TW202340201A - Salt, crystalline form, solvate and hydrate of compound - Google Patents

Abstract

The present invention relates to a salt, crystalline form, solvate or hydrate of 6-(ethylamino)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptane-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, also relates to a pharmaceutical composition containing the salt, crystalline form, solvate or hydrate, and also relates to a use of the salt, crystalline form, solvate or hydrate in the preparation of a drug for treating RET-related diseases.

Description

Salts, crystal forms, solvates and hydrates of compounds

This application is based on the application with CN application number 202210111424.X and the filing date is January 29, 2022, and claims its priority. The disclosure content of the CN application is incorporated into this application as a whole.

The invention belongs to the field of medical technology and relates to 6-(ethylamino)-4-(6-(6-((6-methoxypyridin-3-yl)methyl))-3,6-diazabicyclo [3.1.1]Heptan-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile salts, crystal forms, solvates or hydrates, and also include salts, crystal forms, Pharmaceutical compositions of solvates or hydrates, and also relate to the use of these salts, crystal forms, solvates or hydrates in the preparation of medicaments for the treatment of RET-related diseases.

WO2021115457A discloses a compound that highly specifically and efficiently inhibits wild-type, fusion and mutant (including but not limited to G804 and G810) RET kinases, having the structure shown in Formula I,

The chemical name of this compound is: 6-(ethylamino)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[ 3.1.1]Heptan-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile. Further development of this compound is needed to improve the physical and chemical properties of this compound, such as melting point, stability, solubility and biological properties. availability, etc., and obtain crystal forms suitable for the preparation of pharmaceutical preparations.

The present invention provides a crystal form, salt, solvate or hydrate of the compound represented by formula I.

The present invention also provides a pharmaceutical composition, which contains the crystal form, salt, solvate or hydrate of the compound represented by Formula I, and a pharmaceutically acceptable carrier or excipient.

The present invention also provides the use of the crystal form, salt, solvate or hydrate of the compound represented by Formula I in the preparation of drugs for the treatment of RET-related diseases.

The present invention also provides the use of the pharmaceutical composition in preparing drugs for treating RET-related diseases. Detailed description of the invention

The present invention provides crystal form I of the compound represented by formula I, which is characterized in that, using Cu-Kα radiation, its X-ray powder diffraction pattern expressed at 2θ angle is at 15.3°±0.2°, 15.61°±0.2° and 22.16°. There is a diffraction peak at ±0.2°,

According to one embodiment of the present invention, the crystalline form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is also 6.71°±0.2°, 8.68°±0.2° and There is a diffraction peak at 13.4°±0.2°.

According to one embodiment of the present invention, the crystalline form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is also 14.49°±0.2°, 17.34°±0.2° and There is a diffraction peak at 21.04°±0.2°.

According to one embodiment of the present invention, the crystalline form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 9.49°±0.2°, 18.26°±0.2°, There are diffraction peaks at 18.68°±0.2°, 19°±0.2°, 23.47°±0.2°, 28.07°±0.2°, 29.41°±0.2° and 29.86°±0.2°.

According to one embodiment of the present invention, the crystal form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 12.35°±0.2°, 16.43°±0.2°, There are diffraction peaks at 16.72°±0.2°, 17.5°±0.2°, 17.85°±0.2°, 19.25°±0.2° and 19.93°±0.2°.

According to one embodiment of the present invention, the crystal form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 15.30°±0.2°, 15.61°±0.2°, There are diffraction peaks at 22.16°±0.2°, 6.71°±0.2°, 8.68°±0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34°±0.2° and 21.04°±0.2°.

According to one embodiment of the present invention, the crystal form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 15.30°±0.2°, 15.61°±0.2°, 22.16°±0.2°, 6.71°±0.2°, 8.68°±0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34°±0.2°, 21.04°±0.2°, 9.49°±0.2°, 18.26° There are diffraction peaks at ±0.2°, 18.68°±0.2°, 19°±0.2°, 23.47°±0.2°, 28.07°±0.2° and 29.41°±0.2°.

According to one embodiment of the present invention, the crystal form I of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 15.30°±0.2°, 15.61°±0.2°, 22.16°±0.2°, 6.71°±0.2°, 8.68°±0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34°±0.2°, 21.04°±0.2°, 9.49°±0.2°, 18.26° ±0.2°, 18.68°±0.2°, 19°±0.2°, 23.47°±0.2°, 28.07°±0.2°, 29.41°±0.2°, 12.35°±0.2°, 16.43°±0.2°, 16.72°±0.2 There are diffraction peaks at 17.5°±0.2°, 17.85°±0.2°, 19.25°±0.2° and 19.93°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of Form I of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 1.

According to one embodiment of the present invention, the DSC curve of the crystal form I of the compound represented by formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of crystal form I of the compound represented by formula I is basically the same as Figure 2.

According to one embodiment of the present invention, the DSC curve of crystalline form I of the compound represented by formula I is basically the same as Figure 3.

According to one embodiment of the present invention, the crystalline form I of the compound represented by formula I is a non-solvate. According to one embodiment of the present invention, the crystal form I of the compound represented by formula I is an anhydrous form.

According to one embodiment of the present invention, the unit cell parameters of the crystal form I of the compound represented by formula I are: a=13.4624(2) Å, b=16.1538(2) Å, c=11.6605(2) Å, α= γ= 90°, β=99.8420(10)°, and the space group is P 2 ₁ / c .

According to one embodiment of the present invention, the unit cell parameters of the crystal form I of the compound represented by formula I are: Form I empirical C ₂₇ H ₂₈ N ₈ O Relative molecular mass 480.57 temperature 299.73(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 13.4624(2) Å α = 90° b = 16.1538(2) Å β = 99.8420(10)° c = 11.6605(2) Å γ = 90° Volume 2498.48(7)Å3 Z 4

The present invention also provides a monohydrate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to water is about 1:1.

According to one embodiment of the present invention, the monohydrate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 9.24°±0.2°, 12.54°±0.2°, and 17.89 There are diffraction peaks at °±0.2°, 20.45°±0.2°, 25.22°±0.2° and 29.51°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 15.73°±0.2°, 15.98°±0.2°, There are diffraction peaks at 20.22°±0.2° and 23.99°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 14.89°±0.2°, 14.99°±0.2°, There are diffraction peaks at 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°±0.2° and 26.73°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 9.65°±0.2°, 16.24°±0.2°, There are diffraction peaks at 22.79°±0.2°, 27.33°±0.2° and 27.96°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is also 8.93°±0.2°, 10.13°±0.2°, There are diffraction peaks at 13.07°±0.2°, 16.24°±0.2°, 18.47°±0.2°, 19.27°±0.2° and 19.71°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 9.24°±0.2°, 12.54°±0.2°, and 17.89 There are diffraction peaks at °±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2° and 23.99°±0.2°. .

According to one embodiment of the present invention, the monohydrate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 9.24°±0.2°, 12.54°±0.2°, and 17.89 °±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°± There are diffraction peaks at 0.2°, 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°±0.2° and 26.73°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 9.24°±0.2°, 12.54°±0.2°, and 17.89 °±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°± 0.2°, 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°±0.2°, 26.73°±0.2°, 9.65°±0.2°, 16.24°±0.2° There are diffraction peaks at , 22.79°±0.2°, 27.33°±0.2° and 27.96°±0.2°.

According to one embodiment of the present invention, the monohydrate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 9.24°±0.2°, 12.54°±0.2°, and 17.89 °±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°± 0.2°, 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°±0.2°, 26.73°±0.2°, 9.65°±0.2°, 16.24°±0.2° , 22.79°±0.2°, 27.33°±0.2°, 27.96°±0.2°, 8.93°±0.2°, 10.13°±0.2°, 13.07°±0.2°, 16.24°±0.2°, 18.47°±0.2°, 19.27° There are diffraction peaks at ±0.2° and 19.71°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the monohydrate of the compound represented by Formula I using Cu-Kα radiation and expressed at the 2θ angle is substantially the same as Figure 41.

According to one embodiment of the present invention, the DSC curve of the monohydrate of the compound represented by Formula I has an endothermic peak in the range of 170 to 185°C.

According to one embodiment of the present invention, the TGA curve of the monohydrate of the compound represented by Formula I is basically the same as Figure 42.

According to one embodiment of the present invention, the DSC curve of the monohydrate of the compound represented by Formula I is basically the same as Figure 43.

According to one embodiment of the present invention, the unit cell parameters of the monohydrate of the compound represented by Formula I are: a=11.2944(2) Å, b=11.4048(2) Å, c=11.8672(2) Å, α= 112.572(2)°, β= 107.1220(10)°, γ= 102.2480(10)°, the space group is P .

According to one embodiment of the present invention, the unit cell parameters of the monohydrate of the compound represented by Formula I are: monohydrate empirical C ₂₇ H ₃₀ N ₈ O ₂ Relative molecular mass 498.59 temperature 299.62(10)K Wavelength 1.54184Å Crystal system Triclinic space group P Unit cell parameters a = 11.2944(2) Å α = 112.572(2)° b = 11.4048(2) Å β = 107.1220(10)° c = 11.8672(2) Å γ = 102.2480(10)° Volume 1254.06(4) Å3 Z 2

The present invention also provides an ethanol solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethanol is about 1:1.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.21°±0.2°, 8.33°±0.2° and There is a diffraction peak at 22.32°±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 13.48°±0.2° and 16.2°±0.2°. There are diffraction peaks at , 21.52°±0.2° and 27.82°±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 12.29°±0.2° and 17.54°±0.2°. There are diffraction peaks at , 19.02°±0.2°, 19.81°±0.2° and 25.41°±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 9.41°±0.2° and 10.7°±0.2°. , 11.73°±0.2°, 14.37°±0.2°, 15.13°±0.2°, 15.57°±0.2°, 16.57°±0.2°, 17.03°±0.2°, 17.91°±0.2°, 18.26°±0.2° and 19.81 There is a diffraction peak at °±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.21°±0.2°, 8.33°±0.2°, There are diffraction peaks at 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2° and 27.82°±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.21°±0.2°, 8.33°±0.2°, 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2°, 27.82°±0.2°, 12.29°±0.2°, 17.54°±0.2°, 19.02°±0.2°, 19.81° There are diffraction peaks at ±0.2° and 25.41°±0.2°.

According to one embodiment of the present invention, the ethanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.21°±0.2°, 8.33°±0.2°, 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2°, 27.82°±0.2°, 12.29°±0.2°, 17.54°±0.2°, 19.02°±0.2°, 19.81° ±0.2°, 25.41°±0.2°, 9.41°±0.2°, 10.7°±0.2°, 11.73°±0.2°, 14.37°±0.2°, 15.13°±0.2°, 15.57°±0.2°, 16.57°±0.2 There are diffraction peaks at 17.03°±0.2°, 17.91°±0.2° and 18.26°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the ethanol solvate of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 16.

According to one embodiment of the present invention, the DSC curve of the ethanol solvate of the compound represented by Formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of the ethanol solvate of the compound represented by Formula I is basically the same as Figure 17.

According to one embodiment of the present invention, the DSC curve of the ethanol solvate of the compound represented by Formula I is basically the same as Figure 18.

According to one embodiment of the present invention, the unit cell parameters of the ethanol solvate of the compound represented by Formula I are: a=14.6676(2) Å, b=16.0727(2) Å, c=11.9029(2) Å, α =γ= 90°, β=97.423(2)°, and the space group is P 2 ₁ / c .

According to one embodiment of the present invention, the unit cell parameters of the ethanol solvate of the compound represented by Formula I are: Ethanol solvate empirical C ₂₉ H ₃₄ N ₈ O ₂ Relative molecular mass 526.64 temperature 299.75(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 14.6676(2) Å α = 90° b = 16.0727(2) Å β = 97.423(2)° c = 11.9029(2) Å γ = 90° Volume 2782.57(7) Å3 Z 4

The present invention also provides a methanol solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I and methanol is about 1:1.

According to one embodiment of the present invention, the methanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2°, 12.23°±0.2°, There are diffraction peaks at 22.47°±0.2° and 24.52°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 11.18°±0.2° and 13.44°±0.2°. There are diffraction peaks at , 17.36°±0.2° and 21.62°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 8.27°±0.2° and 17.56°±0.2°. There are diffraction peaks at , 19.79°±0.2°, 25.39°±0.2° and 27.92°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 6.6°±0.2° and 6.77°±0.2°. , 8.66°±0.2°, 10.68°±0.2°, 10.75°±0.2°, 11.84°±0.2°, 14.41°±0.2°, 15.5°±0.2°, 15.71°±0.2°, 15.91°±0.2°, 16.27 There are diffraction peaks at °±0.2°, 16.51°±0.2°, 16.86°±0.2°, 18.22°±0.2°, 18.49°±0.2°, 19.02°±0.2° and 19.29°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2°, 12.23°±0.2°, There are diffraction peaks at 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2° and 21.62°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2°, 12.23°±0.2°, 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2°, 21.62°±0.2°, 8.27°±0.2°, 17.56°±0.2°, 19.79° There are diffraction peaks at ±0.2°, 25.39°±0.2° and 27.92°±0.2°.

According to one embodiment of the present invention, the methanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2°, 12.23°±0.2°, 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2°, 21.62°±0.2°, 8.27°±0.2°, 17.56°±0.2°, 19.79° ±0.2°, 25.39°±0.2°, 27.92°±0.2°, 6.6°±0.2°, 6.77°±0.2°, 8.66°±0.2°, 10.68°±0.2°, 10.75°±0.2°, 11.84°±0.2 °, 14.41°±0.2°, 15.5°±0.2°, 15.71°±0.2°, 15.91°±0.2°, 16.27°±0.2°, 16.51°±0.2°, 16.86°±0.2°, 18.22°±0.2°, There are diffraction peaks at 18.49°±0.2°, 19.02°±0.2° and 19.29°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the methanol solvate of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 32.

According to one embodiment of the present invention, the DSC curve of the methanol solvate of the compound represented by Formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of the methanol solvate of the compound represented by Formula I is basically the same as Figure 33.

According to one embodiment of the present invention, the DSC curve of the methanol solvate of the compound represented by Formula I is basically the same as Figure 34.

The present invention also provides an acetonitrile solvate 1 of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to acetonitrile is about 1:0.5.

According to one embodiment of the present invention, the acetonitrile solvate 1 of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.81°±0.2° and 13.53°±0.2°. There are diffraction peaks at , 15.46°±0.2°, 21.29°±0.2° and 21.72°±0.2°.

According to one embodiment of the present invention, the acetonitrile solvate 1 of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 8.79°±0.2°, 14.66°±0.2 There are diffraction peaks at 17.52°±0.2°, 20.34°±0.2°, 23.45°±0.2°, 27.72°±0.2° and 28.6°±0.2°.

According to one embodiment of the present invention, the acetonitrile solvate 1 of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 18.2°±0.2°, 18.55°±0.2 There are diffraction peaks at 22.42°±0.2° and 29.92°±0.2°.

According to one embodiment of the present invention, the acetonitrile solvate 1 of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.81°±0.2° and 13.53°±0.2°. , 15.46°±0.2°, 21.29°±0.2°, 21.72°±0.2°, 8.79°±0.2°, 14.66°±0.2°, 17.52°±0.2°, 20.34°±0.2°, 23.45°±0.2°, 27.72 There are diffraction peaks at °±0.2° and 28.6°±0.2°.

According to one embodiment of the present invention, the acetonitrile solvate 1 of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.81°±0.2° and 13.53°±0.2°. , 15.46°±0.2°, 21.29°±0.2°, 21.72°±0.2°, 8.79°±0.2°, 14.66°±0.2°, 17.52°±0.2°, 20.34°±0.2°, 23.45°±0.2°, 27.72 There are diffraction peaks at °±0.2°, 28.6°±0.2°, 18.2°±0.2°, 18.55°±0.2°, 22.42°±0.2° and 29.92°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the acetonitrile solvate 1 of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 6,

According to one embodiment of the present invention, the DSC curve of the acetonitrile solvate 1 of the compound represented by Formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of the methanol solvate 1 of the compound represented by Formula I is basically the same as Figure 7.

According to one embodiment of the present invention, the DSC curve of the methanol solvate 1 of the compound represented by Formula I is basically the same as Figure 8.

According to one embodiment of the present invention, the unit cell parameters of the acetonitrile solvate 1 of the compound represented by Formula I are: a=13.3231(2) Å, b=16.1220(2) Å, c=12.0723(2) Å, α=γ= 90°, β=99.0890(10)°, and the space group is P 2 ₁ / c .

According to one embodiment of the present invention, the unit cell parameter of the acetonitrile solvate 1 of the compound represented by formula I is Acetonitrile solvate 1 empirical C ₂₈ H ₂₈ N _8.50 O Relative molecular mass 499.59 temperature 299.96(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 13.3231(2) Å α = 90° b = 16.1220(2) Å β = 99.0890(10)° c = 12.0723(2) Å γ = 90° Volume 2560.51(7) Å3 Z 4

The present invention also provides a DMSO solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to DMSO is about 1:1.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 11.22°±0.2°, 16.43°±0.2°, There are diffraction peaks at 20.08°±0.2°, 20.32°±0.2°, 20.69°±0.2°, 21.23°±0.2°, 23.99°±0.2° and 26.03°±0.2°.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still at 8.38°±0.2° and 10.58°±0.2°. There are diffraction peaks at , 13.36°±0.2°, 19.48°±0.2°, 19.85°±0.2°, 22.75°±0.2° and 27.08°±0.2°.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 14.18°±0.2° and 15.38°±0.2°. There are diffraction peaks at , 15.73°±0.2°, 18.37°±0.2°, 22.88°±0.2° and 28.52°±0.2°.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 11.22°±0.2°, 16.43°±0.2°, 20.08°±0.2°, 20.32°±0.2°, 20.69°±0.2°, 21.23°±0.2°, 23.99°±0.2°, 26.03°±0.2°, 8.38°±0.2°, 10.58°±0.2°, 13.36° There are diffraction peaks at ±0.2°, 19.48°±0.2°, 19.85°±0.2°, 22.75°±0.2° and 27.08°±0.2°.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 11.22°±0.2°, 16.43°±0.2°, 20.08°±0.2°, 20.32°±0.2°, 20.69°±0.2°, 21.23°±0.2°, 23.99°±0.2°, 26.03°±0.2°, 8.38°±0.2°, 10.58°±0.2°, 13.36° ±0.2°, 19.48°±0.2°, 19.85°±0.2°, 22.75°±0.2°, 27.08°±0.2°, 14.18°±0.2°, 15.38°±0.2°, 15.73°±0.2°, 18.37°±0.2 There are diffraction peaks at 22.88°±0.2° and 28.52°±0.2°.

According to one embodiment of the present invention, the DMSO solvate of the compound represented by Formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is substantially the same as Figure 13.

According to one embodiment of the present invention, the DSC curve of the DMSO solvate of the compound represented by formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of the DMSO solvate of the compound represented by Formula I is basically the same as Figure 14.

According to one embodiment of the present invention, the DSC curve of the DMSO solvate of the compound represented by Formula I is basically the same as Figure 15.

The present invention also provides a formic acid solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to formic acid is about 1:1.

According to one embodiment of the present invention, the formic acid solvate of the compound represented by Formula I uses Cu-Kα radiation, and its X-ray powder diffraction pattern expressed at a 2θ angle is at 8.19°±0.2°, 15.91°±0.2°, There are diffraction peaks at 18.59°±0.2°, 22.2°±0.2° and 22.51°±0.2°.

According to one embodiment of the present invention, the formic acid solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 9.55°±0.2° and 15.61°±0.2°. There are diffraction peaks at , 18.35°±0.2° and 28.03°±0.2°.

According to one embodiment of the present invention, the formic acid solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 8.69°±0.2° and 13.01°±0.2°. There are diffraction peaks at , 15.34°±0.2°, 17.71°±0.2°, 23.02°±0.2°, 23.47°±0.2°, 23.84°±0.2° and 25.25°±0.2°.

