Aumolertinib or a pharmaceutically acceptable salt thereof, in particular aumolertinib mesylate

Abstract

A 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivative as represented by formula (I), and a preparation and application thereof as an EGFR inhibitor. The compound has activity of inhibiting the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, may be used to treat diseases mediated alone or in part by EGFR mutant activity, and has a wide application in drugs preventing and treating cancers, particularly non-small cell lung cancer.

Description

This invention belongs to the field of drug synthesis, specifically relating to an EGFR inhibitor and its preparation and application. EGFR (Epidermal Growth Factor Receptor) is a member of the erbB receptor family of transmembrane protein tyrosine kinases. Through binding to its ligands—such as epidermal growth factor (EGF)—EGFR can form homodimers on the cell membrane, or heterodimers with other receptors in the family (such as erbB2, erbB3, or erbB4). The formation of these dimers can induce phosphorylation of key intracellular tyrosine residues of EGFR, thereby activating multiple downstream signaling pathways. These intracellular signaling pathways play important roles in cell proliferation, survival, and anti-apoptosis. Dysregulation of EGFR signaling pathways, including increased expression of ligands and receptors, EGFR gene amplification, and mutations, can promote malignant transformation of cells and play a crucial role in tumor cell proliferation, invasion, metastasis, and angiogenesis. Therefore, EGFR is a rational target for anticancer drug development. First-generation small-molecule EGFR inhibitors, including gefitinib (Iressa™) and erlotinib (Tarceva™), have shown good efficacy in the treatment of lung cancer and have been used as first-line drugs for the treatment of non-small cell lung cancer (NSCLC) with EGFR activating mutations (New England Journal of Medicine (2008) Vol.358, 1160-74, Biochemical and Biophysical Research Communications (2004) Vol.319, 1-11). Compared to wild-type (WT) EGFR, activated mutant EGFR (including L858R and exon 19 deletion delE746_A750) has a decreased affinity for adenosine triphosphate (ATP) and an increased affinity for small molecule inhibitors, thereby increasing the sensitivity of tumor cells to first-generation EGFR inhibitors such as gefitinib or erlotinib, achieving the goal of targeted therapy (Science

