spectra Fig.85a XRPD overlay of free-state Form H sample before and after drying

[0470] Figure 85b XRPD pattern of free form H sample

[0471] Fig.86 XRPD pattern of free form I sample

[0472] Fig.87 TGA / DSC diagram of free crystal form I

[0473] Fig.88 Free form I 1 H NMR spectra

[0474] Fig.89 XRPD overlay of free crystal form I before and after heating experiment

[0475] Fig.90 XRPD pattern of free crystal form J sample

[0476] Fig.91TGA / DSC diagram of free crystal form J

[0477] Fig.92 Free form J 1 H NMR spectra

[0478] Fig.93 VH-XRPD superimposition of free form J

[0479] Fig.94 XRPD pattern of free crystal form K sample

[0480] Fig.95 TGA / DSC diagram of free crystal form K

[0481] Fig.96 1H NMR spectrum of free crystal form K

[0482] Fig.97 XRPD overlay of free crystal form K before and after heating experiment

[0483] Fig.98 Free crystal form K after heating experiment 1 H NMR spectra

[0484] Fig.99a XRPD overlay of free form L sample

[0485] Fig.99b XRPD pattern of free crystal form L sample

[0486] Fig.100 XRPD overlay of free polymorph suspension competition experiment samples (I / II)

[0487] Fig.101 XRPD overlay of free polymorph suspension competition experiment samples (II / II) Fig.102a XRPD overlay of mesylate form D sample

[0488] Fig.102b XRPD pattern of mesylate form D sample

[0489] Fig.103 TGA / DSC diagram of mesylate form D

[0490] Fig.104 1H NMR spectrum of mesylate form D

[0491] Fig.105 XRPD overlay of different crystalline forms of hydrochloride salt (I / II) Fig.106a XRPD overlay of different crystalline forms of hydrochloride salt (II / II) Fig.106b XRPD pattern of hydrochloride form G sample

[0492] Fig.106c XRPD pattern of hydrochloride form H sample

[0493] Fig.106d XRPD pattern of hydrochloride form I sample

[0494] Fig.106e XRPD pattern of hydrochloride form J sample

[0495] Fig.106f XRPD pattern of hydrochloride form K sample

[0496] Figure 106g XRPD pattern of hydrochloride form L sample

[0497] Figure 106h XRPD pattern of hydrochloride form M sample

[0498] Fig.107 XRPD pattern of hydrochloride form D sample

[0499] Fig.108 TGA / DSC diagram of hydrochloride form H

[0500] Fig.109 1H NMR spectrum of hydrochloride form H

[0501] Fig.110 XRPD pattern of hydrochloride form E sample

[0502] Fig.111 XRPD pattern of hydrochloride form F sample

[0503] Fig.112a XRPD overlay of different crystalline forms of mesylate (I / III) Fig.112b XRPD pattern of mesylate form E sample

[0504] Fig.112c XRPD pattern of mesylate form F sample

[0505] Fig.113a XRPD overlay of different crystalline forms of mesylate (II / III) Fig.113b XRPD pattern of mesylate form G sample

[0506] Fig.113c XRPD pattern of mesylate salt form H sample

[0507] Fig.113d XRPD pattern of mesylate salt Form I sample

[0508] Fig.113e XRPD pattern of mesylate salt form J sample

[0509] Fig.113f XRPD pattern of mesylate salt form K sample

[0510] Figure 113g XRPD pattern of mesylate form L sample

[0511] Fig.114a XRPD overlay of different crystalline forms of mesylate (III / III) Fig.114b XRPD pattern of mesylate salt form M sample

[0512] Fig.114c XRPD pattern of mesylate salt form N sample

[0513] Fig.114d XRPD pattern of mesylate form O sample

[0514] Fig.115 TGA / DSC diagram of mesylate form E

[0515] Fig.116 1H NMR spectrum of mesylate form E

[0516] Fig.117 TGA / DSC diagram of mesylate form F

[0517] Fig.118 1H NMR spectrum of mesylate form F

[0518] Fig.119 TGA / DSC graph of mesylate form O

[0519] Fig.120 1H NMR spectrum of mesylate form O

[0520] Fig.121a XRPD overlay of different crystalline forms of ethanesulfonate

[0521] Fig.121b XRPD pattern of ethanesulfonate form C sample

[0522] Fig.121c XRPD pattern of ethanesulfonate form D sample

[0523] Fig.121d XRPD pattern of ethanesulfonate form E sample

[0524] Fig.121e XRPD pattern of ethanesulfonate form F sample

[0525] Fig.122 TGA / DSC diagram of ethanesulfonate form D

[0526] Fig.123 1H NMR spectrum of ethanesulfonate form D

[0527] Fig.124 TGA / DSC diagram of ethanesulfonate crystal form E

[0528] Fig.125 1H NMR spectrum of ethanesulfonate form E

[0529] Fig.126a XRPD overlay of different crystalline forms of 1,2-ethanedisulfonate Fig.126b XRPD pattern of 1,2-ethanedisulfonate Form A sample Fig.126c XRPD pattern of 1,2-ethanedisulfonate Form B sample Fig.126d XRPD pattern of 1,2-ethanedisulfonate Form C sample Fig.127 TGA / DSC graph of 1,2-ethanedisulfonate Form A

[0530] Fig.128 1H NMR spectrum of 1,2-ethanedisulfonate Form A

[0531] Fig.129 TGA / DSC graph of 1,2-ethanedisulfonate Form B

[0532] Fig.130 1H NMR spectrum of 1,2-ethanedisulfonate Form B

[0533] Fig.131 TGA / DSC graph of 1,2-ethanedisulfonate Form C

[0534] Fig.132 1H NMR spectrum of 1,2-ethanedisulfonate Form C

[0535] Fig.133 Single crystal simulated XRPD

[0536] Fig.134 Single crystal diffraction thermal ellipsoid (50%) molecular structure diagram

[0537] Fig.135 Single crystal diffraction molecular structure stacking diagram, the dotted lines in the figure represent hydrogen bonds

[0538] Fig.136 Dynamic solubility curve at 37℃

[0539] Fig.137 XRPD overlay of free form D solubility sample in H2O

[0540] Fig.138 XRPD overlay of solubility samples of free form D in SGF

[0541] Fig.139XRPD overlay of the solubility sample of free form D in FaSSIF

[0542] Fig.140 XRPD overlay of solubility samples of free form D in FeSSIF

[0543] Fig.141 XRPD overlay of sulfate form B solubility sample in H2O

[0544] Fig.142 XRPD overlay of the solubility sample of sulfate form B in SGF

[0545] Fig.143 XRPD overlay of the solubility sample of sulfate form B in FaSSIF

[0546] Fig.144 XRPD overlay of the solubility sample of sulfate form B in FeSSIF

[0547] Fig.145 XRPD overlay of the solubility sample of p-toluenesulfonate Form B in H2O

[0548] Fig.146 XRPD overlay of the solubility sample of p-toluenesulfonate Form B in SGF

[0549] Fig.147 XRPD overlay of the solubility sample of p-toluenesulfonate Form B in FaSSIF

[0550] Fig.148 XRPD overlay of the solubility sample of p-toluenesulfonate Form B in FeSSIF

[0551] Fig.149 XRPD overlay of maleate salt form A solubility sample in H2O

[0552] Fig.150 XRPD overlay of the solubility sample of maleate form A in SGF

[0553] Fig.151 XRPD overlay of solubility samples of maleate form A in FaSSIF

[0554] Fig.152 XRPD overlay of solubility samples of maleate form A in FeSSIF

[0555] Fig.153 XRPD overlay of the solubility sample of mesylate form E in H2O

[0556] Fig.154 XRPD overlay of solubility samples of mesylate form E in SGF

[0557] Fig.155 XRPD overlay of the solubility sample of mesylate form E in FaSSIF

[0558] Fig.156 XRPD overlay of solubility samples of mesylate form E in FeSSIF

[0559] Fig.157 DVS diagram of free crystal form D

[0560] Fig.158 XRPD overlay of free form D before and after DVS testing

[0561] Fig.159 DVS diagram of sulfate crystal form B

[0562] Fig.160 XRPD overlay of sulfate form B before and after DVS testing

[0563] Fig.161 DVS diagram of p-toluenesulfonate crystal form B

[0564] Fig.162 XRPD overlay of p-toluenesulfonate Form B before and after DVS testing

[0565] Fig.163 DVS diagram of maleate crystal form A

[0566] Fig.164 XRPD overlay of maleate form A before and after DVS testing

[0567] Fig.165 DVS diagram of mesylate form E

[0568] Fig.166 XRPD overlay of mesylate form E before and after DVS testing

[0569] Fig.167 XRPD overlay of samples before and after the stability test of free crystal form D

[0570] Fig.168 XRPD overlay of the sulfate crystal form B sample before and after the stability test

[0571] Fig.169 XRPD overlay of p-toluenesulfonate Form B samples before and after stability test

[0572] Fig.170 XRPD overlay of samples of maleate crystal form A before and after stability test

[0573] Fig.171 XRPD overlay of the sample before and after the stability test of the mesylate crystal form E DETAILED DESCRIPTION

[0574] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0575] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0576] Unless otherwise specified, the "free starting sample" in the following examples refers to the compound of formula I prepared according to Example 1.

[0577] 1. The instruments and detection methods used in the present invention are as follows:

[0578] 1.1 X-ray powder diffraction (XRPD)

[0579] The XRPD pattern was collected on an X-ray powder diffraction analyzer produced by PANalytacal, and the scanning parameters are shown in Table A-1 below.

[0580] Table A-1 XRPD test parameters

[0581]

[0582] 1.2 Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC)

[0583] The TGA and DSC graphs were collected on a TA 5500 thermogravimetric analyzer and a TA 2500 differential scanning calorimeter, respectively. The test parameters are listed in Table A-2 below.

[0584] Table A-2 TGA and DSC test parameters

[0585]

[0586] 1.3 Liquid NMR ( 1 H NMR)

[0587] Liquid-state NMR spectra were collected on a Bruker 400M NMR instrument using DMSO-d6 as solvent.

[0588] 1.4 High Performance Liquid Chromatography and Ion Chromatography (HPLC / IC)

[0589] In the experiment, the solubility results were collected by Agilent 1260 high performance liquid chromatograph, and the ion salt molar ratio results were collected by Agilent 1260 high performance liquid chromatograph and ion chromatograph, respectively. The analysis conditions are shown in Table A-3 and Table A-4.

[0590] Table A-3 HPLC test conditions

[0591]

[0592]

[0593] Table A-4 Ion chromatography test conditions

[0594]

[0595] 1.5 Dynamic moisture sorption (DVS)

[0596] Dynamic moisture sorption (DVS) curves were collected on the DVSIntrInsic of SMS (Surface Measurement Systems). The relative humidity at 25°C was calibrated using the deliquescent points of LiCl, Mg(NO3)2, and KCl. The DVS test parameters are listed in Table A-5.

[0597] Table A-5 DVS test parameters

[0598]

[0599] 1.6 Polarized Light Microscope (PLM)

[0600] Polarized light microscopy data were collected at room temperature using a Carl Zeiss Axio Lab.A1 upright microscope.

[0601] 1.7 Karl Fischer titrator (KF)

[0602] The KF test was performed using a Metrohm 870 or Metrohm 831 KF titrator from Metrohm.

[0603] 1.8 Liquid NMR ( 1 H NMR)

[0604] Liquid-state NMR spectra were collected on a Bruker 400M NMR instrument using DMSO-d6 as solvent.

[0605] 1.9 X-ray single crystal diffraction

[0606] Instrument model: D8 Venture

[0607] Testing basis: JY / T 0588-2020 General rules for crystal and molecular structure analysis of small molecule compounds by single crystal X-ray diffractometer Testing environment: Test temperature: -173℃; Room temperature: 24℃; Relative humidity: 30%

[0608] X-ray tube: Ga target

[0609] wavelength:

[0610] Tube voltage: 70kV

[0611] Tube current: 3.57mA

[0612] Scanning method: ω-2θ scanning

[0613] Scanning speed: 0.5 degrees / frame

[0614] Scanning range: 3.582 to 72.451°

[0615] Test temperature: 100(2)K

[0616] 2. The reagents used in the present invention are as shown in Table A-6

[0617] Table A-6 Comparison table of Chinese and English names of solvents used in the test

[0618]

[0619] 3. Preparation of the biosolvent in the present invention

[0620] 3.1 Preparation of simulated gastric fluid (SGF)

[0621] Weigh 100 mg NaCl and 50 mg Trinaton X-100 into a 50-mL volumetric flask and add purified water to dissolve. Add 816 μL 1M hydrochloric acid and adjust the pH to 1.8 with 1M hydrochloric acid or 1M NaOH solution. Add purified water to make up to volume.

[0622] 3.2 Preparation of fasting-simulated intestinal fluid (FaSSIF)

[0623] Weigh 340 mg of anhydrous NaH2PO4 and 620 mg of NaCl into a 100-mL volumetric flask. Add purified water to dissolve, then add 55.44 μL of 50% NaOH solution, and adjust the pH to 6.5 with 1M hydrochloric acid or 1M NaOH solution. Add purified water to make up to volume. Then weigh 110 mg of SIF powder into a 50-mL volumetric flask, dissolve and make up to volume with the above solution.

[0624] 3.3 Preparation of simulated fed intestinal fluid (FeSSIF)

[0625] Take 0.82mL of glacial acetic acid and 1.18g of NaCl into a 100-mL volumetric flask, add purified water to dissolve, then add 528μL of 50% NaOH solution, adjust the pH to 5.0 with 1M hydrochloric acid or 1M NaOH solution, and add purified water to make up to volume. Then weigh 560mg of SIF powder into a 50-mL volumetric flask, dissolve with the above solution and make up to volume.

[0626] Example 1 Preparation of Compounds of Formula I

[0627]

[0628] The compound of formula I can be prepared by referring to the synthesis method disclosed in Chinese patent application CN202310400928.8, and its synthesis route is as follows:

[0629] Step 1: Synthesis of 4-methyl-2-(methylthio)-6-(1H-pyrazol-4-yl)pyrimidine

[0630] 4-Chloro-6-methyl-2-(methylthio)pyrimidine (30 g, 172 mmol) was added to 300 mL of N,N-dimethylformamide, and then 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 g, 258 mmol), potassium carbonate (47.5 g, 344 mmol), 50 mL of water, 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) chloride (12.57 g, 17.18 mmol) were added, and the mixture was heated to 105°C for 16 h. LCMS showed that the reaction of the raw material was complete, and the mixture was concentrated to dryness. The residue was separated and purified by silica gel column (PE:EA (V / V) = 1:1) to obtain 4-methyl-2-(methylthio)-6-(1H-pyrazol-4-yl)pyrimidine (20 g, yield 56.4%). LC-MS, M / Z(ESI):207.2[M+H] +

[0631] Step 2: Synthesis of 4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylthio)pyrimidine

[0632] 4-Methyl-2-(methylthio)-6-(1H-pyrazol-4-yl)pyrimidine (20 g, 97 mmol) was added to 20 mL of N,N-dimethylformamide, and then 1,2-difluoro-4-nitrobenzene (46.3 g, 291 mmol) and cesium carbonate (63.2 g, 194 mmol) were added, and the reaction was carried out at room temperature for 16 h. LCMS showed that the raw material had reacted completely, and the product was concentrated to dryness. The residue was separated and purified by silica gel column (volume ratio: PE:DCM:EA=3:3:1) to obtain 4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylthio)pyrimidine (23 g, yield 68.7%). LC-MS, M / Z(ESI):346.1[M+H] +

[0633] Step 3: Synthesis of 4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylsulfonyl)pyrimidine

[0634] 4-(1-(2-Fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylthio)pyrimidine (23 g, 66.6 mmol) was added to 300 mL of dichloromethane, and then m-chloroperbenzoic acid (40.2 g, 233 mmol) was added. The reaction was carried out at room temperature for 1 h. LCMS showed that the reaction of the raw material was complete. 200 mL of saturated sodium sulfite solution was added and stirred for 30 min. 100 mL of saturated sodium carbonate solution was added and stirred for 10 min. The mixture was extracted with dichloromethane (200 mL×3), separated, and the organic phase was concentrated to dryness. The residue was separated and purified by silica gel column (DCM:EA (V / V)=3:1) to obtain 4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylsulfonyl)pyrimidine (13 g, yield 51.7%). LC-MS, M / Z(ESI):378.1[M+H] +

[0635] Step 4: Synthesis of 2-(4,4-difluoropiperidin-1-yl)-4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methylpyrimidine

[0636] 4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methyl-2-(methylsulfonyl)pyrimidine (6 g, 15.9 mmol) was added to 60 mL of N,N-dimethylformamide, and then 4,4-difluoropiperidine hydrochloride (3.76 g, 23.85 mmol) and potassium carbonate (8.79 g, 63.6 mmol) were added, and the mixture was heated to 105°C and reacted overnight. LCMS showed that the raw material had reacted completely, and the mixture was concentrated to dryness. The residue was separated and purified by silica gel column (volume ratio: PE:DCM:EA=3:3:1) to obtain 2-(4,4-difluoropiperidin-1-yl)-4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methylpyrimidine (6 g, yield 90%). LC-MS, M / Z(ESI):419.1[M+H] +

[0637] Step 5: Synthesis of 6-(2-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-5-nitrophenyl)-6-azaspiro[2.5]octane

[0638] 2-(4,4-difluoropiperidin-1-yl)-4-(1-(2-fluoro-4-nitrophenyl)-1H-pyrazol-4-yl)-6-methylpyrimidine (3 g, 7.17 mmol) was added to 30 mL of dimethyl sulfoxide, and then 6-azaspiro[2.5]octane hydrochloride (1.588 g, 10.76 mmol) and potassium carbonate (3.96 g, 28.7 mmol) were added, and the mixture was heated to 140°C for 8 h. LCMS showed that the raw materials had reacted completely, and the reaction solution was poured into 200 mL of water and filtered to obtain 6-(2-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-5-nitrophenyl)-6-azaspiro[2.5]octane (2.6 g, yield 71.2%). LC-MS, M / Z(ESI):510.2[M+H] +

[0639] Step 6: Synthesis of 4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)aniline

[0640] Add 6-(2-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-5-nitrophenyl)-6-azaspiro[2.5]octane (2.6 g, 5.1 mmol) to 60 mL of ethanol, and then add iron powder (2.85 g, 51 mmol) and ammonium chloride (2.73 g, 51 mmol), and heat to 90°C for 8 hours. LCMS showed that the raw material was completely reacted, filtered and washed with 60 mL of ethanol, the filtrate was concentrated to dryness, and the residue was separated and purified by silica gel column (PE: EA (V / V) = 3: 1) to obtain 4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)aniline (2.4 g, yield 98%). LC-MS, M / Z (ESI): 480.2 [M+H] +

[0641] Step 7: Synthesis of methyl 2-(N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)sulfamoyl)acetate

[0642] Add 4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)aniline (2.4 g, 5 mmol) to 30 mL of dichloromethane, and then add triethylamine (1.94 g, 15.01 mmol) and methyl 2-(chlorosulfonyl)acetate (1.036 g, 5 mmol), and react at room temperature for 1 h. LCMS showed that the raw material was completely reacted. The reaction solution was concentrated to dryness, and the residue was separated and purified by silica gel column (PE:EA (V / V) = 5:1) to obtain methyl 2-(N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)sulfamoyl)acetate (1.9 g, yield 61.7%). LC-MS, M / Z (ESI): 616.2 [M+H] +

[0643] Step 8: Synthesis of N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide

[0644] Methyl 2-(N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)sulfamoyl)acetate (1.90 g, 3.1 mmol) was dissolved in tetrahydrofuran (20 mL), and lithium borohydride (2M, 1.85 mL) was added dropwise at 0°C under nitrogen protection, and the mixture was reacted at 0°C for 1 h. After the reaction was completed, the reaction solution was quenched with saturated ammonium chloride solution (50 mL), extracted with ethyl acetate (200 mL×3), and the organic phase was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product, which was then separated and purified by reverse phase Flash (0.1% HCl). N-(4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide (1.31 g, 2.17 mmol, purity 97.5%, yield 71.0%) was obtained.

[0645] The sample (1.31 g) obtained in this preparation example was added with acetonitrile (20 mL) and stirred at room temperature for 2 h, concentrated to dryness, then added with water (20 mL) and heated to 100° C. and refluxed for 3 h, stirred at room temperature overnight, filtered, and the solid was freeze-dried to obtain a starting sample of the compound represented by Formula I (or may be referred to as a “free starting sample”).

[0646] 1 H NMR (400MHz, CDCl3) δ8.92 (s, 1H), 8.12 (s, 1H), 7.56 (d, J = 8.4Hz, 1H), 7.10 (s ,1H),6.91-6.94(m,1H),6.77(s,1H),6.65(s,1H),4.13-4.16(m,2H),4.05-4. 08(m,4H),3.50(s,1H),3.31-3.34(m,2H),2.80-2.83(m,4H),2.40(s,3H),1. 98-2.07(m,4H),1.41-1.45(m,4H),0.30(s,4H).LC-MS,M / Z(ESI):588.3[M+H] + .

[0647] Example 2 Starting sample 1 of compound of formula I (free crystal form A)

[0648] The starting sample 1 of the compound of formula I prepared in Example 1 was identified by XRPD, TGA / DSC and 1 H NMR characterization. XRPD results ( Figure 1) shows that the starting sample is a crystalline sample, named free crystalline form A. TGA / DSC results are as follows Figure 2 As shown, the TGA results show that the sample has a weight loss of 0.68% when heated to 150°C; the DSC results show that the sample has two endothermic peaks at 167.9°C and 180.3°C (peak temperature), and one exothermic peak at 170.5°C (peak temperature). 1 H NMR was tested using DMSO-d6 as solvent. The specific results are as follows Figure 3a As shown. The XRPD analysis data of the obtained free crystalline form A of the compound of formula I are shown in the following table B1-1. The endothermic and exothermic signals before the 180.3°C melting signal on the DSC of the free crystalline form A sample were studied by heating experiments. The results (Figure) show that after the free crystalline form A sample was heated to 172°C and cooled to room temperature and humidity, it was observed that the sample was converted into free crystalline form F. According to the TGA / DSC and 1 Based on H NMR data, it is inferred that the free crystalline form A is anhydrous crystalline form.

