IRAK4 degrading agent and application thereof

Abstract

The invention relates to an interleukin-1 receptor-associated kinase 4 (IRAK4) degradation agent and application of the IRAK4 degradation agent in preparation of a medicine for treating IRAK4-associated diseases. The invention specifically relates to a compound as shown in a formula (I), and isomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof.

Description

IRAK4 degraders and uses thereof This application claims the following priority: CN202310688429.3, application date: June 9, 2023; CN202410025235.X, application date: January 5, 2024; CN202410437935.X, application date: April 11, 2024. Technical Field The present invention relates to the field of medicinal chemistry, and in particular, provides bifunctional compounds for proteolytic degradation of interleukin-1 receptor associated kinase 4 (IRAK4) and methods for treating diseases regulated by IRAK4. Background Art Interleukin 1 receptor kinase 4 (IRAK4) is a threonine / serine protein kinase composed of 460 amino acids, containing a kinase domain and a death domain. Typically, the N-terminal lobe and the C-terminal lobe can be found in the kinase domain, which converge to form an ATP binding site. The death domain exists to bind and interact with MyD88 during protein recruitment. In addition, there are three phosphorylation sites on the protein that participate in trans-phosphorylation. IRAK4 is considered to be a key protein kinase for early activation of IL-1 receptors and TLRs downstream, initiating signal transduction by rapidly activating IRAK1 and IRAK2, leading to an innate immune response. In addition, other interleukins, such as IL-18 and IL-33, rely on IRAK4 for signal transduction. Clinical pathological studies have shown that individuals with IRAK4 mutations are protected against chronic lung disease and inflammatory bowel disease. IRAK4 deficiency itself is not lethal, and individuals can survive to adulthood, and the risk of infection decreases with age. A lot of evidence shows that inhibiting IRAK4-mediated signal transduction will be a promising treatment method. IRAK4 has become an important therapeutic target and attracted widespread research and development interest. PROTAC (proteolysis targeting chimera) molecules are a class of bifunctional compounds that can simultaneously bind to target proteins and E3 ubiquitin ligases. Such compounds can be recognized by the proteasome of the cell, causing the degradation of the target protein, and can effectively reduce the content of the target protein in the cell. By introducing ligands that can bind to different target proteins into PROTAC molecules, PROTAC technology can be applied to the treatment of various diseases. This technology has also received widespread attention in recent years. Specific degradation of IRAK4 can be achieved by using heterobifunctional small molecules to recruit IRAK4 to ubiquitin ligases and thereby promote ubiquitination and proteasomal degradation of IRAK4, thereby providing therapeutic opportunities in IRAK4-related diseases such as autoimmune diseases, inflammatory diseases, and tumors. Summary of the invention The present invention provides a compound, or a pharmaceutical composition thereof, which can be used as an IRAK4 degrading agent. The present invention further relates to the use of the compound or the pharmaceutical composition thereof for preparing a drug, wherein the drug targets and degrades IRAK4 by the compound. Treating diseases and / or conditions. Specific: In one aspect, the present invention relates to a compound, which is a compound as shown in formula (I), or an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in formula (I), in: Ring A is an 8-13 membered spiro ring having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; Ring B is phenyl, naphthyl, 5-6 membered monocyclic heteroaryl or 9-10 membered bicyclic heteroaryl; R 1 , R 2 and R 3 are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -(C 0-3 Alkylene)-C 3-6 Cycloalkyl or -(C 0-3 Alkylene)-3-8 membered heterocyclic group, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -(C 0-3 Alkylene)-C 3-6 Cycloalkyl and -(C 0-3 The 3- to 8-membered heterocyclic group may be independently and optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, oxo, CN, OH, NO2, NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl and C 1-3 Substituted by a haloalkyl substituent; Each R a and R b are independently hydrogen, deuterium, halogen, oxo, CN, NO2, -R 4 、-OR c 、-SR c 、-N(R c )2. -C(R c )3, -S(=O)2R c、-S(=O)2N(R c )2, -S(=O)R c ,-S(=O)(NR c )R c 、-P(=O)(OR c )2、-P(=O)(N(R c )2)2、-CF(R c )2, -CF2(R c )、-CF3、-C(R c )2-OR c ,-C(R c )2-N(R c )2, -C(=O)R c 、-C(=O)OR c or -C(=O)N(R c )2; or two R on the same atom a The group is optionally combined with its intermediate atom to form a C 3-4 Cycloalkyl or 3-4 membered heterocyclic group; Each R 4 Independently for C 1-6 Alkyl, C 2-6 Alkenyl, phenyl, C 3-7 Cycloalkyl, 3-7 membered heterocyclic or 5-6 membered heteroaryl ring, said R 4 can be independently optionally replaced by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO2, NH2, oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 Substituted by a haloalkyl substituent; Each R c are independently hydrogen, deuterium, C 1-6 Alkyl, phenyl, C 4-7 Cycloalkyl, 4-7 membered heterocyclyl or 5-6 membered heteroaryl, the C 1-6 Alkyl, phenyl, C 4-7 Cycloalkyl, 4-7 membered heterocyclyl and 5-6 membered heteroaryl may be independently optionally substituted by 1, 2 or 3 radicals selected from deuterium, halogen, oxo, CN, OH, NO2, NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 or two R on the same atom c The group is optionally combined with its intermediate atom to form a C 4-7 Cycloalkyl, a 4-11 membered bridged bicyclic or spirocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, said C4-7 The cycloalkyl and 4-11 membered bridged bicyclic or spirocyclic rings having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur may further be any Optionally, 1, 2 or 3 are selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 Substituted by a haloalkyl substituent; m and n are each independently 0, 1, 2, 3, 4, 5, 6, 7 or 8; L is C 1-20 Alkylene, wherein 1, 2, 3, 4 or 5 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d )2-, -Cy-, -O-, -C(=O)- and -N(R d )-unit; wherein each -Cy- is independently C 4-7 Cycloalkyl, 4-11 membered heterocyclyl, 5-11 membered spirocyclyl, 5-11 membered bridged bicyclic radical, phenyl, 5-6 membered heteroaryl, each -Cy- can be independently optionally replaced by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO2, NH2, oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and -C 1-3 Substituted by a haloalkyl substituent; Each R d are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2 or C 1-3 alkyl; And DIM is an E3 ubiquitin ligase binding part. Von Hippel-Lindau (VHL) and cereblon (CRBN) proteins are substrate recognition subunits of two ubiquitously expressed and biologically important Cullin RING E3 ubiquitin ligase complexes. In addition, inhibitor of apoptosis proteins (IAPs) are a family of proteins involved in inhibiting apoptosis. The human IAP family includes 8 members, and many other organisms contain IAP homologs. IAP contains an E3 ligase specific domain and a baculovirus IAP repeat (BIR) domain, which recognizes substrates and promotes their ubiquitination. The DIM of the compound of formula (I) targets VHL, CRBN or IAP of the E3 ligase, which is utilized by the bifunctional compound to induce ubiquitination of IRAK4 and subsequent proteasomal degradation. In some embodiments, Ring A is: in: X1, X2, X3, X4, and X5 are each independently CH2, -C(=O)-, NH, O, or S; a and c are each independently 1 or 2; b and d are each independently 0, 1 or 2, wherein b and d are not both 0 and the sum of b and d is 2, 3 or 4. In some embodiments, each R a are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, -CF3 or C 1-6 Alkyl; or two R on the same atom a Group formation C 3-4 Preferably, each R a are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, -CF3, methyl, ethyl, n-propyl or isopropyl; or two R on the same atom a The group forms a cyclopropyl or cyclobutyl group. In some embodiments, Ring B is: In some embodiments, wherein each R b are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, -COOH, C 1-6 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclyl or 7-8 membered bridged bicyclic ring; 1-6 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclyl and 7-8 membered bridged bicyclic ring may be independently optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, OH, CN, oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 Preferably, each R b are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl and It may be optionally substituted independently with 1, 2 or 3 substituents selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, methyl, ethyl, methoxy, ethoxy, -CHF2, -CF3, -OCHF2 and -OCF3. In some embodiments, wherein Parts are: in: R b1 and R b4 Each is independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, CH3, CH2CH3, -CF2 or -CF3; R b2 and R b3 are each independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, Piperidinyl, piperazinyl, morpholinyl or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl and It may be optionally substituted independently with 1, 2 or 3 substituents selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, methyl, ethyl, methoxy, ethoxy, -CHF2, -CF3, -OCHF2 and -OCF3. or among them Parts are: in: R b1 and R b4 are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH 2、 CH3, CH2CH3, -CF2 or -CF3; R b2 and R b3 are each independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, pyridine or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, pyridine and It may be optionally substituted independently with 1, 2 or 3 substituents selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO2, NH2, methyl, ethyl, methoxy, ethoxy, -CHF2, -CF3, -OCHF2 and -OCF3. In some embodiments, wherein R 1 For hydrogen, deuterium, halogen, CN, OH, NO2, NH2, C 1-6 Alkyl, C 1-6 Alkoxy or C 3-6 Cycloalkyl; R 2 For hydrogen, deuterium, halogen, CN, OH, NO2, NH2, C 1-6 Alkyl, C 1-6 Alkoxy or C 3-6 Cycloalkyl. Preferably R 1 is hydrogen, deuterium, halogen, CN, OH, NO2, NH2, methyl, ethyl, n-propyl, isopropyl, methoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R 2 is hydrogen, deuterium, halogen, CN, OH, NO2, NH2, methyl, ethyl, n-propyl, isopropyl, methoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In some embodiments, wherein R 3 For hydrogen, deuterium, halogen, CN, OH, NO2, NH2, C 1-6 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl or 5-6 membered heterocyclic group, the C 1-6 Alkyl, C 1-4 Alkoxy, C 5-6 The cycloalkyl and 5-6 membered heterocyclic groups may be independently optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, oxo, CN, OH, NO2, NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkoxy, C 1-3 Hydroxyalkyl and C 1-3 Preferably R 3is hydrogen, deuterium, halogen, CN, OH, NO2, NH2, methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl or morpholinyl, and the methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl and morpholinyl may be independently and optionally substituted with 1, 2 or 3 substituents selected from deuterium, halogen, oxo, CN, OH, NO2, NH2, methyl, methoxy, -CH2OH, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -OCHF2, -OCF3, -CH2CHF2 and -C(CH3)2OH. In some embodiments, the DIM moiety is Wherein: X is CH or N; Y is a bond, -CH2-, -NH-, -O-, -C(=O)- or -C(=O)NH-; Ring C is phenyl, 5-6 membered monocyclic heteroaryl or 9-10 membered bicyclic heteroaryl, and the ring C can be independently and optionally substituted by 1, 2 or 3 selected from deuterium, halogen, oxo, CN, OH, NO2, NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 The alkyl group is substituted with a haloalkyl substituent. The DIM part is preferably: In some embodiments, wherein L is C 3-12 Alkylene, wherein 1, 2, 3, 4 or 5 methylene groups may be independently optionally selected from -CR d =CR d -、、-C(R d )2-, -Cy-, -O-, -C(=O)-, -N(R d )-. Preferably L is C 3-9 Alkylene, wherein 1, 2 or 3 methylene groups may be independently optionally selected from -CR d =CR d -、 -C(R d )2-, -O-, -C(=O)-, -NH-, The unit is replaced by may be independently optionally substituted with 1, 2 or 3 substituents selected from deuterium, halogen, CN, OH, NO2, NH2, oxo, methyl, ethyl, isopropyl, methoxy, isopropoxy, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -OCHF2 and -OCF3; each R d are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, methyl, ethyl, n-propyl or isopropyl. In some embodiments, wherein L is wherein L is C 1-9 Alkylene, wherein 1, 2, 3 or 4 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d )2-, -O-, -C(=O)-, -NH-, The unit is replaced by may be independently optionally substituted with 1, 2 or 3 substituents selected from deuterium, halogen, CN, OH, NO2, NH2, oxo, methyl, ethyl, isopropyl, methoxy, isopropoxy, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -OCHF2 and -OCF3; Each R d are independently hydrogen, deuterium, halogen, CN, OH, NO2, NH2, methyl, ethyl, n-propyl or isopropyl. L can be specifically selected as: Some other solutions of the present invention are obtained by arbitrarily combining the above variables. In some embodiments, the compound has a structure represented by formula (II), formula (III), formula (IV), formula (V) or formula (VI): in: Z1, Z3 and Z4 are each independently CH2, -C(=O)-, NH, O or S; Z2 is CH or N; p and q are each independently 1 or 2. The DIM, Ring B, R1, R2, R3, Ra, Rb, L, m and n have the meanings as defined in the present invention. In some embodiments, the compound is a compound having one of the following structures or an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof of a compound having one of the following structures: On the one hand, the present invention relates to a pharmaceutical composition, which comprises a compound of formula (I) of the present invention, or its isomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and a pharmaceutically acceptable excipient, carrier, adjuvant or any combination thereof. In another aspect, the present invention relates to use of the aforementioned compound or a pharmaceutical composition thereof in preparing a medicament for preventing, treating or alleviating a disease associated with IRAK4 in a patient. In some embodiments, the disease is selected from inflammatory diseases, infections such as viral, bacterial, fungal and parasitic infections, HIV-1 infection, sepsis, autoimmune disorders or diseases such as rheumatoid arthritis and multiple sclerosis, gout, juvenile idiopathic arthritis, Muckle-Wells disease, familial Mediterranean fever, Behcet's disease, adult Still's disease, proliferative diseases such as cancer, hyperplasia, restenosis, cardiac hypertrophy, leukemia, intravascular coagulation, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cardiovascular diseases, fibrotic and allergic diseases, asthma, atopic dermatitis, hidradenitis suppurativa, Alzheimer's disease, hormone-related diseases, trauma, hemodialysis, ischemic diseases, non-infectious hepatitis, ultraviolet radiation, closed head injury, pancreatitis, periodontitis, graft-versus-host disease and / or transplant rejection. The invention obtains a series of compounds with high activity, low toxicity, good metabolic stability and excellent drug properties. Related definitions: Unless otherwise indicated, the following terms and phrases used herein are intended to have the following meanings. A particular term or phrase should not be considered to be indefinite or unclear in the absence of special definition, but should be understood according to the ordinary meaning. The present invention is intended to cover all alternatives, variations and equivalents that may be included in the present invention as defined by the claims. Those skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which can be applied in the practice of the present invention. The present invention is in no way limited to the description of methods and materials. Unless otherwise indicated, the structural formulae and compounds described herein include all isomeric forms, N-oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts and prodrugs. Therefore, the compounds of the present invention are also within the scope of the present invention in their individual stereochemical