According to one embodiment of the present invention, the formic acid solvate of the compound represented by Formula I uses Cu-Kα radiation, and its X-ray powder diffraction pattern expressed at a 2θ angle is at 8.19°±0.2°, 15.91°±0.2°, There are diffraction peaks at 18.59°±0.2°, 22.2°±0.2°, 22.51°±0.2°, 9.55°±0.2°, 15.61°±0.2°, 18.35°±0.2° and 28.03°±0.2°.

According to one embodiment of the present invention, the formic acid solvate of the compound represented by Formula I uses Cu-Kα radiation, and its X-ray powder diffraction pattern expressed at a 2θ angle is at 8.19°±0.2°, 15.91°±0.2°, 18.59°±0.2°, 22.2°±0.2°, 22.51°±0.2°, 9.55°±0.2°, 15.61°±0.2°, 18.35°±0.2°, 28.03°±0.2°, 8.69°±0.2°, 13.01° There are diffraction peaks at ±0.2°, 15.34°±0.2°, 17.71°±0.2°, 23.02°±0.2°, 23.47°±0.2°, 23.84°±0.2° and 25.25°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the formic acid solvate of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 20.

According to one embodiment of the present invention, the TGA curve of the formic acid solvate of the compound represented by Formula I is basically the same as Figure 21.

According to one embodiment of the present invention, the DSC curve of the formic acid solvate of the compound represented by Formula I is basically the same as Figure 22.

The present invention provides an ethyl formate solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethyl formate is about 1:1.

According to one embodiment of the present invention, the ethyl formate solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 4.77°±0.2° and 7.76°±0.2 There are diffraction peaks at 9.55°±0.2°, 15.54°±0.2° and 26.03°±0.2°.

According to one embodiment of the present invention, the ethyl formate solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 16.61°±0.2°, 21.46°± There are diffraction peaks at 0.2°, 25.56°±0.2° and 28.91°±0.2°.

According to one embodiment of the present invention, the ethyl formate solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 4.77°±0.2° and 7.76°±0.2 There are diffraction peaks at 9.55°±0.2°, 15.54°±0.2°, 26.03°±0.2°, 16.61°±0.2°, 21.46°±0.2°, 25.56°±0.2° and 28.91°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the ethyl formate solvate of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 23.

According to one embodiment of the present invention, the TGA curve of the ethyl formate solvate of the compound represented by Formula I is basically the same as Figure 24.

According to one embodiment of the present invention, the DSC curve of the ethyl formate solvate of the compound represented by Formula I is basically the same as Figure 25.

The present invention also provides an ethylene glycol methyl ether solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethylene glycol methyl ether is about 1:1.

According to one embodiment of the present invention, the ethylene glycol methyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 20.86°±0.2°, 20.2° There are diffraction peaks at ±0.2°, 13.44°±0.2° and 11.34°±0.2°.

According to one embodiment of the present invention, the ethylene glycol methyl ether solvate of the compound represented by formula I has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.73°±0.2°, 16.95°±0.2°, and 20.59 There are diffraction peaks at °±0.2° and 24.19°±0.2°.

According to one embodiment of the present invention, the ethylene glycol methyl ether solvate of the compound represented by formula I has an X-ray powder diffraction pattern expressed at a 2θ angle of 10.89°±0.2°, 21.04°±0.2°, and 21.41°. There are diffraction peaks at °±0.2°, 26.44°±0.2° and 27.02°±0.2°.

According to one embodiment of the present invention, the ethylene glycol methyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 20.86°±0.2°, 20.2° There are diffraction peaks at ±0.2°, 13.44°±0.2°, 11.34°±0.2°, 6.73°±0.2°, 16.95°±0.2°, 20.59°±0.2° and 24.19°±0.2°.

According to one embodiment of the present invention, the ethylene glycol methyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 20.86°±0.2°, 20.2° ±0.2°, 13.44°±0.2°, 11.34°±0.2°, 6.73°±0.2°, 16.95°±0.2°, 20.59°±0.2°, 24.19°±0.2°, 10.89°±0.2°, 21.04°±0.2 There are diffraction peaks at 21.41°±0.2°, 26.44°±0.2° and 27.02°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern expressed at the 2θ angle of the ethylene glycol methyl ether solvate of the compound represented by Formula I is substantially the same as Figure 26.

According to one embodiment of the present invention, the TGA curve of the ethylene glycol methyl ether solvate of the compound represented by Formula I is basically the same as Figure 27.

According to one embodiment of the present invention, the DSC curve of the ethylene glycol methyl ether solvate of the compound represented by Formula I is basically the same as Figure 28.

The present invention also provides the crystal form II of the compound represented by the formula I. Using Cu-Kα radiation, the X-ray powder diffraction pattern expressed at the 2θ angle is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, There are diffraction peaks at 14.53°±0.2°, 15.32°±0.2° and 22.2°±0.2°.

According to one embodiment of the present invention, the crystal form II of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 13.44°±0.2°, 15.61°±0.2°, 17.38 There are diffraction peaks at °±0.2° and 21.06°±0.2°.

According to one embodiment of the present invention, the crystal form II of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 4.24°±0.2°, 6.96°±0.2°, There are diffraction peaks at 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2° and 29.92°±0.2°.

According to one embodiment of the present invention, the crystalline form II of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is also 17.07°±0.2°, 20.2°±0.2° and There is a diffraction peak at 23.49°±0.2°.

The present invention also provides the crystal form II of the compound represented by the formula I. Using Cu-Kα radiation, the X-ray powder diffraction pattern expressed at the 2θ angle is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, There are diffraction peaks at 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2°, 15.61°±0.2°, 17.38°±0.2° and 21.06°±0.2°.

The present invention also provides the crystal form II of the compound represented by the formula I. Using Cu-Kα radiation, the X-ray powder diffraction pattern expressed at the 2θ angle is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2°, 15.61°±0.2°, 17.38°±0.2°, 21.06°±0.2°, 4.24°±0.2°, 6.96° There are diffraction peaks at ±0.2°, 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2° and 29.92°±0.2°.

The present invention also provides the crystal form II of the compound represented by the formula I. Using Cu-Kα radiation, the X-ray powder diffraction pattern expressed at the 2θ angle is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2°, 15.61°±0.2°, 17.38°±0.2°, 21.06°±0.2°, 4.24°±0.2°, 6.96° There are diffraction peaks at ±0.2°, 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2°, 29.92°±0.2°, 17.07°±0.2°, 20.2°±0.2° and 23.49°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern expressed at the 2θ angle using Cu-Kα radiation of the crystalline Form II of the compound represented by Formula I is substantially the same as Figure 29.

According to one embodiment of the present invention, the TGA curve of crystal form II of the compound represented by formula I is basically the same as Figure 30.

According to one embodiment of the present invention, the DSC curve of crystal form II of the compound represented by formula I is basically the same as Figure 31.

The present invention also provides an n-propanol solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I to n-propanol is about 1:1.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2° and 8.19°±0.2 There are diffraction peaks at 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2° and 24.69°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 18.51°±0.2°, 19.77°± There are diffraction peaks at 0.2°, 25.47°±0.2° and 27.72°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 13.44°±0.2°, 14.06°± There are diffraction peaks at 0.2°, 16.35°±0.2°, 17.3°±0.2°, 21.54°±0.2° and 22.84°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 10.52°±0.2°, 17.73°± There are diffraction peaks at 0.2°, 18.8°±0.2° and 27.2°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2° and 8.19°±0.2 °, 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2°, 24.69°±0.2°, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2° and 27.72°±0.2° Has diffraction peaks.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2° and 8.19°±0.2 °, 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2°, 24.69°±0.2°, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2°, 27.72°±0.2°, There are diffraction peaks at 13.44°±0.2°, 14.06°±0.2°, 16.35°±0.2°, 17.3°±0.2°, 21.54°±0.2° and 22.84°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.15°±0.2° and 8.19°±0.2 °, 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2°, 24.69°±0.2°, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2°, 27.72°±0.2°, 13.44°±0.2°, 14.06°±0.2°, 16.35°±0.2°, 17.3°±0.2°, 21.54°±0.2°, 22.84°±0.2°, 10.52°±0.2°, 17.73°±0.2°, 18.8° There are diffraction peaks at ±0.2° and 27.2°±0.2°.

According to one embodiment of the present invention, the n-propanol solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is substantially the same as Figure 35.

According to one embodiment of the present invention, the DSC curve of the n-propanol solvate of the compound represented by Formula I has an endothermic peak in the range of 175 to 185°C.

According to one embodiment of the present invention, the TGA curve of the n-propanol solvate of the compound represented by Formula I is basically the same as Figure 36.

According to one embodiment of the present invention, the DSC curve of the n-propanol solvate of the compound represented by Formula I is basically the same as Figure 37.

The present invention also provides a ethylene glycol dimethyl ether solvate of the compound represented by formula I, wherein the molar ratio of the compound represented by formula I and ethylene glycol dimethyl ether is about 1:1.

According to one embodiment of the present invention, the ethylene glycol dimethyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 13.4°±0.2°, 20.14 There are diffraction peaks at °±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71°±0.2° and 11.3°±0.2°.

According to one embodiment of the present invention, the ethylene glycol dimethyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still at 21.39°±0.2°, There are diffraction peaks at 20.49°±0.2° and 26.96°±0.2°.

According to one embodiment of the present invention, the ethylene glycol dimethyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still at 8.46°±0.2°, 10.83°±0.2°, 14.39°±0.2°, 14.51°±0.2°, 15.3°±0.2°, 15.59°±0.2°, 15.79°±0.2°, 16.84°±0.2°, 18.24°±0.2° and 19.71° There is a diffraction peak at ±0.2°.

According to one embodiment of the present invention, the ethylene glycol dimethyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 13.4°±0.2°, 20.14 There are diffraction peaks at °±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71°±0.2°, 11.3°±0.2°, 21.39°±0.2°, 20.49°±0.2° and 26.96°±0.2°. .

According to one embodiment of the present invention, the ethylene glycol dimethyl ether solvate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is at 13.4°±0.2°, 20.14 °±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71°±0.2°, 11.3°±0.2°, 21.39°±0.2°, 20.49°±0.2°, 26.96°±0.2°, 8.46°± 0.2°, 10.83°±0.2°, 14.39°±0.2°, 14.51°±0.2°, 15.3°±0.2°, 15.59°±0.2°, 15.79°±0.2°, 16.84°±0.2°, 18.24°±0.2° There are diffraction peaks at 19.71°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 38.

According to one embodiment of the present invention, the TGA curve of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I is basically the same as Figure 39.

According to one embodiment of the present invention, the DSC curve of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I has an endothermic peak in the range of 170 to 185°C.

According to one embodiment of the present invention, the DSC curve of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I is basically the same as Figure 40.

The present invention also provides the oxalate salt of the compound represented by formula I.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53 There are diffraction peaks at °±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2° and 22.73°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is also 5.82°±0.2°, 25.45°±0.2° and There is a diffraction peak at 27.61°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed in 2θ angle is still 15.89°±0.2°, 20.51°±0.2°, There are diffraction peaks at 20.9°±0.2°, 22.47°±0.2° and 24.24°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still at 8.71°±0.2°, 10.83°±0.2°, There are diffraction peaks at 11.57°±0.2°, 17.21°±0.2°, 19.87°±0.2°, 23.23°±0.2°, 26.73°±0.2°, 27.06°±0.2° and 29.14°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53 °±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°± There are diffraction peaks at 0.2° and 27.61°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53 °±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°± There are diffraction peaks at 0.2°, 27.61°±0.2°, 15.89°±0.2°, 20.51°±0.2°, 20.9°±0.2°, 22.47°±0.2° and 24.24°±0.2°.

According to one embodiment of the present invention, the oxalate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53 °±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°± 0.2°, 27.61°±0.2°, 15.89°±0.2°, 20.51°±0.2°, 20.9°±0.2°, 22.47°±0.2°, 24.24°±0.2°, 8.71°±0.2°, 10.83°±0.2° There are diffraction peaks at , 11.57°±0.2°, 17.21°±0.2°, 19.87°±0.2°, 23.23°±0.2°, 26.73°±0.2°, 27.06°±0.2° and 29.14°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern expressed at the 2θ angle using Cu-Kα radiation of the oxalate salt of the compound represented by Formula I is substantially the same as Figure 45.

According to one embodiment of the present invention, the TGA curve of the oxalate salt of the compound represented by Formula I is basically the same as Figure 46.

According to one embodiment of the present invention, the DSC curve of the oxalate salt of the compound represented by Formula I is basically the same as Figure 47.

The present invention also provides phosphate salts of the compounds represented by formula I.

According to one embodiment of the present invention, the phosphate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 3.21°±0.2°, 15.89°±0.2°, and 16.55°. There are diffraction peaks at ±0.2°, 18°±0.2°, 19.36°±0.2°, 21.37°±0.2°, 24.17°±0.2° and 24.52°±0.2°.

According to one embodiment of the present invention, the phosphate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed in 2θ angle is also 12.21°±0.2°, 15.56°±0.2°, 19.89 There are diffraction peaks at °±0.2°, 20.61°±0.2° and 25.1°±0.2°.

According to one embodiment of the present invention, the phosphate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed in 2θ angle is also 12.99°±0.2°, 21.83°±0.2°, 22.07 There are diffraction peaks at °±0.2°, 22.28°±0.2°, 22.63°±0.2°, 25.56°±0.2° and 28.23°±0.2°.

According to one embodiment of the present invention, the phosphate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 3.21°±0.2°, 15.89°±0.2°, and 16.55°. ±0.2°, 18°±0.2°, 19.36°±0.2°, 21.37°±0.2°, 24.17°±0.2°, 24.52°±0.2°, 12.21°±0.2°, 15.56°±0.2°, 19.89°±0.2 There are diffraction peaks at 20.61°±0.2° and 25.1°±0.2°.

According to one embodiment of the present invention, the phosphate of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is 3.21°±0.2°, 15.89°±0.2°, and 16.55°. ±0.2°, 18°±0.2°, 19.36°±0.2°, 21.37°±0.2°, 24.17°±0.2°, 24.52°±0.2°, 12.21°±0.2°, 15.56°±0.2°, 19.89°±0.2 °, 20.61°±0.2°, 25.1°±0.2°, 12.99°±0.2°, 21.83°±0.2°, 22.07°±0.2°, 22.28°±0.2°, 22.63°±0.2°, 25.56°±0.2° and There is a diffraction peak at 28.23°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the phosphate salt of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 49.

According to one embodiment of the present invention, the TGA curve of the phosphate salt of the compound represented by Formula I is basically the same as Figure 50.

According to one embodiment of the present invention, the DSC curve of the phosphate salt of the compound represented by Formula I is basically the same as Figure 51.

The present invention also provides the difumarate salt of the compound represented by formula I.

According to one embodiment of the present invention, the difumarate salt of the compound represented by formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.13°±0.2° and 14.56°±0.2°. There are diffraction peaks at , 18.47°±0.2°, 18.94°±0.2°, 19.83°±0.2°, 21.48°±0.2°, 22.61°±0.2° and 23.23°±0.2°.

According to one embodiment of the present invention, the difumarate salt of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 8.85°±0.2°, 9.41°±0.2 There are diffraction peaks at 14.12°±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°±0.2°, 20.34°±0.2°, 24.48°±0.2° and 28.89°±0.2°.

According to one embodiment of the present invention, the difumarate salt of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 11.36°±0.2°, 12.62°±0.2 There are diffraction peaks at 25.7°±0.2°, 27.57°±0.2° and 30.48°±0.2°.

According to one embodiment of the present invention, the difumarate salt of the compound represented by formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.13°±0.2° and 14.56°±0.2°. , 18.47°±0.2°, 18.94°±0.2°, 19.83°±0.2°, 21.48°±0.2°, 22.61°±0.2°, 23.23°±0.2°, 8.85°±0.2°, 9.41°±0.2°, 14.12 There are diffraction peaks at °±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°±0.2°, 20.34°±0.2°, 24.48°±0.2° and 28.89°±0.2°.

According to one embodiment of the present invention, the difumarate salt of the compound represented by formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 6.13°±0.2° and 14.56°±0.2°. , 18.47°±0.2°, 18.94°±0.2°, 19.83°±0.2°, 21.48°±0.2°, 22.61°±0.2°, 23.23°±0.2°, 8.85°±0.2°, 9.41°±0.2°, 14.12 °±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°±0.2°, 20.34°±0.2°, 24.48°±0.2°, 28.89°±0.2°, 11.36°±0.2°, 12.62°± There are diffraction peaks at 0.2°, 25.7°±0.2°, 27.57°±0.2° and 30.48°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the difumarate salt of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 53.

According to one embodiment of the present invention, the TGA curve of the difumarate salt of the compound represented by Formula I is basically the same as Figure 54.

According to one embodiment of the present invention, the DSC curve of the difumarate salt of the compound represented by Formula I is basically the same as Figure 55.

The present invention also provides the monofumarate salt of the compound represented by formula I.

According to one embodiment of the present invention, the monofumarate salt of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 11.78°±0.2° and 13.94°±0.2°. There are diffraction peaks at , 16.14°±0.2°, 20.98°±0.2°, 21.17°±0.2°, 21.85°±0.2° and 22.42°±0.2°.

According to one embodiment of the present invention, the monofumarate salt of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 11.26°±0.2°, 14.56°±0.2 There are diffraction peaks at 23.7°±0.2°, 23.93°±0.2° and 24.88°±0.2°.

According to one embodiment of the present invention, the monofumarate salt of the compound represented by formula I uses Cu-Kα radiation, and the X-ray powder diffraction pattern expressed at the 2θ angle is still 13.18°±0.2°, 13.44°±0.2 There are diffraction peaks at 14.82°±0.2°, 15.11°±0.2°, 19.75°±0.2°, 24.55°±0.2°, 25.64°±0.2°, 26.58°±0.2° and 27.33°±0.2°.

According to one embodiment of the present invention, the monofumarate salt of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 11.78°±0.2° and 13.94°±0.2°. , 16.14°±0.2°, 20.98°±0.2°, 21.17°±0.2°, 21.85°±0.2°, 22.42°±0.2°, 11.26°±0.2°, 14.56°±0.2°, 23.7°±0.2°, 23.93 There are diffraction peaks at °±0.2° and 24.88°±0.2°.

According to one embodiment of the present invention, the monofumarate salt of the compound represented by Formula I uses Cu-Kα radiation and has an X-ray powder diffraction pattern expressed at a 2θ angle of 11.78°±0.2° and 13.94°±0.2°. , 16.14°±0.2°, 20.98°±0.2°, 21.17°±0.2°, 21.85°±0.2°, 22.42°±0.2°, 11.26°±0.2°, 14.56°±0.2°, 23.7°±0.2°, 23.93 °±0.2°, 24.88°±0.2°, 13.18°±0.2°, 13.44°±0.2°, 14.82°±0.2°, 15.11°±0.2°, 19.75°±0.2°, 24.55°±0.2°, 25.64°± There are diffraction peaks at 0.2°, 26.58°±0.2° and 27.33°±0.2°.

According to one embodiment of the present invention, the X-ray powder diffraction pattern of the monofumarate salt of the compound represented by Formula I using Cu-Kα radiation and expressed at a 2θ angle is substantially the same as Figure 57.

According to one embodiment of the present invention, the TGA curve of the monofumarate salt of the compound represented by Formula I is basically the same as Figure 58.

According to one embodiment of the present invention, the DSC curve of the monofumarate salt of the compound represented by Formula I is basically the same as Figure 59.

The present invention also provides a pharmaceutical composition, which contains the crystalline form I, monohydrate, ethanol solvate, methanol solvate, acetonitrile solvate, DMSO solvate, and formic acid solvent of the compound represented by formula I. Compound, ethyl formate solvate, ethylene glycol methyl ether solvate, crystal form II, n-propanol solvate, ethylene glycol dimethyl ether solvate, oxalate, phosphate, difumarate salt and/or monofumarate, and pharmaceutically acceptable carriers or excipients.

