A salt containing indole derivatives, crystal form and preparation method and application thereof

Abstract

A salt containing indole derivatives, a crystal form, a preparation method and an application thereof. Specifically, it relates to a salt of a compound represented by general formula (I), a crystal form, a preparation method and a pharmaceutical composition containing a therapeutically effective amount of the compound or its crystal form, and its use as a kinase inhibitor, especially as a receptor tyrosine kinase inhibitor (TKI), more specifically, as an EGFR or HER2 inhibitor in the treatment of cancer, inflammation, chronic liver disease, diabetes, cardiovascular disease, AIDS and other related diseases. The compound exhibits good inhibitory activity in EGFR and HER2 exon 20 mutations.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to a salt containing indole derivatives, a crystal form, and a preparation method and application thereof. Background Art

[0002] There are multiple signaling pathways in cells that interact with each other to control cell proliferation, growth, migration and apoptosis. Abnormal activation of signaling pathways can lead to tumorigenesis. Receptor tyrosine kinases play an important role in cell regulation. Epidermal growth factor receptor (EGFR) is a member of the transmembrane protein tyrosine kinase ErbB receptor family (including ErbB1, ErbB2, ErbB3, ErbB4). By binding to its ligand epidermal growth factor (EGF), it can form homodimers on the membrane, or form heterodimers with other receptors in the ErbB family (such as ErbB2, ErbB3, ErbB4), leading to the activation of EGFR tyrosine kinase activity. Activated EGFR can phosphorylate different substrates, thereby activating the downstream PI3K-AKT pathway and RAS-MAPK pathway, etc., and play a role in multiple processes such as cell survival, proliferation and apoptosis.

[0003] The dysregulation of EGFR signaling pathways includes increased expression of ligands and receptors, EGFR gene amplification and mutation, etc., which can promote the malignant transformation of cells, leading to the occurrence of various tumors. About 35% of Chinese non-small cell lung cancer (NSCLC) patients have EGFR mutations, of which the most common mutation types are exon 19 deletion mutation (Del19) and exon 21 L858R activation mutation, which account for about 80% of EGFR mutations. EGFR exon 20 insertion mutation is another major EGFR mutation, accounting for 4% to 10% of EGFR mutations in NSCLC. There are dozens of mutation types, and common mutation types are Ex20Ins D770_N771InsSVD, Ex20Ins V769_D770InsASV, etc.

[0004] Over the years, a large number of targeted drugs have been developed for EGFR mutations in NSCLC, such as the first-generation reversible tyrosinase inhibitors (TKI) gefitinib and erlotinib for classic Del19 mutations and L858R mutations, the second-generation irreversible covalent binding inhibitor afatinib, and the third-generation inhibitor osimertinib for the drug-resistant mutation EGFR T790M, all of which have very good clinical effects. However, the EGFR inhibitors currently on the market have a poor effect on EGFR exon 20 insertion mutations, and the patient's survival is very short. This target requires a more specific inhibitor, and there is a great clinical demand.

[0005] HER2 is another member of the ErbB family, and its amplification and mutation occur in many cancers. Among them, HER2 mutations account for about 4% in NSCLC, and about 90% of HER2 mutations are exon 20 insertion mutations, among which the most common mutation type is p.A775_G776insYVMA, and the EGFR inhibitors currently on the market have a general effect on it.

[0006] At present, many domestic and foreign pharmaceutical companies have actively carried out research on EGFR&HER2 exon 20 insertion mutations. Among them, Spectrum's Poziotinib, Takeda's TAK-788 and Rain Therapeutics' Tarloxotinib have all entered clinical research. In addition, Cullinan&Taiho's compound TAS-6417 has also shown good activity in preclinical experiments. Since many EGFR inhibitors have strong inhibitory effects on wild-type EGFR, leading to clinical side effects such as rashes, and the inhibitory activity of EGFR 20 exon insertion mutations and HER2 20 exon insertion mutation targets needs to be improved, there is still a great demand for compounds with obvious effects on EGFR and HER2 20 exon mutations and high selectivity for wild-type EGFR, which has a good market prospect.

[0007] Patent PCT / CN2020 / 091558 discloses the structures of a series of indole derivative inhibitors. In subsequent research and development, in order to improve the solubility and solid stability of the products, reduce storage costs, extend the product cycle, and improve the bioavailability of the products, the present invention has conducted a comprehensive study on the salt forms and crystal forms of the above-mentioned compounds. Summary of the invention

[0008] All contents involved in patent PCT / CN2020 / 091558 are added to the present invention by citation.

[0009] The object of the present invention is to provide an acid salt of a compound represented by general formula (I).

[0010]

[0011] in:

[0012] R1 is selected from hydrogen, cyano, oxazolyl, pyrazolyl,

[0013] R2 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl;

[0014] R3 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl;.

[0015] In a preferred embodiment of the present invention, R2 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-8 Cycloalkyl or 3-8 membered heterocyclic group;

[0016] R2 is preferably hydrogen, deuterium, halogen, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl or 3-6 membered heterocyclic group;

[0017] R2 is more preferably hydrogen, deuterium, methyl, ethyl, propyl, cyclopropyl or oxetanyl;

[0018] R2 is most preferably hydrogen, methyl, cyclopropyl or oxetanyl.

[0019] In a preferred embodiment of the present invention, R3 is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy or C 1-6 Haloalkoxy;

[0020] R3 is preferably hydrogen, deuterium, halogen, cyano, C 1-3 Alkyl, C 1-3 Deuterated alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy or C 1-3 Haloalkoxy;

[0021] R3 is more preferably hydrogen, deuterium, fluorine, chlorine, bromine, methoxy or ethoxy;

[0022] R3 is most preferably hydrogen, fluorine or methoxy.

[0023] In the preferred embodiment of the present invention, the specific compound structure is as follows:

[0024]

[0025] In a further preferred embodiment of the present invention, the compound is N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((5-cyano-4-(6-methoxy-1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, phenyl)acrylamide, N-(5-((5-cyano-4-(1-cyclopropyl-5-fluoro-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)-5-(oxazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide.

[0026] In a further preferred embodiment of the present invention, the number of the acids is 0.2-3; preferably 0.2, 0.5, 1, 1.5, 2, 2.5 or 3; more preferably 0.5, 1, 2 or 3; further preferably 1.

[0027] In a further preferred embodiment of the present invention, the acid salt is

[0028]

[0029] In a further preferred embodiment of the present invention, the acid salt is a hydrate or an anhydrate; when the acid salt is a hydrate, the number of water is 0.2-3; preferably 0.2, 0.5, 1, 1.5, 2, 2.5 or 3; more preferably 0.5, 1, 2 or 3.

[0030] In a further preferred embodiment of the present invention, the acid salt is crystalline or amorphous.

[0031] In a further preferred embodiment of the present invention, the acid salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide is a crystalline form, preferably a hydrochloride crystalline form, a hydrobromide crystalline form, a p-toluenesulfonate crystalline form, a sulfate crystalline form, a fumarate crystalline form, an oxalate crystalline form, a benzoylglycine salt crystalline form, a phosphate crystalline form, a maleate crystalline form, a malate crystalline form, a methanesulfonate crystalline form, a benzenesulfonate crystalline form, a malonate crystalline form, an adipate crystalline form or a succinate crystalline form of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide. more preferably, the hydrochloride form, hydrobromide form, p-toluenesulfonate form, sulfate form, fumarate form, oxalate form, benzoylglycinate form, phosphate form, maleate form of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide. Preferably, the crystal form is a crystalline form of a methanesulfonate, a benzenesulfonate, a malonate or a succinate; and more preferably, the crystal form is a hydrochloride, a hydrobromide, a p-toluenesulfonate or a benzoylglycine of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

[0032] In a further preferred embodiment of the present invention, the acid salt crystalline form of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide is hydrochloride crystalline form A, hydrobromide crystalline form A, p-toluenesulfonate crystalline form A, sulfate crystalline form A, fumarate crystalline form A, oxalate crystalline form A, benzyl Acylglycinate Form A, Benzoylglycinate Form B, Benzoylglycinate Form C, Benzoylglycinate Form D, Benzoylglycinate Form E, Benzoylglycinate Form F, Phosphate Form A, Maleate Form A, Maleate Form B, Maleate Form C, Maleate Form D, Methanesulfonate Form A, Benzenesulfonate Form A, Malonate Form A, Malonate Form B, Succinate Form A or Succinate Form B, wherein:

[0033] The X-ray powder diffraction spectrum of hydrochloride form A has a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 12.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 25.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 24.9±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks, more preferably including any 6, 7 or 8 thereof;

[0034] The X-ray powder diffraction spectrum of the hydrobromide salt form A has a diffraction peak at 2θ of 24.9±0.2°; or a diffraction peak at 26.3±0.2°; or a diffraction peak at 6.2±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 22.6±0.2°; or a diffraction peak at 14.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 25.8±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above-mentioned diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0035] The X-ray powder diffraction spectrum of p-toluenesulfonate crystalline form A has a diffraction peak at 2θ of 5.5±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 24.3±0.2°; or a diffraction peak at 26.8±0.2°; or a diffraction peak at 21.1±0.2°; or a diffraction peak at 9.9±0.2°; or a diffraction peak at 23.9±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above-mentioned diffraction peaks, more preferably including any 6, 7 or 8 thereof;

[0036] The X-ray powder diffraction spectrum of sulfate crystalline form A has a diffraction peak at 2θ of 12.0±0.2°; or a diffraction peak at 11.9±0.2°; or a diffraction peak at 6.1±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 9.6±0.2°; or a diffraction peak at 10.4±0.2°; or a diffraction peak at 22.4±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks, more preferably including any 6, 7 or 8 thereof;

[0037] The X-ray powder diffraction spectrum of the fumarate salt form A has a diffraction peak at 2θ of 24.0±0.2°; or a diffraction peak at 15.2±0.2°; or a diffraction peak at 9.4±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 13.8±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 17.6±0.2°; or a diffraction peak at 18.7±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above-mentioned diffraction peaks, more preferably including any 6, 7 or 8 thereof;

[0038] The X-ray powder diffraction spectrum of oxalate crystal form A has a diffraction peak at 2θ of 5.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 20.6±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 27.7±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0039] The X-ray powder diffraction spectrum of benzoylglycine salt form A has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 25.1±0.2°; or a diffraction peak at 10.6±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 18.3±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 19.4 ±0.2°; or at 19.0±0.2°; or at 25.9±0.2°; or at 16.6±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 of them;

[0040] The X-ray powder diffraction spectrum of benzoylglycine salt form B has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 23.1 ±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 22.8±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0041] The X-ray powder diffraction spectrum of benzoylglycine salt form C has a diffraction peak at 2θ of 5.7±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 15.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 18.5 ±0.2°; or a diffraction peak at 16.8±0.2°; or a diffraction peak at 19.4±0.2°; or a diffraction peak at 17.5±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0042] The X-ray powder diffraction spectrum of benzoylglycine salt form D has a diffraction peak at 2θ of 17.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 5.8±0.2°; or a diffraction peak at 25.2±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 15.0±0.2°; or a diffraction peak at 9.7 ±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.8±0.2°; or a diffraction peak at 19.9±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0043] The X-ray powder diffraction spectrum of benzoylglycine salt form E has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 5.3±0.2°; or a diffraction peak at 5.6±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 16.5±0.2°; or a diffraction peak at 21.5±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 18.4±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0044] The X-ray powder diffraction spectrum of benzoylglycine salt form F has a diffraction peak at 2θ of 6.1±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.3±0.2°; or a diffraction peak at 9.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 13.8±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0045] The X-ray powder diffraction spectrum of the phosphate crystal form A has a diffraction peak at 2θ of 10.6±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.2±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 13.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.9±0.2°; or a diffraction peak at 25.3±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 12.1±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0046] The X-ray powder diffraction spectrum of maleate salt form A has a diffraction peak at 2θ of 6.0±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 16.3±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 11.8±0.2°; or a diffraction peak at 7.1±0.2°; or a diffraction peak at 21.7±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0047] The X-ray powder diffraction spectrum of maleate salt form B has a diffraction peak at 2θ of 7.7±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 6.5±0.2°; or a diffraction peak at 19.8±0.2°; or a diffraction peak at 6.0±0.2°; or a diffraction peak at 8.2±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0048] The X-ray powder diffraction spectrum of maleate salt form C has a diffraction peak at 2θ of 17.1±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 13.3±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 25.5±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 13.1±0.2°; or a diffraction peak at 22.9±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0049] The X-ray powder diffraction spectrum of maleate salt form D has a diffraction peak at 2θ of 20.4±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 25.9±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 8.9±0.2°; or a diffraction peak at 24.1±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 21.8±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0050] The X-ray powder diffraction spectrum of the mesylate salt form A has a diffraction peak at 2θ of 5.9±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 17.4±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 18.0±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above-mentioned diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0051] The X-ray powder diffraction spectrum of benzenesulfonate salt form A has a diffraction peak at 2θ of 5.6±0.2°; or a diffraction peak at 21.2±0.2°; or a diffraction peak at 13.4±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 26.6±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.0±0.2°; or a diffraction peak at 10.6±0.2°; preferably including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above-mentioned diffraction peaks; more preferably including any 6, 7 or 8 thereof;

[0052] The X-ray powder diffraction spectrum of the malonate crystalline form A has a diffraction peak at 2θ of 7.5±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 20.3±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 23.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 25.6±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0053] The X-ray powder diffraction spectrum of the malonate salt form B has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 5.9±0.2°; or a diffraction peak at 20.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 27.4±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 13.9±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0054] The X-ray powder diffraction spectrum of the succinate salt form A has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 26.2±0.2°; or a diffraction peak at 19.3±0.2°; or a diffraction peak at 21.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 16.0±0.2°; or a diffraction peak at 14.4±0.2°; preferably comprising any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably comprising any 6, 7 or 8 thereof;

[0055] The X-ray powder diffraction spectrum of the succinate salt form B has a diffraction peak at 2θ of 19.2±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 20.7±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 18.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 27.3±0.2°; or a diffraction peak at 20.8±0.2°; preferably includes any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; more preferably includes any 6, 7 or 8 thereof.

[0056] In a further preferred embodiment of the present invention, a hydrochloride crystalline form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction pattern comprises at least one or more diffraction peaks located at 2θ of 26.4±0.2°, 10.8±0.2°, and 20.9±0.2°, preferably 2 of them, and more preferably 3 of them; optionally, it may further comprise at least one of 2θ of 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, and 21.0±0.2, preferably 2, 3, 4 or 5 of them;

[0057] For example, the X-ray powder diffraction pattern of the hydrochloride salt form A has diffraction peaks at the following positions at 2θ: 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2° and 6.3±0.2°.

[0058] The X-ray powder diffraction pattern of the hydrochloride salt form A optionally further comprises one or more diffraction peaks located at 2θ of 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, 26.1±0.2°; preferably at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0059] For example, the X-ray powder diffraction pattern of the hydrochloride salt form A has diffraction peaks at the following positions at 2θ: 26.4±0.2°, 10.8±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 22.1±0.2°, 24.9±0.2° and 8.8±0.2°.

[0060] The X-ray powder diffraction pattern of the hydrochloride salt form A comprises diffraction peaks at one or more of 2θ of 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, and 26.1±0.2°; preferably, diffraction peaks are selected from 4, 5, 6, 8, and 10;

[0061] For example, the X-ray powder diffraction pattern of the hydrochloride salt form A has diffraction peaks at the following positions of 2θ: 26.4±0.2°, 10.8±0.2°, 20.9±0.2° and 14.2±0.2°;

[0062] or, at 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 6.3±0.2°, and 22.1±0.2°;

[0063] or, at 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 22.1±0.2°, and 18.9±0.2°;

[0064] Alternatively, at 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2°, and 18.9±0.2°.

[0065] The X-ray powder diffraction pattern of the hydrochloride salt form A comprises 2θ of 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, 26.1±0.2°, 20.6±0.2°, 22.9±0.2°, 23.1±0.2°, 10.4±0.2°, 22.6±0.2° has a diffraction peak at one or more places; preferably at least any 2-3 places, or 4-5 places, or 7-8 places, or 10-12 places, or 15-18 places; more preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, 18 places have diffraction peaks;

[0066] For example, the X-ray powder diffraction pattern of the hydrochloride salt form A has diffraction peaks at the following positions at 2θ: 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 22.1±0.2°, 20.6±0.2°, 22.9±0.2° and 18.9±0.2°.

[0067] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 1.

[0068] Table 1

[0069]

[0070] Further preferably, the hydrochloride salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide shown in Example 1 has an X-ray powder diffraction pattern substantially as follows: Figure 1 As shown; its DSC spectrum is basically as Figure 2 As shown; its TGA spectrum is basically as Figure 3 shown.

[0071] In a further preferred embodiment of the present invention, a hydrobromide salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 24.9±0.2°, 26.3±0.2°, and 6.2±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, and 14.0±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0072] For example, the X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions at 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2° and 10.5±0.2°.

[0073] The X-ray powder diffraction pattern of the hydrobromide salt form A optionally further comprises one or more diffraction peaks located at 2θ of 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, and 28.1±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0074] For example, the X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions at 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 21.0±0.2° and 25.8±0.2°;

[0075] or, at 24.9±0.2°, 26.3±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 21.0±0.2°, 25.8±0.2°, and 18.9±0.2°;

[0076] Alternatively, at 24.9±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, and 26.5±0.2°.

[0077] The X-ray powder diffraction pattern of the hydrobromide salt form A comprises one or more diffraction peaks located at 2θ of 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, and 28.1±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 of them;

[0078] For example, the X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions at 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2° and 20.4±0.2°;

[0079] or, at 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, and 21.0±0.2°;

[0080] Alternatively, at 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2°, and 25.8±0.2°.

[0081] The X-ray powder diffraction pattern of the hydrobromide salt form A comprises 2θ of 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, 2 8.1±0.2°, 19.5±0.2°, 22.1±0.2°, 18.5±0.2°, 32.5±0.2°, 8.7±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0082] For example, the X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions at 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 21.0±0.2°, 19.5±0.2°, 22.1±0.2° and 18.9±0.2°.

[0083] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 2.

[0084] Table 2

[0085]

[0086] Further preferably, the hydrobromide salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide shown in Example 1 has an X-ray powder diffraction pattern substantially as follows: Figure 4 As shown; its DSC spectrum is basically as Figure 5 As shown; its TGA spectrum is basically as Figure 6 shown.

[0087] In a further preferred embodiment of the present invention, a p-toluenesulfonate crystalline form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.5±0.2°, 14.1±0.2°, and 21.7±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, and 21.1±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0088] For example, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2° and 24.3±0.2°.

[0089] The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, 8.0±0.2°; preferably at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0090] For example, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 9.9±0.2° and 23.9±0.2°;

[0091] or at 5.5±0.2°, 14.1±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 9.9±0.2°, 23.9±0.2°, and 18.0±0.2°;

[0092] Alternatively, at 5.5±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, and 8.5±0.2°.

[0093] The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises one or more diffraction peaks located at 2θ of 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, and 8.0±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected therefrom;

[0094] For example, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2° and 15.6±0.2°;

[0095] or, at 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 24.3±0.2°, and 9.9±0.2°;

[0096] or, at 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 9.9±0.2°, and 18.0±0.2;

[0097] Alternatively, at 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2°, and 23.9±0.2°.

[0098] The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises 2θ of 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, 8 .0±0.2°, 19.7±0.2°, 20.3±0.2°, 18.5±0.2°, 10.8±0.2°, 21.5±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0099] For example, the X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions at 2θ: or, 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 9.9±0.2°, 19.7±0.2°, 20.3±0.2° and 18.0±0.2.

[0100] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 3.

[0101] Table 3

[0102]

[0103] Further preferably, the p-toluenesulfonate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide shown in Example 1 has an X-ray powder diffraction pattern substantially as follows: Figure 7 As shown; its DSC spectrum is basically as Figure 8 As shown; its TGA spectrum is basically as Fig. 9 shown.

[0104] In a further preferred embodiment of the present invention, a sulfate salt crystalline form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 12.0±0.2°, 11.9±0.2°, and 6.1±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, and 9.6±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0105] For example, the X-ray powder diffraction pattern of the sulfate crystal form A has diffraction peaks at the following positions at 2θ: 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2° and 22.1±0.2°.

[0106] The X-ray powder diffraction pattern of the sulfate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, and 22.0±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0107] For example, the X-ray powder diffraction pattern of the sulfate salt form A has diffraction peaks at the following positions at 2θ: 12.0±0.2°, 11.9±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 10.4±0.2°, 22.4±0.2° and 17.9±0.2°.

[0108] The X-ray powder diffraction pattern of sulfate crystalline form A comprises one or more diffraction peaks located at 2θ of 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, and 22.0±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected therefrom;

[0109] For example, the X-ray powder diffraction pattern of the sulfate crystalline form A has diffraction peaks at the following positions at 2θ: 12.0±0.2°, 11.9±0.2°, 6.1±0.2° and 14.1±0.2°;

[0110] or, at 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, and 10.4±0.2°;

[0111] or, at 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 10.4±0.2°, and 17.9±0.2°;

[0112] Alternatively, at 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2°, and 17.9±0.2°.

[0113] The X-ray powder diffraction pattern of sulfate salt form A comprises 2θ of 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, 22 .0±0.2°, 16.5±0.2°, 25.9±0.2°, 19.9±0.2°, 20.0±0.2°, 23.5±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, 18 thereof have diffraction peaks;

[0114] For example, the X-ray powder diffraction pattern of the sulfate salt form A has diffraction peaks at the following positions at 2θ: 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 10.4±0.2°, 16.5±0.2°, 25.9±0.2° and 17.9±0.2°.

[0115] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 4.

[0116] Table 4

[0117]

[0118]

[0119] Further preferably, the sulfate salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form A, has an X-ray powder diffraction pattern substantially as follows: Fig.10 shown.

[0120] In a further preferred embodiment of the present invention, a crystalline form A of a fumarate of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, wherein the number of acids is 1, and the X-ray powder diffraction pattern thereof has one or more diffraction peaks at 2θ of 24.0±0.2°, 15.2±0.2°, and 9.4±0.2°, preferably two of them, more preferably three of them; optionally, it may further comprise at least one of 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, and 9.7±0.2°; preferably 2, 3, 4 or 5 of them;

[0121] For example, the X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2° and 13.8±0.2°.

[0122] The X-ray powder diffraction pattern of the fumarate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, and 12.2±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0123] For example, the X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 17.6±0.2° and 18.7±0.2°;

[0124] or at 24.0±0.2°, 15.2±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 17.6±0.2°, 18.7±0.2°, and 18.9±0.2°;

[0125] Alternatively, at 24.0±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, and 8.9±0.2°.

[0126] The X-ray powder diffraction pattern of the fumarate salt form A comprises one or more diffraction peaks located at 2θ of 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 9.7±0.2°, 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, and 12.2±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected from them;

[0127] For example, the X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2° and 20.9±0.2°;

[0128] or, at 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, and 17.6±0.2°;

[0129] or at 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 17.6±0.2°, and 18.9±0.2°;

[0130] Alternatively, at 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 9.7±0.2°, 17.6±0.2°, and 18.7±0.2°.

[0131] The X-ray powder diffraction pattern of the fumarate salt form A comprises 2θ of 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 9.7±0.2°, 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, 12. 2±0.2°, 19.4±0.2°, 21.2±0.2°, 22.7±0.2°, 14.7±0.2°, 23.5±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0132] For example, the X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 17.6±0.2°, 19.4±0.2°, 21.2±0.2° and 18.9±0.2°.

[0133] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 5.

[0134] Table 5

[0135]

[0136]

[0137] Further preferably, the fumarate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.11 shown.

[0138] In a further preferred embodiment of the present invention, there is provided a crystalline form A of the oxalate of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1), the number of acids being 1, and its X-ray powder diffraction spectrum having one or more diffraction peaks at 2θ of 5.8±0.2°, 11.6±0.2°, and 21.4±0.2°, preferably comprising two of them, more preferably comprising three; optionally, further comprising at least one of 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, and 23.8±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0139] For example, the X-ray powder diffraction pattern of the oxalate crystal form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2° and 18.4±0.2°.

[0140] The X-ray powder diffraction pattern of the oxalate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, and 18.6±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0141] For example, the X-ray powder diffraction pattern of the oxalate crystalline form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 9.7±0.2° and 27.7±0.2°;

[0142] or at 5.8±0.2°, 11.6±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 9.7±0.2°, 27.7±0.2°, and 8.6±0.2°;

[0143] Alternatively, at 5.8±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, and 17.4±0.2°.

[0144] The X-ray powder diffraction pattern of the oxalate crystalline form A comprises one or more diffraction peaks located at 2θ of 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, and 18.6±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 positions selected therefrom;

[0145] For example, the X-ray powder diffraction pattern of the oxalate crystal form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2° and 20.6±0.2°;

[0146] or, at 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, and 9.7±0.2°;

[0147] or, at 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 27.7±0.2°, and 8.6±0.2°;

[0148] Alternatively, at 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2°, and 27.7±0.2°.

[0149] The X-ray powder diffraction pattern of the oxalate salt form A includes 2θ positions of 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, 18. 6±0.2°, 20.5±0.2°, 16.4±0.2°, 15.7±0.2°, 23.4±0.2°, 22.3±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, 18 thereof have diffraction peaks;

[0150] For example, the X-ray powder diffraction pattern of the oxalate crystal form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 9.7±0.2°, 20.5±0.2°, 16.4±0.2° and 8.6±0.2°.