isomers, enantiomers, diastereomers, geometric isomers, conformers, N-oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts and prodrugs. In addition, unless otherwise indicated, the structural formulae of the compounds described herein include one or more different isotopically enriched atoms. Unless otherwise indicated, the "isomers" of the present invention include all isomeric forms (such as enantiomers, diastereomers, geometric isomers or conformational isomers): for example, R, S configurations containing asymmetric centers, (Z), (E) isomers of double bonds, and (Z), (E) conformational isomers. Therefore, single stereochemical isomers of the compounds of the present invention or mixtures of their enantiomers, diastereomers, geometric isomers or conformational isomers are all within the scope of the present invention. Unless otherwise indicated, the term "nitrogen oxide" used in the present invention means that when a compound contains several amine functional groups, one or more nitrogen atoms can be oxidized to form an N-oxide. Unless otherwise indicated, the "hydrate" of the present invention refers to an association formed when the solvent molecule is water. Unless otherwise indicated, the "solvate" of the present invention refers to an association formed by one or more solvent molecules and the compound of the present invention. Solvents that form solvates include, but are not limited to: water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, aminoethanol. "Metabolite" refers to a product obtained by metabolism in vivo of a specific compound described in the present invention or a pharmaceutically acceptable salt, analog or derivative thereof, which exhibits similar activity in vivo or in vitro to the compound of formula (I). The metabolite of a compound can be identified by techniques known in the art, and its activity can be characterized by experimental methods as described in the present invention. Such a product can be obtained by administering the compound through oxidation, reduction, hydrolysis, amidation, deamidation, esterification, defatting, or enzymatic cleavage. Accordingly, the present invention includes metabolites of compounds, including metabolites produced by contacting the compounds of the present invention with mammals for a period of time. The term "prodrug" as used in the present invention refers to a compound that is converted into a compound of formula (I) in vivo. Such conversion is affected by the hydrolysis of the prodrug in the blood or by the conversion of the prodrug into the parent structure by enzymes in the blood or tissues. The prodrug compounds of the present invention may be esters. In the prior invention, esters that can be used as prodrugs include phenyl esters, aliphatic (C 1-24 ) esters, acyloxymethyl esters, carbonates, carbamates and amino acid esters. For example, a compound of the present invention contains a hydroxyl group, which can be acylated to obtain a prodrug form of the compound. Other prodrug forms include phosphates, such as these phosphate compounds obtained by phosphorylation of the hydroxyl group on the parent. The term "pharmaceutically acceptable" as used herein refers to those compounds, materials, compositions and / or dosage forms which, within the scope of sound medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reaction, or other problems or complications, commensurate with a reasonable benefit / risk ratio. The term "pharmaceutically acceptable salt" refers to salts of compounds of the invention, prepared from compounds of the invention having specific substituents with relatively nontoxic acids or bases. When the compounds of the invention contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of base in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amine or magnesium salts or similar salts. When the compounds of the invention contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of acid in a pure solution or a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts, such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, hydrogen sulfate, hydroiodic acid, phosphorous acid, etc.; and organic acid salts, such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid and methanesulfonic acid, and salts of amino acids (such as arginine, etc.), and salts of organic acids such as glucuronic acid. Certain specific compounds of the present invention contain basic and acidic functional groups, and thus can be converted into any base or acid addition salt. Pharmaceutically acceptable salts of the present invention can be synthesized by conventional chemical methods from parent compounds containing acid radicals or bases. Generally, the preparation method of such salts is: in water or an organic solvent or a mixture of the two, these compounds in free acid or base form are reacted with a stoichiometric amount of an appropriate base or acid to prepare. The term "substituted" means that any one or more hydrogen atoms on a specific atom are replaced by a substituent, which may include variants of deuterium and hydrogen, as long as the valence state of the specific atom is normal and the substituted compound is stable. When the substituent is oxygen (i.e., =O), it means that two hydrogen atoms are replaced. Oxygen substitution does not occur on aromatic groups. The term "optionally substituted" means that it may be substituted or not substituted, and unless otherwise specified, the type and number of substituents can be arbitrary on the basis of chemical achievable. When any variable (such as R) appears more than once in the composition or structure of a compound, its definition in each case is independent. Therefore, for example, if a group is substituted by 0-2 R, the group can be optionally substituted by up to two R, and R in each case has independent options. In addition, the combination of substituents and / or their variants is only allowed if such a combination will produce a stable compound. "Cycloalkyl" or "cycloalkane" means a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic carbon ring system containing 3-12 carbon atoms, which is a saturated ring or a ring containing one or more unsaturated bonds, but never an aromatic ring. In one embodiment, the cycloalkyl contains 3-10 carbon atoms; in another embodiment, the cycloalkyl contains 3-8 carbon atoms; in yet another embodiment, the cycloalkyl contains 3-6 carbon atoms. Such examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The cycloalkyl group can be independently unsubstituted or substituted with one or more substituents described herein. "Heterocyclyl" and "heterocycle" are used interchangeably herein and both refer to saturated or partially unsaturated monocyclic, bicyclic or tricyclic rings containing 3-12 ring atoms, never aromatic rings, wherein at least one ring atom is a heteroatom. In one embodiment, "heterocyclyl" or "heterocycle" contains 3-10 ring atoms; in one embodiment, "heterocyclyl" or "heterocycle" contains 3-8 ring atoms; in another embodiment, "heterocyclyl" or "heterocycle" contains 5-8 ring atoms; in yet another embodiment, "heterocyclyl" or "heterocycle" contains 3-6 ring atoms; in yet another embodiment, "heterocyclyl" or "heterocycle" contains 5-6 ring atoms; in yet another embodiment, "heterocyclyl" or "heterocycle" contains 4-6 ring atoms; unless otherwise specified, heterocyclyl may be carbon or nitrogen radical, and heteroatoms have the meanings as described herein. Examples of heterocyclic groups include, but are not limited to, oxirane, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrazolyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxolane, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepine Base, diazepine Thiazepine Examples of heterocyclic groups in which the -CH2- group is replaced by -C(=O)- include, but are not limited to, 2-oxopyrrolidinyl, oxo-1,3-thiazolidinyl, 2-piperidinone, 3,5-dioxopiperidinyl, and pyrimidinedione. Examples of heterocyclic groups in which the sulfur atom is oxidized include, but are not limited to, cyclopentanesulfonyl and 1,1-dioxothiomorpholinyl. The heterocyclic group may be optionally substituted by one or more substituents described herein. "Aryl" refers to monocyclic, bicyclic and tricyclic carbon ring systems containing 6-14 ring atoms, or 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring is aromatic, wherein each ring contains 3-7 ring atoms, and has one or more points of attachment to the rest of the molecule. The term "aryl" can be used interchangeably with the term "aromatic ring". Examples of aryl groups can include phenyl, naphthyl and anthracene. The aryl groups can be independently optionally substituted with one or more substituents described herein. "Heteroaryl" means monocyclic, bicyclic and tricyclic ring systems containing 5-12 ring atoms, or 5-10 ring atoms, or 5-6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring contains 5-7 atoms and has one or more points of attachment to the rest of the molecule. The term "heteroaryl" can be used interchangeably with the terms "heteroaromatic ring" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, the 5-10 atom heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from O, S and N, wherein the nitrogen atom can be further oxidized. Examples of heteroaryl groups include, but are not limited to, furanyl, imidazolyl (e.g., N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), isoxazolyl, oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), pyrrolyl (e.g., N-pyrrolyl), 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5-triazinyl; also includes the following bicyclic rings, but are by no means limited to these bicyclic rings: benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl (e.g., 2-indolyl), purinyl, quinolyl (e.g., 2-quinolyl, 3-quinolyl, 4-quinolyl), 1,2,3,4-tetrahydroisoquinolyl, 1,3-benzodioxolyl, indolinyl, isoquinolyl (e.g., 1-isoquinolyl, 3-isoquinolyl or 4-isoquinolyl), imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl and [1,2,4]triazolo[1,5-a]pyridinyl, and the like. "Spiro" means a 5 to 20-membered polycyclic group in which saturated or partially unsaturated monocyclic rings share a carbon atom (called a spiro atom), and may contain 0 to 5 heteroatoms. Preferably, it is 6 to 14 members, more preferably 8 to 13 members, and more preferably 8 to 10 members. Unless otherwise specified, the spiro group is optionally substituted by one or more substituents as described in the present invention. Non-limiting examples include: etc. "Bridged bicyclic" means a saturated or partially unsaturated bicyclic system with at least one bridge, which may contain 0 to 5 heteroatoms. "Bridge" is an atom that is not branched or connects two bridgeheads or a valence bond, wherein "bridgehead" is any skeleton atom of a ring system bonded to three or more skeleton atoms (except hydrogen). In certain embodiments, the bridged bicyclic group has 5-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. This type of bridged bicyclic group is well known in the art, wherein each group is connected to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, the bridged bicyclic group is optionally substituted by one or more substituents as described in the present invention. Additionally or alternatively, any substitutable nitrogen of the bridged bicyclic group is optionally substituted. Its non-limiting examples include: etc. "Heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus or silicon (including any oxidized form of nitrogen, sulfur, phosphorus or silicon; the quaternized form of any basic nitrogen; a substitutable nitrogen of a heterocycle, such as N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+ (as in N-substituted pyrrolidinyl). "Halogen" refers to F, Cl, Br or I. "Deuterium" means heavy hydrogen, D. "Alkyl" refers to a straight or branched chain saturated hydrocarbon group consisting of several carbon atoms. "Alkenyl" refers to a straight or branched hydrocarbon group consisting of multiple carbon atoms containing at least one carbon-carbon double bond, which may be located at any position of the group. "Alkylene" means a saturated divalent hydrocarbon radical derived from a straight or branched chain saturated hydrocarbon by eliminating two hydrogen atoms. "Alkoxy" means a linear or branched monovalent residue of the formula -OR, wherein R is an alkyl group as defined above. "Haloalkyl" or "haloalkoxy" means an alkyl or alkoxy group substituted with one or more halogen atoms. "Hydroxyalkyl" means an alkyl group substituted with one or more hydroxy groups. As used herein, a substituent is connected to a ring by a bond to form a ring system, which means that the substituent can be substituted at any substitutable position on the ring. For example, formula (a) means that the substituent R can be substituted mono- or poly-substituted at any substitutable position on the pyridine ring. As used herein, a wavy line intersecting a bond in a chemical structure represents the point in the chemical structure at which the atom to which the wavy bond is attached is attached to the rest of the molecule or to the rest of a fragment of a molecule. As used herein, a ring system formed by a linker attached to a ring (as shown in formula b) represents that the linker can be attached to the rest of the molecule at any available position on the ring system. Formula b represents that any available position on the octahydrocyclopenta[c]pyrrole ring can be attached to the rest of the molecule. The order in which chemical groups are written or named does not indicate or imply directionality unless required chemically or structurally. If there is a discrepancy between the structure and the name, the structure shall prevail. General synthesis process The compounds of the present invention can be prepared by a variety of synthetic methods well known to those skilled in the art, including the specific embodiments listed below, embodiments formed by combining them with other chemical synthesis methods, and equivalent substitutions well known to those skilled in the art. Preferred embodiments include but are not limited to the embodiments of the present invention. The present invention uses the following abbreviations: mg milligram mmol millimole DIEA N,N-DiisopropylethylamineDMF N,N-Dimethylformamide HATU 2-(7-azabenzotriazole) ((2-( ... min minute wt% mass percentage DCM Dichloromethane ACN, MeCN Acetonitrile PE Petroleum ether EA Ethyl acetate MeOH Methanol Pd / C Palladium on carbon THF Tetrahydrofuran TBSCl tert-Butyldimethylsilyl chloride TFA Trifluoroacetic acid MsCl Methanesulfonyl chloride ppm per million TMS Tetramethylsilane DMSO Dimethyl sulfoxide TPSA p-Toluenesulfonic acid LDA Lithium diisopropylamide (Boc)2O Di-tert-butyl dicarbonate TEA Triethylamine LAH Lithium aluminum hydride DMAP 4-Dimethylaminopyridine TBAF Tetrabutylammonium fluoride Pd(PPh3)2Cl Bis(triphenylphosphine)palladium(II) chlorideEtOH Ethanol t-BuOK Potassium tert-butoxide AcOH Acetic acid t-BuONa Sodium tert-butoxide Unless otherwise specified, the raw materials, reagents, etc. used in the following examples are derived from commercially available or known synthetic routes in the literature. The equipment and testing conditions are described as follows: 1 H NMR spectra were recorded using a Bruker 500 MHz NMR spectrometer. 1H NMR spectra were recorded using CDCl3, DMSO-d6, CD3OD or acetone-d6 as solvents (in ppm) and TMS (0 ppm) or chloroform (7.26 ppm) as a reference standard. When multiple peaks appear, the following abbreviations are used: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broadened), brs (broadened singlet), dd (doublet of doublets), dt (doublet of triplets). The coupling constant, J, is expressed in Hertz (Hz). The determination conditions of low-resolution mass spectrometry (MS) data were: Agilent G6125C quadrupole HPLC-MS (chromatographic column model: XBridge BEH C18, 4.6 x 50 mm, 2.5 microns, 6 min, flow rate of 1 mL / min. Mobile phase: 0%-95% (ACN) in (H2O containing 0.1% formic acid: ACN = 90:10), using electrospray ionization (ESI), at 210 nm / 254 nm, with DAD detection. The compounds were named according to conventional nomenclature in the art or using software, and commercially available compounds were named according to the supplier's catalog name. DETAILED DESCRIPTION The examples provide the preparation of representative compounds represented by formula (I) and related structural identification data. It must be noted that the following examples are only used to illustrate the present invention and are not intended to limit the present invention. Synthesis of intermediates Intermediate 1 (M1): Step 1: M1-1 (preparation process refers to the preparation method of Example 142 of WO2017108723A2) (58 mg, 0.16 mmol) was placed in a 50 mL single-mouth bottle, and 4-hydroxymethylpiperidine (37 mg, 0.33 mmol), potassium carbonate (57 mg, 0.41 mmol), and ACN (1 mL) were added respectively, and heated to an external temperature of 60°C for 1 h. The reaction solution was filtered to obtain a filtrate, the residue was dissolved in water (5 mL), and EA (5 mL×2) was added for extraction, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by column chromatography, PE:EA=92:8~60:40, to obtain an orange solid M1-2 (54 mg, yield: 76.0%). ESI-MS (m / z): 448.4 [M+H] + . 