Salt form of PARP inhibitor-fused heterocyclic deuterated compound, and preparation method therefor and use thereof

Abstract

The present invention belongs to the technical field of chemical medicines. Disclosed are a salt form of a PARP inhibitor-fused heterocyclic deuterated compound, and a preparation method therefor and the use thereof. Provided in the present invention are various salt forms of a compound of formula (1), and a preparation method therefor and the use thereof. The present invention provides support for dosage form study by means of studying various salt forms of the compound, such as fumarate, tartrate, various sulfonates such as 2-naphthalenesulfonate, p-toluenesulfonate and methanesulfonate, and saccharin co-crystal, and studying crystal forms of each salt form, thereby more effectively preventing / treating PARP-related diseases, and meeting different clinical medication requirements.

Description

Salt forms of a deuterated compound of a PARP inhibitor and heterocycle class, and methods of making and uses thereof TECHNICAL FIELD

[0001] The present application belongs to the field of chemical medicine technology, and specifically relates to a plurality of salt forms of a deuterated small-molecule compound of a PARP inhibitor and heterocycle class having PARP inhibitory activity, a preparation method thereof, and use thereof in the preparation of a drug for treating related diseases. BACKGROUND

[0002] During the growth of a cell, its DNA is continuously damaged by internal and external adverse factors. Among DNA damage, the most serious damage types are single-strand breaks and double-strand breaks, of which single-strand breaks are more common. If these breaks are not repaired in a timely and accurate manner, they will lead to genomic instability, and further cause cancer, or even directly cause cell death. For single-strand breaks in DNA, its repair mainly depends on PARP enzymes. For double-strand breaks, there are two repair methods for double-strand DNA: non-homologous end joining and homologous recombination repair. Homologous recombination repair is a high-fidelity, error-free repair method, and is also the main way of double-strand DNA repair. Homologous recombination repair involves many proteins, of which the most well-known is the BRCA protein. Two studies in 2005 (Farmer H, McCabe N, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J]. Nature, 2005, 434(7035): 917-921. Bryant, H., Schultz, N., Thomas, H. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose)polymerase. Nature 434, 913-917 (2005)) showed that tumor cells lacking BRCA1 or BRCA2 are selectively inhibited by PARP inhibitors. Based on this research result, scholars proposed the concept of synthetic lethality: the absence of either BRCA or PARP is not fatal, but the simultaneous inactivation of both leads to cell death. Based on the synthetic lethality theory, PARP inhibitors (PARPi) are developed for selective targeting of BRCA1 / 2 mutant cancer cells.

[0003] PARP inhibitors have shown excellent clinical efficacy in homologous recombination deficient cancer patients, however, hematologic toxicities (anemia, neutropenia and thrombocytopenia) and other toxicities limit the use of these drugs, either as monotherapy or in combination therapy. Related studies have shown (Harris P A, Boloor A, Cheung M, et al. Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. [J]. Journal of Medicinal Chemistry, 2008, 51(15): 4632.) that this part of adverse reactions can come from the inhibition of PARP2 by marketed PARP inhibitors, while PARP2 is not necessary for efficacy. A highly selective PARP1 inhibitor can reduce hematologic toxicity, improve the safety window of treatment, and increase the potential for combination with other chemotherapy or targeted drugs. Therefore, there is an unmet clinical need for an effective and safe PARP inhibitor, especially a PARP inhibitor selective for PARP1.

[0004] When used to treat humans, it is important that a crystalline form of a therapeutic agent, like 1'-((7-(ethyl-d5)-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-N-methyl-1 ',2',3',6'-tetrahydro-[3,4'-bipyridine]-6-carboxamide, retains its polymorphic stability and chemical stability, solubility, and other physicochemical properties over time and in different manufacturing batches of the agent. If these physicochemical properties change over time and in batches, the administration of a therapeutically effective dose is problematic and can result in toxic side effects or ineffective treatment, especially when a particular polymorph decomposes into a less active, inactive, or toxic compound before use. Therefore, it is important to select a crystalline form of an agent that is stable, reproducibly manufactured, and has physicochemical properties that are advantageous for its use as a therapeutic agent. SUMMARY

[0005] The present application studies a salt form of a compound represented by formula 1, 1'-((7-(ethyl-d5)-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-N-methyl-1',2',3',6'-tetrahydro-[3,4'-bipyridine]-6-carboxamide, a preparation method thereof, and a pharmaceutical composition and a medical use thereof, and provides a plurality of salt forms of the compound with the advantages of high selectivity, good activity, low toxicity and side effects, and the salt forms have the excellent characteristics of high purity, good solubility, stable physical and chemical properties, high temperature resistance, high humidity resistance, strong light resistance, and low hygroscopicity.

[0006] The present application first provides a salt form of a compound represented by formula 1:

[0007] The salt form is a pharmaceutically acceptable salt selected from a fumarate, an L-tartrate, a 1,5-naphthalenedisulfonate, a 2-naphthalenesulfonate, an L-malate, an L-camsylate, a benzenesulfonate, a malonate, an oxalate, a p-toluenesulfonate, a methanesulfonate, a sulfate, a gentisate, a maleate, a citrate, a hydrobromide, a hydrochloride, an ethanesulfonate, or a saccharin co-crystal.

[0008] In the above-mentioned salt form of the compound represented by formula 1, the pharmaceutically acceptable salt is a fumarate, the fumarate salt of the compound represented by formula 1 is a crystal form I, the salt formation ratio of the compound represented by formula 1 to fumaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate salt crystal form I has the following characteristic diffraction peaks with excellent stability and repeatability at 2θ positions of 18.94±0.2°, 19.78±0.2°, 20.81±0.2°, and 23.55±0.2°.

[0009] Preferably, in some specific embodiments, the salt formation ratio of the compound represented by formula 1 to fumaric acid in the fumarate salt crystal form I is 1:1.

[0010] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the fumarate salt crystal form I has the following characteristic diffraction peaks with less stability and repeatability at 2θ positions of 14.07±0.2°, 15.42±0.2°, 16.08±0.2°, 18.94±0.2°, 19.78±0.2°, 20.80±0.2°, 21.53±0.2°, 22.99±0.2°, 23.54±0.2°, 23.71±0.2°, 24.60±0.2°, 25.80±0.2°, and 27.37±0.2°.

[0011] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of Formula 1 is Form II, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form II is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate salt Form II has the following characteristic diffraction peaks with excellent stability and reproducibility at the 2θ positions of 9.98±0.2°, 14.77±0.2°, 21.34±0.2°, 22.91±0.2°, and 24.05±0.2°.

[0012] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form II is 1:1.

[0013] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the fumarate salt Form II has the following characteristic diffraction peaks with less stability and reproducibility at the 2θ positions of 9.98±0.2°, 14.16±0.2°, 14.63±0.2°, 14.77±0.2°, 18.31±0.2°, 20.36±0.2°, 21.08±0.2°, 21.34±0.2°, 22.21±0.2°, 22.76±0.2°, 22.91±0.2°, 24.05±0.2°, and 24.90±0.2°.

[0014] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of Formula 1 is Form III, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form III is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate salt Form III has the following characteristic diffraction peaks with excellent stability and reproducibility at the 2θ positions of 9.55±0.2°, 11.03±0.2°, 11.33±0.2°, 19.22±0.2°, 19.89±0.2°, 24.32±0.2°, and 26.46±0.2°.

[0015] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form III is 1:1.

[0016] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of Formula 1 is Form IV, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form IV is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate salt Form IV has the following characteristic diffraction peaks with excellent stability and reproducibility at the 2θ positions of 21.11±0.2°, 22.57±0.2°, 25.01±0.2°, 25.41±0.2°, and 26.33±0.2°.

[0017] Preferably, in some embodiments, the ratio of the compound of Formula 1 to fumaric acid in the fumarate salt Form IV is 1:1.

[0018] Preferably, in some embodiments, the fumarate salt Form IV has the X-ray powder diffraction pattern with the following characteristic peaks of decreasing stability and reproducibility at the following 2Θ positions: 9.12±0.2°, 9.89±0.2°, 16.04±0.2°, 21.11±0.2°, 21.80±0.2°, 22.56±0.2°, 23.02±0.2°, 24.35±0.2°, 25.01±0.2°, 25.41±0.2°, 26.33±0.2°.

[0019] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form V, the ratio of the compound of Formula 1 to fumaric acid is 1:0.5-3, and the fumarate salt Form V has the X-ray powder diffraction pattern with the following characteristic peaks of excellent stability and reproducibility at the following 2Θ positions: 9.62±0.2°, 16.63±0.2°, 20.83±0.2°, 24.96±0.2°, 28.37±0.2°.

[0020] Preferably, in some embodiments, the ratio of the compound of Formula 1 to fumaric acid in the fumarate salt Form V is 1:0.6.

[0021] Preferably, in some embodiments, the fumarate salt Form V has the X-ray powder diffraction pattern with the following characteristic peaks of decreasing stability and reproducibility at the following 2Θ positions: 8.75±0.2°, 9.62±0.2°, 16.63±0.2°, 18.13±0.2°, 20.83±0.2°, 21.71±0.2°, 22.56±0.2°, 23.08±0.2°, 24.96±0.2°, 26.43±0.2°, 27.60±0.2°, 28.37±0.2°.

[0022] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form VI, the ratio of the compound of Formula 1 to fumaric acid is 1:0.5-3, and the fumarate salt Form VI has the X-ray powder diffraction pattern with the following characteristic peaks of excellent stability and reproducibility at the following 2Θ positions: 10.43±0.2°, 16.35±0.2°, 25.48±0.2°, 26.59±0.2°, 26.97±0.2°.

[0023] Preferably, in some embodiments, the ratio of the compound of Formula 1 to fumaric acid in the fumarate salt Form VI is 1:1.

[0024] Preferably, in certain embodiments, the fumarate salt Form VI has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility: 10.43±0.2°, 16.35±0.2°, 17.42±0.2°, 18.15±0.2°, 20.92±0.2°, 21.25±0.2°, 23.55±0.2°, 25.48±0.2°, 26.59±0.2°, 26.97±0.2°.

[0025] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form VII, the salt formation ratio of the compound of Formula 1 and fumaric acid is 1:0.5-3, and the fumarate salt Form VII has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 4.97±0.2°, 9.92±0.2°, 10.35±0.2°, 16.06±0.2°.

[0026] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form VII is 1:0.5.

[0027] Preferably, in certain embodiments, the fumarate salt Form VII has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility: 4.97±0.2°, 9.92±0.2°, 10.35±0.2°, 12.32±0.2°, 14.89±0.2°, 16.06±0.2°, 17.58±0.2°, 19.42±0.2°, 20.33±0.2°, 25.40±0.2°, 26.53±0.2°.

[0028] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form VIII, the salt formation ratio of the compound of Formula 1 and fumaric acid is 1:0.5-3, and the fumarate salt Form VIII has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 4.55±0.2°, 4.90±0.2°, 9.10±0.2°, 9.86±0.2°.

[0029] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form VIII is 1:0.5.

[0030] Preferably, in certain embodiments, the fumarate salt Form VIII has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility: 4.55±0.2°, 4.90±0.2°, 9.10±0.2°, 9.86±0.2°, 17.31±0.2°, 18.22±0.2°, 19.77±0.2°, 21.33±0.2°, 27.52±0.2°, 36.96±0.2°.

[0031] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form IX, the salt formation ratio of the compound of Formula 1 and fumaric acid is 1:0.5-3, and the fumarate salt Form IX has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 4.79±0.2°, 7.46±0.2°, 8.95±0.2°, 9.65±0.2°, 16.51±0.2°, 18.08±0.2°, 20.84±0.2°, 21.62±0.2°, 22.60±0.2°, 23.10±0.2°, 24.44±0.2°, 27.62±0.2°, 28.30±0.2°.

[0032] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form IX is 1:1.

[0033] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is fumarate salt, the fumarate salt of the compound of Formula 1 is Form X, the salt formation ratio of the compound of Formula 1 and fumaric acid is 1:0.5-3, and the fumarate salt Form X has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 9.96±0.2°, 14.76±0.2°, 14.99±0.2°, 18.66±0.2°, 20.33±0.2°, 21.34±0.2°, 22.19±0.2°, 22.39±0.2°, 22.68±0.2°, 22.86±0.2°, 23.69±0.2°.

[0034] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and fumaric acid in the fumarate salt Form X is 1:1.

[0035] In the salt form of the compound of formula 1 described above, the pharmaceutically acceptable salt is L-tartrate salt, the L-tartrate salt of the compound of formula 1 is crystalline form I, the salt formation ratio of the compound of formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate salt crystalline form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 7.58±0.2°, 25.99±0.2°, 27.19±0.2°.

[0036] Preferably, in some specific embodiments, the salt formation ratio of the compound of formula 1 and L-tartaric acid in the L-tartrate salt crystalline form I is 1:1.

[0037] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartrate salt crystalline form I has the following characteristic diffraction peaks with less excellent stability and reproducibility at 2θ positions of 7.58±0.2°, 7.94±0.2°, 16.01±0.2°, 18.42±0.2°, 19.82±0.2°, 21.49±0.2°, 22.50±0.2°, 25.99±0.2°, 27.19±0.2°.

[0038] In the salt form of the compound of formula 1 described above, the pharmaceutically acceptable salt is L-tartrate salt, the L-tartrate salt of the compound of formula 1 is crystalline form II, the salt formation ratio of the compound of formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate salt crystalline form II has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 7.62±0.2°, 22.71±0.2°, 26.18±0.2°, 27.40±0.2°.

[0039] Preferably, in some specific embodiments, the salt formation ratio of the compound of formula 1 and L-tartaric acid in the L-tartrate salt crystalline form II is 1:1.

[0040] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartrate salt crystalline form II has the following characteristic diffraction peaks with less excellent stability and reproducibility at 2θ positions of 7.62±0.2°, 7.98±0.2°, 14.24±0.2°, 16.14±0.2°, 18.72±0.2°, 19.97±0.2°, 21.62±0.2°, 22.71±0.2°, 26.18±0.2°, 27.40±0.2°.

[0041] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is L-tartrate salt, the L-tartrate salt of the compound of Formula 1 is crystal form III, the salt formation ratio of the compound of Formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate salt crystal form III has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.09±0.2°, 8.19±0.2°, 12.30±0.2°, 16.95±0.2°, 21.08±0.2°, 28.82±0.2°, and 28.98±0.2°.

[0042] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and L-tartaric acid in the L-tartrate salt crystal form III is 1:1.

[0043] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartrate salt crystal form III has the following characteristic diffraction peaks with less excellent stability and reproducibility at 2θ positions of 4.09±0.2°, 8.19±0.2°, 12.30±0.2°, 16.95±0.2°, 20.53±0.2°, 20.88±0.2°, 21.08±0.2°, 24.76±0.2°, 28.82±0.2°, and 28.98±0.2°.

[0044] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is L-tartrate salt, the L-tartrate salt of the compound of Formula 1 is crystal form IV, the salt formation ratio of the compound of Formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate salt crystal form IV has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.33±0.2°, 23.67±0.2°, 25.30±0.2°, and 26.26±0.2°.

[0045] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and L-tartaric acid in the L-tartrate salt crystal form IV is 1:1.

[0046] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartrate salt crystal form IV has the following characteristic diffraction peaks with less excellent stability and reproducibility at 2θ positions of 4.33±0.2°, 15.48±0.2°, 18.13±0.2°, 19.14±0.2°, 23.67±0.2°, 25.30±0.2°, 25.77±0.2°, 26.26±0.2°, and 27.42±0.2°.

[0047] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is L-tartaric acid salt, the L-tartaric acid salt of the compound of Formula 1 is crystalline form V, the salt formation ratio of the compound of Formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartaric acid salt crystalline form V has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.35±0.2°, 8.69±0.2°, and 16.73±0.2°.

[0048] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and L-tartaric acid in the L-tartaric acid salt crystalline form V is 1:1.

[0049] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartaric acid salt crystalline form V has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 4.35±0.2°, 8.69±0.2°, 13.06±0.2°, 16.73±0.2°, 17.46±0.2°, 23.95±0.2°, and 25.88±0.2°.

[0050] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is L-tartaric acid salt, the L-tartaric acid salt of the compound of Formula 1 is crystalline form VI, the salt formation ratio of the compound of Formula 1 and L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartaric acid salt crystalline form VI has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 7.59±0.2°, 18.38±0.2°, 26.01±0.2°, and 27.25±0.2°.

[0051] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and L-tartaric acid in the L-tartaric acid salt crystalline form VI is 1:1.

[0052] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the L-tartaric acid salt crystalline form VI has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 7.59±0.2°, 7.95±0.2°, 15.98±0.2°, 18.38±0.2°, 19.83±0.2°, 21.50±0.2°, 22.44±0.2°, 26.01±0.2°, and 27.25±0.2°.

[0053] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is 1,5-naphthalenedisulfonate salt, the compound of Formula 1 1,5-naphthalenedisulfonate salt is in crystalline Form I, the salt formation ratio of the compound of Formula 1 and 1,5-naphthalenedisulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the 1,5-naphthalenedisulfonate salt crystalline Form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 10.59±0.2°, 16.62±0.2°, 17.10±0.2°, 21.21±0.2°, 22.29±0.2°, 23.30±0.2°.

[0054] Preferably, in some embodiments, the salt formation ratio of the compound of Formula 1 and 1,5-naphthalenedisulfonic acid in the 1,5-naphthalenedisulfonate salt crystalline Form I is 1:1.

[0055] Preferably, in some embodiments, the X-ray powder diffraction pattern of the 1,5-naphthalenedisulfonate salt crystalline Form I has the following characteristic diffraction peaks with less excellent stability and reproducibility at 2θ positions of 5.65±0.2°, 10.59±0.2°, 11.64±0.2°, 15.98±0.2°, 16.62±0.2°, 17.10±0.2°, 19.32±0.2°, 20.75±0.2°, 21.21±0.2°, 22.29±0.2°, 22.90±0.2°, 23.30±0.2°, 24.14±0.2°, 24.68±0.2°, 26.35±0.2°.

[0056] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is 2-naphthalenesulfonic acid salt, the compound of Formula 1 2-naphthalenesulfonic acid salt is in crystalline Form I, the salt formation ratio of the compound of Formula 1 and 2-naphthalenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the 2-naphthalenesulfonate salt crystalline Form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.40±0.2°, 18.22±0.2°, 18.95±0.2°, 20.29±0.2°, 22.36±0.2°.

[0057] Preferably, in some embodiments, the salt formation ratio of the compound of Formula 1 and 2-naphthalenesulfonic acid in the 2-naphthalenesulfonate salt crystalline Form I is 1:0.8.

[0058] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the 2-napsylate salt Form II has the following characteristic peaks of stability and reproducibility next to the best in the following 2Θ positions: 4.81 ± 0.2°, 9.61 ± 0.2°, 13.09 ± 0.2°, 17.04 ± 0.2°, 17.96 ± 0.2°, 18.58 ± 0.2°, 19.60 ± 0.2°, 20.30 ± 0.2°, 21.00 ± 0.2°, 21.33 ± 0.2°, 23.78 ± 0.2°, 24.14 ± 0.2°.

[0059] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is L-malate, the compound of Formula 1 L-malate is in Form I, the salt formation ratio of the compound of Formula 1 and L-malic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-malate Form I has the following characteristic peaks of stability and reproducibility next to the best in the following 2Θ positions: 8.95 ± 0.2°, 15.79 ± 0.2°, 20.85 ± 0.2°, 22.55 ± 0.2°, 25.89 ± 0.2°.

[0060] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and L-malic acid in the L-malate Form I is 1:1.

[0061] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the L-malate Form I has the following characteristic peaks of stability and reproducibility next to the best in the following 2Θ positions: 8.95 ± 0.2°, 9.61 ± 0.2°, 13.09 ± 0.2°, 17.04 ± 0.2°, 17.96 ± 0.2°, 18.58 ± 0.2°, 19.60 ± 0.2°, 20.30 ± 0.2°, 21.00 ± 0.2°, 21.33 ± 0.2°, 23.78 ± 0.2°, 24.14 ± 0.2°, 25.89 ± 0.2°.

[0062] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is L-malate, the compound of Formula 1 L-malate is in Form I, the salt formation ratio of the compound of Formula 1 and L-malic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-malate Form I has the following characteristic peaks of stability and reproducibility next to the best in the following 2Θ positions: 8.95 ± 0.2°, 15.79 ± 0.2°, 20.85 ± 0.2°, 22.55 ± 0.2°, 25.89 ± 0.2°.

[0063] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and L-malic acid in the L-malate Form I is 1:1.

[0064] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the L-malate salt Form I has the following characteristic peaks with good stability and reproducibility: 8.95±0.2°, 9.24±0.2°, 13.22±0.2°, 15.79±0.2°, 17.25±0.2°, 19.54±0.2°, 20.31±0.2°, 20.85±0.2°, 21.04±0.2°, 22.55±0.2°, 23.72±0.2°, 24.94±0.2°, 25.89±0.2°, 26.24±0.2°, 26.95±0.2°, 27.37±0.2°.

[0065] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is L-camphorsulfonate, the L-camphorsulfonate salt of the compound of Formula 1 is in Form I, the salt formation ratio of the compound of Formula 1 and L-camphorsulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-camphorsulfonate salt Form I has the following characteristic peaks with excellent stability and reproducibility: 5.80±0.2°, 12.80±0.2°, 18.61±0.2°, 19.06±0.2°, 19.83±0.2°, 20.03±0.2°, 20.86±0.2°.

[0066] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and L-camphorsulfonic acid in the L-camphorsulfonate salt Form I is 1:1.

[0067] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the L-camphorsulfonate salt Form I has the following characteristic peaks with good stability and reproducibility: 5.80±0.2°, 11.58±0.2°, 12.80±0.2°, 16.87±0.2°, 17.77±0.2°, 18.06±0.2°, 18.61±0.2°, 19.06±0.2°, 19.83±0.2°, 20.03±0.2°, 20.86±0.2°, 21.41±0.2°, 22.72±0.2°, 23.04±0.2°, 24.46±0.2°.

[0068] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is L-camphorsulfonate, the L-camphorsulfonate salt of the compound of Formula 1 is in Form II, the salt formation ratio of the compound of Formula 1 and L-camphorsulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-camphorsulfonate salt Form II has the following characteristic peaks with excellent stability and reproducibility: 12.00±0.2°, 13.39±0.2°, 16.09±0.2°, 20.59±0.2°.

[0069] Preferably, in certain embodiments, the ratio of the compound of Formula 1 to L- camphorsulfonic acid in the L-camphorsulfonate salt Form II is 1:1.

[0070] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the L- camphorsulfonate salt Form II has the following characteristic peaks with good stability and reproducibility in the order of intensity: 9.17±0.2°, 9.84±0.2°, 12.00±0.2°, 13.39±0.2°, 16.09±0.2°, 19.09±0.2°, 20.05±0.2°, 20.38±0.2°, 20.59±0.2°, 21.10±0.2°, 21.78±0.2°, 25.14±0.2°, 26.29±0.2°, 28.13±0.2°.

[0071] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is benzenesulfonate, the benzenesulfonate salt of the compound of Formula 1 is Form I, the ratio of the compound of Formula 1 to benzenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the benzenesulfonate salt Form I has the following characteristic peaks with excellent stability and reproducibility in the order of intensity: 4.68±0.2°, 9.35±0.2°, 14.04±0.2°.

[0072] Preferably, in certain embodiments, the ratio of the compound of Formula 1 to benzenesulfonic acid in the benzenesulfonate salt Form I is 1:1.

[0073] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the benzenesulfonate salt Form I has the following characteristic peaks with good stability and reproducibility in the order of intensity: 4.68±0.2°, 9.35±0.2°, 14.04±0.2°, 14.81±0.2°, 18.25±0.2°, 22.02±0.2°, 23.50±0.2°, 24.94±0.2°.

[0074] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is benzenesulfonate, the benzenesulfonate salt of the compound of Formula 1 is Form II, the ratio of the compound of Formula 1 to benzenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the benzenesulfonate salt Form II has the following characteristic peaks with excellent stability and reproducibility in the order of intensity: 4.67±0.2°, 14.07±0.2°, 18.12±0.2°.

[0075] Preferably, in certain embodiments, the ratio of the compound of Formula 1 to benzenesulfonic acid in the benzenesulfonate salt Form II is 1:1.