[0151] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 6.

[0152] Table 6

[0153]

[0154]

[0155] Further preferably, the oxalate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.12 shown.

[0156] In a further preferred embodiment of the present invention, a benzoylglycine salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.4±0.2°, 25.1±0.2°, and 10.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, and 19.0±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0157] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form A has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2° and 14.6±0.2°.

[0158] The X-ray powder diffraction pattern of the benzoylglycine salt form A optionally further comprises one or more diffraction peaks located at 2θ of 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, and 17.2±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0159] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form A has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 25.9±0.2° and 16.6±0.2°;

[0160] or, at 5.4±0.2°, 25.1±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 25.9±0.2°, 16.6±0.2°, and 23.3±0.2°;

[0161] Alternatively, at 5.4±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, and 9.8±0.2°.

[0162] The X-ray powder diffraction pattern of benzoylglycine salt form A comprises one or more diffraction peaks located at 2θ of 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, and 17.2±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8, or 10 of them;

[0163] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form A has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2° and 21.3±0.2°;

[0164] or, at 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, and 25.9±0.2°;

[0165] or at 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 25.9±0.2°, and 23.3±0.2°;

[0166] Alternatively, at 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2°, and 16.6±0.2°.

[0167] The X-ray powder diffraction pattern of benzoylglycine salt form A includes 2θ of 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, One or more diffraction peaks among 17.2±0.2°, 24.5±0.2°, 19.2±0.2°, 14.4±0.2°, 23.6±0.2°, 20.5±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0168] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form A has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 25.9±0.2°, 24.5±0.2°, 19.2±0.2° and 23.3±0.2°.

[0169] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 7.

[0170] Table 7

[0171]

[0172]

[0173] Further preferably, the benzoylglycine salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.13 shown.

[0174] In a further preferred embodiment of the present invention, a benzoylglycine salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.4±0.2°, 24.7±0.2°, and 19.1±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, and 14.4±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0175] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form B has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2° and 23.1±0.2°.

[0176] The X-ray powder diffraction pattern of benzoylglycine salt form B optionally further comprises one or more diffraction peaks located at 2θ of 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, and 14.3±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0177] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form B has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 10.8±0.2° and 22.8±0.2°;

[0178] or at 5.4±0.2°, 24.7±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 10.8±0.2°, 22.8±0.2°, and 17.3±0.2°;

[0179] Alternatively, at 5.4±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, and 25.7±0.2°.

[0180] The X-ray powder diffraction pattern of benzoylglycine salt form B comprises one or more diffraction peaks located at 2θ of 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, and 14.3±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 positions selected therefrom;

[0181] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form B has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2° and 18.9±0.2°;

[0182] or, at 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, and 10.8±0.2°;

[0183] or, at 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 10.8±0.2°, and 17.3±0.2°;

[0184] Alternatively, at 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2°, and 22.8±0.2°.

[0185] The X-ray powder diffraction pattern of benzoylglycine salt form B includes 2θ of 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, One or more diffraction peaks among 14.3±0.2°, 29.0±0.2°, 14.8±0.2°, 16.6±0.2°, 18.0±0.2°, 13.4±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0186] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form B has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 10.8±0.2°, 29.0±0.2°, 14.8±0.2° and 17.3±0.2°.

[0187] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 8.

[0188] Table 8

[0189]

[0190]

[0191] Further preferably, the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form B, has an X-ray powder diffraction pattern substantially as follows: Fig.14 shown.

[0192] In a further preferred embodiment of the present invention, a benzoylglycine salt form C of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.7±0.2°, 20.4±0.2°, and 26.4±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, and 16.8±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0193] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form C has diffraction peaks at the following positions at 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2° and 11.1±0.2°.

[0194] The X-ray powder diffraction pattern of benzoylglycine salt form C optionally further comprises one or more diffraction peaks located at 2θ of 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, and 21.6±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0195] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form C has diffraction peaks at the following positions at 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 19.4±0.2° and 17.5±0.2°;

[0196] or, at 5.7±0.2°, 20.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 19.4±0.2°, 17.5±0.2°, and 18.9±0.2°;

[0197] Alternatively, at 5.7±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 19.4±0.2°, 17.5±0.2°, 18.9±0.2° and 10.5±0.2°.

[0198] The X-ray powder diffraction pattern of benzoylglycine salt form C comprises one or more diffraction peaks located at 2θ of 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, and 21.6±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 positions selected therefrom;

[0199] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form C has diffraction peaks at the following positions at 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2° and 14.5±0.2°;

[0200] or, at 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, and 19.4±0.2°;

[0201] or, at 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 19.4±0.2°, and 18.9±0.2°;

[0202] Alternatively, at 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2° and 17.5±0.2°.

[0203] The X-ray powder diffraction pattern of benzoylglycine salt form C includes 2θ of 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, One or more diffraction peaks of 21.6±0.2°, 23.4±0.2°, 25.0±0.2°, 20.8±0.2°, 25.7±0.2°, 24.7±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0204] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form C has diffraction peaks at the following positions at 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 19.4±0.2°, 23.4±0.2°, 25.0±0.2° and 18.9±0.2°.

[0205] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 9.

[0206] Table 9

[0207]

[0208]

[0209] Further preferably, the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form C, has an X-ray powder diffraction pattern substantially as follows: Fig.15 shown.

[0210] In a further preferred embodiment of the present invention, a benzoylglycine salt form D of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 17.6±0.2°, 21.0±0.2°, and 5.8±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 10.2±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0211] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form D has diffraction peaks at the following positions of 2θ: 17.6±0.2° and 21.0±0.2°; or, 21.0±0.2° and 5.8±0.2°;

[0212] or, at 17.6 ± 0.2°, 21.0 ± 0.2°, and 5.8 ± 0.2°;

[0213] or, at 17.6±0.2°, 5.8±0.2°, 16.6±0.2°, and 25.2±0.2°;

[0214] or, at 17.6 ± 0.2°, 5.8 ± 0.2°, 16.6 ± 0.2°, and 15.0 ± 0.2°;

[0215] or, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, and 16.6±0.2°;

[0216] or, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 10.2±0.2°;

[0217] or, at 17.6±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 10.2±0.2°;

[0218] Alternatively, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 15.0±0.2°, and 9.7±0.2°.

[0219] The X-ray powder diffraction pattern of the benzoylglycine salt form D optionally further comprises one or more diffraction peaks located at 2θ of 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, 18.8±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0220] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form D has diffraction peaks at the following positions at 2θ: 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 15.0±0.2°, 10.2±0.2°, 19.9±0.2° and 14.8±0.2°;

[0221] Alternatively, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, and 19.9±0.2°.

[0222] The X-ray powder diffraction pattern of the benzoylglycine salt form D comprises one or more diffraction peaks located at 2θ of 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, and 18.8±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8, or 10 of them;

[0223] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form D has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 9.7±0.2°, 14.8±0.2°, and 25.2±0.2°;

[0224] or, at 17.6 ± 0.2°, 21.0 ± 0.2°, 5.8 ± 0.2°, and 25.2 ± 0.2°;

[0225] or, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, and 15.0±0.2°;

[0226] or, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, and 9.7±0.2°;

[0227] or, at 5.8±0.2°, 9.7±0.2°, 14.1±0.2°, 15.0±0.2°, 16.6±0.2°, 17.6±0.2°, 21.0±0.2°, and 25.2±0.2°;

[0228] or, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 19.9±0.2°;

[0229] or, at 5.8±0.2°, 9.7±0.2°, 10.2±0.2°, 15.0±0.2°, 16.6±0.2°, 17.6±0.2°, 18.8±0.2°, 19.9±0.2°, 21.0±0.2°, and 25.2±0.2°;

[0230] Alternatively, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, and 19.9±0.2°.

[0231] The X-ray powder diffraction pattern of benzoylglycine salt form D includes 2θ of 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, One or more diffraction peaks among 18.8±0.2°, 22.4±0.2°, 17.9±0.2°, 18.9±0.2°, 25.8±0.2°, 19.8±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0232] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form D has diffraction peaks at the following positions at 2θ: 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 22.4±0.2°, 17.9±0.2° and 25.2±0.2°;

[0233] or at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 22.4±0.2°, 17.9±0.2°, and 14.8±0.2°;

[0234] or at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 19.9±0.2°, 22.8±0.2°, 18.8±0.2°, and 14.1±0.2°;

[0235] or at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, 22.4±0.2°, 17.9±0.2°, and 19.9±0.2°;

[0236] Alternatively, at 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 19.9±0.2°, 22.4±0.2°, 17.9±0.2°, and 14.1±0.2°.

[0237] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 10.

[0238] Table 10

[0239]

[0240] Further preferably, the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form D, has an X-ray powder diffraction pattern substantially as follows: Fig.16 As shown; its DSC spectrum is basically as Fig.17As shown; its TGA spectrum is basically as Fig.18 shown.

[0241] In a further preferred embodiment of the present invention, a benzoylglycine salt form E of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.4±0.2°, 5.3±0.2°, and 5.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, and 21.5±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0242] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2° and 24.7±0.2°.

[0243] The X-ray powder diffraction pattern of the benzoylglycine salt form E optionally further comprises one or more diffraction peaks located at 2θ of 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, and 26.3±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0244] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 14.5±0.2° and 18.4±0.2°;

[0245] or at 5.4±0.2°, 5.3±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 14.5±0.2°, 18.4±0.2°, and 12.3±0.2°;

[0246] Alternatively, at 5.4±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, and 21.1±0.2°.

[0247] The X-ray powder diffraction pattern of the benzoylglycine salt form E comprises one or more diffraction peaks located at 2θ of 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, and 26.3±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8, or 10 of them;

[0248] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2° and 10.7±0.2°; or, 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2° and 14.5±0.2°; or, 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2° and 14.5±0.2°;

[0249] Alternatively, at 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2°, and 18.4±0.2°.

[0250] The X-ray powder diffraction pattern of benzoylglycine salt form E includes 2θ of 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, One or more diffraction peaks of 26.3±0.2°, 18.5±0.2°, 15.5±0.2°, 8.3±0.2°, 26.1±0.2°, 11.0±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0251] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 18.5±0.2°, 15.5±0.2° and 10.7±0.2°;

[0252] or, at 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 18.5±0.2°, 15.5±0.2°, and 14.5±0.2°;

[0253] Alternatively, at 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 18.5±0.2°, 15.5±0.2°, and 14.5±0.2°.

[0254] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 11.

[0255] Table 11

[0256]

[0257]

[0258] Further preferably, the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form E, has an X-ray powder diffraction pattern substantially as follows: Fig.19 shown.

[0259] In a further preferred embodiment of the present invention, a benzoylglycine salt form F of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 6.1±0.2°, 6.3±0.2°, and 10.3±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, and 5.5±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0260] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions at 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2° and 9.8±0.2°.

[0261] The X-ray powder diffraction pattern of the benzoylglycine salt form F optionally further comprises one or more diffraction peaks located at 2θ of 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, 22.1±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0262] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions of 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.1±0.2° and 13.8±0.2°; or, 6.1±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 11.1±0.2°, 13.8±0.2°, 26.1±0.2° and 18.9±0.2°.

[0263] The X-ray powder diffraction pattern of the benzoylglycine salt form F comprises one or more diffraction peaks located at 2θ of 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, and 22.1±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 of them;

[0264] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions at 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2° and 12.3±0.2°;

[0265] or, at 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, and 11.1±0.2°;

[0266] or, at 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.1±0.2°, and 26.1±0.2°;

[0267] Alternatively, at 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2° and 13.8±0.2°.

[0268] The X-ray powder diffraction pattern of benzoylglycine salt Form F includes 2θ of 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0. 2°, 22.1±0.2°, 19.6±0.2°, 19.2±0.2°, 25.8±0.2°, 23.9±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0269] For example, the X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions at 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 19.6±0.2°, 19.2±0.2° and 12.3±0.2°;

[0270] or, at 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 19.6±0.2°, 19.2±0.2°, and 11.1±0.2°;

[0271] Alternatively, at 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.1±0.2°, 19.6±0.2°, 19.2±0.2° and 26.1±0.2°.

[0272] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 12.

[0273] Table 12

[0274]

[0275]

[0276] Further preferably, the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form F, has an X-ray powder diffraction pattern substantially as follows: Fig. 20 shown.

[0277] In a further preferred embodiment of the present invention, a phosphate crystal form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 10.6±0.2°, 12.3±0.2°, and 9.2±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, and 25.3±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0278] For example, the X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions at 2θ: 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2° and 6.3±0.2°.

[0279] The X-ray powder diffraction pattern of the phosphate crystal form A optionally further comprises one or more diffraction peaks located at 2θ of 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; preferably, at least any 2-3 of them; more preferably, any 2 or 3 of them;

[0280] For example, the X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions at 2θ: 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 11.7±0.2° and 12.1±0.2°;

[0281] or, at 10.6±0.2°, 12.3±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 11.7±0.2°, and 12.1±0.2°;

[0282] Alternatively, at 10.6±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°.

[0283] The X-ray powder diffraction pattern of the phosphate crystal form A comprises one or more diffraction peaks located at 2θ of 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 25.3±0.2°, 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 of them;

[0284] For example, the X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions of 2θ: 10.6±0.2°, 12.3±0.2°, 9.2±0.2° and 21.4±0.2°;

[0285] or, at 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, and 11.7±0.2°;

[0286] or, at 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 11.7±0.2°, and 12.6±0.2°;

[0287] Alternatively, at 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 25.3±0.2°, 11.7±0.2°, and 12.6±0.2°.

[0288] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 13.

[0289] Table 13

[0290]

[0291] Further preferably, the phosphate crystal form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.21 shown.

[0292] In a further preferred embodiment of the present invention, a maleate crystalline form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 6.0±0.2°, 22.3±0.2°, and 8.2±0.2°, preferably comprising two of them, more preferably comprising three; optionally, further comprising at least one of 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, and 11.8±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0293] For example, the X-ray powder diffraction pattern of the maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2° and 19.5±0.2°.

[0294] The X-ray powder diffraction pattern of maleate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, 7.7±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0295] For example, the X-ray powder diffraction pattern of the maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 7.1±0.2° and 21.7±0.2°;

[0296] or, at 6.0±0.2°, 22.3±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 7.1±0.2°, 21.7±0.2°, and 19.8±0.2°;

[0297] Alternatively, at 6.0±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, and 16.6±0.2°.

[0298] The X-ray powder diffraction pattern of maleate salt form A comprises one or more diffraction peaks located at 2θ of 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, 7.7±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 positions selected therefrom;

[0299] For example, the X-ray powder diffraction pattern of the maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2° and 16.3±0.2°;

[0300] or, at 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, and 7.1±0.2°;

[0301] or, at 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 7.1±0.2°, and 19.8±0.2°;

[0302] Alternatively, at 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2°, and 21.7±0.2°.

[0303] The X-ray powder diffraction pattern of maleate salt form A comprises 2θ of 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, 7. 7±0.2°, 24.2±0.2°, 25.9±0.2°, 13.8±0.2°, 25.3±0.2°, 11.2±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0304] For example, the X-ray powder diffraction pattern of the maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 24.2±0.2°, 25.9±0.2° and 16.3±0.2°;

[0305] or, at 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 24.2±0.2°, 25.9±0.2°, and 7.1±0.2°;

[0306] Alternatively, at 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 7.1±0.2°, 24.2±0.2°, 25.9±0.2°, and 19.8±0.2°.

[0307] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 14.

[0308] Table 14

[0309]

[0310]

[0311] Further preferably, the maleate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig. 22 shown.

[0312] In a further preferred embodiment of the present invention, a maleate crystalline form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 7.7±0.2°, 16.1±0.2°, and 23.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, and 19.8±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0313] For example, the X-ray powder diffraction pattern of the maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2° and 21.7±0.2°.

[0314] The X-ray powder diffraction pattern of maleate salt form B optionally further comprises one or more diffraction peaks located at 2θ of 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, 24.5±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0315] For example, the X-ray powder diffraction pattern of the maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.0±0.2° and 8.2±0.2°;

[0316] or, at 7.7±0.2°, 16.1±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 6.0±0.2°, 8.2±0.2°, and 20.9±0.2°;

[0317] Alternatively, at 7.7±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, and 15.3±0.2°.

[0318] The X-ray powder diffraction pattern of the maleate salt form B comprises 2θ at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, 24.5±0.2°

[0319] One or more diffraction peaks in; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected locations;

[0320] For example, the X-ray powder diffraction pattern of the maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2° and 22.2±0.2°;

[0321] or, at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, and 6.0±0.2°;

[0322] or, at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.0±0.2°, and 20.9±0.2°;

[0323] Alternatively, at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2°, and 8.2±0.2°.

[0324] The X-ray powder diffraction pattern of the maleate salt Form B comprises 2θ values ​​of 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, 24.5±0.2°, 13.8±0.2°, 13.3±0.2°, 17.9±0.2° One or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks; for example, the X-ray powder diffraction pattern of the maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 13.8±0.2°, 13.3±0.2°, and 22.2±0.2°;

[0325] or, at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 13.8±0.2°, 13.3±0.2°, and 6.0±0.2°;

[0326] Alternatively, at 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.0±0.2°, 13.8±0.2°, 13.3±0.2°, and 20.9±0.2°.

[0327] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 15.

[0328] Table 15

[0329]

[0330]

[0331] Further preferably, the maleate salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.23 shown.

[0332] In a further preferred embodiment of the present invention, a maleate salt form C of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 17.1±0.2°, 10.3±0.2°, and 23.8±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, and 23.5±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0333] For example, the X-ray powder diffraction pattern of the maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2° and 24.5±0.2°.

[0334] The X-ray powder diffraction pattern of maleate salt form C optionally further comprises one or more diffraction peaks located at 2θ of 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, 16.0±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0335] For example, the X-ray powder diffraction pattern of the maleate salt form C has diffraction peaks at the following positions at 2θ:

[0336] at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 13.1±0.2°, and 22.9±0.2°;

[0337] alternatively, at 17.1±0.2°, 10.3±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 13.1±0.2°, 22.9±0.2°, and 21.3±0.2°;

[0338] Alternatively, at 17.1±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, and 13.5±0.2°.

[0339] The X-ray powder diffraction pattern of maleate salt form C comprises one or more diffraction peaks located at 2θ of 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, and 16.0±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 positions selected therefrom;

[0340] For example, the X-ray powder diffraction pattern of the maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 23.8±0.2° and 14.3±0.2°;

[0341] or, at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, and 13.1±0.2°;

[0342] or at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 13.1±0.2°, and 21.3±0.2°;

[0343] Alternatively, at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2°, and 22.9±0.2°.

[0344] The X-ray powder diffraction pattern of the maleate salt form C comprises 2θ of 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, One or more diffraction peaks among 16.0±0.2°, 5.4±0.2°, 25.3±0.2°, 17.7±0.2°, 14.1±0.2°, 30.0±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0345] For example, the X-ray powder diffraction pattern of the maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 5.4±0.2°, 25.3±0.2° and 14.3±0.2°;

[0346] or, at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 5.4±0.2°, 25.3±0.2°, and 13.1±0.2°;

[0347] Alternatively, at 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 13.1±0.2°, 5.4±0.2°, 25.3±0.2°, and 21.3±0.2°.

[0348] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 16.

[0349] Table 16

[0350]

[0351]

[0352] Further preferably, the maleate salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form C, has an X-ray powder diffraction pattern substantially as follows: Fig.24 shown.

[0353] In a further preferred embodiment of the present invention, a maleate salt form D of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 20.4±0.2°, 8.2±0.2°, and 14.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, and 24.5±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0354] For example, the X-ray powder diffraction pattern of the maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2° and 8.9±0.2°.

[0355] The X-ray powder diffraction pattern of maleate salt form D optionally further comprises one or more diffraction peaks located at 2θ of 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, 28.8±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0356] For example, the X-ray powder diffraction pattern of the maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 16.1±0.2° and 21.8±0.2°;

[0357] or at 20.4±0.2°, 8.2±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 16.1±0.2°, 21.8±0.2°, and 17.0±0.2°;

[0358] Alternatively, at 20.4±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, and 28.4±0.2°.

[0359] The X-ray powder diffraction pattern of the maleate salt form D comprises one or more diffraction peaks located at 2θ of 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, and 28.8±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8, or 10 of them;

[0360] For example, the X-ray powder diffraction pattern of the maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2° and 25.9±0.2°;

[0361] or, at 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, and 16.1±0.2°;

[0362] or at 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 16.1±0.2°, and 17.0±0.2°;

[0363] Alternatively, at 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2°, and 21.8±0.2°.

[0364] The X-ray powder diffraction pattern of the maleate salt form D comprises 2θ of 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, 28. .8±0.2°, 21.5±0.2°, 10.8±0.2°, 23.2±0.2°, 10.4±0.2°, 17.5±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0365] For example, the X-ray powder diffraction pattern of the maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 21.5±0.2°, 10.8±0.2° and 25.9±0.2°;

[0366] or at 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 21.5±0.2°, 10.8±0.2°, and 16.1±0.2°;

[0367] Alternatively, at 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 16.1±0.2°, 21.5±0.2°, 10.8±0.2°, and 17.0±0.2°.

[0368] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 17.

[0369] Table 17

[0370]

[0371]

[0372] Further preferably, the maleate salt form D of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.25 shown.

[0373] In a further preferred embodiment of the present invention, a mesylate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.9±0.2°, 21.7±0.2°, and 10.2±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, and 17.4±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0374] For example, the X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2° and 25.7±0.2°.

[0375] The X-ray powder diffraction pattern of the mesylate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, 9.5±0.2°; preferably at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0376] For example, the X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 11.7±0.2° and 18.0±0.2°;

[0377] or at 5.9±0.2°, 21.7±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 11.7±0.2°, 18.0±0.2°, and 23.6±0.2°;

[0378] Alternatively, at 5.9±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, and 7.1±0.2°.

[0379] The X-ray powder diffraction pattern of the mesylate salt form A comprises one or more diffraction peaks located at 2θ of 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, and 9.5±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 of them;

[0380] For example, the X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2° and 14.2±0.2°;

[0381] or, at 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, and 11.7±0.2°;

[0382] or, at 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 11.7±0.2°, and 23.6±0.2°;

[0383] Alternatively, at 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2°, and 18.0±0.2°.

[0384] The X-ray powder diffraction pattern of the mesylate salt form A comprises 2θ of 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, 9. .5±0.2°, 16.6±0.2°, 16.2±0.2°, 18.9±0.2°, 23.0±0.2°, 17.8±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, 18 thereof have diffraction peaks;

[0385] For example, the X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 16.6±0.2°, 16.2±0.2° and 14.2±0.2°;

[0386] or at 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 16.6±0.2°, 16.2±0.2°, and 11.7±0.2°;

[0387] Alternatively, at 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 11.7±0.2°, 16.6±0.2°, 16.2±0.2°, and 23.6±0.2°.

[0388] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks represented by 2θ angles and interplanar spacing d values ​​are as shown in Table 18.

[0389] Table 18

[0390]

[0391]

[0392] Further preferably, the mesylate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.26 shown.

[0393] In a further preferred embodiment of the present invention, a benzenesulfonate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 5.6±0.2°, 21.2±0.2°, and 13.4±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, and 26.4±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0394] For example, the X-ray powder diffraction pattern of the benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2° and 23.7±0.2°.

[0395] The X-ray powder diffraction pattern of the benzenesulfonate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, and 22.4±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0396] For example, the X-ray powder diffraction pattern of the benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 10.0±0.2° and 10.6±0.2°;

[0397] or at 5.6±0.2°, 21.2±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 10.0±0.2°, 10.6±0.2°, and 24.5±0.2°;

[0398] Alternatively, at 5.6±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, and 14.9±0.2°.

[0399] The X-ray powder diffraction pattern of the benzenesulfonate salt form A comprises one or more diffraction peaks located at 2θ of 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, and 22.4±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected therefrom;

[0400] For example, the X-ray powder diffraction pattern of the benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2° and 18.9±0.2°;

[0401] or, at 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, and 10.0±0.2°;

[0402] or, at 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 10.0±0.2°, and 24.5±0.2°;

[0403] Alternatively, at 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2°, and 10.6±0.2°.

[0404] The X-ray powder diffraction pattern of the benzenesulfonate salt form A comprises 2θ positions of 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, 2 One or more diffraction peaks of 2.4±0.2°, 28.7±0.2°, 22.7±0.2°, 15.7±0.2°, 17.4±0.2°, 26.9±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0405] For example, the X-ray powder diffraction pattern of the benzenesulfonate salt form A has diffraction peaks at the following positions of 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 28.7±0.2°, 22.7±0.2° and 18.9±0.2°.

[0406] or at 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 28.7±0.2°, 22.7±0.2°, and 10.0±0.2°;

[0407] Alternatively, at 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 10.0±0.2°, 28.7±0.2°, 22.7±0.2°, and 24.5±0.2°.

[0408] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks expressed by 2θ angles and interplanar spacing d values ​​are as shown in Table 19.

[0409] Table 19

[0410]

[0411]

[0412] Further preferably, the benzenesulfonate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig. 27 shown.

[0413] In a further preferred embodiment of the present invention, a malonate crystalline form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 7.5±0.2°, 5.5±0.2°, and 23.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, and 21.0±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0414] For example, the X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2° and 11.7±0.2°.