1 H NMR (500MHz, DMSO-d6) δ7.81 (s, 1H), 6.61 (s, 1H), 4.45 (t, J = 5.1Hz, 1H), 3.57–3.48 (m, 2H),3.41–3.32(m,2H),3.14(d,J=12.0Hz,2H),3.01(s,2H),2.74(t,J=11.5H z,2H),1.83–1.65(m,7H),1.53–1.44(m,1H),1.41(s,9H),1.32–1.20(m,3H). Step 2: M1-2 (54 mg, 0.12 mmol) and Pd / C (10 wt%) (15 mg) were placed in a 50 mL single-mouth bottle, methanol (10 mL) was added, and hydrogen was replaced 3 times with a hydrogen balloon and the hydrogen atmosphere was maintained, and the reaction was carried out at an external temperature of 35°C for 2 h. The reaction solution was filtered through diatomaceous earth to remove Pd / C, and washed with MeOH (20 mL) until the filter cake was colorless, the organic phases were combined, and MeOH was removed by distillation under reduced pressure to obtain a gray solid M1-3 (45 mg, yield: 89.6%). ESI-MS (m / z): 418.5 [M+H] + . 1 H NMR (500MHz, CDCl3) δ6.63 (s, 1H), 6.56 (s, 1H), 3.73 (s, 2H), 3.60 (d, J = 6.2Hz, 2H), 3.42 (t, J = 10.7Hz, 2H), 3.21(d,J=11.3Hz,2H),2.92(s,2H),1.96–1.82(m,5H),1.75–1.60(m,4H),1.57–1.50(m,2H),1.50(s,9H). Step 3: M1-3 (320 mg, 0.82 mmol), pyrazole [1,5-a] pyrimidine-3-carboxylic acid (134 mg, 0.82 mmol), HATU (375 mg, 0.99 mmol), DIEA (531 mg, 4.11 mmol) were placed in a 50 mL single-mouth bottle, DCM (18 mL) was added, and the mixture was stirred at room temperature for 2 h. DCM (20 mL) and water (15 mL) were added to the reaction solution, and the mixture was allowed to stand for separation after sufficient stirring. The organic phase was dried over anhydrous sodium sulfate, spin-dried, and separated by column chromatography. The eluent was: DCM: MeOH = 100: 0 to 98: 2, and a brown slurry M1 (417 mg, yield: 95.0%) was obtained. ESI-MS (m / z): 563.3 [M+H] + . 1 H NMR(400MHz, CDCl3)δ10.51(s,1H)8.75-8.87(m,3H)8.33-8.43(m,1H)7.03(dd, J=6.97,4.16Hz,1H)6.71(s,1H)3.68-3.82(m,2H)3.64(d,J=5.13Hz,2H)3.42(br t,J=10.33Hz,2H)3.16(br d,J=6.60Hz,2H)3.02(s,2H)2.73(br s,2H)1.92(br d,J=13.33Hz,2H)1.70-1.86(m,7H)1.49(s,9H). Intermediate 2 (M2): M1-3 (1.43 g, 3.43 mmol), furan[3,2-b]pyridine-3-carboxylic acid (0.61 g, 3.77 mmol), DIEA (1.7 mL, 10.27mmol), HATU (1.56g, 4.11mmol) were placed in a 100mL single-mouth bottle, anhydrous DMF (10mL) was added, nitrogen was replaced, and the reaction was stirred at room temperature for 3h. Water (80mL) was slowly added dropwise to the reaction solution, and stirred for 30min after the addition. The aqueous phase was poured out, and the aqueous phase was extracted with EA (100mL). After separation, the EA phase was poured into the remaining sticky product mass in the reaction bottle, stirred until completely dissolved and clarified, and then washed with saturated brine (20mL×3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The column chromatography separation was performed with the eluent: DCM:MeOH=100:0~95:5 to obtain a brown solid M2 (1.34g, yield: 69.8%). ESI-MS (m / z): 563.2 [M+H] + 1 H NMR (400MHz, CDCl3) δ10.97(s,1H),8.68-8.75(m,1H),8.64(s,1H),8.33(s,1H) ),7.86-7.94(m,1H),7.33-7.41(m,1H),6.71-6.79(m,1H),3.69-3.82(m,2H), 3.63(d,J=5.88Hz,2H),3.36-3.49(m,2H),3.14-3.26(m,2H),3.02(s,2H),2.7 6(t,J=10.07Hz,2H),1.92(d,J=13.76Hz,2H),1.69-1.87(m,7H),1.49(s,9H). The following intermediates were prepared by similar methods to the above intermediates M1 and M2: Intermediate 24 (M24): Step 1: M24-1 (5.14 g, 30.00 mmol), M24-2 (3.85 g, 30.00 mmol), p-toluenesulfonic acid (0.86 g, 4.50 mmol) were placed in a 100 mL single-mouth bottle, toluene (80 mL) was added, a water separator was added, the temperature was raised to an external temperature of 135°C, and the mixture was refluxed for 20 h. The mixture was concentrated under reduced pressure, water (40 mL) was added to the residue, and the mixture was extracted with EA (80 mL × 2), the organic phases were combined, and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, and separated by column chromatography, with the eluent being PE:EA=100:0-92:8, to obtain compound M24-3, 5.05 g of a white crystalline solid, with a yield of 59.8%. ESI-MS (m / z): 282.1 [M+H] + . 1 H NMR(500MHz, CDCl3) δ6.67(dd,J=8.5,4.5Hz,1H),6.56(dd,J=8.2,2.4Hz,1H),6.50(td,J=9.6,2 .5Hz,1H),4.19(q,J=7.1Hz,2H),3.77–3.61(m,4H),2.00(t,J=5.4Hz,4H),1.30(t,J=7.1Hz,3H). Step 2: M24-3 (4.57 g, 16.25 mmol) was placed in a 100 mL single-mouth bottle, ethanol (64 mL) was added, ice-cooled, and a solution of NaOH (2.60 g, 64.99 mmol) in water (8 mL) was slowly added. After the addition was complete, the temperature was raised to 80 °C and the reaction was refluxed overnight. The mixture was concentrated under reduced pressure, and DCM (100 mL) and water (40 mL) were added to the residue. After sufficient stirring, the mixture was allowed to stand for separation. The upper aqueous phase was extracted once with DCM (50 mL), and the organic phases were combined and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain compound M24-4, 3.38 g of off-white solid, with a yield of 99.5%. ESI-MS (m / z): 210.0 [M+H] + . 1 H NMR (500MHz, CDCl3) δ6.66 (dd, J=8.5, 4.5Hz, 1H), 6.55 (dd, J=8.3, 2.5Hz, 1H), 6.48(td,J=9.6,2.5Hz,1H),3.12–3.04(m,4H),2.07(s,2H),2.04–1.98(m,4H). Step 3: Place M24-4 (3.00 g, 14.34 mmol) in a 100 mL single-mouth bottle, add DCM (30 mL), cool in an ice bath, slowly dropwise add fuming nitric acid (3 mL), and keep in an ice bath for 2 h after the addition. After the reaction is complete, concentrate under reduced pressure to remove DCM, then heat to a water bath temperature of 60°C and continue to concentrate to remove excess fuming nitric acid. After concentration, compound M24-5 is obtained as a yellow solid, which is directly used in the next step. ESI-MS (m / z): 255.1 [M+H] + . Step 4: The yellow solid M24-5 obtained in step 3 was placed in a 100 mL single-mouth bottle, DCM (50 mL) was added and mixed, cooled in an ice bath, di-tert-butyl dicarbonate (4.69 g, 21.51 mmol) was added, triethylamine (4.35 mg, 43.01 mmol) was slowly added dropwise, and the temperature was naturally raised to react overnight after the addition was completed. Water (30 mL) was added to the reaction solution, and after sufficient extraction, the liquid was allowed to stand for separation, and the upper aqueous phase was extracted once with DCM (30 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation, PE: EA = 100: 0 ~ 85: 15, obtained compound M24-6 off-white solid 4.59 g, yield: 85.3%. ESI-MS (m / z): 299.0 [M-55] + . 1H NMR (500MHz, CDCl3) δ7.50 (d, J = 6.4Hz, 1H), 6.70 (d, J = 10.3Hz, 1H), 3.73–3.59 (m, 4H), 2.03 (t, J = 5.6Hz, 4H), 1.51 (s, 9H). Step 5: M24-6 (354 mg, 1.00 mmol) was placed in a 50 mL single-mouth bottle, potassium carbonate (414 mg, 3.00 mmol), 4-hydroxymethylpiperidine (230 mg, 2.00 mmol), and acetonitrile (10 mL) were added in sequence, and the mixture was heated to an external temperature of 60°C for 1 h. Saturated brine (15 mL) was added to the reaction solution, and the mixture was extracted with EA (30 mL). The organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography. The eluent was PE:EA=100:0-50:50, and 449 mg of compound M24-7 was obtained as an orange-yellow solid. The yield was 100%. ESI-MS (m / z): 450.2 [M+H] + . 1 H NMR (500MHz, CDCl3) δ7.41(s,1H),6.69(s,1H),3.68-3.62(m,4H),3.59(d,J=6.3Hz,2H),3.27(d,J=11.6Hz,2H),2.83(t,J =11.4Hz,2H),2.00(t,J=5.3Hz,4H),1.84(d,J=12.4Hz,2H),1.72-1.64(m,2H),1.55(td,J=12.2,2.8Hz,2H),1.51(s,9H). Step 6: M24-7 (440 mg, 0.98 mmol) was placed in a 50 mL single-mouth bottle, methanol (10 mL) was added, and then 10% palladium carbon (100 mg) was added. The hydrogen balloon was replaced three times and then kept the hydrogen balloon, and the reaction was heated to an external temperature of 35°C for 2 hours until the yellow color completely faded. The reaction solution was filtered through diatomaceous earth, and the filter residue was washed with methanol until the filtrate was colorless. The filtrates were combined and concentrated under reduced pressure to obtain 400 mg of compound M24-8 as a gray-dark green foamy solid with a yield of 97.4%, which was directly used in the next step. ESI-MS (m / z): 420.3 [M+H] + . Step 7: M24-8 (400 mg, 0.95 mmol), pyrazole [1, 5-a] pyrimidine-3-carboxylic acid (156 mg, 0.95 mmol), HATU (435 mg, 1.14 mmol), DIEA (616 mg, 4.77 mmol) were placed in a 50 mL single-mouth bottle, DCM (10 mL) was added, and the mixture was stirred at room temperature for 2 h. DCM (30 mL) and water (15 mL) were added to the reaction solution, and the mixture was allowed to stand for separation after sufficient stirring. The aqueous phase was extracted with DCM (20 mL) in sequence, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography. The eluent was: DCM: MeOH = 100: 0 to 98: 2, and 471 mg of compound M24 as a yellow solid was obtained. The yield was 87.5%. ESI-MS (m / z): 565.3 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.67(s,1H),8.81(d,J=4.5Hz,3H),8.13(s,1H),7.04(dd,J=6.2,4.8Hz,1H),6.80(s,1H),3.72–3 .58(m,6H),3.20-3.05(m,2H),2.85-2.70(m,2H),2.05-1.92(m,4H),1.90-1.76(m,4H),1.75-1.55(m,4H),1.51(s,9H). Intermediate 25 (M25): Intermediate 25 (M25) was synthesized in a similar manner to Intermediate 24 (M24). ESI-MS (m / z): 565.3 [M+H] + . 1 H NMR (500MHz, CDCl3) δ11.12(s,1H),8.72(d,J=4.6Hz,1H),8.63(s,1H),8.12(s,1H),7.90(d,J=8.3Hz,1H),7.38(dd,J=8.3,4.8Hz,1H),6.83 (s,1H),3.70-3.60(m,6H),3.14(d,J=10.5Hz,2H),2.84-2.71(m,2H), 2.05-1.95(m,4H),1.90–1.75(m,4H),1.76–1.63(m,2H),1.51(s,9H). Intermediate 26 (M26): Step 1: LDA (2.46 mL, 18.6 mmol, 5.29 eq) was added dropwise to a mixture of THF (7 mL) and M26-2 (0.61 g, 2.92 mmol, 0.83 eq) at -72 °C. After the addition of the reaction solution, the mixture was stirred at -72 °C for 1 h before the addition of M26-1 (1.00 g, 3.52 mmol, 1.00 eq) and stirred at room temperature for 16 h. The reaction solution was slowly poured into water (10 mL) and extracted with ethyl acetate (10 mL × 3). The organic phase was washed with brine (10 mL), dried over anhydrous sodium sulfate, and purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100:1 to 10:1). M26-3 (920 mg, 2.22 mmol, yield 63.2%) was obtained as a light yellow viscous oil. ESI-MS (m / z): 313.0 [M-100+1] + . 1 H NMR (400MHz, CDCl3) δ7.54(d,J=8.58Hz,1H),7.48(d,J=2.50Hz,1H),7.17(dd,J=8.58,2.50Hz,1H),4.12-4.29(m,2H),3.10(s,2H),3.01(br s,2H),1.89(br d,J=12.99Hz,2H),1.67(td,J=13.11,4.29Hz,2H),1.47(s,9H). Step 2: M26-3 (200 g, 48.34 mmol, 1.00 eq) was dissolved in a mixed solution of DMA (140 mL) and water (14.0 mL), and TEA (26.9 mL, 193 mmol, 4.00 eq) and 1,1-bis(diphenylphosphino)ferrocenepalladium chloride (3.54 g, 4.83 mmol, 0.10 eq) were added. After replacing the nitrogen, the mixture was heated to 130 °C and reacted for 12 h. Water (150 mL) was added to the reaction solution, and solids precipitated. After filtering out the solids, the filtrate was extracted with ethyl acetate (150 mL × 3), washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by column chromatography (SiO2, petroleum ether / ethyl acetate = 100:1 to 10:1). M26-4 (13.00 g, 31.97 mmol) was obtained as a light yellow solid. Yield: 66.2%. ESI-MS (m / z): 280.1 [M-55] + . Step 3: M26-4 (14.0 g, 41.69 mmol, 1.00 eq) was placed in a 100 mL single-mouth bottle, and DCM (9 mL) was added followed by dioxane hydrochloride solution (20.0 mL, 4 M). The reaction solution was stirred at room temperature for 12 h. The reaction solution was concentrated under reduced pressure and purified by HPLC. M26-5 (2.15 g, 8.97 mmol) was obtained as a light yellow solid. Yield: 21.5%. ESI-MS (m / z): 236.1 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.70(d,J=8.13Hz,1H)7.46(d,J=0.63Hz,1H),7.36(dt,J=8.19,0.78Hz,1H),3.18(dt ,J=13.01,3.63Hz,2H),3.07(s,2H),2.80(td,J=12.41,2.69Hz,2H),1.85-1.93(m,2H),1.30-1.43(m,2H). Step 4: M26-5 (1.00 g, 4.24 mmol, 1.00 eq) was placed in a 100 mL single-mouth bottle, and DCM (7.0 mL) was added. Fuming nitric acid (10 mL, 220.61 mmol, 53 eq) was slowly added dropwise at 0°C. After the addition was complete, the reaction solution was stirred at 0°C for 10 min, then heated to 45°C and continued to stir for 12 h. The reaction solution was concentrated under reduced pressure to obtain M26-6 (1.30 g, 4.63 mmol) as an orange solid. ESI-MS (m / z): 281.0 [M+1] + . Step 5: Dissolve hexahydropyridin-4-ylmethylphenol (4.1 mL, 35.09 mmol, 5.00 eq) in DCM (14 mL), add M26-6 (1.97 g, 7.02 mmol, 1.00 eq), and stir at 25 °C for 2 h. The reaction solution of M26-7 (2.52 g, 7.01 mmol) was used directly in the next step. reaction. ESI-MS (m / z): 360.2 [M+1] + . Step 6: Boc anhydride (4.5 mL, 21.03 mmol, 3.00 eq) was directly added to the reaction solution of the previous step, and stirred at 25°C for 12 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 5:1 to 0:1) to obtain M26-8 (1.58 g, 3.09 mmol) as a yellow solid. Two-step yield: 44.1%. ESI-MS (m / z): 460.2 [M+1] + . Step 7: THF (20 mL) was added to a 250 mL single-mouth bottle, wet palladium carbon (1.1 g, 10.34 mmol, 3.01 eq) was added under argon protection, M26-8 (1.58 g, 3.44 mmol, 1.00 eq) was dissolved in THF (20 mL) and added to the above reaction solution, and the reaction solution was stirred at room temperature for 3 h under hydrogen (15 psi) pressure. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to obtain M26-9 (1.50 g, 3.32 mmol, yield 96.5%) as an off-white solid. ESI-MS (m / z): 430.3 [M+1] + . Step 8: M26-9 (1.50 g, 3.32 mmol, 1.0 eq) and furano[3,2-b]pyridine-3-carboxylic acid (569 mg, 3.49 mmol, 1.0 eq) were added to a 100 mL single-mouth bottle, and DMF (10 mL), DIEA (1.2 mL, 6.98 mmol, 2.0 eq), HATU (1.46 g, 3.84 mmol, 1.10 eq) were added, and the reaction solution was stirred at 25° C. for 2 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 3:1-1:2) to obtain M26 (1.90 g, 2.24 mmol, yield 64.2%) as a white solid. ESI-MS (m / z): 575.3 [M+1] + . 1H NMR (400MHz, CDCl3) δ10.92 (s, 1H), 8.84 (s, 1H), 8.68 (dd, J = 4.77, 1.19Hz, 1H), 8.63 (s, 1H),7.90(dd,J=8.40,1.13Hz,1H),7.38(dd,J=8.40,4.83Hz,1H),7.21(s,1H),4.14(br d,J=1.55Hz,2H),3.63(d,J=5.36Hz,2H),3.30(br d,J=11.80Hz,2H),3.01(s,4H),2.72-2.80(m,2H),1.85-1.98(m,3H),1.35-1.55(m,13H),0.99(t,J=7.27Hz,2H). Intermediate 27 (M27): Step 1: M27-1 (0.76 g, 2.49 mmol) (preparation process refers to the synthesis process on pages 309-310 of patent WO2019183367A1) and DCM (6 mL) were placed in a 50 mL single-mouth bottle, TFA (1 mL) was added dropwise, and the reaction was stirred at 25 °C for 1 h. M27-2 was obtained by concentration under reduced pressure, 1.0 g of light yellow solid, and the yield was 181%. ESI-MS (m / z): 222.0 [M+H] + . Step 2: M27-2 (1.0 g, 2.49 mmol) was placed in a 50 mL single-mouth bottle, DCM (12.5 mL) was added to dissolve, ice-cooled, fuming nitric acid (25 mL) was added dropwise, and stirred at 0°C for 10 min, and stirred at room temperature for 1 h. After nitration was completed, it was concentrated under reduced pressure, DCM (8 mL) was added to dissolve, cooled to 0°C, di-tert-butyl dicarbonate (0.81 g, 3.72 mmol) was added, triethylamine (0.75 g, 7.44 mmol) was added dropwise, and stirred at 0°C for 10 min, and then stirred at room temperature for 2 h. At 0°C, saturated ammonium chloride solution (10 mL) and saturated sodium chloride solution (10 mL) were slowly added, extracted with EA (10 mL × 3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography. The eluent was: PE: EA = 100: 0 to 85: 15, and M27-3 was obtained as a white solid of 0.4 g, with a yield of 44.0%. ESI-MS (m / z-100): 267.0 [M+H] + . 1H NMR (500MHz, CDCl3) δ8.52 (d, J = 7.7Hz, 1H), 7.04 (d, J = 10.6Hz, 1H), 4.15 (d, J = 7. 2Hz,2H),3.26(s,2H),2.97(s,1H),2.90(s,1H),2.03–1.97(m,2H),1.51(s,9H). Step 3: M27-3 (400 mg, 1.09 mmol), tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (252 mg, 2.18 mmol), potassium carbonate (377 mg, 2.73 mmol), and acetonitrile (4 mL) were placed in a 10 mL single-mouth bottle and stirred at an external temperature of 60°C for 16 hours. The mixture was concentrated under reduced pressure and purified by column chromatography with the eluent being PE:EA=100:0-60:40 to obtain M27-4 as a yellow solid (300 mg) with a yield of 59.5%. ESI-MS (m / z): 462.2 [M+H] + . 1 H NMR (500MHz, CDCl3) δ8.21 (s, 1H), 6.60 (s, 1H), 4.15 (s, 2H), 3.60 (d, J = 6.2Hz, 2H), 3.47 (d,J=12.8Hz,2H),3.22(s,2H),3.05(t,J=11.8Hz,2H),2.00–1.94(m,2H), 1.88(d,J=12.8Hz,2H),1.84–1.76(m,1H),1.64–1.58(m,4H),1.51(s,9H). Step 4: M27-4 (2700 mg, 5.85 mol), Pd / C (600 mg) and methanol (100 mL) were placed in a 250 mL single-mouth bottle, hydrogen was replaced, and stirred at room temperature for 5 hours. Filtered and concentrated under reduced pressure to obtain M27-5, 2524 mg of white solid, yield: 100%. ESI-MS (m / z): 432.3 [M+H] + . Step 5: M27-5 (1100 mg, 2.55 mmol), pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (830 mg, 5.1 mmol), HATU (1450 mg, 3.82 mmol), DIEA (1290 mg, 12.75 mmol) and DCM (10 mL) were placed in a 50 mL single-necked bottle and stirred at room temperature for 16 h. Saturated sodium chloride solution (120 mL) was added, extracted with EA (120 mL×3), concentrated under reduced pressure, and purified by column chromatography with an eluent of PE:EA=100:0-50:50 to obtain M27 as a yellow solid (500 mg) with a yield of 34.0%. ESI-MS (m / z): 577.3 [M+H] + . Intermediate 28 (M28): M27-5 (1400 mg, 3.24 mmol), furano[3,2-b]pyridine-3-carboxylic acid (528 mg, 3.24 mmol), HATU (1850 mg, 4.87 mmol), DIEA (1310 mg, 12.98 mmol) and DCM (20 mL) were placed in a 50 mL single-mouth bottle and stirred at room temperature for 16 hours. Saturated sodium chloride solution (120 mL) was added, extracted with EA (120 mL×3), concentrated under reduced pressure, and purified by column chromatography with an eluent of PE:EA=100:0-50:50 to obtain M28 as a yellow solid (900 mg) with a yield of 95.3%. ESI-MS (m / z): 577.2 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.59(s,1H),8.59(s,1H),8.55(d,J=4.7Hz,1H),8.50(s,1H),7.78(d,J =8.4Hz,1H),7.26(dd,J=8.3,4.8Hz,1H),6.74(s,1H),4.10–3.99(m,2H),3.48(d,J=5.0Hz,2H) ,3.25(d,J=11.6Hz,2H),3.10–3.04(m,2H),2.63(t,J=10.8Hz,2H),1.89–1.86(m,1H),1.83(d d,J=12.9,4.1Hz,2H),1.71(d,J=10.0Hz,2H),1.60(d,J=7.4Hz,2H),1.48(s,2H),1.38(s,9H). Intermediate 29 (M29): The preparation process refers to patent WO2021247897A1