[2004] Vol. 304, 1497-500; New England Journal of Medicine

[2004] Vol. 350, 2129-39). However, after 10-12 months of treatment with first-generation small-molecule EGFR inhibitors, almost all NSCLC patients develop resistance to these inhibitors. The resistance mechanisms include secondary EGFR mutations and parapathic pathway activation. In half of these cases, resistance is due to secondary mutations in the EGFR gate gene residue T790M, which reduces the affinity of the drug for the target, leading to tumor recurrence or disease progression. Given the importance and prevalence of this mutation in inducing resistance to EGFR-targeted therapy in lung cancer, several pharmaceutical companies (Pfizer, BI, AstraZeneca, etc.) have attempted to develop second-generation small-molecule EGFR inhibitors to treat these resistant lung cancer patients by inhibiting the EGFR T790M mutant strain. However, all attempts have failed due to poor selectivity. Even though afatinib has been approved by the FDA for the treatment of lung cancer, it is only used as first-line therapy for patients with EGFR activating mutations. For patients with EGFR T790M mutations, afatinib's stronger inhibitory effect on wild-type EGFR causes severe skin and gastrointestinal toxicity, limiting the dosage and demonstrating no therapeutic effect. Therefore, it is necessary to develop third-generation small-molecule EGFR inhibitors that can selectively inhibit EGFR T790M mutants while exhibiting little or no activity against wild-type EGFR. This high selectivity can significantly reduce skin and gastrointestinal damage caused by wild-type EGFR inhibition, thus achieving the goal of treating tumors resistant to EGFR T790M secondary mutations. Furthermore, retaining inhibitory activity against EGFR activating mutants (including L858R EGFR and exon 19 deletion delE746_A750) is also significant. Due to the weaker inhibition of wild-type EGFR, third-generation EGFR inhibitors have better safety profiles than first-generation EGFR inhibitors and hold promise as first-line treatments. They can treat NSCLC with EGFR activating mutations while simultaneously eliminating small amounts of EGFR T790T mutant strains that may be present in initially treated patients, thus delaying the development of resistance. Lung cancer is a major disease threatening human health, and lung cancer deaths are the leading cause of death from all malignant tumors. In my country, the incidence of lung cancer is rising year by year, with nearly 700,000 new cases annually. In Europe and the United States, lung cancer cases with EGFR activating mutations account for about 10% of all NSCLC cases; while in China, this proportion is as high as 30%. Therefore, China has a larger market for EGFR targets. Summary of the Invention During their research, the inventors discovered that a class of 4-substituted-2-(N-(5-allylamido)phenyl)amino)pyrimidine derivatives with the structure of formula (I) have the activity of inhibiting L858R EGFR mutants, T790M EGFR mutants and exon 19 deletion activation mutants. They can be used to treat diseases mediated by EGFR mutant activity alone or in part, and have wide applications, such as in the prevention and treatment of cancer, especially non-small cell lung cancer drugs. In one aspect, the present invention provides a compound having the following formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof: in: Ring A is selected from the following structure: Q is selected from bond, O, S, NR7 or CR7R8; R is selected from hydrogen or di-C1-8 alkylaminomethyl; X1, X2, and X3 are each independently selected from NR7 or CR8, provided that at least one of X1, X2, and X3 is selected from NR7; R1 is selected from the following structure: The three R6 substituents may be the same or different substituents; R2 is selected from C1-8 alkyl, C3-8 cycloalkyl, and optionally further substituted by one or more substituents selected from halogen, hydroxyl, C1-8 alkyl, C1-8 alkoxy, halosubstituted C1-8 alkoxy, C3-8 cycloalkyl or C3-8 cycloalkoxy; R3 is selected from hydrogen, deuterium, halogen, cyano, nitro, C1-8 alkyl, C1-8 alkoxy, C3-8 cycloalkyl, trifluoromethyl, trifluoromethoxy, SO2R9, C(O)R10, C(O)OR10 or P(O)R11R12; R4 and R5 are each independently selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio. The substituents are substituted by -C0-8-P(O)R11R12, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; or Two R4 or two R5 atoms bonded to the carbon atom of the benzene ring form a 5-7 membered carbon ring, a 5-7 membered heterocycle, a C5-7 aryl group, or a 5-7 membered heteroaryl group; The C1-8 alkyl, C3-8 cycloalkyl, 3-8 heterocyclic, C5-10 aryl, 5-10 heteroaryl, 5-7 carbon ring, 5-7 heterocycle, C5-7 aryl, or 5-7 heteroaryl groups may optionally be further selected from one or more of halogens, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, and C5-10 aryl groups. Substituents of oxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R6 is selected from hydrogen, deuterium, C1-8 alkyl, halosubstituted C1-8 alkyl, or C(O)R10; R7 is selected from hydrogen, deuterium, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, C5-10 aryl, 5-10 heteroaryl, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8 or -C0-8-C(O)NR7R8; The C1-8 alkyl, C3-8 cycloalkyl, 3-8 heterocyclic, C5-10 aryl, or 5-10 heteroaryl groups may optionally be further selected from one or more of halogens, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 ynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- Substituents of 10-membered heteroaryl, 5-10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R8 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroaryl... The substituents are arylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; The C1-8 alkyl, C3-8 cycloalkyl, 3-8 heterocyclic, C5-10 aryl, or 5-10 heteroaryl groups may optionally be further selected from one or more of halogens, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 ynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- Substituents of 10-membered heteroaryl, 5-10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R9 is selected from hydrogen, deuterium, C1-8 alkyl, C3-8 cycloalkyl, halosubstituted C1-8 alkyl, diC1-8 alkylamino, phenyl, or p-methylphenyl; R10, R11, and R12 are each independently selected from hydrogen, deuterium, C1-8 alkyl, C3-8 cycloalkyl, halogenated C1-8 alkyl, or hydroxylated C1-8 alkyl. m can be 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, 4 or 5; r is 0, 1, or 2; o can be 0, 1, 2, 3, or 4; p is 0, 1, 2 or 3; q can be 0, 1, 2, 3, or 4; This indicates a Z-type or E-type structure with R substituents. As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from C1-4 alkyl, C3-6 cycloalkyl, optionally further substituted by one or more substituents selected from halogen, hydroxyl, C1-8 alkyl, C1-8 alkoxy, halosubstituted C1-8 alkoxy, C3-8 cycloalkyl or C3-8 cycloalkoxy; and rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, r, o, p, q as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from C1-4 alkyl, C3-6 cycloalkyl, optionally further substituted by one or more substituents selected from halogens or hydroxyl groups; and rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, r, o, p, q as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from C1-4 alkyl groups, optionally further substituted by one or more substituents selected from fluorine or hydroxyl groups; and rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, r, o, p, q as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from methyl, difluoromethyl or trifluoromethyl; and rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, r as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IA): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; rings A, R, X1, X2, X3, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IIA1) or formula (IIA2): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; rings A, R, X1, X2, X3, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (ⅢA1-1), (ⅢA1-2), (ⅢA1-3), (ⅢA1-4), (ⅢA1-5), or (ⅢA1-6): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IVA1-1) or (IVA1-2): Among them, R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, and q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R3 is selected from hydrogen, deuterium, halogen, C1-8 alkyl, C1-8 alkoxy, C3-8 cycloalkyl, trifluoromethyl or trifluoromethoxy; and R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, trifluoromethyl or trifluoromethoxy; and R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl or trifluoromethyl; and R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q as defined in the compound of formula (I). As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formulas (IVA1-3): Among them, R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, and q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in the compound of formula (I); provided that m is 3 or 4 when R7 and R8 are both hydrogen; m is 2, 3 or 4 when R7 or R8 is hydrogen; and m is 1, 2, 3 or 4 when neither R7 nor R8 is hydrogen. As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl or trifluoromethyl; R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in the compound of formula (I); wherein m is 3 or 4 when R7 and R8 are both hydrogen; m is 2, 3 or 4 when R7 or R8 is hydrogen; and m is 1, 2, 3 or 4 when neither R7 nor R8 is hydrogen. As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein m is 2, 3 or 4; R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl or trifluoromethyl; the two R4 carbon atoms connected to the benzene ring form a 5-7 membered carbon ring, a 5-7 membered heterocycle, a C5-7 aryl or a 5-7 membered heteroaryl, wherein the 5-7 membered carbon ring, 5-7 membered heterocycle, C5-7 aryl or a 5-7 membered heteroaryl is selected from the following structures; The 5-7 membered carbon ring, 5-7 membered heterocycle, C5-7 aryl, or 5-7 membered heteroaryl may optionally be further selected from one or more of halogens, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 membered heteroaryl Substituents of -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R, R1, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein m is 1 or 2 when both R7 and R8 are hydrogen; m is 0 or 1 when either R7 or R8 is hydrogen; and m is 0, 1 or 2 when neither R7 nor R8 is hydrogen; R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl or trifluoromethyl. R4 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0- The substituents are substituted by 8-P(O)R11R12, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; The C1-8 alkyl, C3-8 cycloalkyl, 3-8 heterocyclic, C5-10 aryl, 5-10 heteroaryl, 5-7 carbon ring, 5-7 heterocycle, C5-7 aryl, or 5-7 heteroaryl groups may optionally be further selected from one or more of halogens, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, and C5-10 aryl groups. Substituents of oxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R, R1, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, in the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R4 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio. Substituents of 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; R, R1, R6, R7, R8, R9, R10, R11, R12, r, q are as defined in compound (I); m is as defined above. As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; R4 is selected from substituents of hydrogen, deuterium, hydroxyl, cyano, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 heteroaryloxy, -C0-8-O-R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8; R, R1, R6, R7, R8, R9, R10, R11, R12, q are as defined in compound (I); m is as defined above. As a further preferred embodiment, in the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; R4 is selected from substituents of hydrogen, deuterium, hydroxyl, cyano, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxetane-3-yl, N-R6-azacyclobutane-3-yl, cyclopropoxy, cyclobutoxy, phenyl, phenoxy, -CO-8-O-R10, -CO-8-C(O)OR10, -CO-8-OC(O)R10, -CO-8-NR7R8, -CO-8-C(O)NR7R8; R, R1, R6, R7, R8, R9, R10, R11, R12, q are as defined in compound (I); m is as defined above. As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formulas (ⅢA1-7), (ⅢA1-8), or (ⅢA1-9): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R1 is selected from R2 is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and R, R4, R6, R7, R8, R9, R10, R11, R12, m, r are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formulas (IVA1-4) or (IVA1-5): Wherein, R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; R, R4, R6, R7, R8, R9, R10, R11, R12, m, r are as defined in compound (I). As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IVA1-6) or (IVA1-7): Wherein, R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; R, R4, R6, R7, R8, R9, R10, R11, R12, m, r are as defined in compound (I). As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, is selected from compounds of formula (ⅢA2-1), (ⅢA2-2), (ⅢA2-3), (ⅢA2-4), (ⅢA2-5), or (ⅢA2-6): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and R, R1, R4, R6, R7, R8, R9, R10, R11, R12, m, r, q are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R1 is selected from R2, which is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and R4, R6, R7, R8, R9, R10, R11, R12, m, r are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IB): Wherein, Q, R, R1, R2, R3, R5, R6, R7, R8, R9, R10, R11, R12, n, r, and q are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and Q, R, R1, R5, R6, R7, R8, R9, R10, R11, R12, n, r, q are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R1 is selected from R2 is selected from methyl, difluoromethyl or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; and Q, R5, R6, R7, R8, R9, R10, R11, R12, n, r are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IIB): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; Q, R5, R6, R7, R8, R9, R10, R11, R12, n, r are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IIIB): Wherein, R2 is selected from methyl, difluoromethyl or trifluoromethyl; R5, R6, R7, R8, R9, R10, R11, R12, n, r are as defined in compound (I). As the most preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IC): Wherein, Q, R, R1, R2, R3, R4, R6, R7, R8, R9, R10, R11, R12, r, p, o, and q are as defined in claim 1. As a further preferred embodiment, the compound of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, wherein R2 is selected from difluoromethyl, trifluoromethyl or methyl; R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl, cyano or nitro; and Q, R, R1, R4, R6, R7, R8, R9, R10, r, p, o are as defined in the compound of formula (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IIC1) or formula (IIC2): Wherein, R2 is selected from difluoromethyl, trifluoromethyl or methyl; R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl, cyano or nitro; Q, R, R4, R6, R7, R8, R9, R10, R11, R12, o, r are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from compounds of formula (IIIC1) or formula (IIIC2): R2 is selected from difluoromethyl, trifluoromethyl or methyl; R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl, cyano or nitro; Q, R, R4, R6, R7, R8, R9, R10, r, o are as defined in compound (I). As a further preferred embodiment, the compound of formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof are selected from the following compounds: Another aspect of the present invention provides a method for preparing a compound of formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof, comprising the following steps: Among them, rings A, Q, X1, X2, X3, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, r, o, p, and q are as defined in compound (I). Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective dose of the aforementioned compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Another aspect of the present invention provides the use of the aforementioned compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition in the preparation of a therapeutic remedy for diseases mediated by EGFR mutants, particularly L858R EGFR mutants, T790M EGFR mutants and exon 19 deletion activation mutants. Another aspect of the present invention provides the use of the aforementioned compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition in the preparation of a therapeutic remedy for treating diseases mediated alone or in part by EGFR mutant activity. Another aspect of the present invention provides the use of the aforementioned compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition in the preparation of a medicament for treating cancer. As a further preferred option, the cancer is selected from ovarian cancer, cervical cancer, colorectal cancer, breast cancer, pancreatic cancer, glioma, glioblastoma, melanoma, prostate cancer, leukemia, lymphoma, non-Hodgkin's lymphoma, gastric cancer, lung cancer, hepatocellular carcinoma, gastric cancer, gastrointestinal stromal tumor (GIST), thyroid cancer, bile duct cancer, endometrial cancer, renal cancer, anaplastic large cell lymphoma, acute myeloid leukemia (AML), multiple myeloma, melanoma, or mesothelioma; preferably non-small cell lung cancer. Detailed explanation: Unless otherwise stated, the terms used in the specification and claims shall have the following meanings. "C1-8 alkyl" refers to straight-chain alkyl groups and branched alkyl groups containing 1 to 8 carbon atoms. Alkyl refers to saturated aliphatic hydrocarbon groups. C0-8 refers to alkyl groups that do not contain carbon atoms or are C1-8 alkyl groups, such as 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 or their various branched isomers, etc. The alkyl group can be substituted or unsubstituted. When substituted, the substituent can be replaced at any usable linking point, preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5 The substituents are substituted by -10-membered heteroaryl, 5-10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Cycloalkyl" refers to a substituent in a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon; "C3-8 cycloalkyl" refers to a cycloalkyl group containing 3 to 8 carbon atoms; and "5-10 membered cycloalkyl" refers to a cycloalkyl group containing 5 to 10 carbon atoms. For example: Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, cyclooctyl, etc. Polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups. "Spirocycloalkyl" refers to a polycyclic group in which a single carbon atom (called a spiro atom) is shared between the rings. These groups may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Based on the number of shared spiro atoms between the rings, spirocycloalkyl groups are classified as monospirocycloalkyl, bispirocycloalkyl, or polyspirocycloalkyl. Non-limiting examples of spirocycloalkyl groups include: "Fused cycloalkyl" refers to a polycyclic aromatic hydrocarbon group in which each ring shares an adjacent pair of carbon atoms with the other rings in the system. One or more rings may contain one or more double bonds, but no single ring has a fully conjugated π-electron system. Based on the number of constituent rings, fused cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Non-limiting examples of fused cycloalkyl groups include: "Bridged cycloalkyl" refers to a polycyclic aromatic hydrocarbon group in which any two rings share two non-directly bonded carbon atoms. These groups may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Based on the number of constituent rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyl groups. Non-limiting examples of bridged cycloalkyl groups include: The cycloalkyl ring may be fused to an aryl, heteroaryl, or heterocycloalkyl ring, wherein the ring connected to the parent structure is a cycloalkyl ring, and non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, and 5-10 membered heteroaryl. Substituents of 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Heterocyclic group" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, wherein one or more ring atoms are selected from nitrogen, oxygen, or S(O)r (where r is an integer 0, 1, or 2), but excluding the ring portion of -OO-, -OS-, or -SS-, and the remaining ring atoms are carbon. "5-10 membered heterocyclic group" refers to a cyclic group containing 5 to 10 ring atoms, and "3-8 membered heterocyclic group" refers to a cyclic group containing 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclic groups include pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, etc. Polycyclic heterocyclic groups include spirocyclic, fused-ring, and bridged-ring heterocyclic groups. A "spiroheterocyclic group" refers to a polycyclic heterocyclic group in which one or more ring atoms share a single atom (called a spiro atom), wherein one or more ring atoms are selected from nitrogen, oxygen, or S(O)r (where r is an integer 0, 1, or 2), and the remaining ring atoms are carbon. These may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Spirocycloalkyl groups are classified into monospirocyclic, bispirocyclic, or polyspirocyclic groups based on the number of shared spiro atoms between the rings. Non-limiting examples of spirocycloalkyl groups include: "Fused heterocyclic group" refers to a polycyclic heterocyclic group in which each ring in the system shares an adjacent pair of atoms with the other rings in the system. One or more rings may contain one or more double bonds, but no ring has a fully conjugated π-electron system. One or more ring atoms are selected from nitrogen, oxygen, or S(O)r (where r is an integer 0, 1, or 2) heteroatoms, and the remaining ring atoms are carbon. Based on the number of constituent rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic fused heterocyclic alkyl groups. Non-limiting examples of fused heterocyclic groups include: "Bridged heterocyclic groups" refer to polycyclic heterocyclic groups in which any two rings share two non-directly bonded atoms. These may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. One or more ring atoms are selected from nitrogen, oxygen, or S(O)r heteroatoms (where r is an integer 0, 1, or 2), and the remaining ring atoms are carbon. Based on the number of constituent rings, they can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged alkyl groups. Non-limiting examples of bridged alkyl groups include: The heterocyclic ring may be fused to an aryl, heteroaryl, or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclic group. Non-limiting embodiments include: The heterocyclic group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, and 5-10 membered heteroaryl. Substituents of 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Aryl" refers to an all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent carbon atom pairs) group, a polycyclic (i.e., a ring with adjacent carbon atom pairs) group having a conjugated π-electron system, "C5-10 aryl" refers to an all-carbon aryl containing 5-10 carbons, and "5-10-membered aryl" refers to an all-carbon aryl containing 5-10 carbons, such as phenyl and naphthyl. The aryl ring can be fused to a heteroaryl, heterocyclic, or cycloalkyl ring, wherein the ring connected to the parent structure is an aryl ring. Non-limiting embodiments include: The aryl group can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 membered heteroaryl, 5 The substituents are substituted by -10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Heteroaryl" refers to a heteroaryl system containing 1 to 4 heteroatoms, including nitrogen, oxygen, and S(O)r (where r is an integer 0, 1, or 2). 5-7-membered heteroaryl refers to a heteroaryl system containing 5-7 ring atoms, and 5-10-membered heteroaryl refers to a heteroaryl system containing 5-10 ring atoms, such as furanyl, thiophene, pyridinyl, pyrroleyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, etc. The heteroaryl ring can be fused to an aryl, heterocyclic, or cycloalkyl ring, wherein the ring connected to the parent structure is the heteroaryl ring. Non-limiting embodiments include: The heteroaryl group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, 5-10 membered heteroaryl thio, -CO-8-S(O)rR9, -CO-8-O-R10, -CO-8-C(O)R10. The substituents are replaced by -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Alkenyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond. C2-8 chain alkenyl refers to a straight-chain or branched alkenyl group containing 2-8 carbon atoms. Examples include vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl. The alkenyl group can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 membered heteroaryl, 5 The substituents are substituted by -10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Alynyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon triple bond. C2-8 chain alkynyl refers to a straight-chain or branched alkynyl group containing 2-8 carbon atoms. Examples include ethynyl, 1-propynyl, 2-propynyl, 1-, 2-, or 3-butynyl. The alkynyl group can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 membered heteroaryl, 5 The substituents are substituted by -10-membered heteroaryloxy, 5-10-membered heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Alkoxy" refers to -O-(alkyl), where alkyl is defined as described above. C1-8 alkoxy refers to alkyloxy groups containing 1-8 carbons, and non-limiting examples include methoxy, ethoxy, propoxy, butoxy, etc. The alkoxy group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclic, 3-8 membered heterocyclic oxy, 3-8 membered heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, and 5-10 membered heteroaryl. Substituents of 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10; "Cycloalkoxy" refers to -O- (unsubstituted cycloalkyl), where cycloalkyl is defined as described above. C3-8 cycloalkoxy refers to cycloalkyloxy containing 3-8 carbons, and non-limiting examples include cyclopropoxy, cyclobutoxy, cyclopentoxy, cyclohexoxy, etc. The cycloalkoxy group can be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from halogen, hydroxyl, mercapto, cyano, nitro, azide, C1-8 alkyl, ... The substituents of C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3-8 heterocyclic, 3-8 heterocyclic oxy, 3-8 heterocyclic thio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C0-8-S(O)rR9, -C0-8-O-R10, -C0-8-C(O)R10, -C0-8-C(O)OR10, -C0-8-OC(O)R10, -C0-8-NR7R8, -C0-8-C(O)NR7R8, -N(R7)-C(O)R10 or -N(R7)-C(O)OR10 are substituted. "Halogen-substituted C1-8 alkyl" refers to 1-8 carbon alkyl groups on an alkyl group in which the hydrogen atoms are optionally replaced by fluorine, chlorine, bromine, or iodine atoms, such as difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, etc. "Halogen-substituted C1-8 alkoxy" refers to alkoxy groups consisting of 1-8 carbon atoms of an alkyl group whose hydrogen atom is optionally replaced by a fluorine, chlorine, bromine, or iodine atom. Examples include difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, and tribromomethoxy. "Halogen" refers to fluorine, chlorine, bromine, or iodine. “C(O)R10” refers to a carbonyl group substituted with R10. "-C0-8-P(O)R11R12" refers to a phosphoryl C0-8 alkyl group substituted with R11 and R12, where R11 and R12 may be the same or different substituents. "THF" refers to tetrahydrofuran. "DCM" refers to dichloromethane. "DMF" refers to N,N-dimethylformamide. "DIPEA" refers to diisopropylethylamine. "Optional" or "optionally" means that the event or circumstance described below may, but does not have to, occur. This description includes situations in which the event or circumstance may or may not occur. For example, "optionally alkyl-substituted heterocyclic group" means that an alkyl group may, but does not have to, be present. This description includes cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group. "Substituted" refers to one or more hydrogen atoms in a group, preferably up to five, and more preferably one to three hydrogen atoms, which are independently substituted 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 much effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom having an unsaturated bond (such as an alkene). "Pharmaceutical composition" means a mixture containing one or more of the compounds described herein or their physiologically / pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically / pharmacologically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity. The present invention will be further described in detail and completely below with reference to the embodiments, but this is by no means a limitation of the present invention, nor is the present invention limited to the contents of the embodiments. The structures of the compounds of this invention were determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer with deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as solvents, and tetramethylsilane (TMS) as the internal standard. LC-MS was performed using an Agilent 1200 Infinity Series mass spectrometer. HPLC was performed using an Agilent 1200DAD high-performance liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-performance liquid chromatograph (Gimini C18 150×4.6 mm column). Thin-layer chromatography (TLC) uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The standard size for TLC is 0.15mm to 0.20mm, while the standard size for TLC separation and purification is 0.4mm to 0.5mm. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier. The starting materials used in the embodiments of the present invention are known and commercially available, or can be synthesized using or in accordance with methods known in the art. Unless otherwise specified, all reactions in this invention are carried out under continuous magnetic stirring, in a dry nitrogen or argon atmosphere, using a dry solvent, and the reaction temperature is expressed in degrees Celsius. intermediate preparation 1. Preparation of intermediate 1: 2-(difluoromethoxy)-4-fluoronitrobenzene 5-Fluoro-2-nitrophenol (3.0 g, 19.1 mmol) and potassium carbonate (5.28 g, 38.2 mmol) were dissolved in DMF, and sodium dichlorofluoroacetate (4.37 g, 28.6 mmol) was added. The reaction was heated to 100 °C under nitrogen protection and stirred for 16 hours. The reaction solution was concentrated, and the residue was added with H2O (50 mL) and methyl tert-butyl ether (50 mL). The mixture was extracted and separated. The organic phase was washed three times with water and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and the residue was purified by rapid silica gel column chromatography to obtain 2-(difluoromethoxy)-4-fluoronitrobenzene (3.0 g, 75%). 2. Preparation of intermediate 2: 2-(difluoromethoxy)-4-fluoro-5-nitroaniline 2-(difluoromethoxy)-4-fluoronitrobenzene (3.0 g, 14.5 mmol) was dissolved in methanol (30 mL), and Pd / C (500 mg) was added. The reaction was carried out at room temperature under a hydrogen atmosphere for 2 hours. The reaction was monitored by TLC until complete. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated to obtain a crude product (1.7 g, 66%). This crude product was carefully dissolved in concentrated sulfuric acid (5 mL) under ice bath. After stirring under ice bath until clear, potassium nitrate (1.1 g, 9.5 mmol) was slowly added in portions. The reaction was continued to be stirred under ice bath for 3 hours. LCMS showed that the reaction was complete. The reaction solution was slowly added to a saturated sodium carbonate aqueous solution (100 mL). After the reaction was completely quenched, the aqueous phase was extracted with methyl tert-butyl ether (3 × 20 mL). The organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified by rapid silica gel column chromatography to obtain 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (2.0 g, 90%). 3. Preparation of intermediate 3: 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene 3-Fluoro-trifluoromethoxybenzene (20g) was dissolved in 40 mL of concentrated sulfuric acid under ice water cooling. Potassium nitrate (28g) was added in portions with rapid stirring. The mixture was stirred at 0°C for 3 hours and then at room temperature overnight. The reaction solution was carefully poured onto 1 kg of crushed ice and stirred for 30 minutes. The solution was extracted with ethyl acetate, dried over sodium sulfate, filtered, and the filtrate was distilled off. The residue was purified by column chromatography to obtain 12 g of crude product as a pale yellow liquid. 4. Preparation of intermediate 4: 4-fluoro-2-(trifluoromethoxy)aniline The crude 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene (12 g) prepared in the previous step was dissolved in 100 mL of anhydrous ethanol. Stannous chloride dihydrate (25 g) was added under ice-water cooling, and the reaction mixture was stirred overnight at room temperature. The pH was adjusted to approximately 12 by adding 1 N sodium hydroxide aqueous solution, filtered, and the filtrate was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated. The residue was purified by column chromatography to obtain a pale yellow oily liquid, 4-fluoro-2-(trifluoromethoxy)aniline (4.78 g, 46%). 1H NMR (400MHz, CDCl3) δ6.94 (d, J=8.8Hz, 1H), 6.83 (m, 1H), 6.76 (dd, J=5.4, 8.8Hz, 1H), 3.87-3.59 (br, 2H). 5. Preparation of intermediate 5: 4-fluoro-5-nitro-2-(trifluoromethoxy)aniline 4-Fluoro-2-(trifluoromethoxy)aniline (2.5 g) was dissolved in concentrated sulfuric acid (10 mL) cooled in ice water, potassium nitrate (3 g) was added, and the mixture was stirred at room temperature for 3 hours. The reaction solution was then poured into ice water, and the pH was adjusted to about 10 with 3N sodium hydroxide aqueous solution. The mixture was extracted with ethyl acetate, dried with anhydrous sodium sulfate, filtered, and the solvent was concentrated. The residue was purified by column chromatography to obtain 4-fluoro-5-nitro-2-(trifluoromethoxy)aniline (1.79 g, 58%). 