[0649] Table B1-1 XRPD diffraction peak data of free form A

[0650]

[0651] Example 3 Free Form B / C of Compound I

[0652] The free crystal form B and the crystal form C are obtained by slurrying the starting sample 1 of the compound of formula I in ethanol and MTBE at room temperature for about 3 days, centrifuging and separating the solids and drying them in vacuo at 50°C. The XRPD overlay of the free sample is shown in FIG. Figure 4 shown.

[0653] The XRPD results of free form B are as follows: Figure 5 The TGA / DSC results are listed in Figure 6 Among them, the TGA results showed that the sample had a 4.35% weight loss when heated to 120°C; the DSC results showed that the sample had three endothermic peaks at 108.5°C, 165.8°C and 180.2°C (peak temperature), and one exothermic peak at 167.7°C (peak temperature). 1 H NMR results are as follows Figure 7a The results show that the molar ratio of the residual solvent EtOH to the free state in the sample is 0.45 (about 3.4wt%). The XRPD analysis data of the free crystalline form B are shown in Table B1-2 below. The heating experiment results show that after the free crystalline form B sample is heated to 60°C and cooled to room temperature and humidity, it is observed that the main body of the sample is still free crystalline form B, but multiple peaks are observed; after the free crystalline form B sample is heated to 120°C and cooled to room temperature and humidity, it is observed that the sample is converted to free crystalline form A+F. Combining the characterization and the heated sample1 H NMR results (Fig. Figure 7c ), the molar ratio of EtOH to the free state in the sample after heating at 60°C was 0.10 (~0.8wt%); no EtOH residue was observed in the sample after heating at 120°C, and it was speculated that the free state crystalline form B was an EtOH solvate or a co-solvate of EtOH and water.

[0654] Table B1-2 XRPD diffraction peak data of free crystal form B

[0655]

[0656]

[0657] The XRPD results of free form C are as follows: Figure 8 The TGA / DSC results of free form C are shown in Fig. 9 The TGA results showed that the sample had a 2.77% weight loss when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 53.0°C and 182.3°C (peak temperature). The 1H NMR results are as follows: Fig.10 It shows that no MTBE solvent residue is found in the sample. The XRPD analysis data of free crystal form C are shown in the following Table B1-3:

[0658] Table B1-3 XRPD diffraction peak data of free crystal form C

[0659]

[0660]

[0661] Example 4 Starting sample 2 of compound of formula I

[0662] 4.1 Preparation of Starting Sample 2 of Formula I Compound

[0663]

[0664] Add compound I-8 (2.3 g, 3.74 mmol) and 23 mL of THF, 23mL of anhydrous ethanol, stir to clarify, add anhydrous calcium chloride (1.03g, 9.33mmol) and stir to dissolve, cool to 0°C, add sodium borohydride (0.71g, 18.68mmol) after addition, react at room temperature overnight, LCMS shows that the raw material has reacted, the reaction solution is poured into 46mL of water, 92mL of ethyl acetate is added, stirred for 5min, allowed to stand for stratification, the supernatant is poured out, 92mL of ethyl acetate is added to wash the bottom solid, the organic phase is concentrated and mixed with silica gel column (PE:EA=:4:1-1:1-0:1) to obtain the target product, 30ml of acetonitrile is added to dissolve, concentrated until no liquid drops, 100mL of water is added, heated to 100°C and slurried for 5h, filtered, the filter cake is washed, and 100mL of water is added, heated to 100°C and slurried for 5h, slurried at room temperature overnight, filtered, and the solid is freeze-dried to obtain 1.8037g of the starting sample 2 of the compound of formula I.

[0665] 4.2 Characterization of Starting Sample 2 of Formula I Compound

[0666] The XRPD and TGA / DSC characterization results of the starting sample 2 prepared in 4.1 above are as follows Fig.64 and Fig.65 The XRPD results showed that the starting sample 2 was a crystalline sample, which was a mixed crystal of free crystalline form D and free crystalline form J. The TGA results showed that the sample had a weight loss of 4.12% when heated to 160°C, and the DSC results showed that the sample had two endothermic peaks at 40.9°C and 181.3°C (peak temperature). 1 H NMR was collected using DMSO-d6 as solvent. The specific results are as follows Fig.66 shown.

[0667] Example 5 Free Form D of Compound of Formula I

[0668] The free-state crystalline form D sample was prepared by mixing the free-state starting sample 2 with IPA / H2O (volume ratio 982:18, a w After slurrying at room temperature for about 5 days, the solid was separated by centrifugation and dried at room temperature. The XRPD and TGA / DSC results are shown in Figure 2. Fig.67 and Fig.68 The TGA results showed that the sample had a weight loss of 5.79% when heated to 120°C, and the DSC results showed that the sample had two endothermic peaks at 53.9°C and 182.9°C (peak temperature). 1 H NMR results ( Fig.69 ) shows that the molar ratio of IPA to free form in the sample is 0.01 (~0.1wt%). The free form D was identified by VT-XRPD. The results are ( Fig.70) shows that the free crystalline form D sample was purged under N2 conditions for 20 minutes, heated to 120°C under N2 protection, cooled to 30°C, and exposed to room temperature humidity, and was observed to transform into the free crystalline form J. According to VT-XRPD and characterization results, it is speculated that the free crystalline form D is a hydrate, which is dehydrated to anhydrous crystalline form J after N2 purging or heating. The XRPD analysis data of the free crystalline form D are shown in the following Table B1-4:

[0669] Table B1-4 XRPD diffraction peak data of free crystal form D

[0670]

[0671]

[0672] Example 6 Free Form E of Compound of Formula I

[0673] The free-state crystalline form E sample was obtained by placing the free-state starting sample 2 in a THF atmosphere for gas-solid infiltration and then drying it in the open at room temperature. The XRPD and TGA / DSC results are listed in Fig.71 and Fig.72 The TGA results showed that there was a weight loss of 11.97% when heated to 140°C, and the DSC results showed that the sample had two endothermic peaks at 123.0°C and 182.9°C (peak temperature), and one exothermic peak at 148.0°C (peak temperature). 1 H NMR results are as follows Fig.73 As shown, the molar ratio of THF to free state in the sample is 0.95 (~10.4wt%). The crystal form of the free state crystal form E sample was identified by heating experiment. Heating experiment results Fig.74 It is shown that after heating the free crystal form E sample to 130℃ / 160℃ and cooling to room temperature and humidity, it is observed that the sample is converted to free crystal form J. 1 H NMR results ( Fig.75 ), no residual solvent was observed in the sample after the free crystalline form E was heated to 160°C, and it was speculated that the free crystalline form E was a THF solvate. The XRPD analysis data of the free crystalline form E are shown in the following Table B1-5:

[0674] Table B1-5 XRPD diffraction peak data of free crystal form E

[0675]

[0676]

[0677] Example 7 Free Form F of Compound I

[0678] The free-state Form F sample was obtained by heating the free-state starting sample 2 to 172°C and cooling it to room temperature. The XRPD and TGA / DSC results are listed in Fig.76 and Fig.77 The TGA results showed that the sample had a weight loss of 1.19% when heated to 150°C, and the DSC results showed that the sample had an endothermic peak at 181.1°C (peak temperature). 1 H NMR results are as follows Fig.78 As shown, no solvent residue was observed in the sample. Combined with the preparation method and characterization results of free-state crystalline form F, it is inferred that free-state crystalline form F is anhydrous crystalline form. The XRPD analysis data of free-state crystalline form F are shown in Table B1-6 below:

[0679] Table B1-6 XRPD diffraction peak data of free crystal form F

[0680]

[0681] Example 8 Free Form G of Compound I

[0682] The free crystalline form G sample was obtained by dissolving the free starting sample 2 (first dissolved in 1,4-Dioxane, placed in a H2O atmosphere for gas-liquid diffusion to precipitate solid, and then placed in the air to dry. The XRPD and TGA / DSC results are listed in Fig.79 and Fig.80 The TGA results showed that the sample had a weight loss of 10.40% when heated to 110°C, and the DSC results showed that the sample had three endothermic peaks at 98.1°C, 154.8°C and 180.8°C (peak temperature), and one exothermic peak at 157.8°C (peak temperature). 1 H NMR results are as follows Fig.81 As shown, the molar ratio of 1,4-Dioxane to free form in the sample is 0.72 (~9.7wt%). The free form G was identified by heating experiment. The result is ( Fig.82 ) shows that when the free crystalline form G sample is heated to 120°C and cooled to room temperature, it is observed that the sample is converted to free crystalline form F+ multimodal; when the free crystalline form G sample is heated to 160°C and cooled to room temperature, it is observed that the sample is converted to free crystalline form F. 1 H NMR results ( Fig.83 and Fig.84 ) showed that the molar ratio of the residual solvent 1,4-Dioxane to the free state in the sample heated to 120°C and 160°C was 0.04 (~0.6wt%) and 0.02 (~0.3wt%), respectively. Combining the characterization and heating test results, it is speculated that the free state crystalline form G is a 1,4-Dioxane solvate. The XRPD analysis data of the free state crystalline form G are shown in Table B1-7 below:

[0683] Table B1-7 XRPD diffraction peak data of free crystal form G

[0684]

[0685] Example 9 Free Form H of Compound I

[0686] The free-state crystalline form H sample was obtained by placing the free-state starting sample 2 in a DMSO atmosphere for gas-solid diffusion, and after drying in air, it was observed to be converted into a free-state crystalline form D+ multi-peak. The XRPD overlay is shown in Fig.85a As shown. The XRPD of free crystalline form H is as follows Figure 85b , the analysis data is shown in Table B1-8 below:

[0687] Table B1-8 XRPD diffraction peak data of free crystal form H

[0688]

[0689]

[0690] Example 10 Free Form I of Compound of Formula I

[0691] The free form I sample was obtained by slurrying the free starting sample 2 in MeOH at room temperature for about 5 days and then drying it in the open at room temperature. The XRPD and TGA / DSC results are listed in Fig.86 and Fig.87 The TGA results showed that the sample had a 4.00% weight loss when heated to 120°C, and the DSC results showed that the sample had three endothermic peaks at 54.6°C, 168.0°C, and 181.2°C (peak temperature), and one exothermic peak at 170.5°C (peak temperature). 1 H NMR results ( Fig.88 ) showed that no MeOH solvent residue was observed in the sample. The crystal form of free crystal form I was identified by heating experiment. The results of heating experiment ( Fig.89 ) shows that after the free crystalline form I sample was heated to 100°C and cooled to room temperature and humidity, the sample was observed to be converted to free crystalline form A; after the free crystalline form I sample was heated to 172°C and cooled to room temperature and humidity, the sample was observed to be converted to free crystalline form F. Combining the characterization and heating test results, it is speculated that the free crystalline form I is a hydrate. The XRPD analysis data of the free crystalline form I are shown in the following Table B1-9:

[0692] Table B1-9 XRPD diffraction peak data of free form I

[0693]

[0694] Example 11 Free Form J of Compound I

[0695] The free-state Form J sample was obtained by heating the free-state starting sample 2 to 100°C and cooling it to room temperature. The XRPD and TGA / DSC results are listed in Fig.90 and Fig.91 The TGA results showed that the sample had a weight loss of 1.09% when heated to 150°C, and the DSC results showed that the sample had an endothermic peak at 181.5°C (peak temperature). 1 H NMR results ( Fig.92 ) shows that no residual solvent was observed in the sample. The wet XRPD (VH-XRPD) results of the free-state crystalline form J sample ( Fig.93 ) showed that: when the free crystal form J sample was placed at 30% RH, 10% RH, 20% RH and 40% RH, no crystal form change was observed; when the humidity rose to 60% RH, it was observed to be a mixed crystal of crystal form J and crystal form D; when the humidity continued to rise to 80% RH and 90% RH, it was observed to be a crystal form D; when the humidity dropped back to 30% RH, it was observed to be still crystal form D. Combined with the preparation method, characterization data of free crystal form J and the temperature-variable XRPD results of crystal form D, it is speculated that free crystal form J is an anhydrous crystal form, and has a tendency to turn to hydrate crystal form D under humidity conditions of >40% RH. The XRPD analysis data of free crystal form J are shown in the following Table B1-10:

[0696] Table B1-10 XRPD diffraction peak data of free crystal form J

[0697]

[0698]

[0699] Example 12 Free Form K of Compound of Formula I

[0700] The free form K sample was obtained by slurrying the free starting sample 2 in EtOH at room temperature for about 2 days, centrifuging the solid and drying it in vacuum at room temperature. The XRPD and TGA / DSC results are listed in Fig.94 and Fig.95 The TGA results showed that the sample had a weight loss of 8.24% when heated to 150°C, and the DSC results showed that the sample had three endothermic peaks at 72.0°C, 165.2°C, and 180.2°C (peak temperature), and one exothermic peak at 167.1°C (peak temperature). 1 H NMR results ( Fig.96 ) showed that the molar ratio of EtOH to free form in the sample was 0.27 (~2.1wt%). The free form K was identified by heating experiment. The result was ( Fig.97) shows that after the free crystal form K sample was heated to 100°C and cooled to room temperature, it was observed that the sample turned into free crystal form A+F. 1 H NMR results ( Fig.98 ) showed that no residual solvent was observed in the sample. Combining the preparation conditions, characterization and heating test results, it is speculated that the free form K is an EtOH solvate or a cosolvate of EtOH and water. The XRPD analysis data of the free form K are shown in the following Table B1-11:

[0701] Table B1-11 XRPD diffraction peak data of free crystal form K

[0702]

[0703]

[0704] Example 13 Free Form L of Compound I

[0705] The free-state Form L sample was obtained by slurrying the free-state starting sample 1 in MeOH at room temperature for about 3 days. Fig.99a As shown, the sample is converted into free crystal form D after drying, and the XRPD of free crystal form L is as follows Fig.99b , the analysis data is shown in Table B1-12 below:

[0706] Table B1-12 XRPD diffraction peak data of free crystal form L

[0707]

[0708] Example 14 Study on the transformation relationship of the free crystalline form of the compound of formula I

[0709] In order to study the transformation relationship between the anhydrous crystalline forms, the suspension competition experiments in different solvents at room temperature and 50°C were first carried out on the anhydrous crystalline forms A / F / J. The specific steps are as follows: weigh a certain amount of free crystalline form A sample, add the corresponding solvent, suspend and stir at the corresponding temperature for about 2 hours, and filter with a 0.45μm PTFE filter membrane to obtain a saturated solution. Weigh 2 to 5 mg of free anhydrous crystalline forms A / F / J samples into HPLC vials respectively, transfer the saturated solution to the vials, place them at the corresponding temperature for suspension and stirring for about 4 days, and then separate the remaining solid for XRPD testing. The experimental results are summarized in Table B1-13. The XRPD results are shown in Fig.100 The results show that anhydrous crystalline form J was obtained at room temperature and 50°C in the IPA system and at 50°C in the CPME system; hydrated crystalline form D was obtained after suspension at room temperature in the CPME system.

[0710] The results of the suspension competition experiment between the anhydrous crystalline forms showed that the anhydrous crystalline form J is a more stable crystalline form at room temperature and 50°C, so the suspension competition experiment between the anhydrous crystalline form J and the hydrated crystalline form D / I at different water activities was further studied. The specific steps are as follows: weigh a certain amount of the free starting sample 2 (i.e., the mixed crystals of the free crystalline form D+J), add the corresponding solvent, suspend and stir at the corresponding temperature for about 2 hours, and filter with a 0.45μm PTFE filter membrane to obtain a saturated solution. Weigh 2 to 5 mg of the free crystalline form D / I / J sample into an HPLC vial respectively, transfer the saturated solution to the vial, place it under suspension stirring at the corresponding temperature for ~3 days, and separate the solid for XRPD testing. The experimental results are summarized in Table B1-14. The XRPD results are shown in Fig.101 The results show that except for the ACN system (a w Except for the anhydrous crystal form J obtained under the conditions of water activity (0.2-1.0), the hydrate crystal form D was obtained under the conditions of other water activities (0.2-1.0).

[0711] Table B1-13 Results of suspension competition experiment between anhydrous crystal types

[0712]

[0713] Table B1-14 Results of suspension competition experiment between hydrate and anhydrous crystalline form

[0714]

[0715] Example 15 Preparation and Screening of Salt Forms of Compounds of Formula I

[0716] The starting sample 1 (i.e., free crystalline form A) of the compound of formula I prepared in Example 1 was selected according to the pKa (4.5, basic group) of the compound and the solubility of the starting material in different solvents at room temperature. Ten acidic ligands (the molar feed ratio of free state / acidic ligand is 1:1) and three solvent systems were selected. The specific steps of the screening test are as follows: weigh about 30 mg of the starting free state sample and equimolar amounts of different ligands into an HPLC vial, add 0.6 mL of solvent and mix to obtain a suspension. The liquid acid is first diluted with the corresponding solvent and then mixed with the starting sample. After about 3 days of suspension and stirring at room temperature, the solid is separated by centrifugation and vacuum dried at 50°C. The results of the salt type screening test are summarized in Table B2-1. The XRPD characterization results of the obtained solid showed that a total of 2 free polymorphs and 7 salts with a total of 15 crystalline forms were obtained in the salt type screening test. The screened salt forms were characterized by TGA / DSC and used 1 The molar ratio of the salt was determined by H NMR and HPLC / IC, and the salt characterization results are summarized in Table B2-2.

[0717] Table B2-1 Summary of salt type screening test results

[0718]

[0719]

[0720] *: The sample was observed to gel and then switched to temperature cycle (50-5°C).

[0721] # The samples became clear after stirring at room temperature and 5°C, and then n-heptane was added to induce crystallization.

[0722] Table B2-2 Summary of the characterization results of the salt types obtained by screening

[0723]

[0724] *:pass 1 H NMR or HPLC / IC calculated. ^: Exothermic signal. ND: Not detected.

[0725] Example 16 Hydrochloride Crystal Form A / B / C

[0726] Hydrochloride crystal forms A and B are obtained by slurrying the starting sample 1 of the compound of formula I and an equimolar amount of hydrochloric acid in ethanol and MIBK at room temperature for about 3 days, centrifuging and separating the solid samples, and drying them in vacuum at 50°C. Hydrochloride crystal form C is obtained by slurrying the starting sample 1 of the compound of formula I and 0.3V concentrated hydrochloric acid in 15V acetone at room temperature for about 2 days, centrifuging and separating the solids, and drying them in vacuum at 50°C. The XRPD overlay of the hydrochloride sample is shown in FIG. Fig.11 shown.

[0727] The XRPD results of hydrochloride form A are as follows: Fig.12a The TGA / DSC results are listed in Fig.13 Among them, the TGA results show that the sample has a weight loss of 8.21% when heated to 160°C; the DSC results show that the sample has an endothermic peak at 165.8°C (peak temperature). 1 H NMR results are as follows Fig.14 The results showed that the molar ratio of the residual solvent EtOH to the free state in the sample was 0.93 (about 6.4 wt%). The HPLC / IC results showed that the molar ratio of hydrochloric acid to the free state in the sample was 1.2:1. The XRPD analysis data of the hydrochloride crystal form A are shown in Table B2-3 below:

[0728] Table B2-3 XRPD diffraction peak data of hydrochloride salt form A

[0729]

[0730] The XRPD results of hydrochloride form B are as follows Fig.15 The TGA / DSC results are listed in Fig.16Among them, the TGA results showed that the sample had a weight loss of 16.61% when heated to 180°C; the DSC results showed that the sample had two endothermic peaks at 154.1°C and 171.0°C (peak temperature). 1 H NMR results are as follows Fig.17 The results showed that the molar ratio of the residual solvent MIBK in the sample to the free state was 1.00 (about 13.8 wt%). The HPLC / IC results showed that the molar ratio of hydrochloric acid in the sample to the free state was 1.1:1. The XRPD analysis data of the hydrochloride crystal form B are shown in Table B2-4 below:

[0731] Table B2-4 XRPD diffraction peak data of hydrochloride crystal form B

[0732]

[0733] The XRPD pattern of hydrochloride form C is as follows Fig.18 The TGA / DSC results are listed in Fig.19 The TGA results show that the sample loses 4.67% of its weight when heated to 90°C, and loses 6.00% of its weight when further heated to 170°C. The DSC results show that the sample has two endothermic peaks at 77.8°C and 174.6°C (peak temperature). 1 H NMR results are as follows Fig. 20 The results showed that no acetone solvent residue was found in the sample. The HPLC / IC results showed that the molar ratio of hydrochloric acid to free state in the sample was 2.0:1. The XRPD analysis data of hydrochloride crystal form C are shown in Table B2-5 below:

[0734] Table B2-5 XRPD diffraction peak data of hydrochloride crystal form C

[0735]

[0736]

[0737] Repeat the preparation of hydrochloride crystal form A:

[0738] The hydrochloride salt Form A sample was prepared repeatedly by slurrying ~500 mg of the free starting sample 2 and an equimolar amount of hydrochloric acid in EtOH at room temperature for about 2 days, centrifuging the solid sample and drying it in vacuo at 50°C. The XRPD results are listed in Figure 12b .

[0739] Example 17 Sulfate Crystal Form A / B / C

[0740] Sulfate salt crystal forms A, B and C are obtained by slurrying the starting sample 1 of the compound of formula I and an equimolar amount of sulfuric acid in ethanol, MTBE and MIBK at room temperature for about 3 days, centrifuging the solid sample and drying it in vacuum at 50°C. The XRPD overlay of the sulfate sample is shown in FIG. Fig.21 shown.