[0076] Preferably, in some embodiments, the benzenesulfonate salt Form II has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility in the 2-theta position: 4.67 ± 0.2°, 9.35 ± 0.2°, 14.07 ± 0.2°, 18.12 ± 0.2°, 18.57 ± 0.2°, 22.77 ± 0.2°, 23.02 ± 0.2°, 23.55 ± 0.2°.

[0077] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is malonate salt, the malonate salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and malonic acid is 1:0.5-3, and the malonate salt Form I has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility in the 2-theta position: 15.25 ± 0.2°, 18.28 ± 0.2°, 19.46 ± 0.2°, 19.72 ± 0.2°, 22.96 ± 0.2°.

[0078] Preferably, in some embodiments, the malonate salt Form I has the salt formation ratio of the compound of Formula 1 and malonic acid as 1:1.

[0079] Preferably, in some embodiments, the malonate salt Form I has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility in the 2-theta position: 8.93 ± 0.2°, 15.25 ± 0.2°, 17.90 ± 0.2°, 18.28 ± 0.2°, 18.46 ± 0.2°, 19.46 ± 0.2°, 19.72 ± 0.2°, 21.50 ± 0.2°, 22.96 ± 0.2°, 23.47 ± 0.2°, 24.67 ± 0.2°, 26.52 ± 0.2°.

[0080] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is oxalate salt, the oxalate salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and oxalic acid is 1:0.5-3, and the oxalate salt Form I has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility in the 2-theta position: 7.80 ± 0.2°, 14.68 ± 0.2°, 21.29 ± 0.2°.

[0081] Preferably, in some embodiments, the oxalate salt Form I has the salt formation ratio of the compound of Formula 1 and oxalic acid as 1:1.

[0082] Preferably, in certain embodiments, the oxalate salt Form I has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility: 7.80 ± 0.2°, 14.68 ± 0.2°, 16.27 ± 0.2°, 18.30 ± 0.2°, 18.48 ± 0.2°, 19.16 ± 0.2°, 20.73 ± 0.2°, 21.29 ± 0.2°, 21.89 ± 0.2°, 23.71 ± 0.2°, 24.06 ± 0.2°, 24.56 ± 0.2°.

[0083] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is oxalate salt, the oxalate salt of the compound of Formula 1 is Form II, the salt formation ratio of the compound of Formula 1 and oxalic acid is 1:0.5-3, and the oxalate salt Form II has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 6.30 ± 0.2°, 9.47 ± 0.2°, 15.86 ± 0.2°, 19.06 ± 0.2°.

[0084] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and oxalic acid in the oxalate salt Form II is 1:1.

[0085] Preferably, in certain embodiments, the oxalate salt Form II has the following characteristic X-ray powder diffraction peaks with good stability and reproducibility: 3.10 ± 0.2°, 6.30 ± 0.2°, 9.47 ± 0.2°, 12.67 ± 0.2°, 15.86 ± 0.2°, 16.70 ± 0.2°, 19.06 ± 0.2°, 22.34 ± 0.2°, 22.88 ± 0.2°, 24.16 ± 0.2°, 25.23 ± 0.2°, 25.54 ± 0.2°, 26.05 ± 0.2°.

[0086] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is p-toluenesulfonic acid salt, the p-toluenesulfonic acid salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and p-toluenesulfonic acid is 1:0.5-3, and the p-toluenesulfonic acid salt Form I has the following characteristic X-ray powder diffraction peaks with excellent stability and reproducibility: 4.47 ± 0.2°, 14.15 ± 0.2°, 18.48 ± 0.2°.

[0087] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and p-toluenesulfonic acid in the p-toluenesulfonic acid salt Form I is 1:1.

[0088] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the p-toluenesulfonic acid salt Form I has the following characteristic peaks with good stability and reproducibility: 4.47±0.2°, 8.93±0.2°, 13.41±0.2°, 14.15±0.2°, 16.14±0.2°, 18.48±0.2°, 19.21±0.2°, 22.47±0.2°, 22.77±0.2°, 24.87±0.2°, 25.20±0.2°.

[0089] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is p-toluenesulfonic acid salt, the compound of Formula 1 p-toluenesulfonic acid salt is in Form II, the salt formation ratio of the compound of Formula 1 and p-toluenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the p-toluenesulfonic acid salt Form II has the following characteristic peaks with excellent stability and reproducibility: 3.29±0.2°, 14.23±0.2°, 16.86±0.2°, 22.70±0.2°, 22.85±0.2°, 24.82±0.2°.

[0090] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and p-toluenesulfonic acid in the p-toluenesulfonic acid salt Form II is 1:1.

[0091] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the p-toluenesulfonic acid salt Form II has the following characteristic peaks with good stability and reproducibility: 3.29±0.2°, 11.35±0.2°, 13.25±0.2°, 13.66±0.2°, 14.23±0.2°, 16.86±0.2°, 19.14±0.2°, 22.51±0.2°, 22.70±0.2°, 22.85±0.2°, 23.31±0.2°, 23.47±0.2°, 24.82±0.2°, 25.04±0.2°, 26.86±0.2°.

[0092] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is methanesulfonic acid salt, the compound of Formula 1 methanesulfonic acid salt is in Form I, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the methanesulfonic acid salt Form I has the following characteristic peaks with excellent stability and reproducibility: 7.27±0.2°, 15.45±0.2°, 19.84±0.2°, 21.58±0.2°, 22.17±0.2°, 22.46±0.2°.

[0093] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid in the methanesulfonic acid salt Form I is 1:1.

[0094] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the mesylate salt Form I has the following characteristic peaks with good stability and reproducibility: 5.06±0.2°, 7.27±0.2°, 15.45±0.2°, 16.90±0.2°, 17.43±0.2°, 18.79±0.2°, 19.60±0.2°, 19.84±0.2°, 21.21±0.2°, 21.58±0.2°, 22.17±0.2°, 22.46±0.2°, 25.59±0.2°, 25.81±0.2°, 26.51±0.2°.

[0095] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is mesylate salt, the mesylate salt of the compound of Formula 1 is Form II, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the mesylate salt Form II has the following characteristic peaks with excellent stability and reproducibility: 6.74±0.2°, 13.84±0.2°, 14.02±0.2°, 16.85±0.2°, 18.06±0.2°.

[0096] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid in the mesylate salt Form II is 1:1.

[0097] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the mesylate salt Form II has the following characteristic peaks with good stability and reproducibility: 3.39±0.2°, 6.74±0.2°, 13.84±0.2°, 14.02±0.2°, 16.85±0.2°, 18.06±0.2°, 19.26±0.2°, 20.10±0.2°, 20.68±0.2°, 22.08±0.2°, 23.37±0.2°, 23.65±0.2°, 25.51±0.2°.

[0098] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is mesylate salt, the mesylate salt of the compound of Formula 1 is Form III, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the mesylate salt Form III has the following characteristic peaks with excellent stability and reproducibility: 4.98±0.2°, 6.98±0.2°, 15.65±0.2°, 17.08±0.2°, 21.06±0.2°.

[0099] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid in the mesylate salt Form III is 1:1.

[0100] Preferably, in some embodiments, the methanesulfonate salt Form III has a X-ray powder diffraction pattern with the following characteristic peaks of lesser stability and reproducibility: 4.98±0.2°, 6.98±0.2°, 15.01±0.2°, 15.65±0.2°, 17.08±0.2°, 17.98±0.2°, 20.48±0.2°, 21.06±0.2°, 21.57±0.2°, 23.12±0.2°, 24.16±0.2°, 25.36±0.2°.

[0101] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is methanesulfonate, the methanesulfonate salt of the compound of Formula 1 is Form IV, the salt formation ratio of the compound of Formula 1 and methanesulfonic acid is 1:0.5-3, and the methanesulfonate salt Form IV has a X-ray powder diffraction pattern with the following characteristic peaks of excellent stability and reproducibility: 8.95±0.2°, 18.54±0.2°, 26.22±0.2°, 26.94±0.2°.

[0102] Preferably, in some embodiments, the methanesulfonate salt Form IV has a salt formation ratio of 1:1 of the compound of Formula 1 and methanesulfonic acid.

[0103] Preferably, in some embodiments, the methanesulfonate salt Form IV has a X-ray powder diffraction pattern with the following characteristic peaks of lesser stability and reproducibility: 7.61±0.2°, 8.95±0.2°, 13.90±0.2°, 15.67±0.2°, 18.54±0.2°, 18.78±0.2°, 19.93±0.2°, 20.38±0.2°, 21.61±0.2°, 26.22±0.2°, 26.94±0.2°.

[0104] In the above-mentioned salt form of the compound of Formula 1, the pharmaceutically acceptable salt is sulfate, the sulfate salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and sulfuric acid is 1:0.5-3, and the sulfate salt Form I has a X-ray powder diffraction pattern with the following characteristic peaks of excellent stability and reproducibility: 4.39±0.2°, 8.78±0.2°, 16.95±0.2°.

[0105] Preferably, in some embodiments, the sulfate salt Form I has a salt formation ratio of 1:1 of the compound of Formula 1 and sulfuric acid.

[0106] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the sulfate salt Form I has the following characteristic peaks with good stability and reproducibility: 4.39 ± 0.2°, 4.65 ± 0.2°, 8.78 ± 0.2°, 13.16 ± 0.2°, 16.95 ± 0.2°, 17.58 ± 0.2°, 19.13 ± 0.2°, 23.38 ± 0.2°.

[0107] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is a gentisate salt, the gentisate salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and gentisic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the gentisate salt Form I has the following characteristic peaks with excellent stability and reproducibility: 6.88 ± 0.2°, 19.90 ± 0.2°, 26.79 ± 0.2°.

[0108] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and gentisic acid in the gentisate salt Form I is 1:1.

[0109] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the gentisate salt Form I has the following characteristic peaks with good stability and reproducibility: 6.88 ± 0.2°, 13.78 ± 0.2°, 14.80 ± 0.2°, 16.19 ± 0.2°, 19.90 ± 0.2°, 22.46 ± 0.2°, 26.09 ± 0.2°, 26.79 ± 0.2°.

[0110] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is a maleate salt, the maleate salt of the compound of Formula 1 is Form I, the salt formation ratio of the compound of Formula 1 and maleic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the maleate salt Form I has the following characteristic peaks with excellent stability and reproducibility: 19.00 ± 0.2°, 22.63 ± 0.2°, 24.51 ± 0.2°.

[0111] Preferably, in certain embodiments, the salt formation ratio of the compound of Formula 1 and maleic acid in the maleate salt Form I is 1:1.

[0112] Preferably, in certain embodiments, the X-ray powder diffraction pattern of the maleate salt Form I has the following characteristic peaks with good stability and reproducibility: 8.70 ± 0.2°, 11.86 ± 0.2°, 14.72 ± 0.2°, 15.44 ± 0.2°, 16.88 ± 0.2°, 17.21 ± 0.2°, 18.64 ± 0.2°, 20.50 ± 0.2°, 22.63 ± 0.2°, 23.65 ± 0.2°, 24.05 ± 0.2°, 24.51 ± 0.2°.

[0113] In the above-mentioned salt type of the compound of Formula 1, the pharmaceutically acceptable salt is a maleate salt, the compound of Formula 1 maleate salt is a crystal form II, the salt formation ratio of the compound of Formula 1 and maleic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the maleate salt crystal form II has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 6.18±0.2°, 14.48±0.2°, 15.60±0.2°, 19.83±0.2°, 25.62±0.2°, 25.91±0.2°, and 26.71±0.2°.

[0114] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and maleic acid in the maleate salt crystal form II is 1:1.

[0115] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the maleate salt crystal form II has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 6.18±0.2°, 14.48±0.2°, 15.60±0.2°, 15.87±0.2°, 16.13±0.2°, 19.83±0.2°, 20.03±0.2°, 20.43±0.2°, 21.89±0.2°, 23.18±0.2°, 24.11±0.2°, 25.62±0.2°, 25.91±0.2°, and 26.71±0.2°.

[0116] In the above-mentioned salt type of the compound of Formula 1, the pharmaceutically acceptable salt is a citrate salt, the compound of Formula 1 citrate salt is a crystal form I, the salt formation ratio of the compound of Formula 1 and citric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the citrate salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 16.97±0.2°, 21.13±0.2°, and 25.08±0.2°.

[0117] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and citric acid in the citrate salt crystal form I is 1:1.

[0118] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the citrate salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 8.75±0.2°, 9.04±0.2°, 10.55±0.2°, 12.95±0.2°, 15.96±0.2°, 16.97±0.2°, 17.55±0.2°, 20.56±0.2°, 21.13±0.2°, 21.55±0.2°, 23.37±0.2°, 25.08±0.2°, and 26.05±0.2°.

[0119] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is a hydrobromide salt, the hydrobromide salt of the compound of Formula 1 is a crystal form I, the salt formation ratio of the compound of Formula 1 and hydrobromic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the hydrobromide salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 16.46±0.2°, 16.86±0.2°, 18.41±0.2°, and 20.70±0.2°.

[0120] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and hydrobromic acid in the hydrobromide salt crystal form I is 1:0.8.

[0121] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the hydrobromide salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 9.19±0.2°, 15.32±0.2°, 16.46±0.2°, 16.86±0.2°, 18.41±0.2°, 20.14±0.2°, 20.70±0.2°, 26.46±0.2°, 27.03±0.2°, 29.26±0.2°, and 30.73±0.2°.

[0122] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is a hydrochloride salt, the hydrochloride salt of the compound of Formula 1 is a crystal form I, the salt formation ratio of the compound of Formula 1 and hydrochloric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the hydrochloride salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.49±0.2°, 8.96±0.2°, 13.47±0.2°, and 20.26±0.2°.

[0123] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and hydrochloric acid in the hydrochloride salt crystal form I is 1:0.65.

[0124] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the hydrochloride salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 4.49±0.2°, 8.96±0.2°, 9.32±0.2°, 11.25±0.2°, 13.47±0.2°, 15.72±0.2°, and 20.26±0.2°.

[0125] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is ethanesulfonic acid salt, the ethanesulfonic acid salt of the compound of Formula 1 is crystal form I, the salt formation ratio of the compound of Formula 1 and ethanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.99±0.2°, 14.95±0.2°, 15.43±0.2°, 17.49±0.2°, 20.51±0.2°.

[0126] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and ethanesulfonic acid in the ethanesulfonic acid salt crystal form I is 1:1.

[0127] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 4.99±0.2°, 6.80±0.2°, 11.56±0.2°, 14.95±0.2°, 15.43±0.2°, 16.63±0.2°, 17.49±0.2°, 20.51±0.2°, 23.25±0.2°, 25.67±0.2°.

[0128] In the salt form of the compound of Formula 1 described above, the pharmaceutically acceptable salt is ethanesulfonic acid salt, the ethanesulfonic acid salt of the compound of Formula 1 is crystal form II, the salt formation ratio of the compound of Formula 1 and ethanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form II has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 4.96±0.2°, 6.83±0.2°, 11.56±0.2°, 15.00±0.2°, 15.55±0.2°.

[0129] Preferably, in some specific embodiments, the salt formation ratio of the compound of Formula 1 and ethanesulfonic acid in the ethanesulfonic acid salt crystal form II is 1:1.

[0130] Preferably, in some specific embodiments, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form II has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 4.96±0.2°, 6.83±0.2°, 11.56±0.2°, 15.00±0.2°, 15.55±0.2°, 17.59±0.2°, 19.83±0.2°, 20.40±0.2°, 21.25±0.2°, 23.67±0.2°.

[0131] In the salt form of the compound of formula 1, the pharmaceutically acceptable salt is a saccharin co-crystal, the saccharin co-crystal of the compound of formula 1 is crystal form I, the co-crystal of the compound of formula 1 and saccharin has a ratio of 1:0.5-3, and the X-ray powder diffraction pattern of the saccharin co-crystal crystal form I has the following characteristic diffraction peaks with excellent stability and repeatability at 2θ positions of 11.09±0.2°, 17.12±0.2°, 23.26±0.2°, 25.00±0.2°, 26.54±0.2°.

[0132] Preferably, in some specific embodiments, the saccharin co-crystal crystal form I has a ratio of the compound of formula 1 and saccharin of 1:1.

[0133] Preferably, in some specific embodiments, the saccharin co-crystal crystal form I has the following characteristic diffraction peaks with less excellent stability and repeatability at 2θ positions of 8.98±0.2°, 11.09±0.2°, 13.68±0.2°, 15.58±0.2°, 17.12±0.2°, 17.91±0.2°, 22.00±0.2°, 22.89±0.2°, 23.26±0.2°, 23.48±0.2°, 25.00±0.2°, 26.54±0.2°.

[0134] The present application also provides a preparation method of the above-mentioned salt form, wherein the preparation method of the fumaric acid salt crystal form I comprises the following steps:

[0135] The compound of formula 1 and acetonitrile are mixed at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of fumaric acid are added, and then stirring is performed at room temperature for 1-48 h, filtration and drying are performed to obtain the fumaric acid salt crystal form I.

[0136] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of the fumaric acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and acetonitrile is 40-60 mg: 1 mL.

[0137] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of the fumaric acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and acetonitrile is 50 mg: 1 mL.

[0138] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of the fumaric acid salt crystal form I, the amount of fumaric acid added is 1.05-1.15 equivalents.

[0139] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of the fumaric acid salt crystal form I, the amount of fumaric acid added is 1.1 equivalents.

[0140] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of the fumaric acid salt crystal form I, the stirring time is 12-24 h.

[0141] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the fumarate salt crystal form I is 18 h.

[0142] The present application also provides the preparation method of the salt type, wherein the preparation method of the fumarate salt crystal form II comprises the following steps:

[0143] The fumarate crystal form I obtained by the above method is mixed with methanol at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at room temperature for 1-5 days, filtered and dried to obtain the fumarate salt crystal form II.

[0144] Preferably, in the preparation method of the salt type, the mass-volume ratio of the fumarate crystal form I and methanol in the preparation method of the fumarate salt crystal form II is 40-60 mg: 1 mL.

[0145] Preferably, in the preparation method of the salt type, the mass-volume ratio of the fumarate crystal form I and methanol in the preparation method of the fumarate salt crystal form II is 50 mg: 1 mL.

[0146] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the fumarate salt crystal form II is 2-4 days.

[0147] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the fumarate salt crystal form II is 3 days.

[0148] The present application also provides the preparation method of the salt type, wherein the preparation method of the fumarate salt crystal form III comprises the following steps:

[0149] The fumarate crystal form I obtained by the above method is mixed with dimethyl sulfoxide at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at room temperature for 1-5 days, filtered and dried to obtain the fumarate salt crystal form III.

[0150] Preferably, in the preparation method of the salt type, the mass-volume ratio of the fumarate crystal form I and dimethyl sulfoxide in the preparation method of the fumarate salt crystal form III is 40-60 mg: 1 mL.

[0151] Preferably, in the preparation method of the salt type, the mass-volume ratio of the fumarate crystal form I and dimethyl sulfoxide in the preparation method of the fumarate salt crystal form III is 50 mg: 1 mL.

[0152] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the fumarate salt crystal form III is 2-4 days.

[0153] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the fumarate salt crystal form III is 3 days.

[0154] The present application also provides a preparation method of the above-mentioned salt type, wherein the preparation method of the fumarate salt crystal form IV comprises the following steps:

[0155] The fumarate crystal form I obtained by the above-mentioned method is mixed with water in a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at room temperature for 1-5 days, filtered and dried to obtain the fumarate salt crystal form IV.

[0156] Preferably, in the preparation method of the above-mentioned salt type, the mass-volume ratio of the fumarate crystal form I and water in the preparation method of the fumarate salt crystal form IV is 50 mg: 1 mL.

[0157] Preferably, in the preparation method of the above-mentioned salt type, the mass-volume ratio of the fumarate crystal form I and water in the preparation method of the fumarate salt crystal form IV is 50 mg: 1 mL.

[0158] Preferably, in the preparation method of the above-mentioned salt type, the stirring time in the preparation method of the fumarate salt crystal form IV is 3 days.

[0159] Preferably, in the preparation method of the above-mentioned salt type, the stirring time in the preparation method of the fumarate salt crystal form IV is 3 days.

[0160] The present application also provides a preparation method of the above-mentioned salt type, wherein the preparation method of the fumarate salt crystal form V comprises the following steps:

[0161] The fumarate crystal form I obtained by the above-mentioned method is mixed with water in a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at room temperature for 6-10 days, filtered and dried to obtain the fumarate salt crystal form V.

[0162] Preferably, in the preparation method of the above-mentioned salt type, the mass-volume ratio of the fumarate crystal form I and water in the preparation method of the fumarate salt crystal form V is 50 mg: 1 mL.

[0163] Preferably, in the preparation method of the above-mentioned salt type, the mass-volume ratio of the fumarate crystal form I and water in the preparation method of the fumarate salt crystal form V is 50 mg: 1 mL.

[0164] Preferably, in the preparation method of the above-mentioned salt type, the stirring time in the preparation method of the fumarate salt crystal form V is 7 days.

[0165] Preferably, in the preparation method of the above-mentioned salt type, the stirring time in the preparation method of the fumarate salt crystal form V is 7 days.

[0166] The present application also provides a preparation method of the above-mentioned salt type, wherein the preparation method of the fumarate salt crystal form VI comprises the following steps:

[0167] The fumarate crystal form I obtained by the above method is mixed with tetrahydrofuran at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at 40-60°C for 6-10 days, filtered and dried to obtain the fumarate crystal form VI.

[0168] In the preparation method of the salt form and the preparation method of the fumarate crystal form VI, the mass-volume ratio of the fumarate crystal form I and tetrahydrofuran is 40-60 mg: 1 mL.

[0169] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VI, the mass-volume ratio of the fumarate crystal form I and tetrahydrofuran is 50 mg: 1 mL.

[0170] In the preparation method of the salt form and the preparation method of the fumarate crystal form VI, the stirring temperature is 50°C,

[0171] In the preparation method of the salt form and the preparation method of the fumarate crystal form VI, the stirring time is 6-8 days.

[0172] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VI, the stirring time is 7 days.

[0173] The present application also provides a preparation method of the salt form, wherein the preparation method of the fumarate crystal form VII comprises the following steps:

[0174] The fumarate crystal form I obtained by the above method is mixed with water at a mass-volume ratio of 15-25 mg: 1-10 mL, and then rapidly cooled (cold bath) to 0-10°C and stirred, filtered and dried to obtain the fumarate crystal form VII.

[0175] In the preparation method of the salt form and the preparation method of the fumarate crystal form VII, the mass-volume ratio of the fumarate crystal form I and water is 15-25 mg: 4 mL.

[0176] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VII, the mass-volume ratio of the fumarate crystal form I and water is 20 mg: 4 mL.

[0177] In the preparation method of the salt form and the preparation method of the fumarate crystal form VII, the rapid cooling is to 2-6°C.

[0178] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VII, the rapid cooling is to 4°C.

[0179] The present application also provides a preparation method of the salt form, wherein the preparation method of the fumarate crystal form VIII comprises the following steps:

[0180] The fumarate crystal form I obtained by the above method is mixed with ethanol at a mass-volume ratio of 15-25 mg: 1-10 mL, and then slowly cooled (gradient cooling) to 0-10°C with stirring, filtered and dried to obtain the fumarate crystal form VIII.

[0181] In the preparation method of the salt form and the preparation method of the fumarate crystal form VIII, the mass-volume ratio of the fumarate crystal form I and ethanol is 15-25 mg: 4 mL.

[0182] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VIII, the mass-volume ratio of the fumarate crystal form I and ethanol is 20 mg: 4 mL.

[0183] In the preparation method of the salt form and the preparation method of the fumarate crystal form VIII, the rapid cooling is to 2-6°C.

[0184] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form VIII, the rapid cooling is to 4°C.

[0185] The application also provides a preparation method of the salt form, wherein the preparation method of the fumarate crystal form IX comprises the following steps:

[0186] The compound of formula 1 and ethyl acetate or tetrahydrofuran are mixed at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of fumaric acid is then added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the fumarate crystal form IX.

[0187] In the preparation method of the salt form and the preparation method of the fumarate crystal form IX, the mass-volume ratio of the compound of formula 1 and ethyl acetate or tetrahydrofuran is 40-60 mg: 0.5-10 mL.

[0188] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form IX, the mass-volume ratio of the compound of formula 1 and ethyl acetate or tetrahydrofuran is 50 mg: 1-1.5 mL.