According to one embodiment of the present invention, the pharmaceutical composition of the present invention contains an effective amount of the crystalline form I, monohydrate, ethanol solvate, methanol solvate, and acetonitrile solvent of the compound represented by formula I. Compound, DMSO solvate, formic acid solvate, ethyl formate solvate, ethylene glycol methyl ether solvate, Form II, n-propanol solvate, ethylene glycol dimethyl ether solvate, Oxalates, phosphates, difumarate and/or monofumarate.

The invention also provides crystal form I, monohydrate, ethanol solvate, methanol solvate, acetonitrile solvate, DMSO solvate, formic acid solvate, and ethyl formate solvent of the compound represented by formula I. Compound, glycol methyl ether solvate, Form II, n-propanol solvate, glycol dimethyl ether solvate, oxalate, phosphate, difumarate or monofumaric acid Use of salts in the preparation of medicaments for the treatment of RET-related diseases.

The invention also provides crystal form I, monohydrate, ethanol solvate, methanol solvate, acetonitrile solvate, DMSO solvate, formic acid solvate, and ethyl formate solvent of the compound represented by formula I. Compound, glycol methyl ether solvate, Form II, n-propanol solvate, glycol dimethyl ether solvate, oxalate, phosphate, difumarate or monofumaric acid Use of a salt in the preparation of a medicament for inhibiting RET kinase activity in a cell or subject.

The present invention also provides the use of the pharmaceutical composition in preparing drugs for treating RET-related diseases.

The present invention also provides the use of the pharmaceutical composition in the preparation of medicaments for inhibiting RET kinase activity in cells or subjects.

The present invention also provides a method for treating RET-related diseases, which includes administering to a subject an effective dose of the crystalline form I, monohydrate, ethanol solvate, methanol solvate, and acetonitrile solvate of the compound represented by formula I. substance, DMSO solvate, formic acid solvate, ethyl formate solvate, ethylene glycol methyl ether solvate, crystal form II, n-propanol solvate, ethylene glycol dimethyl ether solvate, grass salt, phosphate, difumarate or monofumarate.

The present invention also provides a method for treating RET-related diseases, comprising administering an effective dose of the pharmaceutical composition to the subject.

The present invention also provides a method for inhibiting RET kinase activity in cells, which includes adding an effective dose of the crystal form I, monohydrate, ethanol solvate, methanol solvate, and acetonitrile solvate of the compound represented by formula I. , DMSO solvate, formic acid solvate, ethyl formate solvate, ethylene glycol methyl ether solvate, crystalline form II, n-propanol solvate, ethylene glycol dimethyl ether solvate, oxalic acid Salt, phosphate, difumarate, monofumarate or the pharmaceutical composition is contacted with the cell.

The present invention also provides a method for inhibiting RET kinase activity in a subject, which includes administering to the subject an effective dose of crystal form I, monohydrate, ethanol solvate, methanol solvate of the compound represented by formula I. substance, acetonitrile solvate, DMSO solvate, formic acid solvate, ethyl formate solvate, ethylene glycol methyl ether solvate, crystalline form II, n-propanol solvate, ethylene glycol dimethyl ether Solvate, oxalate, phosphate, difumarate, monofumarate or the pharmaceutical composition.

According to one embodiment of the invention, the medicament is used to treat disorders associated with RET-related diseases: disorders of the expression or activity or level of the RET gene, RET kinase, or any one thereof.

Further, the RET gene, RET kinase, or the expression or activity or level disorder of any one of them is caused by one or more point mutations in the RET gene, and one or more point mutations in the RET gene are capable of causing RET. The protein has one or more amino acid substitutions or deletion mutations at the following amino acid positions: 378, 385, 618, 620, 630, 631, 633, 804, 810, 883, 918.

Further, RET gene, RET kinase, or the expression or activity or level disorder of any one of them is caused by RET gene fusion; the RET gene fusion is selected from: KIF5B-RET, CDC6-RET, NCOA4-RET, CLIP1- At least one of RET, ERC1-RET, RUFY3-RET, TFG-RET, PRKAR1A-RET and KTN1-RET.

According to one embodiment of the invention, the RET-related diseases include tumors and irritable bowel syndrome.

According to one embodiment of the present invention, RET-related diseases of the present invention include genetic abnormalities (gene fusions, mutations, etc.) encoding RET kinase that cause various diseases, including papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). , Hirschsprung disease, lung adenocarcinoma, irritable bowel syndrome, non-small cell lung cancer, multiple endocrine neoplasia type 2 (MEN2), etc.

Further, the gene fusion is selected from at least one of KIF5B-RET, CDC6-RET, NCOA4-RET, CLIP1-RET, ERC1-RET, RUFY3-RET, TFG-RET, PRKAR1A-RET and KTN1-RET.

Further, the mutation is a mutation that can cause the RET protein to undergo one or more amino acid substitutions or deletions at the following amino acid positions: 378, 385, 618, 620, 630, 631, 633, 804, 810, 883, 918.

According to one embodiment of the invention, the RET-related disease is selected from the group consisting of lung cancer, papillary thyroid cancer, medullary thyroid cancer, differentiated thyroid cancer, recurrent thyroid cancer, refractory differentiated thyroid cancer, multiple endocrine neoplasia type 2A or 2B , at least one of pheochromocytoma, parathyroid hyperplasia, breast cancer, colorectal cancer, papillary renal cell carcinoma, gastrointestinal mucosal gangliomatosis, and cervical cancer. Definition of terms

As used herein, the term "substantially the same" used to qualify a figure is intended to mean that a person skilled in the art would consider the figure to be identical to the reference figure, taking into account acceptable deviations in the art. Such deviations may be caused by factors known in the art related to instrumentation, operating conditions, and human factors. For example, those skilled in the art will appreciate that endothermic onset and peak temperatures measured by differential scanning calorimetry (DSC) can vary significantly from experiment to experiment. In some embodiments, two graphs are considered to be substantially the same when the positions of characteristic peaks of the two graphs do not vary by more than ±5%, ±4%, ±3%, ±2%, or ±1%. . For example, one skilled in the art can readily identify whether two X-ray diffraction patterns or two DSC patterns are substantially the same. In some embodiments, two X-ray diffraction patterns are considered to be substantially the same when the 2θ angle of the characteristic peaks of the two X-ray diffraction patterns does not change by more than ±0.3°, ±0.2°, or ±0.1°.

As used herein, the term "effective amount" refers to an amount sufficient to achieve the desired therapeutic or preventive effect, for example, an amount that reduces symptoms associated with the disease to be treated (e.g., RET-related disease), or is effective in avoiding, An amount that reduces, prevents, or delays the onset of a disease, such as a RET-related disease. Determining such effective amounts is within the ability of those skilled in the art. Generally speaking, the daily dosage of the salt, solvate or hydrate of the compound represented by Formula I of the present invention for treatment can be about 1 to 1000 mg.

As used herein, the term "treatment" is intended to alleviate, lessen, ameliorate, or eliminate the disease state or disorder targeted. If a subject receives a therapeutic amount of the co-crystal or pharmaceutical composition as described herein, the subject exhibits an observable and/or detectable reduction or improvement in one or more signs and symptoms, The subject was successfully "treated". It should also be understood that treatment of a disease state or disorder includes not only complete treatment, but also includes less than complete treatment but achieving some biologically or medically relevant result.

As used herein, the term "about" shall be understood to mean within the normal tolerance range in the art, for example, about may be understood to mean ±10%, ±9%, ±8%, ±7%, ±6% of that value. %, ±5%, ±4%, ±3%, ±2%, ±1%, ±0.5%, ±0.1%, ±0.05% or within ±0.01%. All numerical values provided herein are modified by the term "about" unless otherwise apparent from context.

As used herein, the term "pharmaceutically acceptable carrier or excipient" refers to a diluent, addendum, or vehicle that is administered with a therapeutic agent and that is, within the scope of sound medical judgment, suitable Exposure to human and/or other animal tissue without undue toxicity, irritation, allergic reactions, or other problems or complications commensurate with a reasonable benefit/risk ratio.

Pharmaceutically acceptable carriers that may be used in the pharmaceutical compositions of the present invention include, but are not limited to, sterile liquids, such as water, and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil , sesame oil, etc. When the pharmaceutical composition is administered intravenously, water is an exemplary carrier. Physiological saline and aqueous glucose and glycerol solutions may also be used as liquid carriers, particularly for injections. Suitable excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica, sodium stearate, glyceryl monostearate, talc, sodium chloride, skimmed milk powder, glycerin, propylene glycol, water, ethanol wait. The composition may also contain a small amount of a wetting agent, an emulsifier, a pH buffer, a preservative, an antioxidant, a flavoring agent, a fragrance, a co-solvent, a solubilizer, an osmotic pressure regulator, a coloring agent, etc., if necessary. Oral formulations may contain standard carriers such as binders, fillers, disintegrating agents, lubricants, and the like.

The pharmaceutical composition of the present invention can be administered by methods known in the art, such as but not limited to administration in any of the following ways: oral administration, spray inhalation, rectal administration, nasal administration, buccal administration, topical administration, parenteral administration The drug is administered by subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal and intracranial injection or infusion, or by means of an explanted reservoir. Among them, oral, intramuscular or intravenous injection administration methods are preferred.

For these routes of administration, the pharmaceutical compositions of the present invention can be administered in suitable dosage forms.

The dosage form can be a solid preparation, a semi-solid preparation, a liquid preparation or a gaseous preparation, including but not limited to tablets, capsules, powders, granules, lozenges, hard candies, powders, sprays, creams, ointments, Suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, suspensions, elixirs, syrups.

The pharmaceutical composition of the present invention can be prepared by any method well known in the art, such as by mixing, dissolving, granulating, sugar coating, grinding, emulsifying, lyophilizing and other processes. beneficial effects

The salt, crystal form, solvate or hydrate of the compound represented by Formula I provided by the present invention has one or more of the following advantages: 1) High temperature resistance; 2) Resistant to high humidity; 3) Resistant to light; 4) Good stability; 5) Low hygroscopicity; 6) High solubility; 7) High in vitro dissolution; 8) High relative bioavailability in the body.

The embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will understand that the following examples and experimental examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. If the specific conditions are not indicated in the examples and test examples, the conventional conditions or the conditions recommended by the manufacturer shall be followed. If the reagents or instruments used are not indicated by the manufacturer, they are all conventional products that can be purchased commercially.

The compound represented by formula I used in the embodiments of the present invention can be prepared by referring to the method described in Example 62 of WO2021115457A. Detection method

Nuclear magnetic resonance (NMR) was used to determine the structure of the compound. The solid sample was dissolved in deuterated dimethylsulfoxide (DMSO-d ₆ ) solvent, and NMR analysis was performed on a Bruker AVANCE-III (Bruker, GER).

The X-ray powder diffraction (XRPD) pattern was measured using a German Bruker D8 Advance X-ray polycrystalline diffractometer. Testing conditions: Cu target Ka, voltage 40KV, current 40mA, test angle 3-45°, step size 0.02º, exposure time 0.12 seconds.

The structure of the single crystal was analyzed using a Rigaku SuperNova X-ray single crystal diffractometer and Cu target irradiation (SXRD).

Differential scanning calorimetry (DSC) was performed using a TA Discovery 2500 differential calorimetry scanner (TA Instruments, USA). Accurately weigh 1~2 mg of the sample, place it in a perforated DSC Tzero sample pan, and heat the sample to the final temperature at a rate of 10 °C/min. The nitrogen purge rate in the furnace is 50 mL/min.

Thermogravimetric analysis (TGA) was performed using a Discovery TGA 55 thermogravimetric analyzer (TA Instruments, USA). Place 2~5 mg sample into a balanced open aluminum sample pan, automatically weigh it in the heating furnace of the thermogravimetric analyzer, heat the sample to the final temperature at a rate of 10 °C/min, and purge the sample with nitrogen. The speed is 60 mL/min, and the nitrogen purge speed at the balance is 40 mL/min.

The hygroscopicity of the crystalline form was analyzed using a DVS Intrinsic dynamic moisture adsorption instrument (DVS, SMS Company, UK). At a temperature of 25°C, the gradient mode is used for testing. The humidity change is 50%-95%-0%-50%. The humidity change amount of each gradient in the range of 0% to 90% is 10%. The gradient end point The dm/dt method is used for judgment, and the gradient end point is when dm/dt is less than 0.002% and maintained for 10 minutes.

The purity of the samples was analyzed using a Waters Acquity Arc liquid chromatograph from the United States.

Experimental conditions: column Waters Cortecs C18 4.6 x 150 mm, 2.7 µm mobile phase A: 0.1% trifluoroacetic acid in water B: 0.1% trifluoroacetic acid in acetonitrile solution gradient Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 95 5 3 95 5 15 50 50 18 10 90 twenty one 10 90 21.1 95 5 25 95 5 flow rate 1.0mL/min Detection wavelength 230nm Column temperature 30ºC Injection volume 5 μL diluent 0.1% trifluoroacetic acid in water Example 1 Crystal Form I of the compound represented by formula I

Weigh 20 mg of the compound of formula I and place it in a 4 mL EP tube. Add 0.5 mL of dioxane at room temperature to completely dissolve it. Then add 6.0 mL of methyl tert-butyl ether dropwise. After stirring for a period of time, a solid will precipitate. , centrifuge the precipitated solid and dry it under vacuum at room temperature to obtain a white solid, which is the crystal form I of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern is shown in Figure 1. After testing, the white solid obtained is in crystal form, that is, the crystal form I of the compound represented by Formula I of the present application. Thermogravimetric analysis (TGA) was performed on it. The obtained TGA spectrum is shown in Figure 2. Differential scanning calorimetry was performed on it. Analysis (DSC), the obtained DSC spectrum is shown in Figure 3. NMR detection was performed on it, and the obtained NMR spectrum is shown in Figure 4.

Crystalline Form I of the compound represented by formula I, using Cu-Kα radiation, the XRPD pattern expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 1: Table 1 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.71 13.18071 26.0 8.68 10.21388 23.3 9.49 9.34249 12.5 12.35 7.20379 5.8 13.40 6.64863 20.9 14.49 6.15863 28.4 15.30 5.83734 29.6 15.61 5.72389 32.3 16.43 5.44678 8.7 16.72 5.35445 5.0 17.34 5.16803 19.0 17.50 5.12353 9.6 17.85 5.02628 7.3 18.26 4.91762 15.9 18.68 4.80896 10.2 19.00 4.73307 10.6 19.25 4.67325 4.4 19.93 4.51989 9.5 20.12 4.47802 7.4 20.88 4.32234 7.6 21.04 4.29182 18.6 22.16 4.08372 100.0 22.86 3.96515 6.9 23.12 3.92414 7.0 23.47 3.86888 11.0 23.89 3.80359 7.7 24.42 3.72670 3.9 24.75 3.68002 6.0 25.35 3.59814 6.7 25.76 3.54493 4.4 26.15 3.49586 3.7 26.28 3.47904 3.4 26.96 3.39761 3.6 27.51 3.33549 8.2 27.72 3.31178 8.8 28.07 3.27380 15.9 28.52 3.22670 3.3 28.99 3.17917 4.0 29.16 3.16176 4.2 29.41 3.13700 10.7 29.86 3.09428 15.7 30.85 3.00420 2.5 31.43 2.95403 2.2 31.90 2.91530 2.5 33.44 2.79594 5.1 33.83 2.76757 2.9 33.94 2.75920 2.6 34.76 2.70227 2.0 35.32 2.66462 4.8 37.83 2.51196 2.6 38.39 2.48065 1.6 40.41 2.37635 1.9 42.44 2.28319 2.0 42.65 2.27393 2.0 44.53 2.19666 3.5

The TGA curve shows that the crystal form I of the compound represented by formula I has a weight loss of about 0.6% at about 150°C, and may decompose at a temperature greater than or equal to about 300°C. The DSC curve shows that the crystal form I of the compound represented by formula I has a melting endothermic peak at about 180.8 °C. The NMR spectrum shows that the structure of the compound represented by formula I has not changed. Combined with the thermal analysis data, it can be determined that the crystal form I of the compound represented by formula I is an anhydrous form. Preparation of single crystal:

Weigh 85.3 mg of the compound of formula I into the bottle, add 2 mL of methylene chloride to dissolve the solution, filter the solution with a 0.2 micron nylon filter, transfer the filtrate to 10 mL of diethyl ether, and seal the sample bottle. After standing at room temperature for 3 days, crystals of Form I of the compound represented by Formula I with a size suitable for single crystal detection (approximately 50*50*50 μM) were obtained in the solution.

The single crystal structure analysis data is shown in Table 2, and the atomic displacement ellipsoid diagram is shown in Figure 5. Table 2 Form I empirical C ₂₇ H ₂₈ N ₈ O Relative molecular mass 480.57 temperature 299.73(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 13.4624(2) Å α = 90° b = 16.1538(2) Å β = 99.8420(10)° c = 11.6605(2) Å γ = 90° Volume 2498.48(7)Å3 Z 4 Example 2 Acetonitrile solvate 1 of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I and place it in a 10 mL EP tube, add 6.5 mL of acetonitrile to dissolve the solid, leave the resulting solution exposed, and evaporate at room temperature under dry air purging to obtain White solid, acetonitrile solvate 1 of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern was shown in Figure 6. Thermogravimetric analysis (TGA) was performed on it, and the obtained TGA pattern was shown in Figure 7. Differential scanning calorimetry (DSC) was performed on it, and the result The DSC spectrum is shown in Figure 8. After detection, the white solid obtained was the acetonitrile solvate 1 of the compound represented by Formula I of the present application, in which the molar ratio of the compound represented by Formula I to acetonitrile was approximately 1:0.5.

Acetonitrile solvate 1 of the compound represented by formula I, using Cu-Kα radiation, the XRPD pattern expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 3: Table 3 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.81 12.99347 48.9 8.79 10.07944 15.7 9.34 9.49667 6.2 10.81 8.21182 1.2 12.19 7.29423 2.7 13.53 6.58303 43.3 14.66 6.08674 19.1 14.93 5.97828 3.1 15.46 5.78004 46.0 15.92 5.61493 5.5 16.37 5.46564 4.4 17.52 5.11802 18.6 17.97 4.99472 3.5 18.20 4.93283 9.3 18.55 4.84298 11.0 18.96 4.74242 4.8 19.35 4.65067 4.4 19.87 4.53261 3.0 20.34 4.43291 14.8 21.29 4.24321 28.1 21.72 4.16359 100.0 22.42 4.04002 13.0 23.06 3.93352 6.0 23.45 3.87190 15.1 23.95 3.79488 8.2 24.71 3.68544 4.3 25.04 3.63989 6.4 25.37 3.59557 5.7 26.36 3.46952 3.8 26.83 3.41355 3.5 27.16 3.37512 8.6 27.43 3.34421 4.5 27.72 3.31178 16.7 28.60 3.21867 17.9 29.37 3.14078 7.9 29.92 3.08880 12.5 31.08 2.98389 2.4 31.42 2.95567 1.9 31.98 2.90896 2.1 32.72 2.85035 2.6 33.20 2.81331 6.4 33.59 2.78451 1.8 34.14 2.74538 3.8 35.11 2.67875 3.4 35.57 2.64817 2.4 36.66 2.58011 1.4 38.18 2.49240 2.6 39.64 2.41505 1.7 39.79 2.40718 1.7 40.51 2.37163 1.4 41.21 2.33838 1.7 42.12 2.29686 1.7 42.49 2.28065 3.6 42.84 2.26560 1.7 43.52 2.23712 1.7 44.67 2.19138 2.1

The TGA curve shows that the acetonitrile solvate 1 of the compound represented by formula I has a weight loss of about 4.0% during heating to about 200 °C, and may decompose when it is greater than or equal to about 300 °C. The DSC curve shows that acetonitrile solvate 1 of the compound represented by formula I has a small endothermic peak at about 123.5°C and a melting endothermic peak at about 180.5°C. Preparation of single crystal

Weigh 84.7 mg of crystal form I of the compound represented by formula I into the bottle, add 20 mL of acetonitrile, and heat it to 60 °C to obtain a clear liquid. The resulting clear liquid was dried over magnesium sulfate, then filtered with a 0.2 micron nylon filter, and 10 mL of the filtrate was placed in a nitrogen environment to evaporate. After the solvent is partially evaporated, a crystal of the acetonitrile solvate 1 of the compound represented by formula I is obtained with a size suitable for single crystal detection (generally 50*50*50 μm).