[0443] Synthesis of Intermediate HP. Intermediate 30 (M30): The preparation process refers to the synthesis of B32-2 on page 573 of patent WO2020206424 A1. Intermediate 31 (M31): Its salt type The preparation process refers to the synthesis of intermediate APT on page 90 of patent WO2021247899A1. Intermediate 32 (M32): The preparation process refers to the preparation method of intermediate WW on page 195 of patent WO2021158634A1. Intermediate 33 (M33): Step 1: M33-1 (30.0 g, 174 mmol) was placed in a 1L three-necked flask and tetrahydrofuran (300 mL) was added. The reaction solution was cooled to 0°C, and a tetrahydrofuran solution of lithium aluminum hydride (105 mL, 261 mmol, 2.5 M) was slowly added dropwise at 0°C. After the addition was complete, the reaction was stirred overnight at 25°C. The reaction solution was cooled to 0°C, and sodium sulfate decahydrate was slowly added under an ice bath for quenching. The quenching process lasted for half an hour. After sufficient quenching, the reaction solution was filtered, and the mother liquor obtained by filtration was concentrated under reduced pressure. M33-2 (22.0 g, 169 mmol) was obtained as a white solid. Yield: 97.0%. ESI-MS (m / z): No MS response. 1 H NMR(400MHz,CD3OD)δ3.64-3.42(m,1H),3.36-3.34(m,2H),2.03-1.90(m,2H) ,1.87-1.76(m,2H),1.45-1.33(m,1H),1.30-1.16(m,2H),1.06-0.92(m,2H). Step 2: M33-2 (43.5 g, 334.13 mmol) was dissolved in DCM (400 mL) solution, and chlorodimethyl (2-methylprop-2-yl) silane (57.9 mL, 334.13 mmol, 1.00 eq), TEA (35.5 g, 350.83 mmol, 1.05 eq) and DMAP (0.41 g, 3.34 mmol, 0.01 eq) were added to the reaction solution, and the reaction solution was stirred at 25 ° C for 12 h. Water (400 mL) was added to the reaction solution, and the aqueous phase was extracted with DCM (400 mL × 3) and the combined organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 10: 1-1: 1). M33-3 (63.0 g, 257.72 mmol, yield 77.1%) was obtained as a light yellow oil. ESI-MS (m / z): No MS response. Step 3: M33-3 (15.25 g, 62.38 mmol) was dissolved in THF (150 mL) solution, the reaction solution was cooled to 0 ° C, and NaH (3.74 g, 93.58 mmol, 1.5 eq) was slowly added under nitrogen protection. After the addition, the reaction solution was stirred at 0 ° C for 30 min, and then bromopropyne (8.1 mL, 74.86 mmol, 1.2 eq) was added to the above mixed reaction solution, and the reaction solution was stirred at 25 ° C for 12 h. The reaction solution was cooled to 0 ° C, and water was slowly added to the reaction solution to quench NaH. After quenching, it was extracted with ethyl acetate (200 mL × 3), the organic phase was backwashed once with saturated brine (300 mL) and dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA = 10: 1-5: 1). M33-4 (5.33 g, 18.87 mmol, 30.2%) was obtained as a yellow oil. ESI-MS (m / z): No MS response. Step 4: Place M33-4 (40.6 g, 143.72 mmol) in a 1 L single-necked bottle, add THF (400 mL), cool to 0°C, add TBAF (287.4 mL, 287.43 mmol), stir at room temperature overnight, concentrate the reaction solution under reduced pressure, and purify by column chromatography (PE / EA=10 / 1-2 / 1) to obtain M33-5 (25 g, 148.60 mmol) as a brown oil. ESI-MS (m / z): No MS response. 1H NMR (400MHz, DMSO-d6) δ4.17(d,J=2.38Hz,2H),3.34-3.39(m,2H),3.24(br t,J=5.57Hz,2H),2.54(br s,1H),1.97-2.07(m,3H),1.72-1.85(m,2H),1.27-1.42(m,1H),1.06-1.18(m,2H),0.84-1.00(m,2H). Step 5: M33-5 (6 g, 35.66 mmol, 2.0 eq) was placed in a 100 mL single-mouth bottle, and DMF (60 mL) and M29 (6.03 g, 17.83 mmol) were added. Cesium carbonate (11.62 g, 35.66 mmol, 2.0 eq) and bistriphenylphosphine palladium dichloride (1.39 g, 1.78 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100 ° C for 2 h under nitrogen protection. Tetrahydrofuran (150 mL) was added to the reaction solution, and the mixture was filtered after stirring for 1 h. The filter cake was rinsed with THF (50 mL × 2), and the filtrate was concentrated under reduced pressure and purified by column chromatography (petroleum ether: tetrahydrofuran = 3:1-1:2) to obtain M33-6 (2.37 g, 5.57 mmol, yield 31.2%) as a yellow solid. ESI-MS (m / z): 426.3 [M+1] + . 1 H NMR (400MHz, DMSO-d6) δ11.15(s,1H),7.18(d,J=7.8Hz,1H),7.12(d,J=7.7Hz,1H),7.04(t,J=7.8Hz ,1H),5.41(dd,J=12.6,5.3Hz,1H),4.47(s,2H),4.41(t,J=5.3Hz,1H),3.65(s,3H),3.43(td,J=10.7 ,5.3Hz,1H),3.21(t,J=5.7Hz,2H),2.97–2.82(m,1H),2.71(ddd,J=35.6,22.0,10.6Hz,2H),2.05(d, J=11.3Hz,3H),1.76(d,J=12.2Hz,2H),1.36–1.25(m,1H),1.20–1.09(m,2H),0.92(q,J=11.0Hz,2H). Step 6: M33-6 (0.70 g, 1.65 mmol) was dissolved in DCM (10.0 mL), the reaction solution was cooled to 0°C, and Dess-Martin (1.05 g, 2.47mmol, 1.50eq) was added to the above reaction solution, and the reaction was stirred at room temperature for 12h after the addition was completed. Saturated sodium bicarbonate aqueous solution was added to the reaction solution to quench the Dess-Martin oxidant, filtered through diatomaceous earth, and the filtrate was extracted with DCM (20.0mL×3). The combined organic phase was backwashed with saturated brine (30mL) and then dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (PE / EA=1:1-1:5) to obtain M33 (340mg, 0.80mmol, yield 48.8%) as a light yellow solid. ESI-MS (m / z): 424.1 [M+1] + . 1 H NMR (400MHz, CDCl3) δ9.59(s,1H),8.08(s,1H),7.10(d,J=7.9Hz,1H),6.92(t,J=7.9Hz,1H),6.69(d,J=7.9Hz,1H),5.13(dd,J=12.5, 5.3Hz,1H),4.39(s,2H),3.71(s,3H),3.51–3.41(m,1H),2.91–2.60(m,3H),2.24–2.12(m,2H),2.11–1.98(m,4H),1.40–1.26(m,4H). Intermediate 34 (M34): Intermediate 34 (M34) was synthesized using (1s, 4s)-ethyl 4-hydroxycyclohexanecarboxylate as the starting material using the same synthetic method as intermediate 33 (M33). ESI-MS (m / z): 424.2 [M+1] + . 1 H NMR (400MHz, CDCl3) δ9.65 (s, 1H), 8.12 (br s,1H),7.17(d,J=7.88Hz,1H),6.94-7.04(m,1H),6.73-6.82(m,1H),5.20(dd,J=12.57,5.32Hz,1H),4.39- 4.45(m,2H),3.75-3.82(m,4H),2.67-2.96(m,3H),2.15-2.35(m,2H),1.87-2.09(m,4H),1.62-1.76(m,4H). Intermediate 35 (M35): Step 1: 3-Bromo-2-fluorobenzonitrile (100g, 500mmol) was placed in a 2L three-necked round-bottom flask and ethanol (700mL) was added. Methylhydrazine (267.8mL, 1999.90mmol, 4eq, 40% aqueous solution) was slowly added dropwise to the above reaction solution. After the addition was complete, the reaction temperature was raised to 80°C and stirred overnight. The reaction solution was vacuum concentrated, water (500mL) was added, and ethyl acetate (500mL×3) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography. The eluent was: PE:EA=5:1~1:1. M35-1 (51.0g, 225.58mmol) was obtained as a yellow solid. Yield: 45.1%. ESI-MS (m / z): 226.0 [M+1] + . 1 H NMR (400MHz, DMSO-d6) δ7.72(dd,J=0.8,7.9Hz,1H),7.48(dd,J=0.8,7.4Hz,1H),6.82(t,J=7.7Hz,1H),5.59(s,2H),4.01(s,3H). Step 2: DBU (33.7 mL, 225.58 mmol) and lactic acid (16.9 mL, 225.58 mmol) were mixed in an equimolar mixture in a 100 mL round-bottom flask, and the reaction was stirred at 25°C overnight. Ethyl acrylate (184.1 mL, 1691.88 mmol, 7.5 eq) and M35-1 (51.0 g, 225.58 mmol, 1 eq) were placed in a 1 L round-bottom flask, and an equimolar mixture of lactic acid (16.9 mL, 225.58 mmol) and DBU (33.7 mL, 225.58 mmol) was added, and stirred at 80°C for 120 h. Water (500 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography. The eluent was: PE:EA=10:1-3:1. M35-2 (30.0 g, 91.97 mmol) was obtained as a brown oil with a yield of 40.8%. ESI-MS (m / z): 326.0 [M+1] + . Step 3: M35-2 (30.0 g, 91.97 mmol, 1 eq) was placed in a 500 mL round-bottom flask, glacial acetic acid (120 mL) was added, and then potassium cyanate (10.9 mL, 275.91 mmol, 3 eq) was added to the above reaction solution. After the addition was completed, the reaction was stirred at 25 ° C overnight. The reaction solution was concentrated under reduced pressure to remove AcOH, water (100 mL) was poured into the reaction system, and ethyl acetate (100 mL × 3) was extracted. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography. The eluent was: DCM: MeOH = 30: 1 to 20: 1. M35-3 (14.0 g, 37.92 mmol) was obtained as a brown solid. Yield: 41.2%. ESI-MS (m / z): 369.0 [M+1] + . Step 4: M35-3 (5.00 g, 13.54 mmol, 1.0 eq) was placed in a 100 ml round bottom flask and added to an acetonitrile (25.0 mL) solution, then benzyltrimethylammonium hydroxide (3.7 mL, 20.31 mmol, 1.5 eq, 40 wt.% methanol solution) was added dropwise to the above mixed reaction solution, and the reaction was stirred at 25 ° C for 45 minutes. Water (50 mL) was poured into the reaction system, extracted with ethyl acetate (50 mL × 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography, the eluent was: PE: EA = 5: 1 to 1: 1. M35-4 (2.00 g, 6.19 mmol) was obtained as a light yellow solid. Yield: 45.7%. ESI-MS (m / z): 323.0 [M+1] + . Step 5: M35-4 (1.00 g, 3.09 mmol, 1.0 eq) was placed in a 100 ml round bottom flask and DMF (10 mL) was added, followed by tert-butyl 4-(prop-2-yn-1-oxy)piperidin-1-carboxylate (0.89 g, 3.71 mmol, 1.2 eq) and cesium carbonate (2.02 g, 6.19 mmol, 2.0 eq). After the addition was completed, the nitrogen atmosphere was replaced three times and dichlorobis(triphenylphosphine)palladium (II) (0.24 g, 0.31 mmol, 0.1 eq) was added to the above reaction solution. After the addition was completed, the reaction was stirred at 80°C for 2 hours under nitrogen protection. After the reaction solution was vacuum concentrated to remove DMF, water (50 mL) was poured into the reaction system, extracted with ethyl acetate (50 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography. The eluent was: PE:EA=5:1~1:1. M35-5 (130 mg, 0.27 mmol) was obtained as a brown oil. Yield: 8.7%. ESI-MS (m / z): 426.3 [M-55] - Step 6: M35-5 (130 mg, 0.27 mmol, 1.0 eq) was placed in a 50 mL round-bottom flask, and DCM (6.00 mL) was added. After the reaction solution was cooled to 0°C, a hydrochloric acid solution of dioxane (2.00 mL) was slowly added dropwise, and stirred at 25°C for 12 h. The reaction solution was concentrated under reduced pressure to obtain M35 (100 mg, 0.26 mmol) as a brown solid. Yield: 97.1%. ESI-MS (m / z): 382.2 [M+1] + . Intermediate 36 (M36): Step 1: M35-4 (1.00 g, 3.09 mmol) was placed in a 50 mL single-mouth bottle, dioxane (10.0 mL) was added, tributyl-λ4-stannylmethanol (1.49 g, 4.64 mmol, 1.5 eq) was added to the above reaction solution, nitrogen was replaced 3 times, tetrakistriphenylphosphine palladium (0.18 g, 0.15 mmol) was added to the above reaction solution, and the reaction was stirred at 90 ° C for 12 h. Pour water (30.0 mL) into the reaction system, extract with ethyl acetate (30.0 mL × 3), combine the organic phases, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Column chromatography separation, eluent: EA: MeOH = 20: 1 ~ 9: 1. M36-1 (0.1 g, 0.36 mmol, yield 11.8%) was obtained as a light yellow oil. ESI-MS (m / z): 275.2 [M+1] + . Step 2: M36-1 (100 mg, 0.36 mmol) was placed in a 50 mL single-mouth bottle, dichloromethane (10.0 mL) was added, and manganese dioxide (626 mg, 7.20 mmol, 20 eq) was added to the above reaction solution. After the addition was completed, it was stirred at 25°C for 12 h. The reaction solution was filtered, the filter cake was washed with dichloromethane (20.0 mL) for 5 times, and the filtrate was concentrated under reduced pressure. M36 (99 mg, 0.36 mmol, yield 99.7%) was obtained as a yellow solid. ESI-MS (m / z): 273.2 [M+1] +. 1H NMR (400MHz, DMSO-d6) δ10.77-10.45(m,1H),10.28(s,1H),8.05(br dd,J=7.8,11.9Hz,2H),7.35(t,J=7.6Hz,1H),4.29(s,3H),3.94(br t,J=6.4Hz,2H),2.78(br t,J=6.4Hz,2H). Intermediate 37 (M37): Step 1: M37-1 (5.00 g, 34.9 mmol, 1.0 eq) was placed in a 250 mL single-necked bottle, THF (50 mL) and methyl formate (2.73 g, 45.3 mmol, 1.3 eq) were added, and a solution of potassium tert-butoxide in tetrahydrofuran (38.4 mL, 38.4 mmol, 1 M, 1.1 eq), stirred for 2 h, then added n-hexane (40 mL), the system was heated to 10 °C and stirred for 0.1 h, the reaction solution was allowed to stand to precipitate a white solid, filtered and the filter cake was rinsed with a mixed solvent of (THF: Hexane = 1:1), the solid was collected and concentrated under reduced pressure to obtain M37-2 (900 mg, 4.30 mmol, yield 12.3%) as a white solid. 