[0189] In the preparation method of the salt form and the preparation method of the fumarate crystal form IX, the amount of fumaric acid added is 1.05-1.15 equivalents.

[0190] Preferably, in the preparation method of the salt form and the preparation method of the fumarate crystal form IX, the amount of fumaric acid added is 1.1 equivalents.

[0191] In the preparation method of the salt form and the preparation method of the fumarate crystal form IX, the stirring time is 12-24 hours.

[0192] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form IX, the stirring time is 18 h.

[0193] The present application also provides the preparation method of the salt type, wherein the preparation method of the fumarate salt crystal form X comprises the following steps:

[0194] The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg:0.5-10 mL, 0.5-4 equivalents of fumaric acid is added, then stirred at room temperature for 1-48 h, filtered and dried to obtain the fumarate salt crystal form X.

[0195] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the mass-volume ratio of the compound of formula 1 and the mixed solvent is 40-60 mg:1 mL.

[0196] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the mass-volume ratio of the compound of formula 1 and the mixed solvent is 50 mg:1 mL.

[0197] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25:1.

[0198] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the volume ratio of acetone and water in the mixed solvent of acetone and water is 19:1.

[0199] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the amount of fumaric acid added is 1.05-1.15 equivalents.

[0200] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the amount of fumaric acid added is 1.1 equivalents.

[0201] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the stirring time is 12-24 h.

[0202] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form X, the stirring time is 18 h.

[0203] The present application also provides the preparation method of the salt type, wherein the preparation method of the L-tartrate salt crystal form I comprises the following steps:

[0204] The compound of formula 1 is mixed with ethanol at a mass-volume ratio of 40-60 mg:0.5-10 mL, 0.5-4 equivalents of L-tartaric acid is added, then stirred at room temperature for 1-48 h, filtered and dried to obtain the L-tartrate salt crystal form I.

[0205] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the mass / volume ratio of the compound of Formula 1 and ethanol is 40 to 60 mg: 1 mL.

[0206] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the mass / volume ratio of the compound of Formula 1 and ethanol is 50 mg: 1 mL.

[0207] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the amount of L-tartaric acid added is 1.05 to 1.15 equivalents.

[0208] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the amount of L-tartaric acid added is 1.1 equivalents.

[0209] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the stirring time is 12 to 24 hours.

[0210] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form I, the stirring time is 18 hours.

[0211] The present application also provides a method for preparing the salt form, wherein the method for preparing the L-tartrate salt Form II comprises the following steps:

[0212] The L-tartrate salt Form I obtained by the above method is mixed with methanol in a mass / volume ratio of 80 to 120 mg: 1 to 10 mL, stirred at room temperature for 1 to 5 days, filtered and dried to obtain the L-tartrate salt Form II.

[0213] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form II, the mass / volume ratio of the L-tartrate salt Form I and methanol is 80 to 120 mg: 4 mL.

[0214] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form II, the mass / volume ratio of the L-tartrate salt Form I and methanol is 100 mg: 4 mL.

[0215] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form II, the stirring time is 2 to 4 days.

[0216] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form II, the stirring time is 3 days.

[0217] The application also provides a preparation method of the salt type, wherein the preparation method of the L-tartrate salt crystal form III comprises the following steps:

[0218] The L-tartrate salt crystal form I obtained by the above method is mixed with water in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature for 6-10 days, filtered and dried to obtain the L-tartrate salt crystal form III.

[0219] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and water in the preparation method of the L-tartrate salt crystal form III is 100 mg: 1 mL.

[0220] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and water in the preparation method of the L-tartrate salt crystal form III is 100 mg: 1 mL.

[0221] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form III is 7 days.

[0222] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form III is 7 days.

[0223] The application also provides a preparation method of the salt type, wherein the preparation method of the L-tartrate salt crystal form IV comprises the following steps:

[0224] The L-tartrate salt crystal form I obtained by the above method is mixed with water in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature for 1-5 days, filtered and dried to obtain the L-tartrate salt crystal form IV.

[0225] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and water in the preparation method of the L-tartrate salt crystal form IV is 100 mg: 1 mL.

[0226] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and water in the preparation method of the L-tartrate salt crystal form IV is 100 mg: 1 mL.

[0227] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form IV is 3 days.

[0228] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form IV is 3 days.

[0229] The application also provides a preparation method of the salt type, wherein the preparation method of the L-tartrate salt crystal form V comprises the following steps:

[0230] The L-tartrate salt crystal form I obtained by the above method is mixed with a mixed solvent in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature-60°C for 1-5 days, filtered and dried to obtain the L-tartrate salt crystal form V; the mixed solvent is a mixed solvent of methanol, tetrahydrofuran or acetonitrile and water in a volume ratio of 0.5-5.

[0231] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and the mixed solvent in the preparation method of the L-tartrate salt crystal form V is 100 mg: 1 mL.

[0232] Preferably, in the preparation method of the salt type, the mass-volume ratio of the L-tartrate salt crystal form I and the mixed solvent in the preparation method of the L-tartrate salt crystal form V is 100 mg: 1 mL.

[0233] Preferably, in the preparation method of the salt type, the volume ratio of methanol, tetrahydrofuran or acetonitrile and water in the mixed solvent in the preparation method of the L-tartrate salt crystal form V is 1:1.

[0234] Preferably, in the preparation method of the salt type, the volume ratio of methanol, tetrahydrofuran or acetonitrile and water in the mixed solvent in the preparation method of the L-tartrate salt crystal form V is 1:1.

[0235] Preferably, in the preparation method of the salt type, the temperature of the stirring in the preparation method of the L-tartrate salt crystal form V is room temperature-50°C.

[0236] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form V is 2-4 days.

[0237] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the L-tartrate salt crystal form V is 3 days.

[0238] The application also provides a preparation method of the salt type, wherein the preparation method of the L-tartrate salt crystal form VI comprises the following steps:

[0239] The L-tartrate salt crystal form I obtained by the above method is mixed with an organic solvent in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature-80°C for 1-10 days, filtered and dried to obtain the L-tartrate salt crystal form VI; the organic solvent is methyl tert-butyl ether, ethyl acetate, isopropyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, acetonitrile, 2-butanone, toluene or n-heptane.

[0240] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form VI, the mass / volume ratio of the L-tartrate salt Form I and the organic solvent is 80-120 mg:2 mL.

[0241] Preferably, in the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form VI, the mass / volume ratio of the L-tartrate salt Form I and the organic solvent is 100 mg:2 mL.

[0242] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form VI, the temperature for stirring is room temperature, 50°C or 80°C.

[0243] In the above method for preparing the salt form, in the method for preparing the L-tartrate salt Form VI, the time for stirring is 3-7 days.

[0244] The present application also provides the above method for preparing the salt form, wherein the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I comprises the following steps:

[0245] The compound of Formula 1 is mixed with ethanol or a mixed solvent of acetone and water at a mass / volume ratio of 40-60 mg:0.5-10 mL, 0.5-4 equivalents of 1,5-naphthalenedisulfonic acid is added, and then stirring is carried out at room temperature for 1-48 hours, filtration and drying are carried out to obtain the 1,5-naphthalenedisulfonic acid salt Form I.

[0246] In the above method for preparing the salt form, in the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I, the mass / volume ratio of the compound of Formula 1 and ethanol or the mixed solvent of acetone and water is 40-60 mg:1 mL.

[0247] Preferably, in the above method for preparing the salt form, in the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I, the mass / volume ratio of the compound of Formula 1 and ethanol or the mixed solvent of acetone and water is 50 mg:1 mL.

[0248] In the above method for preparing the salt form, in the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I, the volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25:1.

[0249] Preferably, in the above method for preparing the salt form, in the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I, the volume ratio of acetone and water in the mixed solvent of acetone and water is 19:1.

[0250] In the above method for preparing the salt form, in the method for preparing the 1,5-naphthalenedisulfonic acid salt Form I, the amount of 1,5-naphthalenedisulfonic acid added is 1.05-1.15 equivalents.

[0251] Preferably, in the method for preparing the salt type, the method for preparing the 1,5-naphthalenedisulfonic acid salt crystal form I, the amount of 1,5-naphthalenedisulfonic acid added is 1.1 equivalents.

[0252] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0253] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0254] The present application also provides the method for preparing the salt type, wherein the method for preparing the 2-naphthalenesulfonic acid salt crystal form I comprises the following steps:

[0255] The compound of formula 1 and ethyl acetate or dimethyl sulfoxide are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of 2-naphthalenesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the 2-naphthalenesulfonic acid salt crystal form I.

[0256] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 50 mg: 1 mL.

[0257] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 50 mg: 1 mL.

[0258] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the amount of 2-naphthalenesulfonic acid added is 1.05-1.15 equivalents.

[0259] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the amount of 2-naphthalenesulfonic acid added is 1.1 equivalents.

[0260] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0261] Preferably, in the method for preparing the salt type, the method for preparing the 2-naphthalenesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0262] The present application also provides the method for preparing the salt type, wherein the method for preparing the 2-naphthalenesulfonic acid salt crystal form II comprises the following steps:

[0263] The compound of formula 1 is mixed with a mixed solvent of acetone and water in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of 2-naphthalenesulfonic acid is added, and then stirred at room temperature for 1-48 hours. After filtration and drying, the 2-naphthalenesulfonic acid salt crystal form II is obtained.

[0264] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 40-60 mg: 1 mL.

[0265] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 40-60 mg: 1 mL.

[0266] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0267] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0268] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the amount of 2-naphthalenesulfonic acid added is 1.05-1.15 equivalents.

[0269] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the amount of 2-naphthalenesulfonic acid added is 1.05-1.15 equivalents.

[0270] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the stirring time is 12-24 hours.

[0271] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the stirring time is 12-24 hours.

[0272] The present application also provides a preparation method of the salt type, wherein the preparation method of the L-malate crystal form I comprises the following steps:

[0273] The compound of formula 1 is mixed with ethanol in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of L-malic acid is added, and then stirred at room temperature for 1-48 hours. After filtration and drying, the L-malate crystal form I is obtained.

[0274] In the preparation method of the salt type and the preparation method of the 2-naphthalenesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 40-60 mg: 1 mL.

[0275] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0276] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0277] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0278] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0279] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0280] The present application also provides a preparation method of the salt type, wherein the preparation method of the L-camphorsulfonate salt Form I comprises the following steps:

[0281] The compound of formula 1 and ethyl acetate are mixed in a mass / volume ratio of 40-60 mg: 0.5-10 mL, and then 0.5-4 equivalents of L-camphorsulfonic acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the L-camphorsulfonate salt Form I.

[0282] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0283] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0284] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0285] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0286] Preferably, in the preparation method of the salt type, the mass / volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0287] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form I, the stirring time is 18 h.

[0288] The present application also provides the method for preparing the salt type, wherein the method for preparing the L-camphorsulfonate salt crystal form II comprises the following steps:

[0289] The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of L-camphorsulfonic acid is added, and then stirred at room temperature for 1-48 h, filtered and dried to obtain the L-camphorsulfonate salt crystal form II.

[0290] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the mass-volume ratio of the compound of formula 1 to the mixed solvent of acetone and water is 50 mg: 1 mL.

[0291] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the mass-volume ratio of the compound of formula 1 to the mixed solvent of acetone and water is 50 mg: 1 mL.

[0292] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0293] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0294] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0295] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0296] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0297] Preferably, in the method for preparing the salt type, the method for preparing the L-camphorsulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0298] The present application also provides the method for preparing the salt type, wherein the method for preparing the benzenesulfonate salt crystal form I comprises the following steps:

[0299] The compound of formula 1 is mixed with ethanol in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of benzenesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the benzenesulfonate salt crystal form I.

[0300] In the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the mass-volume ratio of the compound of formula 1 to ethanol is 40-60 mg: 1 mL.

[0301] Preferably, in the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the mass-volume ratio of the compound of formula 1 to ethanol is 50 mg: 1 mL.

[0302] In the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the amount of benzenesulfonic acid added is 1.05-1.15 equivalents.

[0303] Preferably, in the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the amount of benzenesulfonic acid added is 1.1 equivalents.

[0304] In the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the stirring time is 12-24 hours.

[0305] Preferably, in the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form I, the stirring time is 18 hours.

[0306] The application also provides a preparation method of the salt type, wherein the preparation method of the benzenesulfonate salt crystal form II comprises the following steps:

[0307] The compound of formula 1 is mixed with an organic solvent in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of benzenesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the benzenesulfonate salt crystal form II; the organic solvent is tetrahydrofuran or dimethyl sulfoxide, or a mixed solvent of acetone and water.

[0308] In the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form II, the mass-volume ratio of the compound of formula 1 to the organic solvent is 40-60 mg: 1 mL.

[0309] Preferably, in the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form II, the mass-volume ratio of the compound of formula 1 to the organic solvent is 50 mg: 1 mL.

[0310] In the preparation method of the salt type and the preparation method of the benzenesulfonate salt crystal form II, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0311] Preferably, in the method for preparing the salt form, the method for preparing the benzenesulfonate salt Form II, the volume ratio of the acetone and water in the mixed solvent of acetone and water is 19:1.

[0312] Preferably, in the method for preparing the salt form, the method for preparing the benzenesulfonate salt Form II, the amount of the benzenesulfonic acid added is 1.05 to 1.15 equivalents.

[0313] Preferably, in the method for preparing the salt form, the method for preparing the benzenesulfonate salt Form II, the amount of the benzenesulfonic acid added is 1.1 equivalents.

[0314] Preferably, in the method for preparing the salt form, the method for preparing the benzenesulfonate salt Form II, the stirring time is 18 h.

[0315] Preferably, in the method for preparing the salt form, the method for preparing the benzenesulfonate salt Form II, the stirring time is 18 h.

[0316] The present application also provides the method for preparing the salt form, wherein the method for preparing the malonate salt Form I comprises the following steps:

[0317] The compound of Formula 1 and acetonitrile or ethyl acetate are mixed in a mass-volume ratio of 40 to 60 mg: 0.5 to 10 mL, 0.5 to 4 equivalents of malonic acid are added, and then stirring is performed at room temperature for 1 to 48 hours, and the malonate salt Form I is obtained by filtration and drying.

[0318] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the mass-volume ratio of the compound of Formula 1 and acetonitrile or ethyl acetate is 50 mg: 1 to 1.5 mL.

[0319] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the mass-volume ratio of the compound of Formula 1 and acetonitrile or ethyl acetate is 50 mg: 1 to 1.5 mL.

[0320] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the amount of the malonic acid added is 1.1 equivalents.

[0321] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the amount of the malonic acid added is 1.1 equivalents.

[0322] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the stirring time is 18 h.

[0323] Preferably, in the method for preparing the salt form, the method for preparing the malonate salt Form I, the stirring time is 18 h.

[0324] The present application also provides a preparation method of the salt type, wherein the preparation method of the oxalate salt crystal type I comprises the following steps:

[0325] The compound of formula 1 and ethanol are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of oxalic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the oxalate salt crystal type I.

[0326] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0327] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0328] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0329] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0330] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0331] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0332] The present application also provides a preparation method of the salt type, wherein the preparation method of the oxalate salt crystal type II comprises the following steps:

[0333] The compound of formula 1 and acetonitrile, or a mixed solvent of acetone and water, are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of oxalic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the oxalate salt crystal type II.

[0334] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type II, the mass-volume ratio of the compound of formula 1 and acetonitrile, or a mixed solvent of acetone and water, is 50 mg: 1 mL.

[0335] Preferably, in the preparation method of the salt type, the preparation method of the oxalate salt crystal type II, the mass-volume ratio of the compound of formula 1 and acetonitrile, or a mixed solvent of acetone and water, is 50 mg: 1 mL.

[0336] In the preparation method of the salt type, the preparation method of the oxalate crystal form II, the volume ratio of the acetone and water in the mixed solvent of acetone and water is 15-25:1.

[0337] Preferably, in the preparation method of the salt type, the preparation method of the oxalate crystal form II, the volume ratio of the acetone and water in the mixed solvent of acetone and water is 19:1.

[0338] In the preparation method of the salt type, the preparation method of the oxalate crystal form II, the oxalic acid is added in an amount of 1.05-1.15 equivalents.

[0339] Preferably, in the preparation method of the salt type, the preparation method of the oxalate crystal form II, the oxalic acid is added in an amount of 1.1 equivalents.

[0340] In the preparation method of the salt type, the preparation method of the oxalate crystal form II, the stirring time is 12-24 hours.

[0341] Preferably, in the preparation method of the salt type, the preparation method of the oxalate crystal form II, the stirring time is 18 hours.

[0342] The application also provides a preparation method of the salt type, wherein the preparation method of the p-toluenesulfonate crystal form I comprises the following steps:

[0343] The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg:0.5-10 mL, 0.5-4 equivalents of p-toluenesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the p-toluenesulfonate crystal form I; the organic solvent is ethanol, acetonitrile, ethyl acetate, tetrahydrofuran or dimethyl sulfoxide.

[0344] In the preparation method of the salt type, the preparation method of the p-toluenesulfonate crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg:1 mL.

[0345] Preferably, in the preparation method of the salt type, the preparation method of the p-toluenesulfonate crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 50 mg:1 mL.

[0346] In the preparation method of the salt type, the preparation method of the p-toluenesulfonate crystal form I, the p-toluenesulfonic acid is added in an amount of 1.05-1.15 equivalents.

[0347] Preferably, in the preparation method of the salt type, the preparation method of the p-toluenesulfonate crystal form I, the p-toluenesulfonic acid is added in an amount of 1.1 equivalents.

[0348] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0349] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0350] The present application also provides a preparation method of the salt type, wherein the preparation method of the p-toluenesulfonate salt crystal form II comprises the following steps:

[0351] The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of p-toluenesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the p-toluenesulfonate salt crystal form II.

[0352] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0353] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0354] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0355] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0356] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0357] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0358] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0359] Preferably, in the preparation method of the salt type, the stirring time in the preparation method of the p-toluenesulfonate salt crystal form I is 18 h.

[0360] The present application also provides a preparation method of the above-mentioned salt type, wherein the preparation method of the methanesulfonic acid salt crystal form I comprises the following steps:

[0361] The compound of formula 1 and ethanol or acetonitrile are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonic acid salt crystal form I.

[0362] In the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethanol or acetonitrile is 40-60 mg: 1 mL.

[0363] Preferably, in the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethanol or acetonitrile is 50 mg: 1 mL.

[0364] In the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the amount of methanesulfonic acid added is 1.05-1.15 equivalents.

[0365] Preferably, in the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the amount of methanesulfonic acid added is 1.1 equivalents.

[0366] In the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the stirring time is 12-24 hours.

[0367] Preferably, in the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0368] The present application also provides a preparation method of the above-mentioned salt type, wherein the preparation method of the methanesulfonic acid salt crystal form II comprises the following steps:

[0369] The compound of formula 1 and ethyl acetate are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonic acid salt crystal form II.

[0370] In the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate is 40-60 mg: 1 mL.

[0371] Preferably, in the preparation method of the above-mentioned salt type, the preparation method of the methanesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate is 50 mg: 1 mL.

[0372] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form II, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0373] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form II, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0374] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form II, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0375] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form II, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0376] The present application also provides the above method for preparing the salt form, wherein the method for preparing the mesylate salt Form III comprises the following steps:

[0377] The compound of Formula 1 and tetrahydrofuran are mixed in a mass-volume ratio of 40 to 60 mg: 0.5 to 10 mL, 0.5 to 4 equivalents of methanesulfonic acid is added, and then stirred at room temperature for 1 to 48 hours, filtered and dried to obtain the mesylate salt Form III.

[0378] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the mass-volume ratio of the compound of Formula 1 and tetrahydrofuran is 40 to 60 mg: 1 mL.

[0379] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the mass-volume ratio of the compound of Formula 1 and tetrahydrofuran is 40 to 60 mg: 1 mL.

[0380] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0381] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0382] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0383] In the above method for preparing the salt form, in the method for preparing the mesylate salt Form III, the amount of the methanesulfonic acid added is 1.05 to 1.15 equivalents.

[0384] The present application also provides the above method for preparing the salt form, wherein the method for preparing the mesylate salt Form IV comprises the following steps:

[0385] The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid is added, and then stirred at room temperature for 1-48 hours. The methanesulfonic acid salt crystal form IV is obtained by filtration and drying.

[0386] In the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the mass-volume ratio of the compound of formula 1 and the mixed solvent of acetone and water is 40-60 mg: 1 mL.

[0387] Preferably, in the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the mass-volume ratio of the compound of formula 1 and the mixed solvent of acetone and water is 50 mg: 1 mL.

[0388] In the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25: 1.

[0389] Preferably, in the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the volume ratio of acetone and water in the mixed solvent of acetone and water is 19: 1.

[0390] In the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the amount of methanesulfonic acid added is 1.05-1.15 equivalents.

[0391] Preferably, in the preparation method of the salt type, the preparation method of the methanesulfonic acid salt crystal form IV, the amount of methanesulfonic acid added is 1.1 equivalents.

[0392] In the preparation method of the salt type, the preparation method of the fumarate salt crystal form IV, the stirring time is 12-24 h.

[0393] Preferably, in the preparation method of the salt type, the preparation method of the fumarate salt crystal form IV, the stirring time is 18 h.

[0394] The application also provides a preparation method of the salt type, wherein the preparation method of the sulfate salt crystal form I comprises the following steps:

[0395] The compound of formula 1 is mixed with ethanol at a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of sulfuric acid is added, and then stirred at room temperature for 1-48 hours. The sulfate salt crystal form I is obtained by filtration and drying.

[0396] In the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethanol is 40-60 mg: 1 mL.

[0397] Preferably, in the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the mass-volume ratio of the compound of formula 1 and ethanol is 50 mg: 1 mL.

[0398] In the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the amount of sulfuric acid added is 1.05-1.15 equivalents.

[0399] Preferably, in the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the amount of sulfuric acid added is 1.1 equivalents.

[0400] In the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the stirring time is 12-24 h.

[0401] Preferably, in the preparation method of the salt type, the preparation method of the sulfate salt crystal form I, the stirring time is 18 h.

[0402] The present application also provides a preparation method of the salt type, wherein the preparation method of the gentisate salt crystal form I comprises the following steps:

[0403] The compound of formula 1 and acetonitrile or ethyl acetate are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of gentisic acid are added, and then stirred at room temperature for 1-48 h, filtered and dried to obtain the gentisate salt crystal form I.

[0404] In the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the mass-volume ratio of the compound of formula 1 and acetonitrile or ethyl acetate is 40-60 mg: 1 mL.

[0405] Preferably, in the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the mass-volume ratio of the compound of formula 1 and acetonitrile or ethyl acetate is 50 mg: 1 mL.

[0406] In the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the amount of gentisic acid added is 1.05-1.15 equivalents.

[0407] Preferably, in the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the amount of gentisic acid added is 1.1 equivalents.

[0408] In the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the stirring time is 12-24 h.

[0409] Preferably, in the preparation method of the salt type, the preparation method of the gentisate salt crystal form I, the stirring time is 18 h.

[0410] The application also provides a preparation method of the salt type, wherein the preparation method of the maleate salt crystal form I comprises the following steps:

[0411] The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of maleic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the maleate salt crystal form I; the organic solvent is ethanol, acetonitrile or ethyl acetate, or a mixed solvent of acetone and water.

[0412] In the preparation method of the salt type, the mass-volume ratio of the compound of formula 1 and the organic solvent in the preparation method of the maleate salt crystal form I is 40-60 mg: 1 mL.

[0413] Preferably, in the preparation method of the salt type, the mass-volume ratio of the compound of formula 1 and the organic solvent in the preparation method of the maleate salt crystal form I is 50 mg: 1 mL.

[0414] In the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0415] Preferably, in the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0416] In the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the amount of maleic acid added is 1.05-1.15 equivalents.

[0417] Preferably, in the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the amount of maleic acid added is 1.1 equivalents.

[0418] In the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the stirring time is 12-24 hours.

[0419] Preferably, in the preparation method of the salt type, the preparation method of the maleate salt crystal form I, the stirring time is 18 hours.

[0420] The application also provides a preparation method of the salt type, wherein the preparation method of the maleate salt crystal form II comprises the following steps:

[0421] The compound of formula 1 and tetrahydrofuran are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of maleic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the maleate salt crystal form II.

[0422] In the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the mass / volume ratio of the compound of Formula 1 and tetrahydrofuran is 40-60 mg: 1 mL.