The single crystal structure analysis data is shown in Table 4, and the atomic displacement ellipsoid diagram is shown in Figure 9. Table 4 Acetonitrile solvate 1 empirical C ₂₈ H ₂₈ N _8.50 O Relative molecular mass 499.59 temperature 299.96(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 13.3231(2) Å α = 90° b = 16.1220(2) Å β = 99.0890(10)° c = 12.0723(2) Å γ = 90° Volume 2560.51(7) Å3 Z 4 Example 3 Acetonitrile solvate 2 of the compound represented by formula I

Referring to the preparation method described in Example 2, an acetonitrile solvate 2 of the compound represented by Formula I was prepared, wherein the molar ratio of the compound represented by Formula I to acetonitrile was 1:0.5. Perform XRPD detection on it, and the obtained XRPD spectrum is shown in Figure 10. Perform thermogravimetric analysis (TGA) on it, and the obtained TGA spectrum is shown in Figure 11. Perform differential scanning calorimetry (DSC) on it, and obtain the DSC spectrum. As shown in Figure 12. After testing, the molar ratio of the compound represented by Formula I to acetonitrile in the acetonitrile solvate 2 of the compound represented by Formula I is approximately 1:0.5.

Acetonitrile solvate 2 of the compound represented by formula I, using Cu-Kα radiation, the XRPD pattern expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 5: Table 5 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 8.85 10.01357 3.0 9.16 9.67641 100.0 9.57 9.26729 6.4 10.04 8.84066 1.6 12.48 7.12652 36.3 12.97 6.86387 1.2 14.82 6.02427 2.7 14.93 5.97828 2.4 15.65 5.71003 6.8 15.91 5.62161 5.8 16.24 5.51019 1.9 16.72 5.35445 3.8 17.81 5.03689 8.9 18.37 4.88747 15.0 19.19 4.68691 3.6 20.12 4.47802 3.8 20.40 4.42077 16.5 21.04 4.29182 2.3 21.52 4.19938 2.4 22.75 3.98438 1.6 22.96 3.94927 1.1 23.93 3.79778 2.3 24.17 3.76329 3.2 25.18 3.62149 13.2 26.17 3.49345 1.8 26.67 3.43198 3.7 27.28 3.36179 1.6 27.92 3.29056 1.4 28.46 3.23276 1.1 28.91 3.18698 1.0 29.47 3.13135 5.2 30.50 3.03528 0.6 31.14 2.97886 0.6 31.75 2.92807 0.8 32.62 2.85790 0.7 33.22 2.81185 0.9 34.10 2.74813 1.6 34.72 2.70491 0.4 37.25 2.54545 0.8 40.24 2.38491 1.1

The TGA curve shows that the acetonitrile solvate 2 of the compound represented by formula I has a weight loss of about 4.0% during heating to about 140 ºC, and may decompose at temperatures greater than or equal to about 280 ºC. The DSC curve shows that the acetonitrile solvate 2 of the compound represented by formula I has an endothermic peak at about 120.1 ºC and an exothermic peak at about 135.5 ºC, which may correspond to the recrystallization process; a melting peak appears at about 180 ºC. Example 4 DMSO solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I, add 1.0 mL of dimethylsulfoxide into a 4 mL EP tube, stir magnetically at room temperature for 7 days, crystals precipitate, centrifuge, and vacuum dry to obtain a white solid.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 15. After detection, the white solid obtained was the DMSO solvate of the compound represented by Formula I, where the molar ratio of the compound represented by Formula I to DMSO was approximately 1:1.

The DMSO solvate of the compound represented by formula I uses Cu-Kα radiation and the XRPD pattern expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 6: Table 6 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 8.38 10.56639 15.2 10.04 8.84066 7.8 10.58 8.39071 18.7 11.22 7.91676 42.7 12.06 7.37531 3.6 13.36 6.66763 18.6 14.18 6.29087 10.0 15.01 5.94803 3.6 15.38 5.80854 10.1 15.73 5.68251 10.5 16.43 5.44678 39.7 16.78 5.33638 6.6 17.40 5.15125 3.3 17.77 5.04755 5.7 17.89 5.01571 5.4 18.37 4.88747 11.0 18.55 4.84298 8.5 19.13 4.70066 6.1 19.48 4.61944 18.5 19.85 4.53687 17.9 20.08 4.48633 100.0 20.32 4.43697 38.3 20.69 4.36114 49.0 21.23 4.25432 71.1 21.50 4.20299 8.0 22.11 4.09394 9.6 22.46 4.03339 8.3 22.75 3.98438 16.2 22.88 3.96196 9.8 23.50 3.86284 6.1 23.99 3.78909 62.7 24.73 3.68273 4.4 25.14 3.62673 8.2 25.35 3.59814 7.8 25.49 3.58021 6.2 26.03 3.51042 32.0 26.81 3.41584 4.9 27.08 3.38408 14.9 27.72 3.31178 4.4 28.07 3.27380 4.7 28.52 3.22670 10.4 28.69 3.20869 7.5 29.04 3.17335 4.4 29.43 3.13512 3.6 29.65 3.11454 4.1 30.31 3.05288 3.7 30.68 3.01965 4.8 30.89 3.00079 4.1 31.49 2.94912 3.6 31.88 2.91688 4.0 32.41 2.87468 5.6 33.67 2.77884 4.5 34.10 2.74813 9.5 34.58 2.71422 4.8 36.49 2.59075 3.0 36.93 2.56379 4.2 37.23 2.54658 3.1 38.39 2.48065 3.1 39.33 2.43102 3.7 40.12 2.39067 5.1 40.24 2.38491 6.0 40.43 2.37540 4.5 41.00 2.34840 3.6 41.19 2.33929 3.0 42.90 2.26311 2.7 43.72 2.22917 3.2 44.57 2.19515 3.2

The TGA curve shows that the DMSO solvate of the compound represented by formula I has a weight loss of about 15.0% when heated to about 200 ºC, and may decompose when it is greater than or equal to about 300 ºC. The DSC curve shows that the DMSO solvate of the compound represented by formula I has endothermic peaks at about 159.9 ºC and about 179 ºC. Example 5 Ethanol solvate of the compound represented by formula I

Weigh 16 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, add 3.0 mL of ethanol, raise the temperature to 50 ºC, stir magnetically for 1 day, crystals precipitate, centrifuge, and vacuum dry to obtain a white solid, which is formula Ethanol solvate of the compound shown in I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 18. After detection, the white solid obtained was the ethanol solvate of the compound represented by Formula I, where the molar ratio of the compound represented by Formula I to ethanol was approximately 1:1.

The XRPD pattern of the ethanol solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 7: Table 7 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.21 14.24908 29.6 8.33 10.63985 36.3 9.41 9.41895 4.2 10.70 8.30028 14.0 11.73 7.58007 4.2 12.29 7.23744 19.2 13.48 6.61098 21.0 14.37 6.20754 14.0 15.13 5.90324 4.2 15.57 5.73782 4.8 16.20 5.52306 24.3 16.57 5.40328 14.2 17.03 5.25951 5.7 17.54 5.11253 18.8 17.91 5.01045 9.7 18.26 4.91762 11.8 19.02 4.72841 19.8 19.81 4.54542 16.0 20.71 4.35723 5.2 21.52 4.19938 24.1 22.32 4.05670 100.0 23.02 3.93980 9.2 23.56 3.85382 9.6 24.61 3.69908 8.4 24.88 3.66117 6.1 25.41 3.59043 17.1 25.91 3.52512 4.3 26.09 3.50313 4.7 26.71 3.42735 4.9 26.94 3.39988 4.4 27.26 3.36401 7.0 27.82 3.30113 20.7 28.01 3.28006 12.8 28.93 3.18503 4.5 29.39 3.13889 4.4 30.48 3.03703 2.7 31.32 2.96390 5.5 31.94 2.91212 4.9 32.64 2.85638 6.9 33.42 2.79738 2.4 34.60 2.71289 2.1 34.78 2.70095 2.2 35.22 2.67102 2.0 35.77 2.63569 1.9 36.16 2.61115 1.6 36.64 2.58129 2.9 37.62 2.52410 1.8 38.80 2.45861 1.9 39.44 2.42500 1.4 40.04 2.39452 1.6 41.89 2.30727 2.3 43.45 2.24032 2.0 43.68 2.23075 1.9 44.79 2.18688 1.9

The TGA curve shows that the ethanol solvate of the compound represented by formula I has a weight loss of about 7.0% when heated to about 140 ºC, and may decompose at temperatures greater than or equal to about 300 ºC. The DSC curve shows that the ethanol solvate of the compound represented by formula I has endothermic peaks corresponding to TGA weight loss at about 84.2 ºC and about 123.2 ºC, and a melting endothermic peak at about 180.9 ºC. Preparation of single crystal

Weigh 92.6 mg of crystal form I of the compound represented by formula I into the bottle, add 20 mL of ethanol, and raise the temperature to 60 ºC to obtain a suspension. Take 10 mL of the suspension, filter it with a 0.2 micron nylon filter, transfer the filtrate to 10 mL of n-heptane, and seal the sample bottle. After standing at room temperature for 1 day, ethanol solvate crystals of the compound represented by formula I with a size suitable for single crystal detection (generally 50*50*50 μm) were obtained in the solution.

The single crystal structure analysis data is shown in Table 8, and the atomic displacement ellipsoid diagram is shown in Figure 19. Table 8 Ethanol solvate empirical C ₂₉ H ₃₄ N ₈ O ₂ Relative molecular mass 526.64 temperature 299.75(10)K Wavelength 1.54184Å Crystal system Monoclinic space group P 2 ₁ / c Unit cell parameters a = 14.6676(2) Å α = 90° b = 16.0727(2) Å β = 97.423(2)° c = 11.9029(2) Å γ = 90° Volume 2782.57(7) Å3 Z 4 Example 6 Formic acid solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, add 1.0 mL of butyl formate and 1.0 mL of n-heptane, heat to 50ºC and stir magnetically for 3 days, the crystals will precipitate, centrifuge, and dry under vacuum. A white solid is obtained, which is the formic acid solvate of the compound represented by formula I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 22. After detection, the white solid obtained was the formic acid solvate of the compound represented by Formula I, in which the molar ratio of the compound represented by Formula I to formic acid was approximately 1:2.

The XRPD pattern of the formic acid solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 9: Table 9 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 5.95 14.85140 8.4 6.75 13.10517 6.8 8.19 10.81538 37.7 8.69 10.19122 14.0 9.55 9.28598 21.6 11.86 7.49436 6.3 12.56 7.08311 8.5 13.01 6.84371 17.7 13.65 6.52785 11.5 14.51 6.15055 13.2 15.34 5.82291 19.0 15.61 5.72389 22.3 15.91 5.62161 37.3 16.39 5.45934 12.1 16.90 5.30061 10.5 17.19 5.21335 10.4 17.38 5.15683 10.1 17.71 5.06363 14.3 18.35 4.89247 26.8 18.59 4.83321 41.9 19.17 4.69148 12.4 19.54 4.60619 7.3 19.77 4.55399 10.7 19.97 4.51145 8.6 20.69 4.36114 9.0 21.08 4.28427 11.7 22.20 4.07693 39.8 22.51 4.02348 100.0 23.02 3.93980 18.5 23.47 3.86888 14.3 23.84 3.81235 14.4 24.17 3.76329 12.1 24.55 3.70732 10.5 24.98 3.64784 9.3 25.25 3.61107 14.5 26.36 3.46952 5.3 26.58 3.44361 5.7 27.43 3.34421 7.1 28.03 3.27797 22.0 29.04 3.17335 6.9 29.41 3.13700 6.8 29.76 3.10345 7.7 30.17 3.06534 11.9 31.49 2.94912 5.0 31.94 2.91212 4.3 32.08 2.90108 4.0 32.72 2.85035 6.2 33.09 2.82209 4.4 33.51 2.79021 3.7 33.81 2.76897 4.2 34.25 2.73716 3.4 35.07 2.68134 2.7 35.57 2.64817 3.6 36.51 2.58957 2.5 36.92 2.56494 2.7 39.27 2.43404 3.1 39.99 2.39743 2.9 40.90 2.35300 3.3 41.04 2.34657 3.6 41.21 2.33838 3.6 43.15 2.25245 3.1 43.25 2.24838 3.5 44.69 2.19063 3.1

The TGA curve shows that the formic acid solvate of the compound represented by formula I has a weight loss of about 10.2% when heated to about 150 ºC, and may decompose when it is greater than or equal to about 300 ºC. The DSC curve shows that the formic acid solvate of the compound represented by formula I has endothermic peaks at about 136.9 ºC and about 175.5 ºC. Example 7 Ethyl formate solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, heat it to 60ºC and stir magnetically, slowly add 1.0 mL of ethyl formate dropwise until the solid is completely dissolved, and filter the solution with a 0.22 μm organic filter at about 60ºC. After filtration, the filtrate was quickly transferred to room temperature for cooling, crystals were precipitated, centrifuged, and dried under vacuum to obtain a white solid, which is the ethyl formate solvate of the compound represented by Formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern was shown in Figure 23. Thermogravimetric analysis (TGA) was performed on it, and the obtained TGA pattern was shown in Figure 24. Differential scanning calorimetry (DSC) was performed on it, and the obtained The DSC spectrum is shown in Figure 25. After detection, the white solid obtained was the ethyl formate solvate of the compound represented by formula I, where the molar ratio of the compound represented by formula I to ethyl formate was approximately 1:1.

The XRPD pattern of the ethyl formate solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 10: Table 10 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 4.77 18.53180 100.0 7.76 11.40723 22.8 8.91 9.94855 2.7 9.55 9.28598 51.0 11.90 7.47024 2.8 13.15 6.77411 2.8 14.02 6.35922 1.8 14.31 6.23230 2.1 15.54 5.75182 24.4 15.79 5.66206 6.3 16.02 5.58175 4.6 16.45 5.44052 9.9 16.61 5.39099 16.2 17.09 5.24210 3.2 17.95 4.99995 2.0 18.59 4.83321 2.3 19.15 4.69607 4.2 20.26 4.44920 2.5 20.73 4.35332 4.6 20.98 4.30321 8.0 21.46 4.21024 16.4 22.55 4.01691 2.3 23.39 3.88101 3.3 24.53 3.71008 7.9 24.92 3.65583 5.4 25.25 3.61107 6.3 25.56 3.57005 15.6 26.03 3.51042 22.4 28.91 3.18698 17.5 29.53 3.12572 2.8 30.27 3.05643 2.0 31.88 2.91688 1.8 33.13 2.81916 1.8 33.83 2.76757 2.2 36.53 2.58838 1.4 37.67 2.52078 1.1 38.06 2.49888 1.0 38.80 2.45861 2.0 39.95 2.39937 1.1 42.47 2.28150 0.9 44.34 2.20427 1.3

The TGA curve shows that the ethyl formate solvate of the compound represented by formula I has a weight loss of about 9.9% during heating to about 140 ºC, and may decompose at temperatures greater than or equal to about 280 ºC. The DSC curve shows that the ethyl formate solvate of the compound represented by Formula I has an endothermic peak at about 121.8 ºC and an exothermic peak at about 130.3 ºC, which may correspond to the recrystallization process; a melting peak appears at about 172.1 ºC. Example 8 Ethylene glycol methyl ether solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 4 mL EP tube. Add 0.2 mL of ethylene glycol methyl ether and 2.0 mL of cyclohexane at room temperature. Stir magnetically for 7 days. Crystals will precipitate and be separated by centrifugation. After vacuum drying, a white solid is obtained, which is the ethylene glycol methyl ether solvate of the compound represented by formula I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 28. After detection, the white solid obtained was the ethyl formate solvate of the compound represented by formula I, in which the molar ratio of the compound represented by formula I to ethylene glycol methyl ether was approximately 1:1.

The XRPD pattern of the ethylene glycol methyl ether solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 11: Table 11 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.73 13.14282 21.0 8.48 10.44618 10.9 10.37 8.56181 10.3 10.89 8.15390 18.9 11.34 7.83638 30.6 12.33 7.21497 2.1 13.44 6.62975 100.0 14.41 6.19115 5.5 14.70 6.07099 1.9 15.48 5.77296 3.3 15.69 5.69624 4.6 15.92 5.61493 3.5 16.95 5.28292 25.9 17.83 5.03158 2.1 18.18 4.93793 5.6 19.11 4.70526 2.1 19.68 4.57559 5.2 19.77 4.55399 5.3 20.20 4.46150 46.0 20.59 4.38083 24.8 20.86 4.32619 36.1 21.04 4.29182 17.6 21.41 4.22117 18.1 21.83 4.14243 10.0 22.11 4.09394 5.6 22.67 3.99733 4.2 23.12 3.92414 5.0 23.27 3.89937 3.5 23.72 3.83001 2.8 24.19 3.76045 29.1 24.81 3.67192 5.6 25.35 3.59814 2.9 25.56 3.57005 3.8 25.84 3.53500 2.5 26.44 3.46005 11.0 27.02 3.39083 12.0 27.53 3.33332 3.1 27.98 3.28425 4.2 28.48 3.23073 2.0 29.01 3.17723 3.6 29.39 3.13889 4.8 31.14 2.97886 2.3 31.30 2.96556 2.8 32.62 2.85790 1.2 33.07 2.82356 1.9 34.37 2.72901 3.9 37.52 2.52968 1.4 39.87 2.40326 1.2 40.28 2.38300 1.7 40.76 2.35947 2.0 41.35 2.33207 1.7

The TGA curve shows that the ethylene glycol methyl ether solvate of the compound represented by Formula I has a weight loss of approximately 11.1% during heating to approximately 200 ºC, and may decompose at temperatures greater than or equal to approximately 300 ºC. The DSC curve shows that the ethylene glycol methyl ether solvate of the compound represented by Formula I has an endothermic peak of weight loss at about 110.5 ºC, an exothermic peak at about 114.3 ºC, and a melting endothermic peak at about 173.5 ºC. Example 9 Crystal Form II of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 10.0 mL EP tube, add 10.0 mL of isopropanol, stir magnetically at room temperature for 7 days, precipitate, centrifuge, and vacuum dry to obtain a white solid. That is, the crystal form II of the compound represented by formula I.

The obtained white solid was detected by The DSC spectrum is shown in Figure 31. After detection, the white solid obtained was the crystal form II of the compound represented by formula I.