[0741] The XRPD results of sulfate form A are as follows: Fig. 22 The TGA / DSC results are listed in Fig.23 The TGA results showed that the sample had a weight loss of 5.78% when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 52.9°C and 167.1°C (peak temperature). 1 H NMR results are as follows Fig.24 The results showed that the molar ratio of the residual solvent ethanol to the free state in the sample was 0.93 (about 5.8 wt%). The HPLC / IC results showed that the molar ratio of sulfuric acid to the free state in the sample was 1.1:1. The XRPD analysis data of sulfate crystal form A are shown in Table B2-6 below:

[0742] Table B2-6 XRPD diffraction peak data of sulfate crystal form A

[0743]

[0744] The XRPD results of sulfate form B are as follows: Fig.25 The TGA / DSC results are listed in Fig.26 Among them, the TGA results show that the sample has a weight loss of 1.16% when heated to 150°C; the DSC results show that the sample has two endothermic peaks at 69.7°C and 238.5°C (peak temperature). 1 H NMR results are as follows Fig. 27 The results showed that no MTBE solvent residue was found in the sample. The HPLC / IC results showed that the molar ratio of sulfuric acid to free state in the sample was 1.2:1. The XRPD analysis data of sulfate crystal form B are shown in Table B2-7 below:

[0745] Table B2-7 XRPD diffraction peak data of sulfate crystal form B

[0746]

[0747] The XRPD results of sulfate crystal form C are as follows Fig.28 The TGA / DSC results are listed in Fig.29 Among them, the TGA results showed that the sample had a 2.83% weight loss when heated to 100°C; the DSC results showed that the sample had four endothermic peaks at 92.4°C, 159.3°C, 184.8°C and 216.8°C (peak temperature), and one exothermic peak at 224.0°C (peak temperature). 1 H NMR results are as follows Fig.30 The results showed that no MIBK solvent residue was found in the sample. The HPLC / IC results showed that the molar ratio of sulfuric acid to free state in the sample was 1.6:1. The XRPD analysis data of sulfate crystal form C are shown in Table B2-8 below:

[0748] Table B2-8 XRPD diffraction peak data of sulfate crystal form C

[0749]

[0750]

[0751] Example 18 Maleate Crystal Form A

[0752] Method 1: Maleate salt form A is prepared by slurrying the starting sample 1 of the compound of formula I and an equimolar amount of maleic acid in MIBK at 5°C for about 3 days, clarifying the sample, adding n-heptane to induce crystallization, and then transferring the sample to a temperature cycle of 50°C to 5°C to obtain a suspension, and centrifuging the solid sample and vacuum drying it at 50°C to obtain a suspension.

[0753] Method 2: 1) weigh about 50 mg of the starting sample of the compound of formula I and about 9.8 mg of maleic acid in 500 μL MIBK and dissolve; 2) add a small amount of maleate salt form A seed to the solution in step 1), stir magnetically at room temperature, and age for about 30 minutes after turbidity; 3) slowly add 500 μL of n-heptane to the solution in step 2), and no gel formation is observed during the process. After continuing to stir magnetically at room temperature for about 1 day, separate the solid and vacuum dry it at 50°C overnight to obtain about 47.0 mg of sample.

[0754] XRPD of maleate form A is as follows Fig.31 For details of TGA / DSC results, see Fig.32 Among them, the TGA results showed that the sample had a weight loss of 0.42% when heated to 130°C, and the DSC results showed that the sample had an endothermic peak at 142.1°C (peak temperature). 1 H NMR results are as follows Fig.33 The results show that the molar ratio of maleic acid to free state in the sample is 1.0, and the molar ratio of residual solvent MIBK to free state is 0.04 (about 0.4 wt%). The XRPD analysis data of maleate salt form A is shown in Table B2-9 below:

[0755] Table B2-9 XRPD diffraction peak data of maleate salt form A

[0756]

[0757]

[0758] Example 19 Phosphate Crystalline Form A

[0759] Phosphate crystal form A is obtained by subjecting the starting sample 1 of the compound of formula I and an equimolar amount of phosphoric acid to a gelatinous solid after being subjected to a temperature cycle of 50°C to 5°C in MIBK for about 6 days, centrifuging the gelatinous solid sample and vacuum drying it at 50°C. The XRPD of phosphate crystal form A is shown in FIG. Fig.34 For details of TGA / DSC results, see Fig.35 The TGA results showed that the sample had a weight loss of 3.71% when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 41.5°C and 169.6°C (peak temperature), and one exothermic peak at 91.8°C (peak temperature). 1 H NMR results are as follows Fig.36 The results showed that the molar ratio of the residual solvent MIBK to the free state in the sample was 0.16 (about 1.6 wt%). The HPLC / IC results showed that the molar ratio of phosphoric acid to the free state in the sample was 4.3:1. The XRPD analysis data of the phosphate crystal form A are shown in Table B2-10 below:

[0760] Table B2-10 XRPD diffraction peak data of phosphate crystal form A

[0761]

[0762]

[0763] Example 20 p-Toluenesulfonate Crystalline Form A / B

[0764] The p-toluenesulfonate salt form A / B is prepared by slurrying the starting sample 1 of the compound of formula I and an equimolar amount of p-toluenesulfonic acid in ethanol and MTBE at room temperature for about 3 days, centrifuging the solid sample and drying it in vacuo at 50°C. The XRPD overlay of the p-toluenesulfonate salt sample is shown in FIG. Fig.37 shown.

[0765] The XRPD results of p-toluenesulfonate Form A are as follows: Fig.38 The TGA / DSC results are listed in Fig.39 The TGA results showed that the sample had a 4.15% weight loss when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 81.6°C and 156.0°C (peak temperature). 1 The HNMR results are as follows Fig.40 The results show that the molar ratio of p-toluenesulfonic acid to the free state in the sample is 1.0, the molar ratio of the residual solvent EtOH to the free state is 0.52 (about 2.7 wt%), and the molar ratio of MIBK to the free state is 0.95 (about 10.8 wt%). The XRPD analysis data of p-toluenesulfonate crystal form A are shown in Table B2-11 below:

[0766] Table B2-11 XRPD diffraction peak data of p-toluenesulfonate crystal form A

[0767]

[0768] The XRPD results of p-toluenesulfonate Form B are as follows: Fig.41 The TGA / DSC results are listed in Fig.42 The TGA results showed that the sample had a weight loss of 1.92% when heated to 150°C; the DSC results showed that the sample had an endothermic peak at 204.3°C (peak temperature). 1 H NMR results are as follows Fig.43 The results show that the molar ratio of p-toluenesulfonic acid to the free state in the sample is 1.0, and the molar ratio of the residual solvent MTBE to the free state is 0.03 (about 0.4 wt%). The XRPD analysis data of p-toluenesulfonate crystal form B are shown in Table B-15 below:

[0769] Table B2-12 XRPD diffraction peak data of p-toluenesulfonate crystal form B

[0770]

[0771]

[0772] Example 21 Methanesulfonate Crystal Form A / B / C / D

[0773] Methanesulfonate crystal form A / B is obtained by slurrying the starting sample 1 of the compound of formula I and an equal molar amount of methanesulfonic acid in ethanol and MTBE at room temperature for about 3 days, centrifuging the solid sample and drying it in vacuum at 50°C. Methanesulfonate crystal form C is obtained by cycling the starting sample of the compound of formula I and an equal molar amount of methanesulfonic acid in MIBK at 50°C to 5°C for about 3 days, centrifuging the solid sample and drying it in vacuum at 50°C. The XRPD overlay of the methanesulfonate sample is shown in FIG. Fig.44 shown.

[0774] The XRPD results of mesylate form A are as follows: Fig.45 The TGA / DSC results are listed in Fig.46 Among them, the TGA results showed that the sample had a weight loss of 3.08% when heated to 150°C; the DSC results showed that the sample had an endothermic peak at 153.8°C (peak temperature). 1 H NMR results are as follows Fig.47 The results show that the molar ratio of methanesulfonic acid to free state in the sample is 1.0, and the molar ratio of residual solvent EtOH to free state is 0.60 (about 3.9 wt%). The XRPD analysis data of mesylate crystal form A are shown in Table B2-13 below:

[0775] Table B2-13 XRPD diffraction peak data of mesylate salt form A

[0776]

[0777] The XRPD results of mesylate form B are as follows: Fig.48 The TGA / DSC results are listed in Fig.49 Among them, the TGA results showed that the sample had a weight loss of 0.67% when heated to 150°C; the DSC results showed that the sample had three endothermic peaks at 161.8°C, 168.3°C and 194.9°C (peak temperature). 1 H NMR results are as follows Fig.50 The results show that the molar ratio of methanesulfonic acid to free state in the sample is 1.1, and the molar ratio of residual solvent MTBE to free state is 0.02 (about 0.2 wt%). The XRPD analysis data of mesylate crystal form B is shown in Table B2-14 below:

[0778] Table B2-14 XRPD diffraction peak data of mesylate crystal form B

[0779]

[0780] The XRPD results of mesylate form C are as follows: Fig.51 The TGA / DSC results are listed in Fig.52 Among them, the TGA results showed that the sample had a 14.14% weight loss when heated to 150°C; the DSC results showed that the sample had three endothermic peaks at 111.7°C, 135.8°C and 139.6°C (peak temperature). 1 H NMR results are as follows Fig.53 The results show that the molar ratio of methanesulfonic acid to free state in the sample is 1.1, and the molar ratio of residual solvent MIBK to free state is 0.90 (about 11.5 wt%). The XRPD analysis data of mesylate crystal form C are shown in Table B2-15 below:

[0781] Table B2-15 XRPD diffraction peak data of mesylate salt form C

[0782]

[0783] The mesylate salt Form D was obtained by slurrying ~500 mg of the free starting sample 2 and 1.5 moles of methanesulfonic acid in EtOH at room temperature for about 2 days, centrifuging the solid sample and drying it in vacuo at 50°C. The XRPD overlay of the mesylate salt Form AD is shown in Fig.102a The XRPD of mesylate salt form D is as follows Fig.102b . TGA / DSC results of mesylate form D ( Fig.103 ) showed that the sample had a 2.62% weight loss when heated to 150°C, and had two endothermic peaks at 40.3°C and 156.6°C (peak temperatures). 1 HNMR results ( Fig.104) shows that the molar ratio of methanesulfonic acid to free state in the sample is 1.1, and the molar ratio of EtOH to free state is 0.05 (~0.3wt%). The XRPD analysis data of mesylate crystal form D are shown in the following Table B2-16:

[0784] Table B2-16 XRPD diffraction peak data of mesylate salt form D

[0785]

[0786] Example 22 Ethysulfonate Crystal Form A / B

[0787] Ethylate salt form A / B is obtained by slurrying the starting sample 1 of the compound of formula I and an equimolar amount of ethanesulfonic acid in ethanol and MIBK at room temperature for about 3 days, centrifuging the solid sample and drying it in vacuo at 50°C. The XRPD overlay of the ethanesulfonate salt sample is shown in FIG. Fig.54 shown.

[0788] The XRPD results of ethanesulfonate form A are as follows: Fig.55 The TGA / DSC results are listed in Fig.56 The TGA results showed that the sample had a weight loss of 8.29% when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 36.3°C and 141.5°C (peak temperature). 1 H NMR results are as follows Fig.57 The results show that the molar ratio of ethanesulfonic acid to free state in the sample is 1.1, the molar ratio of residual solvent EtOH to free state is 0.46 (about 2.7 wt%), and the molar ratio of MIBK to free state is 0.60 (about 7.6 wt%). The XRPD analysis data of ethanesulfonate crystal form A are shown in Table B2-17 below:

[0789] Table B2-17 XRPD diffraction peak data of ethanesulfonate crystal form A

[0790]

[0791] The XRPD results of ethanesulfonate Form B are as follows: Fig.58a The TGA / DSC results are listed in Fig.59 The TGA results showed that the sample had a 6.30% weight loss when heated to 150°C; the DSC results showed that the sample had two endothermic peaks at 107.1°C and 145.3°C (peak temperature). 1 H NMR results are as follows Fig.60 The results show that the molar ratio of ethanesulfonic acid to free state in the sample is 1.1, and the molar ratio of residual solvent MIBK to free state is 0.35 (about 4.7 wt%). The XRPD analysis data of ethanesulfonate crystal form B are shown in Table B2-18 below:

[0792] Table B2-18 XRPD diffraction peak data of ethanesulfonate crystal form B

[0793]

[0794] Repeated preparation of ethanesulfonate salt form B:

[0795] The ethanesulfonate salt Form B sample was prepared by slurrying 500 mg of the free starting sample 2 and an equal molar amount of ethanesulfonic acid in MIBK at room temperature for about 4 days, centrifuging the solid sample and drying it in vacuo at 50°C. XRPD results ( Fig.58b ) shows that the repeated preparation samples are ethanesulfonate form B.

[0796] Example 23 Preparation and Screening of Salt Forms of Formula I Compound II Starting with the repeatedly prepared hydrochloride crystal form A (described in Example 16), methanesulfonate crystal form D (described in Example 21) and repeatedly prepared ethanesulfonate crystal form B (described in Example 22), different solvent systems were selected to carry out suspension stirring experiments at room temperature and 50°C to screen out crystal forms with better solid properties. The experimental steps are as follows: weigh about 20 mg of each corresponding strong acid salt sample into an HPLC vial, add 0.5 mL of the solvent listed in Table B2-19 to Table B2-21, respectively, place the obtained suspension under magnetic stirring at the corresponding temperature for about 3 days, centrifuge to separate the solid and perform XRPD testing.

[0797] The experimental results are summarized in Table B2-19 to Table B2-21. The results show that in the polymorph screening, 12 crystal forms were observed for the hydrochloride, namely hydrochloride crystal forms A / B / D to M; 12 crystal forms were observed for the methanesulfonate, namely methanesulfonate crystal forms A / E to O; and 5 crystal forms were observed for the ethanesulfonate, namely ethanesulfonate crystal forms B to F. Representative crystal samples with more crystal forms obtained in various solvent systems were selected for TGA / DSC characterization and used 1 The molar ratio of the salt was determined by H NMR or HPLC / IC. The characterization results are summarized in Table B-22.

[0798] Table B2-19 Summary of hydrochloride suspension stirring test results

[0799]

[0800]

[0801] Table B2-20 Summary of the results of the mesylate suspension stirring experiment

[0802]

[0803]

[0804] *: The sample was observed to be gelled and dark brown in color.

[0805] Table B2-21 Summary of the results of the ethanesulfonate suspension stirring experiment

[0806]

[0807] Table B2-22 Summary of the characterization results of the salt types obtained by screening

[0808]

[0809]

[0810] # :Depend on 1 H NMR or HPLC / IC calculated; ND: not detected; ^: exothermic peak.

[0811] Example 24 Hydrochloride Crystal Forms D to M

[0812] Hydrochloride crystal form D is obtained by slurrying the repeatedly prepared hydrochloride crystal form A sample in MeOAc at room temperature for about 6 days; hydrochloride crystal forms E / F / G are obtained by slurrying the repeatedly prepared hydrochloride crystal form A sample in 2-MeTHF, DMSO / IPAc (1:9, v / v) and 1,4-Dioxane at 50°C for about 3 days; hydrochloride crystal form H is obtained by slurrying the repeatedly prepared hydrochloride crystal form A sample in Toluene at room temperature for ~6 days, centrifuging and drying the solid in the air at room temperature; hydrochloride crystal forms I / J / K / L / M are obtained by slurrying the repeatedly prepared hydrochloride crystal form A sample in DCM / MeOH / Acetone / ACN / THF at room temperature for ~6 days. The XRPD overlay of different hydrochloride crystal samples is shown below. Fig.105 and 106a shown.

[0813] The TGA / DSC results of the hydrochloride form H sample (obtained by slurrying in Toluene) are listed in Fig.108 The TGA results showed that the sample had a weight loss of 7.61% when heated to 170°C, and the DSC results showed that the sample had two endothermic peaks at 155.5°C and 191.5°C (peak temperature). 1 H NMR results are as follows Fig.109 As shown, no residual Toluene solvent was found in the sample. HPLC / IC results showed that the molar ratio of hydrochloric acid to free state in the hydrochloride crystal form H sample was 1.3.

[0814] The XRPD of hydrochloride crystal forms D, E and F are as follows: Fig.107 , 110, 111, and the XRPD analysis data are shown in Tables B2-23 to B2-25. The XRPD of hydrochloride crystal forms G, H, I, J, K, L, and M are shown in Tables B2-23 to B2-25. Fig.106b , 106c , 106d, 106e, 106f, 106g, and 106h, and the XRPD analysis data are shown in the following Tables B2-26 to B2-32, respectively.

[0815] Table B2-23 XRPD diffraction peak data of hydrochloride salt form D

[0816]

[0817] Table B2-24 XRPD diffraction peak data of hydrochloride salt form E

[0818]

[0819]

[0820] Table B2-25 XRPD diffraction peak data of hydrochloride salt form F

[0821]

[0822] Table B2-26 XRPD diffraction peak data of hydrochloride salt form G

[0823]

[0824] Table B2-27 XRPD diffraction peak data of hydrochloride salt form H

[0825]

[0826] Table B2-28 XRPD diffraction peak data of hydrochloride salt form I

[0827]

[0828]

[0829] Table B2-29 XRPD diffraction peak data of hydrochloride salt form J

[0830]

[0831] Table B2-30 XRPD diffraction peak data of hydrochloride salt form K

[0832]

[0833]

[0834] Table B2-31 XRPD diffraction peak data of hydrochloride crystal form L

[0835]

[0836] Table B2-32 XRPD diffraction peak data of hydrochloride salt form M

[0837]

[0838] Example 25 Methanesulfonate Crystal Forms E to O

[0839] Methanesulfonate Form E is obtained by slurrying a methanesulfonate Form D sample in IPAc at 50°C for about 3 days, centrifuging and separating the solid and drying it in the open at room temperature; Methanesulfonate Form F is obtained by slurrying a methanesulfonate Form D sample in Acetone at room temperature for 6 days, centrifuging and separating the solid and drying it in the open at room temperature; Methanesulfonate Form G is obtained by slurrying a methanesulfonate Form D sample in Toluene at 50°C for 3 days; Methanesulfonate Forms H / I / J / K / L are obtained by slurrying a methanesulfonate Form D sample in EtOH / Ethyl formate / ACN / Anisole / DMSO / EtOAc (1:9, v / v) was obtained after slurrying at room temperature for ~6 days; mesylate crystal form M / N was obtained by slurrying the mesylate crystal form D sample in 1,4-Dioxane / H2O (9:1, v / v) and t-BuOH at room temperature for ~6 days; mesylate crystal form O was obtained by slurrying the mesylate crystal form D sample in MeOH / IPE (1:4, v / v) at room temperature for ~6 days, centrifuging and drying the solid in the air at room temperature. The XRPD overlays of different mesylate crystal forms are listed in Fig.112a , 113a 、114a.

[0840] The XRPD of mesylate forms E and F are as follows: Fig.112b , 112c As shown, the XRPD of mesylate forms G, H, I, J, K, and L are respectively as shown in Figures 113b to 113g As shown, the XRPD of mesylate crystal forms M, N, and O are respectively as shown in Fig.114b , 114c The XRPD analysis data of the above crystal forms are shown in the following Tables B2-33 to B2-43 respectively.

[0841] Table B2-33 XRPD diffraction peak data of mesylate crystal form E

[0842]

[0843] Table B2-34 XRPD diffraction peak data of mesylate salt form F

[0844]

[0845]

[0846] Table B2-35 XRPD diffraction peak data of mesylate salt form G

[0847]

[0848] Table B2-36 XRPD diffraction peak data of mesylate salt form H

[0849]

[0850]

[0851] Table B2-37 XRPD diffraction peak data of mesylate salt form I

[0852]

[0853] Table B2-38 XRPD diffraction peak data of mesylate salt form J

[0854]

[0855] Table B2-39 XRPD diffraction peak data of mesylate salt form K

[0856]

[0857]

[0858] Table B2-40 XRPD diffraction peak data of mesylate salt form L

[0859]

[0860] Table B2-41 XRPD diffraction peak data of mesylate salt form M

[0861]

[0862]

[0863] Table B2-42 XRPD diffraction peak data of mesylate salt form N

[0864]

[0865] Table B2-43 XRPD diffraction peak data of mesylate salt form O

[0866]

[0867] The TGA / DSC of the mesylate form E sample is shown in Fig.115 The TGA results showed that the sample had a weight loss of 0.85% when heated to 150°C, and the DSC results showed that the sample had an endothermic peak at 198.2°C (peak temperature). 1 H NMR results are as follows Fig.116 As shown, the molar ratio of methanesulfonic acid to free state in the sample was 1.0, and no residual IPAc solvent was found.

[0868] The TGA / DSC of the mesylate Form F sample is shown in Fig.117 The TGA results showed that the sample had a 2.18% weight loss when heated to 160°C, and the DSC results showed that the sample had two endothermic peaks at 154.8°C and 195.6°C (peak temperature). 1 H NMR results are as follows Fig.118 As shown, the molar ratio of methanesulfonic acid to the free state in the sample is 1.0, and the molar ratio of acetone to the free state is 0.09 (-0.8 wt %).

[0869] The TGA / DSC of the mesylate form O sample is shown in Fig.119 The TGA results showed that the sample had a weight loss of 0.17% when heated to 150°C, and the DSC results showed that the sample had two endothermic peaks at 185.9°C and 194.8°C (peak temperature). 1 H NMR results are as follows Fig.120 As shown, the molar ratio of methanesulfonic acid to free state in the sample was 1.0, and no MeOH and IPE solvent residues were found.

[0870] Example 26 Ethysulfonate C / D / E / F

[0871] Ethylate Form C was obtained by slurrying the repeatedly prepared ethylsulfonate Form B sample in IPA at 50°C for 3 days; Ethylate Form D / E was obtained by slurrying the repeatedly prepared ethylsulfonate Form B sample in EtOH and Acetone at room temperature for 5 days, centrifuging and drying the solid in the air at room temperature; Ethylate Form F was obtained by slurrying the repeatedly prepared ethylsulfonate Form B sample in THF / H2O (9:1, v / v) at room temperature for 5 days. The XRPD overlays of different ethylsulfonate crystal samples are listed in Fig.121a .

[0872] The TGA / DSC of ethanesulfonate Form D is shown in Fig.122 The TGA results showed that the sample had a weight loss of 1.70% when heated to 150°C, and the DSC results showed that the sample had three endothermic peaks at 55.5°C, 142.4°C and 184.2°C (peak temperature), and one exothermic peak at 91.6°C (peak temperature). 1 H NMR results are as follows Fig.123As shown, the molar ratio of ethanesulfonic acid to the free state in the sample was 1.0, and no residual EtOH solvent was observed.

[0873] The TGA / DSC of ethanesulfonate Form E is shown in Fig.124 The TGA results showed that the sample had a weight loss of 0.61% when heated to 80°C, and a weight loss of 4.64% when further heated to 110°C. The DSC results showed that the sample had three endothermic peaks at 48.4°C, 104.0°C and 188.3°C (peak temperature). 1 H NMR results are as follows Fig.125 As shown, the molar ratio of ethanesulfonic acid to the free state in the sample is 1.1, and the molar ratio of solvent acetone to the free state is 0.54 (~4.2wt%).