[0423] Preferably, in the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the mass / volume ratio of the compound of Formula 1 and tetrahydrofuran is 50 mg: 1 mL.

[0424] In the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the amount of maleic acid added is 1.05-1.15 equivalents.

[0425] Preferably, in the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the amount of maleic acid added is 1.1 equivalents.

[0426] In the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the stirring time is 12-24 h.

[0427] Preferably, in the above method for preparing the salt form, in the method for preparing the maleate salt Form II, the stirring time is 18 h.

[0428] The present application also provides a method for preparing the above salt form, wherein the method for preparing the citrate salt Form I comprises the following steps:

[0429] The compound of Formula 1 and an organic solvent are mixed in a mass / volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of citric acid is then added, and the mixture is stirred at room temperature for 1-48 h, filtered and dried to obtain the citrate salt Form I; the organic solvent is ethanol, acetonitrile, ethyl acetate or tetrahydrofuran, or a mixed solvent of acetone and water.

[0430] In the above method for preparing the salt form, in the method for preparing the citrate salt Form I, the mass / volume ratio of the compound of Formula 1 and the organic solvent is 40-60 mg: 1 mL.

[0431] Preferably, in the above method for preparing the salt form, in the method for preparing the citrate salt Form I, the mass / volume ratio of the compound of Formula 1 and the organic solvent is 50 mg: 1 mL.

[0432] In the above method for preparing the salt form, in the method for preparing the citrate salt Form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1.

[0433] Preferably, in the above method for preparing the salt form, in the method for preparing the citrate salt Form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0434] In the above method for preparing the salt type, in the method for preparing the citrate crystal form I, the citric acid is added in an amount of 1.05 to 1.15 equivalents.

[0435] Preferably, in the above method for preparing the salt type, in the method for preparing the citrate crystal form I, the citric acid is added in an amount of 1.1 equivalents.

[0436] In the above method for preparing the salt type, in the method for preparing the citrate crystal form I, the stirring is performed for 12 to 24 hours.

[0437] Preferably, in the above method for preparing the salt type, in the method for preparing the citrate crystal form I, the stirring is performed for 18 hours.

[0438] The present application also provides the above method for preparing the salt type, wherein the method for preparing the hydrobromide crystal form I comprises the following steps:

[0439] The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40 to 60 mg: 0.5 to 10 mL, 0.5 to 4 equivalents of hydrobromic acid is added, and then stirring is performed at room temperature for 1 to 48 hours, and the hydrobromide crystal form I is obtained by filtration and drying; the organic solvent is ethanol, acetonitrile, ethyl acetate, tetrahydrofuran or dimethyl sulfoxide, or a mixed solvent of acetone and water.

[0440] In the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 40 to 60 mg: 1 mL.

[0441] Preferably, in the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 50 mg: 1 mL.

[0442] In the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 15 to 25: 1.

[0443] Preferably, in the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the volume ratio of acetone to water in the mixed solvent of acetone and water is 19: 1.

[0444] In the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the hydrobromic acid is added in an amount of 1.05 to 1.15 equivalents.

[0445] Preferably, in the above method for preparing the salt type, in the method for preparing the hydrobromide crystal form I, the hydrobromic acid is added in an amount of 1.1 equivalents.

[0446] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 12-24 h.

[0447] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0448] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0449] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0450] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0451] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0452] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0453] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0454] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0455] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0456] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0457] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0458] The preparation method of the salt type, the preparation method of the hydrobromide salt crystal form I, wherein the stirring time is 18 h.

[0459] The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of ethanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the ethanesulfonic acid salt crystal form I; the organic solvent is ethanol, acetonitrile or dimethyl sulfoxide.

[0460] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL.

[0461] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the mass-volume ratio of the compound of formula 1 and the organic solvent is 50 mg: 1 mL.

[0462] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the amount of ethanesulfonic acid added is 1.05-1.15 equivalents.

[0463] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the amount of ethanesulfonic acid added is 1.1 equivalents.

[0464] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the stirring time is 12-24 hours.

[0465] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form I, the stirring time is 18 hours.

[0466] The application also provides a preparation method of the salt type, wherein the preparation method of the ethanesulfonic acid salt crystal form II comprises the following steps:

[0467] The compound of formula 1 and ethyl acetate or tetrahydrofuran are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of ethanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the ethanesulfonic acid salt crystal form II.

[0468] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate or tetrahydrofuran is 40-60 mg: 1 mL.

[0469] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form II, the mass-volume ratio of the compound of formula 1 and ethyl acetate or tetrahydrofuran is 50 mg: 1 mL.

[0470] In the preparation method of the salt type and the preparation method of the ethanesulfonic acid salt crystal form II, the amount of ethanesulfonic acid added is 1.05-1.15 equivalents.

[0471] Preferably, in the preparation method of the above-mentioned salt form, in the preparation method of the ethanesulfonic acid salt crystal form II, the amount of ethanesulfonic acid added is 1.1 equivalents.

[0472] Wherein, in the preparation method of the above-mentioned salt form, in the preparation method of the ethanesulfonate salt crystal form II, the stirring time is 12 to 24 hours.

[0473] Preferably, in the preparation method of the above-mentioned salt form, in the preparation method of the ethanesulfonate salt crystal form II, the stirring time is 18 hours.

[0474] The present invention also provides a method for preparing the above-mentioned salt form, wherein the method for preparing saccharin cocrystal form I comprises the following steps:

[0475] The compound of formula 1 and acetonitrile are mixed in a mass volume ratio of 40-60 mg:0.5-10 mL, and then 0.5-4 equivalents of saccharin are added. The mixture is then stirred at room temperature for 1-48 hours, filtered and dried to obtain saccharin cocrystal Form I.

[0476] Among them, in the preparation method of the above-mentioned salt form and the preparation method of saccharin cocrystal form I, the mass volume ratio of the compound of formula 1 and acetonitrile is 40-60 mg:1 mL.

[0477] Preferably, in the preparation method of the above-mentioned salt form, the preparation method of saccharin cocrystal form I, the mass volume ratio of the compound of formula 1 and acetonitrile is 50 mg:1 mL.

[0478] Among them, in the preparation method of the above-mentioned salt form, in the preparation method of saccharin cocrystal form I, the amount of saccharin added is 1.05 to 1.15 equivalents.

[0479] Preferably, in the preparation method of the above-mentioned salt form, in the preparation method of saccharin cocrystal form I, the amount of saccharin added is 1.1 equivalents.

[0480] Wherein, in the preparation method of the above-mentioned salt form and the preparation method of saccharin cocrystal form I, the stirring time is 12 to 24 hours.

[0481] Preferably, in the preparation method of the above-mentioned salt form and the preparation method of saccharin cocrystal form I, the stirring time is 18 hours.

[0482] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of each of the above salt forms and a pharmaceutically acceptable carrier and / or excipient.

[0483] Preferably, in the above pharmaceutical composition, the therapeutically effective amount is 1 to 600 mg calculated as the free base of the compound of formula 1.

[0484] More preferably, in the above pharmaceutical composition, the therapeutically effective amount is 1 to 400 mg calculated as the free base of the compound of formula 1.

[0485] Most preferably, in the above pharmaceutical composition, the therapeutically effective amount is 1-200 mg as the free base of the compound of Formula 1.

[0486] The present application also provides the use of each of the above salt forms and the above pharmaceutical composition in the preparation of a PARP inhibitor.

[0487] Preferably, in the above use, the PARP inhibitor is a PARP1 inhibitor.

[0488] The present application also provides the use of each of the above salt forms and the above pharmaceutical composition in the preparation of a medicament for treating and / or preventing a PARP-mediated related disease.

[0489] Preferably, in the above use, the PARP-mediated related disease is a tumor.

[0490] More preferably, in the above use, the tumor is breast cancer, ovarian cancer, primary peritoneal cancer, pancreatic cancer, prostate cancer, hematological cancer, gastrointestinal cancer, glioblastoma or lung cancer.

[0491] Preferably, in the above use, the therapeutically effective amount of the main drug of the medicament is 1-600 mg as the free base of the compound of Formula 1.

[0492] Preferably, in the above use, the therapeutically effective amount of the main drug of the medicament is 1-400 mg as the free base of the compound of Formula 1.

[0493] More preferably, in the above use, the therapeutically effective amount of the main drug of the medicament is 1-200 mg as the free base of the compound of Formula 1.

[0494] An "effective amount" or "therapeutically effective amount" as described herein refers to a sufficient amount of a crystalline form disclosed herein being administered, which will relieve to some extent one or more of the symptoms of the disease or condition being treated. In some embodiments, the result is reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an "effective amount" for therapeutic uses is the amount of a composition comprising a crystalline form disclosed herein that is needed to provide a clinically significant decrease in disease symptoms. Examples of a therapeutically effective amount, calculated as the free base, include but are not limited to 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-250 mg, 1-200 mg, 1-150 mg, 1-125 mg, 1-100 mg, 1-80 mg, 1-60 mg, 1-50 mg, 1-40 mg, 1-25 mg, 1-20 mg, 2-500 mg, 2-400 mg, 2-300 mg, 2-200 mg, 2-150 mg, 2-125 mg, 2-100 mg, 2-90 mg, 2-80 mg, 2-70 mg, 2-60 mg, 2-50 mg, 2-40 mg, 2-30 mg, 2-20 mg, 5-300 mg, 5-250 mg, 5-200 mg, 5-150 mg, 5-125 mg, 5-100 mg, 5-90 mg, 5-70 mg, 5-80 mg, 5-60 mg, 5-50 mg, 5-40 mg, 5-30 mg, 5-25 mg, 5-20 mg, 10-600 mg, 10-500 mg, 10-450 mg, 10-400 mg, 10-300 mg, 10-250 mg, 10-200 mg, 10-150 mg, 10-125 mg, 10-100 mg, 10-90 mg, 10-80 mg, 10-70 mg, 10-60 mg, 10-50 mg, 10-40 mg, 10-30 mg, 10-20 mg, 20-600 mg, 20-500 mg, 20-400 mg, 20-350 mg, 20-300 mg, 20-250 mg, 20-200 mg, 20-150 mg, 20-125 mg, 20-100 mg, 20-90 mg, 20-80 mg, 20-70 mg, 20-60 mg, 20-50 mg, 20-40 mg, 20-30 mg.

[0495] In some embodiments, the pharmaceutical compositions or formulations of the present application contain a therapeutically effective amount of a crystalline form of the present application as described above.

[0496] The present application relates to a pharmaceutical composition or a pharmaceutical preparation comprising a therapeutically effective amount of the crystalline form according to the present application and a carrier and / or excipient. The pharmaceutical composition can be in the form of a unit preparation (the amount of the main drug in the unit preparation is also referred to as "the preparation specification"). In some embodiments, the pharmaceutical composition comprises, but is not limited to, 1 mg, 1.25 mg, 2.5 mg, 5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg of the crystalline form according to the present application in the form of a free base.

[0497] The present application relates to a kit which can comprise the crystalline form in a single dose or multiple doses, the kit comprising the crystalline form according to the present application, the amount of the crystalline form according to the present application being the same as described above for the pharmaceutical composition. The amount of the crystalline form according to the present application in the present application is in each case converted to the form of a free base.

[0498] "dosage form" refers to the weight of the drug substance present in each unit of the dosage form. The crystalline forms described herein are present in about 5% to about 100% by weight of the drug substance; in certain embodiments, about 10% to about 100% by weight of the drug substance; in certain embodiments, about 15% to about 100% by weight of the drug substance; in certain embodiments, about 20% to about 100% by weight of the drug substance; in certain embodiments, about 25% to about 100% by weight of the drug substance; in certain embodiments, about 30% to about 100% by weight of the drug substance; in certain embodiments, about 35% to about 100% by weight of the drug substance; in certain embodiments, about 40% to about 100% by weight of the drug substance; in certain embodiments, about 45% to about 100% by weight of the drug substance; in certain embodiments, about 50% to about 100% by weight of the drug substance; in certain embodiments, about 55% to about 100% by weight of the drug substance; in certain embodiments, about 60% to about 100% by weight of the drug substance; in certain embodiments, about 65% to about 100% by weight of the drug substance; in certain embodiments, about 70% to about 100% by weight of the drug substance; in certain embodiments, about 75% to about 100% by weight of the drug substance; in certain embodiments, about 80% to about 100% by weight of the drug substance; in certain embodiments, about 85% to about 100% by weight of the drug substance; in certain embodiments, about 90% to about 100% by weight of the drug substance; in certain embodiments, about 95% to about 100% by weight of the drug substance; in certain embodiments, about 98% to about 100% by weight of the drug substance; in certain embodiments, about 99% to about 100% by weight of the drug substance; in certain embodiments, substantially all of the drug substance is substantially pure crystalline, i.e., about 100% by weight of the drug substance.

[0499] The good solvent and the poor solvent described herein are relative terms. In a pair of solvents, the one with higher solubility is the good solvent, and the one with lower solubility is the poor solvent. The solvent used in the above preparation method can be a single solvent, or a combination of two or more solvents, unless otherwise specified.

[0500] The X-ray powder diffraction or DSC pattern, TGA pattern disclosed herein, and those substantially identical thereto, are also within the scope of the present application.

[0501] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0502] "IC 50 "IC50" refers to the concentration of a compound that results in a 50% inhibition of the maximum response.

[0503] The crystal form structures of the present application can be analyzed using a variety of analytical techniques known to one of ordinary skill in the art, including but not limited to, X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and / or Thermogravimelric Analysis (TGA), also known as Thermogravimetry (TG).

[0504] The "2Θ or 2Θ angle" as used herein refers to the peak position in degrees (°) set in an X-ray diffraction experiment and is typically the unit of the abscissa in a diffraction pattern. If a reflection is diffracted when the incident beam forms an angle of Θ with a certain lattice plane, the experimental setup requires that the reflected beam is recorded in terms of a 2Θ angle. It should be understood that the specific 2Θ values mentioned herein for a particular crystal form are intended to represent the 2Θ values (in degrees) measured using the X-ray diffraction experimental conditions described herein, with an error range of ± 0.3, ± 0.2, or ± 0.1.

[0505] It is understood that the numerical values described and claimed herein are approximations. Variations in the numerical values within the stated ranges are permitted due to the nature of the devices, the error in the devices, the purity of the crystals, the size of the crystals, the size of the sample, and other factors.

[0506] It is understood that the crystal forms of the present application are not limited to having exactly the same characteristic patterns described in the figures disclosed herein, such as XRD, DSC, TGA, and any crystal form having substantially the same or essentially the same characteristic patterns as those described in the figures fall within the scope of the present application.

[0507] It is understood that the height of the melting peak of a DSC curve depends on many factors related to sample preparation and instrument geometry, as is well known in the art of differential scanning calorimetry (DSC), while the position of the peak is relatively insensitive to experimental details. Thus, in some embodiments, the crystalline compounds of the present application have a DSC pattern with a characteristic peak position having substantially the same properties as the DSC patterns provided in the figures herein, with a measurement error tolerance of ± 5 °C, and generally within ± 3 °C.

[0508] "Carriers" refer to systems that do not cause significant irritation to an organism, do not eliminate the biological activity and characteristics of the given compound, and can change the way the drug enters the human body and its distribution in the body, control the release rate of the drug, and deliver the drug to the target organ, non-limiting examples of which include microcapsules and microspheres, nanoparticles, liposomes, and the like.

[0509] "Excipient" refers to a substance, not itself a therapeutic agent, used as a diluent, adjuvant, binder, and / or vehicle, added to a pharmaceutical composition to improve its handling or storage properties or to allow or facilitate the formation of a compound or pharmaceutical composition into a unit dosage form for administration. As known to those skilled in the art, pharmaceutical excipients can serve various functions and can be described as wetting agents, buffering agents, suspending agents, lubricating agents, emulsifiers, disintegrants, absorbents, preservatives, surfactants, colorants, flavorants, and sweeteners. Examples of pharmaceutical excipients include, but are not limited to: (1) sugars, such as lactose, dextrose, and sucrose; (2) starches, such as corn starch and potato starch; (3) celluloses and their derivatives, such as sodium methylcellulose, ethylcellulose, cellulose acetate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, and crosscarmellose (e.g., crosscarmellose sodium); (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, soybean oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laureate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) pH buffered solutions; (21) polyesters, polycarbonates, and / or polyanhydrides; (22) other non-toxic compatible substances used in pharmaceutical formulations.

[0510] Advantages of the present application:

[0511] The present application provides a fumarate salt, a tartrate salt, various sulfonate salts, and a saccharin co-crystal of compound 1, and studies the crystal forms of each salt type, thereby providing support for dosage form research, and more effectively preventing / treating PARP-related diseases and meeting different clinical medication needs. BRIEF DESCRIPTION OF DRAWINGS

[0512] FIG. 1 is an X-ray powder diffraction pattern of the fumarate salt crystal form I of compound 1.

[0513] FIG. 2 is a differential scanning calorimetry analysis profile of the fumarate salt crystal form I of compound 1.

[0514] FIG. 3 is a thermogravimetric analysis profile of the fumarate salt crystal form I of compound 1.

[0515] FIG. 4 is an X-ray powder diffraction pattern of the fumarate salt crystal form II of compound 1.

[0516] FIG. 5 is a differential scanning calorimetry profile of Form II fumarate salt of Compound 1.

[0517] FIG. 6 is a thermogravimetric analysis profile of Form II fumarate salt of Compound 1.

[0518] FIG. 7 is an X-ray powder diffraction pattern of Form III fumarate salt of Compound 1.

[0519] FIG. 8 is a differential scanning calorimetry profile of Form III fumarate salt of Compound 1.

[0520] FIG. 9 is a thermogravimetric analysis profile of Form III fumarate salt of Compound 1.

[0521] FIG. 10 is an X-ray powder diffraction pattern of Form IV fumarate salt of Compound 1.

[0522] FIG. 11 is a differential scanning calorimetry profile of Form IV fumarate salt of Compound 1.

[0523] FIG. 12 is a thermogravimetric analysis profile of Form IV fumarate salt of Compound 1.

[0524] FIG. 13 is an X-ray powder diffraction pattern of Form V fumarate salt of Compound 1.

[0525] FIG. 14 is a differential scanning calorimetry profile of Form V fumarate salt of Compound 1.

[0526] FIG. 15 is a thermogravimetric analysis profile of Form V fumarate salt of Compound 1.

[0527] FIG. 16 is an X-ray powder diffraction pattern of Form VI fumarate salt of Compound 1.

[0528] FIG. 17 is an X-ray powder diffraction pattern of Form VII fumarate salt of Compound 1.

[0529] FIG. 18 is a differential scanning calorimetry profile of Form VII fumarate salt of Compound 1.

[0530] FIG. 19 is a thermogravimetric analysis profile of Form VII fumarate salt of Compound 1.

[0531] FIG. 20 is an X-ray powder diffraction pattern of Form VIII fumarate salt of Compound 1.

[0532] FIG. 21 is an X-ray powder diffraction pattern of Form IX fumarate salt of Compound 1.

[0533] FIG. 22 is a differential scanning calorimetry profile and a thermogravimetric analysis profile of Form IX fumarate salt of Compound 1.

[0534] FIG. 23 is an X-ray powder diffraction pattern of Form X of the fumarate salt of Compound 1.

[0535] FIG. 24 is a differential scanning calorimetry profile and a thermogravimetric analysis profile of Form X of the fumarate salt of Compound 1.

[0536] FIG. 25 is an X-ray powder diffraction pattern of Form I of the tartrate salt of Compound 1.

[0537] FIG. 26 is a differential scanning calorimetry profile of Form I of the tartrate salt of Compound 1.

[0538] FIG. 27 is a thermogravimetric analysis profile of Form I of the tartrate salt of Compound 1.

[0539] FIG. 28 is an X-ray powder diffraction pattern of Form II of the tartrate salt of Compound 1.

[0540] FIG. 29 is a differential scanning calorimetry profile of Form II of the tartrate salt of Compound 1.

[0541] FIG. 30 is a thermogravimetric analysis profile of Form II of the tartrate salt of Compound 1.

[0542] FIG. 31 is an X-ray powder diffraction pattern of Form III of the tartrate salt of Compound 1.

[0543] FIG. 32 is a differential scanning calorimetry profile of Form III of the tartrate salt of Compound 1.

[0544] FIG. 33 is a thermogravimetric analysis profile of Form III of the tartrate salt of Compound 1.

[0545] FIG. 34 is an X-ray powder diffraction pattern of Form IV of the tartrate salt of Compound 1.

[0546] FIG. 35 is a differential scanning calorimetry profile of Form IV of the tartrate salt of Compound 1.

[0547] FIG. 36 is a thermogravimetric analysis profile of Form IV of the tartrate salt of Compound 1.

[0548] FIG. 37 is an X-ray powder diffraction pattern of Form V of the tartrate salt of Compound 1.

[0549] FIG. 38 is a differential scanning calorimetry profile of Form V of the tartrate salt of Compound 1.

[0550] FIG. 39 is a thermogravimetric analysis profile of Form V of the tartrate salt of Compound 1.

[0551] FIG. 40 is an X-ray powder diffraction pattern of Form VI of the tartrate salt of Compound 1.

[0552] FIG. 41 is a differential scanning calorimetry profile of the tartrate salt Form VI of compound 1.

[0553] FIG. 42 is a thermogravimetric analysis profile of the tartrate salt Form VI of compound 1.

[0554] FIG. 43 is an X-ray powder diffraction pattern of the 1,5-napthalene disulfonic acid salt Form I of compound 1.

[0555] FIG. 44 is an X-ray powder diffraction pattern of the 2-napthalenesulfonic acid salt Form I of compound 1.

[0556] FIG. 45 is an X-ray powder diffraction pattern of the 2-napthalenesulfonic acid salt Form II of compound 1.

[0557] FIG. 46 is an X-ray powder diffraction pattern of the L-malate salt Form I of compound 1.

[0558] FIG. 47 is an X-ray powder diffraction pattern of the L-camphorsulfonic acid salt Form I of compound 1.

[0559] FIG. 48 is an X-ray powder diffraction pattern of the L-camphorsulfonic acid salt Form II of compound 1.

[0560] FIG. 49 is an X-ray powder diffraction pattern of the benzenesulfonic acid salt Form I of compound 1.

[0561] FIG. 50 is an X-ray powder diffraction pattern of the benzenesulfonic acid salt Form II of compound 1.

[0562] FIG. 51 is an X-ray powder diffraction pattern of the malonic acid salt Form I of compound 1.

[0563] FIG. 52 is an X-ray powder diffraction pattern of the oxalate salt Form I of compound 1.

[0564] FIG. 53 is an X-ray powder diffraction pattern of the oxalate salt Form II of compound 1.

[0565] FIG. 54 is an X-ray powder diffraction pattern of the p-toluenesulfonic acid salt Form I of compound 1.

[0566] FIG. 55 is an X-ray powder diffraction pattern of the p-toluenesulfonic acid salt Form II of compound 1.

[0567] FIG. 56 is an X-ray powder diffraction pattern of the methanesulfonic acid salt Form I of compound 1.

[0568] FIG. 57 is an X-ray powder diffraction pattern of the methanesulfonic acid salt Form II of compound 1.

[0569] FIG. 58 is an X-ray powder diffraction pattern of the methanesulfonic acid salt Form III of compound 1.

[0570] Figure 59 is an X-ray powder diffraction pattern of the methanesulfonic acid salt Form IV of Compound 1.

[0571] Figure 60 is an X-ray powder diffraction pattern of the sulfate salt Form I of Compound 1.

[0572] Figure 61 is an X-ray powder diffraction pattern of the gentisic acid salt Form I of Compound 1.

[0573] Figure 62 is an X-ray powder diffraction pattern of the maleic acid salt Form I of Compound 1.

[0574] Figure 63 is an X-ray powder diffraction pattern of the maleic acid salt Form II of Compound 1.

[0575] Figure 64 is an X-ray powder diffraction pattern of the citric acid salt Form I of Compound 1.

[0576] Figure 65 is an X-ray powder diffraction pattern of the hydrobromic acid salt Form I of Compound 1.

[0577] Figure 66 is an X-ray powder diffraction pattern of the hydrochloric acid salt Form I of Compound 1.

[0578] Figure 67 is an X-ray powder diffraction pattern of the ethanesulfonic acid salt Form I of Compound 1.

[0579] Figure 68 is an X-ray powder diffraction pattern of the ethanesulfonic acid salt Form II of Compound 1.