The XRPD pattern of crystalline form II of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 12: Table 12 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 4.24 20.81832 16.1 6.73 13.14282 32.9 6.96 12.70478 19.7 8.68 10.21388 31.0 9.49 9.34249 9.0 10.04 8.84066 3.4 11.03 8.05452 60.1 11.80 7.53085 5.0 12.39 7.18154 6.1 12.64 7.04025 4.1 13.44 6.62975 23.3 14.53 6.14250 43.3 15.32 5.83012 42.2 15.61 5.72389 29.9 16.41 5.45305 7.5 16.68 5.36657 8.3 17.07 5.24789 13.7 17.38 5.15683 26.5 17.83 5.03158 19.8 18.24 4.92268 15.7 18.70 4.80414 10.0 19.02 4.72841 7.8 19.50 4.61501 4.0 19.95 4.51567 9.4 20.20 4.46150 13.0 21.06 4.28804 29.4 21.78 4.15298 6.4 22.20 4.07693 100.0 22.90 3.95878 6.8 23.17 3.91481 9.0 23.49 3.86585 12.7 23.91 3.80068 9.0 24.40 3.72949 4.5 24.79 3.67461 5.1 25.16 3.62411 4.8 25.41 3.59043 11.0 25.82 3.53747 5.3 26.17 3.49345 4.8 27.00 3.39309 4.9 27.57 3.32898 11.0 27.76 3.30751 9.9 28.11 3.26965 18.7 28.60 3.21867 3.9 29.01 3.17723 5.8 29.22 3.15601 6.8 29.45 3.13323 10.2 29.92 3.08880 19.5 30.87 3.00250 3.4 31.43 2.95403 3.5 31.92 2.91371 3.3 32.39 2.87621 2.7 33.11 2.82062 2.6 33.53 2.78878 6.6 33.90 2.76198 4.0 34.78 2.70095 2.4 35.34 2.66335 4.2 37.89 2.50867 3.8 39.91 2.40131 2.7 40.90 2.35300 2.3 42.26 2.29085 2.8 42.71 2.27142 2.8 43.41 2.24193 2.2 44.59 2.19439 3.3

The TGA curve shows that the crystal form II of the compound represented by formula I has a weight loss of about 1.0% when heated to about 200 ºC, and may decompose when it is greater than or equal to about 300 ºC. The DSC curve shows that the crystal form II of the compound represented by formula I has two endothermic peaks at about 166 ºC and about 174 ºC. Example 10 Methanol solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, heat it to 60ºC, stir magnetically, slowly add 3.4 mL of methanol dropwise until the solid is dissolved, filter the solution with a 0.22 μm organic filter at about 60ºC Quickly transfer to room temperature and cool, crystals precipitate, centrifuge, and vacuum dry to obtain a white solid, which is the methanol solvate of the compound represented by formula I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 34. After detection, the white solid obtained was the methanol solvate of the compound represented by Formula I, where the molar ratio of the compound represented by Formula I to methanol was approximately 1:1.

The XRPD pattern of the methanol solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 13: Table 13 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.15 14.38368 100.0 6.60 13.41269 4.8 6.77 13.06772 5.2 8.27 10.71437 12.4 8.66 10.23663 3.4 9.53 9.30474 1.8 10.68 8.31522 9.4 10.75 8.25581 8.6 11.18 7.94392 17.2 11.84 7.50649 2.7 12.23 7.27141 59.1 13.44 6.62975 15.5 14.41 6.19115 6.0 15.50 5.76589 3.9 15.71 5.68937 4.3 15.91 5.62161 3.1 16.27 5.49738 8.1 16.51 5.42183 5.2 16.86 5.31248 3.1 17.36 5.16242 15.1 17.56 5.10705 10.8 18.22 4.92775 4.4 18.49 4.85772 7.9 19.02 4.72841 5.9 19.29 4.66419 4.5 19.79 4.54970 12.6 20.98 4.30321 5.6 21.35 4.23216 4.9 21.62 4.18140 18.5 22.16 4.08372 9.7 22.47 4.03008 57.8 23.15 3.91792 3.9 23.64 3.84187 5.9 23.95 3.79488 4.0 24.52 3.71284 26.9 25.16 3.62411 4.5 25.39 3.59300 13.2 26.05 3.50799 2.5 26.91 3.40442 7.8 27.33 3.35517 5.0 27.92 3.29056 13.1 28.38 3.24087 4.9 28.97 3.18112 3.9 29.34 3.14457 2.9 30.04 3.07792 2.9 30.77 3.01104 2.9 31.28 2.96721 6.3 31.80 2.92326 1.9 32.21 2.89014 2.9 32.74 2.84884 4.2 34.66 2.70889 1.4 35.17 2.67488 1.6 36.06 2.61723 1.2 36.88 2.56726 1.5 37.56 2.52744 2.0 38.20 2.49133 1.3 38.86 2.45550 1.2 43.64 2.23234 2.1

The TGA curve shows that the methanol solvate of the compound represented by formula I has a weight loss of about 5.6% when heated to about 150 ºC, and may decompose after being heated to about 300 ºC or greater. The DSC curve shows that the methanol solvate of the compound represented by formula I has an endothermic peak corresponding to the weight loss of TGA at about 110.7 ºC, and a melting endothermic peak at about 180.9 ºC. Example 11 n-propanol solvate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, heat it to 60ºC, stir magnetically, slowly add 3.3 mL of n-propanol dropwise until the solid is dissolved, filter the solution with 0.22 μm organic filter at about 60ºC Quickly transfer to room temperature and cool, crystals precipitate, centrifuge, and vacuum dry to obtain a white solid, which is the n-propanol solvate of the compound represented by formula I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 37. After detection, the white solid obtained was the n-propanol solvate of the compound represented by formula I, where the molar ratio of the compound represented by formula I to n-propanol was approximately 1:1.5.

The n-propanol solvate of the compound represented by formula I uses Cu-Kα radiation and the XRPD pattern expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 14: Table 14 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.15 14.38368 24.6 8.19 10.81538 31.3 9.22 9.61574 5.3 10.52 8.43669 11.2 11.61 7.65515 3.5 12.29 7.23744 67.6 13.44 6.62975 15.7 14.06 6.34199 15.5 14.91 5.98590 5.3 15.42 5.79425 4.4 16.16 5.53599 25.0 16.35 5.47196 17.9 16.88 5.30654 6.2 17.30 5.17928 18.1 17.73 5.05826 14.5 18.04 4.97391 7.0 18.51 4.85279 21.6 18.80 4.78020 11.2 19.27 4.66871 5.0 19.77 4.55399 20.8 20.05 4.49467 6.5 20.34 4.43291 6.7 21.09 4.28050 9.8 21.54 4.19577 15.2 22.22 4.07354 100.0 22.84 3.96834 15.9 23.08 3.93039 8.1 23.50 3.86284 9.1 24.69 3.68816 39.2 24.98 3.64784 6.9 25.47 3.58276 24.0 25.91 3.52512 4.2 26.48 3.45533 8.3 27.20 3.37067 11.8 27.72 3.31178 24.4 28.25 3.25518 3.2 28.56 3.22268 3.7 28.91 3.18698 4.9 29.30 3.14838 3.7 30.19 3.06355 2.7 31.12 2.98054 4.4 31.42 2.95567 5.2 31.71 2.93129 6.1 32.64 2.85638 7.7 33.38 2.80026 2.1 34.49 2.72092 2.7 35.30 2.66590 2.5 36.12 2.61358 1.6 36.82 2.57075 3.5 37.36 2.53866 3.1 38.02 2.50104 2.9 40.12 2.39067 2.3 41.00 2.34840 2.2 41.77 2.31252 2.6 42.59 2.27644 2.2 43.91 2.22130 4.0 44.67 2.19138 1.6

The TGA curve shows that the n-propanol solvate of the compound represented by formula I has a weight loss of about 9.4% when heated to about 150 ºC, and may decompose when it is greater than or equal to about 300 ºC. The DSC curve shows that the n-propanol solvate of the compound represented by formula I has an endothermic peak corresponding to the weight loss of TGA at about 62.9 ºC, and a melting endothermic peak at about 180.5 ºC. Example 12 Glyme solvate of the compound represented by formula I

Weigh 30 mg of crystal form I of the compound represented by formula I into a 3.7 mL glass bottle, heat it to 60ºC, stir magnetically, slowly add 0.6 mL of ethylene glycol dimethyl ether dropwise until the solid is dissolved, and dissolve the solution with 0.22 μm at about 60ºC. After organic filtration, the solution was quickly transferred to room temperature for cooling, crystals were precipitated, centrifuged, and dried under vacuum to obtain a white solid, which is the ethylene glycol dimethyl ether solvate of the compound represented by formula I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 40. After detection, the white solid obtained was the ethylene glycol dimethyl ether solvate of the compound represented by formula I, in which the molar ratio of the compound represented by formula I to ethylene glycol dimethyl ether was approximately 1:1.

The XRPD pattern of the glycol dimethyl ether solvate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 15: Table 15 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.71 13.18071 22.6 8.46 10.46999 4.9 8.68 10.21388 2.6 9.49 9.34249 1.2 10.29 8.62581 2.3 10.83 8.19726 4.5 11.30 7.86298 17.9 13.40 6.64863 100.0 14.39 6.19933 3.5 14.51 6.15055 3.7 15.30 5.83734 3.4 15.59 5.73085 3.7 15.79 5.66206 3.9 16.84 5.31843 6.0 17.36 5.16242 2.6 17.87 5.02099 1.7 18.24 4.92268 4.1 19.71 4.56692 4.5 20.14 4.47388 48.1 20.49 4.40070 10.4 20.82 4.33390 32.0 21.00 4.29941 3.5 21.39 4.22483 11.0 21.70 4.16714 3.2 22.18 4.08032 8.8 22.42 4.04002 2.1 22.71 3.99084 3.5 23.25 3.90245 1.9 23.47 3.86888 1.9 23.66 3.83890 2.0 24.13 3.76899 31.1 24.67 3.69089 2.1 25.31 3.60330 2.3 25.47 3.58276 2.8 25.76 3.54493 1.9 26.38 3.46714 6.7 26.96 3.39761 10.1 27.51 3.33549 2.3 27.76 3.30751 1.8 28.11 3.26965 2.0 28.95 3.18307 2.3 29.22 3.15601 1.6 29.88 3.09245 2.0 30.95 2.99570 1.2 31.20 2.97386 1.6 32.93 2.83391 1.0 33.81 2.76897 1.1 34.27 2.73580 3.6 37.44 2.53416 1.2 39.97 2.39840 0.9 40.24 2.38491 1.4 40.67 2.36413 1.8 41.27 2.33567 1.8

The TGA curve shows that the ethylene glycol dimethyl ether solvate of the compound represented by Formula I has a weight loss of approximately 9.6% during heating to approximately 130 ºC, and may decompose at temperatures greater than or equal to approximately 300 ºC. The DSC curve shows that the ethylene glycol dimethyl ether solvate of the compound represented by formula I has an endothermic peak corresponding to the weight loss of TGA at about 94.6 ºC, and a melting endothermic peak at about 178.6 ºC. Example 13 Monohydrate of the compound represented by formula I

Weigh 20 mg of crystal form I of the compound represented by formula I into a 4 mL EP tube, add 4.0 mL of water, stir magnetically at room temperature for 7 days, precipitate crystals, centrifuge, and vacuum dry to obtain a white solid, which is formula Monohydrate of the compound shown in I.

The resulting white solid was subjected to The DSC spectrum is shown in Figure 43. After testing, the white solid obtained was the monohydrate of the compound represented by Formula I, in which the molar ratio of the compound represented by Formula I to water was approximately 1:1.

The XRPD pattern of the monohydrate of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 16: Table 16 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 8.93 9.92706 9.8 9.24 9.59568 45.2 9.65 9.19331 12.5 10.13 8.75675 7.7 12.54 7.09391 89.8 13.07 6.81370 6.1 14.89 5.99353 16.4 14.99 5.95556 15.3 15.73 5.68251 25.2 15.98 5.59497 27.6 16.24 5.51019 11.0 16.78 5.33638 19.7 17.89 5.01571 31.2 18.47 4.86265 9.1 19.27 4.66871 9.1 19.71 4.56692 4.9 20.22 4.45739 23.9 20.45 4.40871 100.0 21.13 4.27299 9.6 21.60 4.18498 16.2 22.14 4.08712 5.0 22.79 3.97795 12.4 23.04 3.93666 9.5 23.99 3.78909 23.7 24.24 3.75195 15.3 24.83 3.66922 7.0 25.22 3.61627 88.3 26.23 3.48623 15.5 26.73 3.42504 15.6 26.96 3.39761 9.9 27.33 3.35517 10.6 27.96 3.28635 11.4 28.54 3.22469 9.4 28.99 3.17917 7.2 29.51 3.12760 32.7 30.46 3.03878 4.8 31.22 2.97219 5.6 31.82 2.92167 7.1 32.68 2.85336 6.7 33.07 2.82356 5.7 33.28 2.80749 6.6 34.16 2.74400 7.8 35.22 2.67102 4.1 36.06 2.61723 4.9 36.80 2.57192 4.4 36.99 2.56032 4.3 40.28 2.38300 5.1

The TGA curve shows that the monohydrate of the compound represented by formula I has a weight loss of about 4.9% when heated to about 130 ºC, and may decompose when it is greater than or equal to about 300 ºC. The DSC curve shows that the monohydrate of the compound represented by formula I has an endothermic peak corresponding to the weight loss of TGA at about 111.4 ºC, an exothermic peak at about 154.1 ºC, and a melting endothermic peak at about 178.6 ºC. Preparation of single crystal

Weigh 71.6 mg of crystal form I of the compound represented by formula I into the bottle, add 20 mL of acetonitrile, filter with a 0.2 micron nylon filter, transfer 10 mL of the filtrate to the bottle and seal it with aluminum foil. After punching three small holes in the aluminum foil, let the solution stand at room temperature to evaporate. After the solution is partially evaporated, monohydrate crystals of the compound represented by Formula I of a size suitable for single crystal testing (generally 50*50*50 μm) are obtained.

The single crystal structure analysis data is shown in Table 17, and the atomic displacement ellipsoid diagram is shown in Figure 44. Table 17 monohydrate empirical C ₂₇ H ₃₀ N ₈ O ₂ Relative molecular mass 498.59 temperature 299.62(10)K Wavelength 1.54184Å Crystal system Triclinic space group P Unit cell parameters a = 11.2944(2) Å α = 112.572(2)° b = 11.4048(2) Å β = 107.1220(10)° c = 11.8672(2) Å γ = 102.2480(10)° Volume 1254.06(4) Å3 Z 2 Example 14 Oxalate salt of the compound represented by formula I

Weigh 24 mg of crystal form I of the compound represented by formula I and 14 mg of oxalic acid (2.2 equivalents), add 1.0 mL of methanol, stir magnetically at room temperature for 2 days, centrifuge the suspension, and dry under vacuum to obtain a white solid, namely The oxalate salt of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern is shown in Figure 45. After testing, the white solid obtained was the oxalate of the compound represented by formula I. Thermogravimetric analysis (TGA) was performed on it, and the obtained TGA spectrum was shown in Figure 46. Differential scanning calorimetry (DSC) was performed on it, and the result was The DSC spectrum is shown in Figure 47. NMR detection was performed on it, and the obtained NMR spectrum is shown in Figure 48.

The XRPD pattern of the oxalate salt of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 18: Table 18 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 5.82 15.19747 41.5 8.71 10.16867 16.6 9.71 9.13860 55.0 10.83 8.19726 23.8 11.24 7.90324 48.0 11.57 7.68051 17.1 12.31 7.22619 14.4 12.56 7.08311 13.1 14.53 6.14250 100.0 15.52 5.75885 10.5 15.89 5.62831 24.6 16.57 5.40328 14.4 17.21 5.20764 21.7 17.50 5.12353 59.9 18.12 4.95328 13.0 18.92 4.75180 9.2 19.42 4.63277 79.3 19.56 4.60179 46.7 19.87 4.53261 18.2 20.51 4.39671 24.8 20.90 4.31850 31.5 21.21 4.25804 65.5 21.43 4.21752 61.4 21.93 4.12497 11.4 22.47 4.03008 29.6 22.73 3.98761 52.3 23.23 3.90553 21.3 24.24 3.75195 32.9 24.65 3.69362 11.2 25.20 3.61888 14.8 25.45 3.58531 35.3 26.25 3.48383 9.2 26.73 3.42504 15.3 27.06 3.38633 21.0 27.61 3.32467 38.6 28.40 3.23884 7.7 29.14 3.16369 15.5 29.69 3.11083 14.0 30.19 3.06355 13.1 31.22 2.97219 11.5 31.78 2.92486 8.9 32.52 2.86549 8.1 32.78 2.84584 7.9 33.30 2.80604 8.1 33.94 2.75920 7.5 34.86 2.69568 8.4 35.38 2.66080 12.3 36.57 2.58601 7.4 37.95 2.50539 5.7 39.33 2.43102 6.9 40.24 2.38491 6.8 41.25 2.33657 6.5 42.03 2.30118 7.0 42.55 2.27813 7.3 43.13 2.25326 4.8 43.95 2.21974 6.2 44.36 2.20351 6.5

The TGA curve shows that the oxalate salt of the compound represented by formula I has a weight loss of about 5.9% during heating to about 130 ºC, and may decompose at temperatures greater than or equal to about 170 ºC. The DSC curve shows that the oxalate of the compound represented by formula I has an endothermic signal corresponding to the weight loss of TGA in the range of 25-130 ºC, and an exothermic peak appears at about 175 ºC.

The NMR spectrum shows that the compound has a broadened peak at about 8.28 ppm, the four peaks at 7.57-8.15 ppm change into two peaks, the peak at 5.95 ppm disappears, and the three peaks at 3.39-3.78 ppm shift, indicating that the sample has formed a salt. Example 15 Phosphate salt of the compound represented by formula I

Weigh 24 mg of crystal form I of the compound represented by formula I and 0.11 mL of phosphoric acid (acid solution diluted with 1 mol/L water), add 1.0 mL of methanol, stir magnetically at room temperature for 2 days, centrifuge the suspension, and vacuum After drying, a white solid is obtained, which is the phosphate salt of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern is shown in Figure 49. After testing, the white solid obtained was the phosphate of the compound represented by formula I. Thermogravimetric analysis (TGA) was performed on it, and the obtained TGA spectrum is shown in Figure 50. Differential scanning calorimetry (DSC) was performed on it, and the obtained DSC The spectrum is shown in Figure 51. NMR detection was performed on it, and the obtained NMR spectrum is shown in Figure 52.

The XRPD pattern of the phosphate salt of the compound represented by Formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 19: Table 19 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 3.21 27.48038 100.0 6.36 13.90223 8.9 9.49 9.34249 4.1 12.21 7.28280 18.0 12.66 7.02962 9.0 12.99 6.85378 11.3 14.10 6.32485 8.5 14.56 6.12646 7.6 15.28 5.84459 7.2 15.56 5.74481 17.6 15.89 5.62831 26.7 16.55 5.40945 24.7 17.17 5.21907 8.8 17.40 5.15125 8.1 18.00 4.98429 31.2 19.36 4.64618 28.7 19.89 4.52837 14.1 20.61 4.37687 14.1 21.37 4.22849 49.1 21.83 4.14243 10.7 22.07 4.10080 11.8 22.28 4.06342 12.3 22.63 4.00383 10.5 23.76 3.82410 7.2 24.17 3.76329 20.9 24.52 3.71284 26.6 25.10 3.63198 18.0 25.56 3.57005 11.1 25.97 3.51776 7.9 26.26 3.48144 8.5 26.77 3.42044 5.4 27.08 3.38408 8.2 28.23 3.25724 10.9 28.77 3.20076 7.6 29.61 3.11826 5.6 30.02 3.07973 5.5 30.54 3.03179 4.5 30.91 2.99909 6.9 31.42 2.95567 5.4 32.64 2.85638 5.3 33.07 2.82356 4.3 33.94 2.75920 3.3 35.38 2.66080 5.5 36.02 2.61967 3.8 36.78 2.57309 3.4 40.28 2.38300 3.8 41.81 2.31076 4.1 44.42 2.20122 3.2

The TGA curve shows that the phosphate of the compound represented by formula I has a weight loss of about 4.9% during heating to about 140 ºC, and may decompose at temperatures greater than or equal to about 250 ºC. The DSC curve shows that the phosphate of the compound represented by formula I has an endothermic peak corresponding to the weight loss of TGA at about 151 ºC, and exothermic peaks at about 170.1 ºC and about 242.0 ºC respectively.

The NMR spectrum shows that the peak of the compound at 7.69 ppm has a small shift, and the three peaks at 3-4 ppm have shifted, indicating that the sample has formed a salt. Example 16 Disfumarate salt of the compound represented by formula I

Weigh 24 mg of crystal form I of the compound represented by formula I and 13 mg of fumaric acid (2.2 equivalents), add 1.0 mL of acetone, stir magnetically at room temperature for 2 days, centrifuge the suspension, and dry under vacuum to obtain a white solid , that is, the disfumarate salt of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern is shown in Figure 53. After testing, the white solid obtained was the disfumarate salt of the compound represented by formula I. Thermogravimetric analysis (TGA) was performed on it. The obtained TGA spectrum is shown in Figure 54. Differential scanning calorimetry (DSC) was performed on it. , the obtained DSC spectrum is shown in Figure 55. NMR detection was performed on it, and the obtained NMR spectrum is shown in Figure 56.