[0415] The X-ray powder diffraction pattern of the malonate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, and 22.0±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0416] For example, the X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 14.3±0.2° and 25.6±0.2°;

[0417] or at 7.5±0.2°, 5.5±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 14.3±0.2°, 25.6±0.2°, and 19.4±0.2°;

[0418] Alternatively, at 7.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, and 19.7±0.2°.

[0419] The X-ray powder diffraction pattern of the malonate salt form A comprises one or more diffraction peaks located at 2θ of 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, and 22.0±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected therefrom;

[0420] For example, the X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2° and 20.3±0.2°;

[0421] or, at 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, and 14.3±0.2;

[0422] or, at 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 14.3±0.2°, and 19.4±0.2°;

[0423] Alternatively, at 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2°, and 25.6±0.2°.

[0424] The X-ray powder diffraction pattern of the malonate salt form A comprises 2θ positions of 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, 22 .0±0.2°, 15.2±0.2°, 22.8±0.2°, 27.2±0.2°, 18.7±0.2°, 16.6±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, 18 thereof have diffraction peaks;

[0425] For example, the X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 15.2±0.2°, 22.8±0.2° and 20.3±0.2°;

[0426] or, at 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 15.2±0.2°, 22.8±0.2°, and 14.3±0.2;

[0427] Alternatively, at 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 14.3±0.2°, 15.2±0.2°, 22.8±0.2°, and 19.4±0.2°.

[0428] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks expressed by 2θ angles and interplanar spacing d values ​​are as shown in Table 20.

[0429] Table 20

[0430]

[0431]

[0432] Further preferably, the malonate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.28 shown.

[0433] In a further preferred embodiment of the present invention, a malonate salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 21.4±0.2°, 5.9±0.2°, and 20.5±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, and 27.4±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0434] For example, the X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2° and 20.8±0.2°.

[0435] The X-ray powder diffraction pattern of the malonate salt form B optionally further comprises one or more diffraction peaks located at 2θ of 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, and 27.0±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0436] For example, the X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 18.4±0.2° and 13.9±0.2°;

[0437] or at 21.4±0.2°, 5.9±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 18.4±0.2°, 13.9±0.2°, and 15.2±0.2°;

[0438] Alternatively, at 21.4±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, and 18.8±0.2°.

[0439] The X-ray powder diffraction pattern of the malonate salt form B comprises one or more diffraction peaks located at 2θ of 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, and 27.0±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected from them;

[0440] For example, the X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2° and 11.4±0.2°;

[0441] or, at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, and 18.4±0.2°;

[0442] or, at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 18.4±0.2°, and 15.2±0.2°;

[0443] Alternatively, at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2°, and 13.9±0.2°.

[0444] The X-ray powder diffraction pattern of the malonate salt form B comprises 2θ at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, 2 One or more diffraction peaks of 7.0±0.2°, 24.7±0.2°, 17.7±0.2°, 14.1±0.2°, 28.4±0.2°, 11.0±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0445] For example, the X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 24.7±0.2°, 17.7±0.2° and 11.4±0.2°;

[0446] or at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 24.7±0.2°, 17.7±0.2°, and 18.4±0.2°;

[0447] Alternatively, at 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 18.4±0.2°, 24.7±0.2°, 17.7±0.2°, and 15.2±0.2°.

[0448] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks expressed by 2θ angles and crystal plane spacing d values ​​are as shown in Table 21.

[0449] Table 21

[0450]

[0451]

[0452] Further preferably, the malonate salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.29 shown.

[0453] In a further preferred embodiment of the present invention, a succinate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 21.4±0.2°, 10.7±0.2°, and 16.6±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, and 21.0±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0454] For example, the X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions of 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2° and 19.3±0.2°;.

[0455] The X-ray powder diffraction pattern of the succinate salt form A optionally further comprises one or more diffraction peaks located at 2θ of 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, and 15.7±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0456] For example, the X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 16.0±0.2° and 14.4±0.2°;

[0457] or at 21.4±0.2°, 10.7±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 16.0±0.2°, 14.4±0.2°, and 10.2±0.2°;

[0458] Alternatively, at 21.4±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, and 23.7±0.2°.

[0459] The X-ray powder diffraction pattern of the succinate salt form A comprises one or more diffraction peaks located at 2θ of 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, and 15.7±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 selected from them;

[0460] For example, the X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2° and 19.6±0.2°;

[0461] or, at 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, and 16.0±0.2°;

[0462] or at 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 16.0±0.2°, and 10.2±0.2°;

[0463] Alternatively, at 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2°, and 14.4±0.2°.

[0464] The X-ray powder diffraction pattern of the succinate salt form A comprises 2θ of 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, 1 5.7±0.2°, 25.5±0.2°, 12.9±0.2°, 8.0±0.2°, 29.9±0.2°, 25.1±0.2°, one or more diffraction peaks; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0465] For example, the X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 25.5±0.2°, 12.9±0.2° and 19.6±0.2°;

[0466] or at 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 25.5±0.2°, 12.9±0.2°, and 16.0±0.2°;

[0467] Alternatively, at 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 16.0±0.2°, 25.5±0.2°, 12.9±0.2°, and 10.2±0.2°.

[0468] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks expressed by 2θ angles and interplanar spacing d values ​​are as shown in Table 22.

[0469] Table 22

[0470]

[0471]

[0472] Further preferably, the succinate salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.30 shown.

[0473] In a further preferred embodiment of the present invention, a succinate salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (Example 1) is provided, the number of acids is 1, and its X-ray powder diffraction spectrum has one or more diffraction peaks at 2θ of 19.2±0.2°, 21.3±0.2°, and 20.7±0.2°, preferably comprising two of them, more preferably comprising three; optionally, it may further comprise at least one of 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, and 23.7±0.2°; preferably comprising 2, 3, 4 or 5 of them;

[0474] For example, the X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions at 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2° and 18.5±0.2°.

[0475] The X-ray powder diffraction pattern of the succinate salt form B optionally further comprises one or more diffraction peaks located at 2θ of 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, and 18.7±0.2°; preferably, at least any 2-3, or 4-5, or 6-7 thereof; further preferably, any 2, 3, 4, 5, 6, or 7 thereof;

[0476] For example, the X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions at 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 27.3±0.2° and 20.8±0.2°;

[0477] or, at 19.2±0.2°, 21.3±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 27.3±0.2°, 20.8±0.2°, and 22.0±0.2°;

[0478] Alternatively, at 19.2±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, and 16.2±0.2°.

[0479] The X-ray powder diffraction pattern of the succinate salt form B comprises one or more diffraction peaks located at 2θ of 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, and 18.7±0.2°; preferably, there are diffraction peaks at 4, 5, 6, 8 or 10 of them;

[0480] For example, the X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions at 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2° and 14.1±0.2°;

[0481] or, at 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, and 27.3±0.2°;

[0482] or, at 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 27.3±0.2°, and 22.0±0.2°;

[0483] Alternatively, at 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2°, and 20.8±0.2°.

[0484] The X-ray powder diffraction pattern of the succinate salt form B comprises 2θ of 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, One or more diffraction peaks among 18.7±0.2°, 17.8±0.2°, 7.1±0.2°, 15.3±0.2°, 9.3±0.2°, 24.8±0.2°; preferably at least any 2-3, or 4-5, or 7-8, or 10-12, or 15-18 thereof; further preferably, any 2, 3, 4, 5, 6, 8, 10, 12, 16, or 18 thereof have diffraction peaks;

[0485] For example, the X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions at 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 17.8±0.2°, 7.1±0.2° and 14.1±0.2°;

[0486] or, at 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 17.8±0.2°, 7.1±0.2°, and 27.3±0.2°;

[0487] Alternatively, at 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 27.3±0.2°, 17.8±0.2°, 7.1±0.2°, and 22.0±0.2°.

[0488] Most preferably, Cu-Kα radiation is used, and the X-ray characteristic diffraction peaks expressed by 2θ angles and interplanar spacing d values ​​are as shown in Table 23.

[0489] Table 23

[0490]

[0491]

[0492] Further preferably, the succinate salt form B of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide has an X-ray powder diffraction pattern substantially as follows: Fig.31 shown.

[0493] In a further preferred embodiment of the present invention, the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A, hydrobromide form A, p-toluenesulfonate form A, sulfate form A, fumarate form A, oxalate form A, benzoylglycine form A, benzoylglycine salt form A, The positions of the top ten diffraction peaks with the highest relative peak intensity in the X-ray powder diffraction patterns of Form B, Form C of benzoylglycine, Form D of benzoylglycine, Form E of benzoylglycine, Form F of benzoylglycine, Form A of phosphate, Form A of maleate, Form B of maleate, Form C of maleate, Form D of maleate, Form A of methanesulfonate, Form A of benzenesulfonate, Form A of malonate, Form B of malonate, Form A of succinate, and Form B of succinate are respectively Figure 1 , Figure 4 , Figure 7 , Fig.10 , Fig.11 , Fig.12 , Fig.13 , Fig.14 , Fig.15 , Fig.16 , Fig.19 , Fig. 20 , Fig.21 , Fig. 22 , Fig.23 , Fig.24 , Fig.25 , Fig.26 , Fig. 27 , Fig.28 , Fig.29 , Fig.30 and Fig.31 The 2θ error of the diffraction peak at the corresponding position is ±0.2° to ±0.5°, preferably ±0.2° to ±0.3°, and most preferably ±0.2°.

[0494] In a preferred embodiment of the present invention, the acid salt crystal form of any compound described in general formula (I) is a hydrate or an anhydrate; when the acid salt crystal form is a hydrate, the number of water is 0.2-3, preferably 0.2, 0.5, 1, 1.5, 2, 2.5 or 3, more preferably 0.5, 1, 2 or 3; further, the water in the hydrate is pipeline water or crystal water or a combination of the two.

[0495] It is well known to those skilled in the art that XRPD may produce certain displacement and intensity deviations due to the detection method, conditions and instruments. As a specific example of the crystal form of the present invention, its XRPD is shown in spectrum X, but it is understood by those skilled in the art that when the 2θ deviation of the key characteristic peak displacement is ±0.5, especially around ±0.2, it can be identified as the same crystal form.

[0496] The present invention also provides a method for preparing an acid salt of the compound represented by general formula (I), comprising the following steps:

[0497] 1) Weigh an appropriate amount of free base and dissolve it in a benign solvent;

[0498] 2) Weigh an appropriate amount of acid and dissolve it in an organic solvent; the amount of the acid is preferably 1.0 to 1.5 equivalents;

[0499] 3) combining the above two solutions, stirring to precipitate or adding a poor solvent dropwise and stirring to precipitate;

[0500] 4) Rapidly centrifuge or allow to dry to obtain the target product;

[0501] in:

[0502] The benign solvent is selected from acetone, toluene, acetonitrile, methanol, dichloromethane, tetrahydrofuran, ethyl formate, ethyl acetate, 2-methyl-tetrahydrofuran, 2-butanone, n-butanol, 1,4-dioxane, isobutanol, N,N-dimethylformamide, N,N-dimethylacetamide, n-propanol or tert-butanol; preferably toluene, ethyl acetate, acetone, methanol or acetonitrile;

[0503] The organic solvent is selected from methanol, ethanol, ethyl acetate, dichloromethane, acetone, n-hexane, petroleum ether, benzene, toluene, chloroform, acetonitrile, carbon tetrachloride, dichloroethane, tetrahydrofuran, 2-methyl-tetrahydrofuran, 2-butanone, 3-pentanone, heptane, methyl tert-butyl ether, isopropyl ether, 1,4-dioxane, tert-butanol or N,N-dimethylformamide; preferably methanol, ethanol or acetonitrile; the above benign solvent and organic solution need to be miscible when used;

[0504] The poor solvent is selected from heptane, water, methyl tert-butyl ether, cyclohexane, toluene, isopropyl ether, ethyl acetate, acetone or acetonitrile; preferably water, methyl tert-butyl ether or isopropyl ether;

[0505] The acid is selected from hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, phosphoric acid, 2,5-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, acetic acid, dichloroacetic acid, trichloroacetic acid, acetohydroxamic acid, adipic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, 4-aminobenzoic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclohexanesulfamic acid, camphorsulfonic acid, Aspartic acid, camphoric acid, gluconic acid, glucuronic acid, glutamic acid, isoascorbic acid, lactic acid, malic acid, mandelic acid, pyroglutamic acid, tartaric acid, dodecyl sulfate, dibenzoyltartaric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactosyl acid, gentisic acid, glutaric acid, 2-ketoglutaric acid, glycolic acid, benzoylglycine, isethionic acid, lactobionic acid, ascorbic acid, aspartic acid, Cinnamic acid, camphoric acid, maleic acid, malonic acid, methanesulfonic acid, 1,5-naphthalene disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, thiocyanic acid, pamoic acid, formic acid, undecylenic acid, trifluoroacetic acid, benzenesulfonic acid, p-toluenesulfonic acid or L-malic acid; preferably hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid Acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid, succinic acid, isethionic acid, 1,5-naphthalenedisulfonic acid, tartaric acid, adipic acid, formic acid, lauric acid or stearic acid; more preferably hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid or succinic acid; most preferably benzoylglycine.

[0506] The present invention also provides a method for preparing an acid salt of the compound represented by general formula (I), comprising the following steps:

[0507] 1) Weigh an appropriate amount of free base and suspend it with a poor solvent;

[0508] 2) Weigh an appropriate amount of acid and dissolve it in an organic solvent; the amount of the acid is preferably 1.0 to 1.5 equivalents;

[0509] 3) adding the above solution to the above suspension and stirring, preferably stirring for 2 hours;

[0510] 4) Rapidly centrifuge or dry to obtain the target product;

[0511] in:

[0512] The poor solvent is selected from ethanol, acetone, ethyl acetate, ethyl formate, isopropanol, isopropyl acetate, methyl tert-butyl ether, methanol, 1,4-dioxane, 2-butanone, 2-methyl-tetrahydrofuran, anisole, acetonitrile, chlorobenzene, benzene, toluene, n-butanol, isobutanol or 3-pentanone; preferably ethanol, 2-methyl-tetrahydrofuran, anisole or ethyl acetate;

[0513] The organic solvent is selected from methanol, ethanol, ethyl acetate, dichloromethane, acetone, n-hexane, petroleum ether, benzene, toluene, chloroform, acetonitrile, carbon tetrachloride, dichloroethane, tetrahydrofuran, 2-methyl-tetrahydrofuran, 2-butanone, 3-pentanone, heptane, methyl tert-butyl ether, isopropyl ether, 1,4-dioxane, tert-butanol or N,N-dimethylformamide; preferably methanol, ethanol or acetonitrile; the above benign solvent and organic solution need to be miscible when used;

[0514] The acid is selected from hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, phosphoric acid, 2,5-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, acetic acid, dichloroacetic acid, trichloroacetic acid, acetohydroxamic acid, adipic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, 4-aminobenzoic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclohexanesulfamic acid, camphorsulfonic acid, aspartic acid, camphoric acid, gluconic acid, glucuronic acid, glutamic acid, isoascorbic acid, lactic acid, malic acid, mandelic acid, pyroglutamic acid, tartaric acid, dodecyl sulfuric acid, dibenzoyltartaric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactonic acid, gentian Preferably, the present invention is selected from the group consisting of 1,2-diaminobenzenesulfonic acid, ...

[0515] The present invention also provides a method for preparing a crystalline form of an acid salt of a compound represented by general formula (I), comprising the following steps:

[0516] 1) Weigh an appropriate amount of compound salt and suspend it with a poor solvent, and the suspension density is preferably 50 to 200 mg / mL;

[0517] 2) The suspension obtained above is shaken at a certain temperature for a certain time, preferably at 25 to 50° C., and the time is preferably 1 to 15 days;

[0518] 3) The above suspension is centrifuged quickly, the supernatant is removed, and the remaining solid is dried to constant weight to obtain the target product, preferably placed in a 50° C. vacuum drying oven and dried to constant weight to obtain the target product;

[0519] in:

[0520] The poor solvent is selected from methanol, ethanol, dichloromethane, 1,4-dioxane, acetonitrile, dichloromethane, chlorobenzene, benzene, toluene, acetone, ethyl acetate, water, 88% acetone, isopropyl acetate, 3-pentanone, ethyl formate, tetrahydrofuran, 2-methyl-tetrahydrofuran, isopropanol, n-butanol, isobutanol, n-propanol, methyl tert-butyl ether, n-heptane, tert-butanol or 2-butanone.

[0521] The present invention also aims to provide a pharmaceutical composition, which contains a therapeutically effective amount of the acid salt of the compound of the general formula (I) and its crystal form, and one or more pharmaceutically acceptable carriers or excipients.

[0522] The present invention also aims to provide the use of the acid salt of the compound of the general formula (I) and its crystal form and pharmaceutical composition in the preparation of kinase inhibitor drugs.

[0523] The present invention also aims to provide an acid salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide and its crystalline form, as well as the use of the pharmaceutical composition in the preparation of kinase inhibitor drugs.

[0524] The kinase inhibitor is a receptor tyrosine kinase inhibitor, preferably a HER2 inhibitor, an EGFR inhibitor, an EGFR monoclonal antibody, and related drugs used in combination, more preferably a HER2 exon 20 mutant inhibitor, an EGFR20 exon mutant inhibitor, an EGFR20 exon mutant monoclonal antibody, and related drugs used in combination.

[0525] The object of the present invention is to provide an acid salt of the compound represented by the general formula (I) and its crystal form and the use of the pharmaceutical composition in drugs for treating cancer, inflammation, chronic liver disease, diabetes, cardiovascular disease and AIDS-related diseases. Preferably, the cancer, inflammation, chronic liver disease, diabetes, cardiovascular disease and AIDS-related diseases are diseases mediated by HER2 exon 20 mutation and / or EGFR20 exon mutation.

[0526] The present invention also aims to provide an acid salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide and its crystalline form, as well as the use of the pharmaceutical composition in drugs for treating cancer, inflammation, chronic liver disease, diabetes, cardiovascular disease and AIDS-related diseases. Preferably, the cancer, inflammation, chronic liver disease, diabetes, cardiovascular disease and AIDS-related diseases are diseases mediated by HER2 exon 20 mutations and / or EGFR20 exon mutations.

[0527] The cancer is selected from breast cancer, cervical cancer, colon cancer, lung cancer, stomach cancer, rectal cancer, pancreatic cancer, brain cancer, liver cancer, solid tumors, glioma, glioblastoma, leukemia, lymphoma, myeloma and non-small cell lung cancer.

[0528] The third-generation EGFR inhibitors are mainly highly inhibitory against EGFR activation mutants and T790M drug-resistant mutants. The compounds of the present invention have the following significant advantages over the third-generation EGFR inhibitors in terms of EGFR and / or HER2 exon 20 insertion mutation targets:

[0529] 1. Significantly improve the inhibitory activity of Ba / F3 EGFR mutant cell lines, and the activity of the preferred compounds is more than 10 times, or even 20 times higher;

[0530] 2. Improve the selectivity of the proliferation inhibition activity in Ba / F3EGFR mutant cell lines and A431 cell lines, preferably with a compound that is more than 3 times, or even 10 times higher;

[0531] 3. The in vivo efficacy and tumor inhibition rate of the drug also showed significant advantages in the mouse original B cell Ba / F3EGFR-D770-N771ins_SVD transplanted tumor model.

[0532] Detailed description of the invention

[0533] Unless stated otherwise, the terms used in the specification and claims have the following meanings.

[0534] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms, and most preferably an alkyl group containing 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched chain isomers thereof. More preferred are lower alkyl groups having 1 to 6 carbon atoms, non-limiting examples of which include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, and the like. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any available attachment point. The substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate groups. Methyl, ethyl, isopropyl, tert-butyl, haloalkyl, deuterated alkyl, alkoxy-substituted alkyl and hydroxy-substituted alkyl are preferred in the present invention.

[0535] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 carbon atoms, and most preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, etc.; polycyclic cycloalkyls include cycloalkyls of spirocyclic, fused and bridged rings, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl and cycloheptyl.

[0536] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which is selected from nitrogen, oxygen or S(O). m (wherein m is an integer from 0 to 2) heteroatoms, but excluding the ring part of -OO-, -OS- or -SS-, the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 8 ring atoms; most preferably, it contains 3 to 6 ring atoms. Non-limiting examples of monocyclic heterocyclic groups include oxetanyl, thietanyl, pyrrolidinyl, pyrrolidonyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, pyranyl, etc., preferably oxetanyl, pyrrolidonyl, tetrahydrofuranyl, pyrazolidinyl, morpholinyl, piperazinyl and pyranyl. Polycyclic heterocyclic groups include spirocyclic, condensed and bridged heterocyclic groups; the spirocyclic, condensed and bridged heterocyclic groups involved are optionally connected to other groups through single bonds, or further connected to other cycloalkyl, heterocyclic, aryl and heteroaryl groups through any two or more atoms on the ring.

[0537] The heterocyclyl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0538] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6- to 10-membered, such as phenyl and naphthyl. More preferably phenyl. The aryl ring may be fused to a heteroaryl, heterocyclic or cycloalkyl ring, including benzo 3-8-membered cycloalkyl, benzo 3-8-membered heteroalkyl, preferably benzo 3-6-membered cycloalkyl, benzo 3-6-membered heteroalkyl, wherein the heterocyclic group is a heterocyclic group containing 1-3 nitrogen atoms, oxygen atoms, and sulfur atoms; or further comprising a three-membered nitrogen-containing fused ring containing a benzene ring, wherein the ring connected to the parent structure is an aryl ring.

[0539] The aryl group may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0540] The term "heteroaryl" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. The heteroaryl is preferably 5 to 10-membered, more preferably 5-membered or 6-membered, such as imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, thiadiazole, pyrazinyl, etc., preferably triazolyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, pyrimidyl or thiazolyl; more preferably pyrazolyl and oxazolyl. The heteroaryl ring can be fused to an aryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaryl ring.

[0541] The term "alkoxy" refers to-O-(alkyl) and-O-(unsubstituted cycloalkyl), wherein the definition of alkyl is as described above. The non-limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy. Alkoxy can be optionally substituted or unsubstituted, and when substituted, substituents are preferably one or more of the following groups, which are independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0542] "Haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[0543] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[0544] "Alkenyl" refers to a chain alkenyl group, also known as an alkene group, wherein the alkenyl group can be further substituted by other related groups, for example: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0545] "Alkynyl" refers to (CH≡C-), wherein the alkynyl can be further substituted by other related groups, for example: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0546] "Hydroxy" refers to an -OH group.

[0547] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0548] "Amino" refers to -NH2.

[0549] "Cyano" refers to -CN.

[0550] "Nitro" refers to -NO2.

[0551] "Carboxy" refers to -C(O)OH.

[0552] "THF" refers to tetrahydrofuran.

[0553] "EtOAc" means ethyl acetate.

[0554] "MeOH" refers to methanol.

[0555] "DMF" refers to N,N-dimethylformamide.

[0556] "DIPEA" refers to diisopropylethylamine.

[0557] "TFA" refers to trifluoroacetic acid.

[0558] "MeCN" refers to acetylene.

[0559] "DMA" refers to N,N-dimethylacetamide.

[0560] "Et2O" refers to diethyl ether.

[0561] "DCE" refers to 1,2-dichloroethane.

[0562] "DIPEA" refers to N,N-diisopropylethylamine.

[0563] "NBS" refers to N-bromosuccinimide.

[0564] "NIS" refers to N-iodosuccinimide.

[0565] "Cbz-Cl" refers to benzyl chloroformate.

[0566] "Pd2(dba)3" refers to tris(dibenzylideneacetone)dipalladium.

[0567] "Dppf" refers to 1,1'-bis(diphenylphosphino)ferrocene.

[0568] "HATU" refers to 2-(7-oxybenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0569] "KHMDS" refers to potassium hexamethyldisilazide.

[0570] "LiHMDS" refers to lithium bistrimethylsilylamide.

[0571] "MeLi" refers to methyllithium.

[0572] "n-BuLi" refers to n-butyllithium.

[0573] "NaBH(OAc)3" refers to sodium triacetoxyborohydride.

[0574] "DMAP" refers to 4-dimethylaminopyridine.

[0575] "SEM-Cl" refers to chloromethyltrimethylsilylethyl ether.

[0576] "Xantphos" refers to 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene.

[0577] "DCM" refers to dichloromethane.

[0578] Different expressions such as “X is selected from A, B, or C”, “X is selected from A, B and C”, “X is A, B or C”, “X is A, B and C” all express the same meaning, that is, X can be any one or more of A, B, C.

[0579] The hydrogen atoms described in the present invention can be replaced by their isotope deuterium, and any hydrogen atom in the example compounds of the present invention can also be replaced by a deuterium atom.

[0580] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs or does not occur. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may but need not be present, and the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[0581] "Substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms in the group are replaced independently by the corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (such as olefinic) bond. Optional substituents include deuterium, halogen, amino, hydroxyl, cyano, oxo, thio, alkyl, alkenyl, alkynyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, alkylthio, haloalkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, preferably deuterium, halogen, amino, hydroxyl, cyano, oxo, thio, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Halogenated alkoxy, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl and 5-14 membered heteroaryl.

[0582] "Pharmaceutical composition" means a mixture containing one or more compounds described herein or their physiologically / pharmaceutically acceptable salts or prodrugs and other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitate the absorption of the active ingredient, and thus exert biological activity.

[0583] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention, which are safe and effective when used in mammals and have the desired biological activity.