[0874] The XRPDs of ethanesulfonate forms C, D, E, and F are shown in Table 1. Fig.121b , 121c , 121d, and 121e, and the XRPD analysis data are shown in the following Tables B2-44 to B2-47, respectively.

[0875] Table B2-44 XRPD diffraction peak data of ethanesulfonate crystal form C

[0876]

[0877] Table B2-45 XRPD diffraction peak data of ethanesulfonate crystal form D

[0878]

[0879]

[0880] Table B2-46 XRPD diffraction peak data of ethanesulfonate crystal form E

[0881]

[0882] Table B2-47 XRPD diffraction peak data of ethanesulfonate crystal form F

[0883]

[0884] Example 27 1,2-Ethanedisulfonate Crystalline Form A / B / C

[0885] 1,2-ethanedisulfonate crystal form A / B is obtained by slurrying the free starting sample 2 and an equimolar amount of 1,2-ethanedisulfonic acid in EtOH and EtOAc at room temperature for about 2 days, centrifuging the solid sample and drying it in vacuum at 50°C; 1,2-ethanedisulfonate crystal form C is obtained by slurrying the free starting sample 2 and an equimolar amount of 1,2-ethanedisulfonic acid in 2-MeTHF at room temperature overnight to form a gel, transferring the slurry to a temperature cycle of 50°C to 5°C for 1 day, and then discarding the gel sample, centrifuging the solid sample and drying it in vacuum at 50°C. XRPD overlay is shown in the figure Fig.126a As shown. XRPD of 1,2-ethanedisulfonate forms A, B, and C are as follows Fig.126b , 126c , 126d, and the XRPD analysis data are shown in the following Tables B2-48 to B2-50.

[0886] Table B2-48 XRPD diffraction peak data of 1,2-ethanedisulfonate crystal form A

[0887]

[0888]

[0889] Table B2-49 XRPD diffraction peak data of 1,2-ethanedisulfonate crystal form B

[0890]

[0891] Table B2-50 XRPD diffraction peak data of 1,2-ethanedisulfonate crystal form C

[0892]

[0893]

[0894] The TGA / DSC of 1,2-ethanedisulfonate Form A is shown in Fig.127 The TGA results showed that the sample had a weight loss of 1.47% when heated to 150°C, and the DSC results showed that the sample had three endothermic peaks at 33.9°C, 238.5°C and 249.0°C (peak temperature), and one exothermic peak at 256.0°C (peak temperature). 1 H NMR results are as follows Fig.128 As shown, the molar ratio of 1,2-ethanedisulfonic acid to the free state in the sample is 1.1, and the molar ratio of EtOH to the free state is 0.07 (-0.4 wt %).

[0895] The TGA / DSC of 1,2-ethanedisulfonate Form B is shown in Fig.129The TGA results showed that the sample had a weight loss of 2.18% when heated to 150°C, and the DSC results showed that the sample had an endothermic peak at 233.6°C (peak temperature) and an exothermic peak at 238.3°C (peak temperature). 1 H NMR results are as follows Fig.130 As shown, the molar ratio of 1,2-ethanedisulfonic acid to the free state in the sample was 1.1, and no residual EtOAc solvent was observed.

[0896] The TGA / DSC of 1,2-ethanedisulfonate Form C is shown in Fig.131 The TGA results showed that the sample had a weight loss of 1.76% when heated to 150°C, and the DSC results showed that the sample had two endothermic peaks at 45.5°C and 247.8°C (peak temperature), and one exothermic peak at 254.4°C (peak temperature). 1 H NMR results are as follows Fig.132 As shown, the molar ratio of 1,2-ethanedisulfonic acid to the free state in the sample was 1.2, and no residual 2-MeTHF solvent was observed.

[0897] Embodiment 28

[0898] Weigh 20 mg of the compound of formula I (prepared according to Example 1) and add it to an EP tube. Add methanol (3 mL) and shake until the sample is completely dissolved. Add purified water (0.5 mL) and filter the solution through a microporous membrane into a 4 mL glass bottle. Seal the bottle with a sealing film, pierce three small holes, and allow to evaporate. After 5 days, transparent crystals were observed to precipitate. The crystals were tested for single crystals. For single crystal simulated XRPD, see Fig.133 , which is consistent with the XRPD of the Form D powder sample. The molecular structure diagram of the single crystal diffraction thermal ellipsoid (50%) is shown in Fig.134 , proving that the single crystal sample contains one crystal water, indicating that the crystal form D is a monohydrate. The single crystal diffraction molecular structure stacking diagram can be found in Fig.135 The X-ray single crystal diffraction results are shown in Table B3-1.

[0899]

[0900] Test Example 1

[0901] The solid feed concentration was 1 mg / mL (in free form) and rotated and mixed at room temperature, and the solubility of each sample in water, SGF and FaSSIF was measured at different time points (2 and 24 hours). After sampling at each time point, the samples were centrifuged (10000rpm) and filtered (0.22μm PTFE filter head), the HPLC concentration and pH value of the filtrate were measured, and the solid samples after centrifugation were tested by XRPD. The solubility test results are summarized in Table C-1, and the room temperature solubility curves of free form C, sulfate form B, maleate form A, p-toluenesulfonate form B and hydrochloride form C in H2O, SGF and FaSSIF are shown in Figure 61-63 .

[0902] Table C-1 Summary of room temperature solubility test results

[0903]

[0904] S: solubility (mg / mL).

[0905] LOQ: Limit of Quantitation, refers to the lowest amount of the analyte in the sample that can be quantitatively determined.

[0906] Test Example 2

[0907] The dynamic solubility, hygroscopicity and solid state stability of the crystalline form of the present invention were evaluated.

[0908] (I) Dynamic solubility

[0909] The solid feed concentration was 10 mg / mL (in free form) and the samples were mixed by rotation at 37°C. The solubility of each sample in H2O, SGF, FaSSIF and FeSSIF was measured at different time points (1, 2, 4 and 24 hours). After sampling at each time point, the samples were centrifuged (10000 rpm) and filtered (0.45 μm PTFE). The HPLC concentration and pH value of the filtrate were measured, and the solid samples after centrifugation were tested by XRPD. The solubility test results are summarized in Table C-2, and the solubility curves are shown in Fig.136 The XRPD results of the samples after solubility test are shown in Figure 137-Figure 156 The experimental results show that compared with the free state, the solubility of all candidate salt forms in H2O, SGF, FaSSIF and FeSSIF at 37°C for 1 / 2 / 4 / 24 hours is improved to varying degrees. XRPD results show that all salt samples have different degrees of crystal form changes after the dynamic solubility test, and the crystal form of the free state samples remains unchanged after the dynamic solubility test.

[0910] Table C-2 Summary of 37℃ dynamic solubility test results

[0911]

[0912]

[0913] S: solubility (mg / mL); FC: crystal form change;

[0914] (II) Hygroscopicity

[0915] The hygroscopicity of sulfate form B, p-toluenesulfonate form B, maleate form A, methanesulfonate form E and free form D was evaluated by dynamic moisture sorption (DVS). The mass change percentage of the samples was collected under constant temperature of 25°C and with humidity changes (0% RH-95% RH). The DVS test results and the XRPD results of the samples before and after the DVS test are shown in Figure 2. Figures 157 to 166 The results show that the moisture adsorption of free crystal form D, sulfate crystal form B, p-toluenesulfonate crystal form B, maleate crystal form A and methanesulfonate crystal form E at 25℃ / 80%RH are 3.129%, 0.445%, 0.171%, 0.235% and 2.324%, respectively. Except for free crystal form D, which turns into free crystal form D+J after DVS test, the crystal forms of other samples remain unchanged before and after DVS test.

[0916] (III) Solid-state stability

[0917] The sulfate salt form B, p-toluenesulfonate salt form B, maleate salt form A, methanesulfonate salt form E and free form D were placed in a closed container at 80°C for 1 day and in an open container at 25°C / 60%RH and 40°C / 75%RH for 1 week, and then the physical and chemical stability of the samples were tested by XRPD and HPLC. The purity data are listed in Table C-3, and the XRPD results are listed in Figures 167 to 171 The stability evaluation results showed that no significant purity changes were observed in all samples after testing. XRPD results showed that except for the free crystal form D which turned into the free crystal form J+D after being placed at 80℃ / closed for 1 day, the crystal forms of other samples remained unchanged.

[0918] Table C-3 Summary of solid state stability evaluation

[0919]

[0920] Test Example 3 Inhibition test of KIF18A enzyme activity by compounds of formula I

[0921] The recombinant protein KIF18A (kinesin domain: aa 1-467) used in this test was expressed by Invitrogen's Bac-to-Bac baculovirus expression system, and the resulting protein was purified and used in this test (Seki, M. et al. 2003 Nucleic Acids Res.). KIF18A enzyme activity was quantitatively detected using ADP-Glo TM Kinase detection kit (Promega Inc) was used, and the relevant operations strictly followed the product instructions, which are briefly described as follows:

[0922] The reaction system consists of the test compound, recombinant protein KIF18A (aa 1-467), ATP (Promega Inc) and experimental buffer. The test compound was prepared into a 0.5mM stock solution with DMSO (Sigma Inc) and gradient dilution was performed using DMSO. The experimental buffer consists of 15mM Tris, 10mM MgCl2 (Sigma Inc), 0.01% Pluronic F-68 (LifeTechnologies Inc), 1μM paclitaxel (Cytoskeleton Inc), 30μg / mL porcine tubulin (Cytoskeleton Inc) and 2% DMSO in water. KIF18A protein (final concentration of 80nM) and different concentrations of compounds (1μL) were added to the prepared experimental buffer (50μL) and incubated at room temperature for 15min; ATP (final concentration of 80μM) was then added to the reaction mixture and incubated at room temperature for 3hr. After the reaction, 5 μL of ADP-Glo ​​was added to a 384-well plate (Grenier Inc). TM The reagent and 2.5 μL of the reaction mixture were mixed evenly, sealed with aluminum foil and incubated at room temperature in the dark for 40 min; finally, 10 μL of ADP-Glo ​​was added to each reaction well. TM Detection reagent, incubate at room temperature in the dark for 40 minutes. After all reactions are completed, the luminescence value of each well is read using an enzyme reader (Molecular Device_SpectraMax Id5) and the inhibition rate is calculated. The inhibition rate calculation formula is as follows: inhibition rate = (1-(compound group-blank group) / (negative control group-blank group)) × 100%, and according to the inhibition rate of different concentrations of compounds, the IC of the test compound is calculated in GraphPad Prism8 software 50 IC of the compound of formula I 50 The value is 0.011 μM.

[0923] Test Example 4. Experiment on the inhibition of tumor cell OVCAR3 cell proliferation by the compound of formula I

[0924] NIH:OVCAR-3 (ATCC, Cat No.HTB-161, purchased from Co-Bier) cells were seeded in T75 culture flasks and cultured in RPMI 1640 medium containing 20% ​​FBS for 3 days in preparation for subsequent culture and inoculation in 96-well plates for cell proliferation assay. OVCAR3 cells were seeded in 96-well cell plates at a density of 3000 cells / 100 μL / well, and the cell plates were placed in an incubator for 18 hours (37°C, 5% CO2). On the second day, drug treatment was started, and 100 μL / well gradient dilutions of the test compound solution (the starting concentration of each drug was 10 μM, the dilution solution was DMSO, the dilution ratio was 1:3, and each drug was diluted to nine gradient points) or DMSO (negative control) were added to the culture plate culture medium. A blank group was set up in which no cell line was inoculated and only the culture medium was added. After the addition of the drug, the culture plate was placed in an incubator for another 3 days (37°C, 5% CO2). On the fourth day, 100 μL of CellTiter-Glo (Promega G9243) reagent was added to each well, shaken for 5 minutes, and then allowed to stand at room temperature for 5 minutes. 2104) Measure the chemiluminescent signal value of each well. Cell proliferation inhibition rate = (1-(compound group-blank group) / (DMSO group-blank group)) × 100%, and use GraphPad Prism8 software to calculate the IC of the tested compound 50 IC of the compound of formula I 50 The value is 0.096μM.

[0925] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A crystalline form of a compound of formula I, characterized in that: The structure of the compound of formula I is shown below:

2. The crystalline form of the compound of formula (I) according to claim 1, characterized in that: The crystal form is the free crystal form A of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.8074, 11.3487, 15.1458, 15.4196, 16.2456, and 18.9612; further, the X-ray powder diffraction spectrum of the free crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 3.8074, 9.8108, 10.3581, 11.3487, 13 .4688, 15.1458, 15.4196, 16.2456, 16.8635, 17.3003, 18.9612, 22.6628, and 30.5503; further, the X-ray powder diffraction spectrum of the free crystalline form A represented by a diffraction angle of 2θ±0.2° is 3.8074, 9.8108, 10.3581, 11.3487, 12.7984, 13.4688, 15.1458, 15.41 96, 16.2456, 16.8635, 17.3003, 18.9612, 20.7248, 22.6628, 23.6322, 30.5503, 26.6666, 27.4293, 28.2276 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form A represented by a diffraction angle of 2θ±0.2° is 3.8074, 9.8108, 10.3581, 11.3487, 12.7984 , 13.4688, 15.1458, 15.4196, 16.2456, 16.8635, 17.3003, 18.9612, 20.7248, 22.6628, 23.6322, 24.5787, 25.7207, 26.6666, 27.4293, 28.2276, 30.5503, and 35.7206 have diffraction peaks; further, the free form A has an XRPD spectrum substantially as shown in Figure 1; Preferably, the free crystalline form A has one, two or three of the following characteristics: (1) The TGA curve of the free crystalline form A shows a weight loss of 0-2% at 150.0±3°C, preferably about 0-1% (e.g., 0.1%, 0.2%, 0.3％，0.4％，0.5％，0.6％，0.7％，0.8％)； (2) The DSC curve of free form A has two endothermic peaks at 167.9±3℃ and 180.3±3℃; (3) The DSC curve of free form A has an exothermic peak at 170.5°C ± 3°C; Preferably, the free crystalline form A has one, two or three of the following characteristics: (1) The TGA curve of free form A shows a weight loss of approximately 0.68% at 150.0±3°C; (2) The DSC curve of free form A has two endothermic peaks at 167.9±3℃ and 180.3±3℃; (3) The DSC curve of free form A has an exothermic peak at 170.5°C ± 3°C; Preferably, the TGA / DSC graph of the free crystalline form A is substantially as shown in FIG2 ; 1 The H NMR pattern is essentially as shown in Figure 3a; Preferably, the free crystalline form is an anhydrate; Or the crystal form is the free crystal form B of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7812, 18.1668, 18.5510, 19.0431, 20.2387, and 21.1776; further, the X-ray powder diffraction spectrum of the free crystal form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7812, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, Further, the X-ray powder diffraction spectrum of the free crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7812, 9.9884, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, and 21.1776; further, the X-ray powder diffraction spectrum of the free crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.2508, 9.7812, 9. 9884, 15.0024, 15.2215, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, 21.1776, 22.0900, 27.6189, 28.2642 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form B represented by a diffraction angle of 2θ±0.2° is 9.2508, 9.7812, 9.9884, 10.8644, 13.3822, 14.5151 , 15.0024, 15.2215, 16.3081, 16.7223, 17.1474, 18.1668, 18.5510, 19.0431, 19.3191, 19.7143, 20.2387, 21.1776, 22.0900, 23.0450, 23.7619, 25.7395, 27.6189, 28.2642, and 30.0557 have diffraction peaks; further, the free form B has an XRPD spectrum substantially as shown in Figure 5; Preferably, the free crystalline form B has one, two or three of the following characteristics: (1) The TGA curve of the free crystalline form B shows a weight loss of 2-6% at 120.0±3°C, preferably about 3-5% (e.g., 3.0%, 3.5%, 4.0％，4.5％)； (2) The DSC curve of free form B has three endothermic peaks at 108.5±3℃, 165.8±3℃ and 180.2±3℃; (3) The DSC curve of free form B has an exothermic peak at 167.7℃±3℃; Preferably, the free crystalline form B has one, two or three of the following characteristics: (1) The TGA curve of free form B shows a weight loss of approximately 4.35% at 120.0±3°C; (2) The DSC curve of free form B has three endothermic peaks at 108.5±3℃, 165.8±3℃ and 180.2±3℃; (3) The DSC curve of free form B has an exothermic peak at 167.7℃±3℃; Preferably, the TGA / DSC graph of the free crystalline form B is substantially as shown in FIG6 ; 1 The H NMR pattern is essentially as shown in Figure 7 a; Alternatively, the crystalline form is a free crystalline form C of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5020, 16.1724, 16.5974, 21.5887, and 25.8930; further, the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5020, 15.3140, 16.1724, 16.5974, 18.8700, 19.9398, 20.51 80, 21.0065, 21.5887, and 25.8930; further, the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5020, 10.7612, 15.3140, 16.1724, 16.5974, 18.5313, 18.8700, 19.1799, 19.9398, 20.5180, 21.0065, 21.5887, 25.8930, and 28.4921; Furthermore, the X-ray powder diffraction spectrum of the free crystalline form C represented by a diffraction angle of 2θ±0.2° is 3.1461, 8.1061, 9.1126, 9.5020, 10.7612, 11.2726, 12.2849, 13.1097, 14.2058, 14.7763, 15.3140, 16.1724, 16.5974, 17.5352, 18.5313, 18.8700, 19.1799, 19.9398, 20.5180, 2 1.0065, 21.2198, 21.5887, 22.1453, 22.7421, 23.2908, 24.1476, 24.6794, 25.4796, 25.8930, 27.4465, 28.4921, 29.8280, 30.7213, 31.4381, 32.6390, 35.3421, 36.5656, 38.4547; further, the free form C has an XRPD spectrum substantially as shown in Figure 8; Preferably, the free crystalline form C has one or two of the following characteristics: (1) The TGA curve of the free crystalline form C shows a weight loss of 1-6% at 150.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5%, 2.0％，2.5％，3.0％，3.5％，4.0％)； (2) The DSC curve of free form C has two endothermic peaks at 53.0±3℃ and 182.3±3℃; Preferably, the free crystalline form C has one or two of the following characteristics: (1) The TGA curve of free form C shows a weight loss of approximately 2.77% at 150.0±3°C; (2) The DSC curve of free form C has two endothermic peaks at 53.0±3℃ and 182.3±3℃; Preferably, the TGA / DSC graph of the free crystalline form C is substantially as shown in FIG9 ; 1 The H NMR pattern is basically shown in Figure 10; Or the crystal form is the free crystal form D of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.8461, 16.5793, 18.4363, 20.3590, 21.3940, 21.7745, and 26.5122; further, the X-ray powder diffraction spectrum of the free crystal form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.8461, 13.9909, 16.5793, 16.8857, 18.4363, 20.3590, 21.3940, 21.7745, 26.5122 has a diffraction peak; further, the free form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 13.9909, 14.9577, 16.5793, 16.8857, 18.4363, 20.1677, 20.3590, 21.3940, 21.7745, and 26.5122 has a diffraction peak; further, the free form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 10.8461, 11.8218, 13.9909, 14.9577, 16.5793, 16.8857, 18.4363, 18.7513, 18.9436, 20.1677, 20.3590, 21.3940, 21.7745, 22.2999, 23.7694, 24.2605, 24.4938, 25.2628, 26.5122, 29.7635, 30.8099 have diffraction peaks; further, the free state crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.2985, 9.4241, 10.8461, 11.8218, 12.52 67; Further, the free form D has an XRPD spectrum substantially as shown in Figure 67; Preferably, the free crystalline form D has one or more of the following characteristics: (1) The TGA curve at 120±3°C shows a weight loss of 3.0-8.0%, preferably about 4.0-7.0% (e.g., 5.0%, 5.5%, 6.0%, 6.5%), more preferably about 5.79%; (2) The DSC curve has two endothermic peaks at 53.9±3℃ and 182.9±3℃; Preferably, the TGA / DSC graph of the free crystalline form D is substantially as shown in FIG. 68 ; 1 The H NMR pattern is essentially as shown in Figure 69; Preferably, the free crystalline form D is a hydrate; Preferably, the water content of the free crystalline form D is 2.0-3.5%, preferably 2.0-3.0%; Preferably, the free crystalline form D is a monohydrate; Preferably, the free state crystalline form D has the following crystal parameters: Crystal Triclinic Space group P-1 Unit cell parameters α=95.3240(10)°, β=97.7830(10)°, γ=100.4940(10)°; Preferably, the free crystalline form D has the parameters listed in Table B3-1; Or the crystalline form is the free crystalline form E of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 17.2384, 18.3327, 19.1326, 20.5505, 21.4769, and 24.8471; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 16.7268, 17.2384, 18.3327, 19.1326, 20.5505, 21.4769, 21.8496, 24.8471; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.1459, 12.1780, 16.7268, 17.2384, 18.3327, 18.9674, 19.1326, 20.5505, 21.4769, 21.8496, and 24.8471; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.6847, 8.9272, 9.14 59, 12.1780, 12.7789, 16.7268, 17.2384, 18.1543, 18.3327, 18.9674, 19.1326, 19.8795, 20.2931, 20.5505, 21.4769, 21.8496, 24.8471, 28.5466; further, the X-ray powder diffraction spectrum of the free crystalline form E represented by a diffraction angle of 2θ±0.2° is 8.6847, 8.9272, 9.1459, 9.4934, 12.17 80, 12.7789, 15.3545, 16.7268, 17.2384, 18.1543, 18.3327, 18.9674, 19.1326, 19.8795, 20.2931, 20.5505, 21.4769, 21.8496, 22.1726, 23.0433, 24.8471, 25.6946, 26.8264, 28.5466, and 29.5968; further, the free form E has an XRPD spectrum substantially as shown in Figure 71; Preferably, the free crystalline form E has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 9-14% at 140±3°C, preferably about 10-13% (e.g., 10.5%, 11.0%, 11.5%, 12.0%, 12.5%); more preferably, about 11.97%; (2) The DSC curve has two endothermic peaks at 123.0±3℃ and 182.9±3℃; (3) The DSC curve has an exothermic peak at 148.0±3℃; Preferably, the TGA / DSC graph of the free crystalline form E is substantially as shown in FIG. 72; 1 The H NMR pattern is essentially as shown in Figure 73; Preferably, the free crystalline form E is a solvate; Preferably, the free crystalline form E is a THF solvate; Preferably, in the THF solvate of the free crystalline form E, the molar ratio of THF to the free state is 0.95:1; Or the crystal form is the free crystal form F of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.9091, 14.5589, 15.7854, 18.2249, and 18.5345; further, the X-ray powder diffraction spectrum of the free crystal form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7443, 10.9091, 14.5589, 15.7854, 17.1471, 18.2249, and 18.5345 There are diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.7443, 10.9091, 14.5589, 15.7854, 17.1471, 17.7727, 18.2249, 18.5345, and 20.2138; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.2680, 9.7443, 10.9091, 13.5597, 14 .5589, 15.7854, 17.1471, 17.7727, 18.2249, 18.5345, 20.2138, and 24.7687; further, the X-ray powder diffraction spectrum of the free crystalline form F represented by a diffraction angle of 2θ±0.2° is 7.2680, 9.7443, 10.9091, 12.6503, 13.5597, 14.5589, 15.0095, 15.7854, 17.1471, 17.7727, 18.224 9, 18.5345, 19.4299, 20.2138, 21.2140, 21.5620, 22.3451, 23.2974, 23.7177, 24.7687, 25.6111, 27.5720, 28.4674, 29.3309, 30.7039, 31.5840, 34.3936, 35.1042, 36.9389, 38.7357; Still further, the free form F has an XRPD spectrum substantially as shown in Figure 76; Preferably, the free crystalline form F has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 0.5-2.5% at 150±3°C, preferably about 0.5-2.0% (e.g., 0.5%, 1.0%, 1.5%); more preferably, about 1.19%; (2) The DSC curve has an endothermic peak at 181.1±3°C (peak temperature); Preferably, the TGA / DSC graph of the free crystalline form F is substantially as shown in FIG. 77 ; 1 The H NMR pattern is essentially as shown in Figure 78; Preferably, the free crystalline form F is an anhydrate; Alternatively, the crystalline form is the free crystalline form G of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1695, 12.2893, 18.5441, 19.4906, and 22.7762; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1695, 10.5406, 12.2893, 14.5010, 18.5441, 19.4906, and 22 .7762 has a diffraction peak; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1695, 9.2517, 9.4965, 10.5406, 12.2893, 14.5010, 18.5441, 18.8489, 19.4906, and 22.7762; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1695, 9.2517, 9.4965, 10.5406, 12.2893, 14.5010, 18.5441, 18.8489, 19.4906, and 22.7762. , 9.4965, 10.5406, 12.2893, 14.5010, 16.9986, 18.5441, 18.8489, 19.4906, 21.1520, 21.6669, 22.4742, 22.7762, and 24.7980 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form G represented by a diffraction angle of 2θ±0.2° is 6.1695, 9.2517, 9.4965, 10.2696, 10.540 6, 10.9989, 12.2893, 14.5010, 16.5003, 16.9986, 18.5441, 18.8489, 19.4906, 20.6318, 21.1520, 21.6669, 22.4742, 22.7762, 24.7980, 25.3519, 26.0012, 26.8697, 28.1782 have diffraction peaks; further, the free state crystalline form G has an XRPD spectrum substantially as shown in Figure 79; Preferably, the free crystalline form G has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 8-13% at 110±3°C, preferably about 9-11% (e.g., 9.5%, 10.0%, 10.5%, 11.0%); more preferably, about 10.40%; (2) The DSC curve has three endothermic peaks at 98.1±3℃, 154.8±3℃ and 180.8±3℃; (3) The DSC curve has an exothermic peak at 157.8±3℃; Preferably, the TGA / DSC graph of the free crystalline form G is substantially as shown in FIG80; 1 The H NMR pattern is essentially as shown in Figure 81; Preferably, the free crystalline form G is a solvate; Preferably, the free crystalline form G is a 1,4-dioxane solvate; in some embodiments, the molar ratio of 1,4-Dioxane to the free form in the solvate is 0.04 (-0.6 wt%) or 0.02 (-0.3 wt%); Or the crystal form is the free crystal form H of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form H expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 5.1382, 17.0866, 18.9850, 19.4851, 20.1891, and 21.3352; further, the X-ray powder diffraction spectrum of the free crystal form H expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 5.1382, 14.9595, 17.0866, 17.5191, 17.7454, 18.9850, 19.4851, 20. 1891, 21.3352; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° is 5.1382, 14.9595, 17.0866, 17.5191, 17.7454, 18.9850, 19.4851, 20.1891, 21.3352, 21.5416, 24.7905; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° is 5.1382, 14.9595 , 17.0866, 17.5191, 17.7454, 18.9850, 19.4851, 20.1891, 20.5085, 21.3352, 21.5416, 24.5735, 24.7905 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form H represented by a diffraction angle of 2θ±0.2° is 5.1382, 8.6958, 10.2939, 11.0299, 11.5587, 12.1517, 13.0908, 14.5022, 14.95 85a, 85b, 86.7742, 87.9143, 88.7066, 86.7243, 87.7826, 88.7647, 88.7728, 88.7647, 88.7648, 88.7649, 88.7729, 88.7647, 88.7649, 88.7647, 88.7649, 88.7649, 88.7647, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649, 88.7649 Alternatively, the crystalline form is a free crystalline form I of the compound of formula I, and the free crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5592, 17.8352, 19.3336, 19.8678, 20.1554, and 27.1065; further, the free crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5592, 12.8988 , 17.8352, 19.3336, 19.8678, 20.1554, and 27.1065; further, the X-ray powder diffraction spectrum of the free crystalline form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5592, 12.8988, 17.8352, 19.3336, 19.8678, 20.1554, 20.9976, and 27.1065; further The X-ray powder diffraction spectrum of the free crystalline form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5592, 12.8988, 17.8352, 18.1790, 19.3336, 19.8678, 20.1554, 20.7214, 20.9976, 27.1065, and 28.0012; further, the X-ray powder diffraction spectrum of the free crystalline form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5592, 12.8988, 17.8352, 18.1790, 19.3336, 19.8678, 20.1554, 20.7214, 20.9976, 27.1065, and 28.0012. The X-ray powder diffraction spectrum has diffraction peaks at 9.5592, 12.8988, 14.7994, 15.8059, 17.8352, 18.1790, 19.3336, 19.8678, 20.1554, 20.7214, 20.9976, 23.2310, 27.1065, and 28.0012; further, the free form I has an XRPD spectrum substantially as shown in Figure 86; Preferably, the free crystalline form I has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 2-7% at 120±3°C, preferably about 3-6% (e.g., 3.5%, 4.0%, 4.5%); (2) The DSC curve has three endothermic peaks at 54.6±3℃, 168.0±3℃ and 181.2±3℃; (3) The DSC curve has an exothermic peak at 170.5±3℃; Preferably, the TGA / DSC graph of the free crystalline form I is substantially as shown in FIG. 87; 1 The H NMR pattern is essentially as shown in Figure 88; Preferably, the free crystalline form I is a hydrate; Or the crystalline form is the free crystalline form J of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystalline form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 20.9755, 21.5744, and 25.8914; further, the free crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 18.8695, 20.5033, 2 0.9755, 21.5744, 25.8914; further, the X-ray powder diffraction spectrum of the free state crystalline form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.4887, 10.7503, 15.3049, 16.1644, 16.5855, 18.5225, 18.8695, 19.9313, 20.5033, 20.9755, 21.5744, 25.8914; further, the X-ray powder diffraction spectrum of the free state crystalline form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.4887, 10. 7503, 12.2600, 13.0965, 14.1913, 15.3049, 16.1644, 16.5855, 18.5225, 18.8695, 19.1552, 19.9313, 20.5033, 20.9755, 21.5744, 22.1570, 23.2764, 25.8914, 28.4642 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free form J represented by a diffraction angle of 2θ±0.2° is 9.4887, 10.7503, 12.2600, 13.096 5. There are diffraction peaks at 14.1913, 15.3049, 16.1644, 16.5855, 17.5096, 18.5225, 18.8695, 19.1552, 19.9313, 20.5033, 20.9755, 21.5744, 22.1570, 23.2764, 24.1115, 24.6829, 25.8914, 27.1763, 28.4642, 29.7254, 30.7261, and 32.6167; further, the free state crystalline form J has an XRPD spectrum substantially as shown in Figure 90; Preferably, the free crystalline form J has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 0.5-2.5% at 150±3°C, preferably about 0.5-1.5% (e.g., 0.5%, 1.0%, 1.5%); more preferably, about 1.09%; (2) The DSC curve has an endothermic peak at 181.5±3℃; Preferably, the TGA / DSC graph of the free state crystalline form J is substantially as shown in FIG. 91 ; 1 The H NMR pattern is essentially as shown in Figure 92; Preferably, the free crystalline form J is an anhydrate; Or the crystal form is the free form K of the compound of formula I, and the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 15.0722, 18.7484, 19.0653, 19.7672, 20.4112, and 20.9312; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.8469, 15.0722, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1 881; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is at 9.8469, 10.1208, 15.0722, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1881, 21.6963, and 28.3413; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is at 9.8469, 10.1208, 14.6920, 15 .0722, 15.4155, 16.0745, 16.7829, 17.6356, 18.1386, 18.7484, 19.0653, 19.2235, 19.4283, 19.7672, 20.4112, 20.9312, 21.1881, 21.6963, 24.0591, 28.3413, 28.6573, and 30.5394 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free form K represented by a diffraction angle of 2θ±0.2° is 9.3256, 9.8469, 10.1208, 13 94, 9.0647, 9.2066, 9.2714, 9.2770, 9.4136, 9.2913, 9.8137, 9.7066, 9.2611, 9.2612, 9.8136, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066, 9.2613, 9.8137, 9.7066 Preferably, the free crystalline form K has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 6-11% at 150±3°C, preferably about 7-10% (e.g., 7.0%, 7.5%, 8.0%, 8.5%, 9.0%); more preferably, about 8.24%; (2) The DSC curve has three endothermic peaks at 72.0±3℃, 165.2±3℃, and 180.2±3℃; (3) The DSC curve has an exothermic peak at 167.1±3°; Preferably, the TGA / DSC graph of the free crystalline form K is substantially as shown in FIG. 95 ; 1 The H NMR pattern is substantially as shown in Figure 96; Preferably, the free crystalline form K is a solvate; Preferably, the free crystalline form K is an EtOH solvate or a cosolvate of EtOH and water; Preferably, in the solvate, the molar ratio of EtOH to the free state is 0.27; Or the crystal form is the free crystal form L of the compound of formula I, and the X-ray powder diffraction spectrum of the free crystal form L expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8304, 15.8341, 17.7145, 19.1795, 20.5748, and 25.5115; further, the X-ray powder diffraction spectrum of the free crystal form L expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8304, 15.8341, 17.7145, 19.1795, 20.5748, and 25.5115. 0943, 20.5748, 25.5115 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8304, 15.8341, 17.7145, 19.1795, 20.0943, 20.5748, 22.4409, 25.5115; further, the X-ray powder diffraction spectrum of the free crystalline form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8304 , 11.1727, 15.8341, 16.8550, 17.1190, 17.7145, 19.1795, 19.7076, 20.0943, 20.5748, 22.4409, and 25.5115 have diffraction peaks; further, the X-ray powder diffraction spectrum of the free crystalline form L represented by a diffraction angle of 2θ±0.2° is 8.8304, 9.6805, 10.2446, 10.7612, 11.1727, 14.59 9945, there are diffraction peaks at 73, 15.5971, 15.8341, 16.8550, 17.1190, 17.7145, 18.2884, 19.1795, 19.7076, 20.0943, 20.5748, 22.4409, 25.5115, 28.7935, 29.8794, 31.2614, 32.0233, and 35.9945; further, the free form L has an XRPD spectrum substantially as shown in Figure 99b.

3. A pharmaceutically acceptable salt of a compound of formula I or a crystalline form thereof, characterized in that: The pharmaceutically acceptable salt is selected from the salt formed by the compound of formula I and an acid, and the acid can be selected from an inorganic acid or an organic acid; Wherein, the structure of the compound of formula I is shown below: Preferably, the pharmaceutically acceptable salt of the compound of formula I is selected from the group consisting of hydrochloride, sulfate, maleate, phosphate, p-toluenesulfonate, methanesulfonate, ethanesulfonate, L-aspartate, fumarate, and tartrate of the compound of formula I; Preferably, the pharmaceutically acceptable salt of the compound of formula I is the hydrochloride, sulfate, maleate, phosphate, p-toluenesulfonate, methanesulfonate, ethanesulfonate of the compound of formula I; Preferably, when the compound of formula I forms a salt with an acid, the molar ratio of the acid to the compound of formula I can be 5:1 to 1:5, for example, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:

5.