6. Preparation of intermediate 6: 6-methoxy-1-methyl-1H-indole 1H-indole-6-phenol (1 g, 7.51 mmol) was dissolved in anhydrous DMF (20 mL). NaH (900 mg, 22.53 mmol) was added in portions under an ice-water bath. The reaction was stirred under an ice bath for 20 minutes, and iodomethane (2.67 g, 18.78 mmol) was slowly added dropwise. The reaction was stirred under an ice bath for 2 hours. The reaction was confirmed to be complete by LCMS. The reaction was quenched with saturated NH4Cl (40 mL) under an ice bath. The mixture was extracted with methyl tert-butyl ether (3 × 30 mL), and the combined organic phases were washed with water (20 mL × 2). The mixture was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified by rapid silica gel column chromatography to obtain the product 6-methoxy-1-methyl-1H-indole (1.1 g, 90%). 7. Preparation of intermediate 7: 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole N-methylindole (300 mg, 2.29 mmol), 2,4-dichloropyrimidine (340 mg, 2.30 mmol), and anhydrous aluminum trichloride (460 mg, 3.43 mmol) were dissolved in ethylene glycol dimethyl ether (12 mL). The reaction was carried out under nitrogen protection and heated to 60 °C with stirring for 3 hours. After the reaction was complete, the reaction solution was poured into an ice-water mixture (about 50 mL). The mixture was extracted with methyl tert-butyl ether (20 mL × 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, concentrated, and the residue was purified by column chromatography to obtain the product 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (400 mg, 72%). 8. Preparation of intermediate 8: 3-(2-chloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole 6-Methoxy-1-methyl-1H-indole (300 mg, 1.86 mmol) and 2,4-dichloropyrimidine (330 mg, 2.23 mmol) were dissolved in ethylene glycol dimethyl ether (10 mL), and anhydrous aluminum trichloride (500 mg, 3.72 mmol) was added. The reaction was carried out under nitrogen protection, heated to 60 °C, and stirred for 3 hours. The reaction was monitored by LCMS until complete. The reaction solution was poured into an ice-water mixture (50 mL) and extracted with methyl tert-butyl ether (50 mL × 3). The organic phases were combined and washed successively with saturated sodium bicarbonate (30 mL × 2) and H2O (30 mL). The organic phases were dried, filtered, and the filtrate was concentrated. The residue was purified by rapid silica gel column chromatography to obtain the product 3-(2-chloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (120 mg, 24%). 9. Preparation of intermediate 9: 4-(2-(methylamino)ethyl)morpholin-3-one (2-hydroxyethyl)(methyl)carbamate tert-butyl ester (300 mg, 1.71 mmol) and triethylamine (350 mg, 3.42 mmol) were dissolved in anhydrous dichloromethane (10 mL). The reaction mixture was then added in portions of p-toluenesulfonyl chloride (490 mg, 2.57 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 h, and the reaction was monitored for completeness by LCMS. The reaction solution was washed successively with saturated sodium bicarbonate solution (10 mL), 1N HCl (10 mL), and H₂O (10 mL × 2). After drying with anhydrous magnesium sulfate, the solution was filtered. The filtrate was concentrated to obtain crude 2-((tert-butoxycarbonyl)(methyl)amino)ethyl 4-methylbenzenesulfonate (560 mg, 99%), which was used directly in the next reaction without further processing. Morpholin-3-one (180.5 mg, 1.79 mmol) was dissolved in anhydrous DMF. NaH (136 mg, 3.4 mmol) was added at 0 °C, and the reaction was stirred in an ice bath for 10 minutes. 2-((tert-butoxycarbonyl)(methyl)amino)ethyl-4-methylbenzenesulfonate (560 mg, 1.7 mmol) was added to the reaction solution, and the reaction was stirred in an ice bath at room temperature for 16 hours. LCMS was used to monitor the reaction until complete. The reaction solution was quenched with saturated NH4Cl aqueous solution (20 mL), extracted with dichloromethane (10 mL × 2), and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, concentrated, and the residue was dissolved in 4N dioxane hydrochloride solution (10 mL). The mixture was stirred at room temperature for 1 hour, and LCMS was used to monitor the reaction until complete. The reaction solution was concentrated to obtain crude 4-(2-(methylamino)ethyl)morpholin-3-one (150 mg, 98%), which could be used directly in the next reaction without further purification. 10. Preparation of intermediate 10: 1-(2-((tert-butyldimethylsilyl)oxo)ethyl)-1H-indole Indole (4.45 g, 38 mmol) was dissolved in 100 mL of DMF, and then 60% sodium hydroxide (4.6 g, 113.9 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes, and then ((tert-butyldimethylsilyl)oxo)-2-bromoethyl (10 g, 41.81 mmol) was added dropwise. The reaction was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was poured into water, extracted three times with ethyl acetate, and the organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain 1-(2-((tert-butyldimethylsilyl)oxo)ethyl)-1H-indole (9.54 g, 90%). 11. Preparation of intermediate 11: 1-(2-((tert-butyldimethylsilyl)oxo)ethyl)-3-(2-chloropyrimidin-4-yl)-1H-indole 1-(2-((tert-butyldimethylsilyl)oxo)ethyl)-1H-indole (2 g, 7.26 mmol), 2,4-dichloropyrimidine (1.2 g, 8.00 mmol), and aluminum trichloride (1.45 g, 10.89 mmol) were dissolved in 30 mL of DME, and the reaction mixture was stirred overnight at 75 °C. After the reaction was complete, the reaction solution was poured into ice water, extracted three times with methyl tert-butyl ether, and the organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was then purified by rapid silica gel column chromatography to obtain the product (1.1%, 39%). 12. Preparation of intermediate 12, 5-methoxy-1-methyl-1H-indole 5-Methoxy-1H-indole (2.2 g, 15 mmol) was dissolved in THF (30 mL) and cooled to 0 °C. NaH (0.9 g, 32 mmol) was added to the solution with stirring. The reaction was stirred at 0 °C for 1 hour. Iodomethane (4.2 g, 30 mmol) was added at 0 °C, and the reaction was allowed to proceed to room temperature overnight with stirring. LC-MS showed that the starting material had disappeared. The solution was adjusted to pH 3 with HCl (1 N aqueous solution), THF was removed under reduced pressure, CH2Cl2 (60 mL) was added, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and then subjected to column chromatography (eluent: PE ~ PE: EtOAc = 10:1) to give 5-methoxy-1-methyl-1H-indole (0.9 g, 35%). 1H NMR (400MHz, CD3OD): δ7.25(d,J=8.4Hz,1H), 7.10(d,J=2.8Hz,1H), 7.06(d, J=2.0Hz,1H),6.83(d,J=2.4Hz,1H),6.34(m,1H),3.82(s,3H),3.77(s,3H); MS m / z(ESI): 162.2[M+H]+. Preparation of compounds in the examples Example 1: Preparation of N-(4-(difluoromethoxy)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)acryloylamide Step 1: Preparation of 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-N1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-nitrobenzene-1,4-diamine N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (250 mg, 0.58 mmol) was dissolved in DMF, and diisopropylethylamine (150 mg, 1.16 mmol) and trimethylethylenediamine (120 mg, 1.16 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the residue was extracted with dichloromethane (10 mL) and H2O (10 mL). The organic phase was separated by preparative thin-layer chromatography to obtain the product 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-N1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-nitrobenzene-1,4-diamine (150 mg, 50%). Step 2: 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-N1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-nitrobenzene-1,4-diamine (60 mg, 0.12 mmol) was dissolved in methanol, and Pd / C (10 mg) was added. The reaction was stirred at room temperature under hydrogen atmosphere for 2 hours. The reaction was monitored by LCMS until complete. The reaction was filtered, and the filtrate was concentrated to obtain the product 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (55 mg, 95%), which was directly used in the next step of the reaction. Step 3: N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (55 mg, 0.11 mmol) and triethylamine (58 mg, 0.57 mmol) were dissolved in anhydrous tetrahydrofuran (15 mL). The reaction mixture was stirred in an ice-water bath for 10 minutes, and then acryloyl chloride (0.17 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in an ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with 3 mL of saturated NH4Cl aqueous solution. The reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain the product N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (12.3 mg, 20%). 1H NMR (400MHz, CDCl3) δ10.17(s,1H),9.81(s,1H),8.89(s,1H),8.33(d,J=5.3Hz,1H),8.00(dd,J=6.7,2.0Hz,1H),7.40(s,1H),7.32(dd,J=6.8,1.9H z,1H),7.25–7.13(m,1H),6.98(s,1H),6.66–6.20(m,3H),5.74–5.58(m,1 H),3.90(s,3H),2.92–2.77(m,2H),2.62(s,3H),2.27(s,2H),2.22(s,6H); MS m / z(ESI): 536.2[M+H]+. Example 2: Preparation of N-(4-(difluoromethoxy)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)acryloylamide Step 1: Preparation of N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (250 mg, 1.0 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (230 mg, 1.0 mmol), and p-toluenesulfonic acid monohydrate (200 mg, 1.1 mmol) were dissolved in 2-pentanol (2 mL). The reaction was carried out by microwave heating to 120 °C for 1 hour. The reaction was confirmed to be complete by LCMS. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give the crude product N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1-methyl-1H-indole-3-yl)pyrimidin-2-amine (250 mg). Step 2: Preparation of N-(2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidine-2-amine N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (150 mg, 0.35 mmol) and methylpiperazine (105 mg, 1.05 mmol) were dissolved in DMF (2 mL). The reaction was carried out in a microwave oven at 120 °C for 30 min. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain N-(2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (50 mg, 28%). Step 3: Preparation of 6-(difluoromethoxy)-N1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)phenyl-1,3-diamine N-(2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (50 mg, 98.0 μmmol) was dissolved in methanol (10 mL), and Pd / C (10 mg) was added. The reaction was hydrogenated at room temperature for 2 hours. The reaction was confirmed to be complete by LCMS. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated to obtain the crude product 6-(difluoromethoxy)-N1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)phenyl-1,3-diamine (40 mg, 85%), which was directly used in the next step of the reaction. Step 4: Preparation of N-(4-(difluoromethoxy)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)acryloylamide 6-(difluoromethoxy)-N-1-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)phenyl-1,3-diamine (40 mg, 83.4 μmol) and triethylamine (50 mg, 0.50 mmol) were dissolved in anhydrous tetrahydrofuran (15 mL). The reaction was stirred in an ice bath for 10 minutes, and then acryloyl chloride (0.15 mL, 0.15 mmol, 1 M in THF) was slowly added. The reaction was stirred in an ice bath for 2 hours. The reaction was confirmed to be complete by LCMS. The reaction was quenched with saturated NH4Cl (5 mL). The reaction solution was concentrated, and the remaining aqueous solution was extracted with dichloromethane (10 mL × 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified by preparative thin-layer chromatography to obtain N-(4-(difluoromethoxy)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)acryloylamide (12 mg, 27%). 1H NMR (400MHz, CDCl3) δ9.76 (s, 1H), 8.82 (s, 1H), 8.66 (s, 1H), 8.33 (d, J = 5.3Hz ,1H),8.05–7.97(m,1H),7.44(s,1H),7.33(dd,J=6.9,1.8Hz,1H),7.23(dd,J =7.1,1.4Hz,2H),7.18(d,J=5.3Hz,1H),7.00(s,1H),6.64–6.20(m,3H),5.75 (dd,J=10.0,1.5Hz,1H),3.90(s,3H),2.90(s,4H),2.68(s,4H),2.41(s,3H); MS m / z(ESI): 534.3[M+H]+. Example 3: Preparation of N-(4-(difluoromethoxy)-2-(methyl(2-(3-carbonylmorpholino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 4-(2-((5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)morpholin-3-one N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (200 mg, 0.46 mmol), 4-(2-(methylamino)ethyl)morpholin-3-one (110 mg, 0.69 mmol), and diisopropylethylamine (180 mg, 1.4 mmol) were dissolved in DMF. The reaction was carried out at 120 °C for 30 minutes under microwave conditions. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain the product 4-(2-((5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)morpholin-3-one (100 mg, 38%). Step 2: 4-(2-((2-amino-5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)morpholin-3-one 4-(2-((5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)morpholin-3-one (100 mg, 0.17 mmol) was dissolved in methanol (5 mL), and Pd / C (10 mg) was added. The reaction was hydrogenated at room temperature for 2 hours. The reaction was confirmed to be complete by LCMS. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated to obtain the product 4-(2-((2-amino-5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)morpholin-3-one (40 mg, 40%). Step 3: N-(4-(difluoromethoxy)-2-(methyl(2-(3-carbonylmorpholino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide 4-(2-((2-amino-5-(difluoromethoxy)-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)morpholin-3-one (40 mg, 74.4 μmmol) and triethylamine (40 mg, 0.37 mmol) were dissolved in anhydrous tetrahydrofuran (15 mL). The reaction was stirred in an ice bath for 10 minutes. Then, acryloyl chloride (0.1 mL, 100 μmol, 1 M infusion) was slowly added in an ice bath. The reaction was stirred in an ice bath for 30 minutes. LCMS analysis showed the reaction was complete. The reaction was quenched with saturated NH4Cl (5 mL), concentrated, and the remaining aqueous solution was extracted with dichloromethane (5 mL × 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified using a preparative plate to obtain the product N-(4-(difluoromethoxy)-2-(methyl(2-(3-carbonylmorpholino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (10 mg, 23%). 1H NMR (400MHz, CDCl3) δ9.79 (s, 1H), 8.83 (d, J = 44.6Hz, 2H), 8.30 (d, J = 5.4Hz, 1H), 7.99 (dd, J=6.7,1.8Hz,1H),7.33(dd,J=6.9,1.8Hz,1H),7.25–7.20(m,2H),7.18(s,1H),6.96(s,1H ),6.71–6.30(m,3H),5.74(dd,J=9.5,2.2Hz,1H),4.08(s,2H),3.90(s,3H),3.73(dd,J=5. 7,4.5Hz,2H),3.49(t,J=6.1Hz,2H),3.24–3.19(m,2H),3.05(t,J=6.1Hz,2H),2.61(s,3H); MS m / z(ESI): 592.3[M+H]+. Example 4: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 3-(2-chloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole 6-Methoxy-1-methyl-1H-indole (300 mg, 1.86 mmol) and 2,4-dichloropyrimidine (330 mg, 2.23 mmol) were dissolved in ethylene glycol dimethyl ether (10 mL), and anhydrous aluminum trichloride (500 mg, 3.72 mmol) was added. The reaction was carried out under nitrogen protection, heated to 60 °C, and stirred for 3 hours. The reaction was confirmed to be complete by LCMS. The reaction solution was poured into about 50 mL of ice water and extracted with methyl tert-butyl ether (50 mL × 3). The organic phases were combined and washed successively with saturated sodium bicarbonate aqueous solution (30 mL × 2) and H2O (30 mL). The organic phases were dried, filtered, and the filtrate was concentrated. The residue was purified by rapid silica gel column chromatography to obtain the product 3-(2-chloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (120 mg, 24%). Step 2: Preparation of N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (120 mg, 0.44 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (120 mg, 0.53 mmol), and p-toluenesulfonyl chloride (110 mg, 0.57 mmol) were dissolved in 2-pentanol (5 mL). The reaction was heated to 120 °C and stirred for 16 hours. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated, and the layers were separated by extraction with DCM (10 mL) and saturated sodium bicarbonate aqueous solution (10 mL). The organic phase was dried, filtered, and the filtrate was concentrated to obtain crude N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indole-3-yl)pyrimidin-2-amine (200 mg, 98%), which was directly used in the next step. Step 3: Preparation of 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N1-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-methyl-5-nitrobenzene-1,4-diamine N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-amine (100 mg, 0.21 mmol), triethylamine (100 mg, 0.98 mmol), and trimethylethylenediamine (60 mg, 0.59 mmol) were dissolved in DMF (1 mL). The reaction was carried out by microwave heating to 120 °C and stirring for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain the product 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N1-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-methyl-5-nitrobenzene-1,4-diamine (20 mg, 18%). Step 4: Preparation of 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine 2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N1-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-methyl-5-nitrobenzene-1,4-diamine (20 mg, 36.9 μmol) was dissolved in methanol (5 mL), and Pd / C (5 mg) was added. The reaction was hydrogenated at room temperature for 2 hours. The reaction was confirmed to be complete by LCMS. The reaction was filtered through diatomaceous earth, and the filtrate was concentrated to obtain the product 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine (15 mg, 80%), which was directly used in the next step of the reaction. Step 5: N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide 5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine (15 mg, 29.4 μmmol) and triethylamine (50 mg) were added to anhydrous tetrahydrofuran (15 mL). The reaction was stirred in an ice bath for 10 minutes. Then, acryloyl chloride (0.1 mL, 100 μmol, 1 M infusion) was slowly added in an ice bath. The reaction was stirred in an ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with saturated NH4Cl aqueous solution (5 mL), concentrated, and the remaining aqueous solution was extracted with dichloromethane (5 mL × 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified by preparative thin-layer chromatography to obtain N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (5.0 mg, 30%). 1H NMR (400MHz, CDCl3) δ10.01 (s, 1H), 9.70 (s, 1H), 8.63 (s, 1H), 8.25 (d, J = 5.3Hz, 1H), 7.83 (d,J=8.8Hz,1H),7.33(s,1H),7.06(d,J=5.3Hz,1H),6.91(s,1H),6.79(dd,J=8.8,2.3Hz, 1H),6.72(d,J=2.2Hz,1H),6.37(dd,J=83.2,64.3Hz,3H),5.63(d,J=11.9Hz,1H),3.78(d ,J=3.4Hz,3H),3.36(s,3H),2.82(s,2H),2.57(s,3H),2.24(s,6H),1.89(d,J=5.9Hz,2H); MS m / z(ESI): 566.2[M+H]+. Example 5: Preparation of N-(5-((5-chloro-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide) The preparation method of N-(5-((5-chloro-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide is similar to that in Example 1. 1H NMR (400MHz, CDCl3) δ9.41 (s, 1H), 8.39 (s, 1H), 8.33 (d, J = 5.3Hz, 2H), 7.60-7.18 (m, 3H), 6.98 (s, 1H), 6.6 6–6.20(m,3H),5.74–5.58(m,1H),3.90(s,3H),2.92–2.77(m,2H),2.62(s,3H),2.27(s,2H),2.22(s,6H); MS m / z(ESI): 571.0[M+H]+. Example 6: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(2-hydroxyethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 2-(3-(2-((2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol 1-(2-((tert-butyldimethylsilyl)oxo)ethyl)-3-(2-chloropyrimidin-4-yl)-1H-indole (619 mg, 1.595 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (322 mg, 1.45 mmol), and p-toluenesulfonic acid monohydrate (276 mg, 1.45 mmol) were dissolved in 2-pentanol (5 mL). The reaction was heated to 120 °C and carried out overnight. The reaction was confirmed to be complete by LCMS. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give the product 2-(3-(2-((2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indole-1-yl)ethane-1-ol (135 mg, 20%). Step 2: Preparation of 2-(3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol 2-(3-(2-((2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol (130 mg, 0.283 mmol) was dissolved in 2 mL of DMF, and triethylamine (87 mg, 0.849 mmol) and trimethylethylenediamine (87 mg, 0.849 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the crude product was separated by preparative thin-layer chromatography to obtain the final product (131 mg, 90%). Step 3: Preparation of 2-(3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol 2-(3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol (130 mg, 0.24 mmol) was dissolved in methanol (5 mL), and Pd / C (10 mg) was added. The reaction was stirred at room temperature for 1 hour under a hydrogen balloon. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the product (104 mg, 85%), which was directly used in the next step of the reaction. Step 4: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(2-hydroxyethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide 2-(3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-ol (97 mg, 0.19 mmol) and triethylamine (19 mg, 0.19 mmol) were dissolved in anhydrous tetrahydrofuran (50 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.6 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred at this temperature for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by thin-layer chromatography to obtain the product N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(2-hydroxyethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (15 mg, 14%). 1H NMR (400MHz, CD3OD) δ8.59(s,1H),8.45(s,1H),8.25(s,1H),8.07(d,J=6.7Hz,1H),7.58(d,J=8 .2Hz,1H),7.53(s,1H),7.44(d,J=6.7Hz,1H),7.41(s,1H),7.35–7.16(m,5H),7.01(dd,J=17.2 ,10.0Hz,2H),6.42(d,J=16.9Hz,1H),5.83(d,J=10.3Hz,1H),4.41(t,J=5.1Hz,2H),3.95(t,J= 5.1Hz,2H),3.50(d,J=5.3Hz,2H),3.44(d,J=5.2Hz,2H),3.37(s,1H),2.93(s,6H),2.81(s,3H); MS m / z(ESI): 566[M+H]+. Example 7: Preparation of N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide Step 1: Preparation of N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidine-2-amine 1-(3-(2-chloropyrimidin-4-yl)-1H-indol-1-yl)ethane-1-one (735 mg, 2.71 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (600 mg, 2.71 mmol), and p-toluenesulfonic acid monohydrate (514 mg, 2.71 mmol) were dissolved in 2-pentanol (20 mL). The reaction was heated to 120 °C and carried out overnight. LC-MS showed that the reaction was complete. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give N-(2-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (250 mg, 20%). Step 2: Preparation of N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-(2-(dimethylamino)ethyl)-methyl-5-nitrobenzene-1,4-diamine N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidine-2-amine (100 mg, 0.241 mmol) was dissolved in 2 mL of DMF, and triethylamine (73 mg, 0.72 mmol) and trimethylethylenediamine (74 mg, 0.72 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated, and the crude product was separated by preparative thin-layer chromatography to obtain the final product (100 mg, 83%). Step 3: Preparation of N-(4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)-N-(2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)acetamide N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-(2-(dimethylamino)ethyl)-methyl-5-nitrobenzene-1,4-diamine (100 mg, 0.20 mmol) was dissolved in acetic anhydride (4 mL), followed by the addition of triethylamine (0.5 mL) and DMAP (3 mg, 0.02 mmol). The reaction mixture was stirred at 120 °C for 30 minutes. After concentration, ethyl acetate and water were added, and the mixture was extracted three times. The combined organic phases were washed successively with saturated sodium bicarbonate aqueous solution, water, and saturated brine. After drying, filtration, and concentration, the crude product was obtained and used directly in the next step. Step 4: Preparation of 1-(3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-one The N-(4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)-N-(2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)acetamide obtained in the previous step was dissolved in methanol (5 mL), and Pd / C (15 mg) was added. The reaction was stirred at 24 °C for 1 hour under hydrogen atmosphere. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product was purified by rapid column chromatography to obtain the product 1-(3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-one (30 mg, 32%). Step 5: Preparation of N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide 1-(3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1H-indol-1-yl)ethane-1-one (30 mg, 0.059 mmol) and triethylamine (6 mg, 0.19 mmol) were dissolved in anhydrous tetrahydrofuran (30 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.2 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred at this temperature for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by thin-layer chromatography to obtain the product N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide (15 mg, 45%). 1H NMR (400MHz, CDCl3) δ9.81 (s, 1H), 9.34 (s, 1H), 8.61 (s, 1H), 8.40 (d, J = 5.4Hz, 1H), 7.90 ( d,J=8.0Hz,1H),7.78(d,J=2.7Hz,1H),7.35(d,J=8.2Hz,1H),7.20(d,J=5.4Hz,1H),7.08( d,J=3.2Hz,1H),6.54–6.33(m,3H),6.22–6.04(m,2H),5.82(dd,J=4.0Hz,1H),5.69(dd,J =4.0Hz,1H),3.07-3.02(m,2H),2.84(s,2H),2.92-2.76(m,3H),2.59(s,3H),2.53(s,6H); MS m / z(ESI): 564[M+H]+. Example 8: Preparation of N-(5-((4-(1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide (12 mg, 0.021 mmol) was dissolved in methanol (2 mL), and 1 N sodium carbonate aqueous solution (1 mL) was added. The reaction was carried out at room temperature for 3 hours. The reaction solution was concentrated to obtain a crude product, which was purified by rapid silica gel column chromatography to obtain the product N-(5-((4-(1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide (4 mg, 36.4%). 1H NMR (400MHz, CD3OD) δ8.54(d,J=3.4Hz,1H),8.38–8.04(m,3H),7.51(d,J=7.3Hz,2H),7.39(t,J=9.9Hz,1H),7.31–7.15(m,3H),6.87(ddd,J=40.9,27 .6,6.5Hz,2H),6.45(d,J=17.0Hz,1H),5.85(d,J=10.3Hz,1H),5.36(t,J=4 .7Hz,1H),3.56-3.47(m,2H),3.45-3.38(m,2H),2.93(s,6H),2.82(s,3H); MS m / z(ESI): 522[M+H]+. Example 9: Preparation of N-(5-((4-(6-cyano-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide is similar to that in Example 4. Example 10: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-6-(isopropylsulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-6-(isopropylsulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 4. Example 11: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-(dimethylphospho)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of (3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indole-6-yl)dimethylphosphine oxide N1-(4-(6-bromo-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-5-nitrobenzene-1,4-diamine (50 mg, 84.6 μmol), dimethyl phosphorus oxide (66.1 mg, 0.85 mmol), palladium acetate (10 mg), triethylamine (0.25 mL), and X-Phos (20 mg) were dissolved in DMF (2 mL). The mixture was bubbled under nitrogen for 10 minutes to remove oxygen, and then heated by microwave at 130°C for 1 hour. The reaction was confirmed to be complete by LCMS. The reaction solution was filtered, the filtrate was evaporated to dryness, and the residue was purified by thin-layer chromatography to obtain (3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indole-6-yl)dimethylphosphine oxide (40 mg, 80%). Step 2: Preparation of (3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indole-6-yl)dimethylphosphine oxide (3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indol-6-yl)dimethylphosphine oxide (40 mg, 68.1 μmol) was dissolved in methanol (5 mL), and Pd / C (10 mg) was added. The reaction was stirred at room temperature under a hydrogen atmosphere for 10 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was filtered, the filtrate was concentrated, and purified by reverse-phase column chromatography to obtain (3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indol-6-yl)dimethylphosphine oxide (15 mg, 27%). Step 3: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-(dimethylphospho)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (15 mg, 26.9 μmol) of (3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-1-methyl-1H-indol-6-yl)dimethylphosphine oxide and triethylamine (0.1 mL) were dissolved in tetrahydrofuran (10 mL), and the reaction solution was cooled to -10 to -5 °C. Acryloyl chloride (0.1 mL, 1 M in THF) was slowly added under nitrogen protection. The reaction was stirred at -10 to -5°C for 30 minutes. After the reaction was completed, methanol (3 mL) was added and stirring was continued for 10 minutes. The reaction solution was concentrated, and the residue was first separated by preparative thin-layer chromatography and then purified by reverse-phase column chromatography to obtain N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-(dimethylphospho)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (3.5 mg, 21%). 1H NMR (400MHz, CD3OD) δ8.67(s,1H),8.39(d,J=7.4Hz,1H),8.25(s,1H),8.20(d,J=6.6Hz,1H),8.00(d, J=13.1Hz,1H),7.58(dd,J=10.6,8.9Hz,1H),7.48(d,J=6.7Hz,1H),7.32(s,1H),6.97(t,J=73.2Hz,2 H),6.62(dd,J=16.9,10.0Hz,1H),6.50(dd,J=16.9,1.7Hz,1H),5.89(dd,J=10.0,1.7Hz,1H),4.05(s ,3H),3.53(t,J=5.9Hz,2H),3.38(t,J=5.9Hz,2H),2.96(s,6H),2.82(s,3H),1.86(d,J=13.3Hz,6H); MS m / z(ESI): 612.3[M+H]+. Example 12: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide Step 1: Preparation of 3-(2-chloropyrimidin-4-yl)-1-cyclopropyl-1H-indole 1-Cyclopropyl-1H-indole (140 mg, 0.89 mmol) and 2,4-dichloropyrimidine (170 mg, 1.14 mmol) were dissolved in ethylene glycol dimethyl ether (10 mL), and anhydrous aluminum chloride (180 mg, 1.35 mmol) was added. The mixture was heated to 100 °C and reacted overnight. After cooling to room temperature, the solvent was concentrated under reduced pressure. The residue was dissolved in dichloromethane (30 mL), and the organic phase was washed twice with water and dried. The organic phase solvent was concentrated, and thin-layer chromatography (petroleum ether: ethyl acetate = 8:1) was used to purify 3-(2-chloropyrimidine-4-yl)-1-cyclopropyl-1H-indole (80 mg). MS m / z(ESI):270.1[M+H]+. Step 2: Preparation of 4-(1-cyclopropyl-1H-indol-3-yl)-N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-1-cyclopropyl-1H-indole (80 mg, 0.29 mmol) and 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (64 mg, 0.29 mmol) were dissolved in 2-pentanol and microwaved for 1 hour. After cooling to room temperature, the solvent was removed by evaporation. The residue was purified by preparative thin-layer chromatography to obtain 4-(1-cyclopropyl-1H-indole-3-yl)-N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)pyrimidin-2-amine (76 mg). MS m / z(ESI):456.1[M+H]+. Step 3: Preparation of N1-(4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-5-nitrobenzene-1,4-diamine 76 mg of 4-(1-cyclopropyl-1H-indol-3-yl)-N-(2-(difluoromethoxy)-4-fluoro-5-nitrophenyl)pyrimidin-2-amine was dissolved in N,N-dimethylacetamide, and 0.1 g of trimethylethylenediamine was added. The mixture was heated to reflux for 2 hours. After cooling to room temperature, the solvent was evaporated to obtain 50 mg of N1-(4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-5-nitrobenzene-1,4-diamine. MS m / z(ESI): 538.3[M+H]+. Step 4: Preparation of N4-(4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)-5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N1-methylphenyl-1,2,4-triamine N1-(4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-N4-(2-(dimethylamino)ethyl)-N4-methyl-5-nitrobenzene-1,4-diamine (50 mg) was dissolved in 6 mL of an ethanol-water mixture (5:1), 65 mg of iron powder and 50 mg of ammonium chloride were added, and the mixture was heated to reflux for 2 hours. After cooling to room temperature, the mixture was filtered, and the filtrate was collected. The ethanol in the filtrate was concentrated under reduced pressure, and water and dichloromethane-methanol (20:1) were added. The organic phase was separated, dried, and concentrated to obtain the crude product (20 mg). MS m / z(ESI): 508.3[M+H]+. Step 5: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acryloylamide N4-(4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)-5-(difluoromethoxy)-N1-(2-(dimethylamino)ethyl)-N1-methylbenzene-1,2,4-triamine (20 mg) was dissolved in anhydrous tetrahydrofuran under nitrogen purging protection. DIPEA (0.1 mL) was added at 0 °C, followed by dropwise addition of 1 M acryloyl chloride tetrahydrofuran solution (0.2 mL). The reaction was carried out at 0 °C for 1 hour. Water and dichloromethane were added to the reaction solution, and the aqueous and organic phases were separated. The aqueous phase was extracted three times with dichloromethane. The organic phases were combined, dried, concentrated, and then purified by thin-layer chromatography to obtain the crude product. The crude product was further purified by reverse-phase column chromatography (water:methanol = 25:75) to obtain the final product (6.2 mg). 