[0584] The same samples of the same crystal form usually have the same main XRPD characteristic peaks, but there may be certain operating errors. When an ordinary technician in the field uses the same instrument and detection method to obtain the isomorphous samples using the corresponding method, the characteristic peak error is usually within ±0.2° (however, different technicians using different instruments may occasionally have a few characteristic peaks with errors exceeding this range. For example, errors within ±0.5° or ±0.3° should be considered to belong to the XRPD characteristic peaks of the same crystal form). Therefore, peaks with characteristic peak errors within ±0.5°, ±0.3° or ±0.2° can be interpreted as being within the scope of protection of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0585] Figure 1 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride.

[0586] Figure 2 This is a DSC chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride.

[0587] Figure 3 This is a TGA chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride.

[0588] Figure 4 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrobromide.

[0589] Figure 5 This is a DSC chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrobromide.

[0590] Figure 6 This is a TGA chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrobromide.

[0591] Figure 7 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide p-toluenesulfonate.

[0592] Figure 8This is a DSC chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide p-toluenesulfonate.

[0593] Fig. 9 This is a TGA chart of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide p-toluenesulfonate.

[0594] Fig.10 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide sulfate form A.

[0595] Fig.11 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide fumarate.

[0596] Fig.12 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide oxalate.

[0597] Fig.13 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form A.

[0598] Fig.14 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form B.

[0599] Fig.15This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form C.

[0600] Fig.16 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form D.

[0601] Fig.17 This is a DSC chart of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form D.

[0602] Fig.18 This is a TGA chart of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form D.

[0603] Fig.19 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form E.

[0604] Fig. 20 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt Form F.

[0605] Fig.21 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide phosphate crystal form A.

[0606] Fig. 22This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide maleate.

[0607] Fig.23 This is an XRPD diagram of Form B of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide maleate.

[0608] Fig.24 This is an XRPD diagram of Form C of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide maleate.

[0609] Fig.25 This is an XRPD diagram of Form D of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide maleate.

[0610] Fig.26 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide methanesulfonate.

[0611] Fig. 27 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzenesulfonate.

[0612] Fig.28 This is an XRPD diagram of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide malonate.

[0613] Fig.29This is an XRPD diagram of Form B of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide malonate.

[0614] Fig.30 This is an XRPD pattern of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide succinic acid form A.

[0615] Fig.31 This is an XRPD diagram of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide succinic acid form B.

[0616] Fig.32 This is an XRPD pattern of Form A of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base. DETAILED DESCRIPTION

[0617] The present invention is further described below in conjunction with examples, but these examples are not intended to limit the scope of the present invention.

[0618] 1. Preparation of Compounds

[0619] Example

[0620] The structure of the compound of the present invention is determined by nuclear magnetic resonance (NMR) or / and liquid chromatography-mass spectrometry (LC-MS). The NMR chemical shift (δ) is given in parts per million (ppm). The NMR is measured using a Bruker AVANCE-400 nuclear magnetic spectrometer, and the measurement solvents are deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD) and deuterated chloroform (CDCl3), and the internal standard is tetramethylsilane (TMS).

[0621] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 1200 Infinity Series mass spectrometer, and HPLC was performed using an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0622] Thin layer chromatography silica gel plates use Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications used for TLC are 0.15mm-0.20mm, and the specifications used for thin layer chromatography separation and purification products are 0.4mm-0.5mm. Column chromatography generally uses 200-300 mesh Yantai Huanghai silica gel as a carrier.

[0623] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized according to methods known in the art.

[0624] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, the solvent is a dry solvent, and the reaction temperature is in degrees Celsius.

[0625] Example 1

[0626] N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0627]

[0628] Step 1: Preparation of 2-chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile

[0629]

[0630] 2,4-Dichloropyrimidine-5-carbonitrile (2g, 12mmol) was dissolved in dichloroethane (30mL), cooled to 0°C, and ferric chloride (3.9g, 24mmol) was added. The reaction was stirred at room temperature for half an hour, and 1-cyclopropyl-1H-indole (2.17g, 14mmol) was added. The reaction was stirred at 60°C for 2 hours. Water (30mL) was added, filtered, and the filtrate was extracted with dichloromethane (30mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and dried by spin drying. The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 100 / 1 to 3 / 1) to obtain 2-chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (1.6g, yield: 47%) as a brown solid.

[0631] Step 2: Preparation of 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-fluoro-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile

[0632]

[0633] 2-Chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (1 g, 3.4 mmol), 4-fluoro-2-methoxy-5-nitroaniline (0.7 g, 3.7 mmol) and p-toluenesulfonic acid (0.7 g, 3.7 mmol) were dissolved in 2-pentanol (40 mL) and the reaction was stirred at 100 °C overnight. The mixture was cooled to room temperature, water (50 mL) was added, and the mixture was extracted with dichloromethane (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried by spin drying. The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 100 / 1~1 / 1~dichloromethane / ethyl acetate: 100 / 1~10 / 1) to give 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-fluoro-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (1 g, 67%) as a brown solid.

[0634] Step 3: Preparation of 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile

[0635]

[0636] 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-fluoro-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (0.4 g, 0.9 mmol) was dissolved in acetonitrile (20 mL), potassium carbonate (0.37 g, 2.7 mmol) and N1,N1,N2-trimethylethane-1,2-diamine (0.11 g, 1.1 mmol) were added, and the reaction was stirred at 80°C for 1 hour. After cooling to room temperature, the reaction solution was filtered and the filtrate was dried to obtain a crude yellow solid of 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (0.48 g, yield: 100%).

[0637] Step 4: Preparation of 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile

[0638]

[0639] 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (0.48 g, 0.97 mmol) was dissolved in ethanol (20 mL), saturated sodium bicarbonate solution (10 mL) and iron powder (0.54 g, 9.7 mmol) were added, and the reaction was stirred at 80°C for 2 hours. After cooling to room temperature, the reaction solution was filtered, the filtrate was extracted with dichloromethane (20 mL x 2), the organic phase was dried over anhydrous sodium sulfate, filtered, and dried to obtain 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.4 g, yield: 88%) as a yellow solid.

[0640] Step 5: Preparation of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0641]

[0642] 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.4 g, 0.8 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, triethylamine (0.12 g, 1.2 mmol) was added, and 3-chloropropionyl chloride (0.12 g, 0.97 mmol) was added, and the reaction was stirred at 0°C for 1 hour. 3M sodium hydroxide solution (3 mL) was added, and the reaction was stirred at room temperature for 1 hour. Water (30 mL) was added, extracted with dichloromethane (30 mL x 2), the organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried, and the crude product was separated and purified by prep-TLC (dichloromethane / MeOH: 20 / 1) to give N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (0.15 g, yield: 34%) as a yellow solid.

[0643] MS m / z(ESI):551.4[M+H] + .

[0644] 1H NMR (400MHz, CDCl3) δ10.08(s,1H),9.42(s,1H),8.68(s,1H),8.49-8.47(m,2H),7.76(s,1H),7.61(d,J=8.0Hz,1H),7.30-7.26(m,2H),6.81( s,1H),6.39(s,2H),5.69-5.67(m,1H),3.89(s,3H),3.48-3.44(m,1H) ,2.93-2.91(m,2H),2.73(s,3H),2.35-2.30(m,8H),1.17-1.11(m,4H).

[0645] Example 2

[0646] N-(5-((5-cyano-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0647]

[0648]

[0649] Step 1: Preparation of 3-(5-bromo-2-chloropyrimidin-4-yl)-1H-indole

[0650]

[0651] Indole (5.0 g, 54.86 mmol) was dissolved in 2-methyltetrahydrofuran (50 mL) under ice bath, and then methylmagnesium bromide (3.0 M 2-methyltetrahydrofuran solution, 18.3 mL, 54.86 mmol) was added dropwise, and the internal temperature was maintained below 30 ° C. After the addition was completed, the mixture was stirred at room temperature for 30 minutes. Then 2,4-dichloro-5-bromopyrimidine in 2-methyltetrahydrofuran solution (5.0 g, 21.94 mmol, 10 mL solvent) was added dropwise. After the addition was completed, the reaction was stirred at room temperature for half an hour, and then heated to 70 ° C and reacted for 14 hours. After cooling to room temperature, the reaction solution was poured into saturated aqueous ammonium chloride solution, and solid precipitated. The solid was filtered to obtain a solid. The obtained solid was resuspended in water, ultrasonicated, filtered to obtain a solid, and dried to obtain the product 3-(5-bromo-2-chloropyrimidin-4-yl)-1H-indole (4.0 g, yield: 59%, yellow solid).

[0652] MS m / z(ESI):308.0[M+H] + .

[0653] 1H NMR (400MHz, DMSO-d6) δ12.21(s,1H),8.86(s,1H),8.80(s,1H),8.46(d,J=7.2Hz,1H),7.55(d,J=7.2Hz,1H),7.30-7.23(m,2H).

[0654] Step 2: Preparation of 5-bromo-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine

[0655]

[0656] 3-(5-bromo-2-chloropyrimidin-4-yl)-1H-indole (0.50 g, 1.62 mmol), 4-fluoro-2-methoxy-5-nitroaniline (0.33 g, 1.78 mmol) and p-toluenesulfonic acid (0.34 g, 1.78 mmol) were dissolved in 2-pentanol (25 mL) and reacted at 100°C for 14 hours. After cooling to room temperature, the reaction solution was neutralized with saturated sodium bicarbonate solution, stirred at room temperature for 20 minutes, filtered, and the filter cake was washed with 2-pentanol and finally with petroleum ether. The filter cake was dried to obtain 5-bromo-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (0.40 g, 54%, khaki solid).

[0657] MS m / z(ESI):458.0, 460.0[M+H] + .

[0658] Step 3: Preparation of N1-(5-bromo-4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine

[0659]

[0660] 5-Bromo-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (0.40 g, 0.87 mmol) was dissolved in acetonitrile (20 mL), potassium carbonate (0.36 g, 2.61 mmol) and N1,N1,N2-trimethylethane-1,2-diamine (0.10 g, 0.96 mmol) were added, and the reaction was stirred at 80°C for two hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed with saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and dried to obtain N1-(5-bromo-4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (0.40 g, yield: 87%, red solid).

[0661] MS m / z(ESI):540.2, 542.2[M+H] + .

[0662] Step 4: Preparation of N1-(5-bromo-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine

[0663]

[0664] At room temperature, N1-(5-bromo-4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (0.30 g, 0.56 mmol), cesium carbonate (0.13 g, 0.72 mmol) and 3-iodo-oxetane (0.36 g, 1.11 mmol) were dissolved in N,N-dimethylformamide (8 mL), microwaved at 110°C for 1.5 hours, and cooled to room temperature. The reaction solution was diluted with ethyl acetate and filtered. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was separated using a silica gel preparation plate (dichloromethane: methanol: 20:1) to give N1-(5-bromo-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (0.12 g, yield: 36%, red solid).

[0665] MS m / z(ESI):596.0[M+H] + .

[0666] Step 5: Preparation of 2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile

[0667]

[0668] At room temperature, N1-(5-bromo-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (0.12 g, 0.20 mmol), Pd2(dba)3 (18.4 mg, 0.02 mmol), X-Phos (19 mg, 0.04 mmol), zinc cyanide (23.5 mg, 0.20 mmol) and zinc powder (13 mg, 0.20 mmol) were dissolved in N,N-dimethylacetamide (3 mL), replaced with nitrogen, and reacted at 110°C in a microwave for 1.5 hours. The mixture was cooled to room temperature, filtered, and the solid was washed with ethyl acetate. The organic phase was concentrated under reduced pressure and the crude product was separated using a preparative plate (dichloromethane: methanol: 20:1) to give 2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.096 g, yield: 88%, yellow solid).

[0669] MS m / z(ESI):543.1[M+H] + .

[0670] Step 6: Preparation of 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile

[0671]

[0672] 2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.12 g, 0.22 mmol) was dissolved in ethanol (10 mL), and then aqueous ammonium chloride solution (0.06 g, 1.1 mmol, water, 2 mL) and iron powder (0.12 g, 2.2 mmol) were added, and the reaction was stirred at 80 °C for 2 hours. The reaction mixture was cooled to room temperature, filtered, and the filter cake was washed with dichloromethane. The organic solvent was removed under reduced pressure, and the residue was dissolved with dichloromethane and water. The layers were separated, and the aqueous phase was extracted with dichloromethane (20 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and spin-dried to give 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.095 g, yield: 83.8%, yellow oil).

[0673] MS m / z(ESI):513.2[M+H] + .

[0674] Step 7: Preparation of N-(5-((5-cyano-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0675]

[0676] 2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.075 g, 0.146 mmol) was dissolved in dichloromethane (5 mL), cooled to 0°C, triethylamine (0.03 g, 0.292 mmol) was added, and 3-chloropropionyl chloride (0.024 g, 0.19 mmol) was added, and the reaction was stirred at 0°C for 1 hour. After the reaction was completed, the crude product was dried by spin drying, and the crude product was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution, washed with saturated brine, and the organic phase was dried with anhydrous sodium sulfate, filtered, and dried by spin drying. The crude product was dissolved in acetonitrile (5 mL), and then sodium hydroxide aqueous solution (0.058 g, 1.46 mmol, water, 0.5 mL) was added, and the reaction was carried out at 40°C for two hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was purified by preparative chromatography to give N-(5-((5-cyano-4-(1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide (0.04 g, yield: 48%, yellow solid).

[0677] MS m / z(ESI):567.2[M+H] + .

[0678] 1 H NMR(400MHz, CDCl3)δ10.15-9.82(br,1H),9.45(s,1H),8.69(s,2H),8.55 -8.38(br,1H)7.80(s,1H),7.61(d,J=8.0Hz,1H),7.33-7.29(m,2H),6.78( s,1H),6.42-6.38(m,1H),5.72-5.66(m,2H),5.28-5.13(m,5H),3.90(s,3H ),3.13-2.95(br,2H),2.74(s,3H),2.61-2.24(br,6H),1.85-1.53(m,2H).

[0679] Example 3

[0680] N-(5-((5-cyano-4-(1-cyclopropyl-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0681]

[0682] The preparation method of Example 3 refers to that of Example 1.

[0683] MS m / z(ESI):581.4[M+H] + .

[0684] 1 H NMR (400MHz, CDCl3) δ10.04(s,1H),9.38(s,1H),8.66(s,1H),8.40-8.38(m,2H),7.71(s,1H),7.06(s,1H),6.92(s,1H),6.77(s,1H),6.42- 6.38(m,1H),5.71-5.68(m,1H),3.91-3.89(m,6H),3.41-3.40(m,1H), 3.10-2.90(m,3H),2.74(s,3H),2.70-2.30(m,8H),1.16-1.10(m,4H).

[0685] Example 4

[0686] N-(5-((5-cyano-4-(1-cyclopropyl-6-fluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0687]

[0688] The preparation method of Example 4 refers to that of Example 1.

[0689] MS m / z(ESI):569.4[M+H] + .

[0690] 1 H NMR (400MHz, CDCl3) δ10.03–9.64(m,1H),9.48–9.26(m,1H),8.66(s,1H),8. 54–8.33(m,2H),7.73(s,1H),7.12–6.92(m,1H),6.76(s,1H),6.38(d,J=17.0 Hz,1H),5.70(d,J=11.4Hz,1H),3.90(s,3H),3.48–3.35(m,1H),3.18–2.98( m,2H),2.74(s,3H),2.71–2.31(m,6H),2.12–1.47(m,4H),1.22–1.02(m,4H).

[0691] Example 5

[0692] N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-6-methoxypyridin-3-yl)acrylamide

[0693]

[0694]

[0695] Step 1: Preparation of 6-chloro-2-methoxypyridin-3-amine

[0696]

[0697] 6-Chloro-2-methoxy-3-nitropyridine (5 g, 26.6 mmol) was dissolved in ethanol (100 mL) and water (30 mL), and ammonium chloride (7.0 g, 133 mmol) was added, and iron powder (7.5 g, 133 mmol) was added in batches, and the reaction was stirred at 85°C for 2 hours. The reaction solution was cooled to room temperature, filtered through diatomaceous earth, and ethyl acetate (150 mL) and saturated brine (120 mL) were added to the filtrate, and the organic layer was separated, dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain 6-chloro-2-methoxypyridine-3-amine (4 g, yield: 95%) as a brown solid.

[0698] MS m / z(ESI):159.1[M+H] + .

[0699] Step 2: Preparation of N-(6-chloro-2-methoxypyridin-3-yl)acetamide

[0700]

[0701] Dissolve 6-chloro-2-methoxypyridin-3-amine (4.0 g, 25.0 mmol) in dichloromethane (100 mL), add diisopropylethylamine (4.8 g, 37.5 mmol), cool to 0°C, add acetyl chloride (2.4 g, 30.0 mmol), and continue stirring for 2 hours. The reaction solution is washed with 80 mL of water, 80 mL of 1N hydrochloric acid and 80 mL of saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain N-(6-chloro-2-methoxypyridin-3-yl)acetamide (4.0 g, yield: 79%) as a brown solid.

[0702] MS m / z(ESI):201.1[M+H] + .

[0703] Step 3: Preparation of N-(6-chloro-2-methoxy-5-nitropyridin-3-yl)acetamide

[0704]

[0705] Dissolve 6-chloro-2-methoxypyridin-3-amine (2.0 g, 10.0 mmol) in trifluoroacetic anhydride (20 mL), cool to -10 ° C, add fuming nitric acid (0.5 mL, 10 mmol) dropwise, and continue stirring for 2 hours. Add crushed ice to the reaction solution, extract with dichloromethane (50 mL), dry with anhydrous sodium sulfate, filter, and spin dry to obtain N-(6-chloro-2-methoxy-5-nitropyridin-3-yl)acetamide (1.6 g, yield: 65%) as a brown solid.

[0706] MS m / z(ESI):244.1[MH] + .

[0707] Step 4: Preparation of N-(6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitropyridin-3-yl)acetamide

[0708]

[0709] N-(6-chloro-2-methoxy-5-nitropyridin-3-yl)acetamide (1.6 g, 6.5 mmol) was dissolved in acetonitrile (30 mL), and N1,N1,N2-trimethylethane-1,2-diamine (1 g, 9.8 mmol) was added, and the reaction was stirred at 80°C for 3 hours. The solvent was dried by rotary evaporation, and the crude product was purified by column chromatography (dichloromethane / methanol: 100 / 1 to 10 / 1) to obtain N-(6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitropyridin-3-yl)acetamide (0.9 g, yield: 45%) as a brown solid.

[0710] MS m / z(ESI):312.1[M+H] + .

[0711] Step 5: Preparation of N2-(2-(dimethylamino)ethyl)-6-methoxy-N2-methyl-3-nitropyridine-2,5-diamine

[0712]

[0713] N-(6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitropyridine-3-yl)acetamide (0.9 g, 2.9 mmol) was dissolved in methanol (30 mL) and concentrated hydrochloric acid (5 mL), and the reaction was stirred at 60°C for 3 hours. The solvent was dried by rotary evaporation, and dichloromethane (50 mL) and saturated sodium bicarbonate (50 mL) were added and stirred until no bubbles were precipitated. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation. The crude product was purified by column chromatography (dichloromethane / methanol: 100 / 1 to 10 / 1) to obtain N2-(2-(dimethylamino)ethyl)-6-methoxy-N2-methyl-3-nitropyridine-2,5-diamine (0.15 g, yield: 19%) as a brown solid.

[0714] MS m / z(ESI):270.1[M+H] + .

[0715] Step 6: Preparation of 4-(1-cyclopropyl-1H-indol-3-yl)-2-((6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitropyridin-3-yl)amino)pyrimidine-5-carbonitrile

[0716]

[0717] N2-(2-(Dimethylamino)ethyl)-6-methoxy-N2-methyl-3-nitropyridine-2,5-diamine (0.11 g, 0.41 mmol), 2-chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (0.12 g, 0.41 mmol), tris(dibenzylideneacetone)dipalladium (0.18 g, 0.2 mmol), x-phos (0.2 g, 0.41 mmol), sodium tert-butoxide (0.12 g, 1.2 mmol) were dissolved in dioxane (5 mL), nitrogen was replaced, and the reaction was stirred at 140 ° C in a microwave for 1 hour. The reaction mixture was cooled to room temperature, filtered, and the filtrate was dried by rotary evaporation. The crude product was separated by prep-TLC (dichloromethane / methanol: 20 / 1) to give 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (0.1 g, yield: 47%) as a yellow solid.

[0718] MS m / z(ESI):528.1[M+H] + .

[0719] Step 7: Preparation of 2-((5-amino-6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxypyridin-3-yl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile

[0720]

[0721] 4-(1-Cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile (80 mg, 0.15 mmol) was dissolved in methanol (10 mL), and Raney nickel (80 mg) and 85% hydrazine hydrate (90 mg, 1.5 mmol) were added at 0°C, and the reaction was stirred at room temperature for 2 hours. The reaction solution was filtered, the filtrate was dried by rotary evaporation, water (15 mL) was added, and the mixture was extracted with dichloromethane (15 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation to give 2-((5-amino-6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxypyridin-3-yl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (80 mg, yield: 100% crude) as a brown solid.

[0722] MS m / z(ESI):498.1[M+H] + .

[0723] Step 8: Preparation of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-6-methoxypyridin-3-yl)acrylamide

[0724]

[0725] 2-((5-amino-6-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxypyridin-3-yl)amino)-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidine-5-carbonitrile (80 mg, 0.16 mmol) was dissolved in dichloromethane (10 mL), cooled to 0°C, triethylamine (24 mg, 0.24 mmol) was added, and 3-chloropropionyl chloride (25 mg, 0.19 mmol) was added, and the reaction was stirred at 0°C for 1 hour. Water (10 mL) was added, and the mixture was extracted with dichloromethane (10 mL x 2), and the organic phase was dried over anhydrous sodium sulfate, filtered, and dried by rotation. Tetrahydrofuran (5 mL) was added, and a solution of sodium hydroxide (64 mg, 1.6 mmol) in water (0.5 mL) was added, and the reaction was stirred at 40°C overnight. Water (10 mL) was added, extracted with ethyl acetate (10 mL x 2), the organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was separated by prep-HPLC to give N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-6-methoxypyridin-3-yl)acrylamide (0.9 mg, yield: 0.7%) as a yellow solid.

[0726] MS m / z(ESI):552.1[M+H] + .

[0727] Example 6

[0728] N-(5-((5-cyano-4-(1-cyclopropyl-5-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0729]

[0730] The preparation method of Example 6 refers to Example 1.

[0731] MS m / z(ESI):581.4[M+H] + .

[0732] 1H NMR (400MHz, CDCl3) δ10.08–9.55(m,1H),9.42(s,1H),8.68(s,1H),8.44(s,1H),8 .03(s,1H),7.76(s,1H),7.51(d,J=8.6Hz,1H),6.97(d,J=8.6Hz,1H),6.77(s,1H) ,6.39(d,J=15.7Hz,1H),5.69(d,J=10.5Hz,1H),3.89(s,6H),3.51–3.38(m,1H),3 .03(s,2H),2.73(s,3H),2.65–2.18(m,6H),1.89–1.54(m,3H),1.23–1.04(m,4H).

[0733] Example 7

[0734] N-(5-((5-cyano-4-(1-cyclopropyl-7-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0735]

[0736] The preparation method of Example 7 refers to Example 1.

[0737] MS m / z(ESI):581.3[M+H] + .

[0738] 1 H NMR(400MHz,Chloroform-d)δ10.32–9.79(m,1H),9.56–9.18(m,1H),8.80–8. 55(m,1H),8.47–8.27(m,1H),8.24–7.97(m,1H),7.88–7.61(m,1H),7.22–7.0 4(m,1H),6.89–6.68(m,2H),6.56–6.21(m,2H),5.83–5.55(m,1H),4.20–3.77 (m,7H),3.16–2.81(m,2H),2.73(s,3H),2.59–2.15(m,8H),1.19–1.02(m,4H).

[0739] Example 8

[0740] N-(5-((5-cyano-4-(1-cyclopropyl-4-fluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0741]

[0742] The preparation method of Example 8 refers to Example 1.

[0743] MS m / z(ESI):569.2[M+H] + .

[0744] 1 H NMR(400MHz,DMSO-d6)δ10.22(s,1H),8.90(s,1H),8.75(s,1H),8.69(s,1H),8.27(s ,1H),7.48(d,J=7.6Hz,1H),7.28-7.23(m,1H),7.09(s,1H),6.92-6.87(m,1H),6.46- 6.39(m,1H),6.30-6.26(m,1H),5.78(d,J=9.6Hz,1H),3.84(s,3H),3.61-3.52(m,1H ),2.96-2.92(m,2H),2.75(s,3H),2.37-2.29(m,2H),2.22(s,6H),1.16-1.04(m,4H).

[0745] Example 9

[0746] N-(5-((5-cyano-4-(1-cyclopropyl-5-fluoro-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0747]

[0748] The preparation method of Example 9 refers to that of Example 1.

[0749] MS m / z(ESI):599.2[M+H] + .

[0750] 1H NMR(400MHz,DMSO-d6)δ10.06(s,1H),9.54(s,1H),8.66(s,1H),8.38(s,1H),8.32(s,1H),7. 75–7.55(m,1H),7.27–7.25(m,1H),7.05(s,1H),6.41–6.34(m,1H),6.17(d,J=16.9Hz,1H),5. 72(d,J=10.3Hz,1H),3.91(s,3H),3.72(s,3H),3.63–3.54(m,1H),2.90–2.88(m,2H),2.75(s, 3H),2.63–2.56(m,1H),2.37–2.35(m,2H),2.21(s,5H),1.18–1.16(m,2H),1.04–0.93(m,2H).