4. A pharmaceutically acceptable salt of a compound of formula I or a crystalline form thereof according to claim 3, characterized in that: The crystal form is a hydrochloride crystal form of the compound of formula I. Preferably, the crystal form is a hydrochloride crystal form A of the compound of formula I. The X-ray powder diffraction spectrum of the hydrochloride crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 18.8832, 19.5324, 20.1382, 21.3379, and 21.7432; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 14.7835, 14.9893, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 21.3379, and 21.7432 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.1755, 14.7835, 14.9893, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 20.9418, 21.3379, 21.7432, 25.7379, 27.2284, and 29.8240; further In the step, the X-ray powder diffraction spectrum of the hydrochloride form A represented by a diffraction angle of 2θ±0.2° is 6.6910, 9.4043, 10.1755, 11.3549, 12.0715, 12.7466, 13.3874, 14.1825, 14.7835, 14.9893, 17.2365, 18.2960, 18.8832, 19.3310, 19.5324, 20.1382, 20.9418, 21.3379, 21.7432, 22.5426, 23.5259, 24.0002, 25.3951, 25.7379, 26.6858, 27.2284, 27.7725, 28.5839, 29.1003, 29.8240, 30.7557, 31.8138, 33.7066, 34.5682, 35.3206, 36.1697, 37.1954, 38.5831, 39.2520 have diffraction peaks; further, the hydrochloride salt form A has an XRPD spectrum substantially as shown in Figure 12a or Figure 12b; Preferably, the hydrochloride salt form A has one or two of the following characteristics: (1) The TGA curve of hydrochloride crystal form A shows a weight loss of 4-12% at 160.0±3°C, preferably about 6-10% (e.g., 6.0%, 6.5％，7.0％，7.5％，8.0％，8.5％，9.0％，9.5％)； (2) The DSC curve of hydrochloride form A has an endothermic peak at 165.8±3°C; In some embodiments, the hydrochloride salt form A has one or two of the following characteristics: (1) The TGA curve of hydrochloride form A shows a weight loss of 8.21% at 160.0±3°C; (2) The DSC curve of hydrochloride form A has an endothermic peak at 165.8±3°C; Preferably, the TGA / DSC diagram of the hydrochloride salt form A is substantially as shown in FIG13; 1 The H NMR pattern is essentially as shown in Figure 14 ; Preferably, the crystalline form is a hydrochloride crystalline form B of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.8284, 12.9418, 15.8305, 17.4248, 17.7208, and 25.1539; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.8284, 12.9418, 15.6394, 15.8305, 16.6807, 17.4248, 17.7208, and 20.386 0, 21.1241, 24.6834, 25.1539 have diffraction peaks; further, the hydrochloride crystal form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.8284, 12.9418, 15.6394, 15.8305, 16.6807, 17.4248, 17.7208, 20.3860, 21.1241, 24.6834, 25.1539; further, the hydrochloride crystal form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.828 4, 12.0258, 12.9418, 14.5910, 15.6394, 15.8305, 16.6807, 17.4248, 17.7208, 18.9434, 19.3954, 19.8130, 20.3860, 21.1241, 24.6834, 25.1539 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form B represented by a diffraction angle of 2θ±0.2° is 5.8284, 10.2084, 12.0258, 12.9418, 14.5910, 15.6394, 15.8305, 16.6807, 17.0761, 17.4248, 17.7208, 18.9434, 19.3954, 19.8130, 20.3860, 21.1241, 23.0260, 23.5341, 24.6834, 25.1539, 26.7017, 27.1748, 28.3119, 29.2775, 30.8075, 34.0826 have diffraction peaks; further, the hydrochloride salt form B has an XRPD spectrum substantially as shown in Figure 15; Preferably, the hydrochloride salt form B has one or two of the following characteristics: (1) The TGA curve of the hydrochloride salt form B shows a weight loss of 10-20% at 180.0±3°C, preferably about 12-18% (e.g., 12.0%, 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, 15.0%, 15.5%, 16.0%, 16.5%, 17.0%, 17.5%, 18.0％)； (2) The DSC curve of hydrochloride form B has two endothermic peaks at 154.1±3℃ and 171.0±3℃; Preferably, the hydrochloride salt form B has one or two of the following characteristics: (1) The TGA curve of hydrochloride form B showed a weight loss of 16.61% at 180.0±3°C; (2) The DSC curve of hydrochloride form B has two endothermic peaks at 154.1±3℃ and 171.0±3℃; Preferably, the TGA / DSC diagram of the hydrochloride salt form B is substantially as shown in FIG. 16 ; 1 The H NMR pattern is essentially as shown in Figure 17 ; Preferably, the crystalline form is a hydrochloride crystalline form C of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6027, 5.7758, 13.6699, 14.4660, 21.6765, 23.2062, and 27.1991; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6027, 5.7758, 13.6699, 14.4660, 17.1465, 18.7028, 21.6765, 23.2062, and 27.1 991; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6027, 5.7758, 13.2815, 13.6699, 13.8622, 14.4660, 17.1465, 18.7028, 21.6765, 23.2062, and 27.1991; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6027, 5.7758, 8.7367, 11.1522, 13.2815, 13. 6699, 13.8622, 14.4660, 16.6600, 17.1465, 18.7028, 19.4828, 20.9473, 21.6765, 22.4844, 23.2062, 26.3673, and 27.1991 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form C represented by a diffraction angle of 2θ±0.2° is 5.6027, 5.7758, 8.7367, 9.2140, 11.1522, 11.8436, 13.2815, 13.6699, 13.8622, 14.4 19.692, 18.7028, 19.4828, 20.0737, 20.3774, 20.9473, 21.6765, 22.0633, 22.4844, 23.2062, 24.0140, 24.9698, 25.8392, 26.3673, 27.1991, 28.0148, 29.1691, and 37.7780; further, the hydrochloride salt form C has an XRPD spectrum substantially as shown in Figure 18; Preferably, the hydrochloride salt form C has one, two or three of the following characteristics: (1) The TGA curve of hydrochloride crystal form C shows a weight loss of 2-10% at 90.0±3°C, preferably about 3-6% (e.g., 3.0%, 3.5%, 4.0％，4.5％，5.0％，5.5％，6.0％)； (2) The TGA curve of hydrochloride crystal form C shows a weight loss of 2-10% at 170.0±3°C, preferably about 5-8% (e.g., 5.0%, 5.5%, 6.0％，6.5％，7.0％，7.5％，8.0％)； (3) The DSC curve of hydrochloride form C has two endothermic peaks at 77.8±3℃ and 174.6±3℃; Preferably, the hydrochloride salt form C has one, two or three of the following characteristics: (1) The TGA curve of hydrochloride form C shows a weight loss of 4.67% at 90.0±3°C; (2) The TGA curve of hydrochloride form C shows a weight loss of 6.00% at 170.0±3°C; (3) The DSC curve of hydrochloride form C has two endothermic peaks at 77.8±3℃ and 174.6±3℃; Preferably, the TGA / DSC diagram of the hydrochloride salt form C is substantially as shown in FIG. 19 ; 1 The H NMR pattern is essentially as shown in Figure 20; Preferably, the crystalline form is a hydrochloride crystalline form D of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2274; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5782, 11.865 5, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2274; further, the X-ray powder diffraction spectrum of the hydrochloride form D represented by a diffraction angle of 2θ±0.2° is 6.5782, 9.9619, 11.8655, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, and 21.2 274; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form D represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5782, 9.9619, 11.1481, 11.8655, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, 21.2274, and 26.6683; still further, the hydrochloride crystal form D represented by a diffraction angle of 2θ±0. The X-ray powder diffraction spectrum represented by a diffraction angle of 2° has diffraction peaks at 6.5782, 9.9619, 11.1481, 11.8655, 12.8040, 14.4539, 14.6720, 18.0560, 18.7688, 20.3323, 21.2274, 26.6683, and 29.0358; further, the hydrochloride salt form D has an XRPD spectrum substantially as shown in Figure 107; Preferably, the crystalline form is a hydrochloride crystalline form E of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.9750, 12.8980, 15.2093, 15.6063, 17.9714, and 25.4838; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.9750, 12.8980, 15.2093, 15.6063, 17.971 4, 24.9674, and 25.4838; further, the X-ray powder diffraction spectrum of the hydrochloride form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.9750, 12.8980, 15.0507, 15.2093, 15.6063, 17.8054, 17.9714, 24.9674, and 25.4838; further, the X-ray powder diffraction spectrum of the hydrochloride form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.975 0, 12.8980, 15.0507, 15.2093, 15.6063, 16.0284, 17.8054, 17.9714, 19.8405, 20.5435, 22.5488, 24.9674, 25.4838, 26.1257 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form E represented by a diffraction angle of 2θ±0.2° is 5.9750, 12.8980, 13.7925, 15.0507, 15.2093, 15.6063, 16.0284, 17.8054, 17.9714, 18.9298, 19.8405, 20.5435, 21.0218, 21.9935, 22.5488, 24.9674, 25.4838, 26.1257, 27.4268, 29.8322, 30.4635, 31.7533; further, the hydrochloride salt form E has an XRPD spectrum substantially as shown in Figure 110; Preferably, the crystalline form is the hydrochloride crystalline form F of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0385, 15.9019, 18.1478, 20.5749, and 25.4190; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0385, 12.6362, 15.9019, 17.1363, 18.1478, 20.5749, and 25.4190; more Further, the X-ray powder diffraction spectrum of the hydrochloride form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0385, 12.6362, 13.0399, 15.9019, 17.1363, 18.1478, 18.8427, 20.5749, 21.8092, and 25.4190; further, the X-ray powder diffraction spectrum of the hydrochloride form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0385, 12.6362, 13.0399, 15.9019, 17.1363, 18.1478, 18.8427, 20.5749, 21.8092, and 25.4190. 2, 17.1363, 18.1478, 18.4776, 18.8427, 19.3354, 20.5749, 21.3694, 21.8092, 25.1076, and 25.4190 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form F represented by a diffraction angle of 2θ±0.2° is 6.0385, 12.0772, 12.6362, 13.0399, 13.5971, 14.9525, 15.9019, 16.8142, 17.1363, There are diffraction peaks at 18.1478, 18.4776, 18.8427, 19.3354, 20.5749, 21.3694, 21.8092, 23.2223, 25.1076, 25.4190, 27.1737, 27.8200, 28.2136, 28.9299, 29.9049, 31.9291, 34.1705, 35.2232, 36.7164, and 39.1368; further, the hydrochloride salt form F has an XRPD spectrum substantially as shown in Figure 111; Preferably, the crystalline form is the hydrochloride crystalline form G of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.4719, 18.6112, 19.0898, 20.7520, and 24.9637; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5684, 9.47 19, 15.5605, 18.6112, 19.0898, 20.7520, 24.9637 have diffraction peaks; further, the hydrochloride crystal form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5684, 7.0798, 9.4719, 15.5605, 18.6112, 19.0898, 20.7520, 24.9637 diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5684, 7.0798, 9.4719, 15.5605, 18.6112, 19.0898, 20.7520, 22.1933, 24.9637, and 28.7471; still further, the hydrochloride crystal form G has a diffraction peak at 2θ±0.2°. The X-ray powder diffraction spectrum represented by the incident angle has diffraction peaks at 6.5684, 7.0798, 9.4719, 13.6772, 14.4725, 15.5605, 18.6112, 19.0898, 20.7520, 22.1933, 24.9637, and 28.7471; further, the hydrochloride salt form G has an XRPD spectrum substantially as shown in Figure 106b; Preferably, the crystalline form is a hydrochloride crystalline form H of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 12.9273, 15.1559, 15.5659, 17.6473, 18.2972, 19.4651, 19.7972, and 20.4603; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 12.9273, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 19.4651, 19.7972, 20.4603, 20.71 47; further, the X-ray powder diffraction spectrum of the hydrochloride form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 12.4381, 12.9273, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147; further, the X-ray powder diffraction spectrum of the hydrochloride form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 8.4236, 10.0644, 10.4677, 12.0841, 12.4381 , 12.9273, 13.5430, 15.1559, 15.5659, 16.8381, 17.6473, 18.2972, 18.7344, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147, 20.9217, 21.5046, 21.7941, 22.4391, 22.7460, 23.8221, 25.3590, 27.6629; further, the X-ray powder diffraction spectrum of the hydrochloride salt form H represented by a diffraction angle of 2θ±0.2° is 7.5428, 8.4236, 10.0644, 10. 4677, 12.0841, 12.4381, 12.9273, 13.5430, 15.1559, 15.5659, 16.2484, 16.8381, 17.6473, 18.2972, 18.7344, 19.1721, 19.4651, 19.7972, 20.4603, 20.7147, 20.9217, 21.5046, 21.7941, 22.4391, 22.7460, 23.8221, 25.3590, 25.9795, 26.4453, 27.1720, 27.6629, 28.6111, 29.0095, 30.There is a diffraction peak at 6017; further, the hydrochloride salt form H has an XRPD spectrum substantially as shown in Figure 106c;. Preferably, the hydrochloride salt form H has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 5-10% at 170±3°C, preferably about 6-9% (e.g., 7.0%, 7.5%, 8.0%); more preferably, about 7.61%; (2) The DSC curve has two endothermic peaks at 155.5°C and 191.5°C; Preferably, the TGA / DSC diagram of the hydrochloride salt form H is substantially as shown in FIG. 108 ; 1 The H NMR pattern is essentially as shown in Figure 109; Preferably, the crystalline form is a hydrochloride crystalline form I of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2065, 7.0236, 13.8915, 14.6038, 20.8063, 21.1874, and 24.9901; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2065, 7.0236, 13.8915, 14.6038, 20.8063, 21.1874, and 24.9901. 3.8915, 14.6038, 17.7770, 20.8063, 21.1874, and 24.9901 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form I represented by a diffraction angle of 2θ±0.2° is 6.2065, 7.0236, 13.8915, 14.6038, 15.6403, 17.7770, 20.8063, 21.1874, 24.9901, 25.488 3; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.2065, 7.0236, 11.6337, 13.8915, 14.6038, 15.6403, 17.7770, 19.2571, 20.8063, 21.1874, 24.9901, and 25.4883; further, the hydrochloride crystal form I has a diffraction peak at 2θ±0.2 The X-ray powder diffraction spectrum represented by the diffraction angle of 1.447° has diffraction peaks at 6.2065, 7.0236, 11.6337, 13.8915, 14.6038, 15.6403, 17.0255, 17.7770, 19.2571, 20.8063, 21.1874, 23.6537, 24.9901, and 25.4883; further, the hydrochloride salt form I has an XRPD spectrum substantially as shown in Figure 106d; Preferably, the crystalline form is the hydrochloride crystalline form J of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.3031, 15.0739, 18.8389, 19.8236, 20.0800, and 21.4914; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.3031, 15.0739, 18.5121, 18.8389, 19.8236, 20.0800, 21.4914, and 22.0336; further, the The X-ray powder diffraction spectrum of the hydrochloride salt form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.3031, 12.9670, 15.0739, 18.5121, 18.8389, 19.8236, 20.0800, 21.4914, 21.7526, 22.0336, and 22.2164; further, the X-ray powder diffraction spectrum of the hydrochloride salt form J represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.7191, 9.4898, 10.3031, 11.5598, 12.9670, 13.7721, 14.2248, 15.07 39, 17.8940, 18.5121, 18.8389, 19.5450, 19.8236, 20.0800, 21.0834, 21.4914, 21.7526, 22.0336, 22.2164, 22.5454, 25.6500, 26.1804, 27.4986, and 30.2463 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form J represented by a diffraction angle of 2θ±0.2° is 6.7191, 9.4898, 10.3031, 11.5598, 12.9670, 13.7721, 1 106e, 10740, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820, 10840, 10820 Preferably, the crystalline form is a hydrochloride crystalline form K of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 11.2365, 12.9493, 15.6381, 20.5819, and 25.3451; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 11.2365, 12.9493, 15.6381, 20.5819, and 25.3451. 1, 18.5078, 20.5819, 25.3451; further, the X-ray powder diffraction spectrum of the hydrochloride crystal form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 11.2365, 12.9493, 15.6381, 17.8017, 18.5078, 20.5819, 25.3451, 26.0590, 26.3085; further, the hydrochloride crystal form K represented by a diffraction angle of 2θ±0. The X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 7.6126, 11.2365, 12.9493, 13.9646, 15.6381, 17.8017, 18.5078, 19.8165, 20.5819, 25.3451, 26.0590, and 26.3085; further, the X-ray powder diffraction spectrum represented by the hydrochloride salt form K at a diffraction angle of 2θ±0.2° has diffraction peaks at 6.1719, 7.6126, 11.2365, 12.9493, 13.9646, 15.6381, 17.8017, 18.5078, 19.8165, 20.5819, 25.3451, 26.0590, and 26.3085. .6126, 11.2365, 12.9493, 13.9646, 15.6381, 16.6189, 17.1911, 17.8017, 18.5078, 19.8165, 20.5819, 21.7916, 22.5977, 25.3451, 26.0590, 26.3085, and 30.7181; further, the hydrochloride salt form K has an XRPD spectrum substantially as shown in Figure 106f; Preferably, the crystalline form is a hydrochloride crystalline form L of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.7752, 13.8951, 17.1547, 21.4837, and 24.0925; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.7752, 13.8951, 15.3025, 17.1547, 17.8681, 21 .4837, 24.0925, and 26.5641 have diffraction peaks; further, the X-ray powder diffraction spectrum of the hydrochloride form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.7752, 13.8951, 15.3025, 17.1547, 17.8681, 21.4837, 23.4738, 24.0925, and 26.5641; further, the X-ray powder diffraction spectrum of the hydrochloride form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.7752, 13.8951, 15.3025, 17.1547, 17.8681, 21.4837, 23.4738, 24.0925, and 26.5641. The figure has diffraction peaks at 7.7752, 10.4411, 13.8951, 15.3025, 16.3403, 17.1547, 17.8681, 19.2621, 21.4837, 23.4738, 24.0925, 25.5726, 26.5641, 28.1186, and 30.8899; further, the X-ray powder diffraction spectrum of the hydrochloride form L represented by a diffraction angle of 2θ±0.2° is 7.7752, 10.44 11, 13.2333, 13.8951, 15.3025, 16.3403, 17.1547, 17.8681, 19.2621, 19.9563, 21.4837, 22.4156, 23.4738, 24.0925, 25.5726, 26.5641, 28.1186, 30.8899, 38.4894 have diffraction peaks; further, the hydrochloride salt form L has an XRPD spectrum substantially as shown in Figure 106g; Preferably, the crystalline form is a hydrochloride crystalline form M of the compound of formula I, and the X-ray powder diffraction spectrum of the hydrochloride crystalline form M represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.8040, 14.8344, 18.8157, 19.2503, 20.6275, and 21.0461; further, the X-ray powder diffraction spectrum of the hydrochloride crystalline form M represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.5546, 9.8040, 14.8344, 18.8157, The hydrochloride salt form M has diffraction peaks at 6.5546, 9.8040, 12.0038, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, and 21.0461; further, the hydrochloride salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° and ... The X-ray powder diffraction spectrum represented by the hydrochloride salt form M has diffraction peaks at 6.5546, 9.8040, 10.8235, 12.0038, 13.1333, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461, 26.8393, and 28.6992; further, the X-ray powder diffraction spectrum represented by the hydrochloride salt form M at a diffraction angle of 2θ±0.2° is 6.5546 , 9.8040, 10.8235, 12.0038, 13.1333, 14.2374, 14.8344, 17.8676, 18.8157, 19.2503, 20.6275, 21.0461, 22.8294, 24.8213, 26.8393, 28.6992, 29.5703, and 33.9685; further, the hydrochloride salt form M has an XRPD spectrum substantially as shown in Figure 106h.

5. The pharmaceutically acceptable salt of the compound of formula I or its crystalline form according to claim 3, characterized in that: The crystal form is a sulfate crystal form of the compound of formula I. Preferably, the crystal form is sulfate crystal form A of the compound of formula I. The sulfate crystal form A has diffraction peaks at 6.5297, 7.4156, 11.2590, 17.2920, and 19.5870 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the sulfate crystal form A has diffraction peaks at 6.5297, 7.4156, 11.2590, 17.2920, 18.3831, 18. 9056, 19.5870, 23.1076, and 25.1201 have diffraction peaks; further, the sulfate crystal form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5297, 7.4156, 11.2590, 17.2920, 18.3831, 18.9056, 19.5870, 19.8280, 23.1076, and 25.1201; further, the sulfate crystal form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.5297, 7.4156, 11.2590, 14.8207, 15.0692, 17.2920, 17.5479, 18.3831, 18.9056, 19.5870, 19.8280, 21.1050, 23.1076, 23.6024, 25.1201; further, the X-ray powder diffraction spectrum of the sulfate crystal form A expressed at a diffraction angle of 2θ±0.2° is 6.5297, 7.4156, 9.8272, 11.2590, 11. 29.8446, and 32.6299; further, the sulfate salt form A has an XRPD spectrum substantially as shown in FIG22; Preferably, the sulfate crystal form A has one or two of the following characteristics: (1) The TGA curve of sulfate crystal form A shows a weight loss of 2-10% at 150.0±3°C, preferably about 4-7% (e.g., 4.0%, 4.5%, 5.0％，5.5％，6.0％，6.5％，7.0％)； (2) The DSC curve of sulfate form A has two endothermic peaks at 52.9±3℃ and 167.1±3℃; Preferably, the sulfate crystal form A has one or two of the following characteristics: (1) The TGA curve of sulfate form A shows a weight loss of 5.78% at 150.0±3°C; (2) The DSC curve of sulfate form A has two endothermic peaks at 52.9±3℃ and 167.1±3℃; Preferably, the TGA / DSC graph of the sulfate salt crystal form A is substantially as shown in FIG. 23; 1 The H NMR pattern is essentially as shown in Figure 24; Preferably, the crystal form is a sulfate crystal form B of the compound of formula I, and the sulfate crystal form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8491, 16.5561, 17.1270, 17.8255, and 19.6977; further, the sulfate crystal form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8491, 16.5561, 17.1270, 17.8255, and 18 .1372, 19.6977, 19.0468, 22.6654, and 26.1622; further, the X-ray powder diffraction spectrum of the sulfate crystal form B represented by a diffraction angle of 2θ±0.2° is 6.3375, 9.8491, 13.0250, 16.5561, 17.1270, 17.8255, 18.1372, 19.6977, 19.0468, 22.2378, 22.6654, 25 .7586, 26.1622, and 29.7168; further, the X-ray powder diffraction spectrum of the sulfate crystal form B represented by a diffraction angle of 2θ±0.2° is 6.3375, 8.6916, 9.1864, 9.8491, 11.7001, 12.1619, 13.0250, 14.4700, 15.1807, 16.5561, 17.1270, 17.8255, 18.1372, 19. 0468, 19.6977, 21.6775, 22.2378, 22.6654, 23.4512, 23.8100, 24.8186, 25.4720, 25.7586, 26.1622, 27.1217, 29.0464, 29.7168, 30.9706, 33.1687, and 34.5562; further, the sulfate salt form B has an XRPD spectrum substantially as shown in Figure 25; Preferably, the sulfate crystal form B has one or two of the following characteristics: (1) The TGA curve of sulfate crystal form B shows a weight loss of 0-5% at 150.0±3°C, preferably about 1-3% (e.g., 1.0%, 1.5%, 2.0％，2.5％，3.0％)； (2) The DSC curve of sulfate form B has two endothermic peaks at 69.7±3℃ and 238.5±3℃; Preferably, the sulfate crystal form B has one or two of the following characteristics: (1) The TGA curve of sulfate form B shows a weight loss of 1.16% at 150.0±3°C; (2) The DSC curve of sulfate form B has two endothermic peaks at 69.7±3℃ and 238.5±3℃; Preferably, the TGA / DSC graph of the sulfate crystal form B is substantially as shown in FIG. 26 ; 1 The H NMR pattern is essentially as shown in Figure 27; Preferably, the crystal form is a sulfate crystal form C of the compound of formula I, and the sulfate crystal form C has diffraction peaks at 8.9487, 17.5523, 17.9120, 19.9597, and 22.9905 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the sulfate crystal form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.9487, 9.8314, 14.4549, 17.5523, 17.9120, 18.7584, 19.5850, 19.9597 , 20.9974, 22.4850, 22.9905, 24.5952, and 29.4160; further, the X-ray powder diffraction spectrum of the sulfate crystal form C represented by a diffraction angle of 2θ±0.2° is 8.9487, 9.8314, 12.2693, 14.4549, 17.5523, 17.9120, 18.7584, 19.5850, 19.9597, 20.6152, 20.9974, 21.9335, 22.4850, 22.9905, 23. 6939, 23.9937, 24.5952, 26.7497, and 29.4160; further, the X-ray powder diffraction spectrum of the sulfate crystal form C represented by a diffraction angle of 2θ±0.2° is 7.4762, 8.0099, 8.9487, 9.8314, 11.7697, 12.2693, 13.3788, 14.4549, 14.9774, 15.3199, 16.8293, 17.5523, 17.9120, 18.7584, 19.5850, There are diffraction peaks at 19.9597, 20.6152, 20.9974, 21.9335, 22.4850, 22.9905, 23.6939, 23.9937, 24.5952, 24.8904, 25.3759, 26.2847, 26.7497, 28.4461, 29.4160, 31.7091, 33.4595, 34.8478, 36.5099, and 38.0959; further, the sulfate salt form C has an XRPD spectrum substantially as shown in Figure 28; Preferably, the sulfate crystal form C has one, two or three of the following characteristics: (1) The TGA curve of sulfate crystal form C shows a weight loss of 1-5% at 100.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5%, 2.0％，2.5％，3.0％，3.5％，4.0％)； (2) The DSC curve of sulfate form C has four endothermic peaks at 92.4±3℃, 159.3±3℃, 184.8±3℃ and 216.8±3℃; (3) The DSC curve of sulfate form C has an exothermic peak at 224.0±3℃; In some embodiments, the sulfate salt crystalline form C has one, two or three of the following characteristics: (1) The TGA curve of sulfate crystal form C shows a weight loss of 2.83% at 100.0±3℃; (2) The DSC curve of sulfate form C has four endothermic peaks at 92.4±3℃, 159.3±3℃, 184.8±3℃ and 216.8±3℃; (3) The DSC curve of sulfate form C has an exothermic peak at 224.0±3℃; In some embodiments, the TGA / DSC graph of the sulfate salt crystalline form C is substantially as shown in FIG. 29; 1 The HNMR chart is shown in FIG30 .

6. The pharmaceutically acceptable salt of the compound of formula I or its crystalline form according to claim 3, characterized in that: The crystalline form is a maleate crystalline form A of the compound of formula I, and the maleate crystalline form A has diffraction peaks at 13.7865, 16.3294, 18.2795, 20.3336, and 20.8824 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the maleate crystalline form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 13.7865, 15.9646, 16.3294, 18.2795, 20.3336, 20.8824, 2 1.3104, 21.5283, 23.1978, and 24.1136 have diffraction peaks; further, the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 10.4550, 13.7865, 15.9646, 16.3294, 17.7554, 18.2795, 20.3336, 20.8824, 21.3104, 21.5283, 23.1978, 24.1136, and 24.7430; further Further, the maleate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.4318, 8.1664, 10.4550, 11.4963, 13.7865, 14.9748, 15.6098, 15.9646, 16.3294, 17.2388, 17.7554, 18.2795, 18.7232, 19.2252, 19.9626, 20.3336, 20.8824, 21.3104, 21.5283, 21.82 37.8027; further, the maleate salt form A has an XRPD spectrum substantially as shown in Figure 31; Preferably, the maleate salt form A has one or two of the following characteristics: (1) The TGA curve of maleate crystalline form A shows a weight loss of 0-4% at 130.0±3°C, preferably about 0-3% (e.g., 0.5%, 1.0％，1.5％，2.0％，2.5％，3.0％)； (2) The DSC curve of maleate salt form A has an endothermic peak at 142.1±3℃; Preferably, the maleate salt form A has one or two of the following characteristics: (1) The TGA curve of maleate form A shows a weight loss of 0.42% at 130.0±3°C; (2) The DSC curve of maleate salt form A has an endothermic peak at 142.1±3℃; Preferably, the TGA / DSC graph of the maleate salt form A is substantially as shown in FIG. 32 ; 1 The HNMR chart is shown in Figure 33.

7. A pharmaceutically acceptable salt of a compound of formula I or a crystalline form thereof according to claim 3, characterized in that: The crystal form is a phosphate crystal form A of the compound of formula I, and the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.3607, 17.8932, 19.3716, 19.8946, 20.5448, 21.1372, and 22.4294; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.8155, 9.3607, 17.8932, 18.4384, 19.3716, 19.8946, 20.5448, 21.1372, 22.4294, 24.5486 have diffraction peaks; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° is 8.8155, 9.3607, 11.1767, 16.4840, 17.8932, 18.4384, 19.3716, 1 9.8946, 20.5448, 21.1372, 22.4294, 23.1105, 23.9976, 24.5486, 24.5486, 25.7922, and 26.3981; further, the X-ray powder diffraction spectrum of the phosphate crystal form A represented by a diffraction angle of 2θ±0.2° is 3.2059, 8.8155, 9.3607, 11.1767, 13.9605, 16 .4840, 17.8932, 18.4384, 19.3716, 19.8946, 20.5448, 21.1372, 22.4294, 23.1105, 23.9976, 24.5486, 25.7922, 26.3981, 26.9789, 28.2812, and 30.2804; further, the phosphate crystal form A has an XRPD spectrum substantially as shown in Figure 34; Preferably, the phosphate crystal form A has one, two or three of the following characteristics: (1) The TGA curve of the phosphate crystal form A shows a weight loss of 1-6% at 150.0±3°C, preferably about 2-5% (e.g., 2.0%, 2.5%, 3.0％，3.5％，4.0％，4.5％，5.0％)； (2) The DSC curve of phosphate form A has two endothermic peaks at 41.5±3℃ and 169.6±3℃; (3) The DSC curve of phosphate form A has an exothermic peak at 91.8℃±3℃; Preferably, the phosphate crystal form A has one, two or three of the following characteristics: (1) The TGA curve of phosphate form A shows a weight loss of 3.71% at 150.0±3°C; (2) The DSC curve of phosphate form A has two endothermic peaks at 41.5±3℃ and 169.6±3℃; (3) The DSC curve of phosphate form A has an exothermic peak at 91.8℃±3℃; In some embodiments, the TGA / DSC graph of the phosphate crystal form A is substantially as shown in FIG. 35; 1 The HNMR chart is shown in Figure 36.