1H NMR(400MHz,CD3OD)δ8.56(s,1H),8.26(m,2H),8.08(d,1H),7.71(d,1H),7.50(d,1H),7.32(m,3H),6.96(m,1H),6.79(m,1 H),6.44(dd,1H),5.85(d,1H),3.62(m,1H),3.52(m,2H),3.40(m,2H),2.94(s,6H),2.82(s,3H),1.24(m,2H),1.14(m,2H); 19F NMR (376MHz, CD3OD) δ-83.26; MS m / z(ESI): 562.2[M+H]+. Example 13: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide Step 1: Preparation of 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene 1-Fluoro-3-(trifluoromethoxy)benzene (7.5 g, 41.6 mmol) was dissolved in concentrated sulfuric acid (30 mL) and cooled to 0 °C. KNO3 (1.04 g, 10.25 mmol) was slowly added in portions. The internal temperature was maintained below 5 °C. After the addition was complete, stirring was continued for 2 hours. Approximately 50 mL of an ice-water mixture was added to the reaction mixture. Extraction was performed with methyl tert-butyl ether (20 × 3 mL), the organic phases were combined, dried, filtered, and the filtrate was concentrated and purified by rapid silica gel column chromatography to obtain 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene (4.0 g, 42%). Step 2: Preparation of 4-fluoro-2-(trifluoromethoxy)aniline 4-Fluoro-1-nitro-2-(trifluoromethoxy)benzene (4.0 g, 17.8 mmol) was dissolved in methanol (50 mL), and Pd / C (200 mg) was added. The reaction was stirred under hydrogen for 2 hours, and LC-MS showed that the reaction was complete. The reaction solution was filtered, the filtrate was concentrated, and the residue was purified by reverse-phase column chromatography to obtain 4-fluoro-2-(trifluoromethoxy)aniline (3.0 g, 86%). Step 3: Preparation of 4-fluoro-5-nitro-2-(trifluoromethoxy)aniline 4-Fluoro-2-(trifluoromethoxy)aniline (2.0 g, 10.25 mmol) was dissolved in concentrated sulfuric acid (10 mL) and cooled to -20 °C. KNO3 (1.04 g, 10.25 mmol) was slowly added in portions. The internal temperature was maintained below -10 °C. After the addition was complete, stirring was continued for 1 hour. Approximately 50 mL of an ice-water mixture was added to the reaction mixture. Extraction was performed with methyl tert-butyl ether (20 mL × 3). The organic phases were combined, dried, filtered, and the filtrate was concentrated and purified by rapid silica gel column chromatography to obtain 4-fluoro-5-nitro-2-(trifluoromethoxy)aniline (500 mg, 20%). Step 4: Preparation of N-(4-fluoro-5-nitro-2-(trifluoromethoxy)phenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidine-2-amine 4-Fluoro-5-nitro-2-(trifluoromethoxy)aniline (500 mg, 2.08 mmol), 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (508 mg, 2.08 mmol), and p-toluenesulfonic acid monohydrate (400 mg, 2.08 mmol) were dissolved in 1,4-dioxane (10 mL). The reaction mixture was heated to 110 °C and stirred for 16 hours. The reaction was confirmed to be complete by LCMS. A saturated NaHCO3 aqueous solution (20 mL) was added to the reaction mixture, and the mixture was stirred for 20 minutes. The mixture was filtered, and the filter cake was washed with methyl tert-butyl ether to obtain crude N-(4-fluoro-5-nitro-2-(trifluoromethoxy)phenyl)-4-(1-methyl-1H-indole-3-yl)pyrimidin-2-amine (400 mg, 43%). Step 5: Preparation of N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitro-5-(trifluoromethoxy)benzene-1,4-diamine N-(4-fluoro-5-nitro-2-(trifluoromethoxy)phenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine (400 mg, 0.89 mmol), N,N,N-trimethylethylenediamine (180 mg, 1.79 mmol), and triethylamine (1 mL) were dissolved in DMF (5 mL). The reaction was heated to 110 °C and reacted for 2 hours. The reaction was confirmed to be complete by LCMS. Dichloromethane (10 mL) and water (10 mL) were added to the reaction solution. The organic phase was washed three times with water, dried over anhydrous magnesium sulfate, filtered, concentrated, and the residue was purified by rapid silica gel column chromatography to give N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitro-5-(trifluoromethoxy)phenyl-1,4-diamine (80 mg, 17%). Step 6: Preparation of N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-(trifluoromethoxy)benzene-1,2,4-triamine N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitro-5-(trifluoromethoxy)benzene-1,4-diamine (80 mg, 0.15 mmol) was dissolved in methanol (5 mL), and Pd / C (10 mg) was added. The reaction was stirred at room temperature under a hydrogen atmosphere for 10 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was filtered, and the filtrate was concentrated to obtain N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-(trifluoromethoxy)benzene-1,2,4-triamine (50 mg, 70%), which was used directly in the next step of the reaction without purification. Step 7: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-(trifluoromethoxy)benzene-1,2,4-triamine (50 mg, 0.24 mmol) and triethylamine (0.2 mL) were dissolved in tetrahydrofuran (10 mL), and the reaction solution was cooled to -10 to -5 °C. Acryloyl chloride (0.35 mL, 1 min THF) was slowly added under nitrogen protection. The reaction was stirred at -10 to -5°C for 30 minutes. After the reaction was completed, methanol (3 mL) was added and stirring was continued for 10 minutes. The reaction solution was concentrated under reduced pressure. The residue was first separated by preparative thin-layer chromatography and then purified by reverse-phase column chromatography to obtain N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide (19.0 mg, 14%). 1H NMR (400MHz, CD3OD) δ8.53(s,1H),8.47(s,1H),8.14(d,J=7.8Hz,1H),8.07(d,J=6.8Hz,1 H),7.51(d,J=8.2Hz,1H),7.47(d,J=0.9Hz,1H),7.42(d,J=6.9Hz,1H),7.19(t,J=7.5Hz, 1H),6.72(dd,J=16.9,10.2Hz,1H),6.47(dd,J=16.9,1.5Hz,1H),5.88(dd,J=10.3,1.5Hz ,1H),3.93(s,3H),3.51(t,J=5.9Hz,2H),3.40(t,J=5.8Hz,2H),2.95(s,6H),2.82(s,3H); MS m / z(ESI): 554.2[M+H]+. Example 14: Preparation of N-(5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(4-methylpiperazin-1-yl)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 2. Example 15: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 4. Example 16: Preparation of N-(5-((4-(6-cyano-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 4. Example 17: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 1. Example 18: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(2-hydroxyethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(2-hydroxyethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 6. Example 19: Preparation of N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(5-((4-(1-acetyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 4. Example 20: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-(dimethylphospho)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-(dimethylphospho)-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-(trifluoromethoxy)phenyl)acryloylamide is similar to that in Example 4. Example 21: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-(difluoromethoxy)-(2-(dimethylamino)ethyl)-methyl-5-nitrobenzene-1,4-diamine (100 mg, 0.201 mmol) was dissolved in 10 mL of DMF and cooled to 0 °C in an ice bath. Sodium hydride (24 mg, 0.603 mmol) was then added, and the reaction was carried out at 0 °C for 10 minutes. Dimethylaminosulfonyl chloride (35 mg, 0.241 mmol) was then added dropwise. The reaction was brought to room temperature and stirred for 30 minutes. After quenching the reaction, dichloromethane and water were added, and the mixture was extracted three times. The combined organic phases were washed successively with saturated sodium bicarbonate solution, water, and saturated sodium chloride solution. After drying, filtration, and concentration, the crude product was obtained. The crude product (95 mg, 78%) was purified by rapid silica gel column chromatography. Step 2: Preparation of 3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide 3-(2-((2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide was dissolved in 5 mL of methanol, and Pd / C (15 mg) was added. The reaction was stirred at room temperature for 1 hour under a hydrogen balloon. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product (35 mg, 39%) was obtained by rapid silica gel column purification. Step 3: Preparation of N-(4-(difluoromethoxy)-2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide 3-(2-((5-amino-2-(difluoromethoxy)-4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (35 mg, 0.061 mmol) and triethylamine (18 mg, 0.183 mmol) were dissolved in anhydrous tetrahydrofuran (30 mL). The reaction mixture was stirred at -78 °C for 10 min, and then acryloyl chloride (0.2 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred at this temperature for 30 min, and LCMS showed that the reaction was complete. The reaction was quenched with methanol, the reaction mixture was concentrated, and the residue was purified by preparative agar to obtain the product (25 mg, 65%). 1H NMR(400MHz,CD3OD)δ8.57(s,1H),8.39(s,1H),8.36–8.18(m,2H),7.97(d, J=8.4Hz,1H),7.52(d,J=6.2Hz,1H),7.37(t,J=7.7Hz,1H),7.33–7.18(m,2 H),7.16–6.58(m,2H),6.45(d,J=16.0Hz,1H),5.96–5.77(m,1H),3.49(t,J =5.6Hz,2H),3.37(t,J=5.6Hz,2H),2.93(s,6H),2.89(s,6H),2.78(s,3H); MS m / z(ESI): 629.2[M+H]+. Example 22: Preparation of N-(5-((4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 6-bromo-1-methyl-1H-indole Under ice-water bath conditions, NaH (60%, 734 mg, 18.4 mmol) was added to a DMF solution (30 mL) of 6-bromo-1H-indole (3.00 g, 15.3 mmol), and the mixture was stirred at this temperature for 20 minutes. Then, a DMF solution (10 mL) of MeI (1.14 mL, 18.4 mmol) was added dropwise, and the mixture was stirred at this temperature for another 30 minutes. Approximately 100 mL of water was added, and the mixture was extracted with EtOAc. The EtOAc phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (eluent: pure PE) to give the title compound 6-bromo-1-methyl-1H-indole (2.70 g, 84%). Step 2: Preparation of 6-cyclopropyl-1-methyl-1H-indole 6-Bromo-1-methyl-1H-indole (1.44 g, 6.85 mmol) and cyclopropylboronic acid (1.18 g, 13.7 mmol) were mixed in a mixture of toluene (20 mL) and water (3 mL) and bubbled under nitrogen for 5 minutes to remove oxygen. Then, Pd(OAc)₂ (231 mg, 1.03 mmol) and anhydrous potassium phosphate (4.37 g, 20.6 mmol) were added, and the mixture was bubbled under nitrogen for another 10 minutes. Finally, tricyclohexylphosphine (769 mg, 2.74 mmol) was added, and the mixture was bubbled under nitrogen for 5 minutes. The mixture was stirred overnight in an oil bath at 100 °C under nitrogen protection. After cooling, the organic solvent was removed by rotary evaporation. EtOAc and water were added to separate the phases. The EtOAc phase was then washed with saturated brine, dried with anhydrous sodium sulfate, concentrated, and subjected to column chromatography (eluent: pure PE) to give the title compound 6-cyclopropyl-1-methyl-1H-indole (770 mg, 66%). 1H NMR (400MHz, CDCl3): δ7.55(d,J=8.0Hz,1H),7.09(d,J=0.8Hz,1H),7.01(d,J=3.2Hz,1H),6 .93(m,1H),6.46(dd,J=3.2,0.8Hz,1H),3.79(s,3H),2.09(m,1H),1.01(m,2H),0.80(m,2H). Step 3: Preparation of 3-(2-chloropyrimidin-4-yl)-6-cyclopropyl-1-methyl-1H-indole FeCl3 (864 mg, 5.33 mmol) was added to a 10 mL solution of 6-cyclopropyl-1-methyl-1H-indole (760 mg, 4.44 mmol) and 2,4-dichloropyrimidine (674 mg, 4.44 mmol) in ethylene glycol dimethyl ether. The mixture was stirred overnight at 60 °C. After cooling, a large amount of EtOAc and water were added to separate the layers. Insoluble matter was removed with diatomaceous earth, and the aqueous phase was separated. The organic phase was washed successively with saturated sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (eluent: PE:EtOAc = 3:1) to give the title compound (533 mg, 42%). MS m / z(ESI): 284.2[M+H]+. Step 4: Preparation of 4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-6-cyclopropyl-1-methyl-1H-indole (533 mg, 1.88 mmol), 4-fluoro-2-methoxy-5-nitroaniline (350 mg, 1.88 mmol), and TsOH·H2O (429 mg, 2.25 mmol) were mixed in 10 mL of 2-pentanol and reacted at 125 °C for 3 hours. After cooling and filtration, the solid was dissolved in CH2Cl2, washed successively with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound 4-(6-cyclopropyl-1-methyl-1H-indole-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidin-2-amine (750 mg, 92%). MS m / z(ESI): 434.2[M+H]+. Step 5: Preparation of N1-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine 4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidin-2-amine (647 mg, 1.49 mmol), N1,N1,N2-trimethylethane-1,2-diamine (229 mg, 2.24 mmol), and DIPEA (0.740 mL, 4.48 mmol) were dissolved in DMA (10 mL) and reacted at 85 °C for 3 hours. After cooling, water and EtOAc were added to separate the phases. The organic phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain 1.4 g of crude N1-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine, which was used directly in the next step. MS m / z(ESI): 516.3[M+H]+. Step 6: Preparation of N4-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylphenyl-1,2,4-triamine N1-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (1.4 g, crude), reduced iron powder (1.22 g, 21.7 mmol), and ammonium chloride (100 mg, 1.90 mmol) were mixed in EtOH (30 mL) and water (10 mL) and heated under reflux for three hours. After cooling, a large amount of EtOH was added, and the insoluble matter was removed by diatomaceous earth filtration. The EtOH was removed under reduced pressure, and the aqueous phase was extracted with EtOAc. The EtOAc phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography [eluent: CH2Cl2 → CH2Cl2: MeOH (containing 10% concentrated ammonia) = 17:1] to give the title compound N4-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylphenyl-1,2,4-triamine (490 mg, two-step yield 68%). MS m / z(ESI): 486.3[M+H]+. Step 7: Preparation of N-(5-((4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Under ice-water bath conditions, a THF solution of acryloyl chloride (22.0 mg, 0.247 mmol) was added dropwise to a 2 mL solution of N4-(4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylphenyl-1,2,4-triamine (80.0 mg, 0.164 mmol) and TEA (50.0 mg, 0.492 mmol) in THF. After the addition was complete, the mixture was stirred at the same temperature for 15 minutes, and then methanol was added to quench the reaction. The reaction solution was concentrated under reduced pressure, and thin-layer chromatography (CH2Cl2:MeOH:concentrated ammonia water = 100:10:1) was performed to obtain the title compound N-(5-((4-(6-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide (45 mg, 51%). 1H NMR (400MHz, CDCl3): δ10.1(br s,1H),9.83(s,1H),9.00(s,1H),8.36(d,J=5.2Hz,1H),7.93(d,J=8.4Hz,1H),7.71(s,1 H),7.16(d,J=5.2Hz,1H),7.10(s,1H),7.00(dd,J=8.4,1.6Hz,1H),6.79(s,1H),6.39-6 .44(m,2H),5.70(dd,J=9.6,2.0Hz,1H),3.95(s,3H),3.87(s,3H),2.89(t,J=5.6Hz,2H) ,2.69(s,3H),2.27(t,J=5.6Hz,2H),2.25(s,6H),2.06(m,1H),1.00(m,2H),0.78(m,2H); MS m / z(ESI): 540.3[M+H]+. Example 23: Preparation of N-(5-((4-(5-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ10.0(brs,1H),9.76(s,1H),8.99(s,1H),8.31(d,J=5.2Hz,1H),7.72 (s,1H),7.65(s,1H),7.21(s,1H),7.13(d,J=5.2Hz,1H),6.94(dd,J=8.4,1.6Hz,1H),6.72(s ,1H),6.36(m,2H),5.63(dd,J=8.8,2.8Hz,1H),3.89(s,3H),3.82(s,3H),2.84(t,J=6.0Hz, 2H),2.62(s,3H),2.25(t,J=6.0Hz,2H),2.20(s,6H),2.00(m,1H),0.93(m,2H),0.75(m,2H); MS m / z(ESI): 540.4 [M+H]+. Example 24: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ10.09(s,1H),9.76(s,1H),8.97(s,1H),8.30(d,J=5. 2Hz,1H),7.64(s,1H),7.44(d,J=2.4Hz,1H),7.20(d,J=9.2Hz,1H),7.05(d,J =5.2Hz,1H),6.85(m,1H),6.72(s,1H),6.36(m,2H),5.63(m,1H),3.89(s,3H ),3.85(s,3H),3.81(s,3H),2.81(t,J=5.6Hz,2H),2.63(s,3H),2.20(m,8H); MS m / z(ESI): 530.2[M+H]+. Example 25: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ9.99(d,J=29.8Hz,1H),9.75(s,1H),8.85(s,1H),8.29(d,J=5.3Hz,1H ),7.87(d,J=8.8Hz,1H),7.64(s,1H),7.06(d,J=5.3Hz,1H),6.83(dd,J=8.7,2.3Hz,1H),6.7 5(t,J=8.0Hz,1H),6.70(s,1H),6.50-6.24(m,2H),5.76-5.53(m,1H),3.85(s,3H),3.82(d,J =4.9Hz,3H),3.80(s,3H),2.94-2.74(m,2H),2.62(s,3H),2.24(d,J=4.8Hz,2H),2.20(s,6H); MS m / z(ESI): 530.3[M+H]+. Example 26: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ9.78(s,1H),9.74(s,1H),8.55(s,1H),8.39(d,J=5.3Hz,1H),8.11(d,J=7.0 Hz,1H),7.74-7.55(m,2H),7.18(d,J=5.3Hz,1H),6.76(s,1H),6.62(dd,J=16.8,10.1Hz,1H),6.46 (dd,J=16.9,1.9Hz,1H),6.24(m,1H),5.80-5.59(m,1H),3.88(s,3H),3.55-3.34(m,1H),3.02(t,J =5.8Hz,2H),2.68(s,3H),2.57(t,J=5.7Hz,2H),2.42(s,6H),1.24-1.17(m,2H),1.14-1.04(m,2H); MS m / z(ESI): 526.3[M+H]+. Example 27: Preparation of N-(4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(2-oxa-6-azaspiro[3.3]heptane-6-yl)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(2-oxa-6-azaspiro[3.3]heptane-6-yl)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ8.76 (s, 1H), 8.32 (d, J = 26.6Hz, 1H), 8.20 (dd, J = 20.7 ,6.3Hz,1H),8.11-7.97(m,1H),7.48-7.36(m,1H),7.36-7.24(m,2H),6.97(d d,J=25.1,11.6Hz,1H),6.44-6.30(m,1H),6.24(dd,J=16.9,10.0Hz,1H),6.1 3-6.01(m,1H),5.66(dd,J=9.9,1.5Hz,1H),4.69(s,4H),3.95-3.67(m,10H); MS m / z(ESI): 497.2[M+H]+. Example 28: Preparation of N-(5-((4-(5,6-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,6-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ10.06 (s, 1H), 9.83-9.46 (m, 1H), 8.86 (s, 1H), 8.30 (d, J = 5.3H z,1H),7.78(dd,J=11.4Hz,1H),7.62(s,1H),7.11-6.99(m,1H),6.93(t,J=6.2Hz,1H) ,6.72(s,1H),6.34(d,J=5.6Hz,2H),5.72-5.51(m,1H),3.84(d,J=6.4Hz,3H),3.81(d ,J=4.4Hz,3H),2.92-2.76(m,2H),2.72-2.54(m,3H),2.21(s,6H),1.36-1.07(m,2H); MS m / z(ESI): 536.2[M+H]+. Example 29: Preparation of N-(5-((4-(4,6-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(4,6-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ9.97(s,1H),9.71(s,1H),9.00(s,1H),8.53-8.19(m,1H),7 .71-7.56(m,1H),7.33(d,J=5.4Hz,1H),6.79(dd,J=8.8,2.1Hz,1H),6.71(s,1H),6 .65(ddd,J=11.9,9.7,2.1Hz,1H),6.42-6.22(m,2H),5.68-5.53(m,1H),3.87(s,3H ),3.81(s,3H),2.94-2.77(m,2H),2.62(d,J=9.2Hz,3H),2.28(s,2H),2.23(s,6H); MS m / z(ESI): 536.2[M+H]+. Example 30: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4,5,6,7-tetrafluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4,5,6,7-tetrafluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. Example 31: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1,5,6-trimethyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1,5,6-trimethyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. Example 32: Preparation of N-(5-((4-(4,6-difluoro-1,7-dimethyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(4,6-difluoro-1,7-dimethyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 33: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-4,6-dimethoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-4,6-dimethoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 34: Preparation of N-(5-((4-(5,7-difluoro-6-(trifluoromethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,7-difluoro-6-(trifluoromethyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 35: Preparation of N-(5-((4-(4,6-difluoro-5-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(4,6-difluoro-5-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 36: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4,5,6,7-tetrafluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4,5,6,7-tetrafluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. Example 37: Preparation of N-(5-((4-(1-cyclopropyl-4,6-dimethyl-5-(methanesulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-4,6-dimethyl-5-(methanesulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 38: Preparation of N-(5-((4-(1,5-dicyclopropyl-4,6-difluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1,5-dicyclopropyl-4,6-difluoro-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 39: Preparation of N-(5-((4-(1-cyclopropyl-5,7-difluoro-6-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-5,7-difluoro-6-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. Example 40: Preparation of N-(5-((4-(1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 1-(2-chloropyrimidin-4-yl)-1H-indazole Take a 100 mL single-necked flask, add 2,4-dichloropyrimidine (1.18 g, 8 mmol) and DMF (40 mL), cool to 0 °C, add NaH (0.4 g, 10 mmol) in portions to the above solution, stir at room temperature for half an hour, cool to 0 °C, add indazole (1.49 g, 12.6 mmol), the reaction is slowly raised to room temperature with stirring for 4 hours, the reaction is quenched with water, extracted with ethyl acetate, and silica gel column chromatography (PE / EA = 20 / 1) to give the title compound 1-(2-chloropyrimidine-4-yl)-1H-indazole (450 mg, 26%). Step 2: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indazol-1-yl)pyrimidine-2-amine Take a 50 mL single-necked flask and add 1-(2-chloropyrimidin-4-yl)-1H-indazole (450 mg, 1.96 mmol), 4-fluoro-2-methoxy-5-nitroaniline (363 mg, 1.96 mmol), p-toluenesulfonic acid (336 mg, 1.96 mmol), and 2-pentanol (20 mL) in sequence. Stir the mixture at 120 °C for 5 hours and concentrate to obtain a black mixture. Analyze the mixture by silica gel column chromatography (1% MeOH / DCM) to obtain the title compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indazole-1-yl)pyrimidin-2-amine (200 mg, 27%). Step 3: Preparation of N1-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine Take a 50 mL single-necked flask and add N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indazol-1-yl)pyrimidin-2-amine (200 mg, 0.53 mmol), trimethylethylenediamine (107 mg, 1.05 mmol), DIPEA (203 mg, 1.57 mmol), and DMF (8 mL) sequentially. Stir at 100 °C for 1 hour. After concentrating the reaction solution, prepare thin-layer chromatography purification (5% MeOH / DCM) to obtain the title compound N1-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (300 mg, 60%). Step 4: Preparation of N4-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylphenyl-1,2,4-triamine Take a 50 mL single-necked flask and add N1-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (300 mg, 0.65 mmol), 5% Pd / C (100 mg), and methanol (50 mL) sequentially. Stir at room temperature for 2 hours, concentrate the reaction solution, and prepare thin-layer chromatography purification (5% MeOH / DCM) to obtain the title compound N4-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (110 mg, 30%). Step 5: Preparation of N-(5-((4-(1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Take a 100 mL single-necked flask, add N4-(4-(1H-indazol-1-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (110 mg, 0.25 mmol), DIPEA (109 mg, 0.84 mmol), and THF (30 mL), cool to 0 °C, then add 0.5 mL of acryloyl chloride (1 M THF solution), continue stirring at 0 °C for 2 hours, quench with methanol, concentrate the reaction solution, and prepare thin-layer chromatography purification (10% MeOH / DCM) to obtain the title compound N-(5-((4-(1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide (20 mg, 16%). 1H NMR(400MHz,CD3OD)δ8.52(d,J=8.6Hz,1H),8.43(s,1H),8.29(dd,J=5.6,3.9Hz,1H), 8.19(d,J=3.5Hz,1H),7.70(d,J=8.0Hz,1H),7.45–7.23(m,2H),7.17(t,J=7.5Hz,1H), 6.90(s,1H),6.42(dd,J=17.0,10.2Hz,1H),6.24(d,J=16.9Hz,1H),5.68(d,J=10.3Hz, 1H),3.83(s,3H),3.16(s,2H),2.79–2.61(m,5H),2.66(d,J=12.3Hz,3H),2.44(s,5H); MS m / z(ESI): 487[M+H]+. Example 41: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. 1H NMR(400MHz,CD3OD)δ8.46(s,1H),8.33(d,J=7.3Hz,1H),8.05(s,1H),7.85(s,1H) ,7.63(d,J=6.4Hz,1H),7.46(t,J=8.0Hz,1H),7.08(s,1H),6.87(d,J=7.9Hz,1H),6 .59(dd,J=16.9,10.0Hz,1H),6.53–6.42(m,1H),5.87(d,J=9.9Hz,1H),4.00(s,3H ),3.96(s,3H),3.57(t,J=5.4Hz,2H),3.40–3.35(m,2H),2.93(s,6H),2.81(s,3H); MS m / z(ESI): 517.3[M+H]+. Example 42: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. 1H NMR(400MHz,CD3OD)δ8.35(s,1H),8.23(d,J=6.3Hz,1H),8.08(s,1H),7.87(s,1H ),7.74(d,J=8.7Hz,1H),7.61(d,J=6.8Hz,1H),7.12–7.04(m,2H),6.63(dd,J=16 .9,10.2Hz,1H),6.41(dd,J=16.9,1.2Hz,1H),5.87–5.79(m,1H),3.94(s,3H),3. 86(s,3H),3.54(t,J=5.6Hz,2H),3.37(t,J=5.6Hz,2H),2.91(s,6H),2.79(s,3H); MS m / z(ESI): 517.3[M+H]+. Example 43: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 5-methoxy-1-(2-(methylthio)pyrimidin-4-yl)-1H-indazole 5-Methoxy-1H-indazole (500 mg, 3.38 mmol) was dissolved in DMF (10 mL), and NaH hydrogen (148 mg, 3.72 mmol) was added at 0 °C. Then 4-chloro-2-(methylthio)pyrimidine (542 mg, 3.38 mmol) was added. The mixture was stirred at this temperature for 2 hours. 30 mL of water was added to the reaction solution, and the mixture was filtered, extracted, and dried to obtain a white solid 5-methoxy-1-(2-(methylthio)pyrimidin-4-yl)-1H-indazole (850 mg, 92%). Step 2: Preparation of 5-methoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole 5-Methoxy-1-(2-(methylthio)pyrimidin-4-yl)-1H-indazole (850 mg, 3.125 mmol) was dissolved in DCM (50 ml), and m-chloroperoxybenzoic acid (1.68 g, 7.8125 mmol) was added. The mixture was stirred at 50 °C for 3 hours, extracted with DCM, and column chromatography was used to obtain 5-methoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole (400 mg, 42%). Step 3: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(5-methoxy-1H-indazol-1-yl)pyrimidine-2-amine 5-Methoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole (100 mg, 0.329 mmol), 4-fluoro-2-methoxy-5-nitroaniline (73 mg, 0.395 mmol), and p-toluenesulfonic acid (57 mg, 0.329 mmol) were dissolved in 1,4-dioxane (5 mL), refluxed overnight, cooled, and an appropriate amount of sodium bicarbonate aqueous solution was added. The mixture was filtered, extracted, and dried to obtain a gray solid (200 mg), which was used directly in the next step. Step 4: N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-amine (120 mg, 0.122 mmol), DIPEA (47 mg, 0.658 mol), and trimethylethylenediamine (37 mg, 0.366 mmol) were dissolved in DMF (5 mL), heated at 100 °C for 1 hour, concentrated, and column chromatography was used to obtain 30 mg of yellow solid, which was directly used in the next step. Step 5: N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine The preparation method of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine is similar to that in Example 40. Step 6: N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.38 (s, 2H), 8.31 (d, J = 6.6Hz, 1H), 7.86 (s, 1H), 7.60 ( d,J=6.7Hz,1H),7.33(d,J=2.4Hz,1H),7.15(dd,J=9.1,2.2Hz,1H),7.08(s,1 H),6.53(dd,J=8.9,5.9Hz,2H),5.88(dd,J=9.2,2.6Hz,1H),3.98(s,3H),3.8 9(s,3H),3.58(t,J=5.7Hz,2H),3.38–3.34(m,2H),2.93(s,6H),2.81(s,3H); MS m / z(ESI): 517[M+H]+. Example 44: Preparation of N-(5-((4-(3-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(3-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.39(s,1H),8.18(d,J=5.2Hz,1H),7.87(d,J=7.3Hz,2H),7.48(d d,J=17.0,7.1Hz,2H),7.40(t,J=7.4Hz,1H),7.09(s,1H),6.64(dd,J=16.9,10.2Hz,1H) ,6.45(d,J=16.8Hz,1H),5.84(d,J=10.2Hz,1H),3.94(s,3H),3.55(d,J=5.2Hz,2H),3. 38(t,J=5.3Hz,2H),2.93(s,6H),2.81(s,3H),2.39–2.29(m,1H),1.19(d,J=6.5Hz,4H); MS m / z(ESI): 527.3[M+H]+. Example 45: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. Example 46: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. Example 47: Preparation of N-(5-((4-(5-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole 5-Bromo-1H-indazole (2.0 g, 10 mmol) was dissolved in DMF (15 mL), and NaH (480 mg, 12 mmol) was added at 0 °C. The reaction temperature was raised to room temperature and stirred for 30 min. After cooling to 0 °C, 2-(trimethylsilyl)ethyl hypochlorite (2.0 g, 12 mmol) was added, and the mixture was stirred for 2 hours. The mixture was then quenched with 30 mL of water and extracted with methyl tert-butyl ether (30 mL × 3). After drying the organic phase with anhydrous sodium sulfate, the crude product was concentrated. The crude product was purified by column chromatography to obtain 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (2.0 g, 63%). Step 2: Preparation of 5-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole 5-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.5 g, 4.6 mmol), cyclopropylboronic acid (790 mg, 9.2 mmol), and potassium phosphate (3.0 g, 13.8 mmol) were dissolved in toluene / water (30 / 10 ml), purged three times with nitrogen, and palladium acetate (103 mg, 0.46 mmol) and tricyclohexylphosphine (258 mg, 0.92 mmol) were added. The mixture was stirred at 100 °C for 16 hours, quenched with 30 mL of water, and extracted with ethyl acetate (50 mL × 3). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain a crude product. The crude product was purified by column chromatography to obtain 5-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.2 g, 89%). Step 3: Preparation of 5-cyclopropyl-1H-indazole 5-Cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.2 g, 4.2 mmol) was dissolved in dichloromethane (30 mL), and trifluoroacetic acid (12 mL) was added. The mixture was reacted at room temperature for 2.5 h, concentrated to dryness, and the crude product was dissolved in dichloromethane (50 mL) and ethylenediamine (18 mL). The mixture was stirred for 1 h, and 30 mL of water was added. The mixture was extracted with dichloromethane (50 mL × 3). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 5-cyclopropyl-1H-indazole (280 mg, 42%). Steps 4 to 9: Preparation of N-(5-((4-(5-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 43. 1H NMR (400MHz, CD3OD) δ8.26 (s, 2H), 8.19 (s, 1H), 7.78 (s, 1H), 7.49 (d, J = 6.7Hz ,1H),7.44(s,1H),7.15(d,J=8.6Hz,1H),6.98(s,1H),6.49(dd,J=16.9,9.9H z,1H),6.38(dd,J=16.9,1.9Hz,1H),5.77(dd,J=9.9,1.9Hz,1H),3.86(s,3H) ,3.46(t,J=5.6Hz,2H),3.26(t,J=5.6Hz,2H),2.82(s,6H),2.69(s,3H),2.00 –1.88(m,1H),0.97–0.89(m,2H),0.67–0.59(m,2H); MS m / z(ESI): 527.3[M+H]+. Example 48: Preparation of N-(5-((5-chloro-4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.49(s,1H),8.20(d,J=10.0Hz,2H),8.00(d,J=9.0Hz,1H),7.21(s,1H),7.03(d,J=9.0Hz,1H), 6.94(s,1H),6.42(s,2H),5.83(s,1H),3.95(s,3H),3.84(s,3H),3.47(s,2H),3.28(s,2H),2.86(s,6H),2.69(s,3H); MS m / z(ESI): 551[M+H]+. Example 49: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.79(s,1H),8.23(s,1H),8.11–8.03(m,1H),7.27(s,1H),7.12-7.04(m,1H),7.01(s,1H),6. 47(s,2H),5.92–5.80(m,1H),3.99(s,3H),3.88(s,3H),3.54(s,2H),3.32–3.29(m,2H),2.90(s,6H),2.76(s,3H); MS m / z(ESI): 585[M+H]+. Example 50: Preparation of N-(5-((4-(5-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 1H-indazole-5-formonitrile 4-Fluoro-3-carboxybenzonitrile (25 g, 16.78 mmol) was dissolved in 100 mL of hydrazine hydrate (85%), stirred at room temperature for 24 hours, and then subjected to column chromatography to give 1H-indazole-5-carboxynitrile (2.1 g, 87%). 1H NMR (400MHz, DMSO) δ13.60(s,1H),8.42(s,1H),8.27(s,1H),7.73(d,J=8.6Hz,1H),7.67(d,J=8.6Hz,1H); MS m / z(ESI): 144[M+H]+. Steps 2 through 6: Preparation of N-(5-((4-(5-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.77–8.68(m,1H),8.53(s,1H),8.47–8.41(m,1H),8.33(s,1H),7.99(s,1H),7.75(s,1H),7.56(d,J=6.2 Hz,1H),7.06(s,1H),6.55(s,1H),6.53(s,1H),5.92(s,1H),4.00(s,3H),3.56(s,2H),3.36(s,2H),2.94(s,6H),2.80(s,3H); MS m / z(ESI): 512[M+H]+. Example 51: Preparation of N-(5-((5-chloro-4-(5-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 50. 1H NMR (400MHz, CD3OD) δ8.60(s,1H),8.46(s,1H),8.33(s,1H),8.25(d,J=8.8Hz,1H),8.20(s,1H),7.63(d,J=8.8Hz,1H),6.98( s,1H),6.59–6.37(m,2H),5.96–5.86(m,1H),4.00(s,3H),3.50(t,J=5.7Hz,2H),3.32–3.28(m,2H),2.90(s,6H),2.72(s,3H); MS m / z(ESI): 546[M+H]+. Example 52: Preparation of N-(5-((4-(5-cyano-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 50. 1H NMR(400MHz,CD3OD)δ8.88(s,1H),8.48(s,1H),8.35(s,1H),8.10(s,1H),7.75–7.60(m,1H),7.02(s,1H ),6.51(s,2H),5.91(d,J=11.7Hz,1H),4.00(s,3H),3.54(s,2H),3.32(s,2H),2.91(s,6H),2.75(s,3H); MS m / z(ESI): 580[M+H]+. Example 53: Preparation of N-(5-((4-(5,6-dimethoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 1-(4,5-dimethoxy-2-nitrophenyl)ethane-1-one 10 g of 1-(3,4-dimethoxyphenyl)ethane-1-one was placed in acetic anhydride (30 mL), cooled to 0 °C, and a mixture of 200 mL of nitric acid and 10 mL of acetic anhydride was added dropwise. After the addition was complete, the mixture was stirred for 4 hours. The reaction solution was poured into 1 L of ice water, filtered, washed with water, and dried to obtain 8 g of 1-(4,5-dimethoxy-2-nitrophenyl)ethane-1-one (67%). Step 2: Preparation of 1-(4,5-dimethoxy-2-aminophenyl)ethane-1-one 1-(4,5-dimethoxy-2-nitrophenyl)ethane-1-one (8 g) and iron powder (20 g) were placed in HOAc (70 mL), water (100 mL), and EtOAc (20 mL) and reacted at 100 °C for 2 hours. The pH was adjusted to 7 with sodium bicarbonate aqueous solution, and 400 mL of ethyl acetate was added. The mixture was filtered, concentrated, and recrystallized from ethyl acetate-petroleum ether to obtain 1-(4,5-dimethoxy-2-aminophenyl)ethane-1-one (1.37 g, 30%). Step 3: Preparation of 1-(2-amino-4,5-dimethoxyphenyl)ethane-1-one oxime 1-(4,5-dimethoxy-2-aminophenyl)ethane-1-one (800 mg, 4.1 mmol), hydroxyamino acid salt (880 mg, 12.3 mmol), and NaOH (1.31 g, 32.8 mmol) were placed in 6 mL of an aqueous solution of ethanol (85%), heated at 60 °C for 1 hour, concentrated, extracted with ethyl acetate, and recrystallized from ethyl acetate-petroleum ether to give 1-(2-amino-4,5-dimethoxyphenyl)ethane-1-one oxime (500 mg, 58%). Step 4: Preparation of 5,6-dimethoxy-3-methyl-1H-indazole 1-(2-amino-4,5-dimethoxyphenyl)ethane-1-one oxime (450 mg, 2.14 mmol) and triethylamine (432 mg, 4.28 mmol) were placed in DCM (15 mL), and 0.2 mL of methanesulfonyl chloride was added dropwise at 0 °C. The mixture was stirred at room temperature for one hour, concentrated, and subjected to column chromatography to give 5,6-dimethoxy-3-methyl-1H-indazole (200 mg, 37%). Steps 5 to 10: Preparation of N-(5-((4-(5,6-dimethoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,6-dimethoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.00(s,1H),7.91–7.80(m,1H),7.75(s,1H),7.37(d,J=7.0Hz,1H),6.98(d,J=12.7Hz,2H),6.53(s,1H),6.32(d,J= 16.7Hz,1H),5.74(s,1H),3.83(s,3H),3.78(s,3H),3.77–3.67(m,3H),3.42(s,2H),3.27(s,2H),2.82(s,6H),2.67(s,2H),2.41(s,3H); MS m / z(ESI): 561[M+1]+. Example 54: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: 6-Methoxy-3-methyl-1H-indazole 1-(2-fluoro-4-methoxyphenyl)ethane-1-one (2 g, 11.9 mmol) was dissolved in 5 mL of hydrazine hydrate (85%) and NMP (15 mL), stirred at 120 °C for 24 hours, and then subjected to column chromatography to give 6-methoxy-3-methyl-1H-indazole (1.5 g, 78%). Steps 2 through 7: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 47. 1H NMR (400MHz, CD3OD) δ8.25–8.13(m,1H),8.11–8.00(m,1H),7.81(s,1H),7.70(d,J=8.7Hz,1H),7.59(d,J=7.0Hz,1H),7.09(s,2H),6. 