[0751] Example 10

[0752] N-(5-((5-cyano-4-(6-methoxy-1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0753]

[0754] The preparation method of Example 10 refers to Example 2.

[0755] MS m / z(ESI):597.2[M+H] + .

[0756] 1 H NMR(400MHz,DMSO-d6)δ10.29-10.22(br,1H),9.42(s,1H),8.67(s,1H),8.59(m,1 H),8.34(s,1H),7.77(s,1H),7.08(s,1H),6.97-6.88(br,1H),6.79(s,1H),6.39( d,J=14.4Hz,1H),5.72-5.69(m,1H),5.61-5.58(m,1H),5.20(d,J=6.4Hz,4H),3.9 0(s,6H),3.06-2.84(br,3H),2.74(s,3H),2.50-2.16(br,6H),1.69-1.50(br,2H).

[0757] two, Biological test evaluation

[0758] The present invention is further described and explained below in conjunction with test examples, but these embodiments are not intended to limit the scope of the present invention.

[0759] 1. Enzyme test

[0760] Test Example 1: Determination of the inhibitory effect of the compounds of the present invention on the kinase activity of EGFR exon 20 insertion mutation

[0761] Purpose of the experiment: The purpose of this test case is to measure the ability of the compound to inhibit the kinase activity of EGFR exon 20 insertion mutation.

[0762] Experimental instruments: centrifuge (Eppendorf 5810R), microplate reader (BioTek Synergy H1), pipette (Eppendorf&Rainin)

[0763] Experimental method: This experiment uses the TR-FRET (time-resolved fluorescence resonance energy transfer) method to study the inhibitory activity of compounds on EGFR exon 20 insertion mutant kinase. This experiment was carried out in a 384-well plate, and the experimental buffer (50mM HEPES, 1mM EGTA, 10mM MgCl2, 2mM DTT, 0.01% Tween-20) was prepared. The compound was gradient diluted to different concentrations using the experimental buffer, and 2.5μL was added to each well of the 384-well plate, and then 2.5μL of the diluted EGFR kinase solution (0.001-0.5nM) was added, incubated at room temperature for 10 minutes, 5μL of ULight-poly GT / ATP mixed solution was added, and incubated at room temperature for 30 minutes to 60 minutes, 5μL of EDTA was added to terminate the reaction and 5μL of Eu-labeled antibody detection solution was added, and incubated at room temperature for 1 hour. The 665nm fluorescence signal value of each plate well was measured by an enzyme reader.

[0764] Experimental data processing method:

[0765] The inhibition rate was calculated using the fluorescence signal value at 665 nm ((positive control well value - sample well value) / (positive control well value - negative control well value)) * 100%, and the concentration and inhibition rate were fitted with a nonlinear regression curve using Graphpad Prism software to obtain the IC 50 The specific data are shown in Table 2.1 below:

[0766] Table 2.1 IC inhibitory activity of compounds against EGFR exon 20 insertion mutation kinase 50

[0767]

[0768] Experimental conclusion:

[0769] Through the above scheme, it is concluded that the example compounds of the present invention have a good inhibitory effect in the EGFR 20 exon insertion mutation kinase activity inhibition experiment.

[0770] Test Example 2: Determination of the inhibitory effect of the compounds of the present invention on the EGFR wild-type kinase activity

[0771] Purpose of the experiment: The purpose of this test case is to measure the inhibitory ability of the compound on the wild-type kinase activity of EGFR.

[0772] Experimental instruments: centrifuge (Eppendorf 5810R), microplate reader (BioTek Synergy H1), pipette (Eppendorf&Rainin)

[0773] Experimental method: This experiment uses the TR-FRET (time-resolved fluorescence resonance energy transfer) method to study the inhibitory activity of compounds on EGFR wild-type kinase. This experiment was carried out in a 384-well plate, and the experimental buffer (50mM HEPES, 1mM EGTA, 10mM MgCl2, 2mM DTT, 0.01% Tween-20) was prepared. The compound was gradient diluted to different concentrations using the experimental buffer, and 2μL was added to each well of the 384-well plate, and then 4μL of the diluted EGFR kinase solution (0.001-0.5nM) was added, incubated at room temperature for 10 minutes, 4μL of ULight-poly GT / ATP mixed solution was added, incubated at room temperature for 30 minutes to 60 minutes, 5μL of ETA was added to terminate the reaction and 5μL of Eu-labeled antibody detection solution was added, incubated at room temperature for 1 hour, and the 665nm fluorescence signal value of each plate well was measured by an enzyme reader.

[0774] Experimental data processing method:

[0775] The inhibition rate was calculated using the fluorescence signal value at 665 nm ((positive control well value - sample well value) / (positive control well value - negative control well value)) * 100%, and the concentration and inhibition rate were fitted with a nonlinear regression curve using Graphpad Prism software to obtain the IC 50 The specific data are shown in Table 2.2 below:

[0776] Table 2.2 IC inhibitory activity of compounds on EGFR wild-type kinase 50

[0777]

[0778] Experimental conclusion:

[0779] The above scheme shows that the example compounds of the present invention have a small inhibitory effect in the EGFR wild-type kinase inhibition test.

[0780] Test Example 3: Determination of the inhibitory effect of the compounds of the present invention on the proliferation of Ba / F3 EGFR mutant cell lines and A431 cell lines

[0781] Experimental purpose: The purpose of this test case is to measure the inhibitory effect of the compound on the proliferation activity of Ba / F3EGFR mutant cell line and A431 cell line.

[0782] Experimental instruments: ELISA reader (BioTek Synergy H1), pipette (Eppendorf & Rainin)

[0783] Experimental methods:

[0784] When Ba / F3EGFR mutant cells were cultured to an appropriate density, the cells were collected and adjusted to an appropriate cell concentration using complete culture medium. The cell suspension was plated on a 96-well plate at 90 μL per well and placed in a 37°C, 5% CO2 incubator to adhere overnight. Compound solutions of different concentrations were prepared using DMSO and culture medium, and a solvent control was set. The compound solution was added to a 96-well plate at 10 μL per well and placed in a 37°C, 5% CO2 incubator for continued culture for 72 h to 144 h. Then, the CellTiter-Glo solution was added, the plate was shaken to mix evenly, incubated in the dark for 10 minutes, and read using a BioTek Synergy H1 microplate reader.

[0785] Experimental methods:

[0786] When A431 cells were cultured to an appropriate density, the cells were collected and adjusted to an appropriate cell concentration using complete culture medium. The cell suspension was plated on a 96-well plate at 90 μL per well and placed in a 37°C, 5% CO2 incubator to adhere overnight. Compound solutions of different concentrations were prepared using DMSO and culture medium, and a solvent control was set. The compound solution was added to a 96-well plate at 10 μL per well and placed in a 37°C, 5% CO2 incubator for continued culture for 72 hours. Then, the CellTiter-Glo solution was added, shaken to mix evenly, incubated in the dark for 10 minutes, and read using a BioTek Synergy H1 microplate reader.

[0787] Experimental data processing method:

[0788] The inhibition rate was calculated using the luminescence signal value, and the concentration and inhibition rate were fitted with a nonlinear regression curve using Graphpad Prism software to obtain the IC 50 The specific data are shown in Table 2.3 below:

[0789] Table 2.3 IC inhibitory activity of compounds on Ba / F3 EGFR mutant cell line and A431 cell line 50

[0790]

[0791] Experimental conclusion:

[0792] Through the above scheme, it is concluded that the example compounds of the present invention have a good inhibitory effect in the inhibition test of the proliferation activity of Ba / F3EGFR mutant cells, and have a poor inhibitory effect on A431 cells. Comparative data show that the series of examples of the present invention have high selectivity in inhibiting the proliferation activity of Ba / F3EGFR mutant cells.

[0793] Test Example 4: In vivo pharmacodynamic study of the compounds of the present invention on the mouse primary B cell Ba / F3EGFR-D770-N771ins_SVD transplanted tumor model

[0794] 4.1 Experimental Purpose:

[0795] The in vivo efficacy of the compounds was evaluated in the mouse primary B cell Ba / F3EGFR-D770-N771ins_SVD transplant tumor model.

[0796] 4.2 Experimental instruments and reagents:

[0797] 4.2.1 Instruments:

[0798] 1. Biological safety cabinet (BSC-1300II A2, Shanghai Boxun Industrial Co., Ltd. Medical Equipment Factory)

[0799] 2. Clean bench (CJ-2F, Suzhou Fengshi Experimental Animal Equipment Co., Ltd.)

[0800] 3. CO2 incubator (Thermo-311, Thermo)

[0801] 4. Centrifuge (Centrifuge 5720R, Eppendorf)

[0802] 5. Fully automated cell counter (Countess II, Life Technologies)

[0803] 6. Vernier caliper (CD-6" AX, Mitutoyo, Japan)

[0804] 7. Cell culture flask (T75 / T225, Corning)

[0805] 8. Electronic balance (CPA2202S, Sartorius)

[0806] 9. Electronic balance (BSA2202S-CW, Sartorius)

[0807] 4.2.2 Reagents:

[0808] 1. RPMI-1640 medium (22400-089, Gibco)

[0809] 2. Fetal bovine serum (FBS) (10099-141C, Gibco)

[0810] 3. Phosphate buffered saline (PBS) (10010-023, Gibco)

[0811] 4. Tween 80 (30189828, Sinopharm Reagents)

[0812] 5. Sodium carboxymethyl cellulose (30036365, Sinopharm Reagent)

[0813] 4.3 Experimental operation and data processing:

[0814] 4.3.1 Animals

[0815] BALB / c nude mice, 6-8 weeks old, ♀, were purchased from Shanghai Xipu-Bikai Experimental Animal Co., Ltd.

[0816] 4.3.2 Cell culture and cell suspension preparation

[0817] a. Take out a strain of Ba / F3EGFR-D770-N771ins_SVD cells from the cell bank, resuscitate the cells with RPMI-1640 medium (RPMI-1640 + 10% FBS), place the resuscitated cells in a cell culture bottle (mark the cell type, date, name of the culturer, etc. on the bottle wall) and culture them in a CO2 incubator (the incubator temperature is 37°C and the CO2 concentration is 5%).

[0818] b, The cells were subcultured every three days, and then continued to be cultured in a CO2 incubator. This process was repeated until the cell number met the in vivo efficacy requirements.

[0819] c. Collect the cultured cells, count them using an automatic cell counter, and resuspend the cells in PBS according to the counting results to make a cell suspension (density 2×10 7 / mL) and placed in an ice box for later use.

[0820] 4.3.3 Cell seeding

[0821] a. Before inoculation, nude mice were marked with disposable ear tags for both large and small mice.

[0822] b. Mix the cell suspension during inoculation, draw 0.1-1mL of cell suspension with a 1mL syringe, remove bubbles, and then place the syringe on an ice pack for later use.

[0823] c. Secure the nude mouse with your left hand, and disinfect the right side of the nude mouse's back near the right shoulder (inoculation site) with 75% alcohol. Start inoculation after 30 seconds.

[0824] d. The experimental nude mice were inoculated sequentially (0.1 mL of cell suspension was inoculated per mouse).

[0825] 4.3.4 Tumor measurement, grouping, and drug administration in tumor-bearing mice

[0826] a, Depending on tumor growth, tumors were measured and their sizes were calculated on days 8-14 after inoculation.

[0827] Tumor volume calculation: Tumor volume (mm 3 ) = length (mm) × width (mm) × width (mm) / 2

[0828] b, Tumor-bearing mice were randomly divided into groups according to their weight and tumor size, with 5 mice in each group.

[0829] c. According to the grouping results, the test drug was started to be administered (administration method: oral administration; administration frequency: once / day; administration cycle: 14 days; solvent: 0.5% CMC / 1% Tween 80).

[0830] d, Tumors were measured and weighed twice a week after the start of the test drug administration.

[0831] e, Animals were euthanized after the experiment.

[0832] f. Use Excel and other software to process data.

[0833] Calculation of compound tumor inhibition rate TGI (%):

[0834] TGI (%) = [(1-average tumor volume of a certain treatment group at the end of drug administration) / average tumor volume of the solvent control group at the end of treatment] × 100%.

[0835] TGI ≥ 60%, the compound is effective in this model;

[0836] With a TGI < 60%, the compound is ineffective in this model.

[0837] 4.4 The test results are shown in Table 2.4:

[0838] Table 2.4 Pharmacodynamic parameters of compounds in transplanted tumor mice

[0839]

[0840] Note: The data in brackets indicate that the example corresponds to the tumor volume of the Vehicle QD x 2w group (i.e., control group) at the corresponding time.

[0841] 4.5 Experimental Results

[0842] The above data show that after continuous oral administration for 14 days, AZD9291 40 mpk is ineffective in the Ba / F3EGFR-D770-N771ins_SVD pharmacodynamic model, while Example 1 is effective at the same dose of 40 mpk.

[0843] Test Example 5: Plasma Stability Test Protocol

[0844] 5.1 Experimental Purpose

[0845] The purpose of this experiment is to detect the stability of the example compounds in mouse, rat and human plasma.

[0846] 5.2 Experimental procedures

[0847] 5.2.1 Solution preparation

[0848] 1. Plasma preparation: After whole blood is collected from animals or humans, it is placed in a test tube containing an anticoagulant, centrifuged at 3500rpm for 10min, and the upper light yellow plasma is collected.

[0849] 2. 1 mM test compound (m / M / V=C), weigh the compound and prepare the stock solution with DMSO.

[0850] 5.2.2 Experimental process:

[0851] 1. In a 96-well plate, add 398 μL of plasma and 2 μL of 1 mM compound (test compound) in sequence and incubate at 37°C.

[0852] 2. Take out 50 μL at 0, 15, 30, 60, and 120 min respectively, and add 400 μL of methanol stop solution containing internal standard.

[0853] 3. After centrifugation (3220 g, 30 min), take 50 μL of supernatant, add 50 μL of DD H2O to dilute and then inject into LC-MS / MS.

[0854] 5.3 Chromatographic conditions

[0855] Instrument: Shimadzu LC-30AD (Nexera X2)

[0856] Column: XSelect HSS T3C 18 (50*2.1mm, 2.5μm particle size);

[0857] Mobile Phase:

[0858] A: 0.1% formic acid solution,

[0859] B: Acetonitrile containing 0.1% formic acid,

[0860] 0~0.3min: 95%A→95%A;

[0861] 0.3~0.8min: 95%A→5%A;

[0862] Flow rate: 0.5 mL / min;

[0863] Running time: 2.0min;

[0864] Injection volume: 3 μL.

[0865] 5.4 Mass spectrometry conditions

[0866] instrument:

[0867] API4000 liquid chromatography-mass spectrometer, AB Company, USA;

[0868] The ion source was electrospray ionization (ESI);

[0869] Drying gas (N2) temperature 500°C;

[0870] The electrospray voltage was 5500 V;

[0871] The detection method is positive ion detection;

[0872] The scanning mode was selected reaction monitoring (MRM);

[0873] Table 2.5 Plasma stability results of Example Compound 1

[0874]

[0875] 5.5 Experimental conclusion:

[0876] The above data show that the plasma stability of Example Compound 1 of the present invention is high and the species difference is small.

[0877] 3. Study on the salts and crystal forms of compounds

[0878] It is well known to those skilled in the art that when the above-mentioned example compounds are proven to have significant pharmacological and pharmacodynamic activity in inhibiting EGFR and / or HER2 exon 20 insertion mutants, their pharmaceutically acceptable salts often have the same pharmacological and pharmacodynamic activity. On this basis, the inventors further studied the physicochemical properties of the salt forms and crystal forms of the corresponding compounds, but the preparation and characterization of the following specific salt forms or crystal forms do not represent a limitation on the scope of protection of the present invention. Those skilled in the art can obtain more salt forms and crystals of the compounds of the present invention based on the present invention through conventional salt formation or crystallization methods, and these salt forms and crystals are all solutions protected by the present invention. Specifically as follows:

[0879] 1. Experimental instruments

[0880] 1.1 Some parameters of physical and chemical testing instruments

[0881]

[0882] 2. Research on salt forms of compounds

[0883] 2.1 Experimental Purpose:

[0884] The salt form of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide was screened.

[0885] 2.2 Experimental steps:

[0886] (1) Instruments and equipment

[0887] name model source Analytical Balance XA105 METTLER TOLEDO Ultrasonic Cleaner SK5200LHC Shanghai Kedao Ultrasound Instrument Pipette Eppendorf (5mL, 100μL) Eppendorf

[0888] (2) Salt-forming step

[0889] 1) Using ethyl acetate as solvent for dissolution or suspension to form salt crystals

[0890] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of ethyl acetate, and add different counter ion acid solutions (base:acid=1:1.2 molar reaction ratio) at 50°C to react. The results are as follows:

[0891]

[0892] Note: N / A means not tested

[0893] 2) Using toluene as solvent for dissolution or suspension to form salt

[0894] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, and add different counter ion acid solutions (base:acid=1:1.2 molar reaction ratio) at 50°C to react. The results are as follows:

[0895]

[0896] Note: N / A means not tested

[0897] As described above, those skilled in the art can obtain more pharmaceutically acceptable salts by using conventional methods based on the present invention.

[0898] In addition, those skilled in the art can refer to the above method for preparing N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide salt to prepare other compounds including N-(5-((5-cyano-4-(6-methoxy-1-(oxetan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide salt. )acrylamide, N-(5-((5-cyano-4-(1-cyclopropyl-5-fluoro-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)-5-(oxazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide.

[0899] 3. Study on the crystal form of compound salts

[0900] 3.1 Study on the Crystalline Form of the Salt of Compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0901] 3.1.1 Experimental Purpose:

[0902] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide was screened for its crystalline salt.

[0903] 3.1.2 Experimental steps:

[0904] 1) Instruments and equipment

[0905] name model source Analytical Balance BSA224S-CW Sartorius Ultrasonic Cleaner SK5200LHC Shanghai Kedao Ultrasound Instrument Pipette Eppendorf (50mL, 1000μL) Eppendorf

[0906] 2) Study on the crystal form of salt

[0907] ①Use acetone and acetonitrile as solvents for dissolution or suspension to form salt crystals

[0908] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of acetone or acetonitrile, and add different counter ion acid solutions (base: acid = 1:1.2 molar reaction ratio) at 50°C to react. The results are as follows:

[0909]

[0910] Note: N / A indicates that the product is an oil and has not been further characterized.

[0911] ②Use methanol as solvent for dissolution or suspension to form salt crystals

[0912] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of methanol, and add different counter ion acid solutions (base: acid = 1:1.2 molar reaction ratio) at 50°C to react. The results are as follows:

[0913]

[0914] Note: N / A indicates that the product is an oil and has not been further characterized.

[0915] ③ Use 2-methyl-tetrahydrofuran and other solvents for dissolution or suspension to form salt crystals

[0916] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of 2-methyl-tetrahydrofuran, ethanol and anisole as reaction solvents, add different counter ion acid liquids or solids in molar ratio (base: acid = 1:1.2 molar reaction ratio) at 50°C for reaction, the results are as follows:

[0917]

[0918] Note: N / A indicates that the product is an oil and has not been further characterized.

[0919] 3.1.3 Experimental Results

[0920] Through the salt crystal screening experiment, and based on the salt crystallinity and the difficulty of the crystallization process, hydrochloride, hydrobromide, p-toluenesulfonate and benzoylglycine salt are the most advantageous.

[0921] 3.2 Crystalline Screening of the Salt of Compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0922] 3.2.1 Experimental Purpose:

[0923] Screening of the crystalline form of the salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

[0924] 3.2.2 Experimental steps:

[0925] (1) Instruments and equipment

[0926] name model source Analytical Balance BSA224S-CW Sartorius Ultrasonic Cleaner SK5200LHC Shanghai Kedao Ultrasound Instrument Pipette Eppendorf (50mL, 1000μL) Eppendorf

[0927] (2) Operation procedures

[0928] I. Preparation of Compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide Free Base Crystalline Form A

[0929]

[0930] 4-(1-cyclopropyl-1H-indol-3-yl)-2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidine-5-carbonitrile 66.0 g and tetrahydrofuran 660 mL were added to a 2 L three-necked flask; palladium carbon (6.6 g) was added and N2 was bubbled under the liquid surface for half an hour; hydrogen was replaced 3 times, heated to 35-40° C. and reacted for 20 h-24 h, filtered, the filter cake was washed with tetrahydrofuran (100 mL), the N2 protected filtrate was filtered, the temperature was lowered to 0-5° C., triethylamine (12.6 g) was added; the mixture was stirred for 3 hours; the mixture was stirred for 5 hours; the mixture was stirred for 1 hour; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 5 hours; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 2 hours; the mixture was stirred for 3 hours; the mixture was stirred for 4 ... To the reaction mixture, a solution of 3-chloropropionyl chloride (23.7 g) in tetrahydrofuran (120 mL) was added dropwise at a temperature of 0-5° C. The addition was completed in about 45 minutes. The reaction was maintained at a temperature of 0-5° C. for 2 to 3 hours, and the mixture was filtered. The filter cake was washed with tetrahydrofuran (100 mL) and then rinsed with 100 ml of n-heptane to obtain N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)3-chloropropionamide hydrochloride (98.9 g, yield 100%).

[0931] 50.0 g of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)3-chloropropionamide hydrochloride and 420 mL of THF were added to a 2L three-necked flask and stirred; 42 mL of an aqueous solution of 42.0 g of potassium hydroxide was added dropwise, and the addition was completed over about 10 minutes, and the mixture was stirred at room temperature for 30 minutes; the temperature was raised to 35-40° C. and the reaction was carried out for 1 hour, and the reaction of the raw materials was complete; the mixture was cooled to room temperature, 500 mL of water was added, and the mixture was allowed to stand for stratification after stirring for 10 minutes, and the organic phase was retained. The aqueous phase was extracted with 300 mL of 2-methyltetrahydrofuran; the organic phases were combined and washed with 200 mL of water and 200 mL of saturated brine in sequence; 2.5 g of activated carbon and 25 g of anhydrous sodium sulfate were added to the organic phase, and the mixture was stirred at room temperature (20±5° C.) for 1 hour; the filtrate was concentrated to 40° C. The reaction mixture was concentrated to give about 70 g of a yellow solid, 150 mL of 2-methyltetrahydrofuran was added, the mixture was heated to 80° C. and refluxed, heated and stirred for 1 hour, and cooled naturally to room temperature; cooled in an ice bath (0-5° C.), stirred for 1 hour, filtered, and the filter cake was washed with 2-methyltetrahydrofuran (50 ml) to give the target product, N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, Form A (24.0 g, yield 69.7%). After detection and analysis, the product had the following properties: Fig.32 XRPD pattern shown.

[0932] 1) Preparation of Hydrochloride Form A

[0933] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of acetonitrile, heat and stir at 50°C, slowly add 22 μL of 1.0M methanol solution of hydrochloric acid to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain hydrochloride form A. After detection and analysis, it has the following characteristics: Figure 1 The XRPD pattern shown in Figure 2 The DSC diagram shown and Figure 3 TGA graph shown.

[0934] 2) Preparation of Hydrobromide Form A

[0935] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of acetone, heat and stir at 50°C, slowly add 22 μL of 1.0M methanol solution of hydrobromic acid to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain hydrobromide salt form A. After detection and analysis, it has the following characteristics: Figure 4 The XRPD pattern shown in Figure 5 The DSC diagram shown and Figure 6 TGA graph shown.

[0936] 3) Preparation of p-toluenesulfonate Form A

[0937] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of ethyl acetate, heat and stir at 50°C, slowly add 22 μL of 1.0M p-toluenesulfonic acid methanol solution to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain p-toluenesulfonate salt form A. After detection and analysis, it has the following characteristics: Figure 7 The XRPD pattern shown in Figure 8 The DSC diagram shown and Fig. 9 TGA graph shown.

[0938] 4) Preparation of Sulfate Crystal Form A

[0939] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of ethyl acetate, heat and stir at 50°C, slowly add 22 μL of 1.0M sulfuric acid methanol solution to the system, and a large amount of solid precipitates after oil formation. After centrifugation and vacuum drying, sulfate form A is obtained. After detection and analysis, it has the following characteristics: Fig.10 XRPD pattern shown.

[0940] 5) Preparation of Fumarate Crystalline Form A

[0941] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of methanol, heat and stir at 50°C, slowly add 88 μL of 0.25M fumaric acid ethanol solution to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain fumarate salt form A. After detection and analysis, it has the following characteristics: Fig.11 XRPD pattern shown.

[0942] 6) Preparation of Oxalate Form A

[0943] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 22 μL of 1.0M oxalic acid methanol solution to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain oxalate form A. After detection and analysis, it has the following characteristics: Fig.12 XRPD pattern shown.

[0944] 7) Preparation of Benzoylglycine Salt Form A

[0945] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 110 μL of 0.2M benzoylglycine ethanol solution to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain benzoylglycine salt form A. After detection and analysis, it has the following characteristics: Fig.13 XRPD pattern shown.

[0946] 8) Preparation of Benzoylglycine Salt Form B

[0947] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of 2-methyl-tetrahydrofuran, heat and stir at 50°C, slowly add 110 μL of 0.2M benzoylglycine ethanol solution to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain benzoylglycine salt form B. After detection and analysis, it has the following characteristics: Fig.14 XRPD pattern shown.