The XRPD pattern of the difumarate salt of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 20: Table 20 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 6.13 14.42911 63.3 8.85 10.01357 39.4 9.41 9.41895 27.7 11.36 7.82315 22.5 12.62 7.05092 21.4 14.12 6.31632 32.3 14.56 6.12646 40.1 15.03 5.94051 27.8 16.26 5.50378 34.7 16.99 5.27119 35.9 18.47 4.86265 55.9 18.94 4.74711 44.0 19.83 4.54114 68.9 20.34 4.43291 38.6 21.48 4.20661 100.0 22.61 4.00709 81.1 23.23 3.90553 43.4 24.48 3.71837 37.0 25.70 3.55243 24.2 27.57 3.32898 22.6 28.89 3.18894 27.8 30.48 3.03703 17.3

The TGA curve shows that the difumarate salt of the compound represented by formula I has a weight loss of about 3.0% during heating to about 120 ºC, and may decompose at temperatures greater than or equal to about 170 ºC. The DSC curve shows that the compound represented by formula I has an endothermic signal corresponding to weight loss at 25-100 ºC, an endothermic peak appears at about 147.1 ºC, and an exothermic peak appears at about 152.7 ºC.

The NMR spectrum shows that the compound has a peak at 6.62 ppm, which is a characteristic peak of fumaric acid. The integration results show that the salt-forming ratio of fumaric acid and the compound represented by formula I is about 2:1. Example 17 Monofumaric acid salt of the compound represented by formula I

Weigh 264.0 mg of crystal form I of the compound represented by formula I, add 140.8 mg fumaric acid and 10 mL acetone in sequence, stir magnetically at room temperature for 2 days, centrifuge the suspension, and dry under vacuum to obtain a white solid, namely A fumarate salt of the compound represented by formula I.

The obtained white solid was subjected to XRPD detection, and the obtained XRPD pattern is shown in Figure 57. After testing, the white solid obtained was the monofumarate salt of the compound represented by formula I. Thermogravimetric analysis (TGA) was performed on it. The obtained TGA spectrum is shown in Figure 58. Differential scanning calorimetry (DSC) was performed on it. , the obtained DSC spectrum is shown in Figure 59.

The XRPD pattern of the monofumarate salt of the compound represented by formula I using Cu-Kα radiation and expressed at the 2θ angle includes characteristic peaks at the diffraction angle (2θ) shown in Table 21: Table 21 Angle [°2Th.] d Value [Å] Rel.Intensity [%] 7.28 12.16452 22.2 10.39 8.54597 12.6 11.26 7.88977 41.6 11.78 7.54310 55.1 13.18 6.75449 39.4 13.44 6.62975 40.6 13.94 6.39397 97.6 14.56 6.12646 46.6 14.82 6.02427 28.4 15.11 5.91065 27.2 16.14 5.54248 73.5 16.55 5.40945 21.3 17.67 5.07441 8.1 18.39 4.88249 12.9 18.94 4.74711 11.1 19.75 4.55830 28.9 20.98 4.30321 100.0 21.17 4.26550 51.2 21.85 4.13892 56.7 22.42 4.04002 49.6 23.70 3.83297 43.1 23.93 3.79778 45.3 24.55 3.70732 40.7 24.88 3.66117 48.0 25.23 3.61367 23.3 25.45 3.58531 20.1 25.64 3.55995 27.2 26.32 3.47427 14.6 26.58 3.44361 29.1 26.89 3.40670 15.0 27.33 3.35517 36.4 28.05 3.27589 14.5 29.90 3.09062 10.8 30.39 3.04581 13.1 31.03 2.98894 15.8 31.80 2.92326 12.4 32.89 2.83688 15.4 33.36 2.80170 11.6 33.86 2.76477 8.9 36.25 2.60511 8.9 36.80 2.57192 8.4 37.56 2.52744 8.9 39.95 2.39937 7.3 40.74 2.36040 7.4 41.95 2.30465 7.4 42.69 2.27225 7.3

The TGA curve shows that the monofumarate salt of the compound represented by formula I has a weight loss of about 1.4% during heating to about 120 ºC, and may decompose at temperatures greater than or equal to about 170 ºC. The DSC curve shows that the monofumarate salt of the compound represented by formula I has an endothermic peak at about 196.4 ºC and an exothermic peak at about 199.0 ºC. Experimental Example 1 Light Stability Experiment

The samples were placed in a pharmaceutical strong light stability test chamber (Labonce-150PS-II, Beijing Lanbeishi Constant Temperature Technology Co., Ltd.) and placed under 25 ºC and 4500lux light conditions. Samples were taken on the 6th and 35th days respectively. Test XRPD and take samples on day 35 to check product purity by HPLC.

The results are shown in Table 22 and Figures 60 to 63. The results show that the oxalate, phosphate, monofumarate and crystal form I of the compound represented by formula I can maintain the stability of the crystal form within 6 days and 35 days under the conditions of 25 ºC and 4500lux light. Table 22 Chemical purity results of samples after 35 days of illumination sample Chemical purity (%) Oxalate salt of compound represented by formula I 93.31 Phosphates of compounds represented by formula I 90.01 Monofumaric acid of the compound represented by formula I 95.03 Crystal form I of the compound represented by formula I 97.04 Experimental Example 2 High Humidity Stability Experiment

The samples were placed in a drug stability test chamber (Labonce-150SD, Beijing Lambeishi Constant Temperature Technology Co., Ltd.) at 25 ºC and 92.5% RH. Samples were taken on the 6th and 35th days respectively to test XRPD. And on the 35th day, samples were taken to detect product purity by HPLC.

The results are shown in Table 23 and Figures 64 to 67. The results show that the oxalate, phosphate, monofumarate and crystal form I of the compound represented by formula I can maintain stable crystal forms within 6 days and 35 days under the conditions of 25 ºC and 92.5% RH. Table 23 Chemical purity results of samples after high humidity storage for 35 days sample Chemical purity (%) Oxalate salt of compound represented by formula I 99.83 Phosphates of compounds represented by formula I 97.39 Monofumaric acid salt of the compound represented by formula I 99.43 Crystal form I of the compound represented by formula I 99.81 Experimental Example 3 High Temperature Stability Experiment

The samples were placed in a drug stability test chamber (Labonce-150SD, Beijing Lambeishi Constant Temperature Technology Co., Ltd.) and placed at 60 ºC. Samples were taken on the 6th and 35th days respectively for XRPD testing. Samples will be taken at 35 days to test product purity by HPLC.

The results are shown in Table 24 and Figures 68 to 71. The results show that the oxalate, phosphate, monofumarate and crystal form I of the compound represented by formula I can maintain stable crystal forms within 6 days and 35 days at 60 ºC. Table 24 Chemical purity results of samples stored at high temperature for 35 days sample Chemical purity (%) Oxalate salt of compound represented by formula I 96.94 Phosphates of compounds represented by formula I 83.34 Monofumaric acid salt of the compound represented by formula I 95.28 Crystal form I of the compound represented by formula I 98.46 Experimental Example 4 Accelerated Stability Experiment 1

The samples were placed in a drug stability test chamber (Labonce-150SD, Beijing Lambestone Constant Temperature Technology Co., Ltd.) at 40 ºC and 75% RH. Samples were taken on the 6th and 35th days respectively for XRPD testing. , and take samples on the 35th day to detect product purity by HPLC.

The results are shown in Table 25 and Figures 72 to 75. The results show that the oxalate, phosphate, monofumarate and crystal form I of the compound represented by formula I can maintain the stability of the crystal form within 6 days and 35 days under the conditions of 40 ºC and 75% RH. Table 25 Chemical purity results of samples stored under accelerated conditions for 35 days sample Chemical purity (%) Oxalate salt of compound represented by formula I 97.41 Phosphates of compounds represented by formula I 96.70 Monofumaric acid salt of the compound represented by formula I 94.70 Crystal form I of the compound represented by formula I 99.34 Experimental example 5 Hygroscopicity test

Dynamic moisture adsorption (DVS) experiments were conducted on the oxalate, phosphate, monofumarate and crystalline form I of the compound represented by formula I. The test was conducted in gradient mode with a humidity change of 50%-95%-0%- 50%, the humidity change amount of each gradient in the range of 0% to 90% is 10%. The gradient end point is judged by dm/dt method. The gradient end point is when dm/dt is less than 0.002% and maintained for 10 minutes. After the test is completed, XRPD analysis is performed on the sample to confirm whether the solid form has changed. The results are shown in Figures 76 to 83.

The DVS results showed that the oxalate of the compound represented by formula I gained 2.24% weight at 95% humidity and lost 3.93% weight at 0% humidity. The XRPD of the sample after the DVS test was generally consistent with that before the test, indicating that the compound represented by formula I had a weight gain of 2.24%. The crystal form of oxalate did not change during the DVS test. It can be seen that the oxalate of the compound represented by formula I has hygroscopicity.

The DVS results showed that the phosphate of the compound represented by formula I gained 2.75% weight at 95% humidity and lost 0.86% weight at 0% humidity; the XRPD of the sample after the DVS test was generally consistent with that before the test, indicating that the phosphate of the compound represented by formula I The salt did not change its crystal form during the DVS test. It can be seen that the phosphate of the compound represented by formula I has hygroscopicity.

The DVS results show that the monofumarate of the compound represented by Formula I gained 1.11% weight at 95% humidity and lost 1.53% weight at 0% humidity; the XRPD of the sample after the DVS test was generally consistent with that before the test, indicating that Formula I The fumarate salt of the compound, Form A, did not change its crystalline form during the DVS test. It can be seen that the monofumarate salt of the compound represented by formula I has slight hygroscopicity.

The DVS results showed that the crystal form I of the compound represented by formula I gained 0.35% weight at 95% humidity and lost 0.28% weight at 0% humidity. The XRPD of the sample after the DVS test was generally consistent with that before the test, indicating that the compound represented by formula I had a weight gain of 0.35% and a weight loss of 0.28% at 0% humidity. Form I did not undergo any crystalline change during the DVS test. It can be seen that the crystalline form I of the compound represented by formula I is slightly hygroscopic. The crystal form I of the compound represented by formula I is superior to the other three salt forms in terms of hygroscopicity.

Based on the data of Experimental Examples 1-5, it can be clearly determined that the crystal form I of the compound represented by formula I is significantly better than the oxalate, phosphate, and monofumarate of the compound represented by formula I in many aspects, and has the best overall performance. good. Experimental Example 6 Long-term stability experiment

Take multiple portions of the crystal form, salt, solvate or hydrate involved in the present invention in two weights of 1.5g and 3.1g respectively, then place them into double-layer low-density polyethylene bags, tie them tightly and place them in Fill the aluminum foil bag with nitrogen and heat seal it, and finally place it in a fiber barrel; then store it under the storage conditions of temperature: 25℃±2℃; humidity: 60%±5%. For each crystal form, salt, and solvent compound substance or hydrate, take out several samples in the 3rd, 6th, 9th, and 12th months, and conduct the following tests: visual appearance inspection, (meter), high performance liquid chromatography to detect purity (area percentage), Karl Fischer titration coulometric method to detect moisture content (weight percentage).

Part of the test results are shown in Table 26. The results show that after 6 months of storage in the accelerated stability test, the crystal form of Form I remained stable, with almost no change in moisture content. The compound had good stability and no obvious degradation occurred. Table 26 Long-term stability experimental results of Form I Test items Day 0 3 months 6 months 9 months 12 months Appearance (visual inspection) white solid white solid white solid white solid white solid Crystal form (XRPD) Form I NA NA NA Form I Purity (HPLC, area %) 99.15% 99.14% 99.15% 99.13% 99.15% Content (HPLC, weight percent, based on anhydrous matter) 99.6% 100.4% 100.5% 99.4% 99.2% Moisture content (Karl Fischer titration coulomb method, weight percent) 0.04% 0.22% 0.14% 0.20% 0.23% Experimental Example 7 Accelerated Stability Experiment 2

Take multiple portions of the crystal form, salt, solvate or hydrate involved in the present invention in two weights of 1.5g and 3.1g respectively, then place them into double-layer low-density polyethylene bags, tie them tightly and place them in Fill the aluminum foil bag with nitrogen and heat seal the aluminum foil bag, and finally place it in a fiber barrel; then store it under the storage conditions of temperature: 40℃±2℃; humidity: 75%±5%. For each crystal form, salt, and solvent compound substances or hydrates, take out several samples in the first, third and sixth months and conduct the following tests: visual appearance inspection, XRPD detection (crystal form detection), high performance liquid chromatography detection of content (weight percentage, based on anhydrous substance) , high performance liquid chromatography to detect purity (area percentage), Karl Fischer titration coulomb method to detect moisture content (weight percentage).

Part of the test results are shown in Table 27. The results show that after 6 months of storage in the accelerated stability test, the crystal form of Form I remained stable, with almost no change in moisture content. The compound had good stability and no obvious degradation occurred. Table 27 Accelerated Stability 2 Experimental Results of Crystal Form I Test items Day 0 1 month 3 months 6 months Appearance (visual inspection) white solid white solid white solid white solid Crystal form (XRPD) Form I NA NA Form I Purity (HPLC, area %) 99.15% 99.15% 99.13% 99.15% Content (HPLC, weight percent, based on anhydrous matter) 99.6% 98.8% 99.9% 100.4% Moisture content (Karl Fischer titration coulomb method, weight percent) 0.04% 0.16% 0.19% 0.13%

Figure 1 shows the XRPD pattern of crystal form I of the compound represented by formula I prepared in Embodiment 1 of the present invention; Figure 2 shows the thermogravimetric analysis (TGA) curve of crystal form I of the compound represented by formula I prepared in Embodiment 1 of the present invention; Figure 3 shows the differential scanning calorimetry (DSC) curve of the crystal form I of the compound represented by formula I prepared in Embodiment 1 of the present invention; Figure 4 shows the NMR spectrum of the crystal form I of the compound represented by Formula I prepared in Embodiment 1 of the present invention; Figure 5 shows the atomic displacement ellipsoid diagram of the crystalline form I of the compound represented by formula I prepared in Embodiment 1 of the present invention; Figure 6 shows the XRPD pattern of the acetonitrile solvate 1 of the compound represented by Formula I prepared in Embodiment 2 of the present invention; Figure 7 shows the thermogravimetric analysis (TGA) curve of the acetonitrile solvate 1 of the compound represented by Formula I prepared in Embodiment 2 of the present invention; Figure 8 shows the differential scanning calorimetry (DSC) curve of the acetonitrile solvate 1 of the compound represented by Formula I prepared in Embodiment 2 of the present invention; Figure 9 shows the atomic displacement ellipsoid diagram of the acetonitrile solvate 1 of the compound represented by Formula I prepared in Embodiment 2 of the present invention; Figure 10 shows the XRPD pattern of acetonitrile solvate 2 of the compound represented by Formula I prepared in Embodiment 3 of the present invention; Figure 11 shows the thermogravimetric analysis (TGA) curve of the acetonitrile solvate 2 of the compound represented by Formula I prepared in Embodiment 3 of the present invention; Figure 12 shows the differential scanning calorimetry (DSC) curve of the acetonitrile solvate 2 of the compound represented by Formula I prepared in Embodiment 3 of the present invention; Figure 13 shows the XRPD pattern of the DMSO compound of the compound represented by Formula I prepared in Embodiment 4 of the present invention; Figure 14 shows the thermogravimetric analysis (TGA) curve of the DMSO solvate of the compound represented by Formula I prepared in Embodiment 4 of the present invention; Figure 15 shows the differential scanning calorimetry (DSC) curve of the DMSO solvate of the compound represented by Formula I prepared in Embodiment 4 of the present invention; Figure 16 shows the XRPD pattern of the ethanol solvate of the compound represented by Formula I prepared in Embodiment 5 of the present invention; Figure 17 shows the thermogravimetric analysis (TGA) curve of the ethanol solvate of the compound represented by Formula I prepared in Embodiment 5 of the present invention; Figure 18 shows the differential scanning calorimetry (DSC) curve of the ethanol solvate of the compound represented by Formula I prepared in Embodiment 5 of the present invention; Figure 19 shows the atomic displacement ellipsoid diagram of the ethanol solvate of the compound represented by Formula I prepared in Embodiment 5 of the present invention; Figure 20 shows the XRPD pattern of the formic acid solvate of the compound represented by Formula I prepared in Embodiment 6 of the present invention; Figure 21 shows the thermogravimetric analysis (TGA) curve of the formic acid solvate of the compound represented by Formula I prepared in Embodiment 6 of the present invention; Figure 22 shows the differential scanning calorimetry (DSC) curve of the formic acid solvate of the compound represented by Formula I prepared in Embodiment 6 of the present invention; Figure 23 shows the XRPD pattern of the ethyl formate solvate of the compound represented by Formula I prepared in Embodiment 7 of the present invention; Figure 24 shows the thermogravimetric analysis (TGA) curve of the ethyl formate solvate of the compound represented by Formula I prepared in Embodiment 7 of the present invention; Figure 25 shows the differential scanning calorimetry (DSC) curve of the ethyl formate solvate of the compound represented by Formula I prepared in Embodiment 7 of the present invention; Figure 26 shows the XRPD pattern of the ethylene glycol methyl ether solvate of the compound represented by Formula I prepared in Embodiment 8 of the present invention; Figure 27 shows the thermogravimetric analysis (TGA) curve of the ethylene glycol methyl ether solvate of the compound represented by Formula I prepared in Embodiment 8 of the present invention; Figure 28 shows the differential scanning calorimetry (DSC) curve of the ethylene glycol methyl ether solvate of the compound represented by Formula I prepared in Embodiment 8 of the present invention; Figure 29 shows the XRPD pattern of the crystal form II of the compound represented by Formula I prepared in Embodiment 9 of the present invention; Figure 30 shows the thermogravimetric analysis (TGA) curve of the crystal form II of the compound represented by Formula I prepared in Embodiment 9 of the present invention; Figure 31 shows the differential scanning calorimetry (DSC) curve of the crystal form II of the compound represented by Formula I prepared in Embodiment 9 of the present invention; Figure 32 shows the XRPD pattern of the methanol solvate of the compound represented by Formula I prepared in Embodiment 10 of the present invention; Figure 33 shows the thermogravimetric analysis (TGA) curve of the methanol solvate of the compound represented by Formula I prepared in Embodiment 10 of the present invention; Figure 34 shows the differential scanning calorimetry (DSC) curve of the methanol solvate of the compound represented by Formula I prepared in Embodiment 10 of the present invention; Figure 35 shows the XRPD pattern of the n-propanol solvate of the compound represented by Formula I prepared in Embodiment 11 of the present invention; Figure 36 shows the thermogravimetric analysis (TGA) curve of the n-propanol solvate of the compound represented by Formula I prepared in Embodiment 11 of the present invention; Figure 37 shows the differential scanning calorimetry (DSC) curve of the n-propanol solvate of the compound represented by Formula I prepared in Embodiment 11 of the present invention; Figure 38 shows the XRPD pattern of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I prepared in Embodiment 12 of the present invention; Figure 39 shows the thermogravimetric analysis (TGA) curve of the ethylene glycol dimethyl ether solvate of the compound represented by formula I prepared in Embodiment 12 of the present invention; Figure 40 shows the differential scanning calorimetry (DSC) curve of the ethylene glycol dimethyl ether solvate of the compound represented by Formula I prepared in Embodiment 12 of the present invention; Figure 41 shows the XRPD pattern of the monohydrate solvate of the compound represented by Formula I prepared in Embodiment 13 of the present invention; Figure 42 shows the thermogravimetric analysis (TGA) curve of the monohydrate solvate of the compound represented by Formula I prepared in Embodiment 13 of the present invention; Figure 43 shows the differential scanning calorimetry (DSC) curve of the monoaqueous solvate of the compound represented by Formula I prepared in Embodiment 13 of the present invention; Figure 44 shows the atomic displacement ellipsoid diagram of the monohydrate of the compound represented by Formula I prepared in Embodiment 13 of the present invention; Figure 45 shows the XRPD pattern of the oxalate salt of the compound represented by Formula I prepared in Embodiment 14 of the present invention; Figure 46 shows the thermogravimetric analysis (TGA) curve of the oxalate salt of the compound represented by Formula I prepared in Embodiment 14 of the present invention; Figure 47 shows the differential scanning calorimetry (DSC) curve of the oxalate salt of the compound represented by Formula I prepared in Embodiment 14 of the present invention; Figure 48 shows the NMR spectrum of the oxalate salt of the compound represented by Formula I prepared in Embodiment 14 of the present invention; Figure 49 shows the XRPD pattern of the phosphate of the compound represented by Formula I prepared in Embodiment 15 of the present invention; Figure 50 shows the thermogravimetric analysis (TGA) curve of the phosphate of the compound represented by Formula I prepared in Embodiment 15 of the present invention; Figure 51 shows the differential scanning calorimetry (DSC) curve of the phosphate salt of the compound represented by Formula I prepared in Embodiment 15 of the present invention; Figure 52 shows the NMR spectrum of the phosphate salt of the compound represented by Formula I prepared in Embodiment 15 of the present invention; Figure 53 shows the XRPD pattern of the difumarate salt of the compound represented by Formula I prepared in Embodiment 16 of the present invention; Figure 54 shows the thermogravimetric analysis (TGA) curve of the difumarate salt of the compound represented by Formula I prepared in Embodiment 16 of the present invention; Figure 55 shows the differential scanning calorimetry (DSC) curve of the difumarate salt of the compound represented by Formula I prepared in Embodiment 16 of the present invention; Figure 56 shows the NMR spectrum of the difumarate salt of the compound represented by Formula I prepared in Embodiment 16 of the present invention; Figure 57 shows the XRPD pattern of the monofumarate salt of the compound represented by Formula I prepared in Embodiment 17 of the present invention; Figure 58 shows the thermogravimetric analysis (TGA) curve of the monofumarate salt of the compound represented by Formula I prepared in Embodiment 17 of the present invention; Figure 59 shows the differential scanning calorimetry (DSC) curve of the monofumarate salt of the compound represented by Formula I prepared in Embodiment 17 of the present invention; Figure 60 shows the XRPD comparison pattern of the oxalate of the compound represented by formula I under light conditions; Figure 61 shows the XRPD comparison pattern of the phosphate of the compound represented by formula I under illumination conditions; Figure 62 shows the XRPD comparison pattern of the monofumarate salt of the compound represented by formula I under illumination conditions; Figure 63 shows the XRPD comparison pattern of crystal form I of the compound represented by formula I under illumination conditions; Figure 64 shows the XRPD comparison pattern of the oxalate salt of the compound represented by formula I under high humidity conditions; Figure 65 shows the XRPD comparison pattern of the phosphate of the compound represented by formula I under high humidity conditions; Figure 66 shows the XRPD comparison pattern of the monofumarate salt of the compound represented by formula I under high humidity conditions; Figure 67 shows the XRPD comparative pattern of the crystal form I of the compound represented by formula I under high humidity conditions; Figure 68 shows the XRPD comparison pattern of the oxalate salt of the compound represented by formula I under high temperature conditions; Figure 69 shows the XRPD comparison pattern of the phosphate of the compound represented by formula I under high temperature conditions; Figure 70 shows the XRPD comparison pattern of the monofumarate salt of the compound represented by formula I under high temperature conditions; Figure 71 shows the XRPD comparison pattern of the crystal form I of the compound represented by formula I under high temperature conditions; Figure 72 shows the XRPD comparison pattern of the oxalate salt of the compound represented by formula I under accelerated conditions; Figure 73 shows the XRPD comparison pattern of the phosphate of the compound represented by formula I under accelerated conditions; Figure 74 shows the XRPD comparison pattern of the monofumarate salt of the compound represented by formula I under accelerated conditions; Figure 75 shows the XRPD comparison pattern of crystal form I of the compound represented by formula I under accelerated conditions; Figure 76 shows the dynamic moisture adsorption (DVS) curve of the oxalate salt of the compound represented by formula I; Figure 77 shows the dynamic moisture adsorption (DVS) curve of the phosphate salt of the compound represented by formula I; Figure 78 shows the dynamic moisture adsorption (DVS) curve of the monofumarate salt of the compound represented by formula I; Figure 79 shows the dynamic moisture adsorption (DVS) curve of crystalline form I of the compound represented by formula I; Figure 80 shows the XRPD pattern of the oxalate of the compound represented by formula I after DVS detection; Figure 81 shows the XRPD pattern of the phosphate of the compound represented by formula I after DVS detection; Figure 82 shows the XRPD pattern of the monofumarate salt of the compound represented by formula I after DVS detection; Figure 83 shows the XRPD pattern of crystal form I of the compound represented by formula I after DVS detection.