8. The pharmaceutically acceptable salt of the compound of formula I or its crystalline form according to claim 3, characterized in that: The crystal form is a p-toluenesulfonate crystal form of the compound of formula I. Preferably, the crystal form is a p-toluenesulfonate crystal form A of the compound of formula I. The p-toluenesulfonate crystal form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6569, 6.5865, 9.0105, 14.4962, 17.1789, and 19.7973. Further, the p-toluenesulfonate crystal form A has an XRPD spectrum substantially as shown in FIG. 38; Preferably, the p-toluenesulfonate salt form A has one or two of the following characteristics: (1) The TGA curve of p-toluenesulfonate crystalline form A shows a weight loss of 2-8% at 150.0±3°C, preferably about 2-6% (e.g., 2.0%, 2.5％，3.0％，3.5％，4.0％，4.5％，5.0％，5.5％，6.0％)； (2) The DSC curve of p-toluenesulfonate Form A has two endothermic peaks at 81.6±3℃ and 156.0±3℃; Preferably, the p-toluenesulfonate crystalline form A has one or two of the following characteristics: (1) The TGA curve of p-toluenesulfonate Form A shows a weight loss of 4.15% at 150.0±3°C; (2) The DSC curve of p-toluenesulfonate Form A has two endothermic peaks at 81.6±3℃ and 156.0±3℃; Preferably, the TGA / DSC graph of the p-toluenesulfonate crystalline form A is substantially as shown in FIG. 39 ; 1 The H NMR graph is shown in Figure 40; Preferably, the crystalline form is a p-toluenesulfonate crystalline form B of the compound of formula I, and the p-toluenesulfonate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6660, 16.2695, 17.6681, 19.5433, 20.3312, and 21.3520; further, the p-toluenesulfonate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6660, 11.1056, 14.5769, 16.269 5, 17.6681, 19.5433, 20.3312, 20.7694, 21.3520, and 26.0500; further, the p-toluenesulfonate salt form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6660, 11.1056, 14.5769, 14.9845, 16.2695, 17.6681, 19.5433, 20.3312, 20.7694, 21.3520, and 22.8795 , 24.5060, 26.0500, and 28.2460; further, the X-ray powder diffraction spectrum of the p-toluenesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 6.8890, 7.6660, 9.9665, 11.1056, 11.8448, 12.6617, 13.1706, 13.6098, 13.8415, 14.5769, 14.9845, 16.2695, 17.6681, 18.8718, 1 9.5433, 19.9700, 20.3312, 20.7694, 21.3520, 21.6902, 22.8795, 24.5060, 26.0500, 26.4583, 27.2822, 28.2460, 29.2107, 30.0879, 31.8132, 32.8460, 33.7653, and 37.7617; further, the p-toluenesulfonate salt form B has an XRPD spectrum substantially as shown in Figure 41; Preferably, the p-toluenesulfonate salt form B has one or two of the following characteristics: (1) The TGA curve of the p-toluenesulfonate crystalline form B shows a weight loss of 1-6% at 150.0±3°C, preferably about 1-4% (e.g., 1.0%, 1.5％，2.0％，2.5％，3.0％，3.5％，4.0％)； (2) The DSC curve of p-toluenesulfonate Form B has an endothermic peak at 204.3±3°C; Preferably, the p-toluenesulfonate salt form B has one or two of the following characteristics: (1) The TGA curve of p-toluenesulfonate Form B shows a weight loss of 1.92% at 150.0±3°C; (2) The DSC curve of p-toluenesulfonate Form B has an endothermic peak at 204.3±3°C; Preferably, the TGA / DSC graph of the p-toluenesulfonate crystalline form B is substantially as shown in FIG. 42 ; 1 The H NMR graph is substantially as shown in FIG43 .

9. The pharmaceutically acceptable salt of the compound of formula I or its crystalline form according to claim 3, characterized in that: The crystal form is a mesylate crystal form of the compound of formula I. Preferably, the crystal form is a mesylate crystal form A of the compound of formula I. The mesylate crystal form A has diffraction peaks at 7.1654, 7.7112, 10.2242, 15.4030, 16.8120, and 19.2492 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the mesylate crystal form A has diffraction peaks at 7.1654, 7.7112, 10.2242, 15.4030, 16.8120, and 19.2492 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°. , 11.4305, 15.4030, 16.8120, 17.7499, 18.3934, 18.9572, 19.2492, and 20.0359 have diffraction peaks; further, the mesylate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.1654, 7.7112, 10.2242, 11.4305, 15.4030, 16.8120, 17.7499, 18.3934, 18.9572, 19.249 2, 19.6796, 20.0359, 21.4943, 23.1420, and 25.5679 have diffraction peaks; further, the mesylate salt form A has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4245, 7.1654, 7.7112, 10.2242, 11.4305, 12.1973, 14.3852, 14.9410, 15.4030, 16.8120, 17.3257, 17.7499, 18.39 45; 46.4047, 48.7066, 46.710, 47.779, 48.611, 49.904, 50.7137, 51.2066, 52.4770, 53.9133, 54.7069, 55.1113, 56.1114, 57.7066, 58.8113, 59.8137, 61.2066, 62.8133, 63.7134, 64.7066, 65.1113, 66.7135, 67.7136, 68.8137, 69.9066, 70.9067, 71.2066, 72.8137, 73.7138, 74.7139, 75.1134, 76.1135, 77.1136, 78.1137, 79.1143, 80.1143, 81.1137, 82.8 Preferably, the mesylate salt form A has one or two of the following characteristics: (1) The TGA curve of the mesylate salt form A shows a weight loss of 1-6% at 150.0±3°C, preferably about 2-5% (e.g., 2.0%, 2.5％，3.0％，3.5％，4.0％，4.5％，5.0％)； (2) The DSC curve of mesylate form A has an endothermic peak at 153.8±3°C; Preferably, the mesylate salt form A has one or two of the following characteristics: (1) The TGA curve of mesylate form A shows a weight loss of 3.08% at 150.0±3°C; (2) The DSC curve of mesylate form A has an endothermic peak at 153.8±3°C; Preferably, the TGA / DSC diagram of the mesylate salt form A is substantially as shown in FIG. 46 ; 1 The HNMR graph is shown in Figure 47; Preferably, the crystalline form is a mesylate crystalline form B of the compound of formula I, and the mesylate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9334, 17.1889, 17.9047, 19.4932, and 20.3844 having diffraction peaks; further, the mesylate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9334, 16.2948, 1 7.1889, 17.9047, 18.9481, 19.4932, 20.3844, 21.2069, 23.9181, and 26.8731; further, the X-ray powder diffraction spectrum of the mesylate salt form B represented by a diffraction angle of 2θ±0.2° is 7.9334, 12.4699, 13.8134, 14.2662, 16.2948, 17.1889, 17.9047, 18.9481, 19.4932, 20.3844, 21.2069, 23.9181, and 26.8731. .9047, 18.9481, 19.4932, 20.3844, 21.2069, 22.9645, 23.9181, and 26.8731; further, the X-ray powder diffraction spectrum of the mesylate salt form B represented by a diffraction angle of 2θ±0.2° is 7.9334, 10.5237, 11.7673, 12.4699, 13.8134, 14.2662, 16 .2948, 17.1889, 17.9047, 18.9481, 19.4932, 20.3844, 21.2069, 22.3570, 22.9645, 23.9181, 25.0848, 26.8731, 28.8447, 30.5888, and 36.0120; further, the mesylate salt form B has an XRPD spectrum substantially as shown in Figure 48; Preferably, the mesylate salt form B has one or two of the following characteristics: (1) The TGA curve of the mesylate salt form B shows a weight loss of 0-3% at 150.0±3°C, preferably about 0-2% (e.g., 0.5%, 1.0％，1.5％，2.0％)； (2) The DSC curve of mesylate form B has three endothermic peaks at 161.8±3℃, 168.3±3℃ and 194.9±3℃; Preferably, the mesylate salt form B has one or two of the following characteristics: (1) The TGA curve of mesylate Form B shows a weight loss of 0.67% at 150.0±3°C; (2) The DSC curve of mesylate form B has three endothermic peaks at 61.8±3℃, 168.3±3℃ and 194.9±3℃; Preferably, the TGA / DSC diagram of the mesylate salt form B is substantially as shown in FIG. 49 ; 1 The HNMR graph is essentially as shown in Figure 50; Preferably, the crystalline form is a mesylate crystalline form C of the compound of formula I, and the mesylate crystalline form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6360, 9.3088, 15.7926, 17.1524, 17.5174, and 20.4316. Further, the mesylate crystalline form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 5.6360, 9.3088, 13 .6745, 15.7926, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 25.2739, 25.6773; further, the X-ray powder diffraction spectrum of the mesylate salt form C expressed at a diffraction angle of 2θ±0.2° is 5.6360, 9.3088, 12.6477, 13.6745, 15.7926, 16. 1257, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 23.0206, 23.4450, 25.2739, 25.6773; further, the X-ray powder diffraction spectrum of the mesylate salt form C represented by a diffraction angle of 2θ±0.2° is 5.6360, 8.5661, 9.3088, 11.6453, 12. 6477, 13.6745, 15.7926, 16.1257, 17.1524, 17.5174, 18.1940, 19.2689, 20.4316, 21.5116, 23.0206, 23.4450, 25.2739, 25.6773, 29.4554, and 32.4112; further, the mesylate salt form C has an XRPD spectrum substantially as shown in Figure 51; Preferably, the mesylate salt form C has one or two of the following characteristics: (1) The TGA curve of the mesylate salt form C shows a weight loss of 10-20% at 150.0±3°C, preferably about 12-16% (e.g., 12.0%, 12.5％，13.0％，13.5％，14.0％，14.5％，15.0％，15.5％，16.0％)； (2) The DSC curve of the mesylate salt form C has three endothermic peaks at 111.7±3℃, 135.8±3℃ and 139.6±3℃; Preferably, the mesylate salt form C has one or two of the following characteristics: (1) The TGA curve of mesylate form C shows a weight loss of 14.14% at 150.0±3°C; (2) The DSC curve of the mesylate salt form C has three endothermic peaks at 111.7±3℃, 135.8±3℃ and 139.6±3℃; Preferably, the TGA / DSC diagram of the mesylate salt form C is substantially as shown in FIG. 52 ; 1 The HNMR pattern is basically as shown in Figure 53; Preferably, the crystalline form is a mesylate crystalline form D of the compound of formula I, and the mesylate crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 17.0139, 17.2434, 17.5216, 19.2452, and 20.3331. Further, the mesylate crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 19.245 2, 19.8274, 20.3331, 25.3625; further, the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 18.7631, 19.2452, 19.8274, 20.3331, and 25.3625; further, the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.3614, 8.5975, 11.1942, 12.9868, 13.4101, 14.7295, 14.9968, 17.0139, 17.2434, 17.5216, 18.0167, 18.3980, 18.7631, 19.2452, 19.8274, 20.3331, 21.8273, 22.4894, 23.0593, 25.3625 have diffraction peaks; further, the mesylate salt form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.3734, 7.3614, 8.597 5.9.8950, 11.1942, 12.9868, 13.4101, 14.7295, 14.9968, 15.9124, 17.0139, 17.2434, 17.5216, 18.0167, 18.3980, 18.7631, 19.2452, 19.8274, 20.3331, 21.8273, 22.4894, 23.0593, 24.4152, and 25.3625 have diffraction peaks; further, the mesylate salt form D has an XRPD spectrum substantially as shown in Figure 102b; Preferably, the mesylate salt form D has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 1-4% at 150±3°C, preferably about 1.5-3% (e.g., 1.5%, 2.0%, 2.5%, 3.0%); more preferably, about 2.62%; (2) The DSC curve has two endothermic peaks at 40.3±3℃ and 156.6±3℃; Preferably, the TGA / DSC diagram of the mesylate salt form D is substantially as shown in FIG. 103 ; 1 The HNMR graph is substantially as shown in Figure 104; Preferably, the crystalline form is a mesylate crystalline form E of the compound of formula I, and the mesylate crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6948, 13.5466, 18.9557, 19.4674, and 26.1850; further, the mesylate crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6948, 13.5466, 18.9557, 19.4674, 20.0144, 23.7738, and 26.1850; further, the mesylate crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6948, 13.5466, 18.9557, 19.4674, 20.0144, 23.7738, and 26.1850. The X-ray powder diffraction spectrum of the salt form E represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.6948, 13.5466, 18.9557, 19.4674, 20.0144, 22.3698, 23.7738, and 26.1850; further, the mesylate salt form E represented by an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.6948, 13.5466, 14.5860, 16.1727, 17.5309, 17.8641, 18.9557, 19.4674, 20.0144, 2 0.3406, 20.8237, 21.6960, 22.3698, 23.7738, 25.1077, 26.1850, and 29.2032 have diffraction peaks; further, the mesylate salt form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.6948, 11.0258, 12.4963, 13.5466, 14.2591, 14.5860, 15.3154, 16.1727, 16.8137, 17.0486, 17.5309, 17.8641, 18.955 7, 19.4674, 20.0144, 20.3406, 20.8237, 21.6960, 22.3698, 22.8750, 23.1733, 23.7738, 25.1077, 25.3713, 25.7306, 26.1850, 26.8900, 27.6964, 28.4667, 29.2032, 30.5281, 31.4140, 33.7897, and 35.9511 have diffraction peaks; further, the mesylate salt form E has an XRPD spectrum substantially as shown in Figure 112b; Preferably, the crystalline form is a mesylate crystalline form F of the compound of formula I, and the mesylate crystalline form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 15.7726, 17.0258, 17.8165, 20.2728, and 23.7446. Further, the mesylate crystalline form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 15.7726, 17.0258, 17.8165, 20.2728, and 23.7446. 5.7726, 17.0258, 17.8165, 20.2728, 23.7446, 25.3530 have diffraction peaks; further, the mesylate salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207, 23.7446, 25.3530 diffraction peaks; further, the mesylate salt form F has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.8706, 11.8701, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207, 23.7446, 25.3530, and 26.3257; still ... The X-ray powder diffraction spectrum shown has diffraction peaks at 5.0171, 7.8706, 11.8701, 13.4221, 14.3209, 15.7726, 17.0258, 17.8165, 20.2728, 21.4207, 23.7446, 25.3530, and 26.3257; further, the mesylate salt form F has an XRPD spectrum substantially as shown in Figure 112c; Preferably, the crystalline form is a mesylate crystalline form G of the compound of formula I, and the mesylate crystalline form has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 16.1377, 17.7027, 18.1620, 19.1132, and 21.0530. Further, the mesylate crystalline form G has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, and 21.0 530, 24.3157; further, the X-ray powder diffraction spectrum of the mesylate salt form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 13.4333, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, 21.0530, 24.3157, 24.8063, and 26.2930; further, the X-ray powder diffraction spectrum of the mesylate salt form G represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.60 41, 10.1340, 12.6682, 13.4333, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, 21.0530, 22.0640, 24.3157, 24.8063, 25.5461, 26.2930, 28.8940; further, the X-ray powder diffraction spectrum of the mesylate salt form G represented by a diffraction angle of 2θ±0.2° is 8.6041, 10.1340, 11.2069, 12.6682, 13.4333, 14.4922, 15.4837, 16.1377, 16.5841, 17.7027, 18.1620, 19.1132, 21.0530, 22.0640, 24.3157, 24.8063, 25.5461, 26.2930, 26.9311, 27.7204, 28.8940; further, the mesylate salt form G has an XRPD spectrum substantially as shown in Figure 113b; Preferably, the crystalline form is a mesylate crystalline form H of the compound of formula I, and the mesylate crystalline form has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5858, 16.4833, 17.2040, 19.7648, and 22.2051. Further, the mesylate crystalline form H has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.5858, 9.8551, 12.8418, 16.4833, 17.2040, 1 9.7648, 22.2051; further, the X-ray powder diffraction spectrum of the mesylate salt form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5858, 9.8551, 12.8418, 16.4833, 17.2040, 19.7648, 22.2051, 25.4281, and 26.1391; further, the X-ray powder diffraction spectrum of the mesylate salt form H represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.58 58, 9.8551, 12.8418, 16.4833, 17.2040, 17.7099, 18.5860, 19.7648, 21.8135, 22.2051, 25.4281, 26.1391, and 29.8198; further, the X-ray powder diffraction spectrum of the mesylate salt form H represented by a diffraction angle of 2θ±0.2° is 5.6472, 9.5858, 9.8551, 12.8418, 15.206 7, 16.4833, 17.2040, 17.7099, 18.5860, 19.2029, 19.7648, 21.8135, 22.2051, 23.4137, 24.9851, 25.4281, 26.1391, 27.6138, 29.8198, 30.9209, 32.0327, and 35.9179; further, the mesylate salt form H has an XRPD spectrum substantially as shown in Figure 113c; Preferably, the crystalline form is a mesylate crystalline form I of the compound of formula I, and the mesylate crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 24.0274, and 25.6562. Further, the mesylate crystalline form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9648, 15.9556, 17.3872, 17.7652, 18.1048, 24.0274, and 25.6562. , 17.3872, 17.7652, 18.1048, 22.8525, 24.0274, 25.6562 have diffraction peaks; further, the mesylate salt form I has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9648, 15.1578, 15.9556, 17.3872, 17.7652, 18.1048, 22.8525, 24.0274, 25.6562 having diffraction peaks; Furthermore, the X-ray powder diffraction spectrum of the mesylate salt form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.9648, 11.3739, 15.1578, 15.9556, 16.6385, 17.3872, 17.7652, 18.1048, 20.2628, 22.8525, 24.0274, and 25.6562; Still further, the mesylate salt form I represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 7.9648, 11.3739, 15.1578, 15.9556, 16.6385, 17.3872, 17.7652, 18.1048, 20.2628, 22.8525, 24.0274, and 25.6562. The X-ray powder diffraction spectrum has diffraction peaks at 7.9648, 11.3739, 15.1578, 15.9556, 16.6385, 17.3872, 17.7652, 18.1048, 19.1430, 20.2628, 21.6954, 22.8525, 24.0274, 25.0167, and 25.6562; further, the mesylate salt form I has an XRPD spectrum substantially as shown in Figure 113d; Preferably, the crystalline form is a mesylate crystalline form J of the compound of formula I, and the mesylate crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.6620, 13.5049, 16.1555, 18.1900, 21.9852, 22.2107, and 22.9624 having diffraction peaks; further, the mesylate crystalline form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.6620, 10.0632, 11.4255 , 13.5049, 16.1555, 18.1900, 21.9852, 22.2107, and 22.9624; further, the X-ray powder diffraction spectrum of the mesylate salt form J represented by a diffraction angle of 2θ±0.2° is 8.6620, 10.0632, 11.4255, 13.5049, 16.1555, 17.5647, 18.1900, 19.7621, 21.9852, 22.2107, and 22.96 24 has diffraction peaks; further, the mesylate salt form J has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.6620, 10.0632, 11.4255, 13.5049, 16.1555, 17.5647, 18.1900, 19.7621, 21.9852, 22.2107, 22.9624, and 24.6246 ... The X-ray powder diffraction spectrum has diffraction peaks at 8.6620, 10.0632, 11.4255, 13.5049, 14.5059, 15.1512, 16.1555, 17.5647, 18.1900, 19.7621, 20.5741, 21.9852, 22.2107, 22.9624, 24.6246, and 30.6181; further, the mesylate salt form J has an XRPD spectrum substantially as shown in Figure 113e; Preferably, the crystalline form is a mesylate crystalline form K of the compound of formula I, and the mesylate crystalline form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4362, 17.2898, 17.5619, 18.6931, 21.1887, and 25.1553. Further, the mesylate crystalline form K has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 15.4362, 17.2898, 17.5619, 18.6931, 19.52 56, 21.1887, and 25.1553; further, the X-ray powder diffraction spectrum of the mesylate salt form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 15.4362, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256, 21.1887, 21.9878, and 25.1553; further, the X-ray powder diffraction spectrum of the mesylate salt form K represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.6859 , 15.4362, 16.5219, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256, 21.1887, 21.9878, 22.9735, 25.1553, 26.0704, 28.8383, and 30.0689; further, the X-ray powder diffraction spectrum of the mesylate salt form K represented by a diffraction angle of 2θ±0.2° is 8.6859, 9.9129, 12.6815, 13.450 0, 14.0343, 15.4362, 16.5219, 17.2898, 17.5619, 18.0642, 18.6931, 19.5256, 21.1887, 21.9878, 22.9735, 25.1553, 26.0704, 27.0875, 28.8383, 30.0689, 31.9147, 33.0164; further, the mesylate salt form K has an XRPD spectrum substantially as shown in Figure 113f; Preferably, the crystalline form is a mesylate crystalline form L of the compound of formula I, and the mesylate crystalline form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.0867, 18.6275, 19.6478, and 21.1470; further, the mesylate crystalline form L has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 8.0867, 11.8848, 18.6275, 19.6478, and 21.14 70, 21.6729, 21.9361; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0867, 11.8848, 18.6275, 19.6478, 21.1470, 21.6729, 21.9361, and 29.6831; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.0867, 11.8848, 18.6275, 19.6478, 21.1470, 21.6729, 21.9361, and 29.6831. The X-ray powder diffraction spectrum has diffraction peaks at 8.0867, 11.8848, 18.6275, 19.6478, 20.5586, 21.1470, 21.6729, 21.9361, 23.0719, 23.4214, 27.7310, and 29.6831; further, the X-ray powder diffraction spectrum of the mesylate salt form L represented by a diffraction angle of 2θ±0.2° is 8.0867, 11.8848, 14.2858, There are diffraction peaks at 15.7466, 16.2087, 18.6275, 19.6478, 20.5586, 21.1470, 21.6729, 21.9361, 22.3422, 23.0719, 23.4214, 23.9149, 27.7310, 28.6368, 29.6831, and 38.4394; further, the mesylate salt form L has an XRPD spectrum substantially as shown in Figure 113g; Preferably, the crystalline form is a mesylate crystalline form M of the compound of formula I, and the mesylate crystalline form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 16.0880, 17.4084, 17.6442, 18.6200, 18.8984, and 20.6457 having diffraction peaks; further, the mesylate crystalline form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0854, 16.0880, 16.2048, 17.4084, 17.6442, 18.6200, 18.89 84, 20.6457; further, the X-ray powder diffraction spectrum of the mesylate salt form M represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0854, 9.8088, 15.6545, 16.0880, 16.2048, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, and 20.6457; further, the X-ray powder diffraction spectrum of the mesylate salt form M represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 6.0854, 8.6714, 9.8088, 13.3246, 15.6545, 16.0880, 16.2048, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 19.7051, 20.6457, 21.0719, 22.1260, 24.4928, 25.3051 have diffraction peaks; further, the mesylate salt form M has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.0854, 8.6714, 9.8088, 12.3906 , 13.3246, 13.8974, 15.6545, 16.0880, 16.2048, 16.8014, 17.4084, 17.6442, 18.2844, 18.6200, 18.8984, 19.7051, 20.6457, 21.0719, 22.1260, 22.9780, 24.4928, 25.3051, 26.3685, 28.9539 have diffraction peaks; further, the mesylate salt form M has an XRPD spectrum substantially as shown in Figure 114b; Preferably, the crystalline form is a mesylate crystalline form N of the compound of formula I, and the mesylate crystalline form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 17.4887, 17.7573, 18.3532, 19.4978, 19.7328, and 27.6786 having diffraction peaks; further, the mesylate crystalline form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.1585, 17.4887, 17.7573, 18.3532, 19.4978, 19.732 8, 27.6786; further, the X-ray powder diffraction spectrum of the mesylate salt form N represented by a diffraction angle of 2θ±0.2° is 9.1585, 17.4887, 17.7573, 18.0588, 18.3532, 19.4978, 19.7328, 20.2234, 21.1657, 25.2039, 27.6786; further, the X-ray powder diffraction spectrum of the mesylate salt form N represented by a diffraction angle of 2θ±0.2° is 9.1585, 1 0.5913, 13.8291, 15.3223, 17.4887, 17.7573, 18.0588, 18.3532, 19.4978, 19.7328, 20.2234, 21.1657, 21.6656, 23.4530, 25.2039, 26.7244, 27.6786, 30.5646 have diffraction peaks; further, the mesylate salt form N has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.1585, 10.591 3. There are diffraction peaks at 13.8291, 15.3223, 17.4887, 17.7573, 18.0588, 18.3532, 19.0631, 19.4978, 19.7328, 20.2234, 21.1657, 21.6656, 22.4118, 23.4530, 25.2039, 26.7244, 27.6786, 30.5646, and 34.8974; further, the mesylate salt form N has an XRPD spectrum substantially as shown in Figure 114c; Preferably, the crystalline form is a mesylate crystalline form O of a compound of formula I, and the mesylate crystalline form O has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8632, 16.4454, 17.1724, 17.8526, 19.5652, and 19.7882 having diffraction peaks; further, the mesylate crystalline form O has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 9.8632, 16.4454, 17.1724, 17.8526, 19.1922, 19.5652, and 1 9.7882 has a diffraction peak; further, the X-ray powder diffraction spectrum of the mesylate salt form O represented by a diffraction angle of 2θ±0.2° is at 9.8632, 16.4454, 17.1724, 17.8526, 19.1922, 19.5652, 19.7882, 21.5123, 22.6207, 25.3282, and 26.0079; further, the X-ray powder diffraction spectrum of the mesylate salt form O represented by a diffraction angle of 2θ±0.2° is at 9.8632, 13.01 02, 16.4454, 17.1724, 17.8526, 18.5219, 19.1922, 19.5652, 19.7882, 20.7837, 21.5123, 22.1595, 22.6207, 23.3625, 25.3282, 26.0079, 29.5124 have diffraction peaks; further, the X-ray powder diffraction spectrum of the mesylate salt form O represented by a diffraction angle of 2θ±0.2° is 9.8632, 11.9975, 13.0102, 14.1 114d, there are diffraction peaks at 723, 16.4454, 17.1724, 17.8526, 18.5219, 19.1922, 19.5652, 19.7882, 20.7837, 21.5123, 22.1595, 22.6207, 23.3625, 24.6883, 25.3282, 26.0079, 29.5124, 30.2740, 31.3467, and 32.7120; further, the mesylate salt form O has an XRPD spectrum substantially as shown in Figure 114d.