[0948] 9) Preparation of Benzoylglycine Salt Form C

[0949] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M benzoylglycine 2-methyl-tetrahydrofuran solution to the system, heat and stir at 50°C, the suspension changes from yellow to white, centrifuge and vacuum dry to obtain benzoylglycine salt form C. After detection and analysis, it has the following characteristics: Fig.15 XRPD pattern shown.

[0950] 10) Preparation of Benzoylglycine Salt Form D

[0951] Weigh 10 mg of benzoylglycine salt form C, add 100 μL of methanol to the system, slurry at 50°C for 1 week, centrifuge and vacuum dry to obtain benzoylglycine salt form D. After detection and analysis, it has the following characteristics: Fig.16 The XRPD pattern shown, the DSC pattern shown in Figure 2917 and the TGA pattern shown in Figure 3018.

[0952] 11) Preparation of Benzoylglycine Salt Form E

[0953] Weigh 10 mg of benzoylglycine salt form C, add 100 μL of acetone to the system, slurry at 25°C for 1 week, centrifuge and vacuum dry to obtain benzoylglycine salt form E. After detection and analysis, it has the following characteristics: Fig.19 XRPD pattern shown.

[0954] 12) Preparation of Benzoylglycine Salt Form F

[0955] Weigh 10 mg of benzoylglycine salt form C, add 100 μL of dichloromethane to the system, slurry at 25°C for 1 week, centrifuge and vacuum dry to obtain benzoylglycine salt form F. After detection and analysis, it has the following characteristics: Fig. 20 XRPD pattern shown.

[0956] 13) Preparation of Phosphate Crystalline Form A

[0957] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of ethyl acetate, heat and stir at 50°C, slowly add 22 μL of 1.0M phosphoric acid methanol solution to the system, and a small amount of solid precipitates after oil formation. After centrifugation and vacuum drying, phosphate form A is obtained. After detection and analysis, it has the following characteristics: Fig.21 XRPD pattern shown.

[0958] 14) Preparation of Maleate Crystalline Form A

[0959] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of ethyl acetate, heat and stir at 50°C, slowly add 22 μL of 1.0M methanol solution of maleic acid to the system, suspend, stir overnight, centrifuge and vacuum dry to obtain maleate form A. After detection and analysis, it has the following characteristics: Fig. 22 XRPD pattern shown.

[0960] 15) Preparation of Maleate Crystal Form B

[0961] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 22 μL of 1.0M methanol solution of maleic acid to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain maleate salt form B. After detection and analysis, it has the following characteristics: Fig.23 XRPD pattern shown.

[0962] 16) Preparation of Maleate Crystal Form C

[0963] Weigh 20 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 44 μL of 1.0M methanol solution of maleic acid to the system, dissolve and precipitate a large amount of solid, centrifuge and vacuum dry to obtain maleate salt form C. After detection and analysis, it has the following characteristics: Fig.24 XRPD pattern shown.

[0964] 17) Preparation of Maleate Crystalline Form D

[0965] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M maleic acid toluene solution to the system, suspend, stir overnight, centrifuge and vacuum dry to obtain maleate form D. After detection and analysis, it has the following characteristics: Fig.25 XRPD pattern shown.

[0966] 18) Preparation of Methanesulfonate Form A

[0967] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M methanesulfonic acid 2-methyl-tetrahydrofuran solution to the system, heat and stir at 50°C, and precipitate solid after oil formation. Centrifuge and vacuum dry to obtain mesylate form A. After detection and analysis, it has the following characteristics: Fig.26 XRPD pattern shown.

[0968] 19) Preparation of benzenesulfonate crystal form A

[0969] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M benzenesulfonic acid 2-methyl-tetrahydrofuran solution to the system, heat and stir at 50°C, precipitate solid after oiling, centrifuge and vacuum dry to obtain benzenesulfonate salt form A. After detection and analysis, it has the following characteristics: Fig. 27 XRPD pattern shown.

[0970] 20) Preparation of Malonate Crystalline Form A

[0971] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M malonic acid 2-methyl-tetrahydrofuran solution to the system, heat and stir at 50°C, precipitate solid after oiling, centrifuge and vacuum dry to obtain malonate form A. After detection and analysis, it has the following characteristics: Fig.28 XRPD pattern shown.

[0972] 21) Preparation of malonate crystal form B

[0973] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 22 μL of 1.0M malonic acid methanol solution to the system, dissolve and precipitate a small amount of solid, centrifuge and vacuum dry to obtain malonate form B. After detection and analysis, it has the following characteristics: Fig.29 XRPD pattern shown.

[0974] 22) Preparation of Succinate Crystalline Form A

[0975] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, slowly add 200 μL of 0.11M succinic acid 2-methyl-tetrahydrofuran solution to the system, heat and stir at 50°C, suspend, stir overnight, centrifuge and vacuum dry to obtain succinate salt form A. After detection and analysis, it has the following characteristics: Fig.30 XRPD pattern shown.

[0976] 23) Preparation of Succinate Crystal Form B

[0977] Weigh 10 mg of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide free base form A, add 200 μL of toluene, heat and stir at 50°C, slowly add 22 μL of 1.0M succinic acid methanol solution to the system, dissolve and precipitate a small amount of solid, centrifuge and vacuum dry to obtain succinate salt form B. After detection and analysis, it has the following characteristics: Fig.31 XRPD pattern shown.

[0978] 4. Quantitative study of compound salts

[0979] 4.1 Quantitative Study of the Hydrochloride Salt of the Compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0980] 4.1.1 Experimental Purpose:

[0981] The number of bound acids in the hydrochloride salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide was quantified by HPLC-ELSD test.

[0982] 4.1.2 Experimental steps:

[0983] Weigh an appropriate amount of NaCl and prepare a series of linear solutions of different concentrations using the diluent acetonitrile-water (50:50); weigh an appropriate amount of hydrochloride from different batches and prepare solutions containing 2 mg / mL of hydrochloride using the diluent acetonitrile-water (50:50).

[0984] Take the above solution to filter the linear solution and hydrochloride sample, and then filter and put it into HPLC-ELSD. Specific HPLC-ELSD analysis method:

[0985] Chromatographic columns HILIC ZIC (4.6*150mm, 3.5um) Mobile phase A: 75 mM ammonium acetate; B: acetonitrile Proportion 70％B ELSD temperature 80℃ Run time 8min

[0986] 4.1.3 Experimental results:

[0987] Table 3.1 Quantitative study results of hydrochloride

[0988]

[0989] 4.1.4 Experimental conclusion:

[0990] According to the calculation of Cl in different batches of hydrochloride - The percentage content confirms that the number of hydrochloride salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide combined with hydrochloric acid is 1.

[0991] 4.2 Quantification of benzoylglycinate of compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

[0992] 4.2.1 Experimental Purpose:

[0993] The number of bound acids in the benzoylglycine salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide was quantified by HPLC-ELSD test.

[0994] 4.2.2 Experimental steps:

[0995] Weigh an appropriate amount of benzoylglycine and prepare a series of linear solutions of different concentrations using the diluent acetonitrile-water (50:50); weigh an appropriate amount of hydrochloride from different batches and prepare solutions containing 2 mg / mL of benzoylglycine salt using the diluent acetonitrile-water (50:50).

[0996] Take the above solution to filter the linear solution and benzoylglycine salt sample, filter and then enter HPLC-ELSD. Specific HPLC-ELSD analysis method:

[0997] Chromatographic columns HILIC ZIC (4.6*150mm, 3.5um) Mobile phase A: 75 mM ammonium acetate; B: acetonitrile Proportion 80％B ELSD temperature 80℃ Run time 3.5min

[0998] 4.2.3 Experimental results:

[0999] Table 3.2 Quantitative study results of benzoylglycinate

[1000]

[1001] 4.2.4 Experimental conclusion:

[1002] Based on the calculation of the percentage of benzoylglycine in benzoylglycine salt in different batches, it was confirmed that the number of benzoylglycine bound to crystalline form C and crystalline form D of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide was 1.

[1003] 5. Solid stability test

[1004] 5.1 Experimental Purpose:

[1005] The physicochemical stability of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide salt was investigated under the conditions of light illumination of 5000lx, high temperature of 60°C, high humidity of 92.5%RH, and high temperature and humidity of 50°C75%RH, to provide a basis for the storage of the compound.

[1006] 5.2 Instruments and liquid phase analysis conditions

[1007] 5.2.1 Instruments and equipment:

[1008] Instrument Name model Analytical Balance Sartorius BSA224S-CW Water Purifier Milli-Q Plus, Millipore High performance liquid chromatography Agilent1260 Pump Agilent G1311B

[1009] Injector G1329B Column oven G1316A Detector G1315D

[1010] 5.2.2 Chromatographic conditions:

[1011]

[1012] 5.3 Experimental plan:

[1013] About 1 mg of each of different salt forms of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloyl was taken and observed for 5 days and 10 days under light illumination of 5000lx, high temperature of 60°C, high humidity of 92.5%RH, and high temperature and high humidity of 50°C and 75%RH. The content was determined by HPLC and the external standard method, and the changes in related substances were calculated by the chromatographic peak area normalization method.

[1014] 5.4 Experimental Results:

[1015] Table 3.3 Stability results

[1016]

[1017] 5.5 Experimental conclusion:

[1018] The above data show that the benzoylglycine salt form D and the hydrochloride salt form A of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide are both stable under light, high temperature and high humidity conditions.

[1019] 6. Dynamic hygroscopicity test

[1020] 6.1 Experimental Purpose:

[1021] The hygroscopicity of the crystal form of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide salt under different relative humidity conditions was investigated to provide a basis for the crystal screening and storage of the compound salt.

[1022] 6.2 Experimental plan:

[1023] The compounds N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A, benzoylglycine salt form D, p-toluenesulfonate salt form A and hydrobromide salt form A were respectively placed in saturated water vapor at different relative humidity to allow the compounds to reach dynamic equilibrium with the water vapor, and the percentage of weight gain due to moisture absorption of the compounds after equilibrium was calculated.

[1024] 6.3 Experimental results:

[1025] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A absorbs moisture at RH80% and gains a weight of 0.3608%. After two cycles of moisture absorption and desorption at a relative humidity of 0-95%, the XRPD spectrum of the hydrochloride form A did not change, that is, the crystal form did not change.

[1026] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide glycine salt form D absorbs moisture and gains weight by 0.2218% under RH80% conditions; after two cycles of moisture absorption and desorption under 0-95% relative humidity conditions, the XRPD spectrum of benzoylglycine salt form D did not change, that is, the crystal form did not change.

[1027] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide p-toluenesulfonate form A absorbs moisture at RH80% and gains a weight of 1.443%. After two cycles of moisture absorption and desorption at a relative humidity of 0-95%, the XRPD spectrum of the hydrochloride form A did not change, that is, the crystal form did not change.

[1028] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrobromide form A absorbs moisture at RH80% and gains a weight of 0.577%. After two cycles of moisture absorption and desorption at a relative humidity of 0-95%, the XRPD spectrum of the hydrochloride form A did not change, that is, the crystal form did not change.

[1029] 6.4 Experimental conclusion:

[1030] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A, benzoylglycine salt form D, p-toluenesulfonate salt form A and hydrobromide salt form A are stable in a humid environment.

[1031] 7. Solubility experiments in different media

[1032] 7.1 Experimental Purpose:

[1033] The solubility of compounds N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A, benzoylglycine salt form C, and benzoylglycine salt form D in simulated artificial gastrointestinal fluid was compared to provide a basis for evaluating the drugability of the salts.

[1034] 7.2 Experimental plan:

[1035] About 2 mg of compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A, benzoylglycinate form C, and benzoylglycinate form D were weighed and suspended in 1 mL of non-fasting artificial simulated colon fluid (FeSSCoF) and pure water for 4 hours, respectively. The thermodynamic solubility of the compound at 37°C was determined by HPLC and the external standard method.

[1036] 7.3 Experimental results:

[1037] Table 3.4 Solubility results

[1038]

[1039] 7.4 Experimental conclusion:

[1040] Comparing the above data, it can be seen that the solubility of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide in water and FeSSCoF is significantly improved after salt formation due to the change in environmental pH value.

[1041] 8. Thermodynamic stability experiment

[1042] 8.1 Experimental Purpose:

[1043] Through polycrystalline screening and crystal competition tests, a thermodynamically stable crystal form is obtained.

[1044] 8.2 Experimental plan:

[1045] (1) Polycrystalline screening test:

[1046] An organic solvent with a certain solubility is selected, and the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamidebenzoylglycine salt form D is suspended in the solvent system, stirred and slurried at 50°C for 1 week, centrifuged, and the supernatant was discarded. The solid was vacuum dried (-0.1Mpa) at 50°C for 16 hours, and the XRPD of the solid was measured and compared with the XRPD of the raw compound salt.

[1047] (2) Crystal competition test

[1048] Appropriate amounts of compounds N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide benzoylglycine salt form A, benzoylglycine salt form B, benzoylglycine salt form C, benzoylglycine salt form E and benzoylglycine salt form F were weighed and mixed with benzoylglycine salt form D respectively, and a crystal form competitive test was carried out. 100 μL of methyl tert-butyl ether was added, and XRPD was measured after slurrying at 50° C. for 1 week to determine the most stable crystal form.

[1049] 8.3 Experimental results:

[1050] (1) The results of the polycrystalline screening test are as follows:

[1051] Table 3.5 Polycrystalline screening test results

[1052] Solvents result Methanol Benzoylglycine salt form D Ethanol Benzoylglycine salt form D acetone Benzoylglycine salt form E Acetonitrile Benzoylglycine salt form D Isopropyl alcohol Benzoylglycine salt form D Toluene Benzoylglycine salt form A Dichloromethane Benzoylglycine salt Form F Tetrahydrofuran Benzoylglycine salt form B 2-Methyltetrahydrofuran Benzoylglycine salt form B 2-Butanone Benzoylglycine salt form D 3-Pentanone Benzoylglycine salt form D Isopropyl acetate Benzoylglycine salt form D Ethyl acetate Benzoylglycine salt form D

[1053] (2) The results of the crystal competition test are as follows:

[1054] Table 3.6 Crystal competitive test results

[1055] Crystal combination result Benzoylglycine salt form A + Benzoylglycine salt form D Benzoylglycine salt form D Benzoylglycine salt form B + Benzoylglycine salt form D Benzoylglycine salt form D Benzoylglycine salt form C + Benzoylglycine salt form D Benzoylglycine salt form D Benzoylglycine salt form E + Benzoylglycine salt form D Benzoylglycine salt form D Benzoylglycine salt form F + Benzoylglycine salt form D Benzoylglycine salt form D

[1056] 8.4 Experimental conclusion:

[1057] By beating, changing the crystallization solvent and the crystallization method, a total of 6 crystal forms of benzoylglycine salt were obtained, namely, benzoylglycine salt crystal form A, crystal form B, crystal form C, crystal form D, crystal form E and crystal form F. By comparing the DSC spectra of different crystal forms and the results of crystal form competition tests, it can be judged that benzoylglycine salt crystal form D is the most thermodynamically stable crystal form among these crystal forms and is anhydrous.

[1058] 9. Pharmacokinetic study in rats

[1059] 9.1 Experimental Purpose:

[1060] The pharmacokinetic parameters of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride Form A and Benzoylglycine Form D were compared in rats through animal PK studies.

[1061] 9.2 Experimental instruments and reagents:

[1062] 9.2.1 Instruments:

[1063]

[1064] 9.2.2 Reagents:

[1065] Reagents supplier batch number Remark DMSO Vetech WXBD0293V Acetonitrile Sigma-Aldrich WXBD0232V Methyl Alcohol Sigma-Aldrich WXBC6573V Formic Acid Fisher Scientific 193497 Dexamethasone Solebao 822A0523 Internal Standard HP-β-CD Shandong Binzhou Zhiyuan Biotechnology Co., Ltd. 20190517 HPMC K4M Damas-beta P1575251

[1066] 9.3 Experimental Animals:

[1067] Animal species strain age gender supplier Rat SD 7 weeks, weight 200g male Zhaoyan (Suzhou) New Drug Research Center Co., Ltd.

[1068] 9.4 Test Compounds:

[1069] Compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A and benzoylglycine salt form D.

[1070] 9.5 Experimental plan:

[1071] The compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A and benzoylglycine salt form D were uniformly suspended in an aqueous solution containing 0.5% HPMC (hydroxypropyl methylcellulose) K4M (1% Tween80), and then gavage was performed on rats. Three rats were dosed at a dose of 30 mg / kg, and all the amounts of the compounds were converted into the same amount of free base.

[1072] 9.6 Experimental results:

[1073] Table 3.7 Results of pharmacokinetic experiments in rats

[1074]

[1075]

[1076] 9.7 Experimental conclusion:

[1077] It can be seen from the rat pharmacokinetic test results in the table that at a dose of 30 mg / kg, the compounds of the present invention, N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide hydrochloride form A and benzoylglycine salt form D, exhibited good metabolic properties.

Claims

1. An acid salt of a compound as described below, It is characterized in that The acid in the acid salt is selected from an inorganic acid or an organic acid, wherein the inorganic acid is selected from hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid or phosphoric acid; the organic acid is selected from 2,5-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, acetic acid, dichloroacetic acid, trichloroacetic acid, acetohydroxamic acid, adipic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, 4-aminobenzoic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclohexanesulfamic acid, camphorsulfonic acid, aspartic acid, camphoric acid, gluconic acid, glucuronic acid, glutamic acid, isoascorbic acid, lactic acid, malic acid, mandelic acid, pyroglutamic acid, tartaric acid , dodecyl sulfuric acid, dibenzoyltartaric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactosonic acid, gentisic acid, glutaric acid, 2-ketoglutaric acid, glycolic acid, benzoylglycine, isethionic acid, lactobionic acid, ascorbic acid, aspartic acid, lauric acid, camphoric acid, maleic acid, malonic acid, methanesulfonic acid, 1,5-naphthalene disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, thiocyanic acid, pamoic acid, formic acid, undecylenic acid, trifluoroacetic acid, benzenesulfonic acid, p-toluenesulfonic acid, or L-malic acid.

2. The acid salt of the compound according to claim 1, characterized in that The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid, adipic acid or succinic acid.

3. The acid salt of the compound according to claim 1, characterized in that: The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid or succinic acid.

4. The acid salt of the compound according to claim 1, characterized in that The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid or benzoylglycine.

5. The acid salt of the compound according to claim 1, characterized in that: The number of acids is 0.2-3.

6. The acid salt of the compound according to claim 1, characterized in that: The number of acids is 0.2, 0.5, 1, 1.5, 2, 2.5 or 3.

7. The acid salt of the compound according to any one of claims 1, characterized in that The number of acids is 0.5, 1, 2 or 3.

8. The acid salt of the compound according to claim 1, characterized in that: The number of acids is 1.

9. The acid salt of the compound according to claim 1, characterized in that: Acid salt is 10. The acid salt of the compound according to claim 1, characterized in that: The acid salt is a hydrate or an anhydrous form; when the acid salt is a hydrate, the number of water is 0.2-3.

11. The acid salt of the compound according to claim 10, characterized in that: When the acid salt is a hydrate, the number of water is 0.2, 0.5, 1, 1.5, 2, 2.5 or 3.

12. The acid salt of the compound according to claim 11, characterized in that When the acid salt is a hydrate, the number of water is 0.5, 1, 2 or 3.

13. The acid salt of the compound according to claim 1, characterized in that: The acid salt is crystalline or amorphous.

14. The acid salt of the compound according to claim 1, characterized in that: The acid salt is a crystalline form of the acid salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

15. The acid salt of the compound according to claim 1, characterized in that: The acid salt is a hydrochloride salt, hydrobromide salt, p-toluenesulfonate salt, sulfate salt, fumarate salt, oxalate salt, benzoylglycine salt, phosphate salt, maleate salt, malate salt, methanesulfonate salt, benzenesulfonate salt, malonate salt, adipate salt or succinate salt of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

16. The acid salt of the compound according to claim 1, characterized in that: The acid salt is a hydrochloride salt, a hydrobromide salt, a p-toluenesulfonate salt, a sulfate salt, a fumarate salt, an oxalate salt, a benzoylglycine salt, a phosphate salt, a maleate salt, a methanesulfonate salt, a benzenesulfonate salt, a malonate salt or a succinate salt of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

17. The acid salt of the compound according to claim 1, characterized in that: The acid salt is a hydrochloride salt, a hydrobromide salt, a p-toluenesulfonate salt or a benzoylglycine salt of N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide.

18. The acid salt crystalline form of the compound according to claim 14, characterized in that: The acid salt crystalline forms of the compound N-(5-((5-cyano-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide are hydrochloride crystalline form A, hydrobromide crystalline form A, p-toluenesulfonate crystalline form A, sulfate crystalline form A, fumarate crystalline form A, oxalate crystalline form A, benzoylglycine salt crystalline form A , benzoylglycine salt form B, benzoylglycine salt form C, benzoylglycine salt form D, benzoylglycine salt form E, benzoylglycine salt form F, phosphate salt form A, maleate salt form A, maleate salt form B, maleate salt form C, maleate salt form D, methanesulfonate salt form A, benzenesulfonate salt form A, malonate salt form A, malonate salt form B, succinate salt form A or succinate salt form B, wherein: The X-ray powder diffraction spectrum of hydrochloride form A has a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 12.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 25.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 24.9±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the hydrobromide salt form A has a diffraction peak at 2θ of 24.9±0.2°; or a diffraction peak at 26.3±0.2°; or a diffraction peak at 6.2±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 22.6±0.2°; or a diffraction peak at 14.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 25.8±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of p-toluenesulfonate crystalline form A has a diffraction peak at 2θ of 5.5±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 24.3±0.2°; or a diffraction peak at 26.8±0.2°; or a diffraction peak at 21.1±0.2°; or a diffraction peak at 9.9±0.2°; or a diffraction peak at 23.9±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of sulfate crystalline form A has a diffraction peak at 2θ of 12.0±0.2°; or a diffraction peak at 11.9±0.2°; or a diffraction peak at 6.1±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 9.6±0.2°; or a diffraction peak at 10.4±0.2°; or a diffraction peak at 22.4±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the fumarate salt form A has a diffraction peak at 2θ of 24.0±0.2°; or a diffraction peak at 15.2±0.2°; or a diffraction peak at 9.4±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 13.8±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 17.6±0.2°; or a diffraction peak at 18.7±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of oxalate crystalline form A has a diffraction peak at 2θ of 5.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 20.6±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 27.7±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form A has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 25.1±0.2°; or a diffraction peak at 10.6±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 18.3±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 19.4±0.2°; or a diffraction peak at 19.0±0.2°; or a diffraction peak at 25.9±0.2°; or a diffraction peak at 16.6±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form B has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 23.1±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 22.8±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form C has a diffraction peak at 2θ of 5.7±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 15.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 18.5±0.2°; or a diffraction peak at 16.8±0.2°; or a diffraction peak at 19.4±0.2°; or a diffraction peak at 17.5±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form D has a diffraction peak at 2θ of 17.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 5.8±0.2°; or a diffraction peak at 25.2±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 15.0±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.8±0.2°; or a diffraction peak at 19.9±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form E has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 5.3±0.2°; or a diffraction peak at 5.6±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 16.5±0.2°; or a diffraction peak at 21.5±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 18.4±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzoylglycine salt form F has a diffraction peak at 2θ of 6.1±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.3±0.2°; or a diffraction peak at 9.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 13.8±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the phosphate crystal form A has a diffraction peak at 2θ of 10.6±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.2±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 13.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.9±0.2°; or a diffraction peak at 25.3±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 12.1±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of maleate salt form A has a diffraction peak at 2θ of 6.0±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 16.3±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 11.8±0.2°; or a diffraction peak at 7.1±0.2°; or a diffraction peak at 21.7±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of maleate salt form B has a diffraction peak at 2θ of 7.7±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 6.5±0.2°; or a diffraction peak at 19.8±0.2°; or a diffraction peak at 6.0±0.2°; or a diffraction peak at 8.2±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of maleate salt form C has a diffraction peak at 2θ of 17.1±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 13.3±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 25.5±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 13.1±0.2°; or a diffraction peak at 22.9±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of maleate salt form D has a diffraction peak at 2θ of 20.4±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 25.9±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 8.9±0.2°; or a diffraction peak at 24.1±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 21.8±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the mesylate salt form A has a diffraction peak at 2θ of 5.9±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 17.4±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 18.0±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of benzenesulfonate salt form A has a diffraction peak at 2θ of 5.6±0.2°; or a diffraction peak at 21.2±0.2°; or a diffraction peak at 13.4±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 26.6±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.0±0.2°; or a diffraction peak at 10.6±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the malonate crystalline form A has a diffraction peak at 2θ of 7.5±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 20.3±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 23.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 25.6±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the malonate salt form B has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 5.9±0.2°; or a diffraction peak at 20.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 27.4±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 13.9±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the succinate salt form A has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 26.2±0.2°; or a diffraction peak at 19.3±0.2°; or a diffraction peak at 21.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 16.0±0.2°; or a diffraction peak at 14.4±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks; The X-ray powder diffraction spectrum of the succinate salt form B has a diffraction peak at 2θ of 19.2±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 20.7±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 18.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 27.3±0.2°; or a diffraction peak at 20.8±0.2°; including any 2-5, or 3-5, or 3-6, or 3-8, or 5-8, or 6-8 of the above diffraction peaks.