69–6.56(m,1H),6.45(s,1H),5.86(s,1H),3.95(s,3H),3.87(s,3H),3.56(s,2H),3.38(s,2H),2.92(s,6H),2.81(s,3H),2.58(s,3H); MS m / z(ESI): 531[M+1]+. Example 55: Preparation of N-(5-((4-(6-cyano-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. Example 56: Preparation of N-(5-((4-(5-cyano-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR(400MHz,CD3OD)δ8.67–8.55(m,1H),8.36(d,J=6.4Hz,1H), 8.28(s,1H),7.94(s,1H),7.73(d,J=8.7Hz,1H),7.51(d,J=6.5Hz,1H),7.08(s,1H),6.55(dd,J=7.9,5.9Hz,2H) ,5.91(d,J=11.8Hz,1H),4.00(s,3H),3.57(s,2H),3.38(d,J=5.9Hz,2H),2.95(s,6H),2.80(s,3H),2.64(s,3H); MS m / z(ESI): 526[M+H]+. Example 57: Preparation of N-(5-((4-(5,6-difluoro-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,6-difluoro-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. Example 58: Preparation of N-(5-((4-(5,7-difluoro-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,7-difluoro-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. Example 59: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 2-chloro-N-(4-methoxy-2-nitrophenyl)pyrimidine-4-amine In a 100 mL round-bottom flask, 2-chloropyrimidin-4-amine (518.2 mg, 4 mmol) and DMF (10 mL) were added. Under N2 protection, the mixture was heated to 0 °C in an ice-salt bath. NaH (295 mg, 8 mmol) was added, and the mixture was stirred for 30 minutes. Then, 1-fluoro-4-methoxy-2-nitrobenzene (684.5 mg, 4 mmol) was added, and the mixture was slowly brought back to room temperature and stirred for 1 h. The mixture was then heated to 0 °C in an ice-salt bath, and 30 mL of water was added. A solid precipitated, which was filtered. The filter cake dissolved in dichloromethane. The solution was dried over anhydrous sodium sulfate and concentrated to obtain 2-chloro-N-(4-methoxy-2-nitrophenyl)pyrimidin-4-amine (1 g, 89%). MS m / z(ESI): 281.0[M+H]+. Step 2: Preparation of N1-(2-chloropyrimidin-4-yl)-4-methoxyphenyl-1,2-diamine In a 100 mL round-bottom flask, 2-chloro-N-(4-methoxy-2-nitrophenyl)pyrimidin-4-amine (980.0 mg, 3.5 mmol), ethanol (15 mL), and water (5 mL) were added, followed by iron powder (1.37 g, 24.5 mmol) and ammonium chloride (131.5 mg, 2.5 mmol). The mixture was reacted at 80 °C for 3 h. The mixture was filtered, the filtrate was concentrated, and the residue was dissolved in ethyl acetate (50 mL), diluted with 30 mL of water, dried over anhydrous sodium sulfate, filtered, and concentrated to give N1-(2-chloropyrimidin-4-yl)-4-methoxyphenyl-1,2-diamine (676.9 mg, 77%). MS m / z(ESI): 251.1[M+H]+. Step 3: Preparation of 1-(2-chloropyrimidin-4-yl)-5-methoxy-1H-benzis[d]imidazole In a 100 mL round-bottom flask, N1-(2-chloropyrimidin-4-yl)-4-methoxyphenyl-1,2-diamine (300 mg, 1.2 mmol), ethanol (10 mL), trimethyl orthoformate (1.0 g, 9.6 mmol), and p-toluenesulfonic acid (20 mg, 0.12 mmol) were added, and the mixture was reacted at 80 °C for 1 h. After cooling to room temperature, the reaction solution was concentrated, and the residue was subjected to column chromatography to give 1-(2-chloropyrimidin-4-yl)-5-methoxy-1H-benzo[d]imidazole (195 mg, 62%). MS m / z(ESI):261.1[M+H]+. Step 4: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidine-2-amine In a 100 mL round-bottom flask, 1-(2-chloropyrimidin-4-yl)-5-methoxy-1H-benzo[d]imidazole (195 mg, 0.75 mmol), 4-fluoro-2-methoxy-5-nitroaniline (140 mg, 0.75 mmol), p-toluenesulfonic acid (129 mg, 0.75 mmol), and 2-pentanol (5 mL) were added, and the mixture was reacted at 100 °C for 4 h. After cooling to room temperature, the reaction solution was concentrated, and the residue was subjected to column chromatography to obtain N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(5-methoxy-1H-benzo[d]imidazole-1-yl)pyrimidin-2-amine (62 mg, 20%). MS m / z(ESI): 411.1[M+H]+. Step 5: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine In a 100 mL round-bottom flask, N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine (62 mg, 0.15 mmol), N1,N1,N2,N2-tetramethylethane-1,2-diamine (30.6 mg, 0.3 mmol), DIPEA (58 mg, 0.45 mmol), and DMF (5 mL) were added, and the mixture was reacted at 80 °C for 1 h. After cooling to room temperature, the reaction mixture was concentrated, and the residue was subjected to column chromatography to obtain N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (40 mg, 54%). MS m / z(ESI): 493.3[M+H]+. Step 6: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine In a 100 mL round-bottom flask, N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (39.4 mg, 0.08 mmol) and methanol (20 mL) were added. A hydrogen balloon was added, and the mixture was reacted at room temperature for 30 minutes. The mixture was filtered, and the reaction solution was concentrated to give N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methylbenzene-1,2,4-triamine (32 mg, 85%). MS m / z(ESI): 463.1[M+H]+. Step 7: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide In a 100 mL round-bottom flask, add N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine (32 mg, 0.07 mmol) and anhydrous tetrahydrofuran (20 mL), protect with N2, heat to 0 °C in an ice-salt bath, add DIPEA (18 mg, 0.14 mmol), and add 1 M acryloyl chloride (0.2 mL, 0.1 mmol) dropwise. React at 0 °C for 30 minutes. The reaction was terminated by adding 0.5 mL of water. The reaction solution was concentrated and the residue was subjected to column chromatography to obtain N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (10 mg, 28%). 1H NMR (400MHz, CD3OD) δ9.36(s,1H),8.57(d,J=5.4Hz,1H),8.26(s,2H),7.39–7.24(m,2H),7.12–6.97(m,2H),6.52(qd,J=17.0,5.8Hz ,2H),5.86(dd,J=9.7,1.8Hz,1H),3.99(s,3H),3.89(s,3H),3.51(d,J=5.5Hz,2H),3.33(s,2H),2.90(d,J=5.1Hz,6H),2.75(s,3H); MS m / z(ESI): 517.2[M+H]+. Example 60: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.21 (s, 1H), 8.58 (d, J = 5.6Hz, 1H), 8.34 (s, 1H), 7.86 (s, 1H), 7.6 9(d,J=8.9Hz,1H),7.30(d,J=5.6Hz,1H),7.11(dd,J=8.7,2.1Hz,1H),7.00(s,1H),6.5 7(dd,J=16.9,10.0Hz,1H),6.44(dd,J=16.9,1.6Hz,1H),5.84(dd,J=10.1,1.6Hz,1H), 3.98(s,3H),3.86(s,3H),3.50(t,J=5.7Hz,2H),3.32(s,2H),2.89(s,6H),2.74(s,3H); MS m / z(ESI): 517.3[M+H]+. Example 61: Preparation of N-(5-((4-(5-cyano-1H-benzimidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 62: Preparation of N-(5-((4-(6-cyano-1H-benzimidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.19 (s, 1H), 8.78 (s, 1H), 8.52 (d, J = 5.7Hz, 1H), 8.24 (s, 1H), 7 .86(d,J=8.3Hz,1H),7.66(dd,J=8.3,1.2Hz,1H),7.31(d,J=5.8Hz,1H),7.07(s,1H) ,6.59(dd,J=16.9,10.2Hz,1H),6.35(d,J=16.8Hz,1H),5.81(dd,J=10.3,1.2Hz,1H) ,3.97(s,3H),3.53(t,J=5.8Hz,2H),3.36(t,J=5.8Hz,2H),2.92(s,6H),2.77(s,3H); MS m / z(ESI): 512.2[M+H]+. Example 63: Preparation of N-(5-((5-chloro-4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.25(s,1H),8.74(s,1H),8.25(s,1H),7.85(d,J=8.2Hz,1H),7.33(s,1H),7.08(d,J=9.0Hz,1H),6.98(s,1H),6.47– 6.41(m,2H),5.85(dd,J=7.8,3.9Hz,1H),4.00(s,3H),3.91(s,3H),3.49(t,J=5.7Hz,2H),3.28(t,J=5.6Hz,2H),2.86(s,6H),2.71(s,3H); MS m / z(ESI): 551.2[M+H]+. Example 64: Preparation of N-(5-((5-chloro-4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 65: Preparation of N-(5-((5-chloro-4-(5-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 66: Preparation of N-(5-((5-chloro-4-(6-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(6-cyano-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 67: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ8.98(s,1H),8.87(s,1H),8.15(s,1H),7.73(d,J=8.7Hz,1H),7.32(s,1H),7.10(s,1H),6.98(s,1H),6.43( s,2H),5.84(d,J=11.1Hz,1H),3.98(s,3H),3.91(s,3H),3.49(t,J=5.3Hz,2H),3.29(d,J=5.4Hz,2H),2.85(s,6H),2.71(s,3H); MS m / z(ESI): 585.3[M+H]+. Example 68: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 69: Preparation of N-(5-((4-(5-cyano-1H-benzimidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 70: Preparation of N-(5-((4-(6-cyano-1H-benzimidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 71: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 72: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 73: Preparation of N-(5-((4-(5-cyano-2-methyl-1H-benzi[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 74: Preparation of N-(5-((4-(6-cyano-2-methyl-1H-benzis[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 75: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-2-methyl-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 76: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 77: Preparation of N-(5-((4-(6-cyano-2-methyl-1H-benzi[d]imidazol-1-yl)-5-fluoropyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-5-fluoropyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 78: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-5-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-5-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 79: Preparation of N-(5-((4-(5-cyclopropyl-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyclopropyl-2-methyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 80: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(2-methyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 59. Example 81: Preparation of N-(5-((4-(2-cyclopropyl-5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(2-cyclopropyl-5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 82: Preparation of N-(5-((4-(2-cyclopropyl-5-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(2-cyclopropyl-5-methoxy-1H-benzo[d]imidazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 83: Preparation of N-(5-((4-(5-cyano-2-cyclopropyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-2-cyclopropyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 84: Preparation of N-(5-((5-chloro-4-(5-cyano-2-cyclopropyl-1H-benzi[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-cyano-2-cyclopropyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 85: Preparation of N-(5-((4-(2-cyclopropyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(2-cyclopropyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 86: Preparation of N-(5-((4-(2-cyclopropyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(2-cyclopropyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 87: Preparation of N-(5-((5-chloro-4-(2-cyclopropyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(2-cyclopropyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. Example 88: Preparation of N-(5-((4-(2-cyclopropyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(2-cyclopropyl-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CDCl3): δ10.3(br s,1H),8.75(s,1H),8.46(d,J=6.0Hz,1H),8.00(dd,J=4.8,1.6Hz,1H),7.64(dd,J=6.0,1.6Hz,1H),7.21(m,3H),6.96(d,J=6.4Hz,1H),6.82(s, 1H),6.45(m,2H),5.73(d,J=9.2Hz,1H),3.84(s,3H),2.99(m,1H),2.89( m,2H),2.73(s,3H),2.36(m,2H),2.31(s,6H),1.04(m,2H),0.87(m,2H); MS m / z(ESI): 527.2[M+H]+. Example 89: Preparation of N-(5-((4-(5,7-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,7-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ10.2(br s,1H),9.79(s,1H),9.14(s,1H),8.37(d,J=5.2Hz,1H),7.72(s,1H),7.40(d,J=5.2Hz,1H),6.87(dd,J=8.8,1.6Hz,1H) ,6.79(s,1H),6.74(m,1H),6.41(m,2H),5.70(m,1H),3.95(s,3H),3.88(s,3H),2.91(m,2H),2.57(s,3H),2.22(m,8H); MS m / z(ESI): 527.3[M+H]+. Example 90: Preparation of N-(5-((4-(4,5-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(4,5-difluoro-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CD3OD): δ9.20 (s, 1H), 8.36 (s, 1H), 8.18 (d, J = 5.6Hz, 1H), 7.99 (m,1H),7.26(m,1H),7.04(d,J=5.6Hz,1H),6.97(s,1H),6.56(m,1H),6.29(d d,J=17.2Hz,2.0Hz,1H),5.74(dd,J=10.4Hz,1.6Hz,1H),3.91(s,3H),3.80(s ,3H),3.06(t,J=6.4Hz,2H),2.70(s,3H),2.46(t,J=6.0Hz,1H),2.31(m,6H); MS m / z(ESI): 536.2[M+H]+. Example 91: Preparation of N-(5-((4-(7-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(7-cyclopropyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3): δ10.08(s,1H),9.83(s,1H),8.96(s,1H),8.36(d,J=5.2Hz,1H), 7.91(d,J=8.0Hz,1H),7.73(s,1H),7.17(d,J=5.2Hz,1H),7.10(t,J=7.6Hz,1H),6.99 (d, J=7.2Hz,1H),6.79(s,1H),6.44(m,2H),5.71(m,1H),4.45(s,3H),3.88(s,3H),2. 91(t,J=5.6Hz,2H),2.71(s,3H),2.46(m,1H),2.28(m,8H),1.01(m,2H),0.90(m,2H); MS m / z(ESI): 540.2[M+H]+. Example 92: N-(5-((4-(7-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(7-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3) δ10.27(s,1H),10.13(s,1H),9.83(s,1H),9.04(s,1H),8.36(d,J=5.3Hz, 1H),7.89(d,J=8.0Hz,1H),7.72(s,1H),7.16(d,J=5.3Hz,1H),7.09(t,J=7.7Hz,1H),6.79(d,J =5.6Hz,2H),6.71–6.50(m,1H),6.39(s,1H),5.82–5.58(m,1H),3.88(s,3H),3.08–2.83(m,2H ),2.70(s,3H),2.39–2.20(m,8H),2.16(t,J=5.1Hz,1H),0.96–0.73(m,2H),0.73–0.55(m,2H); MS m / z(ESI): 526.7 [M+H]+. Example 93: Preparation of N-(5-((4-(1-cyclopropyl-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. TFA salt of N-(5-((4-(1-cyclopropyl-6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide 1H NMR (400MHz, CD3OD): δ8.41(s,1H),8.15(br,1H),7.98(d,J=6.8Hz,1H),7.89(s,1H),7.40(d,J=6.8Hz,1H),7.17(d,J=2.4Hz,1H),7.06(s,1H), 6.87(m,1H),6.50(m,2H),5.87(m,1H),3.95(s,3H),3.88(s,3H),3.55( m,3H),3.35(m,2H),2.92(s,6H),2.80(s,3H),1.22(m,2H),0.90(m,2H); MS m / z(ESI): 556.2[M+H]+. Example 94: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(7-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(7-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CD3OD): δ8.40 (s, 1H), 8.03 (d, J = 6.8Hz, 1H), 7.46 (d, J =6.8Hz,1H),7.12(m,1H),7.09(s,1H),6.77(d,J=8.0Hz,1H),6.51(m,2H),5.87(m, 1H),3.98(s,3H),3.87(s,3H),3.57(m,2H),3.36(m,2H),2.92(m,6H),2.80(s,3H); MS m / z(ESI): 516.2[M+H]+. Example 95: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 6-iodo-1H-indole At room temperature, NaI (4.59 g, 30.6 mmol), CuI (290 mg, 1.53 mmol), and N,N'-dimethylethylenediamine (0.35 mL) were added to a 30 mL solution of 6-bromo-1H-indole (3.00 g, 15.3 mmol) in dioxane. The solution was bubbled with nitrogen for 5 minutes to remove oxygen. Under nitrogen protection, the solution was stirred overnight in an oil bath at 110 °C. After cooling, the solution was concentrated under reduced pressure to remove the organic solvent. EtOAc and water were added to separate the phases. The EtOAc phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated for column chromatography (eluent: pure PE) to give the title compound 6-iodo-1H-indole (2.1 g, 57%). MS m / z(ESI): 244.0[M+H]+. Step 2: Preparation of 6-iodo-1-methyl-1H-indole Under ice-water bath conditions, NaH (60%, 734 mg, 18.4 mmol) was added to a DMF solution (30 mL) of 6-iodo-1H-indole (2.00 g, 8.23 ​​mmol), and the mixture was stirred at this temperature for 20 minutes. Then, a DMF solution (10 mL) of MeI (1.14 mL, 18.4 mmol) was added dropwise, and the mixture was stirred at this temperature for another 30 minutes. Approximately 100 mL of water was added, and the mixture was extracted with EtOAc. The EtOAc phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (eluent: pure PE) to give the title compound 6-iodo-1-methyl-1H-indole (1.98 g, 94%). MS m / z(ESI): 258.1 [M+H]+. Step 3: Preparation of 3-(2-chloropyrimidin-4-yl)-6-iodo-1-methyl-1H-indole FeCl3 (441 mg, 2.72 mmol) was added to a 10 mL solution of 6-iodo-1-methyl-1H-indole (700 mg, 2.72 mmol) and 2,4-dichloropyrimidine (405 mg, 2.72 mmol) in ethylene glycol dimethyl ether. The mixture was stirred overnight at 60 °C. After cooling, a large amount of EtOAc and water were added to separate the layers. Insoluble matter was removed with diatomaceous earth, and the aqueous phase was separated. The organic phase was washed successively with saturated sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography (eluent: PE:EtOAc = 3:1) to give the title compound 3-(2-chloropyrimidin-4-yl)-6-iodo-1-methyl-1H-indole (533 mg, 53%). MS m / z(ESI): 370.59[M+H]+. Step 4: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-iodo-1-methyl-1H-indol-3-yl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-6-iodo-1-methyl-1H-indole (283 mg, 0.765 mmol), 4-fluoro-2-methoxy-5-nitroaniline (142 mg, 0.765 mmol), and TsOH·H₂O (175 mg, 0.918 mmol) were mixed in 10 mL of 2-pentanol and reacted at 125 °C for 3 h. After cooling and filtration, the solid was dissolved in CH₂Cl₂, washed successively with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-iodo-1-methyl-1H-indole-3-yl)pyrimidin-2-amine (350 mg, 88%). MS m / z(ESI): 520.2[M+H]+. Step 5: Preparation of N1-(2-(dimethylamino)ethyl)-N4-(4-(6-iodo-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-iodo-1-methyl-1H-indol-3-yl)pyrimidin-2-amine (100 mg, 0.192 mmol), N1,N1,N2-trimethylethane-1,2-diamine (39 mg, 0.385 mmol), and DIPEA (42 mg, 0.385 mmol) were dissolved in DMA (10 mL) and reacted at 85 °C for 3 hours. After cooling, water and EtOAc were added to separate the phases. The organic phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give 105 mg of crude N1-(2-(dimethylamino)ethyl)-N4-(4-(6-iodo-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine, which was used directly in the next step. MS m / z(ESI): 602.4[M+H]+. Step 6: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine N1-(2-(dimethylamino)ethyl)-N4-(4-(6-iodo-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine (100 mg, 0.166 mmol), (trimethylsilyl)acetylene (48 mg, 0.498 mmol), and triethylamine (51 mg, 0.498 mmol) were mixed in THF (10 mL) and DMF (5 mL), followed by the addition of CuI (16 mg, 0.083 mmol) and tetrakis(triphenylphosphine)palladium (40 mg, 0.041 mmol). After purging with nitrogen three times, the mixture was heated in an oil bath to 70°C overnight. The solvent was removed under reduced pressure, the aqueous phase was extracted with EtOAc, the EtOAc phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography [eluent: CH2Cl2 → CH2Cl2:MeOH = 20:1] to give the title compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine (65 mg, 68%). MS m / z(ESI): 572.7[M+H]+. Step 7: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine (200 mg, 0.35 mmol), reduced iron powder (136 mg, 2.45 mmol), and ammonium chloride (20.6 mg, 0.386 mmol) were mixed in EtOH (30 mL) and water (10 mL) and heated under reflux for three hours. After cooling, a large amount of EtOH was added, and the insoluble matter was removed by diatomaceous earth filtration. The EtOH was removed under reduced pressure, and the aqueous phase was extracted with EtOAc. The EtOAc phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography [eluent: CH2Cl2 → CH2Cl2: MeOH (containing 10% concentrated ammonia) = 17:1] to give the title compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (166 mg, 88%). MS m / z(ESI): 542.3[M+H]+. Step 8: Preparation of N1-(2-(dimethylamino)ethyl)-N4-(4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methylphenyl-1,2,4-triamine N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-6-((trimethylsilyl)ethynyl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (90 mg, 0.166 mmol) was dissolved in THF (10 mL) and MeOH (10 mL), and then potassium carbonate (69 mg, 0.50 mmol) was added. The mixture was stirred at room temperature for 3 hours, the solvent was removed under reduced pressure, water and EtOAc were added to separate the phases, the organic phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound N1-(2-(dimethylamino)ethyl)-N4-(4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methylphenyl-1,2,4-triamine (71 mg, 91%). MS m / z(ESI): 470.26[M+H]+. Step 9: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Under ice-water bath conditions, a THF solution of acryloyl chloride (22.0 mg, 0.247 mmol) was added dropwise to a 2 mL solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-5-methoxy-N1-methylphenyl-1,2,4-triamine (80 mg, 0.169 mmol) and TEA (50 mg, 0.492 mmol) in THF. After the addition was complete, the mixture was stirred at the same temperature for 15 minutes, and then methanol was added to quench the reaction. The reaction solution was concentrated under reduced pressure, and thin-layer purification was performed (CH2Cl2:MeOH:concentrated ammonia water = 100:10:1) to obtain the title compound N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-ethynyl-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide (45 mg, 51%). 1H NMR (400MHz, CDCl3) δ10.03 (s, 1H), 9.74 (d, J = 6.2Hz, 1H), 9.07 (s, 1H), 8.31 (d, J = 5. 3Hz,1H),7.91(d,J=8.3Hz,1H),7.65(s,1H),7.48(s,1H),7.29(dd,J=8.3,1.2Hz,1H ),7.08(d,J=5.3Hz,1H),6.70(s,1H),6.37(d,J=16.3Hz,2H),5.81–5.57(m,1H),3.8 9(d,J=13.0Hz,3H),3.81(s,3H),3.02(s,1H),2.85(s,2H),2.62(s,3H),2.24(m,8H); MS m / z(ESI): 524.6[M+H]+. Example 96: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-6-vinyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-6-vinyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 95. 1H NMR (400MHz, CDCl3) δ9.96 (s, 1H), 9.76 (d, J = 4.7Hz, 1H), 8.99 (s, 1H), 8.30 (d, J = 5.3Hz ,1H),7.92(d,J=8.7Hz,1H),7.64(s,1H),7.30(dd,J=4.3,2.8Hz,2H),7.11(t,J=5.1Hz, 1H),6.80(dd,J=17.5,10.9Hz,1H),6.69(s,1H),6.38(d,J=16.7Hz,2H),5.90–5.52(m,2 H),5.19–5.06(m,1H),3.91(s,3H),3.80(s,3H),2.88(s,2H),2.63(s,3H),2.28(m,8H); MS m / z(ESI): 526.6[M+H]+. Example 97: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3) δ10.29(s,1H),9.85(s,1H),9.70(d,J=14.2Hz,1H),8.29(s,1H),8.16(s,1H),7.88(d,J=9.4Hz,1H),7.56(s,1H),6.88 (s,1H),6.79–6.60(m,3H),6.43(d,J=15.5Hz,2H),5.62(d,J=10.3Hz,1H),3.81(s,3H),3.62(s,3H),2.84(s,2H),2.64(s,3H),2.21(m,8H); MS m / z(ESI): 516.6[M+H]+. Example 98: Preparation of N-(5-((5-chloro-4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 6-methoxy-1-methyl-1H-indole 6-Methoxy-1H-indole (500 mg, 3.4 mmol) was dissolved in nitrodimethylformamide (16 mL), cooled to an ice bath, and sodium hydroxide (320 mg, 6.8 mmol) was added. After stirring for 15 min, iodomethane (0.25 mL, 3.7 mmol) was added dropwise. After the addition was complete, the mixture was allowed to rise naturally to room temperature for 2 h. The reaction was quenched with saturated ammonium chloride aqueous solution (20 mL) and extracted with ethyl acetate (30 mL × 3). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 6-methoxy-1-methyl-1H-indole (480 mg, 88%). Step 2: Preparation of 3-(2,5-dichloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole 6-Methoxy-1-methyl-1H-indole (480 mg, 3.0 mmol) and 2,4,5-trichloropyrimidine (660 mg, 3.6 mmol) were dissolved in ethylene glycol dimethyl ether (20 mL), and the mixture was heated to 80 °C and reacted for 20 min. Anhydrous aluminum trichloride (720 mg, 5.4 mmol) was added, and the mixture was stirred for 1 hour under nitrogen protection. The reaction solution was quenched in an ice-water mixture (approximately 50 mL), and the mixture was extracted with methyl tert-butyl ether (20 mL × 3). The organic phases were combined, dried over magnesium sulfate, filtered, and concentrated to obtain crude 3-(2,5-dichloropyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (320 mg, 30%). The crude product was used directly in the next reaction step. Steps 3 to 6: Preparation of N-(5-((5-chloro-4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CD3OD) δ8.48(s,1H),8.29–8.21(m,2H),8.19(s,1H),7.01(s,1H),6.96(d,J=2.2Hz,1H),6.78(dd,J=8.9,2.2Hz,1H),6.49–6.44(m, 2H),5.84(dd,J=7.7,4.1Hz,1H),3.97(s,3H),3.86(d,J=10.8Hz,6H),3.53(t,J=5.7Hz,2H),3.33–3.31(m,2H),2.91(s,6H),2.76(s,3H); MS m / z(ESI): 564.3[M+1]+. Example 99: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 6-methoxy-1-methyl-1H-indole The starting material, 6-methoxy-1H-indole (1 g, 6.793 mmol), was dissolved in DMF (20 mL) and cooled to 0 °C. Then, NaH (815 mg, 20.38 mmol) was added, and the mixture was stirred at 0 °C for ten minutes. Iodomethane (1.447 g, 10.19 mmol) was then added, and the mixture was allowed to react at room temperature for 1 hour. The reaction mixture was poured into ice water, extracted with ethyl acetate, and the organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. This crude product was purified by rapid silica gel column chromatography to obtain 6-methoxy-1-methyl-1H-indole (850 mg, 77.3%). Step 2: Preparation of 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole The starting materials 6-methoxy-1-methyl-1H-indole (850 mg, 5.27 mmol), 2,4-dichloro-5-(trifluoromethyl)pyrimidine (1.26 g, 5.8 mmol), and aluminum trichloride (1.05 g, 7.91 mmol) were dissolved in DME (30 mL), and the reaction mixture was stirred overnight at 70 °C. After the reaction was complete, the reaction solution was poured into ice water, extracted three times with methyl tert-butyl ether, and the organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain the product 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (700 mg, 39%). Step 3: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidine-2-amine Compound 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1-methyl-1H-indole (700 mg, 2.05 mmol), starting material 4-fluoro-2-methoxy-5-nitroaniline (419 mg, 2.25 mmol) and p-toluenesulfonic acid monohydrate (390 mg, 2.05 mmol) were dissolved in 2-pentanol (10 mL). The reaction was heated to 120 °C and carried out overnight. The reaction was confirmed to be complete by LCMS. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give the product N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indole-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine (600 mg, 60%). Step 4: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine The compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine (100 mg, 0.204 mmol) was dissolved in DMF (5 mL), and triethylamine (31 mg, 0.305 mmol) and compound N1,N1,N2-trimethylethane-1,2-diamine (42 mg, 0.407 mmol) were added. The reaction was heated to 120°C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the crude product was separated by preparative plate to obtain the product N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (90 mg, 77%). Step 5: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methylphenyl-1,2,4-triamine The compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (90 mg, 0.157 mmol) was dissolved in 10 mL of methanol, and Pd / C (15 mg) was added. The reaction was carried out under a hydrogen balloon at 24 °C for 1 hour. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methylbenzene-1,2,4-triamine (80 mg) was purified by rapid silica gel column chromatography. Step 6: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide Compounds N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methylbenzene-1,2,4-triamine (80 mg, 0.147 mmol) and triethylamine (45 mg, 0.442 mmol) were added to anhydrous tetrahydrofuran (20 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.4 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in a dry ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by preparative plate to obtain the product N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide (20 mg, 25%). 1H NMR (400MHz, CD3OD) δ8.64(s,1H),8.37(s,1H),8.09(d,J=8.6Hz,1H),7.75(s,1H),7.02–6.95(m,2H),6.78(dd,J=8.8,1.8Hz,1H),6.46–6.34( m,2H),5.83(dd,J=8.3,3.5Hz,1H),4.00(s,3H),3.87(d,J=8.4Hz,6H),3.51(t,J=5.7Hz,2H),3.30(t,J=5.7Hz,2H),2.88(s,6H),2.72(s,3H); MS m / z(ESI): 598.4[M+H]+. Example 100: Preparation of N-(5-((5-chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 98. 1H NMR (400MHz, CD3OD) δ8.44(s,1H),8.37(d,J=8.0Hz,1H),8.31(d,J=10.3Hz,2H),7.66( d,J=8.2Hz,1H),7.31–7.23(m,1H),7.16(dd,J=11.2,4.0Hz,1H),6.99(s,1H),6.45(d,J =6.2Hz,2H),5.88–5.80(m,1H),3.99(d,J=2.8Hz,3H),3.52(dt,J=7.1,3.7Hz,3H),3.32 –3.29(m,2H),2.89(s,6H),2.73(s,3H),1.20(dt,J=7.2,3.6Hz,2H),1.08–1.00(m,2H); MS m / z(ESI): 560.3[M+H]+. Example 101: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 98. 1H NMR(400MHz,CD3OD)δ8.68(s,1H),8.41(s,1H),8.19(d,J=7.8Hz,1H),7.82(s,1H),7 .67(d,J=8.2Hz,1H),7.26(t,J=7.6Hz,1H),7.14(t,J=7.5Hz,1H),6.99(s,1H),6.44( dt,J=14.3,7.1Hz,2H),5.85(dd,J=9.2,2.6Hz,1H),4.01(s,3H),3.60–3.44(m,3H),3 .29(t,J=5.6Hz,2H),2.87(s,6H),2.71(s,3H),1.25–1.18(m,2H),1.06–0.98(m,2H); MS m / z(ESI): 594.3[M+H]+. Example 102: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 3-(2-chloropyrimidin-4-yl)-1H-indole 3-(2-chloropyrimidin-4-yl)-1H-indole (1 g, 4.37 mmol), 2-(difluoromethoxy)-4-fluoro-5-nitroaniline (810 mg, 4.37 mmol), and p-toluenesulfonic acid (750 mg, 4.37 mmol) were dissolved in 2-pentanol (40 mL). The mixture was heated at 110 °C for 3 hours. The reaction was confirmed to be complete by LCMS. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (methyl tert-butyl ether) to give 3-(2-chloropyrimidin-4-yl)-1H-indole (1.3 g, 79%). Step 2: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidine-2-amine Compound 3-(2-chloropyrimidin-4-yl)-1H-indole (500 mg, 2.177 mmol), starting material 4-fluoro-2-methoxy-5-nitroaniline (445 mg, 2.394 mmol) and p-toluenesulfonic acid monohydrate (414 mg, 2.177 mmol) were dissolved in 2-pentanol (20 mL). The reaction was heated to 120 °C and carried out overnight. LCMS showed that the reaction was complete. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give the product N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indole-3-yl)pyrimidin-2-amine (180 mg, 22%). Step 3: Preparation of N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine The compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (178 mg, 0.469 mmol) was dissolved in DMF (2 mL), and triethylamine (142 mg, 1.41 mmol) and trimethylethylenediamine (144 mg, 1.41 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the crude product was separated by preparative plate to obtain the product N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (217 mg, 100%). Step 4: Preparation of 3-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide The compound N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (217 mg, 0.47 mmol) was dissolved in DMF (10 mL), cooled to 0 °C in an ice bath, and then NaH (56 mg, 1.41 mmol) was added. After reacting at 0 °C for ten minutes, dimethylaminosulfonyl chloride (74 mg, 0.52 mmol) was added dropwise. The reaction was then brought to room temperature and stirred for 30 minutes. After the reaction was quenched, dichloromethane and water were added, and the mixture was extracted three times. The organic phases were combined, washed with saturated sodium bicarbonate, water, and brine, and then filtered and concentrated to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain the product 3-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (160 mg, 60%). Step 5: Preparation of 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide Compound 3-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide was dissolved in methanol (5 mL), and Pd / C (15 mg) was added. The reaction was stirred at 24 °C for 1 hour under a hydrogen balloon. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain the product 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (90 mg, 59%). Step 6: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Compound 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (90 mg, 0.167 mmol) and triethylamine (51 mg, 0.501 mmol) were added to anhydrous tetrahydrofuran (30 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.5 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in a dry ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by preparative plate to obtain the product N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide (10 mg, 10%). 1H NMR (400MHz, CD3OD) δ8.62(s,1H),8.44(d,J=7.9Hz,1H),8.27(d,J=6.2Hz,1H),8.10(s,1H) ,8.00(d,J=8.3Hz,1H),7.54(d,J=6.3Hz,1H),7.37(dt,J=15.0,7.3Hz,2H),7.06(s,1H),6. 58(dd,J=16.9,10.0Hz,1H),6.46(dd,J=16.9,1.8Hz,1H),5.86(dd,J=10.0,1.7Hz,1H),3.9 8(s,3H),3.55(t,J=5.7Hz,2H),3.36(d,J=5.9Hz,2H),2.92(d,J=3.7Hz,12H),2.79(s,3H); MS m / z(ESI): 593.5[M+H]+. Example 103: Preparation of N-(2-((2-(diethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(diethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine The compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (120 mg, 0.316 mmol) was dissolved in DMF (2 mL), and triethylamine (96 mg, 0.949 mmol) and compound N,N-diethyl-N-methylethane-1,2-diamine (124 mg, 0.949 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the crude product was separated by preparative plate to obtain the product N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(diethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (155 mg, 100%). Step 2: Preparation of 3-(2-((4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide The compound N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(diethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (155 mg, 0.316 mmol) was dissolved in DMF (10 mL), cooled to 0 °C in an ice bath, and then NaH (38 mg, 0.945 mmol) was added. After reacting at 0 °C for ten minutes, dimethylaminosulfonyl chloride (55 mg, 0.38 mmol) was added dropwise. The reaction was then brought to room temperature and stirred for 30 minutes. After the reaction was quenched, dichloromethane and water were added, and the mixture was extracted three times. The organic phases were combined, washed with saturated sodium bicarbonate solution, water, and brine, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain the product 3-(2-((4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (130 mg, 19%). Step 3: Preparation of 3-(2-((5-amino-4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide Compound 3-(2-((4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide was dissolved in methanol (5 mL), and Pd / C (15 mg) was added. The reaction was carried out under a hydrogen balloon at 24 °C for 1 hour. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product 3-(2-((5-amino-4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide 118 mg was purified by rapid silica gel column chromatography. Step 4: Preparation of N-(2-((2-(diethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Compound 3-(2-((5-amino-4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (118 mg, 0.208 mmol) and triethylamine (63 mg, 0.624 mmol) were added to anhydrous tetrahydrofuran (30 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.62 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in a dry ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain the product N-(2-((2-(diethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide (4.8 mg, 3.7%). 1H NMR (400MHz, CD3OD) δ8.61(s,1H),8.46(d,J=8.0Hz,1H),8.33(d,J=6.1Hz,1H),8.08( s,1H),8.02(d,J=8.3Hz,1H),7.55(d,J=6.1Hz,1H),7.45–7.26(m,2H),7.04(s,1H),6 .48(qd,J=17.0,5.9Hz,2H),5.87(dd,J=9.4,2.5Hz,1H),4.01(s,3H),3.57(t,J=5.7H z,2H),3.25(dt,J=19.4,7.2Hz,4H),2.93(s,6H),2.79(s,3H),1.29(t,J=7.3Hz,6H); MS m / z(ESI): 621.5[M+H]+. Example 104: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of 3-(2-chloropyrimidin-4-yl)-1-(oxobutylcyclo-3-yl)-1H-indole 3-(2-chloropyrimidin-4-yl)-1H-indole (500 mg, 2.18 mmol), 3-iodooxadiazine (480 mg, 2.61 mmol), and cesium carbonate (1.42 g, 4.36 mmol) were mixed in DMF (5 mL) and reacted in a microwave oven at 110 °C for 1 hour. After cooling, the mixture was diluted with CH2Cl2, the organic phase was washed three times with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to give the title compound 3-(2-chloropyrimidin-4-yl)-1-(oxadiazine-3-yl)-1H-indole (110 mg, 18%). 