1 H NMR (400MHz, CD3OD) δ5.14-5.37(m,1H),4.74(s,1H),3.63(q,J=7.11Hz,4H),1.12-1.28(m,6H). Step 2: 3-Aminopyrazole-4-carboxylic acid (607 mg, 4.78 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, acetic acid (5.5 mL, 95.56 mmol, 20 eq) was added, and the mixture was stirred at 10 °C for 0.1 h. M37-2 (1000 mg, 4.78 mmol, 1.0 eq) was dissolved in EtOH (16 mL) and added dropwise to the above reaction solution. The mixture was heated to 80 °C and stirred for 2 h. A white solid was precipitated. The solid was collected by filtration and concentrated under reduced pressure to obtain M37 (520 mg, 2.76 mmol, yield 57.8%) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ10.05(d,J=2.03Hz,1H),8.96(d,J=2.03Hz,1H),8.69(s,1H) Intermediate 38 (M38): Step 1: 2-Bromomalonaldehyde (5.86 g, 38.8 mmol, 1.0 eq) was placed in a 100 mL single-necked bottle, EtOH (60 mL) was added, the temperature was raised to 70 ° C, ethyl 5-amino-1H-pyrazole-4-carboxylate (6.02 g, 38.8 mmol, 1.0 eq) and AcOH (28.9 mL, 504 mmol, 13 eq) were added, and the system was stirred at 70 ° C for 0.5 h. The reaction system was placed in an ice bath, and a brown solid gradually precipitated. After filtration, the filter cake was concentrated under reduced pressure to obtain M38-1 (5.80 g, 21.4 mmol, yield: 55.3%) as a brown solid. ESI-MS (m / z): 270.0, 272.0 [M+H] + 1 H NMR (400MHz, DMSO-d6) δ9.76(d,J=2.13Hz,1H),8.91(d,J=2.13Hz,1H),8.61(s,1H),4.30(q,J=7.05Hz,2H),1.31(t,J=7.07Hz,3H) Step 2: M38-1 (1.00 g, 3.70 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, and dioxane (9 mL) and water (1 mL) were added. Methyl trifluoroborate potassium acetate (870 mg, 0.14 mmol, 1.3 eq), Pd(dba)2 (320 mg, 0.56 mmol, 0.15 eq), RuPhos (0.52 g, 1.11 mmol, 0.3 eq) and sodium carbonate (0.59 g, 5.55 mmol, 1.5 eq) were added to the reaction solution and stirred at 110 ° C for 10 h. After the reaction solution was concentrated under reduced pressure, water (30 mL) was added, and ethyl acetate (80 mL × 3) was extracted. The organic phases were combined and anhydrous sulfur was added. The residue was dried over sodium bicarbonate and separated and purified by column chromatography (petroleum ether:ethyl acetate=2:1-0:1) to obtain M38-2 (450 mg, 2.03 mmol, yield: 54.9%) as a light yellow solid. ESI-MS (m / z): 222.1 [M+H] + 1 H NMR (400MHz, DMSO-d6) δ9.12 (s, 1H), 8.83 (d, J = 1.91Hz, 1H), 8.59 (s, 1H), 5.57 (br s,1H),4.63(s,2H),4.30(q,J=7.15Hz,2H),1.31(t,J=7.09Hz,4H). Step 3: M38-2 (370 mg, 1.67 mmol, 1.0 eq) was placed in a 100 mL single-necked bottle, EtOH (5 mL) was added, and a solution of NaOH (100 mg, 2.51 mmol, 1.5 eq) in water (5 mL) was added, and stirred at 50°C for 2 h. Hydrochloric acid (1 M) was added dropwise to the reaction solution until pH = 6, and the mixture was concentrated under reduced pressure to obtain M38 (323 mg, 1.67 mmol) as a light yellow solid, which was directly used in the next step. ESI-MS (m / z): 194.0 [M+H] + . Example Embodiment 1: Step 1: M1 (3 g, 5.33 mmol) was placed in a 250 mL single-mouth bottle, and DCM (15 mL) and HCl in dioxane solution (15 mL, 60.00 mmol) were added, and the reaction was stirred at room temperature for 2 h. The reaction solution was concentrated under reduced pressure, and then saturated sodium bicarbonate aqueous solution (30 mL) was added, stirred for 30 min, and then filtered. The filter cake was washed twice with water, and the filter cake was collected and added with ethyl acetate (15 mL). After stirring for 2 h, it was filtered and the filter cake was collected to obtain compound 1-1 (1.8 g, 3.89 mmol, 73.0%) as a yellow solid. ESI-MS (m / z): 463.2 [M+H] + . Step 2: KOAc (196 mg, 2.00 mmol), 1-1 (232 mg, 0.50 mmol), and tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (114 mg, 0.50 mmol) were placed in a 25 mL single-necked bottle, replaced with nitrogen, and anhydrous DMF (1.5 mL) was added. The mixture was stirred at room temperature for 30 min. Then sodium triacetoxyborohydride (212 mg, 1.00 mmol) was added and the reaction was continued at room temperature with stirring for 2 h. The reaction solution was filtered with a membrane filter and washed with a small amount of DMF. The filtrate was sent to preparative chromatography for purification to obtain compound 1-2 as a gray solid (199 mg). Yield: 59.1%. ESI-MS (m / z): 674.7 [M+H] + . Step 3: 1-2 (199 mg, 0.30 mmol) was placed in a 50 mL single-necked bottle, DCM (10 mL) was added and stirred to dissolve, 4.0 M hydrochloric acid dioxane solution (6 mL) was slowly added, and the mixture was stirred at room temperature for 2 h. The reaction solution was directly concentrated under reduced pressure to obtain compound 1-3 as a brown-yellow solid, which was directly used in the next step. Step 4: M30 (92 mg, 0.25 mmol), 1-3 (172 mg, 0.30 mmol), potassium carbonate (103.82 mg, 0.75 mmol), triethylamine (152 mg, 1.50 mmol) were placed in a 25 mL single-mouth bottle, anhydrous acetonitrile (5 mL) and anhydrous DMF (3 mL) were added, and the mixture was heated to an external temperature of 70°C and reacted overnight after nitrogen replacement. The reaction solution was filtered, and the filtrate was evaporated to remove low-boiling point solvents such as acetonitrile, and the remaining DMF solution was sent to preparative chromatography for purification to obtain Example 1, a light yellow solid of 50 mg, with a yield of 23.6%. ESI-MS (m / z): 845.8 [M+H] + . 1 H NMR(500MHz, CDCl3)δ10.49(s,1H),8.87–8.76(m,3H),8.47(s,2H),8.25(br s,1H),7.04(dd,J=6.9,4.2Hz,1H),6.98(t,J=7.8Hz,1H),6.91(d,J=7.6Hz,1H),6.7 7(d,J=7.7Hz,1H),6.67(s,1H),5.23(dd,J=12.2,5.1Hz,1H),3.81(s,3H),3.71–3.58 (m,4H),3.41–3.29(m,2H),3.17–3.02(m,6H),3.02–2.62(m,10H),3.38–2.21(m,3H), 2.11(d,J=14.0Hz,2H),2.01(t,J=11.3Hz,2H),1.88–1.62(m,9H),1.50–1.34(m,2H). Embodiment 2: Step 1: M3 (1300 mg, 2.43 mmol) was placed in a 100 mL single-necked bottle, DCM (30 mL) was added to dissolve, and 4.0 M 5 mL of dioxane hydrochloride solution was added, and the mixture was stirred at room temperature for 3 h. The reaction solution was directly concentrated under reduced pressure to obtain compound 2-1 as a brown-yellow solid, which was directly used in the next step. Step 2: In a 25 mL single-mouth bottle, KOAc (197 mg, 2.01 mmol), 2-1 (232 mg, 0.50 mmol), 4-(2-oxoethyl)piperidine-1-carboxylic acid tert-butyl ester (114 mg, 0.50 mmol) were mixed in anhydrous DMF (3 mL), stirred at room temperature for 30 min, sodium triacetoxyborohydride (212 mg, 1.00 mmol) was added, and the reaction was continued at room temperature for 2 h. Water (20 mL) was added to the reaction solution, extracted with EA (40 mL × 2), the organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Column chromatography was used for separation, and the eluent was: DCM: MeOH = 100: 0 to 90: 10, to obtain compound 2-2 as a light yellow solid 324 mg, yield: 100%. ESI-MS (m / z): 646.8 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.37 (s, 1H), 8.76 (d, J = 6.3Hz, 1H), 8.72-8.67 (m, 2H), 8.38(s,1H),7.00(dd,J=6.6,4.2Hz,1H),6.59(s,1H),4.10-3.95(m,2H),3.9 1-3.85(m,4H),3.35-2.84(m,12H),2.69-2.57(m,2H),2.28-2.02(m,4H),1.7 5-1.55(m,4H),1.53-1.43(m,1H),1.38(s,9H),1.10(dd,J=20.9,11.6Hz,2H). Step 3: 2-2 (315 mg, 0.49 mmol) was placed in a 50 mL single-mouth bottle, DCM (10 mL) was added to dissolve, 4.0 M hydrochloric acid dioxane solution (2 mL) was slowly added, and the mixture was stirred at room temperature for 3 h. The reaction solution was directly concentrated under reduced pressure to obtain compound 2-3 as a brown-yellow solid, which was directly used in the next step. Step 4: M30 (73 mg, 0.20 mmol), 2-3 (108 mg, 0.20 mmol), potassium carbonate (82 mg, 0.60 mmol), triethylamine (121 mg, 1.19 mmol) were placed in a 25 mL single-mouth bottle, DMF (1 mL) and acetonitrile (5 mL) were added, and the mixture was heated to an external temperature of 50°C and stirred to react overnight. Water (15 mL) was added to the reaction solution, and the mixture was extracted with DCM (40 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and separated by column chromatography. The eluent was: DCM:MeOH=100:0-95:5, and Example 2 was obtained as a light yellow solid of 79 mg, with a yield of 84.5%. ESI-MS (m / z): 817.7 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.37 (s, 1H), 8.76 (dd, J = 6.9, 1.3Hz, 1H), 8.73-8.67 (m, 2H), 8.36 (s, 1H), 8.19 (br s,1H),6.98(dd,J=6.9,4.1Hz,1H),6.88(t,J=7.7Hz,1H),6.82(d,J=7.5Hz,1H),6.67(d,J=7.6Hz,1H),6.59(s,1H),5.14(dd,J=12.1,5.2Hz,1H ),3.95-3.85(m,4H),3.73(s,3H),3.61–3.46(m,2H),2.97(s,2H),2.90 –2.50(m,12H),2.20–1.87(m,4H),1.67–1.48(m,4H),1.36–1.08(m,8H). The following examples were synthesized using a method similar to that of Examples 1 and 2: Embodiment 18: Step 1: 2-1 (218 mg, 0.50 mmol) was placed in a 25 mL single-mouth bottle, anhydrous DMF (6 mL) was added, and the mixture was stirred at room temperature to dissolve, and potassium carbonate (208 mg, 1.51 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (480 mg, 2.01 mmol) were added, and the mixture was heated to an external temperature of 60°C and stirred to react overnight. DCM (50 mL) was added to the reaction solution, and the mixture was washed with water (15 mL), separated, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and separated by column chromatography. The eluent was DCM:MeOH = 100:0 to 90:10, and compound 18-1 was obtained as a light yellow solid of 244 mg, with a yield of 82.0%. ESI-MS (m / z): 593.6 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.36 (s, 1H), 8.74 (dd, J = 7.0, 1.4Hz, 1H), 8.70 (s, 1H) ,8.68(dd,J=3.9,1.4Hz,1H),8.35(s,1H),6.97(dd,J=6.9,4.1Hz,1H),6.60( s,1H),3.95–3.81(m,4H),3.78-3.71(m,2H),2.93(s,2H),2.82(dd,J=12.3, 8.0Hz,4H),2.75-2.50(m,6H),1.95-1.85(m,4H),0.83(s,9H),-0.00(s,6H). Step 2: 18-1 (235 mg, 0.40 mmol) was placed in a 50 mL single-mouth bottle, THF (8 mL) was added, stirred at room temperature to dissolve, cooled in an ice bath, 1.0 M TBAF (0.5 mL, 0.48 mmol) was slowly added, the ice bath was removed after the addition, and the reaction was carried out at 30°C for 4 h. The reaction solution was directly concentrated under reduced pressure and separated by column chromatography, the eluent was: DCM: MeOH = 100: 0 to 90: 10, and compound 18-2 was obtained as a yellow solid 165 mg, yield: 87.0%. ESI-MS (m / z): 479.5 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.38 (s, 1H), 8.76 (dd, J = 7.0, 1.4Hz, 1H), 8.73-8.67 (m, 2H), 8.37 ( s,1H),6.99(dd,J=6.9,4.1Hz,1H),6.61(s,1H),3.94–3.81(m,4H),3.63(t,J=4.9Hz,2H), 2.96(s,2H),2.89–2.79(m,4H),2.76-2.58(m,6H),2.00–1.80(m,4H). Step 3: 18-2 (161 mg, 0.34 mmol) was placed in a 25 mL single-mouth bottle, triethylamine (170 mg, 1.68 mmol) and DCM (8 mL) were added, stirred at room temperature until dissolved, cooled in an ice bath, and MsCl (58 mg, 0.50 mmol) was slowly added. After the addition, the ice bath was removed and the reaction was carried out at room temperature for 3 h. Water (15 mL) was added to the reaction solution, extracted with DCM (30 mL × 2), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain compound 18-3, a light yellow solid of 164 mg, with a yield of 87.6%, which was directly used in the next step. ESI-MS (m / z): 497.4 [M+H] + . Step 4: In a 25 mL single-mouth bottle, M31 (67 mg, 0.17 mmol) was mixed with acetonitrile (3 mL), 18-3 (82 mg, 0.15 mmol) and potassium carbonate (61 mg, 0.44 mmol) were added, and DMF (1 mL) was added, and the mixture was heated to an external temperature of 60°C and stirred to react overnight. The reaction solution was filtered through a membrane filter, and the filtrate was purified by preparative chromatography and freeze-dried to obtain Example 18 as an off-white solid of 74 mg, with a yield of 58.6%. ESI-MS (m / z): 857.7 [M+H] + . Embodiment 19: Step 1: Compound 1-1 (600 mg, 1.30 mmol) and triethylamine (0.4 mL, 2.59 mmol) were added to DMF (8 mL), stirred for 10 minutes, and then 1-bromo-2-chloroethane (923 mg, 6.50 mmol) and sodium bicarbonate (218 mg, 2.59 mmol) were added. The solution was reacted overnight at room temperature, concentrated under reduced pressure, added with water (20 mL), extracted with dichloromethane (20 mL×3), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and silica gel column chromatography (DCM / MeOH=20:1) was performed to obtain compound 19-1, a yellow solid product of 450 mg, with a yield of 66.1%. ESI-MS (m / z): 525.2[M+H] + . Step 2: M31 (40 mg, 0.10 mmol) and triethylamine (20 mg, 0.20 mmol) were added to DMF (5 mL), stirred for 10 minutes, and then 19-1 (50 mg, 0.10 mmol) and sodium bicarbonate (17 mg, 0.20 mmol) were added. The solution was reacted at 50 ° C for 5 h, cooled to room temperature, concentrated under reduced pressure, separated and purified by preparative liquid phase, and lyophilized to obtain Example 19, 6.5 mg of light yellow solid product, with a yield of 7.7%. ESI-MS (m / z): 885.4 [M+H] + . 1 H NMR(400MHz, DMSO-d6)δ11.12(s,1H),10.48(s,1H),9.36(dd,J=7.0,1.6Hz,1H),8.91–8.87(m,1H),8.67(s,1H),8.33(s,1H),7.36–7.30(m ,1H),7.18(d,J=7.8Hz,1H),7.14–7.10(m,1H),7.03(t,J=8.0Hz,1H),6.72(s,1H),5.40(dd,J=12.6,5.4Hz,1H),4.47(s,2H),3.64(s,3H), 3.61–3.52(m,2H),3.44–3.37(m,4H),3.01–2.88(m,5H),2.82–2.56(m,8H),2.46( s,4H),2.22–2.11(m,2H),2.08–1.99(m,1H),1.93–1.68(m,8H),1.64–1.44(m,5H). The following examples were synthesized using a method similar to that of Examples 18 and 19: Embodiment 31: Step 1: 18-3 (82 mg, 0.15 mmol), 2-tert-butyloxycarbonyl-2,7-diazaspiro[3.5]nonane (50 mg, 0.22 mmol), potassium carbonate (61 mg, 0.44 mmol) were placed in a 25 mL single-necked flask, acetonitrile (2 mL) was added, and the mixture was heated to an external temperature of 60°C and reacted overnight. DCM (50 mL) was added to the reaction solution, washed once with water (20 mL), separated, and the organic phase was dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and separated by column chromatography, and the eluent was DCM:MeOH=100:0-90:10 to obtain compound 31-1 as a yellow solid of 85 mg, with a yield of 84.0%. ESI-MS (m / z): 687.6 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.37(s,1H),8.75(dd,J=7.0,1.5Hz,1H),8.73–8.64(m,2H),8.36(s,1H),6.98(dd,J=6.9,4.1Hz,1H),6.60(s,1H),3.92–3 .82(m,4H),3.54(s,4H),2.94(s,2H),2.87–2.80(m,4H),2.71–2.47(m,6 H),2.43–2.11(m,6H),1.98-1.78(m,4H),1.75-1.65(m,4H),1.37(s,9H). Step 2: 31-1 (80 mg, 0.12 mmol) was placed in a 25 mL single-mouth bottle, DCM (5 mL) was added to dissolve, and dioxane hydrochloride solution (1.5 mL) was slowly added dropwise at room temperature. After the addition was complete, the mixture was stirred at room temperature for 2 h. The reaction solution was directly concentrated under reduced pressure to obtain compound 31-2 as a light pink solid, which was directly used in the next step. ESI-MS (m / z): 587.6 [M+H] + . Step 3: M30 (46.84 mg, 0.13 mmol), 31-2 (68 mg, 0.12 mmol), triethylamine (70 mg, 0.70 mmol), potassium carbonate (64 mg, 0.46 mmol) were placed in a 25 mL single-necked flask, and then anhydrous acetonitrile (3 mL) and anhydrous DMF (1 mL) were added, and the mixture was heated to an external temperature of 60°C and stirred to react overnight. DCM (50 mL) was added to the reaction solution, and the mixture was washed once with water (15 mL), and the mixture was allowed to stand for separation. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by preparative thin-layer chromatography to obtain a light yellow solid, which was then purified by preparative liquid phase to obtain Example 31, 15 mg of a light yellow solid, with a yield of 14.6%. ESI-MS (m / z): 858.7 [M+H] + . 1 H NMR (500MHz, CDCl3) δ10.47(s,1H),8.85(dd,J=7.0,1.4Hz,1H),8.81(s,1H),8.79–8.76(m,1H),8.45(s,1H),8.28(br s,1H),7.08(dd,J=6.9,4.2Hz,1H),6.96(dt,J=15.2,7.5Hz,2H),6.75(d,J=7.5Hz,1H),6.69(s,1H),5.22(dd,J=12.3,5.2Hz,1H),4 .03–3.90(m,4H),3.87–3.72(m,5H),3.04-2.96(m,6H),2.96-2.91(m,4H),2.89–2.38(m,12H),2.27–1.96(m,4H),1.92-1.75(m,8H). Embodiment 32: Step 1: Compound 19-1 (60 mg, 0.11 mmol), 2-methylpropan-2-yl 2,7-diazaspiro (3,5) nonane-7-carboxylate (26 mg, 0.11 mmol), triethylamine (23 mg, 0.23 mmol), potassium carbonate (24 mg, 0.17 mmol) were added to DMF (6 mL), respectively, and the solution was reacted at 50 ° C overnight, cooled to room temperature, concentrated under reduced pressure, and purified on a silica gel plate (DCM / MeOH=20:1) to obtain compound 32-1, 50 mg of yellow solid product, with a yield of 61.2%. ESI-MS (m / z): 715.4 [M+H] + . Step 2: Compound 32-1 (50 mg, 0.07 mmol) was added to dichloromethane (5 mL), trifluoroacetic acid (1 mL, 13.46 mmol) was added to the solution, the solution was reacted at room temperature for 2 hours, and concentrated under reduced pressure to obtain compound 32-2, 45 mg of crude oil, which was directly used for Proceed to the next step. ESI-MS (m / z): 615.4 [M+H] + . Step 3: 32-2 (45 mg, 0.07 mmol) was dissolved in anhydrous DMF (6 mL), and triethylamine (15 mg, 0.15 mmol) was added. After the solution was stirred for 5 minutes, glacial acetic acid (41 mg, 0.22 mmol) and M32 (21 mg, 0.07 mmol) were added. The mixture was stirred at room temperature for 30 minutes, and sodium triacetoxyborohydride (6 mg, 0.16 mmol) was added. The solution was reacted overnight at room temperature, concentrated under reduced pressure, prepared and purified (ACN / H2O=1:1) and freeze-dried to obtain Example 32, a light yellow solid product of 8.0 mg, with a yield of 12.3%. ESI-MS (m / z): 886.5 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ11.10(s,1H),10.48(s,1H),9.38–9.33(m,1H),8.92–8.87(m,1H),8.67(s,1H),8.33(s,1 H),7.36–7.31(m,1H),7.06(d,J=8.0Hz,1H),6.95(t,J=7.6Hz,1H),6.86(d,J=7.6Hz,1H),6.72(s,1H),5.37(dd, J=12.6,5.4Hz,1H),4.55(t,J=5.4Hz,1H),3.66(s,3H),3.58(s,2H),3.46–3.37(m,2H),3.04–2.83(m,9H),2.78– 2.54(m,6H),2.48–2.36(m,4H),2.36–2.21(m,5H),2.07–2.07-1.97(m,1H),1.86–1.64(m,7H),1.65–1.45(m,7H). Embodiment 33: Step 1: 2-Methylpropan-2-yl 2,7-diazaspiro(3,5)nonane-7-carboxylate (24 mg, 0.11 mmol) and triethylamine (21 mg, 0.21 mmol) were added to DMF (5 mL). The solution was stirred at room temperature for 5 minutes, and then acetic acid (0.1 mL, 0.31 mmol) and M32 (30 mg, 0.10 mmol) were added. The solution was stirred for 30 minutes, and then sodium triacetoxyborohydride (8 mg, 0.21 mmol) was added. The solution was reacted at room temperature overnight, concentrated under reduced pressure, purified by reverse phase preparative chromatography (ACN / H2O=1:1), and lyophilized to obtain compound 33-1 as a white solid product (40 mg) with a yield of 77.0%. ESI-MS (m / z): 498.3 [M+H] + . Step 2: 33-1 (40 mg, 0.08 mmol) was added to dichloromethane (5 mL), and trifluoroacetic acid (1 mL, 13.46 mmol) was added. The solution was reacted at room temperature for 2 hours and concentrated under reduced pressure to obtain compound 33-2, 45 mg of oily liquid, which was directly used for the next step. ESI-MS (m / z): 398.2 [M+H] + . Step 3: 33-2 (45 mg, 0.11 mmol) and triethylamine (23 mg, 0.23 mmol) were added to DMF (5 mL), and the solution was stirred at room temperature for 10 minutes, and then sodium bicarbonate (29 mg, 0.35 mmol) and 19-1 (60 mg, 0.11 mmol) were added, and the solution was reacted at 50° C. overnight. The mixture was concentrated under reduced pressure, separated and purified by preparative liquid phase (ACN / H2O=1:1), and lyophilized to obtain Example 33, a light yellow solid product of 3 mg, with a yield of 3.0%. ESI-MS (m / z): 886.3 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),10.48(s,1H),9.38–9.33(m,1H),8.91–8.87(m,1H),8.67(s,1H),8.32(s, 1H),7.67–7.49(m,1H),7.35–7.31(m,1H),7.04(d,J=6.8Hz,1H),6.94–6.91(m,1H),6.72(s,1H),5.37(dd,J=12. 