[0580] Figure 69 is an X-ray powder diffraction pattern of the saccharin co-crystal Form I of Compound 1.

[0581] Figure 70 is a plot of the effect of Compound 1 fumarate salt Form I on tumor volume in human breast cancer MDA-MB-436 tumor-bearing mice.

[0582] Figure 71 is a plot of the effect of Compound 1 fumarate salt Form I on body weight in human breast cancer MDA-MB-436 tumor-bearing mice. DETAILED DESCRIPTION

[0583] The technical solutions of the present application are described in detail below in combination with the drawings and examples, but the protection scope of the present application includes but is not limited to this.

[0584] The structure of the compound is determined by nuclear magnetic resonance (NMR) or / and mass spectrometry (MS). The NMR shift (δ) is given in units of 10 -6 (ppm). The determination of NMR is carried out by using a nuclear magnetic instrument (Bruker Avance II 400 and JMTC-400 / 54 / JJ / YH), the determination solvent is deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), deuterated methanol (CD3OD), and the internal standard is tetramethylsilane (TMS).

[0585] MS was measured by Agilent 6120B (ESI) and Agilent 6120B (APCI). HPLC was measured by Waters ALLIANCE E2695 liquid chromatograph and C18, 4.6x250mm, 5μm chromatographic column.

[0586] XRD was measured by X-ray powder diffractometer Rigaku SmartLab SE. According to Appendix IX of the People's Republic of China (2010 edition volume 2) F X-ray powder diffraction method test.

[0587] TGA and DSC graphs were collected on NETZSCH STA 449F3 differential scanning calorimeter, and the test parameters are as follows:

[0588] Detection conditions: nitrogen, 50 mL / min; scanning program: 30-400℃, temperature rise rate: 10℃ / min; sample mass for detection: about 3mg (alumina sample pan); detection basis: JY / T 014-1996 General thermal analysis method.

[0589] The known starting materials of the present application can be synthesized by or according to the methods known in the art, or can be purchased from Titan Kogyo, Anjie Chemical, Jiangsu Aikang, Lianyan Reagent, Bid Pharmaceutical, Chengdu Kelong Chemical, Shaoyuan Chemical Technology, and Bailingwei Technology.

[0590] In the examples, the solution refers to an aqueous solution unless otherwise specified.

[0591] In the examples, room temperature refers to 20-30℃ unless otherwise specified.

[0592] The following will detail the implementation process and beneficial effects of the present application through specific examples, which are intended to help the reader better understand the essence and characteristics of the present application, and do not limit the scope of the present application.

[0593] DMAC: N,N-dimethylacetamide; NMP: N-methylpyrrolidone; MTBE: methyl tert-butyl ether; DCM: dichloromethane.

[0594] Example 1: Preparation of compound 1

[0595] First Step: In a 7ml dioxane, 3ml anhydrous ethanol and 4ml water mixed solvent, compound int-la (1g, 4.6mmol), int-lb (1.7g, 5.5mmol), Pd(dppf)Cl2(0.3g, 0.46mmol) and potassium carbonate (1.6g, 11.5mmol) were added, then replaced with nitrogen three times, and reacted at 90°C for 2h under nitrogen protection. After TLC detection of the complete reaction, the reaction was reduced to room temperature, 30ml dichloromethane and 20ml water were added, and the layers were separated in a separatory funnel. The aqueous phase was extracted twice with dichloromethane, and the combined organic phase was washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary evaporated. The obtained crude product was purified by column chromatography to obtain compound int-lc (1g, white solid).

[0596] Second Step: In a 100ml reaction bottle, int-lc (1g, 3mmol), aqueous methylamine (5g, 161.3mmol) and anhydrous methanol (20ml) were added, and stirred at room temperature overnight. After TLC monitoring of the complete reaction, the reaction was concentrated under reduced pressure to obtain compound int-l d (0.8g, white solid).

[0597] Third Step: Compound int-l d (0.5g, 1.5mmol) was added to 10ml anhydrous methanol, followed by the addition of 10ml 4mol / L hydrochloric acid dioxane solution, and stirred at room temperature for 0.5-1h. After TLC monitoring of the complete reaction, the reaction was concentrated under reduced pressure to obtain compound int-l (0.5g, white solid).

[0598] Fourth Step: 60% sodium hydride (16g, 406mmol) was weighed, added to DME (200mL), replaced with nitrogen three times, cooled to 0°C, and compound la (76g, 338mmol) was added dropwise. The reaction was allowed to warm to room temperature for 2 hours, deuterated bromoethane (50g, 439mmol) was added dropwise, and the reaction was allowed to warm to 60°C for 3 hours. After HPLC monitoring of the reaction progress, the reaction was slowly poured into ice water to quench, extracted with ethyl acetate three times, and the combined organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated. The obtained crude compound lc (83g, colorless liquid).

[0599] Fifth step: In a reaction flask, add 60% sodium hydride (13 g, 322 mmol), add 200 ml of tetrahydrofuran, then replace nitrogen three times. Cool to 0°C, slowly drop compound 1c (83 g, 322 mmol), stir the reaction at 0°C for 10 minutes, warm to room temperature and stir for 10 minutes, then warm to 40°C and stir for 5 minutes, then cool the reaction to -78°C. Slowly drop the solution of compound 1d (48 g, 215 mmol) dissolved in 200 ml of tetrahydrofuran, and stir the reaction at -78°C for 1 hour. After monitoring the reaction to completion by TLC, slowly add the reaction solution to ice saturated aqueous ammonium chloride solution to quench, extract with ethyl acetate three times, combine the organic phase, dry with anhydrous sodium sulfate, filter, and rotary evaporate. The obtained crude product is purified by column chromatography to obtain compound 1e (41 g, yellow-green liquid). LC-MS: ESI [M+H] + = 328.4.

[0600] Sixth step: Add compound 1e (1.0 g, 3.0 mmol) to 10 ml of anhydrous ethanol, then add Pd / C (0.1 g, 10%), then replace hydrogen three times, and stir the reaction at room temperature overnight. After monitoring the reaction to completion by LC-MS, filter the reaction solution, rinse the filter residue with a large amount of ethanol, and combine the filtrate and rotary evaporate to concentrate. Add 4 mol / L hydrochloric acid in 1,4-dioxane solution (12 ml), stir at room temperature for 30 minutes, add ether to precipitate a large amount of solid, filter, and dry to obtain compound 1f (0.51 g, white solid); LC-MS: ESI [M+H] + = 254.3.

[0601] Seventh step: In a 50 ml reaction flask, add compound 1f (0.51 g, 2.0 mmol) and 15 mL of 1,4-dioxane, then add DDQ (0.50 g, 2.2 mmol), and reflux the reaction overnight. After monitoring the reaction to completion by LC-MS, rotary evaporate the reaction solution, add saturated aqueous sodium bicarbonate solution and stir for 1 hour, filter, rinse the filter residue with water, then wash with a small amount of ether, and dry to obtain compound 1g (0.3 g, yellow solid). LC-MS: ESI [M+H] + = 252.3.

[0602] Eighth step: In a reaction flask, add compound 1g (0.3 g, 1.2 mmol) and 15 ml of tetrahydrofuran, cool to 0°C, then add 2.5 mol / L lithium aluminum hydride in tetrahydrofuran solution (1.44 ml, 3.6 mmol), and react at 0°C for 2 hours. After monitoring the reaction to completion by TLC, quench the reaction by adding 1 ml of water, dry with a large amount of anhydrous sodium sulfate, filter, rinse the filter residue with a large amount of dichloromethane, combine the filtrate and rotary evaporate to concentrate, and dry to obtain compound 1h (0.2 g, yellow solid). LC-MS: ESI [M+H]+ = 210.3.

[0603] Step 9: In a 25 ml reaction flask, compound 1h (0.2 g, 0.96 mmol) was added into 10 ml dichloromethane and 0.1 ml N,N-dimethylformamide, and cooled to 0 °C, dropwise added dichloro sulfoxide (0.35 g, 2.9 mmol), and reacted at 0 °C for 1 hour. After TLC monitoring reaction was completed, the reaction solution was concentrated by rotary evaporation, and the obtained crude product was purified by column chromatography to obtain compound 1i (0.2 g, gray solid). LC-MS: ESI [M+H] + = 228.7.

[0604] Step 10: Compound 1i (0.2 g, 0.88 mmol), int-1 (0.25 g, 0.88 mmol), N,N- diisopropylethylamine (0.45 g, 3.52 mmol) and potassium iodide (15 mg, 0.09 mmol) were added into 10 ml anhydrous acetonitrile, and stirred at 85 °C for 2 hours. After TLC monitoring reaction was completed, the reaction solution was concentrated under reduced pressure, and the obtained crude product was purified by column chromatography to obtain compound 1 (160 mg, white solid). LC-MS: ESI [M+H] + = 409.5; 1H NMR (400 MHz, CDCl3) δ 10.97 (s, 1H), 8.57 (d, J = 2.0 Hz, 1H), 8.54 (d, J = 1.7 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.96 (d, J = 4.9 Hz, 1H), 7.86 (s, 1H), 7.80 (dd, J = 8.2, 2.3 Hz, 1H), 7.66 (s, 1H), 6.23 (s, 1H), 3.78 (s, 2H), 3.27 (d, J = 3.1 Hz, 2H), 3.04 (d, J = 5.1 Hz, 3H), 2.79 (t, J = 5.6 Hz, 2H), 2.60 (d, J = 1.4 Hz, 2H).

[0605] Example 2: Preparation of fumarate salt Form I

[0606] About 50 mg of free base sample was weighed in a bottle, added into 1 mL of acetonitrile at room temperature, and then 1.1 equivalent of fumaric acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to obtain a solid.

[0607] According to the displacement of the peak positions in the spectrum, for example 1HNMR (400 MHz, DMSO) δ 8.69 (d, 2H), 8.41 (s, 1H), 7.98 (d, 2H), 7.75 (s, 1H), 7.64 (s, 1H), 6.62 (s, 2H), 6.42 (s, 1H), 3.73 (s, 2H), 3.16 (s, 2H), 2.81 (s, 3H), 2.71 (d, 2H) showed salt ratio 1:1.

[0608] More specifically, by 1 HNMR (400 MHz, DMSO) peak displacement analysis, compound 1 chemical shift 6.42 (s, 1H) is the =CH peak of No. 24, and the peak of 6.62 (s, 2H) is the two =CH peaks of fumaric acid, with a ratio of 1:2, so the ratio of compound 1 to fumaric acid can be analyzed to be 1:1.

[0609] The X-ray powder diffraction pattern (XRD), differential scanning calorimetric analysis curve, and thermogravimetric analysis pattern of the fumarate salt crystal form I of compound 1 are shown in Figures 1-3.

[0610] Example 3: Preparation of fumarate salt crystal form II

[0611] About 50 mg of fumarate salt crystal form I sample was weighed into a bottle, 1 mL of methanol was added at room temperature, and then stirred at room temperature for about 3 days. The solid was obtained by filtration and drying.

[0612] The X-ray powder diffraction pattern (XRD), differential scanning calorimetric analysis curve, and thermogravimetric analysis pattern of the fumarate salt crystal form II of compound 1 are shown in Figures 4-6.

[0613] Example 4: Preparation of fumarate salt crystal form III

[0614] About 50 mg of fumarate salt crystal form I sample was weighed into a bottle, 1 mL of dimethyl sulfoxide was added at room temperature, and then stirred at room temperature for about 3 days. The solid was obtained by filtration and drying.

[0615] The X-ray powder diffraction pattern (XRD), differential scanning calorimetric analysis curve, and thermogravimetric analysis pattern of the fumarate salt crystal form III of compound 1 are shown in Figures 7-9.

[0616] Example 5: Preparation of fumarate salt crystal form IV

[0617] About 50 mg of fumarate salt crystal form I sample was weighed into a bottle, 1 mL of water was added at room temperature, and then stirred at room temperature for about 3 days. The solid was obtained by filtration and drying.

[0618] The X-ray powder diffraction pattern (XRD), differential scanning calorimetric analysis curve, and thermogravimetric analysis pattern of the fumarate salt crystal form IV of compound 1 are shown in Figures 10-12.

[0619] Example 6: Preparation of Form V fumarate salt

[0620] About 50 mg of Form I fumarate salt sample was weighed into a bottle, 1 mL of water was added at room temperature, and then stirred at room temperature for about 7 days. The solid was obtained by filtration and drying.

[0621] The X-ray powder diffraction pattern (XRD) of Form V fumarate salt of Compound 1 is shown in FIGS. 13-15.

[0622] Example 7: Preparation of Form VI fumarate salt

[0623] About 50 mg of Form I fumarate salt sample was weighed into a bottle, 1 mL of tetrahydrofuran was added at room temperature, and then stirred at 50 °C for about 7 days. The solid was obtained by filtration and drying.

[0624] The X-ray powder diffraction pattern (XRD) of Form VI fumarate salt of Compound 1 is shown in FIG. 16.

[0625] Example 8: Preparation of Form VII fumarate salt

[0626] About 20 mg of Form I fumarate salt sample was weighed into a bottle, 4 mL of water was added at room temperature, and then stirred at 4 °C after rapid cooling (using a 4 °C cold bath). The solid was obtained by filtration and drying.

[0627] The X-ray powder diffraction pattern (XRD) of Form VII fumarate salt of Compound 1 is shown in FIGS. 17-19.

[0628] Example 9: Preparation of Form VIII fumarate salt

[0629] About 20 mg of Form I fumarate salt sample was weighed into a bottle, 4 mL of ethanol was added at room temperature, and then stirred at 4 °C after slow cooling (gradient cooling). The solid was obtained by filtration and drying.

[0630] The X-ray powder diffraction pattern (XRD) of Form VIII fumarate salt of Compound 1 is shown in FIG. 20.

[0631] Example 10: Preparation of Form IX fumarate salt

[0632] About 50 mg of free base sample was weighed into a bottle, 1.5 mL of ethyl acetate or 1 mL of tetrahydrofuran was added at room temperature, and then 1.1 equivalent of fumaric acid was added. The solid was obtained by filtration and drying after stirring at room temperature for about 18 hours.

[0633] The X-ray powder diffraction pattern (XRD) of Form IX fumarate salt of Compound 1 is shown in FIGS. 21-22.

[0634] Example 11: Preparation of Fumarate salt Form X

[0635] About 50 mg of the free base sample was weighed into a bottle, 1 mL of a mixed solution of acetone and water (V 丙酮 水 = 19 / 1) was added at room temperature, and 1.1 equivalent of fumaric acid was added, followed by stirring at room temperature for about 18 hours. The solid was filtered and dried to obtain a solid.

[0636] The X-ray powder diffraction pattern (XRD), differential scanning calorimetry curve, and thermogravimetric analysis pattern of the fumarate salt Form X of Compound 1 are shown in Figs. 23-24.

[0637] Example 12: Preparation of L-tartrate salt Form I

[0638] About 50 mg of the free base sample was weighed into a bottle, 1 mL of ethanol was added at room temperature, and 1.1 equivalent of L-tartaric acid was added, followed by stirring at room temperature for about 18 hours. The solid was filtered and dried to obtain a solid.

[0639] According to the peak shift of the part of the spectrum that is focused on, for example 1 HNMR (400 MHz, DMSO) δ 8.70 (d, 2H), 8.42 (s, 1H), 7.98 (d, 2H), 7.76 (s, 1H), 7.64 (s, 1H), 6.42 (s, 1H), 4.29 (s, 2H), 3.75 (s, 2H), 3.18 (s, 2H), 2.81 (s, 3H), 2.73 (d, 2H) shows that the salt ratio is 1:1.

[0640] More specifically, by 1 HNMR (400 MHz, DMSO) δ 8.70 (d, 2H), 8.42 (s, 1H), 7.98 (d, 2H), 7.76 (s, 1H), 7.64 (s, 1H), 6.42 (s, 1H), 4.29 (s, 2H), 3.75 (s, 2H), 3.18 (s, 2H), 2.81 (s, 3H), 2.73 (d, 2H) shows that the salt ratio is 1:1.

[0641] The X-ray powder diffraction pattern (XRD), differential scanning calorimetry curve, and thermogravimetric analysis pattern of the L-tartrate salt Form I of Compound 1 are shown in Figs. 25-27.

[0642] Example 13: Preparation of L-tartrate salt Form II

[0643] About 100 mg of the L-tartrate salt Form I sample was weighed into a bottle, 4 mL of methanol was added at room temperature, and stirring was performed at room temperature for about 3 days. The solid was filtered and dried to obtain a solid.

[0644] ​The X-ray powder diffraction pattern (XRD), differential scanning calorimetry profile, and thermogravimetric profile of L-tartrate Form II of Compound 1 are shown in Figures 28-30.

[0645] Example 14: Preparation of L-tartrate Form III

[0646] About 100 mg of L-tartrate Form I sample was weighed into a vial, 1 mL of water was added at room temperature, and the mixture was stirred at room temperature for about 7 days. The solid was filtered and dried.

[0647] The X-ray powder diffraction pattern (XRD), differential scanning calorimetry profile, and thermogravimetric profile of L-tartrate Form III of Compound 1 are shown in Figures 31-33.

[0648] Example 15: Preparation of L-tartrate Form IV

[0649] About 100 mg of L-tartrate Form I sample was weighed into a vial, 1 mL of water was added at room temperature, and the mixture was stirred at room temperature for about 3 days. The solid was filtered and dried.

[0650] The X-ray powder diffraction pattern (XRD), differential scanning calorimetry profile, and thermogravimetric profile of L-tartrate Form IV of Compound 1 are shown in Figures 34-36.

[0651] Example 16: Preparation of L-tartrate Form V

[0652] About 100 mg of L-tartrate Form I sample was weighed into a vial, 1 mL of different mixed solvents such as methanol / water (v / v = 1 / 1) or tetrahydrofuran / water (v / v = 1 / 1) or acetonitrile / water (v / v = 1 / 1) was added at room temperature, and the mixture was stirred at room temperature for about 3 days or was slurried at 50 °C for about 3 days. The solid was filtered and dried.

[0653] The X-ray powder diffraction pattern (XRD), differential scanning calorimetry profile, and thermogravimetric profile of L-tartrate Form V of Compound 1 are shown in Figures 37-39.

[0654] Example 17: Preparation of L-tartrate Form VI

[0655] About 100 mg of L-tartrate Form I sample was weighed into a vial, 2 mL of different solvents such as methyl tert-butyl ether or ethyl acetate or isopropyl acetate or tetrahydrofuran or 2-methyltetrahydrofuran or acetonitrile or 2-butanone or toluene or n-heptane was added at room temperature, and the mixture was stirred at room temperature for about 3 days or was slurried at room temperature or at 50 °C or at 80 °C for about 3 days or for about 7 days. The solid was filtered and dried.

[0656] The X-ray powder diffraction pattern (XRD) of the L-tartaric acid salt Form VI of Compound 1 is shown in FIGS. 40-42.

[0657] Example 18: Preparation of 1,5-naphthalene disulfonate salt Form I

[0658] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetone / water (v / v = 19 / 1) solution was added at room temperature, and then 1.1 equivalent of 1,5-naphthalene disulfonic acid was added, followed by stirring at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0659] The X-ray powder diffraction pattern (XRD) of the 1,5-naphthalene disulfonate salt Form I of Compound 1 is shown in FIG. 43.

[0660] Example 19: Preparation of 2-naphthalenesulfonic acid salt Form I

[0661] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethyl acetate or dimethyl sulfoxide was added at room temperature, and then 1.1 equivalent of 2-naphthalenesulfonic acid was added, followed by stirring at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0662] The X-ray powder diffraction pattern (XRD) of the 2-naphthalenesulfonic acid salt Form I of Compound 1 is shown in FIG. 44.

[0663] Example 20: Preparation of 2-naphthalenesulfonic acid salt Form II

[0664] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetone / water (v / v = 19 / 1) solution was added at room temperature, and then 1.1 equivalent of 2-naphthalenesulfonic acid was added, followed by stirring at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0665] The X-ray powder diffraction pattern (XRD) of the 2-naphthalenesulfonic acid salt Form II of Compound 1 is shown in FIG. 45.

[0666] Example 21: Preparation of L-malic acid salt Form I

[0667] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol was added at room temperature, and then 1.1 equivalent of L-malic acid was added, followed by stirring at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0668] The X-ray powder diffraction pattern (XRD) of the L-malic acid salt Form I of Compound 1 is shown in FIG. 46.

[0669] Example 22: Preparation of L-camphorsulfonic acid salt Form I

[0670] About 50 mg of free base sample was weighed into a vial, 1 mL of ethyl acetate was added at room temperature, 1.1 equivalent of L-camphorsulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0671] The X-ray powder diffraction pattern (XRD) of L-camphorsulfonic acid salt Form II of Compound 1 is shown in Figure 48.

[0672] Example 23: Preparation of L-camphorsulfonic acid salt Form II

[0673] About 50 mg of free base sample was weighed into a vial, 1 mL of acetone / water (v / v = 19 / 1) was added at room temperature, 1.1 equivalent of L-camphorsulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0674] The X-ray powder diffraction pattern (XRD) of L-camphorsulfonic acid salt Form II of Compound 1 is shown in Figure 48.

[0675] Example 24: Preparation of benzenesulfonic acid salt Form I

[0676] About 50 mg of free base sample was weighed into a vial, 1 mL of ethanol was added at room temperature, 1.1 equivalent of benzenesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0677] The X-ray powder diffraction pattern (XRD) of benzenesulfonic acid salt Form I of Compound 1 is shown in Figure 49.

[0678] Example 25: Preparation of benzenesulfonic acid salt Form II

[0679] About 50 mg of free base sample was weighed into a vial, 1 mL of tetrahydrofuran or dimethylsulfoxide or acetone / water (v / v = 19 / 1) was added at room temperature, 1.1 equivalent of benzenesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0680] The X-ray powder diffraction pattern (XRD) of benzenesulfonic acid salt Form II of Compound 1 is shown in Figure 50.

[0681] Example 26: Preparation of malonic acid salt Form I

[0682] About 50 mg of free base sample was weighed into a vial, 1 mL of acetonitrile or 1.5 mL of ethyl acetate was added at room temperature, 1.1 equivalent of malonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0683] The X-ray powder diffraction pattern (XRD) of malonic acid salt Form I of Compound 1 is shown in Figure 51.

[0684] Example 27: Preparation of oxalic acid salt Form I

[0685] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol was added at room temperature, 1.1 equivalent of oxalic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0686] The X-ray powder diffraction pattern (XRD) of oxalate salt Form I of Compound 1 is shown in Figure 52.

[0687] Example 28: Preparation of oxalate salt Form II

[0688] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetonitrile or acetone / water (v / v = 19 / 1) was added at room temperature, 1.1 equivalent of oxalic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0689] The X-ray powder diffraction pattern (XRD) of oxalate salt Form II of Compound 1 is shown in Figure 53.

[0690] Example 29: Preparation of p-toluenesulfonate salt Form I

[0691] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile or ethyl acetate or tetrahydrofuran or dimethyl sulfoxide was added at room temperature, 1.1 equivalent of p-toluenesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0692] The X-ray powder diffraction pattern (XRD) of p-toluenesulfonate salt Form I of Compound 1 is shown in Figure 54.

[0693] Example 30: Preparation of p-toluenesulfonate salt Form II

[0694] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetone / water (v / v = 19 / 1) was added at room temperature, 1.1 equivalent of p-toluenesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0695] The X-ray powder diffraction pattern (XRD) of p-toluenesulfonate salt Form II of Compound 1 is shown in Figure 55.

[0696] Example 31: Preparation of methanesulfonate salt Form I

[0697] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile was added at room temperature, 1.1 equivalent of methanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was obtained by filtration and drying.

[0698] The X-ray powder diffraction pattern (XRD) of methanesulfonate salt Form I of Compound 1 is shown in Figure 56.

[0699] Example 32: Preparation of mesylate salt Form II

[0700] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethyl acetate was added at room temperature, 1.1 equivalent of methanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0701] The X-ray powder diffraction pattern (XRD) of the mesylate salt Form II of Compound 1 is shown in FIG. 57.

[0702] Example 33: Preparation of mesylate salt Form III

[0703] About 50 mg of the free base sample was weighed into a vial, 1 mL of tetrahydrofuran was added at room temperature, 1.1 equivalent of methanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0704] The X-ray powder diffraction pattern (XRD) of the mesylate salt Form III of Compound 1 is shown in FIG. 58.