1H NMR (400MHz, CDCl3): δ8.54(d,J=5.2Hz,1H),8.38(m,1H),8.33(s,1H),7.60(d,J=5.2Hz, 1H),7.54(m,1H),7.38(m,2H),5.66(m,1H),5.26(t,J=7.6Hz,2H),5.14(t,J=7.6Hz,2H); MS m / z(ESI): 286.1[M+H]+. Step 2: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidine-2-amine 3-(2-chloropyrimidin-4-yl)-1-(oxobutylcyclo-3-yl)-1H-indole (110 mg, 0.385 mmol), 4-fluoro-2-methoxy-5-nitroaniline (86 mg, 0.462 mmol), palladium acetate (9 mg, 0.0385 mmol), and cesium carbonate (376 mg, 1.16 mmol) were mixed in DMA (1 mL) and 1,4-dioxane (2 mL). The mixture was bubbled under a nitrogen atmosphere to remove oxygen for 15 minutes. Then, Xantphos (45 mg, 0.0770 mmol) was added, and the mixture was bubbled for another 5 minutes. Finally, the mixture was reacted in a microwave reactor at 160 °C for 30 minutes. After cooling, the solution was diluted with CH2Cl2, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by thin-layer chromatography to obtain the title compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidine-2-amine (80 mg, 46%). MS m / z(ESI): 436.1 [M+H]+. Step 3: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine Trimethylethylenediamine (0.1 mL) and DIPEA (0.1 mL) were added to a DMA solution (80 mg, 0.18 mmol) of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-amine (80 mg, 0.18 mmol). The mixture was stirred at 85 °C for 3 hours. After cooling, water was added, and a solid precipitated. The solid was purified by preparative thin-layer chromatography to give compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine (35 mg, 38%). MS m / z(ESI): 518.2[M+H]+. Step 4: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(oxobutan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine (28 mg, 0.054 mmol), reduced iron powder (30 mg, 0.54 mmol), and ammonium chloride (2.0 mg, 0.032 mmol) were mixed in ethanol (3 mL) and water (1 mL), heated under reflux for one hour, cooled, filtered through diatomaceous earth, concentrated the filtrate, and purified by thin-layer chromatography to obtain the title compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(oxobutan-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (25 mg, 95%). MS m / z(ESI): 488.3[M+H]+. Step 5: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide At -15°C, a THF solution (0.5 mL) of acryloyl chloride (0.025 mL, 0.31 mmol) was added dropwise to a 2 mL solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (25 mg, 0.051 mmol) and triethylamine (0.050 mL, 0.36 mmol). After the addition was complete, the mixture was stirred at this temperature for another 5 minutes. The compound was quenched with methanol and purified by thin-layer chromatography to obtain the title compound N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(oxobutane-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (7 mg, 25%). 1H NMR (400MHz, CDCl3): δ10.2(br s,1H),9.80(s,1H),9.06(s,1H),8.42(d,J=5.2Hz,1H),8.10(m,1H),7.73(m,2H),7.30(m,2H),7.23(d,J=5.2Hz,1H),6.79(s,1H),6. 44(m,2H),5.89(m,1H),5.74(m,1H),5.38(t,J=6.8Hz,2H),5.15(t,J=7.6Hz,2H),3.89(s,3H),2.92(m,2H),2.71(s,3H),2.29(m,8H); MS m / z(ESI): 542.3[M+H]+. Example 105: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-ethoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 5-ethoxy-1H-indazole 5-Hydroxy-1H-indazole (2.68 g, 20 mmol) was dissolved in DMF (50 mL), and iodoethane (3.28 g, 21 mmol) and potassium carbonate (4.16 g, 30 mmol) were added. The mixture was stirred at room temperature for 24 hours, extracted with ethyl acetate, and subjected to column chromatography to obtain 5-ethoxy-1H-indazole (1.5 g, 46%). 1H NMR (400MHz, CDCl3) δ8.73–8.18(m,1H),8.03(d,J=0.9Hz,1H),7.42(d,J=8.6Hz,1H),7.15–7.06(m,2H),4.10(q,J=7.0Hz,2H),1.48(t,J=7.0Hz,3H); MS m / z(ESI): 163[M+H]+. Steps 2 and 3: Preparation of 5-ethoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole The preparation method of 5-ethoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole is similar to that in Example 43. Step 4: Preparation of 4-(5-ethoxy-1H-indazol-1-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidine-2-amine N-(4-fluoro-2-methoxy-5-nitrophenyl)formamide (134 mg, 0.63 mmol) was dissolved in THF (20 mL), and sodium hydroxide (50 mg, 1.26 mmol) was added at 0 °C. After stirring for 10 minutes, 5-ethoxy-1-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole (200 mg, 0.63 mmol) was added and stirred overnight. An appropriate amount of 1N sodium hydroxide aqueous solution was added, and the mixture was stirred for 30 minutes. The mixture was extracted with DCM and subjected to column chromatography to obtain 4-(5-ethoxy-1H-indazole-1-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidin-2-amine (210 mg, 78%). Steps 5 to 7: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-ethoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-ethoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 43. 1H NMR (400MHz, CD3OD) δ8.39(s,2H),8.33–8.22(m,1H),7.84(s,1H),7.62(d,J=6.8Hz,1H),7.31(s,1H),7.19–7.11(m,1H),7.09(s,1H),6.52(d, J=9.4Hz,2H),5.95–5.84(m,1H),4.12(d,J=7.0Hz,2H),3.97(s,3H),3. 58(s,2H),3.37(s,2H),2.94(s,6H),2.82(s,3H),1.45(t,J=7.0Hz,3H); MS m / z(ESI): 531[M+H]+. Example 106: Preparation of N-(5-((4-(5-cyano-3-methyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 5-bromo-3-methyl-1H-indazole 1-(5-bromo-2-fluorophenyl)ethane-1-one (5 g, 23.04 mmol) and hydrazine hydrate (20 mL) were heated for 2 days and then subjected to column chromatography to give 5-bromo-3-methyl-1H-indazole (2.8 g, 58%). Step 2: Preparation of 5-cyano-3-methyl-1H-indazole 5-Bromo-3-methyl-1H-indazole (500 mg, 2.38 mol), zinc cyanide (418 mg, 3.57 mmol), Pd2(dba)3 (194 mg, 0.238 mmol), and X-Phos (227 mg, 0.476 mol) were added to a microwave tube, deoxygenated under nitrogen, and heated for 1 hour. The mixture was then subjected to column chromatography to obtain 5-cyano-3-methyl-1H-indazole (430 mg, 98%). 1H NMR (400MHz, CDCl3) δ8.12 (s, 1H), 7.61 (s, 1H), 7.56 (d, J = 8.7Hz, 1H), 2.66 (s, 3H); MS m / z(ESI): 158[M+H]+. Steps 3 to 7: Preparation of N-(5-((4-(5-cyano-3-methyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Steps three through seven: The preparation method of N-(5-((4-(5-cyano-3-methyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.85(s,1H),8.48–8.35(m,1H),8.35–8.30(m,1H),8.06(s,1H),7.77–7.62(m,1H),7.01(s,1H),6.59–6.49( m,1H),6.47–6.37(m,1H),5.94–5.86(m,1H),4.01(s,3H),3.61–3.50(m,2H),3.32(s,2H),2.91(s,6H),2.75(s,3H),2.65(s,3H); MS m / z(ESI): 594[M+H]+. Example 107: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-3-methyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-3-methyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 40. 1H NMR(400MHz,CD3OD)δ8.74(s,1H),8.25–8.10(m,1H),8.04(s,1H),7.18(s,1H),7.10–7.03(m,1H),7.00(s,1H),6.47(s,2H) ,5.89–5.83(m,1H),3.98(s,3H),3.89(s,3H),3.54(s,2H),3.01(s,1H),2.90(s,6H),2.88(s,1H),2.76(s,3H),2.57(s,3H); MS m / z(ESI): 599[M+H]+. Example 108: Preparation of N-(5-((5-chloro-4-(5-chloro-3-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 5-chloro-2-hydrazinobenzoic acid 5-Chloro-2-fluorobenzoic acid (5 g, 0.0287 mmol) and hydrazine hydrate (10 ml, 85%) were heated overnight at 100 °C. The reaction solution was concentrated, acidified, filtered, and dried to give 5-chloro-2-hydrazinobenzoic acid (2.5 g, 50%). Step 2: Preparation of 5-chloro-1H-indazole-3-ol 5-Chloro-2-hydrazinobenzoic acid (2.5 g), concentrated hydrochloric acid (10 ml) and water (200 ml) were heated at 100 °C for 3 hours, concentrated to 100 mL, the pH was adjusted to 7.0 with sodium carbonate, filtered and dried to obtain 5-chloro-1H-indazole-3-ol (1.7 g, 60%). 1H NMR (400MHz, DMSO) δ11.73 (s, 1H), 10.67 (s, 1H), 7.65 (d, J = 1.3Hz, 1H), 7.30 (dt, J = 8.9, 5.1Hz, 2H); MS m / z(ESI): 169[M+H]+. Step 3: Preparation of ethyl 5-chloro-3-hydroxy-1H-indazole-1-carboxylic acid ester 5-Chloro-1H-indazole-3-ol (1.7 g, 10.12 mmol) was dissolved in pyridine (10 mL), methyl chloroformate (1.31 g, 12.14 mmol) was added, the mixture was heated at 100 °C for 2 hours, and after the reaction was completed, it was cooled, 150 mL of water was added, filtered, and dried to obtain ethyl 5-chloro-3-hydroxy-1H-indazole-1-carboxylic acid ester (2.2 g, 90%). Step 4: Preparation of ethyl 5-chloro-3-methoxy-1H-indazole-1-carboxylic acid ester Ethyl 5-chloro-3-hydroxy-1H-indazole-1-carboxylic acid ester (2.2 g, 9.17 mmol) and cesium carbonate (3.6 g, 11.0 mmol) were added to acetone (20 mL), followed by the addition of iodomethane (1.56 g, 11.0 mmol). The mixture was heated at 70 °C for 2 hours, and then separated by column chromatography to obtain ethyl 5-chloro-3-methoxy-1H-indazole-1-carboxylic acid ester (0.8 g, 30%). Step 5: Preparation of 5-chloro-3-methoxy-1H-indazole Ethyl 5-chloro-3-methoxy-1H-indazole-1-carboxylic acid ester (610 mg, 2.40 mmol), sodium hydroxide (3.6 mL, 1 N), and ethanol (20 mL) were stirred at room temperature for 2 hours. The pH was adjusted with concentrated hydrochloric acid, and column chromatography was used to obtain 5-chloro-3-methoxy-1H-indazole (360 mg, 60%). 1H NMR (400MHz, DMSO) δ12.14 (s, 1H), 7.62 (s, 1H), 7.37 (dd, J = 27.3, 8.9Hz, 2H), 3.99 (s, 3H); MS m / z(ESI): 183[M+H]+. Steps 6 to 10: Preparation of N-(5-((5-chloro-4-(5-chloro-3-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-chloro-3-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide in steps six to ten is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.41 (s, 1H), 8.13 (d, J=7.7Hz, 2H), 7.61 (d, J= 1.8Hz,1H),7.35(d,J=9.0Hz,1H),6.98(s,1H),6.57–6.37(m,2H),5.87(dd,J=8.2,3.5 Hz,1H),4.13(s,3H),3.99(s,3H),3.51(s,2H),3.30(s,2H),2.90(s,6H),2.73(s,3H); MS m / z(ESI): 585[M+H]+. Example 109: Preparation of N-(5-((4-(5-chloro-3-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-chloro-3-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 108. 1H NMR(400MHz,CD3OD)δ8.62(s,1H),8.38–8.16(m,1H),8.09(s,1H),7.50(s,1H),7.30(s,1H),6.99(s,1H),6.4 8(t,J=15.4Hz,2H),5.85(d,J=11.5Hz,1H),4.05(s,3H),3.96(s,3H),3.52(s,2H),2.91(s,6H),2.75(s,3H); MS m / z(ESI): 619[M+H]+. Example 110: Preparation of N-(5-((4-(5-chloro-3-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-chloro-3-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 108. 1H NMR (400MHz, CD3OD) δ8.20(s,2H),7.88(s,1H),7.58(s,1H),7.41(d,J=8.8Hz,1H),7.30(d,J=6.9Hz,1H),7.10(s,1H),6.66(dd,J=16.9,10.1Hz,1H ),6.49(d,J=16.9Hz,1H),5.87(d,J=11.7Hz,1H),4.15(s,3H),3.96(s,3H ),3.56(d,J=5.7Hz,2H),3.40(d,J=5.6Hz,2H),2.95(s,6H),2.81(s,3H); MS m / z(ESI): 551[M+H]+. Example 111: Preparation of N-(5-((4-(3-cyclopropyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of cyclopropyl(2-fluorophenyl)methanol 2-Fluorobenzaldehyde (1.0 g, 8 mmol) was dissolved in THF (20 mL), cooled to an ice bath, and purged with nitrogen three times. Cyclopropylmagnesium bromide (32 mL, 16 mmol) was added dropwise. After the addition was complete, the mixture was gradually brought to room temperature and reacted for 16 h. The reaction was quenched with 20 mL of saturated ammonium chloride aqueous solution and extracted with ethyl acetate (50 mL × 3). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain cyclopropyl(2-fluorophenyl)methanol (800 mg, 62%). Step 2: Preparation of cyclopropyl (2-fluorophenyl) methyl ketone Cyclopropyl(2-fluorophenyl)methanol (800 mg, 4.8 mmol) was dissolved in dichloromethane (20 mL), Dess-Martin oxidant was added, and the reaction was carried out at room temperature for 5.5 h. The reaction was quenched by adding 20 mL of saturated sodium bicarbonate aqueous solution and 20 mL of 10% sodium sulfite aqueous solution. After stirring for 15 min, the mixture was extracted with dichloromethane (30 mL × 4). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain cyclopropyl(2-fluorophenyl) methyl ketone (430 mg, 54%). Step 3: Preparation of 3-cyclopropyl-1H-indazole Cyclopropyl (2-fluorophenyl) methyl ketone (430 mg, 2.6 mmol) was dissolved in 10 mL of hydrazine hydrate and reacted with microwave at 120 °C for 1 h. The reaction solution was concentrated and the crude product was purified by column chromatography to obtain 3-cyclopropyl-1H-indazole (250 mg, 61%). Steps 4 to 9: Preparation of N-(5-((4-(3-cyclopropyl-2H-indazol-2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(3-cyclopropyl-2H-indazole-2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 43. 1H NMR (400MHz, CD3OD) δ8.43(s,1H),8.19(d,J=6.3Hz,1H),7.91(d,J=7.9Hz,1H),7.83(s,1H ),7.52(d,J=7.0Hz,2H),7.43(t,J=7.4Hz,1H),7.10(s,1H),6.63(dd,J=16.9,10.2Hz,1H), 6.46(dd,J=16.9,1.5Hz,1H),5.85(dd,J=10.2,1.4Hz,1H),3.94(s,3H),3.57(t,J=5.5Hz, 2H),3.39(t,J=5.5Hz,2H),2.93(s,6H),2.82(s,3H),2.42–2.33(m,1H),1.24–1.18(m,4H); MS m / z(ESI): 527.2[M+H]+. Example 112: Preparation of N-(5-((4-(6-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(6-cyano-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 43. 1H NMR(400MHz,CD3OD)δ9.01(s,1H),8.59(d,J=0.7Hz,1H),8.40(d,J=6.5Hz,1H),8.10– 8.02(m,2H),7.67(dd,J=8.2,1.2Hz,1H),7.62(d,J=6.5Hz,1H),7.14(s,1H),6.60(dd, J=16.9,10.2Hz,1H),6.36(dd,J=16.9,1.3Hz,1H),5.82(dd,J=10.3,1.5Hz,1H),3.98 (s,3H),3.57(t,J=6.0Hz,2H),3.39(dd,J=11.1,5.2Hz,2H),2.94(s,6H),2.81(s,3H); MS m / z(ESI): 512.2[M+H]+. Example 113: Preparation of N-(5-((4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 111. 1H NMR (400MHz, CD3OD) δ8.18(dd,J=40.0,6.7Hz,2H),7.85(s,1H),7.40(d,J=7.1Hz,1H),7. 29(d,J=2.3Hz,1H),7.08(d,J=10.5Hz,2H),6.64(dd,J=16.9,10.1Hz,1H),6.47(dd,J=16. 9,1.6Hz,1H),5.86(dd,J=10.2,1.6Hz,1H),3.95(s,3H),3.89(s,3H),3.57(t,J=5.7Hz,2 H),3.39(t,J=5.6Hz,2H),2.94(s,6H),2.81(s,3H),2.35–2.26(m,1H),1.21–1.15(m,4H); MS m / z(ESI): 557.3[M+H]+. Example 114: Preparation of N-(5-((4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Steps 1 to 3: Preparation of 3-cyclopropyl-5-methoxy-1H-indazole The preparation method of 3-cyclopropyl-5-methoxy-1H-indazole is similar to that in Example 111. Steps 4 to 8: Preparation of N-(5-((4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR(400MHz,CD3OD)δ8.70(s,1H),8.19(s,1H),8.03(s,1H),7.30(d,J=2.3H z,1H),7.09–6.97(m,2H),6.47(d,J=5.6Hz,2H),5.91–5.81(m,1H),3.97(s, 3H),3.90(s,3H),3.54(t,J=5.6Hz,2H),3.31(d,J=6.0Hz,2H),2.90(s,6H), 2.76(s,3H),2.28(ddd,J=13.2,6.2,3.8Hz,1H),1.11(dt,J=4.0,2.8Hz,4H); MS m / z(ESI): 625.3[M+H]+. Example 115: Preparation of N-(5-((5-chloro-4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Steps 1 to 3: Preparation of 3-cyclopropyl-5-methoxy-1H-indazole The preparation method of 3-cyclopropyl-5-methoxy-1H-indazole is similar to that in Example 111. Steps 4 to 8: Preparation of N-(5-((5-chloro-4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(3-cyclopropyl-5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.47(s,1H),8.18(s,1H),8.05(d,J=9.1Hz,1H),7.28(d,J=2. 3Hz,1H),7.05(dd,J=9.1,2.4Hz,1H),6.97(s,1H),6.44(dd,J=5.8,4.1Hz,2H),5.8 5(dd,J=8.4,3.4Hz,1H),3.99(s,3H),3.90(s,3H),3.51(t,J=5.6Hz,2H),3.32–3.2 6(m,2H),2.88(s,6H),2.72(s,3H),2.35–2.26(m,1H),1.13(dq,J=4.4,2.4Hz,4H); MS m / z(ESI): 591.3[M+H]+. Example 116: Preparation of N-(5-((5-chloro-4-(5-cyano-3-propyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 1-(5-bromo-2-fluorophenyl)butane-1-ol 5-Bromo-2-fluorobenzaldehyde (5.0 g, 24.6 mmol) was dissolved in THF (30 mL), cooled to an ice bath, and purged three times with nitrogen. Propyl magnesium bromide (25 mL, 49.3 mmol) was added dropwise. After the addition was complete, the mixture was gradually brought to room temperature and reacted for 16 h. The reaction was quenched with 30 mL of saturated ammonium chloride aqueous solution and extracted with ethyl acetate (50 mL × 4). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 1-(5-bromo-2-fluorophenyl)butane-1-ol (2.2 g, 36%). Step 2: Preparation of 1-(5-bromo-2-fluorophenyl)butane-1-one 1-(5-bromo-2-fluorophenyl)butan-1-ol (2.2 g, 8.9 mmol) was dissolved in 50 mL of dichloromethane, and PCC oxidant (3.8 g, 17.8 mmol) was added. The mixture was reacted at room temperature for 16 h, filtered through diatomaceous earth, dried over anhydrous sodium sulfate on the organic phase, and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 1-(5-bromo-2-fluorophenyl)butan-1-one (1.5 g, 71%). Step 3: Preparation of (1-(5-bromo-2-fluorophenyl)butylene)hydrazine 1-(5-bromo-2-fluorophenyl)butane-1-one (1.0 g, 4.1 mmol) was dissolved in 20 mL of hydrazine hydrate and reacted with microwave at 130 °C for 5 h. The reaction solution was concentrated and purified by column chromatography to obtain (1-(5-bromo-2-fluorophenyl)butylene)hydrazine (800 mg, 80%). Step 4: Preparation of 5-bromo-3-propyl-1H-indazole (1-(5-bromo-2-fluorophenyl)butylene)hydrazine (600 mg, 2.3 mmol) was dissolved in 10 mL of N-methylpyrrolidone and reacted by microwave at 150 °C for 1 h. 20 mL of water was added, and the mixture was extracted with ethyl acetate (30 mL × 3). The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 5-bromo-3-propyl-1H-indazole (380 mg, 69%). Step 5: Preparation of 3-propyl-1H-indazole-5-carboxynitrile 5-Bromo-3-propyl-1H-indazole (380 mg, 1.6 mmol), zinc cyanide (223 mg, 1.9 mmol), tris(dibenzylacetone)palladium (140 mg, 0.16 mmol), and 2-bicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (150 mg, 0.32 mmol) were dissolved in N,N-dimethylformamide (10 mL) and reacted with microwave at 150 °C for 1 h. 20 mL of saturated sodium chloride aqueous solution was added, and the mixture was extracted with ethyl acetate (30 mL × 3). After drying the organic phase with anhydrous sodium sulfate, the mixture was concentrated to obtain the crude product. The crude product was purified by column chromatography to obtain 3-propyl-1H-indazole-5-carboxynitrile (110 mg, 38%). Steps 6 to 10: Preparation of N-(5-((5-chloro-4-(5-cyano-3-propyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-cyano-3-propyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide in steps six to ten is similar to that in Example 40. 1H NMR (400MHz, CD3OD) δ8.60(s,1H),8.33(s,1H),8.23(d,J=8.8Hz,1H),8.19(s,1H),7.62(d ,J=8.7Hz,1H),6.98(s,1H),6.51(dd,J=16.9,1.5Hz,1H),6.40(dd,J=17.0,9.9Hz,1H),5.9 1(dd,J=10.0,1.5Hz,1H),4.01(s,3H),3.50(t,J=5.5Hz,2H),3.31–3.24(m,2H),3.04(t,J =7.4Hz,2H),2.89(s,6H),2.71(s,3H),1.91(dd,J=14.8,7.4Hz,2H),1.07(t,J=7.4Hz,3H); MS m / z(ESI): 588.3[M+H]+. Example 117: Preparation of N-(5-((4-(5-cyano-3-ethyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 3-bromo-1H-indazole-5-carboxynitrile In a 100 mL round-bottom flask, 1H-indazole-5-carboxynitrile (544 mg, 3.8 mmol), NBS (812 mg, 4.6 mmol), and DMF (10 mL) were added. The mixture was stirred at room temperature for 2 h under N2 protection. The reaction solution was concentrated to obtain the crude product. It was dissolved in 100 mL of DCM and washed with 50 mL of saturated sodium bicarbonate aqueous solution, water, and saturated brine, respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to give 3-bromo-1H-indazole-5-carboxynitrile (750 mg, 89%). Step 2: Preparation of 3-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxynitrile In a 100 mL round-bottom flask, 3-bromo-1H-indazole-5-carboxynitrile (710 mg, 3.2 mmol) and THF (15 mL) were added. SEM-Cl (640 mg, 3.8 mmol) was added dropwise under an ice-water bath, and the reaction was carried out at 0 °C for 2 h. The reaction was quenched by adding saturated aqueous solution of ammonium chloride (1 mL). The reaction solution was concentrated, and the crude product was separated by column chromatography (60% DCM / PE) to obtain 3-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxynitrile (680 mg, 61%). Step 3: Preparation of 3-ethyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxynitrile In a 100 mL round-bottom flask, 3-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylonitrile (669 mg, 1.9 mmol), ethylboric acid (281 mg, 3.8 mmol), K3PO4 (1.2 g, 5.7 mmol), and PCy3 (213 mg, 0.4 mmol) were added. After three N2 replacements, Pd(OAc)2 (85 mg, 0.2 mmol) was added, and the mixture was reacted at 100 °C for 2 h. After cooling to room temperature, the reaction solution was diluted with 100 mL of ethyl acetate, washed with water (50 mL × 2), and the organic phase was concentrated under reduced pressure. The residue was subjected to column chromatography to obtain 3-ethyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylonitrile (605 mg, 100%). MS m / z(ESI): 302.2[M+H]+. Step 4: Preparation of 3-ethyl-1H-indazole-5-carboxynitrile In a 100 mL round-bottom flask, 3-ethyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxynitrile (603 mg, 1.9 mmol), 1 M TBAF / THF (30 mL), and ethylenediamine (240 mg) were added, and the mixture was reacted at 70 °C for 2 h. The reaction solution was concentrated to obtain the crude product. 100 mL of ethyl acetate was added, and the mixture was washed with water (50 mL × 2). The organic phase was concentrated, and the residue was subjected to reverse-phase column chromatography (25% acetonitrile / water) to give 3-ethyl-1H-indazole-5-carboxynitrile (170 mg, 50%). Steps 5 to 8: Preparation of N-(5-((4-(5-cyano-3-ethyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5-cyano-3-ethyl-1H-indazol-1-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide in steps five to eight is similar to that in Example 106. 1H NMR (400MHz, CD3OD) δ8.80(s,1H),8.39(s,1H),8.27(d,J=0.7Hz,1H),8.12(s,1H),7.63(s,1H),7.02(s,1H),6.56–6.44(m,2H),5.93–5. 87(m,1H),4.00(s,3H),3.53(t,J=5.7Hz,2H),3.36–3.33(m,2H),3.03(q,J=7.5Hz,2H),2.92(s,6H),2.75(s,3H),1.44(t,J=7.5Hz,3H); MS m / z(ESI): 608.3[M+H]+. Example 118: Preparation of N-(5-((5-chloro-4-(5-cyano-3-ethyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((5-chloro-4-(5-cyano-3-ethyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 117. 1H NMR (400MHz, CD3OD) δ8.44(s,1H),8.18(s,1H),8.09(d,J=11.2Hz,2H),7.49(d,J=8.7Hz,1H),6.86(s,1H),6.34(qd,J=16.9,5.7Hz,2H),5.79(dd,J =9.9,1.6Hz,1H),3.89(s,3H),3.39(t,J=5.4Hz,2H),3.18(d,J=5.3Hz,2H ),2.95(q,J=7.5Hz,2H),2.78(s,6H),2.60(s,3H),1.33(t,J=7.5Hz,3H); MS m / z(ESI): 574.3[M+H]+. Example 119: Preparation of N-(5-((4-(1-cyclopropyl-1H-indazol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of (2-fluorophenyl)(2-(methylthio)pyrimidin-4-yl)methyl ketone 4-Chloro-2-(methylthio)pyrimidine (5.00 g, 31.1 mmol), 2-fluorobenzaldehyde (4.64 g, 37.4 mmol), and [mmim][I] (2.09 g, 9.33 mmol) were dissolved in 1,4-dioxane (70 mL), and NaH (1.74 g, 60%, 43.6 mmol) was added in portions. The mixture was then stirred at 100 °C for 1 hour. After cooling, the solution was diluted with EtOAc. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to give the title compound (2-fluorophenyl)(2-(methylthio)pyrimidin-4-yl)methyl ketone (4.3 g, 56%). 1H NMR (400MHz, CDCl3): δ8.71(d,J=5.2Hz,1H),7.68(m,1H),7.51(m,1H),7.44(d,J=5.2Hz,1H),7.20(m,1H),7.07(m,1H),2.38(s,3H); MS m / z(ESI): 249.1 [M+H]+. Step 2: Preparation of 1-cyclopropyl-3-(2-(methylthio)pyrimidin-4-yl)-1H-indazole (2-Fluorophenyl)(2-(methylthio)pyrimidin-4-yl)methyl ketone (1.3 g, 5.24 mmol) and cyclopropylhydrazine hydrochloride (800 mg, 7.33 mmol) were mixed in ethanol, heated under reflux for 2 hours, cooled, and concentrated. The crude product was dissolved in 50 mL of DMF, and sodium hydrogen hydrate (500 mg, 12.5 mmol) was added in portions, followed by stirring at 80 °C for 2 hours. After cooling, water was added to precipitate the solid, which was purified by column chromatography to give the title compound 1-cyclopropyl-3-(2-(methylthio)pyrimidin-4-yl)-1H-indazole (140 mg, two-step yield: 10%). MS m / z(ESI): 283.1[M+H]+. Step 3: Preparation of 1-cyclopropyl-3-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole Under ice-water bath conditions, mCPBA (231 mg, 70%, 1.00 mmol) was added in a single batch to a 3 mL solution of 1-cyclopropyl-3-(2-(methylthio)pyrimidin-4-yl)-1H-indazole (135 mg, 0.478 mmol) in dichloromethane. The solution was slowly heated to room temperature and stirred for 2 hours. The reaction mixture was washed twice with saturated sodium bicarbonate solution, once with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound 1-cyclopropyl-3-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole (185 mg, 100%). MS m / z(ESI): 315.1[M+H]+. Step 4: Preparation of 4-(1-cyclopropyl-1H-indazol-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidine-2-amine Add 0.5 mL of formic acid aqueous solution (85%) to a toluene solution (1.0 g, 5.4 mmol) of 4-fluoro-2-methoxy-5-nitroaniline and heat under reflux overnight. Concentrate the reaction solution by rotary evaporation and use it directly in the next reaction step. The crude product (180 mg, 0.840 mmol) was dissolved in 2 mL of DMF. NaH (41 mg, 1.68 mmol) was added under ice-water bath conditions, and the mixture was stirred for 30 minutes at this temperature. Then, a DMF solution (2 mL) of 1-cyclopropyl-3-(2-(methanesulfonyl)pyrimidin-4-yl)-1H-indazole (184 mg, 0.588 mmol) was added. The mixture was stirred overnight at room temperature. 0.5 mL of water was added, and the mixture was stirred for another 30 minutes. 10 mL of water was added, the mixture was filtered, and column chromatography was performed to give the title compound 4-(1-cyclopropyl-1H-indazole-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidin-2-amine (200 mg, 81%). MS m / z(ESI): 421.1[M+H]+. Step 5: Preparation of N1-(4-(1-cyclopropyl-1H-indazol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine 4-(1-Cyclopropyl-1H-indazol-3-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrimidin-2-amine (200 mg, 0.48 mmol), trimethylethylenediamine (58.0 mg, 0.57 mmol), and DIPEA (0.24 mL, 1.43 mmol) were dissolved in 2 mL of DMA and stirred at 90 °C for 2 hours. After cooling, the solution was diluted with EtOAc, washed several times with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by thin-layer chromatography to give the title compound N1-(4-(1-Cyclopropyl-1H-indazol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (40 mg, 17%). MS m / z(ESI): 503.2[M+H]+. Step 6: Preparation of N4-(4-(1-cyclopropyl-1H-indazol-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine N1-(4-(1-cyclopropyl-1H-indazole-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (40 mg, 0.080 mmol), reduced iron powder (44 mg, 0.80 mmol), and ammonium chloride (3.4 mg, 0.064 mmol) were mixed in 6 mL of ethanol and 2 mL of water and stirred overnight at 70 °C. After cooling, the mixture was filtered through diatomaceous earth, concentrated, and purified by thin-layer chromatography to give the title compound N4-(4-(1-cyclopropyl-1H-indazole-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (19 mg, 50%). MS m / z(ESI): 473.3[M+H]+. Step 7: Preparation of N-(5-((4-(1-cyclopropyl-1H-indazol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide In a dry ice-acetone bath, a THF solution (19 mg, 0.040 mmol) of N4-(4-(1-cyclopropyl-1H-indazole-3-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (0.040 mmol)) in THF was added dropwise to a solution (0.15 mL, 1.1 mmol) of acryloyl chloride (0.045 mL, 0.56 mmol) in THF. The mixture was stirred at this temperature for 5 minutes, and the reaction was quenched by adding 1 mL of methanol. After solvent concentration, the solution was purified by thin-layer chromatography to obtain the title compound N-(5-((4-(1-cyclopropyl-1H-indazole-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide (10 mg, 47%). 1H NMR (400MHz, CDCl3): δ10.1 (br s, 1H), 9.51 (s, 1H), 8.61 (d, J = 8.0Hz, 1H),8.54(d,J=5.2Hz,1H),7.60(m,3H),7.41(m,1H),7.22(m,1H),6.79(s,1H),6.38(m,2H) ,5.66(m,1H),3.89(s,3H),3.68(m,1H),2.95(m,2H),2.72(s,3H),2.40(m,8H),0.88(m,4H); MS m / z(ESI): 527.3[M+H]+. Example 120: Preparation of N-(5-((4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation of N-(5-((4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide was similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.32 (s, 1H), 8.47 (d, J = 5.8Hz, 1H), 8.25 (s, 2H), 7.71 (dd, J = 6 .2,2.8Hz,1H),7.39(dd,J=6.1,3.2Hz,2H),7.27(d,J=5.8Hz,1H),6.93(s,1H),6.5 2(dd,J=16.9,10.0Hz,1H),6.40(dd,J=16.9,1.7Hz,1H),5.78(dd,J=10.0,1.7Hz,1 H),3.89(s,3H),3.42(t,J=5.5Hz,2H),3.28–3.25(m,2H),2.83(s,6H),2.67(s,3H); MS m / z(ESI): 487.3[M+H]+. Example 121: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-(2-methoxyethoxy)-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-(2-methoxyethoxy)-1H-indazol-1-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 105. 1H NMR(400MHz,CD3OD)δ8.37(s,1H),8.27(s,1H),7.84(s,1H),7.59(s,1H),7.32(s,1H),7.15(s,1H),7.09(s,1H),6.70–6.53(m,1H) ,6.50(s,1H),5.88(s,1H),4.18(s,2H),3.96(s,3H),3.80(s,2H),3.57(s,2H),3.46(s,3H),3.38(s,2H),2.94(s,6H),2.81(s,3H); MS m / z(ESI): 561[M+H]+. Example 122: Preparation of (E)-N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)-4-(dimethylamino)but-2-enamide The preparation method of (E)-N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)-4-(dimethylamino)but-2-enamide is similar to that in Example 22. 1H NMR(400MHz, CDCl3) δ9.70(d,J=17.4Hz,2H),8.49(d,J=19.3Hz,1H),8.32(d,J=5.3H z,1H),8.05(m,1H),7.59(m,2H),7.09(d,J=5.3Hz,1H),6.90(m,1H),6.68(s,1H),6.4 6(s,1H),3.81(s,3H),3.39(ddd,J=10.8,7.1,3.8Hz,1H),3.16(d,J=6.0Hz,2H),2.89 (m,2H),2.63(s,3H),2.46(s,2H),2.31(d,J=23.0Hz,12H),1.16(m,2H),1.01(m,2H); MS m / z(ESI): 583.7[M+H]+. Example 123: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3) δ9.66 (s, 1H), 9.49 (s, 1H), 8.42 (s, 1H), 8.32 (d, J = 5.3Hz, 1H), 8.04 (d ,J=6.9Hz,1H),7.28(m,1H),7.68–7.45(m,2H),7.10(d,J=5.3Hz,1H),6.63(s,1H),6.37(d d,J=16.8,1.8Hz,1H),5.63(dd,J=10.2,1.8Hz,1H),3.80(s,3H),3.47–3.16(m,1H),3.07( s,2H),2.82(s,3H),2.62(s,4H),1.92(s,4H),1.30(m,2H),1.18(m,2H),1.06–0.96(m,2H); MS m / z(ESI): 552.7[M+H]+. Example 124: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-morpholinoethyl)amino)phenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-morpholinoethyl)amino)phenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CDCl3) δ9.72 (s, 1H), 9.21 (s, 1H), 8.49 (s, 1H), 8.33 (d, J = 5.3Hz, 1H), 8.0 4(d,J=7.1Hz,1H),7.65–7.42(m,2H),7.34–7.13(m,2H),7.11(d,J=5.3Hz,1H),6.70(s, 1H),6.40(s,2H),5.77–5.51(m,1H),3.80(s,3H),3.65(s,4H),3.50–3.20(m,1H),3.02– 2.79(m,2H),2.59(s,3H),2.32(d,J=37.1Hz,6H),1.20–1.08(m,2H),1.08–0.95(m,2H); MS m / z(ESI): 568.6[M+H]+. Example 125: Preparation of N-(5-((4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 22. 1H NMR (400MHz, CD3OD): δ8.47(s,1H),7.99(m,3H),7.36(d,J=6.8Hz,1H),7.12( t,J=6.8Hz,1H),7.07(s,1H),7.00(d,J=7.2Hz,1H), 6.58(m,1H),6.45(m,1H), 5.85(m,1H),4.30(t,J=6.0Hz,2H),3.95(s,3H),3.54(t,J=6.0Hz,2H),3.36( t,J=5.6Hz,2H),3.00(t,J=5.6Hz,2H),2.90(s,6H),2.80(s,3H),2.25(m,2H); MS m / z(ESI): 526.2[M+H]+. Example 126: Preparation of N-(5-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide Step 1: Preparation of tert-butyl{2-[(4-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-5-methoxy-2-nitrophenyl)(methyl)amino]ethyl}methylcarbamate N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (1.3 g, 3.43 mmol), DIPEA (2.2 g, 7.14 mmol), and tert-butylmethyl (2-(methylamino)ethyl)carbamate (0.77 g, 4.12 mmol) were dissolved in DMA (15 mL), heated overnight at 100 °C, concentrated, and purified by column chromatography to obtain tert-butyl{2-[(4-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-5-methoxy-2-nitrophenyl)(methyl)amino]ethyl}methylcarbamate (1.9 g, 80%). Step 2: Preparation of tert-butyl 3-(2-((tert-butoxycarbonyl)(4-((2-((tert-butoxycarbonyl)(methyl)amino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indole-1-carboxylic acid ester 1.9 g (3.34 mol) of tert-butyl{2-[(4-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-5-methoxy-2-nitrophenyl)(methyl)amino]ethyl}methylcarbamate, 1.87 g (8.58 mmol) of Boc2O, and 84 mg (0.69 mmol) of DMAP were added to tetrahydrofuran (30 mL), stirred overnight at 50 °C, and concentrated to obtain 2.0 g of yellow solid, which was directly used in the next reaction. Step 3: Preparation of tert-butyl(2-((4-((4-(1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxy-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate 2.0 g (2.678 mmol) of tert-butyl 3-(2-((tert-butoxycarbonyl)(4-((2-((tert-butoxycarbonyl)(methyl)amino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indole-1-carboxylic acid ester was dissolved in methanol (20 mL), and then sodium methoxide (29 mg, 0.535 mmol) was added. The mixture was heated to 50 °C, and after 2 hours, the solution was quenched with water, concentrated, extracted with dichloromethane, concentrated, and dried to obtain tert-butyl (2-((4-((4-(1H-indole-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxy-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate (2.3 g, 90%). Step 4: Preparation of tert-butyl 2-((4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxy-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate 200 mg (0.309 mmol) of tert-butyl(2-((4-((4-(1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxy-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate and 11 mg (0.46 mmol) of NaH were added to 10 mL of THF. Vinyl bromide (55 mg, 0.46 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The mixture was then quenched with water, extracted with dichloromethane, concentrated, and dried to obtain 200 mg of tert-butyl2-((4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxy-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate as a yellow solid, which was used directly in the next step. Step 5: Preparation of tert-butyl(2-((4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-2-amino-5-methoxyphenyl)(methyl)amino)ethyl)(methyl)carbamate The raw materials from the previous step (2.4 g, 3.45 mmol), iron powder (2 g, 34.5 mmol), and ammonium chloride (3.7 g, 70 mmol) were added to ethanol (60 mL) and water (20 mL), heated at 60 °C overnight, filtered, concentrated, extracted with dichloromethane, and subjected to column chromatography to obtain tert-butyl(2-((4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-2-amino-5-methoxyphenyl)(methyl)amino)ethyl)(methyl)carbamate (1 g, 50%). 