19. The crystal form according to claim 18, characterized in that: The X-ray powder diffraction spectrum of hydrochloride crystal form A has a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 12.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 25.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 24.9±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the hydrobromide salt form A has a diffraction peak at 2θ of 24.9±0.2°; or a diffraction peak at 26.3±0.2°; or a diffraction peak at 6.2±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 22.6±0.2°; or a diffraction peak at 14.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 25.8±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of p-toluenesulfonate crystalline form A has a diffraction peak at 2θ of 5.5±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 15.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 24.3±0.2°; or a diffraction peak at 26.8±0.2°; or a diffraction peak at 21.1±0.2°; or a diffraction peak at 9.9±0.2°; or a diffraction peak at 23.9±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of sulfate crystalline form A has a diffraction peak at 2θ of 12.0±0.2°; or a diffraction peak at 11.9±0.2°; or a diffraction peak at 6.1±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 9.6±0.2°; or a diffraction peak at 10.4±0.2°; or a diffraction peak at 22.4±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the fumarate salt form A has a diffraction peak at 2θ of 24.0±0.2°; or a diffraction peak at 15.2±0.2°; or a diffraction peak at 9.4±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 13.8±0.2°; or a diffraction peak at 22.1±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 17.6±0.2°; or a diffraction peak at 18.7±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of oxalate crystalline form A has a diffraction peak at 2θ of 5.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 20.6±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 27.7±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form A has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 25.1±0.2°; or a diffraction peak at 10.6±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 18.3±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 19.4±0.2°; or a diffraction peak at 19.0±0.2°; or a diffraction peak at 25.9±0.2°; or a diffraction peak at 16.6±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form B has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 10.5±0.2°; or a diffraction peak at 23.1±0.2°; or a diffraction peak at 20.9±0.2°; or a diffraction peak at 14.4±0.2°; or a diffraction peak at 10.8±0.2°; or a diffraction peak at 22.8±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form C has a diffraction peak at 2θ of 5.7±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 15.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 18.5±0.2°; or a diffraction peak at 16.8±0.2°; or a diffraction peak at 19.4±0.2°; or a diffraction peak at 17.5±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form D has a diffraction peak at 2θ of 17.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 5.8±0.2°; or a diffraction peak at 25.2±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 15.0±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.8±0.2°; or a diffraction peak at 19.9±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form E has a diffraction peak at 2θ of 5.4±0.2°; or a diffraction peak at 5.3±0.2°; or a diffraction peak at 5.6±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 24.7±0.2°; or a diffraction peak at 16.5±0.2°; or a diffraction peak at 21.5±0.2°; or a diffraction peak at 14.5±0.2°; or a diffraction peak at 18.4±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzoylglycine salt form F has a diffraction peak at 2θ of 6.1±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.3±0.2°; or a diffraction peak at 9.8±0.2°; or a diffraction peak at 11.6±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 11.1±0.2°; or a diffraction peak at 13.8±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the phosphate crystal form A has a diffraction peak at 2θ of 10.6±0.2°; or a diffraction peak at 12.3±0.2°; or a diffraction peak at 9.2±0.2°; or a diffraction peak at 21.4±0.2°; or a diffraction peak at 13.5±0.2°; or a diffraction peak at 6.3±0.2°; or a diffraction peak at 10.9±0.2°; or a diffraction peak at 25.3±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 12.1±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of maleate salt form A has a diffraction peak at 2θ of 6.0±0.2°; or a diffraction peak at 22.3±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 16.3±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 11.8±0.2°; or a diffraction peak at 7.1±0.2°; or a diffraction peak at 21.7±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of maleate salt form B has a diffraction peak at 2θ of 7.7±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 19.2±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 6.5±0.2°; or a diffraction peak at 19.8±0.2°; or a diffraction peak at 6.0±0.2°; or a diffraction peak at 8.2±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of maleate salt form C has a diffraction peak at 2θ of 17.1±0.2°; or a diffraction peak at 10.3±0.2°; or a diffraction peak at 23.8±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 13.3±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 25.5±0.2°; or a diffraction peak at 23.5±0.2°; or a diffraction peak at 13.1±0.2°; or a diffraction peak at 22.9±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction pattern of maleate salt form D has a diffraction peak at 2θ of 20.4±0.2°; or a diffraction peak at 8.2±0.2°; or a diffraction peak at 14.6±0.2°; or a diffraction peak at 25.9±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 8.9±0.2°; or a diffraction peak at 24.1±0.2°; or a diffraction peak at 24.5±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 21.8±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the mesylate salt form A has a diffraction peak at 2θ of 5.9±0.2°; or a diffraction peak at 21.7±0.2°; or a diffraction peak at 10.2±0.2°; or a diffraction peak at 14.2±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 25.7±0.2°; or a diffraction peak at 22.2±0.2°; or a diffraction peak at 17.4±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 18.0±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of benzenesulfonate salt form A has a diffraction peak at 2θ of 5.6±0.2°; or a diffraction peak at 21.2±0.2°; or a diffraction peak at 13.4±0.2°; or a diffraction peak at 18.9±0.2°; or a diffraction peak at 26.6±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 19.5±0.2°; or a diffraction peak at 26.4±0.2°; or a diffraction peak at 10.0±0.2°; or a diffraction peak at 10.6±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the malonate crystalline form A has a diffraction peak at 2θ of 7.5±0.2°; or a diffraction peak at 5.5±0.2°; or a diffraction peak at 23.6±0.2°; or a diffraction peak at 20.3±0.2°; or a diffraction peak at 9.7±0.2°; or a diffraction peak at 11.7±0.2°; or a diffraction peak at 23.0±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 14.3±0.2°; or a diffraction peak at 25.6±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the malonate salt form B has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 5.9±0.2°; or a diffraction peak at 20.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 19.1±0.2°; or a diffraction peak at 20.8±0.2°; or a diffraction peak at 16.1±0.2°; or a diffraction peak at 27.4±0.2°; or a diffraction peak at 18.4±0.2°; or a diffraction peak at 13.9±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the succinate salt form A has a diffraction peak at 2θ of 21.4±0.2°; or a diffraction peak at 10.7±0.2°; or a diffraction peak at 16.6±0.2°; or a diffraction peak at 19.6±0.2°; or a diffraction peak at 26.2±0.2°; or a diffraction peak at 19.3±0.2°; or a diffraction peak at 21.6±0.2°; or a diffraction peak at 21.0±0.2°; or a diffraction peak at 16.0±0.2°; or a diffraction peak at 14.4±0.2°; including any 6, 7 or 8 thereof; The X-ray powder diffraction spectrum of the succinate salt form B has a diffraction peak at 2θ of 19.2±0.2°; or a diffraction peak at 21.3±0.2°; or a diffraction peak at 20.7±0.2°; or a diffraction peak at 14.1±0.2°; or a diffraction peak at 20.4±0.2°; or a diffraction peak at 18.5±0.2°; or a diffraction peak at 11.4±0.2°; or a diffraction peak at 23.7±0.2°; or a diffraction peak at 27.3±0.2°; or a diffraction peak at 20.8±0.2°; including any 6, 7 or 8 thereof.

20. The acid salt crystalline form of the compound according to claim 18, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A comprises diffraction peaks at 2θ of 26.4±0.2°, 10.8±0.2°, and 20.9±0.2°; optionally, it may further comprise at least one of 2θ of 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, and 21.0±0.2; The X-ray powder diffraction pattern of the hydrobromide salt form A comprises diffraction peaks at 2θ of 24.9±0.2°, 26.3±0.2°, and 6.2±0.2°; optionally, it may further comprise at least one of 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, and 14.0±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises diffraction peaks at 2θ of 5.5±0.2°, 14.1±0.2°, and 21.7±0.2°; optionally, it may further comprise at least one of 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, and 21.1±0.2°; The X-ray powder diffraction pattern of sulfate crystalline form A comprises diffraction peaks at 2θ of 12.0±0.2°, 11.9±0.2°, and 6.1±0.2°; optionally, it may further comprise at least one of 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, and 9.6±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A comprises diffraction peaks at 2θ of 24.0±0.2°, 15.2±0.2°, and 9.4±0.2°; optionally, it may further comprise at least one of 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, and 9.7±0.2°; The X-ray powder diffraction pattern of the oxalate crystal form A comprises diffraction peaks at 2θ of 5.8±0.2°, 11.6±0.2°, and 21.4±0.2°; optionally, it may further comprise at least one of 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, and 23.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form A comprises diffraction peaks at 2θ of 5.4±0.2°, 25.1±0.2°, and 10.6±0.2°; optionally, it may further comprise at least one of 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, and 19.0±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form B comprises diffraction peaks at 2θ of 5.4±0.2°, 24.7±0.2°, and 19.1±0.2°; optionally, it may further comprise at least one of 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, and 14.4±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C comprises diffraction peaks at 2θ of 5.7±0.2°, 20.4±0.2°, and 26.4±0.2°; optionally, it may further comprise at least one of 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, and 16.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form D comprises diffraction peaks at 2θ of 17.6±0.2°, 21.0±0.2°, and 5.8±0.2°; optionally, it may further comprise at least one of 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 10.2±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E comprises diffraction peaks at 2θ of 5.4±0.2°, 5.3±0.2°, and 5.6±0.2°; optionally, it may further comprise at least one of 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, and 21.5±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F comprises diffraction peaks at 2θ of 6.1±0.2°, 6.3±0.2°, and 10.3±0.2°; optionally, it may further comprise at least one of 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, and 5.5±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A comprises diffraction peaks at 2θ of 10.6±0.2°, 12.3±0.2°, and 9.2±0.2°; optionally, it may further comprise at least one of 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, and 25.3±0.2°; The X-ray powder diffraction pattern of maleate salt form A comprises diffraction peaks at 2θ of 6.0±0.2°, 22.3±0.2°, and 8.2±0.2°; optionally, it may further comprise at least one of 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, and 11.8±0.2°; The X-ray powder diffraction pattern of maleate salt form B comprises diffraction peaks at 2θ of 7.7±0.2°, 16.1±0.2°, and 23.6±0.2°; optionally, it may further comprise at least one of 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, and 19.8±0.2°; The X-ray powder diffraction pattern of maleate salt form C comprises diffraction peaks at 2θ of 17.1±0.2°, 10.3±0.2°, and 23.8±0.2°; optionally, it may further comprise at least one of 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, and 23.5±0.2°; The X-ray powder diffraction pattern of maleate salt form D comprises diffraction peaks at 2θ of 20.4±0.2°, 8.2±0.2°, and 14.6±0.2°; optionally, it may further comprise at least one of 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A comprises diffraction peaks at 2θ of 5.9±0.2°, 21.7±0.2°, and 10.2±0.2°; optionally, it may further comprise at least one of 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, and 17.4±0.2°; The X-ray powder diffraction pattern of the benzenesulfonate salt form A comprises diffraction peaks at 2θ of 5.6±0.2°, 21.2±0.2°, and 13.4±0.2°; optionally, it may further comprise at least one of 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, and 26.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form A comprises diffraction peaks at 2θ of 7.5±0.2°, 5.5±0.2°, and 23.6±0.2°; optionally, it may further comprise at least one of 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, and 21.0±0.2°; The X-ray powder diffraction pattern of the malonate salt form B comprises diffraction peaks at 2θ of 21.4±0.2°, 5.9±0.2°, and 20.5±0.2°; optionally, it may further comprise at least one of 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, and 27.4±0.2°; The X-ray powder diffraction pattern of the succinate salt form A comprises diffraction peaks at 2θ of 21.4±0.2°, 10.7±0.2°, and 16.6±0.2°; optionally, it may further comprise at least one of 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, and 21.0±0.2°; The X-ray powder diffraction pattern of the succinate salt form B includes diffraction peaks at 2θ of 19.2±0.2°, 21.3±0.2°, and 20.7±0.2°; optionally, it may further include at least one of 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, and 23.7±0.2°.

21. The acid salt crystalline form of the compound according to claim 20, characterized in that: The X-ray powder diffraction pattern of hydrochloride form A comprises diffraction peaks at 2θ of 26.4±0.2°, 10.8±0.2°, and 20.9±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 2θ of 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, and 21.0±0.2; The X-ray powder diffraction pattern of the hydrobromide salt form A comprises diffraction peaks at 2θ of 24.9±0.2°, 26.3±0.2°, and 6.2±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, and 14.0±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises diffraction peaks at 2θ of 5.5±0.2°, 14.1±0.2°, and 21.7±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, and 21.1±0.2°; The X-ray powder diffraction pattern of sulfate crystalline form A comprises diffraction peaks at 2θ of 12.0±0.2°, 11.9±0.2°, and 6.1±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, and 9.6±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A comprises diffraction peaks at 2θ of 24.0±0.2°, 15.2±0.2°, and 9.4±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, and 9.7±0.2°; The X-ray powder diffraction pattern of the oxalate crystal form A comprises diffraction peaks at 2θ of 5.8±0.2°, 11.6±0.2°, and 21.4±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, and 23.8±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form A comprises diffraction peaks at 2θ of 5.4±0.2°, 25.1±0.2°, and 10.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, and 19.0±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form B comprises diffraction peaks at 2θ of 5.4±0.2°, 24.7±0.2°, and 19.1±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, and 14.4±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C comprises diffraction peaks at 2θ of 5.7±0.2°, 20.4±0.2°, and 26.4±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, and 16.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form D comprises diffraction peaks at 2θ of 17.6±0.2°, 21.0±0.2°, and 5.8±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, and 10.2±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E comprises diffraction peaks at 2θ of 5.4±0.2°, 5.3±0.2°, and 5.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, and 21.5±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F comprises diffraction peaks at 2θ of 6.1±0.2°, 6.3±0.2°, and 10.3±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, and 5.5±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A comprises diffraction peaks at 2θ of 10.6±0.2°, 12.3±0.2°, and 9.2±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, and 25.3±0.2°; The X-ray powder diffraction pattern of maleate salt form A comprises diffraction peaks at 2θ of 6.0±0.2°, 22.3±0.2°, and 8.2±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, and 11.8±0.2°; The X-ray powder diffraction pattern of maleate salt form B comprises diffraction peaks at 2θ of 7.7±0.2°, 16.1±0.2°, and 23.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, and 19.8±0.2°; The X-ray powder diffraction pattern of maleate salt form C comprises diffraction peaks at 2θ of 17.1±0.2°, 10.3±0.2°, and 23.8±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, and 23.5±0.2°; The X-ray powder diffraction pattern of maleate salt form D comprises diffraction peaks at 2θ of 20.4±0.2°, 8.2±0.2°, and 14.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A comprises diffraction peaks at 2θ of 5.9±0.2°, 21.7±0.2°, and 10.2±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, and 17.4±0.2°; The X-ray powder diffraction pattern of benzenesulfonate salt form A comprises diffraction peaks at 2θ of 5.6±0.2°, 21.2±0.2°, and 13.4±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, and 26.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form A comprises diffraction peaks at 2θ of 7.5±0.2°, 5.5±0.2°, and 23.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, and 21.0±0.2°; The X-ray powder diffraction pattern of the malonate salt form B comprises diffraction peaks at 2θ of 21.4±0.2°, 5.9±0.2°, and 20.5±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, and 27.4±0.2°; The X-ray powder diffraction pattern of the succinate salt form A comprises diffraction peaks at 2θ of 21.4±0.2°, 10.7±0.2°, and 16.6±0.2°; optionally, it may further comprise 2, 3, 4 or 5 of 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, and 21.0±0.2°; The X-ray powder diffraction pattern of the succinate salt form B includes diffraction peaks at 2θ of 19.2±0.2°, 21.3±0.2°, and 20.7±0.2°; optionally, it may further include 2, 3, 4 or 5 of 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, and 23.7±0.2°.

22. The acid salt crystalline form of the compound according to claim 21, characterized in that: The X-ray powder diffraction spectrum of hydrochloride crystal form A has diffraction peaks at the following positions at 2θ: at 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, and 6.3±0.2°; The X-ray powder diffraction spectrum of the hydrobromide salt form A has diffraction peaks at the following positions of 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2° and 10.5±0.2° The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions of 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2° and 24.3±0.2°; The X-ray powder diffraction pattern of sulfate crystal form A has diffraction peaks at the following positions of 2θ: 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2° and 22.1±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2° and 13.8±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2° and 18.4±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form A has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2° and 14.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form B has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2° and 23.1±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C has diffraction peaks at the following positions of 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2° and 11.1±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form D has diffraction peaks at the following positions of 2θ: 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 15.0±0.2° and 9.7±0.2°; or 17.6±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2° and 10.2±0.2°; or, 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 15.0±0.2° and 9.7±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2° and 24.7±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions of 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2° and 9.8±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions at 2θ: 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2° and 6.3±0.2°; The X-ray powder diffraction pattern of maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2° and 19.5±0.2°; The X-ray powder diffraction pattern of maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2° and 21.7±0.2°; The X-ray powder diffraction pattern of maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2° and 24.5±0.2°; The X-ray powder diffraction pattern of maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2° and 8.9±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2° and 25.7±0.2°; The X-ray powder diffraction pattern of benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2° and 23.7±0.2°; The X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2° and 11.7±0.2°; The X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2° and 20.8±0.2°; The X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2° and 19.3±0.2°; The X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions of 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2° and 18.5±0.2°.

23. The acid salt crystalline form of the compound according to claim 18, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, or 26.1±0.2°; The X-ray powder diffraction pattern of the hydrobromide salt form A optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, or 28.1±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, or 8.0±0.2°; The X-ray powder diffraction pattern of sulfate salt form A optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, or 22.0±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, or 12.2±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, or 18.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, or 17.2±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form B optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, or 14.3±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, or 21.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form D optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, or 18.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, or 26.3±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, or 22.1±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A optionally further comprises any two or three diffraction peaks located at 2θ of 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; The X-ray powder diffraction pattern of maleate salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, or 7.7±0.2°; The X-ray powder diffraction pattern of maleate salt form B optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, or 24.5±0.2°; The X-ray powder diffraction pattern of maleate salt form C optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, or 16.0±0.2°; The X-ray powder diffraction pattern of the maleate salt form D optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, or 28.8±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A optionally further comprises any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, or 9.5±0.2°; The X-ray powder diffraction pattern of the benzenesulfonate salt form A optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, or 22.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form A optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, or 22.0±0.2°; The X-ray powder diffraction pattern of the malonate salt form B optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, or 27.0±0.2°; The X-ray powder diffraction pattern of the succinate salt form A optionally further comprises diffraction peaks at any 2, 3, 4, 5, 6, or 7 of 2θ of 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, or 15.7±0.2°; The X-ray powder diffraction pattern of the succinate salt form B optionally further includes any 2, 3, 4, 5, 6, or 7 diffraction peaks located at 2θ of 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, or 18.7±0.2°.

24. The acid salt crystalline form of the compound according to claim 23, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A optionally further comprises diffraction peaks at 2θ of 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, and 26.1±0.2°; The X-ray powder diffraction pattern of the hydrobromide salt form A optionally further comprises diffraction peaks at 2θ of 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, and 28.1±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A optionally further comprises diffraction peaks at 2θ of 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, and 8.0±0.2°; The X-ray powder diffraction pattern of the sulfate salt form A optionally further comprises diffraction peaks at 2θ of 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, and 22.0±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A optionally further comprises diffraction peaks at 2θ of 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, and 12.2±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A optionally further comprises diffraction peaks at 2θ of 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, and 18.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form A optionally further comprises diffraction peaks at 2θ of 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, and 17.2±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form B optionally further comprises diffraction peaks at 2θ of 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, and 14.3±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form C optionally further comprises diffraction peaks at 2θ of 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, and 21.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form D optionally further comprises diffraction peaks at 2θ of 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, and 18.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E optionally further comprises diffraction peaks at 2θ of 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, and 26.3±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt Form F optionally further comprises diffraction peaks at 2θ of 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, and 22.1±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A optionally further comprises diffraction peaks at 2θ of 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; The X-ray powder diffraction pattern of the maleate salt form A optionally further comprises diffraction peaks at 2θ of 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, and 7.7±0.2°; The X-ray powder diffraction pattern of the maleate salt form B optionally further comprises diffraction peaks at 2θ of 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the maleate salt form C optionally further comprises diffraction peaks at 2θ of 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, and 16.0±0.2°; The X-ray powder diffraction pattern of the maleate salt form D optionally further comprises diffraction peaks at 2θ of 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, and 28.8±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A optionally further comprises diffraction peaks at 2θ of 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, and 9.5±0.2°; The X-ray powder diffraction pattern of the benzenesulfonate salt form A optionally further comprises diffraction peaks at 2θ of 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, and 22.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form A optionally further comprises diffraction peaks at 2θ of 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, and 22.0±0.2°; The X-ray powder diffraction pattern of the malonate salt form B optionally further comprises diffraction peaks at 2θ of 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, and 27.0±0.2°; The X-ray powder diffraction pattern of the succinate salt form A optionally further comprises diffraction peaks at 2θ of 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, and 15.7±0.2°; The X-ray powder diffraction pattern of the succinate salt form B optionally further comprises diffraction peaks at 2θ of 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, and 18.7±0.2°.

25. The acid salt crystalline form of the compound according to claim 24, characterized in that: The X-ray powder diffraction pattern of hydrochloride form A has diffraction peaks at the following positions of 2θ: 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 22.1±0.2° and 24.9±0.2°; The X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions of 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 21.0±0.2° and 25.8±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions of 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 9.9±0.2° and 23.9±0.2°; The X-ray powder diffraction pattern of sulfate crystal form A has diffraction peaks at the following positions of 2θ: 12.0±0.2°, 11.9±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 10.4±0.2°, 22.4±0.2° and 17.9±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 17.6±0.2°, 18.7±0.2° and 18.9±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 9.7±0.2°, 27.7±0.2° and 8.6±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form A has diffraction peaks at the following positions of 2θ: 5.4±0.2°, 25.1±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 25.9±0.2°, 16.6±0.2° and 23.3±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form B has diffraction peaks at the following positions of 2θ: 5.4±0.2°, 24.7±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 10.8±0.2°, 22.8±0.2° and 17.3±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C has diffraction peaks at the following positions of 2θ: 5.7±0.2°, 20.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 19.4±0.2°, 17.5±0.2° and 18.9±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form D has diffraction peaks at the following positions of 2θ: 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2° and 14.8±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form E has diffraction peaks at the following positions of 2θ: 5.4±0.2°, 5.3±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 14.5±0.2°, 18.4±0.2° and 12.3±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt Form F has diffraction peaks at the following positions of 2θ: 6.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 11.1±0.2°, 13.8±0.2° and 26.1±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions of 2θ: 10.6±0.2°, 12.3±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 11.7±0.2° and 12.1±0.2°; The X-ray powder diffraction pattern of maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 7.1±0.2°, 21.7±0.2° and 19.8±0.2°; The X-ray powder diffraction pattern of maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 6.0±0.2°, 8.2±0.2° and 20.9±0.2°; The X-ray powder diffraction pattern of maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 13.1±0.2°, 22.9±0.2° and 21.3±0.2°; The X-ray powder diffraction pattern of maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 16.1±0.2°, 21.8±0.2° and 17.0±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 11.7±0.2°, 18.0±0.2° and 23.6±0.2°; The X-ray powder diffraction pattern of benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 10.0±0.2°, 10.6±0.2° and 24.5±0.2°; The X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 14.3±0.2°, 25.6±0.2° and 19.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions of 2θ: 21.4±0.2°, 5.9±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 18.4±0.2°, 13.9±0.2° and 15.2±0.2°; The X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 16.0±0.2°, 14.4±0.2° and 10.2±0.2°; The X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions of 2θ: 19.2±0.2°, 21.3±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 27.3±0.2°, 20.8±0.2° and 22.0±0.2°.

26. The acid salt crystalline form of the compound according to claim 18, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A comprises diffraction peaks at 2θ of 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, and 26.1±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of the hydrobromide salt form A comprises diffraction peaks at 2θ of 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, and 28.1±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises diffraction peaks at 2θ of 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, and 8.0±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of sulfate salt form A comprises diffraction peaks at 2θ of 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, 22.0±0.2°, at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of the fumarate salt form A comprises diffraction peaks at 2θ of 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 9.7±0.2°, 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, and 12.2±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of the oxalate salt form A comprises diffraction peaks at 2θ of 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, and 18.6±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of benzoylglycine salt form A comprises diffraction peaks at 2θ of 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, and 17.2±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of benzoylglycine salt form B comprises diffraction peaks at 2θ of 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, and 14.3±0.2° at any of 4, 5, 6, 8, and 10 locations; The X-ray powder diffraction pattern of benzoylglycine salt form C comprises diffraction peaks at 2θ of 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, and 21.6±0.2°; The X-ray powder diffraction spectrum of the benzoylglycine salt form D comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, and 18.8±0.2°; The X-ray powder diffraction spectrum of the benzoylglycine salt form E comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, and 26.3±0.2°; The X-ray powder diffraction spectrum of the benzoylglycine salt form F comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, and 22.1±0.2°; The X-ray powder diffraction spectrum of the phosphate crystal form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 25.3±0.2°, 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; The X-ray powder diffraction spectrum of the maleate salt form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, and 7.7±0.2°; The X-ray powder diffraction spectrum of the maleate salt form B comprises diffraction peaks at 2θ of 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the maleate salt form C comprises diffraction peaks at 2θ of 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, and 16.0±0.2°; The X-ray powder diffraction pattern of the maleate salt form D comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, and 28.8±0.2°; The X-ray powder diffraction spectrum of the mesylate salt form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, and 9.5±0.2°; The X-ray powder diffraction spectrum of the benzenesulfonate salt form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, and 22.4±0.2°; The X-ray powder diffraction spectrum of the malonate crystalline form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, and 22.0±0.2°; The X-ray powder diffraction spectrum of the malonate crystalline form B comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, and 27.0±0.2°; The X-ray powder diffraction spectrum of the succinate salt crystal form A comprises diffraction peaks at 4, 5, 6, 8, and 10 positions selected from 2θ of 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, and 15.7±0.2°; The X-ray powder diffraction pattern of the succinate salt form B includes diffraction peaks at 2θ of 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, and 18.7±0.2°.