4,5.4Hz,1H),4.55(t,J=5.4Hz,1H),3.81–3.77(m,2H),3.65(s,3H),3.39(t,J=5.4Hz,2H),3.02–2.83(m,9H),2 .78–2.54(m,6H),2.47–2.38(s,4H),2.36–2.25(m,5H),2.07–1.96(m,1H),1.84–1.65(m,7H),1.65–1.43(m,7H). Embodiment 34: M33 (1.3 g, 3.07 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, DMA (15 mL), 1-1 (1.42 g, 3.07 mmol, 1.0 eq), potassium acetate (0.60 g, 6.14 mmol, 2.0 eq), sodium triacetoxyborohydride (0.78 g, 3.68 mmol, 1.2 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. After the reaction solution was filtered, it was separated and purified by high performance liquid chromatography to obtain Example 34 (1.34 g, 1.53 mmol, yield 49.7%) as a yellow solid. ESI-MS (m / z): 870.5 [M+1] + . 1H NMR (400MHz, DMSO-d6) δ11.13(s,1H),10.49(s,1H),9.36(dd,J=7.00,1.50Hz,1H),8.90(dd,J=4.13,1.50Hz,1H),8 .68(s,1H),8.34(s,1H),7.31-7.38(m,1H),7.18(d,J=7.75Hz,1H),7.10-7.15(m,1H),6.99-7.09(m,1H),6.73(s,1H ),5.41(dd,J=12.57,5.32Hz,1H),4.55(t,J=5.32Hz,1H),4.47(s,2H),3.65(s,3H),3.37-3.51(m,3H),2.84-3.03( m,5H),2.53-2.78(m,5H),2.32-2.48(m,3H),2.01-2.15(m,5H),1.68-1.87(m,8H),1.42-1.65(m,4H),1.12-1.27(m, 2H), 0.84-0.98 (m, 2H). The examples in the following table were synthesized using a method similar to Example 34: Embodiment 59: Step 1: Dissolve tert-butyl (2-hydroxyethyl)carbamate (5 g, 31.11 mmol) and 3-bromoprop-1-yne (11 g, 93.16 mmol) in tetrahydrofuran (75 mL), add tetrabutylammonium iodide (1.14 g, 3.11 mmol), sodium iodide (465 mg, 3.11 mmol), potassium hydroxide (5.22 g, 93.33 mmol), and stir at room temperature overnight. After the reaction is completed, quench with water, extract with ethyl acetate (50 mL×3), and concentrate the organic phase under reduced pressure. The crude product is separated by column chromatography, eluent: DCM / MeOH (v / v) = 15 / 1, to obtain compound 59-1, 4.6 g of colorless oily liquid, yield: 74.19%. ESI-MS (m / z): 200.2 [M+H] + . Step 2: 59-1 (710 mg, 3.56 mmol) and cuprous iodide (2.68 g, 0.356 mmol), cesium carbonate (3.471 g, 10.68 mmol), bistriphenylphosphine palladium dichloride (125 mg, 0.18 mmol) were added to DMF (30 mL) and dissolved. Under nitrogen protection, the mixture was stirred at 85 ° C overnight. After the reaction was completed, a small amount of water was added to quench the reaction, and ethyl acetate (50 ml × 3) was used for extraction. The organic phase was concentrated under reduced pressure, dried and mixed, and separated by column. The eluent was DCM / MeOH (v / v) = 15 / 1 to obtain compound 59-2 as a light yellow oily product 400 mg, with a yield of 24.69%. ESI-MS (m / z): 457.1 [M+H] + . Step 3: Dissolve 59-2 (200 mg, 0.44 mmol) in dichloromethane (20 mL), add hydrochloric acid-1,4-dioxane solution (4 mL), and react overnight at room temperature. After the reaction is completed, concentrate under reduced pressure, then add dichloromethane (20 mL×3) for extraction, and the organic phase is spin-dried to obtain compound 59-3, a yellow oil product of 120 mg, with a yield of 76.69%. ESI-MS (m / z): 357.1 [M+H] + . Step 4: 59-3 (50 mg, 0.14 mmol) and 19-1 (73 mg, 0.14 mmol) were dissolved in DMF (20 mL), and sodium bicarbonate (17 mg, 1.4 mmol) was added. The reaction was carried out overnight at room temperature under nitrogen protection. After the reaction was completed, the mixture was concentrated under reduced pressure and separated by preparative chromatography with an eluent of ACN:H2O=1:1. The mixture was lyophilized to obtain Example 59 as a white solid (2.4 mg). Yield: 2%. ESI-MS (m / z): 845.3 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.12(s,1H),10.48(s,1H),9.35(d,J=7.2Hz,1H),8.90(d,J=4.2Hz,1H),8.67( s,1H),8.31(s,1H),7.33–7.31(m,4.2Hz,1H),7.16–7.14(m,2H),7.04–6.97(m,1H),6.72(s,1H),5.40–5 .38(m,1H),4.57–4.55(m,1H),4.47(s,2H),3.66(s,3H),3.64–3.60(m,3H),2.91(d,J=10.0Hz,6H),2.7 6(s,2H),2.69–2.60(m,6H),2.48–2.37(m,6H),2.10–1.87(m,2H),1.81–1.66(m,6H),1.62–1.48(m,3H). Embodiment 60: Step 1: Dissolve 59-2 (200 mg, 0.43 mmol) in methanol (40 ml), add Pd / C (60 mg), Pd(OH)2 (60 mg), and stir under a hydrogen balloon overnight. After the reaction is completed, filter and concentrate under reduced pressure to obtain compound 60-1, 200 mg of colorless oily product, yield: 99.0%. ESI-MS (m / z): 461.1 [M+H] + . Step 2: Dissolve 60-1 (200 mg, 0.44 mmol) in dichloromethane (20 ml), add trifluoroacetic acid (4 ml), and react at room temperature for 2 h. After the reaction is completed, extract and separate by spin drying to obtain compound 60-2 as a colorless oily product (120 mg). Yield: 76.9%. ESI-MS (m / z): 361.1 [M+H] + . Step 3: 19-1 (50 mg, 0.14 mmol) and 60-2 (73 mg, 0.14 mmol) were dissolved in DMF (20 mL), and sodium bicarbonate (17 mg, 1.4 mmol) was added. The reaction was carried out overnight at room temperature under nitrogen protection. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain 60 mg of a crude product, which was sent for preparation. The eluent was ACN:H2O=1:1. After freeze-drying, Example 60 was obtained. The product was a white solid of 2.0 mg with a yield of 1.79%. ESI-MS (m / z): 849.0 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.08(s,1H),10.48(s,1H),9.36(d,J=11.0Hz,1H),8.89(d, J=4.2Hz,1H),8.67(d,J=5.2Hz,1H),8.31(s,1H),7.33(d,J=11.4Hz,1H),7.06–6.82 (m,3H),6.71(s,1H),5.47–5.30(m,1H),4.56(d,J=13.2Hz,1H),3.58(s,3H),3.49–3 .45(m,4H),3.01–2.85(m,9H),2.76–2.58(m,10H),2.33(s,2H),2.03–1.42(m,15H). Example 61: Step 1: 2-Fluoro-5-formylbenzoic acid (6.00 g, 35.69 mmol, 1.0 eq) was dissolved in N, N-dimethylformamide (60 mL), HATU (14.93 g, 39.26 mmol, 1.1 eq) and DIEA (14.7 mL, 89.22 mmol, 2.5 eq) were added to activate for 1 h, and then 3-aminohexahydropyridine-2,6-dione (4.57 g, 35.69 mmol, 1.0 eq) was added and stirred at room temperature for 4 h. After the reaction was completed, the reaction system was slowly poured into ice water, stirred while pouring, extracted twice with ethyl acetate, the organic phases were combined and backwashed once with brine, dried over magnesium sulfate, filtered, and the combined filtrate was concentrated. After concentration, solids precipitated, and green solids were obtained by slurrying with ethyl acetate. The filtrate was purified by column chromatography. Compound 61-1 (3.68 g, yield 37.1%) was obtained as a green solid. ESI-MS (m / z): 279.1 [M+H] + 1 H NMR(400MHz,DMSO-d6)δ10.90(s,1H),10.04(s,1H),8.83(br d,J=8.3Hz,1H),8.21(dd,J=2.0,6.9Hz,1H),8.11(ddd,J=2.1,5.0,8.3Hz,1H),7. 57(dd,J=8.7,9.9Hz,1H),4.94-4.69(m,1H),2.92-2.56(m,2H),2.21-1.94(m,2H). Step 2: M2 (1.00 g, 1.78 mmol) was added with dichloromethane (3 mL), and after all was dissolved, 4.0 M hydrochloric acid dioxane solution (7 mL, 28.00 mmol) was slowly added dropwise, and the reaction solution was stirred at 25° C. for 2 h. The reaction solution was concentrated under reduced pressure to obtain compound 61-2 (900 mg, 1.80 mmol) as a light yellow solid. ESI-MS (m / z): 463.3 [M+H] + Step 3: Methanol (3 mL) was added to 61-2 (200 mg, 0.43 mmol), DIEA (0.1 mL, 0.86 mmol, 2.0 eq) was added to the reaction solution, tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (98 mg, 0.43 mmol, 1.0 eq) was added to the reaction, acetic acid was added to adjust the pH to about 5-6, sodium cyanoborohydride (40 mg, 0.64 mmol, 1.5 eq) was added, and the reaction solution was stirred at 25°C for 2 h. The reaction solution was concentrated under reduced pressure, water (15 mL) was added to the obtained oil, and the organic phases were combined and washed with saturated brine (10 mL) after extraction with ethyl acetate (20 mL × 2). The organic phase was dried and concentrated under reduced pressure, and purified by thin layer chromatography (ethyl acetate: methanol = 10:1) to obtain compound 61-3 (197 mg, 0.26 mmol) as a white solid. Yield: 60.3%. ESI-MS (m / z): 674.4 [M+H] + Step 4: Dichloromethane (4 mL) was added to 61-3 (176 mg, 0.26 mmol), and dioxane hydrochloride solution (4 mL, 16.0 mmol) was added to the reaction solution, and the reaction solution was stirred at 25° C. for 1 h. The reaction solution was concentrated under reduced pressure to obtain compound 61-4 (200 mg, 0.35 mmol) as a yellow solid. ESI-MS (m / z): 574.4 [M+H] + Step 5: 61-4 (103 mg, 0.18 mmol, 1.0 eq) was dissolved in methanol (2 mL), DIEA (0.1 mL, 0.36 mmol, 2.0 eq) was added to the reaction solution, 61-1 (50 mg, 0.18 mmol, 1.0 eq) was added to the reaction solution, glacial acetic acid was added to adjust the pH to 5-6, and then sodium cyanoborohydride (17 mg, 0.27 mmol, 1.5 eq) was added, and the reaction solution was stirred at 50°C for 2 h. The reaction solution was concentrated under reduced pressure to remove methanol, and separated and purified by high performance liquid chromatography (formic acid separation). Example 61 (35 mg, 0.04 mmol, yield 21.9%) was obtained as a light yellow solid. ESI-MS (m / z): 836.5 [M+H] + 1 H NMR (400MHz, CD3OD) δ8.78 (dd, J=4.75, 1.13Hz, 1H), 8.73 (s, 1H), 8.43 (br d,J=5.50Hz,2H),8.30(s,1H),8.10(dd,J=8.44,1.06Hz,1H),7.89(dd,J=6.88,1.75Hz,1H),7.60-7.67 (m,1H),7.53(dd,J=8.44,4.82Hz,1H),7.31(dd,J=10.44,8.57Hz,1H),6.78(s,1H),3.93(s,2H),3.52(d,J=5.88Hz,2H),3.37- 3.46(m,2H),3.27-3.30(m,1H),3.06-3.22(m,8H),2.68-2.91(m,4H),2.46-2.57(m,2H),2.01-2.38(m,7H),1.41-1.96(m,13H). Embodiment 62: 61-4 (84.29 mg, 0.15 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, MeOH (2 mL), DIEA (38 mg, 0.29 mmol, 2.0 eq), M36 (40 mg, 0.15 mmol, 1.0 eq), glacial acetic acid was added to adjust pH to 5-6, sodium triacetoxyborohydride (11.08 mg, 0.18 mmol, 1.2 eq) was added, and the reaction solution was stirred at 45° C. for 16 h. The reaction solution was concentrated under reduced pressure and separated and purified by high performance liquid chromatography to obtain Example 62 (5.78 mg, 0.01 mmol, yield 4.7%) as a white solid. ESI-MS (m / z): 830.5 [M+1]+ . 1 H NMR (400MHz, DMSO-d6) δ10.92(s,1H),10.41-10.63(m,1H),8.96(s,1H),8.74(d,J=4.89Hz,1H),8.31(s,1H),8.25(d ,J=8.53Hz,1H),7.52-7.60(m,2H),7.17(d,J=6.40Hz,1H),7.02(t,J=7.40Hz,1H),6.73(s,1H),4.30(s,3H),3.89(br t,J=6.65Hz,2H),3.74(s,2H)2.98(br s,2H),2.94(br d,J=11.54Hz,3H),2.81-2.84(m,2H),2.77(br t,J=6.59Hz,2H),2.64(br t,J=11.17Hz,3H),2.29-2.38(m,4H),1.99(br t,J=10.16Hz,2H),1.49-1.87(m,14H),1.30-1.40(m,3H),1.10(br d,J=9.66Hz,1H). Embodiment 63: Step 1: 5-Bromo-2-fluorobenzoic acid (7.00 g, 31.9 mmol) was placed in a 100 mL three-necked flask, DCM (70 mL) and DMF (0.2 mL, 3.20 mmol) were added, and oxalyl chloride (2.70 mL, 31.9 mmol, 1 eq) was added dropwise at 0°C. After the addition was complete, the mixture was stirred at 0°C for 10 min and the mixture was resumed. Stir at room temperature for 2h. Concentrate under reduced pressure to remove DCM to obtain 5-bromo-2-fluorobenzoyl chloride (7.00g, 29.5mmol) as a yellow oil. Dissolve 3-aminohexahydropyridine-2,6-dione (3.02g, 23.6mmol) in DCM (30mL), add DIEA (12.2mL, 73.7mmol, 3eq), cool to 0°C, add 5-bromo-2-fluorobenzoyl chloride (7.00g, 29.48mmol, 1.25eq) in DCM (40mL) dropwise, return to room temperature and continue stirring for 4h. After the reaction is completed, the reaction solution is directly filtered, the filter cake is rinsed with dichloromethane, and the filter cake is collected to obtain compound 63-1 (5.02g, 15.2mmol, yield 51.7%) as a yellow solid. ESI-MS (m / z): 329.9, 331.9 [M+1] + . 1H NMR(400MHz,DMSO-d6)δ10.90(s,1H),8.75(br d,J=8.2Hz,1H),7.79-7.70(m,2H),7.37-7.28(m,1H),4.85-4.65(m,1H),2.86-2.68(m,1H),2.59-2.52(m,1H),2.18-1.95(m,2H). Step 2: 63-1 (1.00 g, 3.04 mmol) was dissolved in DMF (10 mL), 2-methylpropane-2-yl 4-(prop-2-ynyloxy)piperidin-1-carboxylate (1.09 g, 4.56 mmol, 1.5 eq), cesium carbonate (3.96 g, 12.15 mmol, 4 eq) and CuI (60 mg, 0.30 mmol, 0.1 eq) were added, molecular sieves were added, and Pd(PPh3)Cl2 (60 mg) was added after nitrogen replacement. After nitrogen replacement three times, the reaction was carried out at 80°C for 2 h. The reaction system was poured into water (50 mL), extracted with ethyl acetate (100 mL×2), the organic phases were combined, backwashed once with saturated brine, dried with sodium sulfate, filtered, concentrated under reduced pressure, and purified by column chromatography (PE:EA=20:1-0:1). Compound 63-2 (902 mg, 1.85 mmol, yield 60.9%) was obtained as a brown solid. ESI-MS (m / z): 488.3 [M+1] + . Step 3: Dissolve 63-2 (900 mg, 1.64 mmol) in DCM (8 mL), add HCl / dioxane (2 mL), and stir at room temperature for 4 h. Filter the reaction solution directly, rinse the filter cake with dichloromethane, and collect the filter cake to obtain compound 63-3 (455 mg, 1.17 mmol, yield 71.6%). ESI-MS (m / z): 388.2 [M+1] + . Step 4: 61-2 (300 mg, 0.65 mmol) was placed in a 40 mL single-mouth bottle, MeOH (3 mL) was added, DIEA (0.3 mL, 1.95 mmol, 3 eq) and 2-chloroacetaldehyde (0.2 mL, 1.30 mmol, 2 eq) were added, and glacial acetic acid was added to adjust the pH to 5-6, sodium cyanoborohydride (81.5 mg, 1.30 mmol, 2 eq) was added, and the reaction was stirred at room temperature for 2 h. The reaction solution was directly filtered, and the filter cake was washed with ethyl acetate (5 mL), and the filter cake was collected to obtain compound 63-4 (80 mg, 0.15 mmol, yield 23.5%) as a white solid. ESI-MS (m / z): 525.3 [M+1] + . 1 H NMR(400MHz,CD3OD)δ8.78(dd,J=4.75,1.13Hz,1H),8.73(s,1H),8.29(s,1H),8. 09(dd,J=8.44,1.06Hz,1H),7.52(dd,J=8.38,4.75Hz,1H),6.78(s,1H),3.97(br t,J=6.25Hz,2H), 3.37-3.57(m,6H),3.15(s,2H),3.08(br d,J=11.01Hz,2H),2.66-2.78(m,2H),1.99-2.28(m,4H),1.55-1.88(m,5H). Step 5: 63-3 (35 mg, 0.09 mmol) was placed in a 40 mL single-mouth bottle, DMF (2 mL) was added, and then 63-4 (40 mg, 0.08 mmol), NaHCO3 (13 mg, 0.15 mmol) and TEA (15 mg, 0.15 mmol) and potassium iodide (4 mg, 0.02 mmol) were added to the reaction solution, and the reaction solution was stirred at 60 ° C for 10 h. The reaction solution was concentrated under reduced pressure and purified by high performance liquid chromatography to obtain Example 63 (2.2 mg, yield 3.3%) as a white solid. ESI-MS (m / z): 875.7 [M+1] + . 1 H NMR(400MHz,DMSO-d6)δ10.81-10.95(m,2H),8.95(s,1H),8.66-8.80(m,2 H),8.22-8.34(m,3H),7.50-7.71(m,3H),7.29-7.39(m,1H),6.73(s,1H), 4.70-4.83(m,1H),4.46-4.58(m,1H),4.40(s,2H),2.89-3.01(m,6H),2.5 3-2.77(m,11H),1.97-2.17(m,5H),1.68-1.92(m,9H),1.41-1.64(m,6H). Embodiment 64: Step 1: Dissolve 64-1 (1 g, 3.09 mmol) and Pd(PPh3)4 (0.36 g, 0.31 mmol) in ACN (20 mL), replace nitrogen, add (tributyltin)methanol (1.99 g, 6.19 mmol) dropwise, heat to an external temperature of 90°C and react for 48 hours. After the reaction is completed, concentrate under reduced pressure, add ethyl acetate (20 mL), stir, filter, and concentrate the filter cake under reduced pressure to obtain 3-(4-(hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (400 mg, 1.46 mmol). 3-(4-(Hydroxymethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (400 mg, 1.46 mmol) was placed in a 100 mL single-mouth bottle, DCM (10 mL) and TEA (0.4 mL) were added, MsCl (0.3 mL, 3.65 mmol) was slowly added dropwise at room temperature, and the mixture was stirred for 2 h at room temperature. After the reaction was completed, DCM (50 mL) and water (50 mL) were added, and the mixture was stirred thoroughly and allowed to stand for separation. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography. The eluent was DCM:MeOH = 1:0 to 10:1 to obtain compound 64-2 as a white solid (180 mg). The yield was 21%. ESI-MS (m / z): 293.1 [M+H] + . 