Claims (21)

A crystal form I of the compound represented by formula I, characterized in that, using Cu-Kα radiation, its X-ray powder diffraction pattern expressed at 2θ angle is 15.3°±0.2°, 15.61°±0.2° and 22.16°±0.2 There is a diffraction peak at °, Preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 6.71°±0.2°, 8.68°±0.2° and 13.4°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is The X-ray powder diffraction pattern also has diffraction peaks at 14.49°±0.2°, 17.34°±0.2° and 21.04°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 9.49° There are diffraction peaks at ±0.2°, 18.26°±0.2°, 18.68°±0.2°, 19°±0.2°, 23.47°±0.2°, 28.07°±0.2°, 29.41°±0.2° and 29.86°±0.2°, Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 12.35°±0.2°, 16.43°±0.2°, 16.72°±0.2°, 17.5°±0.2°, 17.85°±0.2°, 19.25° There are diffraction peaks at ±0.2° and 19.93°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is also at 15.30°±0.2°, 15.61°±0.2°, 22.16°±0.2°, 6.71 There are diffraction peaks at °±0.2°, 8.68°±0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34°±0.2° and 21.04°±0.2°. Preferably, X- expressed in 2θ angle The ray powder diffraction pattern is still at 15.30°±0.2°, 15.61°±0.2°, 22.16°±0.2°, 6.71°±0.2°, 8.68°±0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34° ±0.2°, 21.04°±0.2°, 9.49°±0.2°, 18.26°±0.2°, 18.68°±0.2°, 19°±0.2°, 23.47°±0.2°, 28.07°±0.2° and 29.41°±0.2 There is a diffraction peak at °. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is also at 15.30°±0.2°, 15.61°±0.2°, 22.16°±0.2°, 6.71°±0.2°, 8.68°± 0.2°, 13.4°±0.2°, 14.49°±0.2°, 17.34°±0.2°, 21.04°±0.2°, 9.49°±0.2°, 18.26°±0.2°, 18.68°±0.2°, 19°±0.2° , 23.47°±0.2°, 28.07°±0.2°, 29.41°±0.2°, 12.35°±0.2°, 16.43°±0.2°, 16.72°±0.2°, 17.5°±0.2°, 17.85°±0.2°, 19.25 There are diffraction peaks at °±0.2° and 19.93°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 1. Preferably, its DSC curve is between 175~185°C. There is an endothermic peak within the range. Preferably, the unit cell parameters are: a=13.4624(2) Å, b=16.1538(2) Å, c=11.6605(2) Å, α=γ= 90°, β=99.8420 (10)°, the space group is P 2 ₁ / c . A monohydrate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to water is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 9.24°±0.2°, 12.54°±0.2°, 17.89°±0.2°, 20.45°±0.2°, 25.22°± There are diffraction peaks at 0.2° and 29.51°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2° and 23.99 There is a diffraction peak at °±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 14.89°±0.2°, 14.99°±0.2°, 16.78°±0.2°, and 21.6°±0.2°. There are diffraction peaks at , 24.24°±0.2°, 26.23°±0.2° and 26.73°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 9.65°±0.2° and 16.24°± There are diffraction peaks at 0.2°, 22.79°±0.2°, 27.33°±0.2° and 27.96°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.93°±0.2°, 10.13 There are diffraction peaks at °±0.2°, 13.07°±0.2°, 16.24°±0.2°, 18.47°±0.2°, 19.27°±0.2° and 19.71°±0.2°. Preferably, X- expressed in 2θ angle The ray powder diffraction pattern is at 9.24°±0.2°, 12.54°±0.2°, 17.89°±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°± There are diffraction peaks at 0.2°, 20.22°±0.2° and 23.99°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 9.24°±0.2°, 12.54°±0.2° and 17.89°± 0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98°±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°±0.2° , 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°±0.2° and 26.73°±0.2° have diffraction peaks, preferably, expressed in 2θ angle The X-ray powder diffraction pattern is at 9.24°±0.2°, 12.54°±0.2°, 17.89°±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2°, 15.98 °±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°±0.2°, 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23°± There are diffraction peaks at 0.2°, 26.73°±0.2°, 9.65°±0.2°, 16.24°±0.2°, 22.79°±0.2°, 27.33°±0.2° and 27.96°±0.2°, preferably at an angle of 2θ The X-ray powder diffraction patterns represented are at 9.24°±0.2°, 12.54°±0.2°, 17.89°±0.2°, 20.45°±0.2°, 25.22°±0.2°, 29.51°±0.2°, 15.73°±0.2° , 15.98°±0.2°, 20.22°±0.2°, 23.99°±0.2°, 14.89°±0.2°, 14.99°±0.2°, 16.78°±0.2°, 21.6°±0.2°, 24.24°±0.2°, 26.23 °±0.2°, 26.73°±0.2°, 9.65°±0.2°, 16.24°±0.2°, 22.79°±0.2°, 27.33°±0.2°, 27.96°±0.2°, 8.93°±0.2°, 10.13°±0.2 There are diffraction peaks at 13.07°±0.2°, 16.24°±0.2°, 18.47°±0.2°, 19.27°±0.2° and 19.71°±0.2°. Preferably, the X-ray powder is expressed in 2θ angle The diffraction pattern is basically the same as Figure 41. Preferably, its DSC curve has an endothermic peak in the range of 170~185°C. Preferably, its unit cell parameters are: a=11.2944(2) Å, b=11.4048(2 ) Å, c=11.8672(2) Å, α= 112.572(2)°, β= 107.1220(10)°, γ= 102.2480(10)°, and the space group is P . An ethanol solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethanol is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle has diffraction peaks at 6.21°±0.2°, 8.33°±0.2° and 22.32°±0.2°. Preferably, its The X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2° and 27.82°±0.2°, preferably, it is expressed in 2θ angle The X-ray powder diffraction pattern of The X-ray powder diffraction pattern expressed in angle is still 9.41°±0.2°, 10.7°±0.2°, 11.73°±0.2°, 14.37°±0.2°, 15.13°±0.2°, 15.57°±0.2°, 16.57°± There are diffraction peaks at 0.2°, 17.03°±0.2°, 17.91°±0.2°, 18.26°±0.2° and 19.81°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.21°± There are diffraction peaks at 0.2°, 8.33°±0.2°, 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2° and 27.82°±0.2°, preferably at an angle of 2θ The X-ray powder diffraction patterns represented are at 6.21°±0.2°, 8.33°±0.2°, 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2°, 27.82°±0.2° There are diffraction peaks at , 12.29°±0.2°, 17.54°±0.2°, 19.02°±0.2°, 19.81°±0.2° and 25.41°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle At 6.21°±0.2°, 8.33°±0.2°, 22.32°±0.2°, 13.48°±0.2°, 16.2°±0.2°, 21.52°±0.2°, 27.82°±0.2°, 12.29°±0.2°, 17.54 °±0.2°, 19.02°±0.2°, 19.81°±0.2°, 25.41°±0.2°, 9.41°±0.2°, 10.7°±0.2°, 11.73°±0.2°, 14.37°±0.2°, 15.13°± There are diffraction peaks at 0.2°, 15.57°±0.2°, 16.57°±0.2°, 17.03°±0.2°, 17.91°±0.2° and 18.26°±0.2°. Preferably, the X-rays are expressed in 2θ angles The powder diffraction pattern is basically the same as Figure 16. Preferably, its DSC curve has an endothermic peak in the range of 175~185°C. Preferably, its unit cell parameters are: a=14.6676(2) Å, b=16.0727( 2) Å, c=11.9029(2) Å, α=γ= 90°, β=97.423(2)°, and the space group is P 2 ₁ / c . A methanol solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to methanol is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle has diffraction peaks at 6.15°±0.2°, 12.23°±0.2°, 22.47°±0.2° and 24.52°±0.2°. , preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2° and 21.62°±0.2°, preferably , its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 8.27°±0.2°, 17.56°±0.2°, 19.79°±0.2°, 25.39°±0.2° and 27.92°±0.2°, which is relatively Optimally, its X-ray powder diffraction pattern expressed in 2θ angle is still at 6.6°±0.2°, 6.77°±0.2°, 8.66°±0.2°, 10.68°±0.2°, 10.75°±0.2°, 11.84°± 0.2°, 14.41°±0.2°, 15.5°±0.2°, 15.71°±0.2°, 15.91°±0.2°, 16.27°±0.2°, 16.51°±0.2°, 16.86°±0.2°, 18.22°±0.2° There are diffraction peaks at , 18.49°±0.2°, 19.02°±0.2° and 19.29°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.15°±0.2° and 12.23°±0.2°. , 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2° and 21.62°±0.2° have diffraction peaks, preferably, expressed in 2θ angles The X-ray powder diffraction pattern is at 6.15°±0.2°, 12.23°±0.2°, 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2°, 21.62 There are diffraction peaks at °±0.2°, 8.27°±0.2°, 17.56°±0.2°, 19.79°±0.2°, 25.39°±0.2° and 27.92°±0.2°. Preferably, X- expressed in 2θ angle The ray powder diffraction pattern is at 6.15°±0.2°, 12.23°±0.2°, 22.47°±0.2°, 24.52°±0.2°, 11.18°±0.2°, 13.44°±0.2°, 17.36°±0.2°, 21.62°± 0.2°, 8.27°±0.2°, 17.56°±0.2°, 19.79°±0.2°, 25.39°±0.2°, 27.92°±0.2°, 6.6°±0.2°, 6.77°±0.2°, 8.66°±0.2° , 10.68°±0.2°, 10.75°±0.2°, 11.84°±0.2°, 14.41°±0.2°, 15.5°±0.2°, 15.71°±0.2°, 15.91°±0.2°, 16.27°±0.2°, 16.51 There are diffraction peaks at °±0.2°, 16.86°±0.2°, 18.22°±0.2°, 18.49°±0.2°, 19.02°±0.2° and 19.29°±0.2°. Preferably, X expressed in 2θ angle -The ray powder diffraction pattern is basically the same as Figure 32. Preferably, its DSC curve has an endothermic peak in the range of 175~185°C. An acetonitrile solvate 1 of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to acetonitrile is about 1:0.5, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 6.81°±0.2°, 13.53°±0.2°, 15.46°±0.2°, 21.29°±0.2° and 21.72°± There is a diffraction peak at 0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.79°±0.2°, 14.66°±0.2°, 17.52°±0.2°, 20.34°±0.2°, 23.45 There are diffraction peaks at °±0.2°, 27.72°±0.2° and 28.6°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 18.2°±0.2° and 18.55°±0.2°. , 22.42°±0.2° and 29.92°±0.2° have diffraction peaks. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.81°±0.2°, 13.53°±0.2°, and 15.46°±0.2°. , 21.29°±0.2°, 21.72°±0.2°, 8.79°±0.2°, 14.66°±0.2°, 17.52°±0.2°, 20.34°±0.2°, 23.45°±0.2°, 27.72°±0.2° and 28.6 There is a diffraction peak at °±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.81°±0.2°, 13.53°±0.2°, 15.46°±0.2°, 21.29°±0.2°, 21.72 °±0.2°, 8.79°±0.2°, 14.66°±0.2°, 17.52°±0.2°, 20.34°±0.2°, 23.45°±0.2°, 27.72°±0.2°, 28.6°±0.2°, 18.2°± There are diffraction peaks at 0.2°, 18.55°±0.2°, 22.42°±0.2° and 29.92°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 6, preferably Ground, its DSC curve has an endothermic peak in the range of 175~185°C. Preferably, its unit cell parameters are: a=13.3231(2) Å, b=16.1220(2) Å, c=12.0723(2) Å, α=γ= 90°, β=99.0890(10)°, and the space group is P 2 ₁ / c . A DMSO solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to DMSO is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 11.22°±0.2°, 16.43°±0.2°, 20.08°±0.2°, 20.32°±0.2°, 20.69°± There are diffraction peaks at 0.2°, 21.23°±0.2°, 23.99°±0.2° and 26.03°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.38°±0.2°, 10.58 There are diffraction peaks at °±0.2°, 13.36°±0.2°, 19.48°±0.2°, 19.85°±0.2°, 22.75°±0.2° and 27.08°±0.2°. Preferably, X expressed in 2θ angle -The ray powder diffraction pattern also has diffraction peaks at 14.18°±0.2°, 15.38°±0.2°, 15.73°±0.2°, 18.37°±0.2°, 22.88°±0.2° and 28.52°±0.2°, preferably , the X-ray powder diffraction pattern expressed in 2θ angle is 11.22°±0.2°, 16.43°±0.2°, 20.08°±0.2°, 20.32°±0.2°, 20.69°±0.2°, 21.23°±0.2°, 23.99 °±0.2°, 26.03°±0.2°, 8.38°±0.2°, 10.58°±0.2°, 13.36°±0.2°, 19.48°±0.2°, 19.85°±0.2°, 22.75°±0.2° and 27.08°± There is a diffraction peak at 0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 11.22°±0.2°, 16.43°±0.2°, 20.08°±0.2°, 20.32°±0.2°, 20.69°± 0.2°, 21.23°±0.2°, 23.99°±0.2°, 26.03°±0.2°, 8.38°±0.2°, 10.58°±0.2°, 13.36°±0.2°, 19.48°±0.2°, 19.85°±0.2° , 22.75°±0.2°, 27.08°±0.2°, 14.18°±0.2°, 15.38°±0.2°, 15.73°±0.2°, 18.37°±0.2°, 22.88°±0.2° and 28.52°±0.2°. The diffraction peak, preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 13, and preferably, its DSC curve has an endothermic peak in the range of 175~185°C. A formic acid solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to formic acid is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 8.19°±0.2°, 15.91°±0.2°, 18.59°±0.2°, 22.2°±0.2° and 22.51°± There is a diffraction peak at 0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has at 9.55°±0.2°, 15.61°±0.2°, 18.35°±0.2° and 28.03°±0.2°. The diffraction peak, preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.69°±0.2°, 13.01°±0.2°, 15.34°±0.2°, 17.71°±0.2°, 23.02°±0.2° , 23.47°±0.2°, 23.84°±0.2° and 25.25°±0.2° have diffraction peaks. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 8.19°±0.2° and 15.91°±0.2°. There are diffraction peaks at , 18.59°±0.2°, 22.2°±0.2°, 22.51°±0.2°, 9.55°±0.2°, 15.61°±0.2°, 18.35°±0.2° and 28.03°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 8.19°±0.2°, 15.91°±0.2°, 18.59°±0.2°, 22.2°±0.2°, 22.51°±0.2°, 9.55°±0.2 °, 15.61°±0.2°, 18.35°±0.2°, 28.03°±0.2°, 8.69°±0.2°, 13.01°±0.2°, 15.34°±0.2°, 17.71°±0.2°, 23.02°±0.2°, There are diffraction peaks at 23.47°±0.2°, 23.84°±0.2° and 25.25°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is substantially the same as Figure 20 . An ethyl formate solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethyl formate is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 4.77°±0.2°, 7.76°±0.2°, 9.55°±0.2°, 15.54°±0.2° and 26.03°± There is a diffraction peak at 0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has 16.61°±0.2°, 21.46°±0.2°, 25.56°±0.2° and 28.91°±0.2°. Diffraction peaks, preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 4.77°±0.2°, 7.76°±0.2°, 9.55°±0.2°, 15.54°±0.2°, 26.03°±0.2°, 16.61 There are diffraction peaks at °±0.2°, 21.46°±0.2°, 25.56°±0.2° and 28.91°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 23. An ethylene glycol methyl ether solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethylene glycol methyl ether is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle has diffraction peaks at 20.86°±0.2°, 20.2°±0.2°, 13.44°±0.2° and 11.34°±0.2°. , preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 6.73°±0.2°, 16.95°±0.2°, 20.59°±0.2° and 24.19°±0.2°, preferably , its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 10.89°±0.2°, 21.04°±0.2°, 21.41°±0.2°, 26.44°±0.2° and 27.02°±0.2°, which is relatively Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is 20.86°±0.2°, 20.2°±0.2°, 13.44°±0.2°, 11.34°±0.2°, 6.73°±0.2°, 16.95°±0.2° There are diffraction peaks at 20.59°±0.2° and 24.19°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 20.86°±0.2°, 20.2°±0.2°, and 13.44°±0.2°. , 11.34°±0.2°, 6.73°±0.2°, 16.95°±0.2°, 20.59°±0.2°, 24.19°±0.2°, 10.89°±0.2°, 21.04°±0.2°, 21.41°±0.2°, 26.44 There are diffraction peaks at °±0.2° and 27.02°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 26. A crystal form II of the compound represented by formula I uses Cu-Kα radiation, and its X-ray powder diffraction pattern expressed at 2θ angle is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, 14.53° There are diffraction peaks at ±0.2°, 15.32°±0.2° and 22.2°±0.2°, Preferably, its X-ray powder diffraction pattern expressed in 2θ angle has diffraction peaks at 13.44°±0.2°, 15.61°±0.2°, 17.38°±0.2° and 21.06°±0.2°. Preferably, its The X-ray powder diffraction pattern expressed in 2θ angles also has 4.24°±0.2°, 6.96°±0.2°, 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2° and 29.92°±0.2°. Diffraction peaks, preferably, its X-ray powder diffraction pattern expressed at 2θ angle also has diffraction peaks at 17.07°±0.2°, 20.2°±0.2° and 23.49°±0.2°, preferably, at 2θ angle The X-ray powder diffraction pattern represented is 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2° There are diffraction peaks at , 15.61°±0.2°, 17.38°±0.2° and 21.06°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.73°±0.2° and 8.68°±0.2°. , 11.03°±0.2°, 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2°, 15.61°±0.2°, 17.38°±0.2°, 21.06°±0.2°, 4.24 There are diffraction peaks at °±0.2°, 6.96°±0.2°, 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2° and 29.92°±0.2°. Preferably, X- expressed in 2θ angle The ray powder diffraction pattern is at 6.73°±0.2°, 8.68°±0.2°, 11.03°±0.2°, 14.53°±0.2°, 15.32°±0.2°, 22.2°±0.2°, 3.44°±0.2°, 15.61°± 0.2°, 17.38°±0.2°, 21.06°±0.2°, 4.24°±0.2°, 6.96°±0.2°, 17.83°±0.2°, 18.24°±0.2°, 28.11°±0.2°, 29.92°±0.2° There are diffraction peaks at , 17.07°±0.2°, 20.2°±0.2° and 23.49°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 29. An n-propanol solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to n-propanol is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 