27. The acid salt crystalline form of the compound according to claim 26, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A comprises diffraction peaks at 2θ of 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2°, 24.9±0.2°, 18.9±0.2°, 8.8±0.2°, 26.6±0.2°, 15.7±0.2°, and 26.1±0.2°; The X-ray powder diffraction pattern of the hydrobromide salt form A comprises diffraction peaks at 2θ of 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2°, 25.8±0.2°, 18.9±0.2°, 26.5±0.2°, 20.8±0.2°, 12.4±0.2°, and 28.1±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A comprises diffraction peaks at 2θ of 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2°, 23.9±0.2°, 18.0±0.2°, 8.5±0.2°, 12.1±0.2°, 22.0±0.2°, and 8.0±0.2°; The X-ray powder diffraction pattern of sulfate salt form A comprises diffraction peaks at 2θ of 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2°, 22.4±0.2°, 17.9±0.2°, 18.1±0.2°, 18.2±0.2°, 21.0±0.2°, and 22.0±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A comprises diffraction peaks at 2θ of 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 22.1±0.2°, 9.7±0.2°, 17.6±0.2°, 18.7±0.2°, 18.9±0.2°, 8.9±0.2°, 7.4±0.2°, 23.1±0.2°, and 12.2±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A comprises diffraction peaks at 2θ of 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2°, 27.7±0.2°, 8.6±0.2°, 17.4±0.2°, 21.2±0.2°, 20.8±0.2°, and 18.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form A comprises diffraction peaks at 2θ of 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2°, 16.6±0.2°, 23.3±0.2°, 9.8±0.2°, 22.8±0.2°, 22.7±0.2°, and 17.2±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form B comprises diffraction peaks at 2θ of 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2°, 22.8±0.2°, 17.3±0.2°, 25.7±0.2°, 9.9±0.2°, 24.2±0.2°, and 14.3±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C comprises diffraction peaks at 2θ of 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2°, 17.5±0.2°, 18.9±0.2°, 10.5±0.2°, 13.8±0.2°, 9.9±0.2°, and 21.6±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form D comprises diffraction peaks at 2θ of 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 14.8±0.2°, 19.9±0.2°, 14.1±0.2°, 22.8±0.2°, 18.2±0.2°, 10.5±0.2°, and 18.8±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E comprises diffraction peaks at 2θ of 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2°, 18.4±0.2°, 12.3±0.2°, 21.1±0.2°, 20.4±0.2°, 16.9±0.2°, and 26.3±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F comprises diffraction peaks at 2θ of 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2°, 13.8±0.2°, 26.1±0.2°, 18.9±0.2°, 18.2±0.2°, 20.2±0.2°, and 22.1±0.2°; The X-ray powder diffraction spectrum of the phosphate crystal form A comprises diffraction peaks at 2θ of 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 25.3±0.2°, 11.7±0.2°, 12.1±0.2°, and 12.6±0.2°; The X-ray powder diffraction pattern of the maleate salt form A comprises diffraction peaks at 2θ of 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2°, 21.7±0.2°, 19.8±0.2°, 16.6±0.2°, 15.3±0.2°, 21.1±0.2°, and 7.7±0.2°; The X-ray powder diffraction pattern of the maleate salt form B comprises diffraction peaks at 2θ of 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2°, 8.2±0.2°, 20.9±0.2°, 15.3±0.2°, 11.7±0.2°, 11.0±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the maleate salt form C comprises diffraction peaks at 2θ of 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2°, 22.9±0.2°, 21.3±0.2°, 13.5±0.2°, 20.8±0.2°, 14.9±0.2°, and 16.0±0.2°; The X-ray powder diffraction pattern of the maleate salt form D comprises diffraction peaks at 2θ of 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2°, 21.8±0.2°, 17.0±0.2°, 28.4±0.2°, 22.3±0.2°, 12.6±0.2°, and 28.8±0.2°; The X-ray powder diffraction spectrum of the mesylate salt form A comprises diffraction peaks at 2θ of 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2°, 18.0±0.2°, 23.6±0.2°, 7.1±0.2°, 19.6±0.2°, 20.3±0.2°, and 9.5±0.2°; The X-ray powder diffraction spectrum of the benzenesulfonate salt form A comprises diffraction peaks at 2θ of 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2°, 10.6±0.2°, 24.5±0.2°, 14.9±0.2°, 24.9±0.2°, 14.6±0.2°, and 22.4±0.2°; The X-ray powder diffraction pattern of the malonate salt form A comprises diffraction peaks at 2θ of 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2°, 25.6±0.2°, 19.4±0.2°, 19.7±0.2°, 20.7±0.2°, 18.2±0.2°, and 22.0±0.2°; The X-ray powder diffraction pattern of the malonate salt form B comprises diffraction peaks at 2θ of 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2°, 13.9±0.2°, 15.2±0.2°, 18.8±0.2°, 23.6±0.2°, 21.8±0.2°, and 27.0±0.2°; The X-ray powder diffraction pattern of the succinate salt form A comprises diffraction peaks at 2θ of 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2°, 14.4±0.2°, 10.2±0.2°, 23.7±0.2°, 6.5±0.2°, 22.3±0.2°, and 15.7±0.2°; The X-ray powder diffraction pattern of the succinate salt form B includes diffraction peaks at 2θ of 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2°, 20.8±0.2°, 22.0±0.2°, 16.2±0.2°, 5.8±0.2°, 25.5±0.2°, and 18.7±0.2°.

28. The acid salt crystalline form of the compound according to claim 27, characterized in that: The X-ray powder diffraction pattern of hydrochloride form A has diffraction peaks at the following positions of 2θ: 26.4±0.2°, 10.8±0.2°, 20.9±0.2°, 14.2±0.2°, 12.5±0.2°, 6.3±0.2°, 25.0±0.2°, 21.0±0.2, 22.1±0.2° and 18.9±0.2°; The X-ray powder diffraction pattern of the hydrobromide salt form A has diffraction peaks at the following positions of 2θ: 24.9±0.2°, 26.3±0.2°, 6.2±0.2°, 20.4±0.2°, 15.6±0.2°, 10.5±0.2°, 22.6±0.2°, 14.0±0.2°, 21.0±0.2° and 25.8±0.2°; The X-ray powder diffraction pattern of the p-toluenesulfonate salt form A has diffraction peaks at the following positions of 2θ: 5.5±0.2°, 14.1±0.2°, 21.7±0.2°, 15.6±0.2°, 22.2±0.2°, 24.3±0.2°, 26.8±0.2°, 21.1±0.2°, 9.9±0.2° and 23.9±0.2°; The X-ray powder diffraction pattern of sulfate salt form A has diffraction peaks at the following positions of 2θ: 12.0±0.2°, 11.9±0.2°, 6.1±0.2°, 14.1±0.2°, 21.3±0.2°, 22.1±0.2°, 22.3±0.2°, 9.6±0.2°, 10.4±0.2° and 17.9±0.2°; The X-ray powder diffraction pattern of the fumarate salt form A has diffraction peaks at the following positions at 2θ: 24.0±0.2°, 15.2±0.2°, 9.4±0.2°, 20.9±0.2°, 25.7±0.2°, 13.8±0.2°, 18.7±0.2° and 18.9±0.2°; The X-ray powder diffraction pattern of the oxalate salt form A has diffraction peaks at the following positions at 2θ: 5.8±0.2°, 11.6±0.2°, 21.4±0.2°, 20.6±0.2°, 14.3±0.2°, 18.4±0.2°, 19.6±0.2°, 23.8±0.2°, 9.7±0.2° and 8.6±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form A has diffraction peaks at the following positions of 2θ: 5.4±0.2°, 25.1±0.2°, 10.6±0.2°, 21.3±0.2°, 18.3±0.2°, 14.6±0.2°, 19.4±0.2°, 19.0±0.2°, 25.9±0.2° and 16.6±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form B has diffraction peaks at the following positions of 2θ: 5.4±0.2°, 24.7±0.2°, 19.1±0.2°, 18.9±0.2°, 10.5±0.2°, 23.1±0.2°, 20.9±0.2°, 14.4±0.2°, 10.8±0.2° and 22.8±0.2°; The X-ray powder diffraction pattern of benzoylglycine salt form C has diffraction peaks at the following positions of 2θ: 5.7±0.2°, 20.4±0.2°, 26.4±0.2°, 14.5±0.2°, 15.5±0.2°, 11.1±0.2°, 18.5±0.2°, 16.8±0.2°, 19.4±0.2° and 17.5±0.2°; The X-ray powder diffraction spectrum of the benzoylglycine salt form D has diffraction peaks at the following positions at 2θ: 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, and 25.2±0.2°; or, 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, and 15.0±0.2°; or, 17.6±0.2°, 21.0±0.2°, 5.8±0.2°, 25.2±0.2°, 16.6±0.2°, 15.0±0.2°, 9.7±0.2°, 10.2±0.2°, 19.9±0.2°, and 14.1±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form E has diffraction peaks at the following positions at 2θ: 5.4±0.2°, 5.3±0.2°, 5.6±0.2°, 10.7±0.2°, 20.8±0.2°, 24.7±0.2°, 16.5±0.2°, 21.5±0.2°, 14.5±0.2° and 18.4±0.2°; The X-ray powder diffraction pattern of the benzoylglycine salt form F has diffraction peaks at the following positions at 2θ: 6.1±0.2°, 6.3±0.2°, 10.3±0.2°, 12.3±0.2°, 9.3±0.2°, 9.8±0.2°, 11.6±0.2°, 5.5±0.2°, 11.1±0.2° and 13.8±0.2°; The X-ray powder diffraction pattern of the phosphate crystal form A has diffraction peaks at the following positions at 2θ: 10.6±0.2°, 12.3±0.2°, 9.2±0.2°, 21.4±0.2°, 13.5±0.2°, 6.3±0.2°, 10.9±0.2°, 25.3±0.2°, 11.7±0.2° and 12.6±0.2°; The X-ray powder diffraction pattern of the maleate salt form A has diffraction peaks at the following positions at 2θ: 6.0±0.2°, 22.3±0.2°, 8.2±0.2°, 16.3±0.2°, 23.5±0.2°, 19.5±0.2°, 19.2±0.2°, 11.8±0.2°, 7.1±0.2° and 21.7±0.2°; The X-ray powder diffraction pattern of the maleate salt form B has diffraction peaks at the following positions at 2θ: 7.7±0.2°, 16.1±0.2°, 23.6±0.2°, 22.2±0.2°, 19.2±0.2°, 21.7±0.2°, 6.5±0.2°, 19.8±0.2°, 6.0±0.2° and 8.2±0.2°; The X-ray powder diffraction pattern of the maleate salt form C has diffraction peaks at the following positions at 2θ: 17.1±0.2°, 10.3±0.2°, 23.8±0.2°, 14.3±0.2°, 13.3±0.2°, 24.5±0.2°, 25.5±0.2°, 23.5±0.2°, 13.1±0.2° and 22.9±0.2°; The X-ray powder diffraction pattern of the maleate salt form D has diffraction peaks at the following positions at 2θ: 20.4±0.2°, 8.2±0.2°, 14.6±0.2°, 25.9±0.2°, 18.4±0.2°, 8.9±0.2°, 24.1±0.2°, 24.5±0.2°, 16.1±0.2° and 21.8±0.2°; The X-ray powder diffraction pattern of the mesylate salt form A has diffraction peaks at the following positions at 2θ: 5.9±0.2°, 21.7±0.2°, 10.2±0.2°, 14.2±0.2°, 20.8±0.2°, 25.7±0.2°, 22.2±0.2°, 17.4±0.2°, 11.7±0.2° and 18.0±0.2°; The X-ray powder diffraction spectrum of the benzenesulfonate salt form A has diffraction peaks at the following positions at 2θ: 5.6±0.2°, 21.2±0.2°, 13.4±0.2°, 18.9±0.2°, 26.6±0.2°, 23.7±0.2°, 19.5±0.2°, 26.4±0.2°, 10.0±0.2° and 10.6±0.2°; The X-ray powder diffraction pattern of the malonate salt form A has diffraction peaks at the following positions at 2θ: 7.5±0.2°, 5.5±0.2°, 23.6±0.2°, 20.3±0.2°, 9.7±0.2°, 11.7±0.2°, 23.0±0.2°, 21.0±0.2°, 14.3±0.2° and 25.6±0.2°; The X-ray powder diffraction pattern of the malonate salt form B has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 5.9±0.2°, 20.5±0.2°, 11.4±0.2°, 19.1±0.2°, 20.8±0.2°, 16.1±0.2°, 27.4±0.2°, 18.4±0.2° and 13.9±0.2°; The X-ray powder diffraction pattern of the succinate salt form A has diffraction peaks at the following positions at 2θ: 21.4±0.2°, 10.7±0.2°, 16.6±0.2°, 19.6±0.2°, 26.2±0.2°, 19.3±0.2°, 21.6±0.2°, 21.0±0.2°, 16.0±0.2° and 14.4±0.2°; The X-ray powder diffraction pattern of the succinate salt form B has diffraction peaks at the following positions of 2θ: 19.2±0.2°, 21.3±0.2°, 20.7±0.2°, 14.1±0.2°, 20.4±0.2°, 18.5±0.2°, 11.4±0.2°, 23.7±0.2°, 27.3±0.2° and 20.8±0.2°.

29. The acid salt crystalline form of the compound according to claim 28, characterized in that: The X-ray powder diffraction pattern of the hydrochloride salt form A is shown in FIG1 ; the X-ray powder diffraction pattern of the hydrobromide salt form A is shown in FIG4 ; the X-ray powder diffraction pattern of the p-toluenesulfonate salt form A is shown in FIG7 ; the X-ray powder diffraction pattern of the sulfate salt form A is shown in FIG10 ; the X-ray powder diffraction pattern of the fumarate salt form A is shown in FIG11 ; the X-ray powder diffraction pattern of the oxalate salt form A is shown in FIG12 ; The X-ray powder diffraction pattern of the benzoylglycine salt form A is shown in FIG13 ; the X-ray powder diffraction pattern of the benzoylglycine salt form B is shown in FIG14 ; the X-ray powder diffraction pattern of the benzoylglycine salt form C is shown in FIG15 ; the X-ray powder diffraction pattern of the benzoylglycine salt form D is shown in FIG16 ; the X-ray powder diffraction pattern of the benzoylglycine salt form E is shown in FIG19 ; the benzoylglycine salt The X-ray powder diffraction pattern of Form F is shown in FIG20 ; the X-ray powder diffraction pattern of the phosphate Form A is shown in FIG21 ; the X-ray powder diffraction pattern of the maleate Form A is shown in FIG22 ; the X-ray powder diffraction pattern of the maleate Form B is shown in FIG23 ; the X-ray powder diffraction pattern of the maleate Form C is shown in FIG24 ; the X-ray powder diffraction pattern of the maleate Form D is shown in FIG25 ; The X-ray powder diffraction pattern of the sulfonate salt form A is shown in FIG26 ; the X-ray powder diffraction pattern of the benzenesulfonate salt form A is shown in FIG27 ; the X-ray powder diffraction pattern of the malonate salt form A is shown in FIG28 ; the X-ray powder diffraction pattern of the malonate salt form B is shown in FIG29 ; the X-ray powder diffraction pattern of the succinate salt form A is shown in FIG30 ; the X-ray powder diffraction pattern of the succinate salt form B is shown in FIG31 ; Alternatively, the hydrochloride crystal form A, the hydrobromide crystal form A, the p-toluenesulfonate crystal form A, the sulfate crystal form A, the fumarate crystal form A, the oxalate crystal form A, the benzoylglycine salt crystal form A, the benzoylglycine salt crystal form B, the benzoylglycine salt crystal form C, the benzoylglycine salt crystal form D, the benzoylglycine salt crystal form E, the benzoylglycine salt crystal form F, the phosphate crystal form A, the maleate crystal form A, the maleate crystal form B, the maleate crystal form C, the maleate crystal form D, the methanesulfonate crystal form A, the benzenesulfonate crystal form A, The 2θ errors of the top ten diffraction peak positions with relative peak intensity in the X-ray powder diffraction patterns of malonate form A, malonate form B, succinate form A, and succinate form B are ±0.2° to ±0.5° respectively compared with the diffraction peaks at the corresponding positions in Figures 1, 4, 7, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31; Alternatively, the hydrochloride salt form A has a DSC spectrum as shown in Figure 2; or has a TGA spectrum as shown in Figure 3; the hydrobromide salt form A has a DSC spectrum as shown in Figure 5; or has a TGA spectrum as shown in Figure 6; the p-toluenesulfonate salt form A has a DSC spectrum as shown in Figure 8; or has a TGA spectrum as shown in Figure 9; the benzoylglycine salt form D has a DSC spectrum as shown in Figure 17; or has a TGA spectrum as shown in Figure 18.

30. The acid salt crystalline form of the compound according to claim 29, characterized in that: The hydrochloride crystal form A, hydrobromide crystal form A, p-toluenesulfonate crystal form A, sulfate crystal form A, fumarate crystal form A, oxalate crystal form A, benzoylglycine salt crystal form A, benzoylglycine salt crystal form B, benzoylglycine salt crystal form C, benzoylglycine salt crystal form D, benzoylglycine salt crystal form E, benzoylglycine salt crystal form F, phosphate crystal form A, maleate crystal form A, maleate crystal form B, maleate crystal form C, maleate crystal form D, methanesulfonate crystal form A, benzenesulfonate crystal form A, propanediol The positions of the diffraction peaks with the top ten relative peak intensities in the X-ray powder diffraction patterns of the salt form A, the malonate form B, the succinate form A, and the succinate form B are respectively compared with the diffraction peaks at the corresponding positions in Figures 1, 4, 7, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31, and the 2θ errors are ±0.2° to ±0.3°.

31. The acid salt crystalline form of the compound according to claim 30, characterized in that: The hydrochloride crystal form A, hydrobromide crystal form A, p-toluenesulfonate crystal form A, sulfate crystal form A, fumarate crystal form A, oxalate crystal form A, benzoylglycine salt crystal form A, benzoylglycine salt crystal form B, benzoylglycine salt crystal form C, benzoylglycine salt crystal form D, benzoylglycine salt crystal form E, benzoylglycine salt crystal form F, phosphate crystal form A, maleate crystal form A, maleate crystal form B, maleate crystal form C, maleate crystal form D, methanesulfonate crystal form A, benzenesulfonate crystal form A The 2θ errors of the top ten diffraction peak positions with relative peak intensities in the X-ray powder diffraction patterns of malonate form A, malonate form B, succinate form A, and succinate form B and the diffraction peaks at the corresponding positions in Figures 1, 4, 7, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31 are ±0.2° respectively.

32. A method for preparing the acid salt according to any one of claims 1 to 17, characterized in that: The specific steps include: 1) Weigh an appropriate amount of free base and dissolve it in a benign solvent; 2) weighing an appropriate amount of acid and, optionally, dissolving it in an organic solvent; 3) combining the above two solutions, stirring to precipitate or adding a poor solvent dropwise and stirring to precipitate; 4) Rapidly centrifuge or allow to dry to obtain the target product; in: The benign solvent is selected from acetone, toluene, acetonitrile, methanol, dichloromethane, tetrahydrofuran, ethyl formate, ethyl acetate, 2-methyl-tetrahydrofuran, 2-butanone, n-butanol, 1,4-dioxane, isobutanol, N,N-dimethylformamide, N,N-dimethylacetamide, n-propanol or tert-butanol; The organic solvent is selected from methanol, ethanol, ethyl acetate, dichloromethane, acetone, n-hexane, petroleum ether, benzene, toluene, chloroform, acetonitrile, carbon tetrachloride, dichloroethane, tetrahydrofuran, 2-methyl-tetrahydrofuran, 2-butanone, 3-pentanone, heptane, methyl tert-butyl ether, isopropyl ether, 1,4-dioxane, tert-butanol or N,N-dimethylformamide; the above benign solvent and organic solution need to be miscible when used; The poor solvent is selected from heptane, water, methyl tert-butyl ether, cyclohexane, toluene, isopropyl ether, ethyl acetate, acetone or acetonitrile; Or, specifically include the following steps: 1) Weigh an appropriate amount of free base and suspend it with a poor solvent; 2) Weigh an appropriate amount of acid and dissolve it in an organic solvent; 3) adding the solution of step 2) to the suspension of step 1) and stirring; 4) Rapidly centrifuge or dry to obtain the target product; in: The bad solvent is selected from ethanol, acetone, ethyl acetate, ethyl formate, isopropanol, isopropyl acetate, methyl tert-butyl ether, methanol, 1,4-dioxane, 2-butanone, 2-methyl-tetrahydrofuran, anisole, acetonitrile, chlorobenzene, benzene, toluene, n-butanol, isobutanol or 3-pentanone; The organic solvent is selected from methanol, ethanol, ethyl acetate, dichloromethane, acetone, n-hexane, petroleum ether, benzene, toluene, chloroform, acetonitrile, carbon tetrachloride, dichloroethane, tetrahydrofuran, 2-methyl-tetrahydrofuran, 2-butanone, 3-pentanone, heptane, methyl tert-butyl ether, isopropyl ether, 1,4-dioxane, tert-butanol or N,N-dimethylformamide; the above benign solvent and organic solution need to be miscible when used; The acid is selected from hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, phosphoric acid, 2,5-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, acetic acid, dichloroacetic acid, trichloroacetic acid, acetohydroxamic acid, adipic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, 4-aminobenzoic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclohexanesulfamic acid, camphorsulfonic acid, aspartic acid, camphoric acid, gluconic acid, glucuronic acid, glutamic acid, isoascorbic acid, lactic acid, malic acid, mandelic acid, pyroglutamic acid, tartaric acid, dodecyl sulfuric acid, dibenzoyl tartaric acid acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactosonic acid, gentisic acid, glutaric acid, 2-ketoglutaric acid, glycolic acid, benzoylglycine, isethionic acid, lactobionic acid, ascorbic acid, aspartic acid, lauric acid, camphoric acid, maleic acid, malonic acid, methanesulfonic acid, 1,5-naphthalene disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, thiocyanic acid, pamoic acid, formic acid, undecylenic acid, trifluoroacetic acid, benzenesulfonic acid, p-toluenesulfonic acid, or L-malic acid.

33. The method for preparing the acid salt according to claim 32, characterized in that: The amount of the acid in step 2) is selected from 1.0 to 1.5 equivalents; The benign solvent is selected from toluene, ethyl acetate, acetone, methanol or acetonitrile; The organic solvent is selected from methanol, ethanol or acetonitrile; The poor solvent is selected from water, methyl tert-butyl ether or isopropyl ether; Alternatively, in another step, The amount of the acid in step 2) is selected from 1.0 to 1.5 equivalents; The bad solvent is selected from ethanol, 2-methyl-tetrahydrofuran, anisole or ethyl acetate; The organic solvent is selected from methanol, ethanol or acetonitrile; The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid, succinic acid, isethionic acid, 1,5-naphthalene disulfonic acid, tartaric acid, adipic acid, formic acid, lauric acid or stearic acid.

34. The method for preparing the acid salt according to claim 32, characterized in that: The acid is selected from hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid, sulfuric acid, fumaric acid, oxalic acid, benzoylglycine, phosphoric acid, maleic acid, methanesulfonic acid, benzenesulfonic acid, malonic acid or succinic acid.

35. The method for preparing the acid salt according to claim 32, characterized in that: The acid is selected from benzoylglycine.

36. A method for preparing an acid salt crystalline form of the compound according to any one of claims 18 to 31, characterized in that: The specific steps include: 1) Weigh an appropriate amount of compound salt and suspend it with a poor solvent; 2) shaking the suspension of step 1) at a certain temperature for a certain period of time; 3) rapidly centrifuging the suspension of step 2), removing the supernatant, and drying the remaining solid to a constant weight to obtain the target product; in: The poor solvent is selected from methanol, ethanol, dichloromethane, 1,4-dioxane, acetonitrile, dichloromethane, chlorobenzene, benzene, toluene, acetone, ethyl acetate, water, 88% acetone, isopropyl acetate, 3-pentanone, ethyl formate, tetrahydrofuran, 2-methyl-tetrahydrofuran, isopropanol, n-butanol, isobutanol, n-propanol, methyl tert-butyl ether, n-heptane, tert-butanol or 2-butanone.

37. A pharmaceutical composition comprising a therapeutically effective amount of an acid salt of a compound according to any one of claims 1 to 17 or an acid salt crystalline form according to any one of claims 18 to 31, and one or more pharmaceutically acceptable carriers or excipients.

38. Use of the acid salt of the compound according to any one of claims 1 to 17 or the acid salt crystalline form according to any one of claims 18 to 31, and the pharmaceutical composition according to claim 37 in the preparation of a medicament for treating cancer-related diseases, wherein the cancer-related disease is a disease mediated by HER2 exon 20 mutation and / or EGFR20 exon mutation, and the cancer is non-small cell lung cancer.

Images