1H NMR (400MHz, DMSO) δ8.45(d,J=5.4Hz,1H),8.36(s,1H),8.08(d,J=8.0Hz,1H),7.48(dd,J=9.3,6.9Hz,2H),7.17(t,J=7.1Hz,1H),7.00(t,J=7.4Hz,1H ),6.79(s,1H),6.47(s,1H),6.09–5.97(m,1H),5.19(dd,J=10.3,1.4Hz,1H ),5.06(dd,J=17.1,1.5Hz,1H),4.90(d,J=5.3Hz,2H),4.37(s,2H),3.65(s, 3H), 3.36 (d, J = 6.6Hz, 2H), 2.96 (t, J = 6.7Hz, 2H), 2.75 (d, J = 12.4Hz, 3H), 2.66 (d, J = 11.3Hz, 3H), 1.41 (s, 18H); MS m / z(ESI): 658[M+H]+. Step 6: Preparation of tert-butyl(2-((2-acryloylamido-4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxyphenyl)(methyl)amino)ethyl)(methyl)carbamate The starting material (1 g, 1.52 mmol) and DIPEA (0.56 g, 4.56 mmol) from the previous step were dissolved in tetrahydrofuran (100 mL). The reaction system was cooled to -10 °C, and 2.3 mL of acryloyl chloride tetrahydrofuran solution (1 M) was slowly added dropwise to the reaction flask. The mixture was stirred for 30 minutes, and the reaction was quenched with 1 mL of methanol. The reaction solution was concentrated, extracted with dichloromethane, and subjected to column chromatography to obtain tert-butyl(2-((2-acryloylamide-4-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)(tert-butoxycarbonyl)amino)-5-methoxyphenyl)(methyl)amino)ethyl)(methyl)carbamate (0.9 g, 90%). 1H NMR (400MHz, CDCl3) δ8.73–8.39(m,3H),7.91(s,2H),7.29(d,J=8.3Hz,2H),7.19(t,J= 7.6Hz,1H),7.01(t,J=7.5Hz,1H),6.87(s,1H),6.36(s,2H),6.00(m,1H),5.69(s,1H), 5.26(dd,J=10.3,1.0Hz,1H),5.19–5.10(m,1H),4.77(d,J=5.4Hz,2H),3.80(s,3H),3. 44(s,2H),3.00(d,J=25.1Hz,2H),2.84(s,3H),2.78(s,3H),1.48(s,9H),1.47(s,9H); MS m / z(ESI): 712[M+H]+. Step 7: Preparation of N-(5-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide The raw material (0.9 g) from the previous step was dissolved in a dichloromethane solution (50 mL) containing 20% ​​trifluoroacetic acid by volume. The mixture was stirred at room temperature for 6 hours. The reaction was complete according to TLC. The pH was adjusted to alkaline with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with dichloromethane and concentrated to obtain N-(5-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide (535 mg, 83%). 1H NMR (400MHz, CDCl3) δ9.74 (s, 2H), 8.99–8.92 (m, 1H), 8.38 (d, J = 5.3Hz, 1H), 8.11 (s, 1H) ,7.68(s,1H),7.38(s,1H),7.26–7.23(m,1H),7.19(d,J=5.3Hz,1H),6.71(s,1H),6.67– 6.57(m,1H),6.40(d,J=16.9Hz,1H),6.12–5.98(m,1H),5.69(d,J=11.9Hz,1H),5.23–5. 13(m,2H),4.97(s,2H),3.87(s,3H),2.96(s,2H),2.70(s,2H),2.66(s,3H),2.45(s,3H); MS m / z(ESI): 512[M+H]+. Example 127: Preparation of N-(4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(6-methoxy-1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide is similar to that in Example 126. 1H NMR (400MHz, CD3OD) δ8.32 (s, 1H), 8.07 (s, 1H), 7.87 (d, J = 6.9Hz, 2H), 7.25 (d ,J=7.0Hz,1H),7.01–6.90(m,2H),6.77(dd,J=8.8,2.0Hz,1H),6.48(dd,J=16 .9,10.1Hz,1H),6.34(dd,J=17.0,1.8Hz,1H),5.75(dd,J=10.1,1.8Hz,1H),3 .92–3.70(m,9H),3.43–3.30(m,2H),3.17–3.05(m,2H),2.67(d,J=9.0Hz,6H); MS m / z(ESI): 516.2[M+H]+. Example 128: Preparation of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide The preparation method of N-(5-((4-(1-cyclopropyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)acryloylamide is similar to that in Example 126. 1H NMR (400MHz, CDCl3) δ9.37(s,1H),9.29(s,1H),8.29(d,J=5.3Hz,1H),8.18(s,1H),8.07(d,J=7.2Hz,1H),7.61–7.40(m,2H),7.24–7.15(m,2H),7.06 (d,J=5.3Hz,1H),6.94(dd,J=15.9,9.9Hz,1H),6.45(s,1H),6.17(d,J=16.9Hz,1H),5.58(d,J=10.2Hz,1H) ,3.79(s,3H),3.39–3.15(m,1H),2.93(s,2H),2.65(s,2H),2.44(s,3H),2.26(s,3H),1.01(d,J=5.2Hz,4H); MS m / z(ESI): 512.6[M+H]+. Example 129: Preparation of N-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 126. 1H NMR (400MHz, CDCl3) δ9.90–9.83(m,1H),9.81–9.73(m,1H),9.25–9.12(m,1H),8.39(d,J =5.3Hz,1H),8.12–8.05(m,1H),7.70(s,1H),7.61–7.53(m,1H),7.30(s,2H),7.20(d,J=5 .3Hz,1H),6.75(s,1H),6.62–6.44(m,2H),5.81–5.63(m,1H),5.30(s,1H),5.18(s,2H),3 .88(s,3H),2.97–2.87(m,2H),2.69(s,3H),2.68–2.63(m,2H),2.47(s,3H),2.38(s,1H); MS m / z(ESI): 510[M+H]+. Example 130: Preparation of N-(5-((5-chloro-4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide) The preparation method of N-(5-((5-chloro-4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 126. 1H NMR(400MHz,CD3OD)δ8.74(s,1H),8.53(s,1H),8.30–8.23(m,2H),7.50(d,J=8.3 Hz,1H),7.17–7.10(m,1H),7.03(t,J=7.2Hz,1H),6.86(s,1H),6.38(dd,J=17.0, 10.2Hz,1H),6.17(d,J=17.0Hz,1H),5.69–5.59(m,2H),5.10(t,J=7.4Hz,2H),4. 99–4.93(m,2H),3.81(s,3H),3.02(s,2H),2.59(s,3H),2.47(s,2H),2.27(s,6H); MS m / z(ESI): 576.3 [M+H]+. Example 131: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(oxobutylcyclo-3-yl)-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide The preparation method of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(oxobutane-3-yl)-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)acryloylamide is similar to that in Example 130. 1H NMR(400MHz,CD3OD)δ8.61(s,1H),8.33(s,1H),8.09(d,J=8.0Hz,1H),7.98(s,1H) ,7.55(d,J=8.3Hz,1H),7.15(t,J=7.4Hz,1H),7.05(t,J=7.5Hz,1H),6.87(s,1H), 6.37–6.27(m,2H),5.76–5.64(m,2H),5.13(t,J=7.4Hz,2H),4.95–4.86(m,2H),3. 90(s,3H),3.39(t,J=5.5Hz,2H),3.17(t,J=5.5Hz,2H),2.75(s,6H),2.59(s,3H); MS m / z(ESI): 610.3[M+H]+. Example 132: Preparation of N-(4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide Step 1: Preparation of N-methyl-2-(pyrrolidone-1-yl)ethane-1-amine. An aqueous solution (50 mL) of 1-(2-chloroethyl)pyrrolidine hydrochloride (25 g, 0.147 mmol) was slowly added dropwise to an aqueous solution of methylamine (114 mL). After the addition was complete, the mixture was stirred for 30 minutes. Then, sodium hydroxide (46.25 g, 1.15 mmol) was added, resulting in a yellow supernatant. The supernatant was extracted with methyl tert-butyl ether, concentrated at room temperature, and dried under vacuum to obtain N-methyl-2-(pyrrolidine-1-yl)ethane-1-amine (17 g, 90%). Steps 2 through 7: Preparation of N-(4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation methods for steps two through seven of N-(4-methoxy-5-((4-(6-methoxy-3-methyl-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide are similar to those in Example 54. 1H NMR (400MHz, CD3OD) δ8.19(d,J=7.0Hz,1H),8.05(s,1H),7.78–7.66(m,2H),7.58(d,J=7.0Hz,1H),7.09(dd, J=8.5,2.4Hz,2H),6.62(dd,J=16.9,10.2Hz,1H),6.39(dd,J=16.9,1.5Hz,1H),5.85(dd,J=10.2,1.5Hz,1H), 3.95(s,3H),3.87(s,3H),3.68–3.60(m,2H),3.56(t,J=5.7Hz,2H),3.43(t,J=5. 7Hz,2H),3.13(d,J=8.6Hz,2H),2.82(s,3H),2.58(s,3H),2.17(d,J=6.0Hz,4H); MS m / z(ESI): 557[M+H]+. Example 133: Preparation of N4-(4-(5-ethoxy-1H-indazol-1-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-N1-(2-(pyrrolidone-1-yl)ethyl)phenyl-1,2,4-triamine The preparation method of N4-(4-(5-ethoxy-1H-indazol-1-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-N1-(2-(pyrrolidine-1-yl)ethyl)phenyl-1,2,4-triamine is similar to that in Example 105. 1H NMR (400MHz, CD3OD) δ8.38(s,1H),8.27(d,J=6.6Hz,2H),7.76(s,1H),7.60(d,J=6.9Hz,1H),7.29(d,J= 2.2Hz,1H),7.12(d,J=8.9Hz,1H),7.08(s,1H),6.63–6.53(m,1H),6.43(dd,J=16.9,1.6Hz,1H),5.88(d d,J=10.1,1.5Hz,1H),4.11(q,J=6.9Hz,2H),3.96(s,3H),3.65(d,J=9.9Hz,2H),3.58(t,J=5.6Hz,2H), 3.43(t,J=5.4Hz,2H),3.14(d,J=9.9Hz,2H),2.83(s,3H),2.21(t,J=6.6Hz,4H),1.45(t,J=7.0Hz,3H); MS m / z(ESI): 557[M+H]+. Example 134: Preparation of N-(4-methoxy-5-((4-(5-(2-methoxyethoxy)-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(5-(2-methoxyethoxy)-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 105. 1H NMR(400MHz,CD3OD)δ8.35(s,1H),8.28(m,2H),7.79(s,1H),7.55(d, J=6.6Hz,1H),7.30(s,1H),7.13(d,J=8.7Hz,1H),7.06(s,1H),6.58(dd,J=16.8,10.1Hz,1H),6.42(d,J=16.8Hz,1H),5.86(d,J=10.1Hz ,1H),4.17(m,2H),3.95(s,3H),3.78(m,2H),3.62(m,2H),3.56(m,2H),3.45(s,3H),3.42(m,2H),3.13(m,2H),2.81(s,3H),2.19(m,4H); MS m / z(ESI): 587[M+H]+. Example 135: Preparation of N-(4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide Step 1: Preparation of N-methyl-2-(pyrrolidone-1-yl)ethane-1-amine The preparation method of N-methyl-2-(pyrrolidone-1-yl)ethane-1-amine is similar to that in Example 132. Steps 2 to 7: Preparation of N-(4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide. The preparation method of N-(4-methoxy-5-((4-(4-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 43. 1H NMR (400MHz, CD3OD) δ8.43(s,1H),8.27(d,J=6.9Hz,1H),7.99(s,1H),7.82(s,1H),7.59(d,J=6.9Hz, 1H),7.43(t,J=8.1Hz,1H),7.07(s,1H),6.85(d,J=8.0Hz,1H),6.61(dd,J=16.9,10.1Hz,1H),6.42(dd ,J=16.9,1.6Hz,1H),5.87(dd,J=10.2,1.6Hz,1H),3.99(s,3H),3.96(d,J=5.1Hz,3H),3.64(d,J=10.0 Hz,2H),3.56(t,J=5.6Hz,2H),3.43(t,J=5.6Hz,2H),3.13(d,J=8.9Hz,2H),2.82(s,3H),2.19(s,4H); MS m / z(ESI): 543.3[M+H]+. Example 136: Preparation of N-(4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(6-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 135. 1H NMR (400MHz, CD3OD) δ8.24 (s, 1H), 8.17 (d, J = 5.5Hz, 1H), 8.04 (s, 1H), 7.70 (s, 1H), 7. 65(d,J=8.7Hz,1H),7.50(d,J=6.5Hz,1H),7.02–6.92(m,2H),6.47(dd,J=16.9,10.2Hz ,1H),6.27(d,J=16.9Hz,1H),5.74(d,J=10.1Hz,1H),3.84(s,3H),3.76(s,3H),3.49(s ,2H),3.46–3.42(m,2H),3.31(d,J=5.2Hz,2H),3.01(s,2H),2.69(s,3H),2.06(s,4H); MS m / z(ESI): 543.3[M+H]+. Example 137: Preparation of N-(4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide N-(4-methoxy-5-((4-(5-methoxy-1H-indazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 135. 1H NMR (400MHz, CD3OD) δ8.27(s,1H),8.16(d,J=6.2Hz,2H),7.66(s,1H),7.48(d,J=6.9Hz,1H),7.1 9(d,J=2.3Hz,1H),7.01(d,J=9.1Hz,1H),6.96(s,1H),6.48(dd,J=16.9,10.1Hz,1H),6.31(dd,J =16.9,1.6Hz,1H),5.75(dd,J=10.1,1.6Hz,1H),3.84(s,3H),3.76(s,3H),3.56–3.49(m,2H),3. 49–3.43(m,2H),3.31(t,J=5.6Hz,2H),3.01(d,J=9.6Hz,2H),2.71(s,3H),2.09(d,J=6.8Hz,4H); MS m / z(ESI): 543.3[M+H]+. Example 138: Preparation of N-(4-methoxy-5-((4-(5-methoxy-1H-benzis[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(5-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.49(s,1H),8.56(d,J=5.8Hz,1H),8.22(d,J=10.4Hz,2H),7.34(d,J=5.8Hz ,1H),7.27(d,J=2.1Hz,1H),7.08(dd,J=9.2,1.9Hz,1H),7.01(s,1H),6.59(dd,J=16.9,10.1Hz,1 H),6.43(dd,J=16.9,1.6Hz,1H),5.86(dd,J=10.1,1.6Hz,1H),3.97(s,3H),3.89(s,3H),3.62(s, 2H),3.51(t,J=5.5Hz,2H),3.39(t,J=5.5Hz,2H),3.11(d,J=8.1Hz,2H),2.77(s,3H),2.18(s,4H); MS m / z(ESI): 543.3[M+H]+. Example 139: Preparation of N-(4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide The preparation method of N-(4-methoxy-5-((4-(6-methoxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide is similar to that in Example 59. 1H NMR (400MHz, CD3OD) δ9.44 (s, 1H), 8.58 (d, J = 5.2Hz, 1H), 8.29 (s, 1H),7.88(s,1H),7.72(s,1H),7.33(d,J=5.7Hz,1H),7.14(d,J=5.3Hz,1H),7.0 0(s,1H),6.60(dd,J=16.9,10.2Hz,1H),6.39(dd,J=16.9,1.4Hz,1H),5.84(dd, J=10.2,1.3Hz,1H),3.97(s,3H),3.85(s,3H),3.62(s,2H),3.49(t,J=5.5Hz,2H ),3.38(dd,J=9.6,4.1Hz,2H),3.10(s,2H),2.75(s,3H),2.16(d,J=2.9Hz,4H); MS m / z(ESI): 543.3[M+H]+. Example 140: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide Step 1: Preparation of N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine The preparation method of N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine is similar to that in Example 102. Step 2: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (0.51 g, 1.1 mmol) was dissolved in anhydrous DMF (20 mL), and NaH (47 mg, 1.16 mmol) was added to the solution with stirring at room temperature. After stirring for 30 minutes, the mixture was cooled to 0 °C, and propargyl bromide (137 mg, 1.16 mmol) was added at 0 °C. The reaction mixture was stirred for 20 minutes. LC-MS analysis showed the formation of a product, which was quenched by adding saturated ammonium chloride aqueous solution. The TFA salt of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine (0.25 g, 28%) was separated by reversed column chromatography (eluent: 0.1% TFA aqueous solution to acetonitrile). 1H NMR (400MHz, CD3OD): δ8.62(s,1H),8.57(s,1H),8.28(d,J=8.0Hz,1H),8.17(d ,J=6.8Hz,1H),7.64(d,J=8.0Hz,1H),7.48(d,J=6.4Hz,1H),7.37(t,J=7.6Hz,1 H),7.24(t,J=7.2Hz,1H),7.09(s,1H),5.19(d,J=2.4Hz,2H),4.06(s,3H),3.62 (t,J=6.0Hz,2H),3.52(t,J=6.0Hz,2H),3.36(s,1H),3.01(s,6H),2.98(s,3H); MS m / z(ESI): 500.2[M+H]+. Step 3: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine The TFA salt of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,4-diamine (0.25 g, 0.30 mmol), reduced iron powder (112 mg, 2.0 mmol), and ammonium chloride (0.015 g, 0.3 mmol) were added to a mixture of ethanol (8 mL) and water (2 mL). The reaction was stirred overnight at 75 °C under a nitrogen atmosphere. The next day, the mixture was cooled to room temperature and ethanol (60 mL) was added. The reaction solution was filtered through diatomaceous earth and washed with ethanol (10 mL). The filtrate was concentrated under reduced pressure and DCM (60 mL) was added. The DCM layer was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and concentrated to give N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (130 mg, 90%). The compound was directly introduced into the next step without further purification. MS m / z(ESI): 470.2[M+H]+. Step 4: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)phenyl-1,2,4-triamine (130 mg, 0.28 mmol) and triethylamine (170 mg, 1.7 mmol) were dissolved in THF (20 mL). The solution was cooled to -78 °C. Acryloyl chloride (75 mg, 0.84 mmol) in THF (4 mL) was added dropwise to the reaction solution. The reaction was carried out at this temperature for 5 minutes, quenched with methanol (1 mL), and TFA (200 mg) was added to the reaction solution before concentration under reduced pressure. The compound was separated by reversed-phase column chromatography (eluent: 0.1% TFA aqueous solution to acetonitrile) to give the TFA salt of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acryloylamide (105 mg, 45%). 1H NMR (400MHz, CD3OD): δ8.62 (s, 1H), 8.37 (br, 1H), 8.10 (d, J = 6.8Hz, 1H), 7.96 (s, 1H) ),7.64(d,J=8.0Hz,1H),7.46(d,J=7.2Hz,1H),7.36(m,1H),7.27(t,J=7.2Hz,1H),7 .10(s,1H),6.54(m,2H),5.90(m,1H),5.20(d,J=2.8Hz,2H),3.99(s,3H),3.57(t,J =6.0Hz,2H),3.34(t,J=6.0Hz,2H),3.03(t,J=2.8Hz,1H),2.93(s,6H),2.82(s,3H); MS m / z(ESI): 524.2[M+H]+. Example 141: Preparation of N-(5-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide The preparation method of N-(5-((4-(1-allyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acryloylamide is similar to that in Example 140. 1H NMR (400MHz, CD3OD): δ8.53(s,1H),8.31(b,1H),8.00(d,J=6.8Hz,1H),7.94(s,1H),7.49(d,J=8 .0Hz,1H),7.39(d,J=6.8Hz,1H),7.28(t,J=7.2Hz,1H),7.19(t,J=8.0Hz,1H),7.05(s,1H),6.57 (m,1H),6.42(m,1H),6.07(m,1H),5.82(m,1H),5.25(m,1H),5.23(m,1H),4.92(d,J=5.2Hz,2H), 3.93(s,3H),3.86(m,2H),3.52(t,J=4.4Hz,2H),3.32(t,J=5.6Hz,2H),2.88(s,6H),2.76(s,3H); MS m / z(ESI): 526.2[M+H]+. Example 142: Preparation of N-(5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide) Step 1: Preparation of N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-methoxy-N4-methyl-5-nitro-N4-(2-(pyrrolidin-1-yl)ethyl)phenyl-1,4-diamine The compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (118 mg, 0.312 mmol) was dissolved in DMF (2 mL), and triethylamine (95 mg, 0.936 mmol) and N-methyl-2-(pyrrolidine-1-yl)ethane-1-amine (60 mg, 0.468 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness, and the crude product was separated by preparative plate to obtain N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-methoxy-N4-methyl-5-nitro-N4-(2-(pyrrolidine-1-yl)ethyl)phenyl-1,4-diamine (122 mg, 100%). Step 2: Preparation of 3-(2-((2-methoxy-4-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide) The compound N-(4-(1H-indol-3-yl)pyrimidin-2-yl)-2-methoxy-N4-methyl-5-nitro-N4-(2-(pyrrolidone-1-yl)ethyl)phenyl-1,4-diamine (122 mg, 0.25 mmol) was dissolved in DMF (10 mL), cooled to 0 °C in an ice bath, and then NaH (30 mg, 0.75 mmol) was added. After reacting at 0 °C for ten minutes, dimethylaminosulfonyl chloride (54 mg, 0.374 mmol) was added dropwise. The reaction was then brought to room temperature and stirred for 30 minutes. After the reaction was quenched, dichloromethane and water were added, and the mixture was extracted three times. The organic phases were combined, washed with saturated sodium bicarbonate solution, water, and brine, and then filtered and concentrated to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain 3-(2-((2-methoxy-4-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (60 mg, 40%). Step 3: Preparation of 3-(2-((5-amino-2-methoxy-4-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)phenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide) The above compound 3-(2-((2-methoxy-4-(methyl(2-(pyrrolid-1-yl)ethyl)amino)-5-nitrophenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide was dissolved in methanol (5 mL), and Pd / C (15 mg) was added. The reaction was stirred at 24 °C for 1 hour under a hydrogen balloon. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product 3-(2-((5-amino-2-methoxy-4-(methyl(2-(pyrrolid-1-yl)ethyl)amino)phenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide 15 mg was purified by rapid silica gel column chromatography. Step 4: Preparation of N-(5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)acryloylamide Compound 3-(2-((5-amino-2-methoxy-4-(methyl(2-(pyrrolidone-1-yl)ethyl)amino)phenyl)amino)pyrimidin-4-yl)-N,N-dimethyl-1H-indole-1-sulfonamide (15 mg, 0.027 mmol) and triethylamine (8 mg, 0.08 mmol) were dissolved in anhydrous tetrahydrofuran (20 mL). The reaction solution was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.05 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in a dry ice bath for 30 minutes. LCMS showed that the reaction was complete. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by preparative plate to obtain N-(5-((4-(1-(N,N-dimethylaminosulfonyl)-1H-indol-3-yl)pyrimidin-2-yl)amino)-4-methoxy-2-(methyl(2-(pyrrolidine-1-yl)ethyl)amino)phenyl)acryloylamide (7 mg, 44%). 1H NMR (400MHz, CD3OD) δ8.63 (s, 1H), 8.46 (d, J = 7.9Hz, 1H), 8.32 (s, 1H), 8.11–7.92 (m, 2H), 7. 56(d,J=5.9Hz,1H),7.37(dt,J=15.2,7.3Hz,2H),7.04(s,1H),6.55(dd,J=16.8,10.1Hz,1H ),6.42(dd,J=16.9,1.7Hz,1H),5.87(dd,J=10.0,1.7Hz,1H),3.99(s,3H),3.60(s,2H),3.5 8–3.50(m,2H),3.43–3.36(m,2H),3.10(s,2H),2.93(s,6H),2.79(s,3H),2.27–2.09(m,4H); MS m / z(ESI): 619.6[M+H]+. Example 143: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Step 1: Preparation of 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1H-indole 6-Methoxy-1H-indole (5 g, 33.97 mmol), 2,4-dichloro-5-(trifluoromethyl)pyrimidine (8.1 g, 37.36 mmol), and aluminum trichloride (6.79 g, 50.95 mmol) were dissolved in DME (50 mL), and the reaction mixture was stirred overnight at 70 °C. After the reaction was complete, the reaction mixture was poured into ice water, extracted three times with methyl tert-butyl ether, and the organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by rapid silica gel column chromatography to obtain 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1H-indole (4.3 g, 39%). Step 2: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidine-2-amine Compound 3-(2-chloro-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-1H-indole (165 mg, 0.504 mmol), starting material 4-fluoro-2-methoxy-5-nitroaniline (103 mg, 0.554 mmol) and p-toluenesulfonic acid monohydrate (96 mg, 0.504 mmol) were dissolved in 2-pentanol (20 mL). The reaction was heated to 120 °C and carried out overnight. The reaction was confirmed to be complete by LCMS. The reaction solution was allowed to cool naturally to room temperature, and a dark solid precipitated. The solid was filtered, and the filter cake was washed with methanol (1 mL) and methyl tert-butyl ether (1 mL) to give N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1H-indole-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine (125 mg, 52%). Step 3: Preparation of N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine The compound N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine (125 mg, 0.262 mmol) was dissolved in 2 mL of DMF, and triethylamine (80 mg, 0.786 mmol) and trimethylethylenediamine (80 mg, 0.786 mmol) were added. The reaction was heated to 120 °C by microwave for 30 minutes. LC-MS showed that the reaction was complete. The reaction solution was concentrated to dryness, and the crude product was separated by preparative thin-layer chromatography to obtain N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (146 mg, 99%). Step 4: Preparation of 3-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-N,N-dimethyl-1H-indole-1-sulfonamide The compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine (146 mg, 0.262 mmol) was dissolved in DMF (10 mL), cooled to 0 °C in an ice bath, and then NaH (31 mg, 0.786 mmol) was added. After reacting at 0 °C for 10 minutes, dimethylaminosulfonyl chloride (41 mg, 0.288 mmol) was added dropwise. The reaction was then brought to room temperature and stirred for 30 minutes. After the reaction was quenched, dichloromethane and water were added, and the mixture was extracted three times. The organic phases were combined and washed successively with saturated sodium bicarbonate aqueous solution, water, and saturated brine. After filtration and evaporation, the crude product was obtained. The crude product was purified by rapid silica gel column chromatography to obtain 3-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-N,N-dimethyl-1H-indole-1-sulfonamide (80 mg, 46%). Step 5: Preparation of 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-N,N-dimethyl-1H-indole-1-sulfonamide) The above compound N1-(2-(dimethylamino)ethyl)-5-methoxy-N4-(4-(6-methoxy-1H-indole-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)-N1-methyl-2-nitrobenzene-1,4-diamine was dissolved in methanol (10 mL), and Pd / C (20 mg) was added. The reaction was stirred at 24 °C for 1 hour under a hydrogen balloon. The reaction was confirmed to be complete by LCMS. The reaction was filtered, and the filtrate was concentrated to obtain the crude product. The crude product 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-N,N-dimethyl-1H-indole-1-sulfonamide 44 mg was obtained by rapid silica gel column purification. Step 6: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide Compound 3-(2-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)-6-methoxy-N,N-dimethyl-1H-indole-1-sulfonamide (44 mg, 0.069 mmol) and triethylamine (21 mg, 0.207 mmol) were added to anhydrous tetrahydrofuran (20 mL). The reaction mixture was stirred at -78 °C for 10 minutes, and then acryloyl chloride (0.2 mL, 1 M in THF) was slowly added dropwise. The reaction was stirred in a dry ice bath for 30 minutes. The reaction was confirmed to be complete by LCMS. The reaction was quenched with methanol, the reaction solution was concentrated, and the residue was purified by preparative thin-layer chromatography to obtain N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-(N,N-dimethylaminosulfonyl)-6-methoxy-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acryloylamide (16 mg, 33%). 1H NMR(400MHz,CD3OD)δ8.78(s,1H),8.39(s,1H),7.91(d,J=8.8Hz,1H),7.8 2(s,1H),7.50(d,J=2.1Hz,1H),6.97(s,1H),6.90(d,J=8.2Hz,1H),6.41(d ,J=5.3Hz,2H),5.83(t,J=5.9Hz,1H),4.00(s,3H),3.88(s,3H),3.49(t,J =5.5Hz,2H),3.28(t,J=5.5Hz,2H),2.89(s,6H),2.86(s,6H),2.70(s,3H); MS m / z(ESI): 691.5[M+H]+. Biological test evaluation 1. Enzymatic experiments with EGFR T790M mutant This experiment used fluorescence resonance energy transfer (TR-FRET) to test the inhibitory effect of the compound on the exon 20T790M mutant EGFR enzyme and determined the half-maximal inhibitory concentration (IC50) of the compound on the enzyme activity. 1) Add 1-5 μL of EGFR T790M enzyme solution to a 384-well plate to achieve a final enzyme concentration of 0.1-1 nM. 2) Add 1-5 μL of the graded compound solution. 3) Incubate at room temperature for 10 minutes. 4) Add 1–5 μL of substrate mixture containing a final concentration of substrate peptide of 5–50 nM and a final concentration of ATP of 1–10 μM. 5) Incubate at room temperature for 0.5 to 2 hours. 6) Add 5 μL of EDTA stop solution to terminate the reaction for 5 minutes. 7) Add 5 μL of detection solution containing labeled antibody and incubate at room temperature for 1 hour. 8) Measure the 665nm fluorescence signal value of each plate using an enzyme-linked immunosorbent assay (ELISA) reader. 9) Calculate the inhibition rate using fluorescence signal values. 10) The IC50 of the compound was obtained by curve fitting based on the inhibition rate at different concentrations. 2. Enzymatic assay for EGFR wild-type (WT) This experiment used fluorescence resonance energy transfer (TR-FRET) to test the inhibitory effect of the compound on wild-type EGFR enzyme and determined the half-maximal inhibitory concentration (IC50) of the compound on the enzyme activity. 1) Add 1–5 μL of EGFR wild-type enzyme solution to a 384-well plate to achieve a final enzyme concentration of 0.1–1 nM. 2) Add 1-5 μL of the graded compound solution. 3) Incubate at room temperature for 10 minutes. 4) Add 1–5 μL of substrate mixture containing a final concentration of substrate peptide of 5–50 nM and a final concentration of ATP of 0.1–5 μM. 5) Incubate at room temperature for 0.5 to 2 hours. 6) Add 5 μL of EDTA stop solution to terminate the reaction for 5 minutes. 7) Add 5 μL of detection solution containing labeled antibody and incubate at room temperature for 1 hour. 8) Measure the 665nm fluorescence signal value of each plate using an enzyme-linked immunosorbent assay (ELISA) reader. 9) Calculate the inhibition rate using fluorescence signal values. 10) The IC50 of the compound was obtained by curve fitting based on the inhibition rate at different concentrations. The biochemical activity of the compounds of this invention was determined by the above experiments, and the measured IC50 values ​​are shown in the table below. NT indicates no activity detected. The EGFR IC50 values ​​of compounds in other embodiments of the present invention are similar to those in the above embodiments, exhibiting similar inhibitory activity and regularity. Conclusion: The embodiments of the present invention exhibit strong inhibitory activity against EGFR mutant kinases, while showing weak inhibition against wild-type kinases, thus demonstrating excellent selectivity. 3. NCI-H1975 cell proliferation inhibition experiment This experiment used the CellTiter-Glo method to test the inhibitory effect of the compound on the proliferation of NCI-H1975 cells and determined the half-maximal inhibitory concentration (IC50) of the compound on cell proliferation activity. 1) Inoculate 90 μL of H1975 cell suspension into a 96-well cell culture plate at a density of 1–5 × 10³ cells / ml and incubate the plate in an incubator for 16–24 hours (37°C, 5% CO₂). 2) Add serially diluted solutions of the test compound to the cells in the culture plate and incubate the culture plate in an incubator for 72 hours (37°C, 5% CO2). 3) Add 50-100 μL of CellTiter-Glo reagent to each well, shake for 10 minutes, and let stand at room temperature for 10 minutes. 4) Measure the chemiluminescence signal value of each plate using an enzyme-linked immunosorbent assay (ELISA) reader. 5) Calculate the inhibition rate using the chemiluminescence signal value. 6) The IC50 of the compound was obtained by curve fitting based on the inhibition rate at different concentrations. 4. A431 cell proliferation inhibition experiment This experiment used the CellTiter-Glo method to test the inhibitory effect of the compound on the proliferation of A431 cells and determined the half-maximal inhibitory concentration (IC50) of the compound on cell proliferation activity. 1) Inoculate 90 μL of A431 cell suspension into a 96-well cell culture plate at a density of 1–5 × 10³ cells / mL and incubate the plate in an incubator for 16–24 hours (37°C, 5% CO₂). 2) Add serially diluted solutions of the test compound to the cells in the culture plate and incubate the culture plate in an incubator for 72 hours (37°C, 5% CO2). 3) Add 50-100 μL of CellTiter-Glo reagent to each well, shake for 10 minutes, and let stand at room temperature for 10 minutes. 4) Measure the chemiluminescence signal value of each plate using an enzyme-linked immunosorbent assay (ELISA) reader. 5) Calculate the inhibition rate using the chemiluminescence signal value. 6) The IC50 of the compound was obtained by curve fitting based on the inhibition rate at different concentrations. The biochemical activity of the compounds of this invention was determined by the above experiments, and the measured IC50 values ​​are shown in the table below. The EGFR IC50 values ​​of compounds in other embodiments of the present invention are similar to those in the above embodiments, exhibiting similar inhibitory activity and regularity. Conclusion: The embodiments of the present invention have strong inhibitory activity on the proliferation of EGFR mutant cells H1975, while having low inhibitory activity on the proliferation of wild-type A431 cells. The embodiments have good selectivity for wild-type / mutant cells. Example: Compound PK Test I. PK Analysis in Rats In the preferred embodiment of the present invention, the pharmacokinetic assay of compound AZD-9291 and positive control compound AZD-9291 in rats was conducted using SD rats (Shanghai Shrek). ■Administration method: Single oral gavage. ■ Dosage: 5 mg / 10 ml / kg. ■ Formulation: 0.5% methylcellulose, dissolved by ultrasonication. ■Sampling points: 0.5, 1, 2, 4, 6, 8 and 24 hours after administration. ■Sample processing: 1. Collect 1.0 ml of venous blood and place it in a K2EDTA test tube. Centrifuge at 6000 rpm for 5 min to separate the plasma and store at -80℃. 2. Add 160 μL of acetonitrile to 40 μL of plasma sample to precipitate, mix, and centrifuge at 3500 rpm for 5 minutes. 3. Take 100 μL of the treated solution and perform LC / MS / MS analysis to determine the concentration of the analyte. LC / MS / MS instrument: AB Sciex API 4000. Liquid phase analysis: ●Liquid phase conditions: Shimadzu LC-20AD pump ● Column: Phenomenex Gemiu 5µm C18 50 x 4.6mm ●Mobile phase: Solution A is a 0.1% formic acid aqueous solution, and solution B is acetonitrile. ● Flow rate: 0.8 mL / min ●Eluting time: 0-3.5 minutes, eluent as follows: Time / minute Liquid A Liquid B 0.01 90% 10% 0.5 90% 10% 1.2 5% 95% 2.2 5% 95% 2.21 100% 0 3.5 100% 0 Mass spectrometry analysis: Mass spectrometer settings: Positive ion electrospray ionization (ESI) mode. ■Liquid chromatography-mass analysis results: 1. Compound of Example 26: 1H NMR (400MHz, CDCl3): δ9.78(s,1H),9.74(s,1H),8.55(s,1H),8.39(d,J=5.3Hz,1H),8.11(d,J=7.0 Hz,1H),7.74-7.55(m,2H),7.18(d,J=5.3Hz,1H),6.76(s,1H),6.62(dd,J=16.8,10.1Hz,1H),6.46 (dd,J=16.9,1.9Hz,1H),6.24(m,1H),5.80-5.59(m,1H),3.88(s,3H),3.55-3.34(m,1H),3.02(t,J =5.8Hz,2H),2.68(s,3H),2.57(t,J=5.7Hz,2H),2.42(s,6H),1.24-1.17(m,2H),1.14-1.04(m,2H); MS m / z(ESI): 526.3[M+H]+. Metabolites: 1H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 9.29 (s, 1H), 8.29 (d, J = 5.3Hz, 1H), 8.18 (s, 1H), 8.07 (d ,J=7.2Hz,1H),7.61–7.40(m,2H),7.24–7.15(m,2H),7.06(d,J=5.3Hz,1H),6.94(dd,J=15. 9,9.9Hz,1H),6.45(s,1H),6.17(d,J=16.9Hz,1H),5.58(d,J=10.2Hz,1H),3.79(s,3H),3. 39–3.15(m,1H),2.93(s,2H),2.65(s,2H),2.44(s,3H),2.26(s,3H),1.01(d,J=5.2Hz,4H); MS m / z(ESI): 512.6[M+H]+. The structure is analyzed as follows: 2. The structure of the metabolite of the positive control compound AZD-9291 is analyzed as follows: Compare with the literature (Journal of Medicinal Chemistry (2014), 57(20), 8249-8267) The publicly available data is largely consistent. ■Pharmacokinetics: The main parameters were calculated using WinNonlin 6.1, and the results of the rat pharmacokinetic experiment are shown in Table 11 below: As can be seen from the results of the rat pharmacokinetic experiment in Table 11: 1. The positive control compound AZD-9291 has two metabolites in rat plasma; while the compound of Example 26 of this invention has only one metabolite in rats. 2. The compound in Example 26 of this invention does not produce metabolite-2 of the positive control compound AZD-9291, thus avoiding the problem caused by the poor selectivity of metabolite-2 of AZD-9291 for the T790M mutant / wild-type target protein, and overcoming the defects of the prior art. II. Dog Competitive Analysis In the preferred embodiment of the present invention, the pharmacokinetic study of compound 26 and positive control compound AZD-9291 in dogs was conducted using beagle dogs. ■Administration method: Single oral gavage. ■ Dosage: 2 mg / 2.5 ml / kg. ■ Formulation: 0.5% methylcellulose, dissolved by ultrasonication. ■Sampling points: Sampling points are 0.5, 1, 2, 4, 6, 8 and 24 hours after administration. ■Sample processing: 1. Collect 1.0 ml of venous blood, place it in a Heparin test tube, centrifuge at RT 6000 rpm for 5 min to separate the plasma, and store at -80℃. 2. Add 160 μL of acetonitrile to 40 μL of plasma sample to precipitate, mix, and centrifuge at 3500 rpm for 5 minutes. 3. Take 100 μL of the treated solution and perform LC / MS / MS analysis to determine the concentration of the analyte. LC / MS / MS instrument: AB Sciex API 4000. Liquid phase analysis: ●Liquid phase conditions: Shimadzu LC-20AD pump ● Column: Phenomenex Gemiu 5µm C18 50 x 4.6mm ●Mobile phase: Solution A is a 0.1% formic acid aqueous solution, and solution B is acetonitrile. ● Flow rate: 0.8 mL / min ●Eluting time: 0-3.5 minutes, eluent as follows: Time / minute Liquid A Liquid B 0.01 90% 10% 0.5 90% 10% 1.2 5% 95% 2.2 5% 95% 2.21 100% 0 3.5 100% 0 Mass spectrometry analysis: Mass spectrometer settings: Positive ion electrospray ionization (ESI) mode. ■ The liquid chromatography-mass spectrometry (LC-MS) analysis results are consistent with those of the rat PK analysis. ■Pharmacokinetics: The main parameters were calculated using WinNonlin 6.1, and the results of the canine pharmacokinetic experiments are shown in Table 12 below: As can be seen from the pharmacokinetic results in dogs in Table 12, the pharmacokinetic parameters of the compound in the preferred embodiment 26 of this invention are better than those of the positive control compound AZD-9291. The exposure level can reach more than 6 times that of the positive control compound AZD-9291, and the half-life is also significantly prolonged, which is more in line with the requirements for drug administration in medicine.