6.15°±0.2°, 8.19°±0.2°, 12.29°±0.2°, 16.16°±0.2°, 22.22°± There are diffraction peaks at 0.2° and 24.69°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2° and 27.72° There is a diffraction peak at °±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 13.44°±0.2°, 14.06°±0.2°, 16.35°±0.2°, and 17.3°±0.2°. There are diffraction peaks at , 21.54°±0.2° and 22.84°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 10.52°±0.2°, 17.73°±0.2°, 18.8°± There are diffraction peaks at 0.2° and 27.2°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.15°±0.2°, 8.19°±0.2°, 12.29°±0.2°, and 16.16°± There are diffraction peaks at 0.2°, 22.22°±0.2°, 24.69°±0.2°, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2° and 27.72°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is 6.15°±0.2°, 8.19°±0.2°, 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2°, 24.69°±0.2 °, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2°, 27.72°±0.2°, 13.44°±0.2°, 14.06°±0.2°, 16.35°±0.2°, 17.3°±0.2°, There are diffraction peaks at 21.54°±0.2° and 22.84°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.15°±0.2°, 8.19°±0.2°, 12.29°±0.2°, 16.16°±0.2°, 22.22°±0.2°, 24.69°±0.2°, 18.51°±0.2°, 19.77°±0.2°, 25.47°±0.2°, 27.72°±0.2°, 13.44°±0.2°, 14.06° ±0.2°, 16.35°±0.2°, 17.3°±0.2°, 21.54°±0.2°, 22.84°±0.2°, 10.52°±0.2°, 17.73°±0.2°, 18.8°±0.2° and 27.2°±0.2 There is a diffraction peak at °. Preferably, its X-ray powder diffraction pattern expressed at an angle of 2θ is basically the same as Figure 35. Preferably, its DSC curve has an endothermic peak in the range of 175~185°C. A ethylene glycol dimethyl ether solvate of a compound represented by formula I, wherein the molar ratio of the compound represented by formula I to ethylene glycol dimethyl ether is about 1:1, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 13.4°±0.2°, 20.14°±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71°± There are diffraction peaks at 0.2° and 11.3°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has diffraction peaks at 21.39°±0.2°, 20.49°±0.2° and 26.96°±0.2°. The diffraction peak, preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.46°±0.2°, 10.83°±0.2°, 14.39°±0.2°, 14.51°±0.2°, 15.3°±0.2° There are diffraction peaks at , 15.59°±0.2°, 15.79°±0.2°, 16.84°±0.2°, 18.24°±0.2° and 19.71°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle at 13.4°±0.2°, 20.14°±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71°±0.2°, 11.3°±0.2°, 21.39°±0.2°, 20.49°±0.2° and 26.96 There is a diffraction peak at °±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 13.4°±0.2°, 20.14°±0.2°, 20.82°±0.2°, 24.13°±0.2°, 6.71 °±0.2°, 11.3°±0.2°, 21.39°±0.2°, 20.49°±0.2°, 26.96°±0.2°, 8.46°±0.2°, 10.83°±0.2°, 14.39°±0.2°, 14.51°± There are diffraction peaks at 0.2°, 15.3°±0.2°, 15.59°±0.2°, 15.79°±0.2°, 16.84°±0.2°, 18.24°±0.2° and 19.71°±0.2°. Preferably, they are expressed in 2θ The X-ray powder diffraction pattern expressed in angle is basically the same as Figure 38. Preferably, its DSC curve has an endothermic peak in the range of 170~185°C. An oxalate salt of a compound represented by formula I, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53°±0.2°, 17.5°±0.2°, 19.42°± There are diffraction peaks at 0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2° and 22.73°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is still at 5.82 There are diffraction peaks at °±0.2°, 25.45°±0.2° and 27.61°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 15.89°±0.2° and 20.51°±0.2°. There are diffraction peaks at , 20.9°±0.2°, 22.47°±0.2° and 24.24°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.71°±0.2° and 10.83°± There are diffraction peaks at 0.2°, 11.57°±0.2°, 17.21°±0.2°, 19.87°±0.2°, 23.23°±0.2°, 26.73°±0.2°, 27.06°±0.2° and 29.14°±0.2°, which are relatively Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is 9.71°±0.2°, 11.24°±0.2°, 14.53°±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2° , 21.21°±0.2°, 21.43°±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°±0.2° and 27.61°±0.2° have diffraction peaks, preferably, expressed in 2θ angles The X-ray powder diffraction pattern is at 9.71°±0.2°, 11.24°±0.2°, 14.53°±0.2°, 17.5°±0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43 °±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°±0.2°, 27.61°±0.2°, 15.89°±0.2°, 20.51°±0.2°, 20.9°±0.2°, 22.47°± There are diffraction peaks at 0.2° and 24.24°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 9.71°±0.2°, 11.24°±0.2°, 14.53°±0.2°, 17.5°± 0.2°, 19.42°±0.2°, 19.56°±0.2°, 21.21°±0.2°, 21.43°±0.2°, 22.73°±0.2°, 5.82°±0.2°, 25.45°±0.2°, 27.61°±0.2° , 15.89°±0.2°, 20.51°±0.2°, 20.9°±0.2°, 22.47°±0.2°, 24.24°±0.2°, 8.71°±0.2°, 10.83°±0.2°, 11.57°±0.2°, 17.21 There are diffraction peaks at °±0.2°, 19.87°±0.2°, 23.23°±0.2°, 26.73°±0.2°, 27.06°±0.2° and 29.14°±0.2°. Preferably, X expressed in 2θ angle -The ray powder diffraction pattern is basically the same as Figure 45. A phosphate salt of a compound represented by formula I, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 3.21°±0.2°, 15.89°±0.2°, 16.55°±0.2°, 18°±0.2°, 19.36°± There are diffraction peaks at 0.2°, 21.37°±0.2°, 24.17°±0.2° and 24.52°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 12.21°±0.2°, 15.56 There are diffraction peaks at °±0.2°, 19.89°±0.2°, 20.61°±0.2° and 25.1°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 12.99°±0.2°. , 21.83°±0.2°, 22.07°±0.2°, 22.28°±0.2°, 22.63°±0.2°, 25.56°±0.2° and 28.23°±0.2° have diffraction peaks, preferably, expressed in 2θ angles The X-ray powder diffraction pattern is at 3.21°±0.2°, 15.89°±0.2°, 16.55°±0.2°, 18°±0.2°, 19.36°±0.2°, 21.37°±0.2°, 24.17°±0.2°, 24.52 There are diffraction peaks at °±0.2°, 12.21°±0.2°, 15.56°±0.2°, 19.89°±0.2°, 20.61°±0.2° and 25.1°±0.2°. Preferably, X- expressed in 2θ angle The ray powder diffraction pattern is at 3.21°±0.2°, 15.89°±0.2°, 16.55°±0.2°, 18°±0.2°, 19.36°±0.2°, 21.37°±0.2°, 24.17°±0.2°, 24.52°± 0.2°, 12.21°±0.2°, 15.56°±0.2°, 19.89°±0.2°, 20.61°±0.2°, 25.1°±0.2°, 12.99°±0.2°, 21.83°±0.2°, 22.07°±0.2° , 22.28°±0.2°, 22.63°±0.2°, 25.56°±0.2° and 28.23°±0.2° have diffraction peaks. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 49 same. A difumarate salt of a compound represented by formula I, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 6.13°±0.2°, 14.56°±0.2°, 18.47°±0.2°, 18.94°±0.2°, 19.83°± There are diffraction peaks at 0.2°, 21.48°±0.2°, 22.61°±0.2° and 23.23°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 8.85°±0.2°, 9.41 There are diffraction peaks at °±0.2°, 14.12°±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°±0.2°, 20.34°±0.2°, 24.48°±0.2° and 28.89°±0.2°. , preferably, its X-ray powder diffraction pattern expressed in 2θ angle also has at 11.36°±0.2°, 12.62°±0.2°, 25.7°±0.2°, 27.57°±0.2° and 30.48°±0.2° Diffraction peaks, preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.13°±0.2°, 14.56°±0.2°, 18.47°±0.2°, 18.94°±0.2°, 19.83°±0.2°, 21.48 °±0.2°, 22.61°±0.2°, 23.23°±0.2°, 8.85°±0.2°, 9.41°±0.2°, 14.12°±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°± There are diffraction peaks at 0.2°, 20.34°±0.2°, 24.48°±0.2° and 28.89°±0.2°. Preferably, the X-ray powder diffraction pattern expressed in 2θ angle is at 6.13°±0.2° and 14.56°± 0.2°, 18.47°±0.2°, 18.94°±0.2°, 19.83°±0.2°, 21.48°±0.2°, 22.61°±0.2°, 23.23°±0.2°, 8.85°±0.2°, 9.41°±0.2° , 14.12°±0.2°, 15.03°±0.2°, 16.26°±0.2°, 16.99°±0.2°, 20.34°±0.2°, 24.48°±0.2°, 28.89°±0.2°, 11.36°±0.2°, 12.62 There are diffraction peaks at °±0.2°, 25.7°±0.2°, 27.57°±0.2° and 30.48°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is basically the same as Figure 53. A fumarate salt of a compound represented by formula I, Preferably, Cu-Kα radiation is used, and its X-ray powder diffraction pattern expressed in 2θ angle is 11.78°±0.2°, 13.94°±0.2°, 16.14°±0.2°, 20.98°±0.2°, 21.17°± There are diffraction peaks at 0.2°, 21.85°±0.2° and 22.42°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 11.26°±0.2°, 14.56°±0.2°, 23.7 There are diffraction peaks at °±0.2°, 23.93°±0.2° and 24.88°±0.2°. Preferably, its X-ray powder diffraction pattern expressed in 2θ angle is also at 13.18°±0.2° and 13.44°±0.2°. , 14.82°±0.2°, 15.11°±0.2°, 19.75°±0.2°, 24.55°±0.2°, 25.64°±0.2°, 26.58°±0.2° and 27.33°±0.2° have diffraction peaks, preferably , its X-ray powder diffraction pattern expressed in 2θ angle is 11.78°±0.2°, 13.94°±0.2°, 16.14°±0.2°, 20.98°±0.2°, 21.17°±0.2°, 21.85°±0.2°, There are diffraction peaks at 22.42°±0.2°, 11.26°±0.2°, 14.56°±0.2°, 23.7°±0.2°, 23.93°±0.2° and 24.88°±0.2°. Preferably, its 2θ angle represents X -Ray powder diffraction pattern at 11.78°±0.2°, 13.94°±0.2°, 16.14°±0.2°, 20.98°±0.2°, 21.17°±0.2°, 21.85°±0.2°, 22.42°±0.2°, 11.26° ±0.2°, 14.56°±0.2°, 23.7°±0.2°, 23.93°±0.2°, 24.88°±0.2°, 13.18°±0.2°, 13.44°±0.2°, 14.82°±0.2°, 15.11°±0.2 There are diffraction peaks at 19.75°±0.2°, 24.55°±0.2°, 25.64°±0.2°, 26.58°±0.2° and 27.33°±0.2°. Preferably, the X-ray powder is expressed in 2θ angle The diffraction pattern is basically the same as Figure 57. A pharmaceutical composition comprising the crystal form I of the compound represented by formula I as described in claim 1, the monohydrate of the compound represented by formula I as described in claim 2, and the compound represented by formula I as described in claim 3. The ethanol solvate of the compound represented by formula I described in claim 4, the acetonitrile solvate of the compound represented by formula I described in claim 5, the compound represented by formula I described in claim 6 The DMSO solvate of the compound shown in claim 7, the formic acid solvate of the compound represented by formula I described in claim 7, the ethyl formate solvate of the compound represented by formula I described in claim 8, the ethyl formate solvate of the compound represented by formula I described in claim 9 The ethylene glycol methyl ether solvate of the compound represented by formula I, the crystal form II of the compound represented by formula I described in claim 10, the n-propanol solvate of the compound represented by formula I described in claim 11, The glycol dimethyl ether solvate of the compound represented by formula I described in claim 12, the oxalate of the compound represented by formula I described in claim 13, the compound represented by formula I described in claim 14 Phosphate, the disfumarate salt of the compound represented by formula I described in claim 15 or the monofumarate salt of the compound represented by formula I described in claim 16, and a pharmaceutically acceptable carrier or excipient . The crystal form I of the compound represented by formula I as described in claim 1, the monohydrate of the compound represented by formula I as described in claim 2, the ethanol solvate of the compound represented by formula I as described in claim 3, The methanol solvate of the compound represented by formula I described in claim 4, the acetonitrile solvate of the compound represented by formula I described in claim 5, the DMSO solvate of the compound represented by formula I described in claim 6 , the formic acid solvate of the compound represented by formula I described in claim 7, the ethyl formate solvate of the compound represented by formula I described in claim 8, the ethyl formate solvate of the compound represented by formula I described in claim 9 Glycol methyl ether solvate, crystal form II of the compound represented by formula I described in claim 10, n-propanol solvate of the compound represented by formula I described in claim 11, the formula described in claim 12 The glycol dimethyl ether solvate of the compound represented by I, the oxalate of the compound represented by formula I described in claim 13, the phosphate salt of the compound represented by formula I described in claim 14, the phosphate salt of the compound represented by formula I described in claim 15 The disfumarate salt of the compound shown in formula I described in claim 16, the monofumarate salt of the compound shown in formula I described in claim 16 or the pharmaceutical composition described in claim 17 is used in the preparation of a drug for the treatment of RET-related diseases. Applications in medicine. The crystal form I of the compound represented by formula I as described in claim 1, the monohydrate of the compound represented by formula I as described in claim 2, the ethanol solvate of the compound represented by formula I as described in claim 3, The methanol solvate of the compound represented by formula I described in claim 4, the acetonitrile solvate of the compound represented by formula I described in claim 5, the DMSO solvate of the compound represented by formula I described in claim 6 , the formic acid solvate of the compound represented by formula I described in claim 7, the ethyl formate solvate of the compound represented by formula I described in claim 8, the ethyl formate solvate of the compound represented by formula I described in claim 9 Glycol methyl ether solvate, crystal form II of the compound represented by formula I described in claim 10, n-propanol solvate of the compound represented by formula I described in claim 11, the formula described in claim 12 The glycol dimethyl ether solvate of the compound represented by I, the oxalate of the compound represented by formula I described in claim 13, the phosphate salt of the compound represented by formula I described in claim 14, the phosphate salt of the compound represented by formula I described in claim 15 The disfumarate salt of the compound represented by formula I described in claim 16, the monofumarate salt of the compound represented by formula I described in claim 16, or the pharmaceutical composition described in claim 17 is used in the preparation of cells or subjects. Use in drugs that exhibit RET kinase activity in patients. For the use described in Claim 18 or Claim 19, the drug is used to treat the following disorders associated with RET-related diseases: disorders of the expression or activity or level of the RET gene, RET kinase, or any of them; Preferably, the expression, activity or level of the RET gene, RET kinase, or any one of them is caused by one or more point mutations in the RET gene; more preferably, one or more of the RET genes Point mutations can cause RET protein to undergo one or more amino acid substitutions or deletions at the following amino acid positions: 378, 385, 618, 620, 630, 631, 633, 804, 810, 883, 918; Preferably, the RET gene, RET kinase, or the expression or activity or level disorder of any one of them is caused by a RET gene fusion; more preferably, the RET gene fusion is selected from: KIF5B-RET, CDC6-RET, At least one of NCOA4-RET, CLIP1-RET, ERC1-RET, RUFY3-RET, TFG-RET, PRKAR1A-RET and KTN1-RET. For the use described in claim 18 or claim 19, the RET-related diseases include tumors and irritable bowel syndrome; or The RET-related disease is a variety of diseases caused by abnormality (gene fusion, mutation, etc.) of the gene encoding RET kinase; preferably, the RET-related disease is selected from the group consisting of papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), congenital At least one of megacolon, lung adenocarcinoma, irritable bowel syndrome, non-small cell lung cancer, and multiple endocrine neoplasia type 2 (MEN2); or The RET-related disease is selected from the group consisting of lung cancer, papillary thyroid cancer, medullary thyroid cancer, differentiated thyroid cancer, recurrent thyroid cancer, refractory differentiated thyroid cancer, multiple endocrine neoplasia type 2A or 2B, pheochromocytoma, parathyroid At least one of hyperplasia, breast cancer, colorectal cancer, papillary renal cell carcinoma, gangliomatosis of the gastrointestinal mucosa, and cervical cancer.