1 H NMR(500MHz,DMSO-d6)δ11.13(d,J=10.5Hz,1H),7.96(d,J=4.0Hz,2H),5.69(s,1H),5.16 (dd,J=12.9,5.4Hz,1H),3.32(s,2H),2.92(d,J=17.6Hz,1H),2.66–2.53(m,2H),2.29(s, 1H),2.11–2.04(m,1H),1.24(s,1H). Step 2: 64-2 (105 mg, 0.36 mmol), 1-3 (190 mg, 0.28 mmol), K2CO3 (114.37 mg, 0.83 mmol) and TEA (0.2 mL, 1.66 mmol) were added to acetonitrile (5 mL) and DMF (1 mL), and stirred at 50°C for 12 h. After the reaction was completed, the reaction solution was filtered to remove inorganic salts and purified by preparative liquid chromatography to obtain Example 64 as a light yellow solid (26 mg) with a yield of 11.4%. ESI-MS (m / z): 830.3 [M+H] + . 11H NMR (500 MHz, DMSO-d6) δ 10.96 (s, 1H), 10.47 (s, 1H), 9.34 (d, J = 7.0 Hz, 1H), 8.89 (d, J = 2.7 Hz, 1H), 8.66 (s, 1H), 8.32 (s, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.53 (d, J = 7.4 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.32 (dd, J = 6.9, 4.2 Hz, 1H), 6.71 (s, 1H), 5.12 (dd, J = 13.2, 5.1 Hz, 1H), 4.53–4.47 (m, 2H), 4.39 (d, J = 17.5 Hz, 1H), 3.55 (t, J = 9.0 Hz, 2H), 3.39 (t, J = 5.2 Hz, 2H), 3.25 (s, 1H), 2.97 (s, 2H), 2.92 (d, J = 10.5 Hz, 2H), 2.75 (s, 2H), 2.64 (d, J = 11.1 Hz, 2H), 2.45 (d, J = 4.5 Hz, 1H), 2.43–2.37 (m, 2H), 2.32 (d, J = 7.2 Hz, 2H), 2.05–2.00 (m, 1H), 1.94 (t, J = 11.9 Hz, 2H), 1.79 (s, 2H), 1.72 (d, J = 11.3 Hz, 4H), 1.63 (d, J = 12.4 Hz, 2H), 1.61–1.54 (m, 2H), 1.51 (s, 1H), 1.37 (d, J = 6.6 Hz, 2H), 1.30 (s, 1H), 1.25 (d, J = 11.3 Hz, 2H), 1.14 (d, J = 11.9 Hz, 2H). Example 65: Step 1: Dissolve 65-1 (1.0 g, 3.09 mmol) and Pd(PPh3)4 (0.36 g, 0.31 mmol) in 1,4-dioxane (20 mL), replace nitrogen, add tributyltinmethanol (1.99 g, 6.19 mmol) dropwise, heat to an external temperature of 90°C and react for 48 hours. After the reaction is completed, concentrate under reduced pressure, add ethyl acetate (20 mL), stir, filter, and concentrate the filter cake under reduced pressure to obtain 2-(2,6-dioxyhesperidin-3-yl)-4-(hydroxymethyl)isoindoline-1,3-dione (400 mg, 1.46 mmol). 2-(2,6-dioxyhesperidin-3-yl)-4-(hydroxymethyl)isoindoline-1,3-dione (400 mg, 1.46 mmol) was placed in a 100 mL single-mouth bottle, DCM (10 mL) and TEA (0.4 mL) were added, MsCl (0.3 mL, 3.65 mmol) was added dropwise at room temperature, and the mixture was stirred for 2 h at room temperature. After the reaction was completed, DCM (50 mL) and water (50 mL) were added, and the mixture was stirred thoroughly and allowed to stand for separation. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography. The eluent was DCM:MeOH = 1:0-10:1 to obtain 65-2 as a white solid (180 mg) with a yield of 21%. ESI-MS (m / z): 384.1 [M+18]. Step 2: 65-2 (50 mg, 0.14 mmol), 1-3 (72.31 mg, 0.10 mmol), K2CO3 (43.53 mg, 0.31 mmol), TEA (63 mg, 0.63 mmol), acetonitrile (5 mL) and DMF (1 mL) were added to a 50 mL single-mouth bottle and stirred at 50° C. for 16 h. After the reaction was completed, the mixture was filtered and purified by preparative liquid chromatography to obtain Example 65 as a light yellow solid (20 mg) with a yield of 22%. ESI-MS (m / z): 844.3 [M+H] + . 1H NMR (500MHz, DMSO-d6) δ11.10(s,1H),10.49(s,1H),9.35(d,J=7.0Hz,1H),8.90(d,J=2.7Hz,1H),8.67(s,1H),8.37(s,1 H),7.88(d,J=29.9Hz,3H),7.34(dd,J=6.9,4.2Hz,1H),6.72(s,1H),5.13(d,J=7.3Hz,1H),4.55(d,J=5.1Hz,1H),3.94( s,1H),3.46(d,J=20.4Hz,2H),3.40(t,J=5.1Hz,2H),3.13(s,2H),3.08(d,J=7.0Hz,4H),2.93(d,J=8.4Hz,2H),2.87(d, J=4.8Hz,2H),2.63(s,2H),2.31(s,4H),2.07(s,4H),1.68(dd,J=38.1,13.3Hz,6H),1.53(s,2H),1.19(t,J=7.3Hz,6H). Embodiment 66: Step 1: M33-5 (511 mg, 3.04 mmol, 2.0 eq) was placed in a 40 mL single-mouth bottle, and DMF (5 mL), 63-1 (500 mg, 1.52 mmol), cesium carbonate (990 mg, 3.04 mmol) and bistriphenylphosphine palladium dichloride (118 mg, 0.15 mmol, 0.1 eq) were added. The reaction solution was reacted at 100 ° C for 2 h under nitrogen protection. After the reaction solution was concentrated under reduced pressure, THF (10 mL) was added, stirred for 10 min and filtered, the filtrate was concentrated under reduced pressure, and purified by thin layer chromatography (petroleum ether: tetrahydrofuran = 1:2) to obtain 66-1 (220 mg, 0.53 mmol, yield 34.8%) as a colorless oil. ESI-MS (m / z): 417.3 [M+1] + . Step 2: 66-1 (220 mg, 0.53 mmol) was placed in a 100 mL single-mouth bottle and added with DCM (5 mL), and DMP (336 mg, 0.79 mmol, 1.5 eq) was added at 0°C, and the reaction solution was stirred at room temperature overnight. The reaction solution was added with saturated sodium bicarbonate aqueous solution (10 mL) and stirred for 10 min, extracted with dichloromethane (15 mL×2), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, separated and purified by thin layer chromatography (petroleum ether:THF=1:1), and 66-2 (115 mg, 0.25 mmol, yield 46.5%) was obtained as a white solid. ESI-MS (m / z): 415.2 [M+1] + . 1 H NMR (400MHz, CDCl3) δ9.66 (d, J=0.86Hz, 1H), 8.17 (dd, J=7.34, 2.20Hz, 1H), 8.09 (br s,1H),7.13(dd,J=11.49,8.56Hz,1H),4.75-4.85(m,1H),4.42(s,2H),3. 49-3.57(m,1H),2.70-2.94(m,3H),2.00-2.26(m,6H),1.33-1.43(m,4H). Step 3: 66-2 (40 mg, 0.10 mmol) was placed in a 40 mL single-mouth bottle, DMF (1 mL) and THF (1 mL) were added, 1-1 (89 mg, 0.19 mmol, 2.0 eq) was added, KOAc (19 mg, 0.19 mmol, 2.0 eq) was added at 0°C, the reaction was stirred at room temperature for 0.5 h, sodium triacetoxyborohydride (24 mg, 0.12 mmol, 1.2 eq) was added at 0°C, and the reaction solution was reacted at 0°C for 2 h. The reaction solution was concentrated under reduced pressure and purified by high performance liquid chromatography to obtain Example 66 (28.03 mg, 0.03 mmol, yield 30.5%) as a yellow solid. ESI-MS (m / z): 861.3 [M+1] + . 1 H NMR (400MHz, DMSO-d6) δ10.64-11.06(m,1H),10.49(s,1H),9.35(dd,J=7.00,1.50Hz,1H),8.87-8.93(m,1H),8.73(br d,J=8.38Hz,1H),8.66-8.70(m,1H),8.33(s,1H),7.56-7.79(m,2H),7.29-7.41(m,2H),6.73(s,1H),4 .73-4.81(m,1H),4.54-4.63(m,1H),4.38-4.44(m,2H),2.87-3.05(m,5H),2.75-2.86(m,2H),2.64(br t,J=11.07Hz,3H),2.37(br s,2H),1.98-2.22(m,7H),1.69-1.85(m,8H),1.40-1.64(m,5H),1.10-1.23(m,2H),0.83-0.97(m,2H). Embodiment 67: Step 1: M1-1 (1000 mg, 2.84 mmol), NaOH (283.80 mg, 7.10 mmol), water (5 mL) and DMSO (10 mL) were added to a 50 mL single-mouth bottle and stirred at 70°C for 2 h. After the reaction was completed, ethyl acetate (100 mL) and water (100 mL) were added to the reaction system, extracted, concentrated under reduced pressure, and purified by column chromatography with an eluent of PE:EA=1:0-1:1 to obtain compound 67-1 as a yellow solid of 700 mg. Yield: 70.49%. ESI-MS (m / z): 295.1 [M-55] + . 1 H NMR(500MHz,DMSO-d6)δ7.90(s,1H),6.48(s,1H),3.50(dd,J=11.8,6.7Hz, 2H),3.37(s,2H),3.02(s,2H),1.82–1.72(m,4H),1.44(s,1H),1.41(s,9H). Step 2: 67-1 (650 mg, 1.86 mmol), sodium 2-chloro-2,2-difluoroacetate (850 mg, 5.58 mmol), K2CO3 (897 mg, 6.49 mmol) and DMSO (6.5 mL) were added to a 50 mL single-mouth bottle and stirred at 95°C for 2 h. After the reaction was completed, water (65 mL) was added, and the mixture was extracted with ethyl acetate (65 mL×2), concentrated under reduced pressure, and purified by column chromatography with an eluent of PE:EA=1:0-1:1 to obtain compound 67-2 as a yellow solid (650 mg). Yield: 87.60%. ESI-MS(m / z): No response 1 H NMR(500MHz,DMSO-d6)δ8.01(s,1H),7.43 -7.14(m,1H),6.90(s,1H),3.57–3.53(m,2H),3.36(s,2H),3.12(s,2H),1.84–1.76(m,4H),1.42(s,9H). Step 3: 67-2 (650 mg, 1.62 mmol) was added to methanol (10 mL), palladium carbon (130 mg, 0.162 mmol) was added, and the mixture was stirred at room temperature for 1 h. After the reaction was completed, the mixture was filtered and concentrated under reduced pressure to obtain a black solid (601 mg, 1.62 mmol). The black solid (601 mg, 1.62 mmol), pyrazole [1, 5-a] pyrimidine-3-carboxylic acid (264 mg, 1.62 mmol), N-methylimidazole (465 mg, 5.67 mmol), TCFH (545 mg, 1.94 mmol) and acetonitrile (10 mL) were placed in a 100 mL single-mouth bottle in sequence, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was concentrated under reduced pressure and purified by column chromatography, and the eluent was PE: EA = 1:0 to 1:1 to obtain compound 67-3, a yellow solid of 650 mg. Yield: 59.88%. ESI-MS (m / z): 516.2 [M+H] + . 1 H NMR (500MHz, DMSO-d6) δ10.22(s,1H),9.37(dd,J=7.0,1.4Hz,1H),8.85(dd,J=4.1,1.4Hz,1H),8.69(s,1H),8.29(s,1H),7.33(dd,J=6.9,4.2Hz,1H ),7.43-7.14(t,J,1H),6.78(s,1H),3.54(dd,=11.7,6.5Hz,2H),3.38(s, 2H),3.08(s,2H),1.80(d,J=13.8Hz,2H),1.76–1.70(m,2H),1.42(s,9H). Step 4: Compound 67-3 (500 mg, 0.97 mmol) was dissolved in DCM (10 mL), and a hydrochloric acid solution in dioxane (2 mL) was added dropwise, and the mixture was stirred at room temperature for 1 h. The residue was concentrated under reduced pressure and used directly in the next step to obtain compound 67-4 as a white solid (650 mg). Yield: 124.1%. ESI-MS (m / z): 416.0 [M+H] + . Step 5: 67-4 (166.16 mg, 0.24 mmol), M33 (100 mg, 0.24 mmol), potassium acetate (70 mg, 0.72 mmol), sodium triacetoxyborohydride (99 mg, 0.47 mmol) and DMF (1 mL) were added to a 50 mL single-mouth bottle and stirred at room temperature for 2 h. After the reaction was completed, the mixture was concentrated under reduced pressure and separated by HPLC to obtain Example 67 as a yellow solid (10 mg). Yield: 5.1%. ESI-MS (m / z): 823.3 [M+H] + . 1 H NMR (500MHz, DMSO-d6) δ11.09(s,1H),10.20(s,1H),9.37(d,J=6.9Hz,1H),8.84(d,J=2.5Hz,1H),8.68(s,1H),8.26(s,1H),7. 42-7.28(m,2H),7.17(d,J=7.5Hz,1H),7.12(d,J=7.4Hz,1H),7.03(t,J=7.8Hz,1H),6.76(s,1H),5.39(dd,J=12.3,5.0Hz,1H) ,4.47(s,2H),3.65(s,3H),3.03(s,2H),2.93–2.87(m,1H),2.70(d,J=12.5Hz,1H),2.64(d,J=17.3Hz,2H),2.12(d,J=6.9Hz,2 H),2.05(d,J=17.6Hz,4H),1.87–1.75(m,6H),1.47(s,2H),1.24(s,2H),1.18(d,J=11.1Hz,2H),0.90(dd,J=24.0,11.6Hz,2H). Embodiment 68: Step 1: M33-5 (520 mg, 3.09 mmol, 2.0 eq) was placed in a 40 mL single-mouth bottle, and DMF (5.0 mL), M35-4 (500 mg, 1.55 mmol, 1.0 eq) and Cs2CO3 (1.08 g, 3.09 mmol, 2.0 eq) were added to the reaction solution, and stirred at 100 ° C for 2 h under nitrogen protection. The reaction solution was concentrated under reduced pressure, THF (300 mL) was added, stirred for 1 h, and then filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 2: 1-1: 2) to obtain 68-1 (200 mg, 0.49 mmol, yield 31.5%) as a light yellow solid. ESI-MS (m / z): 411.1 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.56-7.62(m,2H),7.41-7.46(m,1H),7.02(dd,J=8.11,7.27Hz,1H),4.43(s,2H),4.28(s,3H),3.99-4.06(m,2H ),3.38-3.43(m,2H),2.82(t,J=6.74Hz,2H),2.05-2.14(m,2H),1.73-1.88(m,3H),1.36(s,1H),1.20-1.30(m,2H),0.91-1.02(m,2H). Step 2: 68-1 (200 mg, 0.49 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (5.0 mL) and TEA (148 mg, 1.46 mmol, 3.0 eq) were added. TsCl (186 mg, 0.97 mmol, 2.0 eq) was added to the reaction solution at 0 °C and stirred at room temperature overnight. Water (10.0 mL) was added to the reaction solution, and dichloromethane (10.0 mL × 2) was extracted. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thin layer chromatography separation and purification (petroleum ether: THF = 1: 1) was performed to obtain 68-2 (150 mg, 0.19 mmol, yield 38.9%) as an off-white foamy solid. ESI-MS (m / z): 565.2 [M+1] + . Step 3: 68-2 (40.0 mg, 0.07 mmol, 1.0 eq) was placed in a 40.0 mL single-mouth bottle, and DMA (2.0 mL), 1-1 (32.7 mg, 0.07 mmol, 1.0 eq), NaI (31.8 mg, 0.21 mmol, 3.0 eq), and DIEA (54.9 mg, 0.43 mmol, 6.0 eq) were added, and the reaction solution was stirred at 50° C. for 16 h. The reaction solution was concentrated under reduced pressure and purified by high performance liquid chromatography to obtain Example 68 (32.9 mg, 0.04 mmol, yield 54.3%) as a yellow solid. ESI-MS (m / z): 855.5 [M+1] + . 1H NMR (400MHz, DMSO-d6) δ10.59(br s,1H),10.48(br s,1H),9.34(br d,J=6.38Hz,1H),8.88(br s,1H),8.67(s,1H),8.32(br s,1H),7.69(br d,J=7.88Hz,1H),7.52(br d,J=6.75Hz,1H),7.32(br s,1H),7.11(br t,J=7.32Hz,1H),6.71(br s,1H),4.56(br s,1H),4.52(br s,2H),4.28(br s,3H),3.91(br d,J=5.50Hz,3H),2.86-3.02(m,5H),2.59-2.79(m,5H),2.37(br d,J=1.63Hz,3H),1.99-2.20(m,5H),1.67-1.86(m,8H),1.42-1.61(m,4H),1.13-1.24(m,2H),0.83-0.97(m,2H). Embodiment 69: Step 1: 1-tert-Butyloxycarbonylpiperazine (1g, 5.37mmol) was placed in a 50mL single-mouth bottle, acetonitrile (10mL) was added, sodium carbonate (1.71g, 16.11mmol) was added, and the mixture was stirred at room temperature for 20min, 3-bromopropyne (0.7mL, 8.05mmol) was added, and the mixture was transferred to a 50℃ oil bath and stirred for 4h. EA (10mL) was added to the reaction solution, and saturated ammonium chloride solution (10mL×2) was added for washing, dried over anhydrous sodium sulfate, and purified by column chromatography, with the eluent being PE:EA=95:5~75:25, to obtain 69-1, 672mg of a light yellow oily liquid, with a yield of 56.0%. ESI-MS (m / z): 225.0 [M+H] + . 1 H NMR (500MHz, DMSO-d6) δ3.34–3.31(m,4H),3.28(d,J=2.2Hz,2H),3.14(s,1H),2.41–2.35(m,4H),1.42–1.37(m,9H). Step 2: In a 50 mL single-mouth bottle, M29 (452 ​​mg, 1.34 mmol) was dissolved in DMF (4 mL), and 69-1 (300 mg, 1.34 mmol), triethylamine (406 mg, 4.01 mmol), bistriphenylphosphine palladium dichloride (104 mg, 0.13 mmol), CuI (50 mg, 0.27 mmol) were added to the above mixed reaction solution. After nitrogen replacement 3 times, the reaction was stirred at 80 ° C overnight. DCM (15 mL) was added to the reaction solution, and saturated ammonium chloride solution (15 mL × 2) was added for washing. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography. The eluent was: DCM: MeOH = 100: 0 to 95: 5 to obtain 69-2 as a brown foamy solid 176 mg, yield: 25.9%. ESI-MS (m / z): 482.4 [M+H] + . 1 H NMR (500MHz, CDCl3) δ8.38(s,1H),7.16(d,J=7.8Hz,1H),6.98(t,J=7.9Hz,1H),6.76(d, J=7.8Hz,1H),5.19(dd,J=12.6,5.3Hz,1H),3.76(s,3H),3.66(s,2H),3.56(s, 4H), 2.93 (d, J = 17.2Hz, 1H), 2.86–2.63 (m, 6H), 2.26–2.17 (m, 1H), 1.46 (s, 9H). Step 3: 69-2 (65 mg, 0.13 mmol) was placed in a 50 mL single-mouth bottle, DCM (3 mL) was added to dissolve, 4.0 M hydrochloric acid dioxane solution (0.7 mL) was slowly added dropwise, and the mixture was stirred at room temperature for 1 h. The reaction solution was concentrated under reduced pressure to remove the solvent and hydrogen chloride to obtain 69-3 as a brown solid (72 mg), with a yield of 142.1%. ESI-MS (m / z): 382.3 [M+H] + . Step 4: In a 50 mL single-mouth bottle, add 69-3 (49 mg, 0.13 mmol), tert-butyl bromoacetate (38 mg, 0.20 mmol), DIEA (168 mg, 1.30 mmol) and mix in acetonitrile (2 mL), and stir at room temperature for 5 h. Add DCM (15 mL) to the reaction solution, wash with saturated ammonium chloride solution (15 mL), dry over anhydrous sodium sulfate, and purify by column chromatography. The eluent is: DCM: MeOH = 100: 0 to 95: 5, to obtain 69-4 as a brown solid 38 mg, yield: 59.0%. ESI-MS (m / z): 496.5 [M+H] + . 1 H NMR (500MHz, CDCl3) δ8.02(s,1H),7.08(t,J=10.3Hz,1H),6.94–6.84(m,1H),6.66(d,J=7.8Hz,1H),5.11(dd,J=12.5,5.2Hz,1H),3.7 0(s,3H),3.49(s,2H),3.06(s,2H),2.87(d,J=17.4Hz,1H),2.79–2.54(m,7H),2.15(dd,J=13.7,6.2Hz,1H),1.39(s,9H),1.22(s,2H). Step 5: 69-4 (35 mg, 0.07 mmol) was placed in a 50 mL single-mouth bottle, DCM (2 mL) was added to dissolve, 4.0 M TFA (196 μL, 2.55 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 2 h. The solvent and trifluoroacetic acid were removed by concentration under reduced pressure to obtain 69-5 as a black solid (42 mg), with a yield of 135.3%. ESI-MS (m / z): 440.4 [M+H] + . Step 6: 69-5 (30 mg, 0.07 mmol), 1-1 (32 mg, 0.04 mmol), HATU (39 mg, 0.10 mmol), DIEA (54 mg, 0.42 mmol) were placed in a 25 mL single-mouth bottle, DCM (5 mL) was added, and the mixture was stirred at 25°C for overnight reaction. DCM (10 mL) was added to the reaction solution, and saturated ammonium chloride solution (10 mL) was added for washing. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography to obtain Example 69 as a brown solid (29 mg). Yield: 46.9%. Purity: 97.23%. ESI-MS (m / z): 884.6 [M+H] + . 1H NMR (500MHz, DMSO-d6) δ11.09(s,1H),10.49(s,1H),9.34(d,J=6.9Hz,1H),8.90(d,J=2.7Hz,1H),8.66(s,1H),8.36(s,1H),7.33(dd,J=6.9 ,4.2Hz,1H),7.15(dd,J=15.8,7.7Hz,2H),7.02(t,J=7.9Hz,1H),6.73(s,1H),5.40(dd,J=12.8,5.2Hz,1H),4.53(s,1H),4.07(s,6H),3.84 (s,1H),3.68(s,5H),3.52(s,2H),3.41(s,3H),3.04(s,3H),2.94(d,J=1 0.6Hz, 3H), 2.63 (d, J = 11.4Hz, 4H), 2.08–1.79 (m, 5H), 1.78–1.41 (m, 8H). Embodiment 70: Step 1: M29 (1.00 g, 2.96 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, and DMF (10 mL), N-Boc piperazine (0.83 g, 4.44 mmol, 1.5 eq), sodium tert-butoxide (0.85 g, 8.87 mmol, 3.0 eq) and palladium catalyst (CAS: 1814936-54-3) (29 mg, 0.03 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100 ° C for 2 h under nitrogen protection. Water (100 mL) was added to the reaction solution, and dichloromethane (80 mL × 2) was extracted, and the combined organic phases were backwashed once with anhydrous sodium chloride (50 mL), and the organic phase was separated and dried with anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography separation (petroleum ether: ethyl acetate = 2:1-0:1), the obtained sample was added with ethyl acetate (10 mL), stirred for 1 h and then filtered, the filter cake was collected to obtain 70-1 (220 mg, 0.50 mmol, yield 16.8%) as a white solid. ESI-MS (m / z): 444.2 [M+H] + . 