[0705] Example 34: Preparation of mesylate salt Form IV

[0706] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetone / water (v / v = 19 / 1) was added at room temperature, 1.1 equivalent of methanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0707] The X-ray powder diffraction pattern (XRD) of the mesylate salt Form IV of Compound 1 is shown in FIG. 59.

[0708] Example 35: Preparation of sulfate salt Form I

[0709] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol was added at room temperature, 1.1 equivalent of sulfuric acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0710] The X-ray powder diffraction pattern (XRD) of the sulfate salt Form I of Compound 1 is shown in FIG. 60.

[0711] Example 36: Preparation of gentisate salt Form I

[0712] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetonitrile or ethyl acetate was added at room temperature, 1.1 equivalent of gentisic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0713] The X-ray powder diffraction pattern (XRD) of the gentisate salt Form I of Compound 1 is shown in FIG. 61.

[0714] Example 37: Preparation of maleate salt Form I

[0715] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile or ethyl acetate or acetone / water (v / v = 19 / 1) was added at room temperature, then 1.1 equivalent of maleic acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to give a solid.

[0716] The X-ray powder diffraction (XRD) pattern of the maleate salt Form I of Compound 1 is shown in Figure 62.

[0717] Example 38: Preparation of maleate salt Form II

[0718] About 50 mg of the free base sample was weighed into a vial, 1 mL of tetrahydrofuran was added at room temperature, then 1.1 equivalent of maleic acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to give a solid.

[0719] The X-ray powder diffraction (XRD) pattern of the maleate salt Form II of Compound 1 is shown in Figure 63.

[0720] Example 39: Preparation of citrate salt Form I

[0721] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile or ethyl acetate or tetrahydrofuran or acetone / water (v / v = 19 / 1) was added at room temperature, then 1.1 equivalent of citric acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to give a solid.

[0722] The X-ray powder diffraction (XRD) pattern of the citrate salt Form I of Compound 1 is shown in Figure 64.

[0723] Example 40: Preparation of hydrobromide salt Form I

[0724] About 50 mg of the free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile or ethyl acetate or tetrahydrofuran or acetone / water (v / v = 19 / 1) or dimethyl sulfoxide was added at room temperature, then 1.1 equivalent of hydrobromic acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to give a solid.

[0725] The X-ray powder diffraction (XRD) pattern of the hydrobromide salt Form I of Compound 1 is shown in Figure 65.

[0726] Example 41: Preparation of hydrochloride salt Form I

[0727] About 50 mg of the free base sample was weighed into a vial, 1 mL of acetonitrile or ethyl acetate or tetrahydrofuran or acetone / water (v / v = 19 / 1) or dimethyl sulfoxide was added at room temperature, then 1.1 equivalent of hydrochloric acid was added, followed by stirring at room temperature for about 18 hours, and then filtration and drying to give a solid.

[0728] The X-ray powder diffraction pattern (XRD) of the hydrochloride salt Form I of Compound 1 is shown in Figure 66.

[0729] Example 42: Preparation of ethanesulfonic acid salt Form I

[0730] About 50 mg of free base sample was weighed into a vial, 1 mL of ethanol or acetonitrile or dimethylsulfoxide was added at room temperature, 1.1 equivalent of ethanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried. The solid was obtained.

[0731] The X-ray powder diffraction pattern (XRD) of the ethanesulfonic acid salt Form I of Compound 1 is shown in Figure 67.

[0732] Example 43: Preparation of ethanesulfonic acid salt Form II

[0733] About 50 mg of free base sample was weighed into a vial, 1 mL of ethyl acetate or tetrahydrofuran was added at room temperature, 1.1 equivalent of ethanesulfonic acid was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried. The solid was obtained.

[0734] The X-ray powder diffraction pattern (XRD) of the ethanesulfonic acid salt Form II of Compound 1 is shown in Figure 68.

[0735] Example 44: Preparation of saccharin co-crystal Form I

[0736] About 50 mg of free base sample was weighed into a vial, 1 mL of acetonitrile was added at room temperature, 1.1 equivalent of saccharin was added, and then stirred at room temperature for about 18 hours. The solid was filtered and dried.

[0737] The X-ray powder diffraction pattern (XRD) of the saccharin co-crystal Form I of Compound 1 is shown in Figure 69.

[0738] Example 45: Solubility data of pharmaceutically acceptable salts of Compound 1

[0739] L-tartaric acid salt (Form I), hydrobromide salt (Form I), and fumaric acid salt (Form I) of Compound 1 were tested for dynamic solubility in biological media (FaSSIF, FeSSIF, and FaSSGF) and water at 37 °C. About 30 mg of sample of each salt form was weighed into a vial, and then 3 mL of each of the three biological media and water were added to form a suspension. All suspensions were shaken at 200 rpm at 37 °C, and samples were taken at 0.5 h, 2 h, and 24 h. About 0.3 mL of the suspension was filtered each time, and the filtrate was tested by HPLC. In addition, the pH of the filtrate was tested at 24 h.

[0740] HPLC test conditions: detection instrument: Waters ALLIANCE E2695; column: C18, 4.6 x 250 mm, 5 μm; column temperature: 27 °C; mobile phase: A: 0.05% trifluoroacetic acid in water; B: acetonitrile; detection wavelength: 257 nm; gradient (T / B%): 0 / 5%, 12 / 95%, 15 / 95%, 18 / 5%, 20 / 5%; flow rate: 1.0 mL / min; injection volume: 5 μL; diluent: acetonitrile: water (1 / 1, v / v).

[0741] Table 1. Solubility data of pharmaceutical salts of compound 1

[0742] Example 46: Stability test of pharmaceutical salt crystal forms of compound 1

[0743] About 30 mg of L-tartrate (Form I), hydrobromide (Form I) and fumarate (Form I) were placed under three conditions, i.e. light (cool white light, 5000 Lux ± 500 Lux; closed), 60 °C (closed) and 25 °C / 90% RH (open) for 5 days and 10 days, respectively. The solid samples after storage were tested by XRPD and HPLC to analyze the stability of crystal form and chemical stability. The results showed that the three candidate salt forms were basically stable in physical and chemical properties under the above conditions for 10 days. Except that the crystal form of L-tartrate Form I changed under the condition of 25 °C / 90% RH, the crystal form did not change under other conditions.

[0744] HPLC test conditions: detection instrument: Waters ALLIANCE E2695; column: C18, 4.6 x 250 mm, 5 μm; column temperature: 27 °C; mobile phase: A: 0.05% trifluoroacetic acid in water; B: acetonitrile; detection wavelength: 257 nm; gradient (T / B%): 0 / 5%, 12 / 95%, 15 / 95%, 18 / 5%, 20 / 5%; flow rate: 1.0 mL / min; injection volume: 5 μL; diluent: acetonitrile: water (1 / 1, v / v).

[0745] Table 2. Stability data of pharmaceutical salts of compound 1

[0746] Biological activity test

[0747] 1. PARP enzyme inhibition activity assay

[0748] The detection of PARP enzyme activity is carried out by the method of ELISA. First, the substrate coating is blocked: 5x histone mixture is diluted 5 times with PBS, 25 μL of the histone mixture is added to each well of the detection plate, and incubated at 4°C overnight; the detection plate is washed with 100 μL of PBST buffer three times (5 min / time), 25 μL of blocking buffer is added and incubated for 90 min; the detection plate is washed with 100 μL of PBST buffer three times (5 min / time). Then, the enzyme activity detection of PARP is carried out, 100 nL of compound is added to each well of the reaction plate, centrifuged at 1000 rpm for 1 min; 5 μL of PARP enzyme is added to each well, centrifuged at 1000 rpm for 1 min; then 5 μL of substrate mixture is added to each well, centrifuged at 1000 rpm for 1 min and incubated at 25°C for 1 h. Finally, the experimental signal detection is carried out: the detection plate is washed with 100 μL of PBST buffer three times (5 min / time); 25 μL of St-HRP diluted with blocking solution (dilution ratio is 1:2000) is added to each well, and incubated at 25°C for 30 min; the detection plate is washed with 100 μL of PBST buffer three times (5 min / time); 25 μL of ELISA ECL Sub A and ELISA ECL Sub B mixture (mixed in equal volume) is added to each well. The BMG enzyme label is used to read the Luminescence signal value. The IC 50 value of the compound is calculated by the non-linear fitting formula in the GraphPad software, and the inhibition rate calculation formula is as follows:

[0749] Inhibition rate (%) Inh = (signal 化合物 -signal 阴性对照 ) / (signal 阳性对照 -signal 阴性对照 )*100%.

[0750] Negative control: DMSO (highest signal value).

[0751] Positive control: the highest concentration test value of the positive control compound (the lowest signal value).

[0752] Table 3: Experimental materials for PARP enzyme inhibition activity determination

[0753] The test results are as shown in the following table 4:

[0754] Table 4: PARP enzyme test results

[0755] Conclusion: The compound 1 of the present application selectively inhibits the PARP1 enzyme activity.

[0756] 2, Evaluation of compound 1 on PARP1 / 2 DNA capture

[0757] PARP "capture" (PARP DNA trapping) test experiment, using TR-FRET method to measure the DNA complex formation of PARP enzyme. After adding the inhibitor containing 1% DMSO using Echo, 2 μL of PARP1 (ICE, S2202T-H27H) enzyme and PARP1 (ICE, S2203-H31G) enzyme solution with a final concentration of 2 nM was added, centrifuged at 1000 rpm for 1 minute. 2 μL of biotin-labeled PARP-DNA (GenScript) solution with a final concentration of 2 nM was added, centrifuged at 1000 rpm for 1 minute, and then reacted at 25°C for 60 minutes; 1 μL of NAD+ (SIGMA, N6522) reagent with a final concentration of 12 μM was added, and finally a mixed solution containing 0.67 nM Streptavidin-Tb (Cisbio, 61SATLB) and 53.33 nM MAb Anti-6HIS-d2 (Cisbio, 61HISDLB) was added, centrifuged at 1000 rpm for 1 minute, and then reacted at 25°C for 60 minutes. Then the ratio 665 / 620 signal value was read using the BMG instrument, and the data was non-linearly fitted to the S-shaped dose-response curve using GraphPad Prism 8 software to determine the EC 50 The value. Compound Ola parib is purchased from Shanghai MedChemExpress Company.

[0758] Table 5 Compound PARP1 / 2 DNA capture test results

[0759] Conclusion: The compound of the present application can selectively induce PARP1 to capture DNA, and has high selectivity for PARP2 to capture DNA.

[0760] 3. Cell anti-proliferative activity test:

[0761] BRCA mutant cell MDA-MB-436 cells were cultured in DMEM medium containing 10% fetal bovine serum, 100 U / mL of penicillin, 100 μg / mL of streptomycin, and placed in a 37℃ 5% saturated CO2 incubator for culture. When the cells grew to 80% confluence, the cells were collected, centrifuged at 300g for 10 min, and plated at 1200 cells per well in a 96-well plate. After 24 h, different final concentrations of PARPi (0, 0.01, 0.1, 1, 10, 100, 1000 nM) were added, and the culture was continued for 72 h. The cells were treated with a liquid exchange (the same final concentration of PARPi was added again), and the culture was continued for 96 h. The 96-well plate was removed, the OD value at 450 nm was detected by CCK8 method, and the cell inhibition rate was calculated: inhibition rate % = 1- (average OD value of the drug administration group-average OD value of the blank group) / (average OD value of the control group-average OD value of the blank group) * 100%.

[0762] BRCA wild-type cell DLD-1 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum, 100 U / mL of penicillin, 100 μg / mL of streptomycin, and placed in a 37℃ 5% saturated CO2 incubator for culture. When the cells grew to 80% confluence, the cells were collected, centrifuged at 300g for 10 min, and plated at 1000 cells per well in a 96-well plate. After 24 h, different final concentrations of PARPi (0, 1, 10 μM) were added, and the culture was continued for 72 h. The cells were treated with a liquid exchange (the same final concentration of PARPi was added again), and the culture was continued for 96 h. The 96-well plate was removed, the OD value at 450 nm was detected by CCK8 method, and the cell inhibition rate was calculated:

[0763] Inhibition rate % = 1- (average OD value of the drug administration group-average OD value of the blank group) / (average OD value of the control group-average OD value of the blank group) * 100%.

[0764] The test results are as follows in Table 6:

[0765] Table 6 Cell anti-proliferation activity test results

[0766] Conclusion: The compound and salt type of the application have significant inhibitory effect on BRCA mutant MDA-MB-436 cells, and have no obvious inhibitory effect on BRCA wild-type DLD-1 cells, indicating that the compound of the application specifically inhibits homologous recombination-deficient tumor cells.

[0767] 4. Pharmacokinetic evaluation of the compound salt type in Balb / c mice

[0768] Purpose of the experiment: To understand the pharmacokinetics of the compound salt type.

[0769] Experimental basis: Technical guidelines for nonclinical pharmacokinetic studies of chemical drugs, 2014.

[0770] Experimental scheme: Through intravenous administration (1 mg·kg -1 ) and gavage administration (1 mg·kg -1 ) of Balb / c mice, the pharmacokinetics of the compound salt was investigated.

[0771] Sample preparation: about 0.2 mg of the compound was weighed, dissolved in 10 μL of DMSO, and then 10 μL of sodium chloride solution for injection was added to prepare a 0.1 mg·mL -1 compound salt solution, which was used for administration.

[0772] Sample collection: 6 Balb / c mice (Chengdu Dasuo Experimental Animal Co., Ltd., license number: SCXK (Chuan) 2020-030), male, 3 were administered intravenously (IV) at 1 mg·kg -1 , and 3 were administered orally (PO) at 1 mg·kg -1 . About 0.05 mL of blood was collected at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h and 48 h after administration, and the collected blood was centrifuged at 3500 rpm for 15 min. The supernatant plasma was collected and stored at -40℃ for testing. The blood drug concentration was quantitatively analyzed by LC-MS / MS analysis method, and the pharmacokinetic parameters such as peak time (Cmax), area under the curve (AUC(0-t)), half-life (T 1 / 2 ), clearance (CL), tissue distribution (V dss ), and bioavailability (F) were calculated.

[0773] Table 7 Pharmacokinetic test results of the compound salt in Balb / c mice

[0774] Conclusion: The compound salt of the present application has good pharmacokinetic properties in Balb / c mice.

[0775] 5. Pharmacokinetic evaluation of the compound salt in SD rats

[0776] Experimental purpose: To understand the pharmacokinetics of the compound salt.

[0777] Experimental basis: Technical guidelines for nonclinical pharmacokinetic studies of chemical drugs, 2014.

[0778] Experimental scheme: Through oral and intravenous administration of SD rats, the pharmacokinetics of the compound salt was investigated.

[0779] Experimental procedure: the compound was weighed, a small amount of DMSO was added, and then sodium chloride injection was added to prepare a solution, which was used for administration. 6 SD rats, male rats, were administered orally, and about 0.1 mL of blood was collected at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 24 h after administration. Centrifugation was performed at 3500 rpm for 15 min, and the supernatant plasma was collected. 5 μL of plasma was taken into an EP tube, 100 μL of 20 ng·ml -1 The internal standard SAHA was precipitated with acetonitrile, vortexed for 30 s, centrifuged at 13000 rpm for 15 min, and the supernatant was loaded into a sample bottle for testing. The standard curve range was 10-10000 ng·ml -1 .

[0780] The pharmacokinetic evaluation results are as follows in Table 8:

[0781] Table 8 Pharmacokinetic test results of compound salt type in SD rats

[0782] Conclusion: The compound salt type of the present application has good pharmacokinetic properties in SD rats, including good oral bioavailability, exposure, half-life and clearance rate, etc.

[0783] 6, Pharmacodynamic evaluation of compound salt type on human breast cancer MDA-MB-436 mouse model

[0784] 42 female NOD / SCID mice were used for the experiment, and were randomly divided into a blank control group, a compound 1 fumarate salt Form I 0.03, 0.1, 0.3, 1 mg / kg dose group, a positive drug Olaparib 100 mg / kg, AZD5305 0.1 mg / kg group, a total of 7 groups, 6 in each group. Each group was administered orally, once a day, and the body weight was measured every 2 days, and the length and width of the tumor were measured with a vernier caliper. After 28 days of administration, the tumor-bearing mice were anesthetized and sacrificed, the tumor tissue was stripped, weighed and photographed, and the tumor inhibition rate was calculated. The reference compounds Olaparib and AZD5305 were purchased from Shanghai MedChemExpress Company.

[0785] After grouping, compared with the blank control group, the tumor growth of each administration group (Olaparib 100 mg / kg, AZD5305 0.1 mg / kg, Compound 1 fumarate salt Form I 0.03, 0.1, 0.3, 1 mg / kg) had obvious inhibitory effect on the human breast cancer MDA-MB-436 cell line NOD / SCID mouse subcutaneous tumor model, and the tumor inhibition rates of each administration group were 92.51%, 100.00%, 87.17%, 100.00%, 100.00%, and 100.00%, respectively; the relative tumor growth rates T / C% values were 3.5%, 0.0%, 14.3%, 0.0%, 0.0%, and 0.0%, respectively. The tumors of the mice in the Compound 1 fumarate salt (Form I) 0.1, 0.3, and 1 mg / kg groups completely regressed, and the effective dose was less than 0.03 mg / kg. The tumor inhibition effect of the Compound 1 fumarate salt (Form I) 0.1, 0.3, and 1 mg / kg groups was better than that of the positive drug Olaparib 100 mg / kg. During the administration period, the body weights of the mice in each group were normal, and no drug-related toxicity reactions were observed. The experimental results are shown in FIGS. 70 and 71.

Claims

1. A compound of formula 1 in salt form, characterized in that: The salt type is a pharmaceutically acceptable salt selected from the group consisting of a fumarate, an L-tartrate, a 1,5-naphthalenedisulfonate, a 2-naphthalenesulfonate, an L-malate, an L-camsylate, a benzenesulfonate, a malonate, an oxalate, a p-toluenesulfonate, a methanesulfonate, a sulfate, a gentisate, a maleate, a citrate, a hydrobromate, a hydrochlorate, an ethanesulfonate or a saccharin co-crystal.

2. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate, the fumarate of the compound of formula 1 is a crystal form I, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 18.94±0.2°, 19.78±0.2°, 20.81±0.2° and 23.55±0.2°; Preferably, in the fumarate crystal form I, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1. Preferably, the X-ray powder diffraction pattern of the fumarate crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 14.07±0.2°, 15.42±0.2°, 16.08±0.2°, 18.94±0.2°, 19.78±0.2°, 20.80±0.2°, 21.53±0.2°, 22.99±0.2°, 23.54±0.2°, 23.71±0.2°, 24.60±0.2°, 25.80±0.2° and 27.37±0.2°.

3. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate, the fumarate of the compound of formula 1 is a crystal form II, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate crystal form II has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 9.98±0.2°, 14.77±0.2°, 21.34±0.2°, 22.91±0.2° and 24.05±0.2°; Preferably, in the fumarate crystal form II, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1. Preferably, the X-ray powder diffraction pattern of the fumarate crystal form II has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 9.98±0.2°, 14.16±0.2°, 14.63±0.2°, 14.77±0.2°, 18.31±0.2°, 20.36±0.2°, 21.08±0.2°, 21.34±0.2°, 22.21±0.2°, 22.76±0.2°, 22.91±0.2°, 24.05±0.2° and 24.90±0.2°.

4. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form III, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, the X-ray powder diffraction pattern of the fumarate salt crystal form III has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 9.55±0.2°, 11.03±0.2°, 11.33±0.2°, 19.22±0.2°, 19.89±0.2°, 24.32±0.2°, 26.46±0.2°; Preferably, in the fumarate salt crystal form III, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1.

5. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form IV, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, the X-ray powder diffraction pattern of the fumarate salt crystal form IV has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 21.11±0.2°, 22.57±0.2°, 25.01±0.2°, 25.41±0.2°, 26.33±0.2°; Preferably, in the fumarate salt crystal form IV, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1. Preferably, the X-ray powder diffraction pattern of the fumarate salt crystal form IV has the characteristic diffraction peaks with less excellent stability and reproducibility at the following 2θ positions: 9.12±0.2°, 9.89±0.2°, 16.04±0.2°, 21.11±0.2°, 21.80±0.2°, 22.56±0.2°, 23.02±0.2°, 24.35±0.2°, 25.01±0.2°, 25.41±0.2°, 26.33±0.2°.

6. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form V, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, the X-ray powder diffraction pattern of the fumarate salt crystal form V has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 9.62±0.2°, 16.63±0.2°, 20.83±0.2°, 24.96±0.2°, 28.37±0.2°; Preferably, in the fumarate salt crystal form V, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.

6. Preferably, the X-ray powder diffraction pattern of the fumarate salt crystal form V has the characteristic diffraction peaks with less excellent stability and reproducibility at the following 2θ positions: 8.75±0.2°, 9.62±0.2°, 16.63±0.2°, 18.13±0.2°, 20.83±0.2°, 21.71±0.2°, 22.56±0.2°, 23.08±0.2°, 24.96±0.2°, 26.43±0.2°, 27.60±0.2°, 28.37±0.2°.

7. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form VI, the salt formation ratio of the compound of formula 1 and fumaric acid in the fumarate salt crystal form VI is 1:0.5-3, and the X-ray powder diffraction spectrum of the fumarate salt crystal form VI has the following characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 10.43±0.2°, 16.35±0.2°, 25.48±0.2°, 26.59±0.2°, 26.97±0.2°; Preferably, in the fumarate salt crystal form VI, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:1; Preferably, the X-ray powder diffraction spectrum of the fumarate salt crystal form VI has the following characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 10.43±0.2°, 16.35±0.2°, 17.42±0.2°, 18.15±0.2°, 20.92±0.2°, 21.25±0.2°, 23.55±0.2°, 25.48±0.2°, 26.59±0.2°, 26.97±0.2°.

8. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form VII, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, and the X-ray powder diffraction spectrum of the fumarate salt crystal form VII has the following characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 4.97±0.2°, 9.92±0.2°, 10.35±0.2°, 16.06±0.2°; Preferably, in the fumarate salt crystal form VII, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5; Preferably, the X-ray powder diffraction spectrum of the fumarate salt crystal form VII has the following characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 4.97±0.2°, 9.92±0.2°, 10.35±0.2°, 12.32±0.2°, 14.89±0.2°, 16.06±0.2°, 17.58±0.2°, 19.42±0.2°, 20.33±0.2°, 25.40±0.2°, 26.53±0.2°.

9. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate salt, the fumarate salt of the compound of formula 1 is crystal form VIII, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5-3, and the X-ray powder diffraction spectrum of the fumarate salt crystal form VIII has the following characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 4.55±0.2°, 4.90±0.2°, 9.10±0.2°, 9.86±0.2°; Preferably, in the fumarate salt crystal form VIII, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:0.5; Preferably, the X-ray powder diffraction spectrum of the fumarate salt crystal form VIII has the following characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 4.55±0.2°, 4.90±0.2°, 9.10±0.2°, 9.86±0.2°, 11.02±0.2°, 12.32±0.2°, 14.89±0.2°, 16.06±0.2°, 17.58±0.2°, 19.42±0.2°, 20.33±0.2°, 25.40±0.2°, 26.53±0.2°. Preferably, the X-ray powder diffraction pattern of the fumarate salt form VIII has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 4.55±0.2°, 4.90±0.2°, 9.10±0.2°, 9.86±0.2°, 17.31±0.2°, 18.22±0.2°, 19.77±0.2°, 21.33±0.2°, 27.52±0.2°, 36.96±0.2°.

10. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate, the fumarate of the compound of formula 1 is crystalline form IX, the salt ratio of the compound of formula 1 to fumaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate crystalline form IX has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.79±0.2°, 7.46±0.2°, 8.95±0.2°, 9.65±0.2°, 16.51±0.2°, 18.08±0.2°, 20.84±0.2°, 21.62±0.2°, 22.60±0.2°, 23.10±0.2°, 24.44±0.2°, 27.62±0.2°, 28.30±0.2°; Preferably, in the fumarate salt form IX, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1.

11. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is a fumarate, the fumarate of the compound of formula 1 is crystalline form X, the salt ratio of the compound of formula 1 to fumaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the fumarate crystalline form X has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 9.96±0.2°, 14.76±0.2°, 14.99±0.2°, 18.66±0.2°, 20.33±0.2°, 21.34±0.2°, 22.19±0.2°, 22.39±0.2°, 22.68±0.2°, 22.86±0.2°, 23.69±0.2°; Preferably, in the fumarate salt crystalline form X, the salt formation ratio of the compound of formula 1 and fumaric acid is 1:

1.

12. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is in crystalline form I, the salt ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 7.58±0.2°, 25.99±0.2°, and 27.19±0.2°; Preferably, in the L-tartrate crystalline form I, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of the L-tartrate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 7.58±0.2°, 7.94±0.2°, 16.01±0.2°, 18.42±0.2°, 19.82±0.2°, 21.49±0.2°, 22.50±0.2°, 25.99±0.2°, 27.19±0.2°.

13. The salt according to claim 1, characterized by: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is in crystal form II, the salt ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystal form II has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 7.62±0.2°, 22.71±0.2°, 26.18±0.2°, 27.40±0.2°; Preferably, in the L-tartrate crystalline form II, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of L-tartrate salt form II has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 7.62±0.2°, 7.98±0.2°, 14.24±0.2°, 16.14±0.2°, 18.72±0.2°, 19.97±0.2°, 21.62±0.2°, 22.71±0.2°, 26.18±0.2°, 27.40±0.2°.

14. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is crystalline form III, the salt formation ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystalline form III has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.09±0.2°, 8.19±0.2°, 12.30±0.2°, 16.95±0.2°, 21.08±0.2°, 28.82±0.2°, 28.98±0.2°; Preferably, in the L-tartrate crystalline form III, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of L-tartrate salt form III has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 4.09±0.2°, 8.19±0.2°, 12.30±0.2°, 16.95±0.2°, 20.53±0.2°, 20.88±0.2°, 21.08±0.2°, 24.76±0.2°, 28.82±0.2°, 28.98±0.2°.

15. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is crystal form IV, the salt ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystal form IV has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.33±0.2°, 23.67±0.2°, 25.30±0.2°, 26.26±0.2°; Preferably, in the L-tartrate crystalline form IV, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of L-tartrate salt form IV has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 4.33±0.2°, 15.48±0.2°, 18.13±0.2°, 19.14±0.2°, 23.67±0.2°, 25.30±0.2°, 25.77±0.2°, 26.26±0.2°, 27.42±0.2°.

16. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is in crystal form V, the salt ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystal form V has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.35±0.2°, 8.69±0.2°, 16.73±0.2°; Preferably, in the L-tartrate crystalline form V, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of the L-tartrate salt form V has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 4.35±0.2°, 8.69±0.2°, 13.06±0.2°, 16.73±0.2°, 17.46±0.2°, 23.95±0.2°, 25.88±0.2°.

17. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-tartrate, the L-tartrate of the compound of formula 1 is crystalline form VI, the salt ratio of the compound of formula 1 to L-tartaric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-tartrate crystalline form VI has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 7.59±0.2°, 18.38±0.2°, 26.01±0.2°, 27.25±0.2°; Preferably, in the L-tartrate crystalline form VI, the salt ratio of the compound of formula 1 to the L-tartrate is 1:1; Preferably, the X-ray powder diffraction pattern of the L-tartrate salt form VI has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 7.59±0.2°, 7.95±0.2°, 15.98±0.2°, 18.38±0.2°, 19.83±0.2°, 21.50±0.2°, 22.44±0.2°, 26.01±0.2°, 27.25±0.2°.

18. The salt of claim 1, wherein: The pharmaceutically acceptable salt is 1,5-naphthalene disulfonate, the 1,5-naphthalene disulfonate of the compound of formula 1 is in crystal form I, the salt ratio of the compound of formula 1 to 1,5-naphthalene disulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the crystal form I of 1,5-naphthalene disulfonate has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 10.59±0.2°, 16.62±0.2°, 17.10±0.2°, 21.21±0.2°, 22.29±0.2°, 23.30±0.2°; Preferably, in the 1,5-naphthalene disulfonic acid salt crystal form I, the salt ratio of the compound of formula 1 to 1,5-naphthalene disulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of 1,5-naphthalene disulfonate salt form I has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 5.65±0.2°, 10.59±0.2°, 11.64±0.2°, 15.98±0.2°, 16.62±0.2°, 17.10±0.2°, 19.32±0.2°, 20.75±0.2°, 21.21±0.2°, 22.29±0.2°, 22.90±0.2°, 23.30±0.2°, 24.14±0.2°, 24.68±0.2°, 26.35±0.2°.

19. The salt of claim 1, wherein: The pharmaceutically acceptable salt is 2-naphthalenesulfonate, the 2-naphthalenesulfonate of the compound of formula 1 is in crystalline form I, the salt formation ratio of the compound of formula 1 to 2-naphthalenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the crystalline form I of the 2-naphthalenesulfonate has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.40±0.2°, 18.22±0.2°, 18.95±0.2°, 20.29±0.2°, 22.36±0.2°; Preferably, in the 2-naphthalenesulfonate salt form I, the salt ratio of the compound of formula 1 to 2-naphthalenesulfonic acid is 1:0.8; Preferably, the X-ray powder diffraction pattern of the 2-naphthalenesulfonate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 4.40 ± 0.2°, 8.91 ± 0.2°, 11.27 ± 0.2°, 14.18 ± 0.2°, 17.17 ± 0.2°, 18.01 ± 0.2°, 18.22 ± 0.2°, 18.55 ± 0.2°, 18.95 ± 0.2°, 20.29 ± 0.2°, 22.36 ± 0.2°, 22.64 ± 0.2°, 24.22 ± 0.2°, 25.80 ± 0.2°, 26.22 ± 0.2°.

20. The salt of claim 1, wherein: The pharmaceutically acceptable salt is 2-naphthalenesulfonate, the 2-naphthalenesulfonate of the compound of formula 1 is in crystal form II, the salt formation ratio of the compound of formula 1 to 2-naphthalenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the crystal form II of the 2-naphthalenesulfonate has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.81±0.2°, 18.58±0.2°, 21.00±0.2°; Preferably, in the 2-naphthalenesulfonate salt crystal form II, the salt ratio of the compound of formula 1 to 2-naphthalenesulfonic acid is 1:0.8; Preferably, the X-ray powder diffraction pattern of the 2-naphthalenesulfonate salt form II has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 4.81±0.2°, 9.61±0.2°, 13.09±0.2°, 17.04±0.2°, 17.96±0.2°, 18.58±0.2°, 19.60±0.2°, 20.30±0.2°, 21.00±0.2°, 21.33±0.2°, 23.78±0.2°, 24.14±0.2°.

21. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-malate, the L-malate of the compound of formula 1 is in crystalline form I, the salt ratio of the compound of formula 1 to L-malic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-malate crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 8.95±0.2°, 15.79±0.2°, 20.85±0.2°, 22.55±0.2°, 25.89±0.2°; Preferably, in the L-malate crystalline form I, the salt ratio of the compound of formula 1 to L-malic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the L-malate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 8.95±0.2°, 9.24±0.2°, 13.22±0.2°, 15.79±0.2°, 17.25±0.2°, 19.54±0.2°, 20.31±0.2°, 20.85±0.2°, 21.04±0.2°, 22.55±0.2°, 23.72±0.2°, 24.94±0.2°, 25.89±0.2°, 26.24±0.2°, 26.95±0.2°, and 27.37±0.2°.

22. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-camphorsulfonate, the L-camphorsulfonate of the compound of formula 1 is in crystalline form I, the salt ratio of the compound of formula 1 to L-camphorsulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the L-camphorsulfonate crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 5.80±0.2°, 12.80±0.2°, 18.61±0.2°, 19.06±0.2°, 19.83±0.2°, 20.03±0.2°, 20.86±0.2°; Preferably, in the L-camphorsulfonic acid salt crystal form I, the salt ratio of the compound of formula 1 to L-camphorsulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the L-camphorsulfonate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 5.80±0.2°, 11.58±0.2°, 12.80±0.2°, 16.87±0.2°, 17.77±0.2°, 18.06±0.2°, 18.61±0.2°, 19.06±0.2°, 19.83±0.2°, 20.03±0.2°, 20.86±0.2°, 21.41±0.2°, 22.72±0.2°, 23.04±0.2°, 24.46±0.2°.

23. The salt of claim 1, wherein: The pharmaceutically acceptable salt is L-camphorsulfonate, the L-camphorsulfonate of the compound of formula 1 is in crystal form II, the salt ratio of the compound of formula 1 to L-camphorsulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the crystal form II of the L-camphorsulfonate has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 12.00±0.2°, 13.39±0.2°, 16.09±0.2°, 20.59±0.2°; Preferably, in the L-camphorsulfonic acid salt crystal form II, the salt ratio of the compound of formula 1 to L-camphorsulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of L-camphorsulfonate salt form II has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 9.17±0.2°, 9.84±0.2°, 12.00±0.2°, 13.39±0.2°, 16.09±0.2°, 19.09±0.2°, 20.05±0.2°, 20.38±0.2°, 20.59±0.2°, 21.10±0.2°, 21.78±0.2°, 25.14±0.2°, 26.29±0.2°, 28.13±0.2°.

24. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a benzenesulfonate salt, the benzenesulfonate salt of the compound of formula 1 is in crystalline form I, the salt formation ratio of the compound of formula 1 to benzenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the benzenesulfonate salt crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.68±0.2°, 9.35±0.2°, 14.04±0.2°; Preferably, in the benzenesulfonate salt form I, the salt ratio of the compound of formula 1 to benzenesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the benzenesulfonate salt form I has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 4.68±0.2°, 9.35±0.2°, 14.04±0.2°, 14.81±0.2°, 18.25±0.2°, 22.02±0.2°, 23.50±0.2°, 24.94±0.2°.

25. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a benzenesulfonate salt, the benzenesulfonate salt of the compound of formula 1 is in crystal form II, the salt formation ratio of the compound of formula 1 to benzenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the benzenesulfonate crystal form II has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.67±0.2°, 14.07±0.2°, and 18.12±0.2°; Preferably, in the benzenesulfonate salt form II, the salt ratio of the compound of formula 1 to benzenesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the benzenesulfonate salt form II has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 4.67±0.2°, 9.35±0.2°, 14.07±0.2°, 18.12±0.2°, 18.57±0.2°, 22.77±0.2°, 23.02±0.2°, 23.55±0.2°.

26. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a malonate, the malonate of the compound of formula 1 is in crystalline form I, the salt ratio of the compound of formula 1 to malonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the malonate crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 15.25±0.2°, 18.28±0.2°, 19.46±0.2°, 19.72±0.2°, 22.96±0.2°; Preferably, in the malonate salt form I, the salt ratio of the compound of formula 1 to malonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the malonate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 8.93±0.2°, 15.25±0.2°, 17.90±0.2°, 18.28±0.2°, 18.46±0.2°, 19.46±0.2°, 19.72±0.2°, 21.50±0.2°, 22.96±0.2°, 23.47±0.2°, 24.67±0.2°, 26.52±0.2°.

27. The salt of claim 1, wherein: The pharmaceutically acceptable salt is an oxalate salt, the oxalate salt of the compound of formula 1 is in crystal form I, the salt formation ratio of the compound of formula 1 to oxalic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the oxalate crystal form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 7.80±0.2°, 14.68±0.2°, 21.29±0.2°; Preferably, in the oxalate crystalline form I, the salt ratio of the compound of formula 1 to oxalic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the oxalate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 7.80±0.2°, 14.68±0.2°, 16.27±0.2°, 18.30±0.2°, 18.48±0.2°, 19.16±0.2°, 20.73±0.2°, 21.29±0.2°, 21.89±0.2°, 23.71±0.2°, 24.06±0.2°, 24.56±0.2°.

28. The salt of claim 1, wherein: The pharmaceutically acceptable salt is an oxalate salt, the oxalate salt of the compound of formula 1 is in crystal form II, the salt formation ratio of the compound of formula 1 to oxalic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the oxalate crystal form II has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 6.30±0.2°, 9.47±0.2°, 15.86±0.2°, 19.06±0.2°; Preferably, in the oxalate salt form II, the salt ratio of the compound of formula 1 to oxalic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the oxalate salt form II has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 3.10±0.2°, 6.30±0.2°, 9.47±0.2°, 12.67±0.2°, 15.86±0.2°, 16.70±0.2°, 19.06±0.2°, 22.34±0.2°, 22.88±0.2°, 24.16±0.2°, 25.23±0.2°, 25.54±0.2°, 26.05±0.2°.

29. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a p-toluenesulfonate salt, the p-toluenesulfonate salt of the compound of Formula 1 is in crystalline form I, the salt formation ratio of the compound of Formula 1 to p-toluenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the p-toluenesulfonate salt crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.47±0.2°, 14.15±0.2°, and 18.48±0.2°; Preferably, in the p-toluenesulfonate crystalline form I, the salt ratio of the compound of formula 1 to p-toluenesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form I has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 4.47±0.2°, 8.93±0.2°, 13.41±0.2°, 14.15±0.2°, 16.14±0.2°, 18.48±0.2°, 19.21±0.2°, 22.47±0.2°, 22.77±0.2°, 24.87±0.2°, 25.20±0.2°.

30. The salt of claim 1, wherein: The pharmaceutically acceptable salt is p-toluenesulfonate, the p-toluenesulfonate of the compound of formula 1 is in crystal form II, the salt ratio of the compound of formula 1 to p-toluenesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the p-toluenesulfonate crystal form II has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 3.29±0.2°, 14.23±0.2°, 16.86±0.2°, 22.70±0.2°, 22.85±0.2°, 24.82±0.2°; Preferably, in the p-toluenesulfonate crystalline form II, the salt ratio of the compound of formula 1 to p-toluenesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form II has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 3.29 ± 0.2°, 11.35 ± 0.2°, 13.25 ± 0.2°, 13.66 ± 0.2°, 14.23 ± 0.2°, 16.86 ± 0.2°, 19.14 ± 0.2°, 22.51 ± 0.2°, 22.70 ± 0.2°, 22.85 ± 0.2°, 23.31 ± 0.2°, 23.47 ± 0.2°, 24.82 ± 0.2°, 25.04 ± 0.2°, 26.86 ± 0.2°.

31. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a methanesulfonate salt, the methanesulfonate salt of the compound of formula 1 is in crystalline form I, the salt-forming ratio of the compound of formula 1 to methanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the methanesulfonate salt crystalline form I has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 7.27±0.2°, 15.45±0.2°, 19.84±0.2°, 21.58±0.2°, 22.17±0.2°, 22.46±0.2°; Preferably, in the mesylate salt form I, the salt ratio of the compound of formula 1 to methanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the mesylate salt form I has characteristic diffraction peaks with the second best stability and repeatability at the following 2θ positions: 5.06 ± 0.2°, 7.27 ± 0.2°, 15.45 ± 0.2°, 16.90 ± 0.2°, 17.43 ± 0.2°, 18.79 ± 0.2°, 19.60 ± 0.2°, 19.84 ± 0.2°, 21.21 ± 0.2°, 21.58 ± 0.2°, 22.17 ± 0.2°, 22.46 ± 0.2°, 25.59 ± 0.2°, 25.81 ± 0.2°, 26.51 ± 0.2°.

32. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a methanesulfonate salt, the methanesulfonate salt of the compound of formula 1 is a crystalline form II, the salt formation ratio of the compound of formula 1 to methanesulfonic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the crystalline form II of the methanesulfonate salt has characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 6.74±0.2°, 13.84±0.2°, 14.02±0.2°, 16.85±0.2°, 18.06±0.2°; Preferably, in the mesylate salt form II, the salt ratio of the compound of formula 1 to methanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the mesylate salt form II has characteristic diffraction peaks with the following stability and repeatability at the following 2θ positions: 3.39 ± 0.2°, 6.74 ± 0.2°, 13.84 ± 0.2°, 14.02 ± 0.2°, 16.85 ± 0.2°, 18.06 ± 0.2°, 19.26 ± 0.2°, 20.10 ± 0.2°, 20.68 ± 0.2°, 22.08 ± 0.2°, 23.37 ± 0.2°, 23.65 ± 0.2°, 25.51 ± 0.2°.

33. The salt of claim 1, wherein: The pharmaceutically acceptable salt is methanesulfonate, the methanesulfonate of the compound of formula 1 is crystal form III, the salt formation ratio of the compound of formula 1 and methanesulfonic acid in the methanesulfonate crystal form III is 1:0.5-3, the X-ray powder diffraction spectrum of the methanesulfonate crystal form III has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 4.98±0.2°, 6.98±0.2°, 15.65±0.2°, 17.08±0.2°, 21.06±0.2°; Preferably, in the methanesulfonate crystal form III, the salt formation ratio of the compound of formula 1 and methanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction spectrum of the methanesulfonate crystal form III has the characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 4.98±0.2°, 6.98±0.2°, 15.01±0.2°, 15.65±0.2°, 17.08±0.2°, 17.98±0.2°, 20.48±0.2°, 21.06±0.2°, 21.57±0.2°, 23.12±0.2°, 24.16±0.2°, 25.36±0.2°.

34. The salt of claim 1, wherein: The pharmaceutically acceptable salt is methanesulfonate, the methanesulfonate of the compound of formula 1 is crystal form IV, the salt formation ratio of the compound of formula 1 and methanesulfonic acid in the methanesulfonate crystal form IV is 1:0.5-3, the X-ray powder diffraction spectrum of the methanesulfonate crystal form IV has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 8.95±0.2°, 18.54±0.2°, 26.22±0.2°, 26.94±0.2°; Preferably, in the methanesulfonate crystal form IV, the salt formation ratio of the compound of formula 1 and methanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction spectrum of the methanesulfonate crystal form IV has the characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 7.61±0.2°, 8.95±0.2°, 13.90±0.2°, 15.67±0.2°, 18.54±0.2°, 18.78±0.2°, 19.93±0.2°, 20.38±0.2°, 21.61±0.2°, 26.22±0.2°, 26.94±0.2°.

35. The salt of claim 1, wherein: The pharmaceutically acceptable salt is sulfate, the sulfate of the compound of formula 1 is crystal form I, the salt formation ratio of the compound of formula 1 and sulfuric acid in the sulfate crystal form I is 1:0.5-3, the X-ray powder diffraction spectrum of the sulfate crystal form I has the characteristic diffraction peaks with excellent stability and reproducibility at the following 2θ positions: 4.39±0.2°, 8.78±0.2°, 16.95±0.2°; Preferably, in the sulfate crystal form I, the salt formation ratio of the compound of formula 1 and sulfuric acid is 1:1; Preferably, the X-ray powder diffraction spectrum of the sulfate crystal form I has the characteristic diffraction peaks with less stability and reproducibility at the following 2θ positions: 4.39±0.2°, 4.65±0.2°, 8.78±0.2°, 13.16±0.2°, 16.95±0.2°, 17.58±0.2°, 19.13±0.2°, 23.38±0.2°.

36. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a gentisate salt, the gentisate salt of the compound of formula 1 is crystal form I, the salt formation ratio of the compound of formula 1 and gentisic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the gentisate salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 6.88±0.2°, 19.90±0.2°, 26.79±0.2°; Preferably, in the gentisate salt crystal form I, the salt formation ratio of the compound of formula 1 and gentisic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the gentisate salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 6.88±0.2°, 13.78±0.2°, 14.80±0.2°, 16.19±0.2°, 19.90±0.2°, 22.46±0.2°, 26.09±0.2°, 26.79±0.2°.

37. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a maleate salt, the maleate salt of the compound of formula 1 is crystal form I, the salt formation ratio of the compound of formula 1 and maleic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the maleate salt crystal form I has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 19.00±0.2°, 22.63±0.2°, 24.51±0.2°; Preferably, in the maleate salt crystal form I, the salt formation ratio of the compound of formula 1 and maleic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the maleate salt crystal form I has the following characteristic diffraction peaks with less stability and reproducibility at 2θ positions of 8.70±0.2°, 11.86±0.2°, 14.72±0.2°, 15.44±0.2°, 16.88±0.2°, 17.21±0.2°, 18.64±0.2°, 20.50±0.2°, 22.63±0.2°, 23.65±0.2°, 24.05±0.2°, 24.51±0.2°.

38. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a maleate salt, the maleate salt of the compound of formula 1 is crystal form II, the salt formation ratio of the compound of formula 1 and maleic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the maleate salt crystal form II has the following characteristic diffraction peaks with excellent stability and reproducibility at 2θ positions of 6.18±0.2°, 14.48±0.2°, 15.60±0.2°, 19.83±0.2°, 25.62±0.2°, 25.91±0.2°, 26.71±0.2°; Preferably, in the maleate salt crystal form II, the salt formation ratio of the compound of formula 1 and maleic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the maleate salt Form II has the following characteristic diffraction peaks with good stability and reproducibility: 6.18±0.2°, 14.48±0.2°, 15.60±0.2°, 15.87±0.2°, 16.13±0.2°, 19.83±0.2°, 20.03±0.2°, 20.43±0.2°, 21.89±0.2°, 23.18±0.2°, 24.11±0.2°, 25.62±0.2°, 25.91±0.2°, 26.71±0.2°.

39. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a citrate salt, the compound of Formula 1 citrate salt is Form I, the salt formation ratio of the compound of Formula 1 and citric acid is 1:0.5-3, and the X-ray powder diffraction pattern of the citrate salt Form I has the following characteristic diffraction peaks with excellent stability and reproducibility: 16.97±0.2°, 21.13±0.2°, 25.08±0.2°; Preferably, in the citrate salt Form I, the salt formation ratio of the compound of Formula 1 and citric acid is 1:

1. Preferably, the X-ray powder diffraction pattern of the citrate salt Form I has the following characteristic diffraction peaks with good stability and reproducibility: 8.75±0.2°, 9.04±0.2°, 10.55±0.2°, 12.95±0.2°, 15.96±0.2°, 16.97±0.2°, 17.55±0.2°, 20.56±0.2°, 21.13±0.2°, 21.55±0.2°, 23.37±0.2°, 25.08±0.2°, 26.05±0.2°.

40. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a hydrobromide salt, the compound of Formula 1 hydrobromide salt is Form I, the salt formation ratio of the compound of Formula 1 and hydrobromic acid is 1:0.5-3, and the X-ray powder diffraction pattern of the hydrobromide salt Form I has the following characteristic diffraction peaks with excellent stability and reproducibility: 16.46±0.2°, 16.86±0.2°, 18.41±0.2°, 20.70±0.2°; Preferably, in the hydrobromide salt Form I, the salt formation ratio of the compound of Formula 1 and hydrobromic acid is 1:0.

8. Preferably, the X-ray powder diffraction pattern of the hydrobromide salt Form I has the following characteristic diffraction peaks with good stability and reproducibility: 9.19±0.2°, 15.32±0.2°, 16.46±0.2°, 16.86±0.2°, 18.41±0.2°, 20.14±0.2°, 20.70±0.2°, 26.46±0.2°, 27.03±0.2°, 29.26±0.2°, 30.73±0.2°.

41. The salt of claim 1, wherein: The pharmaceutically acceptable salt is hydrochloride, the hydrochloride of the compound of formula 1 is crystal form I, the salt formation ratio of the compound of formula 1 and hydrochloric acid is 1:0.5-3, the X-ray powder diffraction pattern of the hydrochloride crystal form I has the characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.49±0.2°, 8.96±0.2°, 13.47±0.2°, 20.26±0.2°; Preferably, in the hydrochloride crystal form I, the salt formation ratio of the compound of formula 1 and hydrochloric acid is 1:0.65; Preferably, the X-ray powder diffraction pattern of the hydrochloride crystal form I has the characteristic diffraction peaks with less stability and repeatability at the following 2θ positions: 4.49±0.2°, 8.96±0.2°, 9.32±0.2°, 11.25±0.2°, 13.47±0.2°, 15.72±0.2°, 20.26±0.2°.

42. The salt of claim 1, wherein: The pharmaceutically acceptable salt is ethanesulfonic acid salt, the ethanesulfonic acid salt of the compound of formula 1 is crystal form I, the salt formation ratio of the compound of formula 1 and ethanesulfonic acid is 1:0.5-3, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form I has the characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.99±0.2°, 14.95±0.2°, 15.43±0.2°, 17.49±0.2°, 20.51±0.2°; Preferably, in the ethanesulfonic acid salt crystal form I, the salt formation ratio of the compound of formula 1 and ethanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form I has the characteristic diffraction peaks with less stability and repeatability at the following 2θ positions: 4.99±0.2°, 6.80±0.2°, 11.56±0.2°, 14.95±0.2°, 15.43±0.2°, 16.63±0.2°, 17.49±0.2°, 20.51±0.2°, 23.25±0.2°, 25.67±0.2°.