10. The pharmaceutically acceptable salt of the compound of formula I or its crystalline form according to claim 3, characterized in that: The crystal form is an ethanesulfonate crystal form of the compound of formula I. Preferably, the crystal form is an ethanesulfonate crystal form A of the compound of formula I, and the ethanesulfonate crystal form A has diffraction peaks at 7.4322, 14.8852, 16.6572, 17.5439, and 20.0726 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the ethanesulfonate crystal form A has diffraction peaks at 7.4322, 10.3920, 13.3770, 14.4406, 14.8852, 16.6572, 17.5439, 20.0726, and 22.0062 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the ethanesulfonate crystal form A has an XRPD spectrum substantially as shown in Figure 55; Preferably, the ethanesulfonate salt form A has one or two of the following characteristics: (1) The TGA curve of the ethanesulfonate salt form A shows a weight loss of 5-12% at 150.0±3°C, preferably about 6-10% (e.g., 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10.0%); (2) The DSC curve of ethanesulfonate form A has two endothermic peaks at 36.3±3℃ and 141.5±3℃; Preferably, the ethanesulfonate salt form A has one or two of the following characteristics: (1) The TGA curve of ethanesulfonate Form A shows a weight loss of 8.29% at 150.0±3°C; (2) The DSC curve of ethanesulfonate form A has two endothermic peaks at 36.3±3℃ and 141.5±3℃; In some embodiments, the TGA / DSC diagram of the ethanesulfonate salt form A is substantially as shown in Figure 56; 1 The H NMR pattern is essentially as shown in Figure 57; Preferably, the crystalline form is an ethanesulfonate crystalline form B of the compound of formula I, and the ethanesulfonate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 15.3679, 17.7077, 18.9091, 19.5992, and 20.7324. Further, the ethanesulfonate crystalline form B has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 4.9173, 11.9022, 1 The ethanesulfonate salt form B has diffraction peaks at 4.9173, 11.9022, 14.8131, 15.3679, 17.7077, 18.9091, 19.5992, 19.9469, 20.7324, 22.2822, and 24.6012; further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 4.9173, 11.9022, 14.8131, 15.3679, 17.7077, 18.9091, 19.5992, 1 9.9469, 20.7324, 22.2822, 23.7415, 24.6012, 25.4858, and 27.0042 have diffraction peaks; further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 4.9173, 10.3467, 11.9022, 13.3498, 13.9472, 14.8131, 15.3679, 16.5326, There are diffraction peaks at 17.7077, 18.9091, 19.5992, 19.9469, 20.7324, 21.2340, 22.2822, 23.7415, 24.6012, 25.4858, 27.0042, 27.7863, 29.2924, 29.9997, and 31.9631; further, the ethanesulfonate salt form B has an XRPD spectrum substantially as shown in Figure 58a or 58b; Preferably, the ethanesulfonate salt form B has one or two of the following characteristics: (1) The TGA curve of the ethanesulfonate salt form B shows a weight loss of 3-10% at 150.0±3°C, preferably about 4-8% (e.g., 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5% 7.0%, 7.5%, 8.0%); (2) The DSC curve of ethanesulfonate form B has two endothermic peaks at 107.1±3℃ and 145.3±3℃; Preferably, the ethanesulfonate salt form B has one or two of the following characteristics: (1) The TGA curve of ethanesulfonate Form B shows a weight loss of 6.30% at 150.0±3°C; (2) The DSC curve of ethanesulfonate form B has two endothermic peaks at 107.1±3℃ and 145.3±3℃; Preferably, the TGA / DSC diagram of the ethanesulfonate salt form B is as shown in basic figure 59; 1 The HNMR pattern is substantially as shown in Figure 60; Preferably, the crystalline form is ethanesulfonate crystalline form C of the compound of formula I, and the ethanesulfonate crystalline form C has diffraction peaks at 6.3040, 10.4226, 13.6779, 15.9618, 20.3279, and 20.9348 in an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2°; further, the ethanesulfonate crystalline form C has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.3040, 8 .7771, 10.4226, 13.6779, 15.9618, 19.0549, 20.3279, and 20.9348 have diffraction peaks; further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form C represented by a diffraction angle of 2θ±0.2° is 6.3040, 8.7771, 10.4226, 13.6779, 15.9618, 17.6528, 19.0549, 19.8 646, 20.3279, 20.9348, 21.7435, 23.4169, and 26.2647; Still further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form C represented by a diffraction angle of 2θ±0.2° is 6.3040, 8.7771, 10.4226, 12.0274, 12.5635, 13.6779, 14.9315, 15.9618, 17.6 There are diffraction peaks at 528, 18.0467, 19.0549, 19.8646, 20.3279, 20.9348, 21.7435, 23.4169, 24.3601, 26.2647, 26.8633, 28.5527, 29.9377, 32.4837, and 35.6194; further, the ethanesulfonate salt form C has an XRPD spectrum substantially as shown in Figure 121b; Preferably, the crystalline form is the ethanesulfonate crystalline form D of the compound of formula I, and the ethanesulfonate crystalline form D has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 7.9081, 15.7893, 17.4668, 17.7671, 19.9837, 20.9514, and 23.8046. Further, the ethanesulfonate crystalline form D has an XRPD spectrum substantially as shown in Figure 121c; Preferably, the ethanesulfonate salt form D has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 0.5-3% at 150±3°C, preferably about 0.5-2% (e.g., 0.5%, 1.0%, 1.5%, 2.0%); more preferably, about 1.70%; (2) The DSC curve has three endothermic peaks at 55.5±3℃, 142.4±3℃ and 184.2±3℃; (3) The DSC curve has an exothermic peak at 91.6±3℃; Preferably, the TGA / DSC graph of the ethanesulfonate salt form D is substantially as shown in FIG. 122; 1 The HNMR pattern is essentially as shown in Figure 123; Preferably, the crystalline form is the ethanesulfonate crystalline form E of the compound of formula I, and the ethanesulfonate crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, 13.6740, 15.4870, 18.9455, 20.0718, 21.4317, and 23.2933. Further, the ethanesulfonate crystalline form E has an X-ray powder diffraction spectrum represented by a diffraction angle of 2θ±0.2° at 6.4770, 13.6740, 15.4870, 18.9455, 20.0718, 21.4317, and 23.2933. The X-ray powder diffraction spectrum of the ethanesulfonate salt form E has diffraction peaks at 6.4770, 10.9010, 13.6740, 15.4870, 16.1908, 18.9455, 20.0718, 21.4317, and 23.2933; further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form E expressed at a diffraction angle of 2θ±0.2° has diffraction peaks at 6.4770, 9.3320, 10.9010, 12. 3962, 13.6740, 15.4870, 16.1908, 17.8603, 18.9455, 19.6221, 20.0718, 21.4317, 23.2933; Still further, the X-ray powder diffraction spectrum of the ethanesulfonate salt form E expressed at a diffraction angle of 2θ±0.2° is 6.4770, 9.3320, 10.9010, 12.3 There are diffraction peaks at 962, 13.6740, 14.7088, 15.4870, 16.1908, 17.8603, 18.9455, 19.6221, 20.0718, 20.4917, 21.4317, 23.2933, 24.8830, and 27.4600; further, the ethanesulfonate salt form E has an XRPD spectrum substantially as shown in Figure 121d; Preferably, the ethanesulfonate salt form E has one or more of the following characteristics: (1) The TGA curve shows a weight loss of 2-7% at 110±3°C, preferably about 3-6% (e.g., 4.0%, 4.5%, 5.0%, 5.5%); more preferably, about 4.64%; (2) The DSC curve has three endothermic peaks at 48.4±3℃, 104.0±3℃ and 188.3±3℃; Preferably, the TGA / DSC diagram of the ethanesulfonate salt form E is substantially as shown in FIG. 124; 1 The HNMR pattern is essentially as shown in Figure 125; Preferably, the crystalline form is the ethanesulfonate crystalline form F of the compound of formula I, and the X-ray powder diffraction spectrum of the ethanesulfonate crystalline form F represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 8.7081, 9.3273, and 18.7028; further, the ethanesulfonate crystalline form F has an XRPD spectrum substantially as shown in Figure 121e.

11. A pharmaceutically acceptable salt of a compound of formula I according to claim 3 or a crystalline form thereof, characterized in that: The crystal form is a 1,2-ethanedisulfonate crystal form of the compound of formula I. Preferably, the crystal form is a 1,2-ethanedisulfonate crystal form A of the compound of formula I. The X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5776, 9.7934, 16.5380, 17.6744, 19.6187, 20.1184, and 20.7238; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystal form A represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5776, 9.7934, 12.9489, 16.5380, 16.9718, 17.6744, 19.6187, 20.1184, 20.7238 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° is 9.5776, 9.7934, 12.9489, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° is 9.5776, 9.7934, 12.9489, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198 have diffraction peaks -X-ray powder diffraction spectrum has diffraction peaks at 9.5776, 9.7934, 12.9489, 13.3845, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198, 23.1294, 25.3534, 26.0706, 26.5387, and 27.8458; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form A represented by a diffraction angle of 2θ±0.2° is 9.5776, 9.7934, 11.044 7, 12.1309, 12.9489, 13.3845, 14.5687, 15.5203, 16.3117, 16.5380, 16.9718, 17.6744, 18.7068, 19.6187, 20.1184, 20.7238, 22.2198, 23.1294, 24.1339, 25.3534, 26.0706, 26.5387, 27.8458, 30.3527, 31.4653; further, the 1,2-ethanedisulfonate salt form A has an XRPD spectrum substantially as shown in Figure 126b; Preferably, the crystalline form is a 1,2-ethanedisulfonate crystalline form B of the compound of formula I, and the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 9.5593, 16.2913, 16.5067, 17.0648, 17.7815, and 20.1011; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystalline form B represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 5.6887, 9.5593, 12.9139, 16.2913, 16.5067, 17.0648, 17.7815, 20.1011 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 5.6887, 9.5593, 10.0235, 12.9139, 16.2913, 16.5067, 17.0648, 17.7815, 18.6648, 20.1011, and 22.2426 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 5.6887, 9 .5593, 10.0235, 12.9139, 14.9480, 16.2913, 16.5067, 17.0648, 17.7815, 18.6648, 20.1011, 21.5441, 22.2426, 22.8020, 25.8424, 26.4853, 29.8463, and 30.3500 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form B represented by a diffraction angle of 2θ±0.2° is 5.6887, 7.5361, 9.5593, 10.0 12.5, 14.9640, 16.5267, 17.0441, 17.9129, 18.6648, 21.7081, 22.8020, 23.3535, 23.8750, 25.8424, 26.4853, 27.9265, 29.8463, 30.3500, 32.6082; further, the 1,2-ethanedisulfonate salt form B has an XRPD spectrum substantially as shown in Figure 126c; Preferably, the crystalline form is a 1,2-ethanedisulfonate crystalline form C of the compound of formula I, and the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 17.8877, 19.3330, 19.8489, 20.7131, and 21.1631; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate crystalline form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 13.3305, 16.7417, 17.8877, 19.3330 , 19.8489, 20.7131, and 21.1631 have diffraction peaks; further, the X-ray powder diffraction spectrum of the 1,2-ethanedisulfonate salt form C represented by a diffraction angle of 2θ±0.2° has diffraction peaks at 10.9129, 13.3305, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, and 23.0842; further, the 1,2-ethanedisulfonate salt form C has a diffraction peak at 2θ±0.2° The X-ray powder diffraction spectrum represented by the diffraction angle is 10.9129, 12.0262, 13.3305, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, 22.3700, 23.0842, 24.1491, and 27.8056. Further, the X-ray powder diffraction spectrum represented by the diffraction angle of 2θ±0.2° is 7.9970, 9 .8985, 10.9129, 12.0262, 13.3305, 15.5409, 16.7417, 17.8877, 18.3757, 19.3330, 19.8489, 20.7131, 21.1631, 22.3700, 23.0842, 24.1491, 25.2521, 27.8056, and 31.2456; further, the 1,2-ethanedisulfonate salt form C has an XRPD spectrum substantially as shown in Figure 126d.

12. A method for preparing a pharmaceutically acceptable salt of a compound of formula I or a crystalline form thereof according to any one of claims 3 to 11, characterized in that: The preparation method of the free crystalline form A of the compound of formula I comprises the following steps: placing the compound of formula I in an organic solvent and stirring, concentrating and drying, then adding water and heating to reflux; stirring at room temperature overnight, filtering, and drying; the organic solvent is selected from acetonitrile; The preparation method of the free crystalline form B of the compound of formula I comprises the following steps: slurrying the compound of formula I in an organic solvent for 1-5 days, centrifuging and separating the solid and drying; the organic solvent is selected from alcohols, preferably ethanol; the drying is selected from vacuum drying, and the drying temperature is 40-60°C, preferably 50°C; The preparation method of the free crystalline form C of the compound of formula I comprises the following steps: slurrying the compound of formula I in an organic solvent, centrifugally separating the solid and drying; the organic solvent is selected from MTBE; the drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C.; the slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days; The preparation method of the free crystalline form D of the compound of formula I comprises the following steps: Step 1: Add compound I-8, THF, and anhydrous ethanol, stir to dissolve, add anhydrous calcium chloride, stir to dissolve, cool to 0°C, add sodium borohydride, react at room temperature overnight, pour the reaction solution into water, add ethyl acetate, let stand to separate, pour out the supernatant, add ethyl acetate to wash the bottom solid, concentrate the organic phase and purify it through a silica gel column to obtain a compound of formula I, add acetonitrile to dissolve, concentrate until no liquid drops, add water and heat to 90-120°C, beat for 4-6h, filter, wash the filter cake, add water and heat to 90-120°C to beat for 4-6h, beat at room temperature overnight, filter, and freeze-dry the solid to obtain a mixed crystal of the compound of formula I; Step 2, slurrying the mixed crystals of the compound of formula I in IPA / H2O (volume ratio of 982:18) at room temperature for about 5 days, centrifuging and separating the solids and drying them in the open at room temperature to obtain Form D; The preparation method of the free crystalline form E of the compound of formula I comprises the following steps: The mixed crystal of the compound of formula I is placed in a THF atmosphere for gas-solid infiltration, and then air-dried at room temperature to obtain; The method for preparing the free crystalline form F of the compound of formula I comprises the following steps: The mixed crystal of the compound of formula I is heated to 160-180° C. and cooled to room temperature and humidity to obtain; The preparation method of the free crystalline form G of the compound of formula I comprises the following steps: The mixed crystal of the compound of formula I is first dissolved in 1,4-Dioxane, placed in a H2O atmosphere for gas-liquid diffusion to precipitate a solid, and then placed in the air to dry to obtain a solid; The method for preparing the free crystalline form H of the compound of formula I comprises the following steps: The mixed crystal of the compound of formula I is placed in a DMSO atmosphere for gas-solid diffusion to obtain; The method for preparing the free crystalline form I of the compound of formula I comprises the following steps: The mixed crystals of the compound of formula I are placed in MeOH and slurried at room temperature for about 5 days, and then exposed to air at room temperature to obtain; The preparation method of the free crystalline form J of the compound of formula I comprises the following steps: The mixed crystal of the compound of formula I is heated to 100° C. and cooled to room temperature and humidity to obtain; The method for preparing the free crystalline form K of the compound of formula I comprises the following steps: The mixed crystals of the compound of formula I were slurried in EtOH at room temperature for about 2 days, and the solids were separated by centrifugation and dried under vacuum at room temperature to obtain; The method for preparing the free crystalline form L of the compound of formula I comprises the following steps: The compound of formula I is obtained by slurrying in MeOH at room temperature for about 3 days; The preparation of the pharmaceutically acceptable salt of the compound of formula I includes the following methods: Method 1 comprises the following steps: slurrying the compound of formula I or the mixed crystal of the compound of formula I and a salt-forming agent (e.g., the corresponding acid) in solvent A, centrifuging and separating the solid and drying; the solvent A is selected from one or a mixture of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water; the alcohol is selected from methanol and ethanol; the drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C.; the slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days; Method 2 comprises the following steps: slurrying the compound of formula I or a mixed crystal of the compound of formula I and a salt-forming agent (e.g., the corresponding acid) in solvent A, adding solvent B to crystallize into gel, circulating at a temperature of 50° C. to 5° C. to obtain a suspension, centrifuging and separating the solid and drying; the solvent A is selected from one or more of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water; the alcohol is selected from methanol and ethanol; the solvent B is selected from n-heptane; the drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C.; the slurrying time is 1-5 days, for example, 1, 2, 3, 4, 5 days; Method three comprises the following steps: circulating a compound of formula I or a mixed crystal of a compound of formula I with a salt-forming reagent (e.g., a corresponding acid) in solvent A at a temperature of 50° C. to 5° C. to obtain a solid, centrifuging and drying the solid; the solvent A is selected from one or a mixture of alcohols, MTBE, MIBK, MeOAc, 2-MeTHF, DMSO, IPAc, Toluene, CPME, DCM, Acetone, ACN, THF, Ethyl formate, Anisole, EtOAc, IPE, 1,4-Dioxane and water; the alcohol is selected from methanol and ethanol; the drying is selected from vacuum drying, and the drying temperature is 40-60° C., preferably 50° C.; the slurrying time is 1-5 days, for example, 1, 2, 3, 4, or 5 days.

13. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises one or more of the crystalline form of the compound of formula I according to any one of claims 1 to 2 and the pharmaceutically acceptable salt of the compound of formula I according to any one of claims 3 to 11 or its crystalline form.

14. Use of a crystalline form of the compound of formula I according to any one of claims 1 to 2, a pharmaceutically acceptable salt of the compound of formula I according to any one of claims 3 to 11 or a crystalline form thereof, or a pharmaceutical composition according to claim 13 in the preparation of a drug; The drug can inhibit KIF18A; and / or prevent and / or treat KIF18A-related diseases; Preferably, the medicament is intended for the prevention and / or treatment of proliferative disorders of cancer, psoriasis, atopic dermatitis, autoimmune diseases or inflammatory bowel disease; Preferably, the cancer comprises mesothelioma, neuroblastoma, rectal cancer, colon cancer, familiar adenomatous polyposis and hereditary non-polyposis colorectal cancer, esophageal cancer, lip cancer, laryngeal cancer, hypopharyngeal cancer, tongue cancer, salivary gland cancer, gastric cancer, adenocarcinoma, medullary thyroid cancer, papillary thyroid cancer, kidney cancer, renal parenchymal cancer, ovarian cancer, cervical cancer, uterine body cancer, endometrial cancer, choriocarcinoma, pancreatic cancer, prostate cancer, bladder cancer, testicular cancer, breast cancer, urinary cancer, melanoma, brain tumor, lymphoma, head and neck cancer, acute lymphoid leukemia, chronic lymphoid leukemia, acute myeloid leukemia, chronic myeloid leukemia, hepatocellular carcinoma, gallbladder cancer, bronchial cancer, small cell lung cancer, non-small cell lung cancer, multiple myeloma, basal sarcoma, teratoma, retinoblastoma, choroidal melanoma, seminoma, rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myoma, liposarcoma, fibrosarcoma, Ewing sarcoma, and plasmacytoma; Preferably, the autoimmune disease comprises rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, mixed connective tissue disease, dermatomyositis, polymyositis, Reiter's syndrome, autoimmune lymphoproliferative syndrome, multiple sclerosis, myasthenia gravis and encephalomyelitis; Preferably, the inflammatory bowel disease comprises ulcerative colitis or Crohn's disease.

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