Claims

1. A compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof: in: Ring A is selected from the following structure: Q is selected from bond, O, S, NR 7 or CR 7R 8; R is selected from hydrogen or dicarbonyl group. 1-8 Alkylaminomethyl; X1, X2, and X3 are each independently selected from NR 7 or CR 8, wherein at least one of X1, X2, and X3 is selected from NR 7; R1 is selected from the following structure: The three R 6 substituents may be the same or different substituents; R 2 is selected from C 1-8 Alkyl, C 3-8 Cycloalkyl groups, optionally further oxidized by one or more elements selected from halogens, hydroxyl groups, and C64 groups. 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkoxy, C 3-8 cycloalkyl or C 3-8 Substituents of cycloalkoxy groups; R 3 is selected from hydrogen, deuterium, halogen, cyano, nitro, and C. 1-8 Alkyl, C 1-8 Alkoxy, C 3-8 Cycloalkyl, trifluoromethyl, trifluoromethoxy, SO₂R₉, C(O)R 10 C(O)OR 10 or P(O)R 11 R 12 ; R4 and R5 are each independently selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, and C. 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -P(O)R 11 R 12 -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced by the substituents. or, Two R4 or two R5 atoms bonded to a carbon atom in a benzene ring form a 5-7 membered carbon ring, a 5-7 membered heterocycle, or a C ring. 5-7 Aryl or 5-7 membered heteroaryl, The C mentioned therein 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-10 Aryl, 5-10 fused heteroaryl, 5-7 fused carbon ring, 5-7 fused heterocycle, C 5-7 aryl or 5-7 heteroaryl groups may be further selected from one or more halogens, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced; R6 is selected from hydrogen, deuterium, and C. 1-8 Alkyl, halogenated C 1-8 Alkyl or C(O)R 10 ; R 7 is selected from hydrogen, deuterium, and C. 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-10 Aryl, 5-10 heteroaryl, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8 or -C 0-8 -C(O)NR 7R 8, The C mentioned therein 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-10 aryl or 5-10 heteroaryl groups optionally further selected from one or more halogens, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced; R8 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, and C. 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 , The C mentioned therein 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-10 aryl or 5-10 heteroaryl groups optionally further selected from one or more halogens, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced; R9 is selected from hydrogen, deuterium, and C. 1-8 Alkyl, C 3-8 cycloalkyl, halosubstituted C 1-8 Alkyl, diC 1-8 Alkylamino, phenyl, or p-methylphenyl; R 10 R 11 R 12 Each element is independently selected from hydrogen, deuterium, and C. 1-8 Alkyl, C 3-8 cycloalkyl, halosubstituted C 1-8 Alkyl or hydroxy substituted C 1-8 alkyl; m can be 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, 4 or 5; r is 0, 1, or 2; o can be 0, 1, 2, 3, or 4; p is 0, 1, 2 or 3; q can be 0, 1, 2, 3, or 4; This indicates that the R substituent can be of the Z or E type.

2. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, R 2 is selected from C 1-4 Alkyl, C 3-6 Cycloalkyl groups, optionally further oxidized by one or more elements selected from halogens, hydroxyl groups, and C64 groups. 1-8 Alkyl, C 1-8 Alkoxy, halogenated C 1-8 Alkoxy, C 3-8 cycloalkyl or C 3-8 Substituents of cycloalkoxy groups; rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 R 12 m, n, r, o, p, q as defined in claim 1.

3. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 2, characterized in that, R 2 is selected from C 1-4 Alkyl, C 3-6 Cycloalkyl group, optionally further substituted by one or more substituents selected from halogens or hydroxyl groups; cycloa, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 R 12 m, n, r, o, p, q as defined in claim 1.

4. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 3, characterized in that, R 2 is selected from C 1-4 Alkyl group, optionally further substituted with one or more substituents selected from fluorine or hydroxyl; cyclic group A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 R 12 m, n, r, o, p, q as defined in claim 1.

5. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 4, characterized in that, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; rings A, Q, R, X1, X2, X3, R1, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 R 12 m, n, r, o, p, q as defined in claim 1.

6. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 1-5, characterized in that, Selected from compounds of formula (IA): Wherein, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; ring A, R, X1, X2, X3, R1, R3, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

7. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (IIA1) or formula (IIA2): Wherein, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; ring A, R, X1, X2, X3, R1, R3, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

8. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (ⅢA1-1), (ⅢA1-2), (ⅢA1-3), (ⅢA1-4), (ⅢA1-5), or (ⅢA1-6): Wherein, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

9. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (ⅣA1-1) or formula (ⅣA1-2): Among them, R, R 1, R 3, R 4, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

10. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 9, characterized in that, R3 is selected from hydrogen, deuterium, halogens, and C. 1-8 Alkyl, C 1-8 Alkoxy, C 3-8 Cycloalkyl, trifluoromethyl, or trifluoromethoxy; R, R1, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

11. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 9, characterized in that, R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropoxy, cyclopropyl, cyclobutyl, trifluoromethyl, or trifluoromethoxy; R, R1, R4, R6, R7, R8, R9, R 10 R 11 R 12 R, m, r, q are as defined in claim 1; preferably, R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl or trifluoromethyl.

12. The compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 9-11, characterized in that, Selected from the following compounds:

13. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (ⅣA1-3): Among them, R, R 1, R 3, R 4, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

14. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 13, characterized in that, R, R 1, R 3, R 4, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, r, q are as defined in claim 1; wherein m is 3 or 4 when both R7 and R8 are hydrogen; m is 2, 3 or 4 when either R7 or R8 is hydrogen; and m is 1, 2, 3 or 4 when neither R7 nor R8 is hydrogen.

15. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 13, characterized in that, R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl, or trifluoromethyl; R, R1, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1; wherein m is 3 or 4 when both R7 and R8 are hydrogen; m is 2, 3 or 4 when either R7 or R8 is hydrogen; and m is 1, 2, 3 or 4 when neither R7 nor R8 is hydrogen.

16. The compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to any one of claims 13-15, characterized in that, Selected from the following compounds:

17. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 13, characterized in that, When m is 2, 3, or 4; R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl, or trifluoromethyl; the two R4 atoms attached to the carbon atom of the benzene ring form a 5-7 membered carbon ring, a 5-7 membered heterocycle, or a C ring. 5-7 Aryl or 5-7 membered heteroaryl, wherein the 5-7 membered carbon ring, 5-7 membered hetero ring, C 5-7 The aryl or 5-7 membered heteroaryl groups are selected from the groups at the corresponding positions in the following structures; The 5-7 membered carbon ring, 5-7 membered hetero ring, C 5-7 aryl or 5-7 heteroaryl groups may be further selected from one or more halogens, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced; R, R 1, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

18. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 13, characterized in that, When both R7 and R8 are hydrogen, m is 1 or 2; when either R7 or R8 is hydrogen, m is 0 or 1; when neither R7 nor R8 is hydrogen, m is 0, 1, or 2; R3 is selected from hydrogen, fluorine, chlorine, methyl, cyclopropyl, or trifluoromethyl. R 4 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, and C. 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -P(O)R 11 R 12 -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 ; The C mentioned therein 1-8 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic groups, C 5-10 Aryl, 5-10 fused heteroaryl, 5-7 fused carbon ring, 5-7 fused heterocycle, C 5-7 aryl or 5-7 heteroaryl groups may be further selected from one or more halogens, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 The substituents are replaced; R, R 1, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

19. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 18, characterized in that, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R4 is selected from hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, nitro, azide, C 1-8 Alkyl, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group with oxygen, 3-8 membered heterocyclic group with thio group, C 5-10 Aryl, C 5-10 aryloxy group, C 5-10 arylthio, 5-10 heteroaryl, 5-10 heteroaryloxy, 5-10 heteroarylthio, -C 0-8 -S(O)rR 9、-C 0-8 -OR 10 -C 0-8 -C(O)R 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8、-C 0-8 -C(O)NR 7R 8、-N(R 7)-C(O)R 10 or -N(R 7)-C(O)OR 10 ; R, R 1, R 6, R 7, R 8, R 9, R 10 R 11 R 12 r, q are as defined in claim 1; m is as defined in claim 18.

20. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 18, characterized in that, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R4 is selected from hydrogen, deuterium, hydroxyl, cyano, C 2-8 Alkenyl, C 2-8 Alkyne group, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group, 3-8 membered heterocyclic group, C 5-10 Aryl, C 5-10 aryloxy group, 5-10 heteroaryl group, 5-10 heteroaryloxy group, -C 0-8 -OR 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8 or -C 0-8 -C(O)NR 7R 8; R, R1, R6, R7, R8, R 10 R 11 R 12 q is as defined in claim 1; m is as defined in claim 18.

21. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 18, characterized in that, R 3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R 4 is selected from hydrogen, deuterium, hydroxyl, cyano, vinyl, ethynyl, cyclopropyl, cyclobutyl, oxetane-3-yl, NR 6-azacyclobutane-3-yl, cyclopropoxy, cyclobutoxy, phenyl, phenoxy, -C 0-8 -OR 10 -C 0-8 -C(O)OR 10 -C 0-8 -OC(O)R 10 -C 0-8 -NR 7R 8 or -C 0-8 -C(O)NR 7R 8, ; R, R1, R6, R7, R8, R 10 R 11 R 12 q is as defined in claim 1; m is as defined in claim 18.

22. The compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of claims 18-21, characterized in that, Selected from the following compounds:

23. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (ⅢA1-7), formula (ⅢA1-8), or formula (ⅢA1-9): Wherein, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

24. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 23, characterized in that, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R, R1, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

25. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 24, characterized in that, R 1 is selected from 26. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 25, characterized in that, Selected from compounds of formula (ⅣA1-4) or formula (ⅣA1-5): Wherein, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R, R4, R6, R7, R8, R9, R 10 R 11 R 12 m and r are as defined in claim 1.

27. The compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of claims 23-26, characterized in that, Selected from the following compounds:

28. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 23, characterized in that, Selected from compounds of formula (ⅣA1-6) or formula (ⅣA1-7): Wherein, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R, R4, R6, R7, R8, R9, R 10 R 11 R 12 m and r are as defined in claim 1.

29. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 28, characterized in that, Selected from the following compounds:

30. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 6, characterized in that, Selected from compounds of formula (ⅢA2-1), (ⅢA2-2), (ⅢA2-3), (ⅢA2-4), (ⅢA2-5), or (ⅢA2-6): Wherein, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; R, R1, R3, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

31. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 30, characterized in that, R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; R, R1, R4, R6, R7, R8, R9, R 10 R 11 R 12 m, r, q are as defined in claim 1.

32. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 31, characterized in that, R 1 is selected from 33. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Selected from compounds of formula (IB): Among them, Q, R, R 1, R 2, R 3, R 5, R 6, R 7, R 8, R 9, R 10 R 11 R 12 , n, r, q are as defined in claim 1.

34. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 33, characterized in that, R2 is selected from methyl, difluoromethyl, or trifluoromethyl; R3 is selected from hydrogen, fluorine, chlorine, or trifluoromethyl; Q, R, R1, R5, R6, R7, R8, R9, R 10 R 11 R 12 , n, r, q are as defined in claim 1.

35. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 34, characterized in that, R 1 is selected from 36. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 35, characterized in that, Selected from compounds of formula (IIB):

37. The compound having formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof according to claim 36, characterized in that, Selected from compounds of formula (ⅢB):

38. The compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of claims 33-37, characterized in that, Selected from the following compounds:

39. The compound of formula (I) according to claim 1, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, Selected from compounds of formula (IC): Among them, Q, R, R 1, R 2, R 3, R 4, R 6, R 7, R 8, R 9, R 10 R 11 R 12 r, o, p, q as defined in claim 1.

40. The compound of formula (I) according to claim 39, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, R2 is selected from difluoromethyl, trifluoromethyl, or methyl; R3 is selected from hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl, cyano, or nitro; Q, R, R1, R4, R6, R7, R8, R9, R 10 r, o, p, q as defined in claim 1.

41. The compound of formula (I) according to claim 40, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, Selected from compounds of formula (IIC1) or formula (IIC2): Among them, Q, R, R4, R7, R8, R9, R 10 R 11 R 12 r and o are as defined in claim 1.

42. The compound of formula (I) according to claim 41, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, Selected from compounds of formula (ⅢC1) or formula (ⅢC2): Among them, R, R4, R7, R8, R9, R 10 r and o are as defined in claim 1.

43. The compound of formula (I) according to any one of claims 39-42, its stereoisomer, or a pharmaceutically acceptable salt thereof, characterized in that, Selected from the following compounds:

44. A method for preparing a compound of formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, as described in any one of claims 1-43, comprising the following steps: in, Ring A, Q, X 1, X 2, X 3, R, R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10 R 11 R 12 m, n, r, o, p, q as defined in claim 1.

45. A pharmaceutical composition comprising a therapeutically effective dose of a compound having formula (I) according to any one of claims 1-43, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

46. ​​The use of any compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 45, in the preparation of a therapeutic remedy for treating diseases mediated by EGFR mutants and exon 19 deletion activation mutants, preferably, wherein the EGFR mutant is selected from the L858R EGFR mutant or the T790M EGFR mutant.

47. The application according to claim 46, characterized in that, The use of any compound of formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 45, in the preparation of a therapeutic remedy for treating diseases mediated alone or in part by EGFR mutant activity, according to any one of claims 1-43.

48. The application according to claim 46, characterized in that, The use of any one of the compounds of formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, or the pharmaceutical composition of claim 45 in the preparation of a medicament for treating cancer, according to any one of claims 1-43.

49. The application according to claim 48, characterized in that, The cancers selected are ovarian cancer, cervical cancer, colorectal cancer, breast cancer, pancreatic cancer, glioma, glioblastoma, melanoma, prostate cancer, leukemia, lymphoma, non-Hodgkin's lymphoma, gastric cancer, lung cancer, hepatocellular carcinoma, gastrointestinal stromal tumor (GIST), thyroid cancer, bile duct cancer, endometrial cancer, renal cancer, anaplastic large cell lymphoma, acute myeloid leukemia (AML), multiple myeloma, melanoma, or mesothelioma; non-small cell lung cancer is preferred.