43. The salt of claim 1, wherein: The pharmaceutically acceptable salt is ethanesulfonic acid salt, the ethanesulfonic acid salt of the compound of formula 1 is crystal form II, the salt formation ratio of the compound of formula 1 and ethanesulfonic acid is 1:0.5-3, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form II has the characteristic diffraction peaks with excellent stability and repeatability at the following 2θ positions: 4.96±0.2°, 6.83±0.2°, 11.56±0.2°, 15.00±0.2°, 15.55±0.2°; Preferably, in the ethanesulfonic acid salt crystal form II, the salt formation ratio of the compound of formula 1 and ethanesulfonic acid is 1:1; Preferably, the X-ray powder diffraction pattern of the ethanesulfonic acid salt crystal form II has the characteristic diffraction peaks with less stability and repeatability at the following 2θ positions: 4.96±0.2°, 6.83±0.2°, 11.56±0.2°, 15.00±0.2°, 15.55±0.2°, 17.59±0.2°, 19.83±0.2°, 20.40±0.2°, 21.25±0.2°, 23.67±0.2°.

44. The salt of claim 1, wherein: The pharmaceutically acceptable salt is a saccharin co-crystal, the saccharin co-crystal of the compound of formula 1 is crystal form I, the co-crystal of the compound of formula 1 and saccharin has a ratio of 1:0.5-3, and the X-ray powder diffraction pattern of the saccharin co-crystal crystal form I has the following characteristic diffraction peaks with excellent stability and repeatability at 2θ positions of 11.09±0.2°, 17.12±0.2°, 23.26±0.2°, 25.00±0.2°, 26.54±0.2°; Preferably, in the saccharin co-crystal crystal form I, the salt formation ratio of the compound of formula 1 and saccharin is 1:1; Preferably, the X-ray powder diffraction pattern of the saccharin co-crystal crystal form I has the following characteristic diffraction peaks with less stability and repeatability at 2θ positions of 8.98±0.2°, 11.09±0.2°, 13.68±0.2°, 15.58±0.2°, 17.12±0.2°, 17.91±0.2°, 22.00±0.2°, 22.89±0.2°, 23.26±0.2°, 23.48±0.2°, 25.00±0.2°, 26.54±0.2°.

45. A process for the preparation of a salt form according to claim 2, characterized by: The method comprises the following steps: The compound of formula 1 and acetonitrile are mixed at a mass-volume ratio of 40-60 mg:0.5-10 mL, 0.5-4 equivalents of fumaric acid are then added, and then stirring is performed at room temperature for 1-48 h, filtration and drying are performed, and the fumaric acid salt crystal form I is obtained.

46. A process for the preparation of a salt according to claim 45, characterized in that: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and acetonitrile is 40-60 mg:1 mL; preferably 50 mg:1 mL; The amount of fumaric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 h.

47. A process for the preparation of a salt form according to claim 3, characterized by: The method comprises the following steps: The fumaric acid crystal form I obtained in claim 45 or 46 and methanol are mixed at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then stirring is performed at room temperature for 1-5 days, filtration and drying are performed, and the fumaric acid salt crystal form II is obtained.

48. A process for the preparation of a salt according to claim 47, characterized in that: At least one of the following is satisfied: The mass-volume ratio of the fumaric acid crystal form I and methanol is 40-60 mg:1 mL; preferably 50 mg:1 mL; The stirring time is 2-4 days; preferably 3 days.

49. A process for the preparation of a salt form according to claim 4, characterized by: The method comprises the following steps: The fumaric acid crystal form I obtained in claim 45 or 46 and dimethyl sulfoxide are mixed at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then stirring is performed at room temperature for 1-5 days, filtration and drying are performed, and the fumaric acid salt crystal form III is obtained.

50. A process for preparing the salt form of claim 49, wherein: At least one of the following is satisfied: The mass-volume ratio of the fumaric acid crystal form I and dimethyl sulfoxide is 40-60 mg:1 mL; preferably 50 mg:1 mL; The stirring time is 2-4 days; preferably 3 days.

51. A process for the preparation of a salt form according to claim 5, characterized by: The method comprises the following steps: The fumaric acid crystal form I obtained in claim 45 or 46 and water are mixed at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then stirring is performed at room temperature for 1-5 days, filtration and drying are performed, and the fumaric acid salt crystal form IV is obtained.

52. A process for the preparation of a salt according to claim 51, characterized by: At least one of the following is satisfied: The mass-volume ratio of the fumaric acid crystal form I and water is 40-60 mg:1 mL; preferably 50 mg:1 mL; The stirring time is 2-4 days; preferably 3 days.

53. A process for the preparation of a salt form according to claim 6, characterized by: The method comprises the following steps: The fumarate crystal form I obtained in claim 45 or 46 is mixed with water at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at room temperature for 6-10 days, filtered and dried to obtain the fumarate crystal form V.

54. A process for the preparation of a salt according to claim 53, characterized by: At least one of the following is satisfied: The mass-volume ratio of the fumarate crystal form I and water is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The stirring time is 6-8 days; preferably 7 days.

55. A process for the preparation of a salt form according to claim 7, characterized by: The method comprises the following steps: The fumarate crystal form I obtained in claim 45 or 46 is mixed with tetrahydrofuran at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then stirred at 40-60°C for 6-10 days, filtered and dried to obtain the fumarate crystal form VI.

56. A process for the preparation of a salt form according to claim 55, wherein: At least one of the following is satisfied: The mass-volume ratio of the fumarate crystal form I and tetrahydrofuran is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The stirring temperature is 50°C; The stirring time is 6-8 days; preferably 7 days.

57. A process for the preparation of a salt form according to claim 8, characterized by: The method comprises the following steps: The fumarate crystal form I obtained in claim 45 or 46 is mixed with water at a mass-volume ratio of 15-25 mg: 1-10 mL, and then quickly cooled to 0-10°C for stirring, filtered and dried to obtain the fumarate crystal form VII.

58. A process for preparing the salt form of claim 57, wherein: At least one of the following is satisfied: The mass-volume ratio of the fumarate crystal form I and water is 15-25 mg: 4 mL; preferably 20 mg: 4 mL; Quickly cooled to 2-6°C; preferably 4°C.

59. A process for the preparation of a salt form according to claim 9, characterized by: The method comprises the following steps: The fumarate crystal form I obtained in claim 45 or 46 is mixed with ethanol at a mass-volume ratio of 15-25 mg: 1-10 mL, and then slowly cooled to 0-10°C for stirring, filtered and dried to obtain the fumarate crystal form VIII.

60. A process for preparing the salt form of claim 59, wherein: At least one of the following is satisfied: The mass-volume ratio of the fumarate crystal form I and ethanol is 15-25 mg: 4 mL; preferably 20 mg: 4 mL; Quickly cooled to 2-6°C; preferably 4°C.

61. A process for the preparation of a salt form according to claim 10, characterized by: The method comprises the following steps: The compound of formula 1 is mixed with ethyl acetate or tetrahydrofuran at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then 0.5-4 equivalents of fumaric acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the fumarate crystal form IX.

62. A process for preparing the salt form of claim 61, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethyl acetate or tetrahydrofuran is 40-60 mg: 0.5-10 mL; preferably 50 mg: 1-1.5 mL; The amount of fumaric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 hours; preferably 18 hours.

63. A process for the preparation of a salt form according to claim 11, characterized by: The method comprises the following steps: The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg: 0.5-10 mL, and then 0.5-4 equivalents of fumaric acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the fumarate crystal form X.

64. A process for preparing the salt form of claim 63, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the mixed solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25: 1; preferably 19: 1; The amount of fumaric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

65. A process for the preparation of a salt form according to claim 12, characterized by: The method comprises the following steps: The compound of formula 1 and ethanol are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of L-tartaric acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain L-tartrate salt crystal form I.

66. A process for the preparation of a salt form according to claim 65, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of L-tartaric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

67. A process for the preparation of a salt form according to claim 13, characterized by: The method comprises the following steps: The L-tartrate salt crystal form I obtained in claim 65 or 66 is mixed with methanol in a mass-volume ratio of 80-120 mg: 1-10 mL, stirred at room temperature for 1-5 days, filtered and dried to obtain L-tartrate salt crystal form II.

68. A process for preparing the salt form of claim 67, wherein: At least one of the following is satisfied: The mass-volume ratio of the L-tartrate salt crystal form I and methanol is 80-120 mg: 4 mL; preferably 100 mg: 4 mL; The stirring time is 2-4 days; preferably 3 days.

69. A process for the preparation of a salt form according to claim 14, characterized by: The method comprises the following steps: The L-tartrate salt crystal form I obtained in claim 65 or 66 is mixed with water in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature for 6-10 days, filtered and dried to obtain L-tartrate salt crystal form III.

70. A process for preparing the salt form of claim 69, wherein: At least one of the following is satisfied: The mass-volume ratio of the L-tartrate salt crystal form I and water is 80-120 mg: 1 mL; preferably 100 mg: 1 mL; The stirring time is 6-8 days; preferably 7 days.

71. A process for the preparation of a salt form according to claim 15, characterized by: The method comprises the following steps: The L-tartrate salt crystal form I obtained in claim 65 or 66 is mixed with water in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature for 1-5 days, filtered and dried to obtain L-tartrate salt crystal form IV.

72. A process for preparing the salt form of claim 71, wherein: At least one of the following is satisfied: The mass-volume ratio of the L-tartrate salt crystal form I and water is 80-120 mg: 1 mL; preferably 100 mg: 1 mL; The stirring time is 2-4 days; preferably 3 days.

73. A process for the preparation of a salt form according to claim 16, characterized by: The method comprises the following steps: The L-tartrate salt crystal form I obtained in claim 65 or 66 is mixed with a mixed solvent in a mass-volume ratio of 80-120 mg: 0.5-10 mL, stirred at room temperature-60°C for 1-5 days, filtered and dried to obtain L-tartrate salt crystal form V; the mixed solvent is a mixed solvent of methanol, tetrahydrofuran or acetonitrile, and water in a volume ratio of 0.5-5.

74. A process for the preparation of a salt form according to claim 73, wherein: At least one of the following is satisfied: The mass-volume ratio of the L-tartrate salt crystal form I and the mixed solvent is 80-120 mg: 1 mL; preferably 100 mg: 1 mL; The volume ratio of methanol, tetrahydrofuran or acetonitrile to water in the mixed solvent is 0.5-2; preferably 1:1; The temperature of the stirring is room temperature-50°C; The time of the stirring is 2-4 days; preferably 3 days.

75. A process for the preparation of a salt form according to claim 17, characterized by: The method comprises the following steps: The L-tartrate salt crystal form I obtained in claim 65 or 66 is mixed with an organic solvent at a mass-volume ratio of 80-120 mg:0.5-10 mL, and stirred at room temperature-80°C for 1-10 days, filtered and dried to obtain the L-tartrate salt crystal form VI; the organic solvent is methyl tert-butyl ether, ethyl acetate, isopropyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, acetonitrile, 2-butanone, toluene or n-heptane.

76. A process for preparing the salt form of claim 75, wherein: At least one of the following is satisfied: The mass-volume ratio of the L-tartrate salt crystal form I and the organic solvent is 80-120 mg:2 mL; preferably 100 mg:2 mL; The temperature of the stirring is room temperature, 50°C or 80°C; The time of the stirring is 3-7 days.

77. A process for the preparation of a salt form according to claim 18, characterized by: The method comprises the following steps: The compound of formula 1 is mixed with ethanol, or a mixed solvent of acetone and water, at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then 0.5-4 equivalents of 1,5-naphthalenedisulfonic acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the 1,5-naphthalenedisulfonate salt crystal form I.

78. A process for preparing the salt form of claim 77, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol, or a mixed solvent of acetone and water, is 40-60 mg:1 mL; preferably 50 mg:1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of 1,5-naphthalenedisulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The time of the stirring is 12-24 h; preferably 18 hours.

79. A process for the preparation of a salt form according to claim 19, characterized by: The method comprises the following steps: The compound of formula 1 is mixed with ethyl acetate or dimethyl sulfoxide at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then 0.5-4 equivalents of 2-naphthalenesulfonic acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the 2-naphthalenesulfonate salt crystal form I.

80. A process for preparing the salt form of claim 79, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 40-60 mg:1 mL; preferably 50 mg:1 mL; The amount of 2-naphthalenesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The time of the stirring is 12-24 h; preferably 18 hours.

81. A process for the preparation of a salt form according to claim 20, characterized by: The method comprises the following steps: The compound of formula 1 is mixed with a mixed solvent of acetone and water at a mass-volume ratio of 40-60 mg:0.5-10 mL, and then 0.5-4 equivalents of 2-naphthalenesulfonic acid is added, followed by stirring at room temperature for 1-48 hours, filtering and drying to obtain the 2-naphthalenesulfonate salt crystal form II.

82. A process for preparing the salt form of claim 81, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethyl acetate or dimethyl sulfoxide is 40-60 mg:1 mL; preferably 50 mg:1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The 2-naphthalenesulfonic acid is added in an amount of 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24h; preferably 18 hours.

83. A process for preparing the salt form of claim 21, characterized by: The method comprises the following steps: The compound of formula 1 and ethanol are mixed in a mass-volume ratio of 40-60mg: 0.5-10mL, 0.5-4 equivalents of L-malic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain L-malic acid salt crystal form I.

84. A process for preparing the salt form of claim 83, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol is 40-60mg: 1mL; preferably 50mg: 1mL; The L-malic acid is added in an amount of 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24h; preferably 18 hours.

85. A process for preparing the salt form of claim 22, characterized by: The method comprises the following steps: The compound of formula 1 and ethyl acetate are mixed in a mass-volume ratio of 40-60mg: 0.5-10mL, 0.5-4 equivalents of L-camphorsulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain L-camphorsulfonic acid salt crystal form I.

86. A process for the preparation of a salt form according to claim 85, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethyl acetate is 40-60mg: 1mL; preferably 50mg: 1mL; The L-camphorsulfonic acid is added in an amount of 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24h; preferably 18 hours.

87. A process for preparing the salt form of claim 23, characterized by: The method comprises the following steps: The compound of formula 1 and a mixed solvent of acetone and water are mixed in a mass-volume ratio of 40-60mg: 0.5-10mL, 0.5-4 equivalents of L-camphorsulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain L-camphorsulfonic acid salt crystal form II.

88. A process for preparing the salt form of claim 87, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the mixed solvent of acetone and water is 40-60mg: 1mL; preferably 50mg: 1mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1; preferably 19: 1; The L-camphorsulfonic acid is added in an amount of 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24h; preferably 18 hours.

89. A process for preparing the salt form of claim 24, characterized by: The method comprises the following steps: The compound of formula 1 and ethanol are mixed in a mass-volume ratio of 40-60mg: 0.5-10mL, 0.5-4 equivalents of benzene sulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain benzene sulfonic acid salt crystal form I.

90. A process for preparing the salt form of claim 89, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol is 40-60mg: 1mL; preferably 50mg: 1mL; The benzene sulfonic acid is added in an amount of 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24h; preferably 18 hours.

91. A process for preparing the salt form of claim 25, characterized by: The method comprises the following steps: Mixing the compound of formula 1 and an organic solvent with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of benzenesulfonic acid, then stirring at room temperature for 1-48 hours, filtering and drying to obtain the benzenesulfonate salt crystal form II; the organic solvent is tetrahydrofuran or dimethyl sulfoxide, or a mixed solvent of acetone and water.

92. A process for preparing the salt form of claim 91, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25: 1; preferably 19: 1; The amount of added benzenesulfonic acid is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

93. A process for preparing the salt form of claim 26, characterized by: Comprising the following steps: Mixing the compound of formula 1 and acetonitrile or ethyl acetate with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of malonic acid, then stirring at room temperature for 1-48 hours, filtering and drying to obtain the malonate salt crystal form I.

94. A process for preparing the salt form of claim 93, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and acetonitrile or ethyl acetate is 40-60 mg: 1-1.5 mL; preferably 50 mg: 1-1.5 mL; The amount of added malonic acid is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

95. A process for preparing the salt form of claim 27, characterized by: Comprising the following steps: Mixing the compound of formula 1 and ethanol with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of oxalic acid, then stirring at room temperature for 1-48 hours, filtering and drying to obtain the oxalate salt crystal form I.

96. A process for preparing the salt form of claim 95, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of added oxalic acid is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

97. A process for the preparation of a salt form according to claim 28, characterized by: Comprising the following steps: Mixing the compound of formula 1 and acetonitrile, or a mixed solvent of acetone and water, with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of oxalic acid, then stirring at room temperature for 1-48 hours, filtering and drying to obtain the oxalate salt crystal form II.

98. A process for preparing the salt form of claim 97, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and acetonitrile, or a mixed solvent of acetone and water, is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone and water in the mixed solvent of acetone and water is 15-25: 1; preferably 19: 1; The amount of added oxalic acid is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

99. A process for preparing the salt form of claim 29, characterized by: Comprising the following steps: The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of p-toluenesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the p-toluenesulfonic acid salt crystal form I; the organic solvent is ethanol, acetonitrile, ethyl acetate, tetrahydrofuran or dimethyl sulfoxide.

100. A process for preparing the salt form of claim 99, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of p-toluenesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

101. A process for preparing the salt form of claim 30, characterized by: Comprising the following steps: The compound of formula 1 and a mixed solvent of acetone and water are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of p-toluenesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the p-toluenesulfonic acid salt crystal form II.

102. The method of claim 101, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the mixed solvent of acetone and water is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25: 1; preferably 19: 1; The amount of p-toluenesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

103. A process for preparing the salt form of claim 31, characterized by: Comprising the following steps: The compound of formula 1 and ethanol or acetonitrile are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonic acid salt crystal form I.

104. The method of claim 103, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol or acetonitrile is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of methanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

105. A process for preparing the salt form of claim 32, characterized by: Comprising the following steps: The compound of formula 1 and ethyl acetate are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonic acid salt crystal form II.

106. A process for the preparation of a salt form according to claim 105, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethyl acetate is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of methanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

107. A process for preparing the salt form of claim 33, characterized by: Comprising the following steps: The compound of formula 1 and tetrahydrofuran are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonic acid salt crystal form III.

108. A process for preparing the salt form of claim 107, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and tetrahydrofuran is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of methanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

109. A process for the preparation of a salt form according to claim 34, characterized by: Comprising the following steps: The compound of formula 1 is mixed with a mixed solvent of acetone and water in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of methanesulfonic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the methanesulfonate crystal form IV.

110. The method of claim 109, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the mixed solvent of acetone and water is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of methanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

111. A method of making the salt form of claim 35, characterized by: Comprising the following steps: The compound of formula 1 is mixed with ethanol in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of sulfuric acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the sulfate crystal form I.

112. The method of claim 111, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and ethanol is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of sulfuric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

113. A process for preparing the salt form of claim 36, characterized by: Comprising the following steps: The compound of formula 1 is mixed with acetonitrile or ethyl acetate in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of gentisic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the gentisate crystal form I.

114. The method of claim 113, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and acetonitrile or ethyl acetate is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of gentisic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

115. A process for preparing the salt form of claim 37, characterized by: Comprising the following steps: The compound of formula 1 is mixed with an organic solvent in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of maleic acid is added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the maleate crystal form I; the organic solvent is ethanol, acetonitrile or ethyl acetate, or a mixed solvent of acetone and water.

116. The method of claim 115, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of maleic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

117. A method of making the salt form of claim 38, characterized by: Comprising the following steps: The compound of formula 1 and tetrahydrofuran are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of maleic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the maleate salt crystal form II.

118. The method of claim 117, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and tetrahydrofuran is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The amount of maleic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

119. A process for preparing the salt form of claim 39, characterized by: Comprising the following steps: The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of citric acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the citrate salt crystal form I; the organic solvent is ethanol, acetonitrile, ethyl acetate or tetrahydrofuran, or a mixed solvent of acetone and water.

120. The method of claim 119, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of citric acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

121. A method of making the salt form of claim 40, characterized by: Comprising the following steps: The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of hydrobromic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the hydrobromide salt crystal form I; the organic solvent is ethanol, acetonitrile, ethyl acetate, tetrahydrofuran or dimethyl sulfoxide, or a mixed solvent of acetone and water.

122. A process for preparing the salt form of claim 121, wherein: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of hydrobromic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

123. A process for preparing the salt form of claim 41, characterized by: Comprising the following steps: The compound of formula 1 and an organic solvent are mixed in a mass-volume ratio of 40-60 mg: 0.5-10 mL, 0.5-4 equivalents of hydrobromic acid are added, and then stirred at room temperature for 1-48 hours, filtered and dried to obtain the hydrobromide salt crystal form I; the organic solvent is ethanol, acetonitrile, ethyl acetate, tetrahydrofuran or dimethyl sulfoxide, or a mixed solvent of acetone and water.

124. The method of claim 123, wherein the salt form is prepared by: At least one of the following is satisfied: The mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; The volume ratio of acetone to water in the mixed solvent of acetone and water is 15-25:1; preferably 19:1; The amount of hydrobromic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; The stirring time is 12-24 h; preferably 18 hours.

125. A method of making the salt form of claim 42, characterized by: The method comprises the following steps: mixing the compound of formula 1 and an organic solvent with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of ethanesulfonic acid, and then stirring at room temperature for 1-48 hours to obtain the ethanesulfonic acid salt crystal form I; the organic solvent is ethanol, acetonitrile or dimethyl sulfoxide.

126. The method of claim 125, wherein the salt form is prepared by: At least one of the following is satisfied: the mass-volume ratio of the compound of formula 1 and the organic solvent is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; the amount of ethanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; the stirring time is 12-24 hours; preferably 18 hours.

127. A process for preparing the salt form of claim 43, characterized by: The method comprises the following steps: mixing the compound of formula 1 and acetic ether or tetrahydrofuran with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of ethanesulfonic acid, and then stirring at room temperature for 1-48 hours to obtain the ethanesulfonic acid salt crystal form II.

128. A process for preparing the salt form of claim 127, wherein: At least one of the following is satisfied: the mass-volume ratio of the compound of formula 1 and the acetic ether or tetrahydrofuran is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; the amount of ethanesulfonic acid added is 1.05-1.15 equivalents; preferably 1.1 equivalents; the stirring time is 12-24 hours; preferably 18 hours.

129. A process for preparing the salt form of claim 44, characterized by: The method comprises the following steps: mixing the compound of formula 1 and acetonitrile with a mass-volume ratio of 40-60 mg: 0.5-10 mL, adding 0.5-4 equivalents of saccharin, and then stirring at room temperature for 1-48 hours to obtain the saccharin co-crystal crystal form I.

130. A process for preparing the salt form of claim 129, wherein: At least one of the following is satisfied: the mass-volume ratio of the compound of formula 1 and the acetonitrile is 40-60 mg: 1 mL; preferably 50 mg: 1 mL; the amount of saccharin added is 1.05-1.15 equivalents; preferably 1.1 equivalents; the stirring time is 12-24 hours; preferably 18 hours.

131. A pharmaceutical composition characterized by: The pharmaceutical composition contains a therapeutically effective amount of the salt form according to any one of claims 1-44, and a pharmaceutically acceptable carrier and / or excipient; preferably, the therapeutically effective amount is 1-600 mg of the free base of the compound of formula 1; more preferably 1-400 mg; most preferably 1-200 mg.

132. Use of the salt form according to any one of claims 1-44, the pharmaceutical composition according to claim 88, in the preparation of a PARP inhibitor; preferably a PARP1 inhibitor.

133. Use of the salt form according to any one of claims 1-44, the pharmaceutical composition according to claim 88, in the preparation of a medicament for treating and / or preventing a PARP-mediated related disease; preferably, the PARP-mediated related disease is a tumor; more preferably, the tumor is breast cancer, ovarian cancer, primary peritoneal cancer, pancreatic cancer, prostate cancer, hematological cancer, gastrointestinal cancer, glioblastoma or lung cancer.

134. The use of claim 90, wherein: The therapeutically effective amount of the main drug of the medicament is 1-600 mg of the free base of the compound of formula 1; preferably 1-400 mg; more preferably 1-200 mg.

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