1H NMR (400MHz, CDCl3) δ8.23 (s, 1H), 6.98-7.07 (m, 1H), 6.93 (d, J = 8.03Hz, 1H), 6.63 (d, J = 7.78Hz, 1H), 5.24 (br dd,J=11.61,4.83Hz,1H),4.03-4.25(m,2H),3.79(s,3H),2.72-3.17(m,9H),2.18-2.29(m,1H),1.51(s,9H). Step 2: 70-1 (235 mg, 0.53 mmol) was placed in a 40 mL single-necked bottle, a mixed solution of TFA (1 mL) and DCM (9 mL) was added, and the reaction solution was stirred at room temperature for 1 h. The reaction solution was concentrated under reduced pressure to obtain 70-2 (180 mg, 0.52 mmol, 98.9%) as a brown oil. ESI-MS (m / z): 344.1 [M+H] + . Step 3: 1-1 (500 mg, 1.08 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, acetonitrile (5 mL) was added, tert-butyl bromoacetate (316 mg, 1.62 mmol, 1.5 eq) and DIEA (1.39 g, 10.8 mmol, 10 eq) were added, and the reaction solution was stirred at room temperature overnight. The reaction solution was filtered, and the filter cake was washed once with acetonitrile (5 mL), and the filter cake was collected to obtain 70-3 (466 mg, 0.81 mmol, yield 74.8%) as a yellow solid. ESI-MS (m / z): 577.5 [M+H] + . Step 4: 70-3 (466 mg, 0.81 mmol) was placed in a 40 mL single-necked bottle, and DCM (1 mL) and HCl (5 mL) in dioxane were added, and the reaction solution was stirred at room temperature for 2 h. The reaction solution was concentrated under reduced pressure to obtain 70-4 (400 mg, 0.77 mmol, 95.1%) as a yellow solid. ESI-MS (m / z): 521.4 [M+H] + . Step 5: 70-4 (341 mg, 0.52 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DMF (4 mL) was added. 70-2 (180 mg, 0.52 mmol, 1.0 eq) and DIEA (203 mg, 1.57 mmol, 3.0 eq) were added to the reaction solution, and HATU (219 mg, 0.58 mmol, 1.1 eq) was added. The reaction solution was stirred at room temperature for 1 h. After the reaction solution was filtered, the filtrate was separated and purified by high performance liquid chromatography to obtain Example 70 (173 mg, 0.19 mmol, yield 36.6%) as a yellow solid. ESI-MS (m / z): 846.4 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ11.10(br s,1H),10.50(s,1H),9.36(dd,J=6.94,1.56Hz,1H),8.90(dd,J=4.06,1.56Hz,1H),8.68(s,1H),8.3 5(s,1H),7.34(dd,J=6.94,4.19Hz,1H),6.97-7.04(m,1H),6.90-6.97(m,2H),6.74(s,1H),5.37(br dd,J=12.51,5.25Hz,1H),4.56(br s,1H),4.37-4.50(m,1H),4.16-4.33(m,1H),3.67(s,3H),3.40(br s,3H),3.06-3.21(m,3H),3.01(br s,2H),2.79-2.96(m,5H),2.55-2.75(m,9H),1.97-2.06(m,1H),1.66-1.96(m,7H),1.46-1.65(m,3H). Embodiment 71: Step 1: 2-(2,6-dioxypiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione (200 mg, 0.68 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMSO (2 mL), tert-butyl 2-(piperazine-1-yl) acetate (136 mg, 0.68 mmol, 1.0 eq) and DIEA (263 mg, 2.04 mmol, 3.0 eq) were added to the reaction solution, and the reaction solution was stirred at 140°C for 1 h. Water (10 mL) was added to the reaction solution, filtered, and the filter cake was washed twice with water (10 mL×2), and the filter cake was collected to obtain 71-1 (200 mg, 0.40 mmol, yield 59.4%) as a khaki solid. ESI-MS (m / z): 475.2 [M+H] + 1 H NMR (400MHz, DMSO-d6) δ11.12(s,1H),7.74(d,J=11.38Hz,1H),7.47(d,J=7.38Hz,1H),5.11(dd,J=12.82,5.44Hz,1H ),3.22-3.29(m,4H),3.20(s,2H),2.84-2.95(m,1H),2.66-2.72(m,4H),2.55(s,2H),1.98-2.12(m,1H),1.43(s,9H). Step 2: 71-1 (160 mg, 0.34 mmol) was placed in a 40 mL single-necked bottle, and DCM (1 mL) was added, followed by a dioxane solution of HCl (4 mL, 16.00 mmol), and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was concentrated under reduced pressure to obtain 71-2 (160 mg, 0.38 mmol) as a gray solid. ESI-MS (m / z): 419.2 [M+H] + Step 3: 71-2 (70 mg, 0.17 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DMF (2 mL), DIEA (65 mg, 0.50 mmol, 3.0 eq), 1-1 (77 mg, 0.17 mmol, 1.0 eq) were added to the reaction solution, and finally HATU (70 mg, 0.18 mmol, 1.1 eq) was added, and the reaction solution was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure and purified by high performance liquid chromatography to obtain Example 71 (53.45 mg, 0.06 mmol, yield 35.3%) as a yellow solid. ESI-MS (m / z): 863.4 [M+H] + 1H NMR (400MHz, DMSO-d6) δ11.11(s,1H),10.50(s,1H),9.37(dd,J=7.00,1.50Hz,1H),8.90(dd,J=4.19,1.56Hz,1H) ,8.68(s,1H),8.37(s,1H),7.74(d,J=11.38Hz,1H),7.49(d,J=7.38Hz,1H),7.34(dd,J=6.94,4.19Hz,1H),6.76(s ,1H),5.12(dd,J=12.88,5.38Hz,1H),4.56(t,J=5.25Hz,1H),3.56-3.85(m,3H),3.36-3.49(m,4H),3.21-3.30(m ,5H),3.07(s,2H),2.83-2.98(m,3H),2.55-2.73(m,8H),1.99-2.11(m,1H),1.67-1.94(m,6H),1.45-1.65(m,3H). Embodiment 72: 1-3 (70 mg, 0.12 mmol) was placed in a 40 mL single-necked bottle, DMSO (2 mL), 2-(2,6-dioxypiperidin-3-yl)-5,6-difluoroisoindoline-1,3-dione (36 mg, 0.12 mmol, 1.0 eq), and DIEA (32 mg, 0.24 mmol, 2.0 eq) were added to the reaction solution, and stirred at 90° C. for 1 h. The reaction solution was filtered, and the filtrate was separated by high performance liquid chromatography to obtain Example 72 (38 mg, 0.04 mmol, 36.4%) as a yellow solid. ESI-MS (m / z): 848.5 [M+H] + 1H NMR (400MHz, DMSO-d6) δ11.11(s,1H),10.49(s,1H),9.36(dd,J=7.03,1.55Hz,1H),8.90(dd,J=4.17,1.55Hz,1H),8.68(s,1H),8.34(s,1H),7.71(d, J=11.44Hz,1H),7.45(d,J=7.63Hz,1H),7.34(dd,J=6.97,4.23Hz,1H),6. 73(s,1H),5.11(dd,J=12.81,5.42Hz,1H),4.55(t,J=5.25Hz,1H),3.60(br d,J=11.32Hz,2H),3.40(t,J=5.25Hz,2H),2.82-3.04(m,8H),2.60-2.69(m,4H ),2.36-2.42(m,2H),1.67-2.10(m,11H),1.41-1.65(m,7H),1.26-1.39(m,2H). Embodiment 73: Step 1: 2-Methylpropane-2-ylpiperidinium-4-carboxylate (208 mg, 1.12 mmol) was placed in a 40 mL single-mouth bottle, dichloromethane (3 mL) was added, M1-1 (330 mg, 0.94 mmol, 1.0 eq) was added, and stirred at 25 ° C for 12 h. The reaction solution was concentrated under reduced pressure and purified by thin layer chromatography (petroleum ether: ethyl acetate = 3:1) to obtain 73-1 (400 mg, 0.77 mmol, yield 82.5%) as a colorless oil. ESI-MS (m / z): 518.2 [M+H] + 1 H NMR(400MHz,DMSO-d6)δ7.90(s,1H),6.68(s,1H),3.54-3.66(m,2H),3.13-3.24(m,2H),3.07(s ,2H),2.85(t,J=10.6Hz,2H),2.34-2.45(m,1H),2.05(s,1H),1.59-1.94(m,9H),1.47(s,18H). Step 2: 73-1 (250 mg, 0.48 mmol) was placed in a 40 mL single-mouth bottle, ethanol (2 mL) was added, ammonium chloride (129 mg, 2.41 mmol, 5.0 eq) and water (0.40 mL) were added, the system was heated to 60 ° C, iron powder (134 mg, 2.41 mmol, 5.0 eq) was added, and the reaction solution was stirred at 60 ° C for 4 h. The reaction solution was filtered, and the filtrate was collected and concentrated under reduced pressure to obtain 73-2 (180 mg, 0.37 mmol, yield: 76.4%) as a yellow solid. ESI-MS (m / z): 488.2 [M+H] + Step 3: Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (50 mg, 0.31 mmol) was placed in a 40 mL single-mouth bottle, acetonitrile (2 mL) was added, 73-2 (150 mg, 0.31 mmol, 1.0 eq), 1-methylimidazole (75 mg, 0.06 mmol, 3.0 eq) and N,N,N,N-tetramethylchloroformamidine hexafluorophosphate (8 mg, 0.02 mmol, 1.2 eq) were added, and the reaction was carried out at 25°C for 12 h. The reaction solution was concentrated under reduced pressure and purified by thin layer chromatography (petroleum ether: ethyl acetate = 3:1) to obtain 73-3 (100 mg, 0.16 mmol, yield 51.4%) as a yellow solid. ESI-MS (m / z): 633.4 [M+H] + Step 4: 73-3 (100 mg, 0.16 mmol) was placed in a 40 mL single-necked bottle, dichloromethane (1 mL) was added, and dioxane hydrochloride solution (1 mL, 4 M) was added, and stirred at 25°C for 2 h. The reaction solution was concentrated under reduced pressure, and the pH was adjusted to 8 with saturated sodium bicarbonate to precipitate a white solid, which was filtered and the filter cake was collected to obtain 73-4 (50 mg, 0.10 mmol, yield: 66.4%) as a yellow solid. ESI-MS (m / z): 477.3 [M+H] + Step 5: 73-4 (20 mg, 0.04 mmol) was placed in a 40 mL single-mouth bottle, tetrahydrofuran (1 mL) and N, N-dimethylformamide (1 mL) were added, M33 (17 mg, 0.04 mmol, 1 eq) and sodium triacetoxyborohydride (10 mg, 0.05 mmol, 1.2 eq) and potassium acetate (8 mg, 0.08 mmol, 2 eq) were added, and stirred at 25 ° C for 12 h. The reaction solution was filtered and the filtrate was purified by high performance liquid chromatography. Example 73 (19 mg, 0.02 mmol, yield 52.6%) was obtained as a white solid. ESI-MS (m / z): 884.5 [M+H] + 1 H NMR (400MHz, DMSO-d6) δppm 11.12 (s, 1H), 10.54 (s, 1H), 9.36 (d, J = 7.00Hz, 1H), 8.89 (br d,J=3.00Hz,1H),8.68(s,1H),8.37(s,1H),8.17(s,1H),7.34(dd,J=6.94,4.19Hz,1H ),7.17(d,J=7.75Hz,1H),7.09-7.13(m,1H),6.99-7.06(m,1H),6.72(s,1H),5.40(br dd,J=12.51,5.25Hz,1H),4.46(s,2H),3.64(s,3H),3.42-3.46(m,2H),2.9 8(s,2H),2.84-2.92(m,3H),2.59-2.77(m,5H),2.32-2.43(m,3H),2.13(br d,J=6.88Hz,2H),1.98-2.08(m,5H),1.73-1.92(m,8H),1.47(br s,1H),1.12-1.23(m,2H),0.84-0.96(m,2H). Embodiment 74: Step 1: Chromium trioxide (4.75 g, 47.55 mmol, 4.00 eq) was placed in a 500 mL single-mouth bottle, and concentrated sulfuric acid (10.49 g, 106.99 mmol, 9.00 eq) was added while the temperature was controlled at 0°C. After the system was cooled to 0°C, a toluene (60 mL) solution of M33-5 (2.00 g, 11.89 mmol, 1.00 eq) was added, and the system was stirred at 25°C for 2 h. The reaction solution was slowly poured into ice water, and ethyl acetate (100 mL × 3) was added for extraction. The organic phase was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 74-1 (1.20 g, 6.59 mmol, yield: 55.4%) as a green solid. Step 2: M29 (100 mg, 0.30 mmol, 1.00 eq) was placed in a 40 mL single-mouth bottle, and DMF (1 mL), 74-1 (107 mg, 0.59 mmol, 2.00 eq) and cesium carbonate (192 mg, 0.59 mmol, 2.00 eq) were added, and bis(triphenylphosphine)palladium dichloride (46 mg, 0.06 mmol, 0.2 eq) was added, and stirred at 100 ° C for 2 h under nitrogen protection. The reaction solution was filtered, and the filtrate was purified by high performance liquid chromatography to obtain 74-2 (40 mg, 0.09 mmol, yield: 30.8%) as a yellow solid. ESI-MS (m / z): 440.1 [M+H] + Step 3: 74-2 (45 mg, 0.10 mmol, 1.0 eq) was placed in a 40 ml single-mouth bottle, DMF (2 mL) was added, and then 1-1 (47 mg, 0.10 mmol, 1.1 eq), DIEA (39 mg, 0.31 mmol, 3.0 eq) and HATU (42 mg, 0.11 mmol, 1.1 eq) were added, and the reaction solution was stirred at 25 ° C for 2 h. The reaction solution was filtered and the filtrate was purified by high performance liquid chromatography. Example 74 (20 mg, 0.02 mmol, yield: 22.8%) was obtained as a yellow solid. ESI-MS (m / z): 884.4 [M+H] + 1 H NMR(400MHz,DMSO-d6)δ11.10(br s,1H),10.50(s,1H),9.36(dd,J=7.00,1.38Hz,1H),8.90(dd,J=4.00,1.25Hz,1H),8.68(s,1H),8.36(s,1H),7.34(dd,J=7.00,4. 25Hz,1H),7.18(d,J=7.75Hz,1H),7.13(d,J=7.75Hz,1H),7.01-7.06(m,1H),6.76(s,1H),5.41(dd,J=12.63,5.25Hz,1H),4.55(br t,J=5.13Hz,1H),4.48(s,2H),3.75-3.85(m,1H),3.66(s,4H),3.46-3.58 (m,2H),3.37-3.43(m,3H),3.01-3.08(m,2H),2.83-2.97(m,3H),2.60-2.77(m,5 H),2.00-2.13(m,3H),1.51-1.92(m,11H),1.37-1.49(m,2H),1.21-1.34(m,2H). Embodiment 75: Step 1: In a 50 mL single-mouth bottle, add M31 (158 mg, 0.4 mmol), tert-butyl bromoacetate (117 mg, 0.60 mmol), DIEA (516 mg, 4.00 mmol) and mix in acetonitrile (4 mL), stir at room temperature and react overnight. Add DCM (15 mL) to the reaction solution, wash with saturated ammonium chloride solution (15 mL), dry over anhydrous sodium sulfate, and purify by column chromatography, eluent: DCM: MeOH = 100: 0 ~ 95: 5, to obtain 75-1, brown solid 127 mg, yield: 62.2%. ESI-MS (m / z): 511.6 [M+H] + . 1 H NMR (500MHz, CDCl3) δ8.72 (s, 1H), 7.08 (d, J = 7.8Hz, 1H), 6.89 (t, J = 7.9Hz, 1H) ,6.70(d,J=7.8Hz,1H),5.14(dd,J=12.7,5.3Hz,1H),4.36(s,2H),3.69(s,3H), 3.63–3.53(m,1H),3.08(s,2H),2.86–2.58(m,5H),2.38(t,J=8.9Hz,2H),2.17– 2.08(m,1H),1.91(d,J=10.1Hz,2H),1.68(dt,J=16.7,6.1Hz,2H),1.39(s,9H). Step 2: 75-1 (127 mg, 0.25 mmol) was placed in a 50 mL single-mouth bottle, DCM (3 mL) was added to dissolve, TFA (1020 mg, 8.95 mmol) was slowly added, and the mixture was stirred at room temperature for 1.5 h. The reaction solution was concentrated under reduced pressure to obtain 75-2, a brown viscous solid of 148.3 mg, with a yield of 131.2%. ESI-MS (m / z): 455.4 [M+H] + . Step 3: 75-2 (113 mg, 0.25 mmol), 1-1 (191 mg, 0.25 mmol), HATU (142 mg, 0.38 mmol), DIEA (193 mg, 1.50 mmol) were placed in a 25 mL single-mouth bottle, DCM (7 mL) was added, and the mixture was stirred at 25 °C for overnight reaction. DCM (20 mL) was added to the reaction solution, and saturated ammonium chloride solution (20 mL) was added for washing. The organic phase was dried over anhydrous sodium sulfate, purified by column chromatography, and the eluent was 1% ethyl acetate. The reaction mixture was reacted with DCM:MeOH=100:0-93:7 to obtain Example 75 as a light yellow solid (170 mg). Yield: 75.6%. ESI-MS (m / z): 899.7 [M+H] + . 1 H NMR (500MHz, DMSO-d6) δ11.10(s,1H),10.50(s,1H),9.35(d,J=6.0Hz,1H),8.90(d,J=2.7Hz,1H),8.68 (s,1H),8.37(s,1H),7.34(dd,J=6.8,4.2Hz,1H),7.19(d,J=7.7Hz,1H),7.13(d,J=7.6Hz,1H),7.05(t ,J=7.9Hz,1H),6.75(s,1H),5.40(dd,J=12.8,5.2Hz,1H),4.59–4.44(m,3H),3.83(s,1H),3.66(s,3H) ,3.61–3.35(m,5H),3.26(d,J=14.8Hz,3H),3.14–2.84(m,7H),2.77–2.58(m,4H),2.11–1.42(m,15H). Embodiment 76: 70-4 (203 mg, 0.39 mmol), M31 (154 mg, 0.39 mmol), HATU (222 mg, 0.58 mmol), DIEA (302 mg, 2.34 mmol) were placed in a 25 mL single-mouth bottle, DCM (7 mL) was added, and the mixture was stirred at 25° C. for overnight reaction. DCM (15 mL) was added to the reaction solution, and a saturated ammonium chloride solution (15 mL) was added for washing, dried over anhydrous sodium sulfate, and purified by column chromatography, with the eluent being: DCM:MeOH=100:0-95:5, to obtain Example 76 as a light yellow solid (212 mg), with a yield of 60.5%. ESI-MS (m / z): 899.7 [M+H] + . 1H NMR (500MHz, DMSO-d6) δ11.10(s,1H),10.48(s,1H),9.34(d,J=6.6Hz,1H),8.89(d,J=2.7Hz,1H),8.67(s,1H),8.33(s,1H),7 .33(dd,J=6.7,4.3Hz,1H),7.18(d,J=7.7Hz,1H),7.14(d,J=7.7Hz,1H),7.04(t,J=7.8Hz,1H),6.72(s,1H),5.40(dd,J=12.7, 5.2Hz,1H),4.57–4.49(m,3H),3.92–3.78(m,3H),3.66(s,3H),3.43–3.39(m,2H),3.18–3.03(m,2H),3.02–2.84(m,5H),2.77– 2.44(m,11H),2.08–2.00(m,1H),1.98–1.92(m,1H),1.84(d,J=13.1Hz,3H),1.74(dd,J=19.6,10.9Hz,4H),1.64–1.46(m,4H). Embodiment 77: Step 1: 4-Bromo-2,5-difluorobenzonitrile (10.0 g, 45.87 mmol, 1.0 eq) was placed in a 250 mL single-mouth bottle, and EtOH (70 mL), methylhydrazine sulfate (19.8 g, 137.61 mmol, 3.0 eq), triethylamine (25.5 mL, 183.49 mmol, 4.0 eq) were added, and the reaction solution was stirred at 80 ° C for 6 h. After the reaction solution was concentrated under reduced pressure to remove ethanol, water (150 mL) was added to precipitate solids, which were filtered and the filter cake was collected. DCM (20 mL) was added to the filter cake and stirred for 30 min, then filtered and the filter cake was collected to obtain 77-2 (4 g, 16.39 mmol, yield 35.7%) as a white solid. ESI-MS(m / z):Br,244.0,246.0[M+1,M+3] + . 1 H NMR (400MHz, CDCl3) δ7.44 (d, J = 5.25Hz, 1H), 7.24 (d, J = 8.13Hz, 1H), 3.98 (s, 2H), 3.82 (s, 3H). Step 2: 77-2 (4 g, 16.39 mmol) was placed in a 100 mL single-mouth bottle, HCl (30 mL, 2M) was added, acrylic acid (1.54 g, 21.31 mmol, 1.3 eq) was added to the reaction solution, and the reaction solution was stirred at 100 ° C overnight. Saturated sodium bicarbonate aqueous solution was added to the reaction solution until the pH was 7-8, and then acetic acid was added to adjust the pH to 5-6, solid precipitated, filtered, and the filter cake was collected to obtain 77-3 (4.68 g, 14.80 mmol, yield 90.3%) as a gray solid. ESI-MS(m / z):Br,316.0,318.0[M+1,M+3] + . 1 H NMR (400MHz, DMSO-d6) δ7.84 (d, J = 5.50Hz, 1H), 7.67 (d, J = 9.01Hz, 1H), 3.77 (s, 3H), 3.45 (br t, J = 6.75Hz, 2H), 2.59 (br t, J = 6.82Hz, 2H). Step 3: 77-3 (4.58 g, 14.49 mmol) was placed in a 100 mL single-mouth bottle, acetic acid (45 mL) and potassium cyanate (2.35 g, 28.98 mmol, 2.0 eq) were added, and stirred at 60 ° C for 3 h. HCl (45 mL, 2N) was added to the reaction solution and continued to stir at 60 ° C overnight. The reaction solution was cooled and filtered, and the filter cake was washed twice with water. The filter cake was collected to obtain 77-4 (3 g, 8.79 mmol, yield 60.7%) as a white solid. ESI-MS (m / z): Br, 340.9, 342.9 [M+1, M+3] + . 1 H NMR (400MHz, DMSO-d6) δ10.61(s,1H),8.17(d,J=5.63Hz,1H),7.63(d,J=9.13Hz,1H),4.01(s,3H),3.93(t,J=6.69Hz,2H),2.76(t,J=6.69Hz,2H). Step 4: 77-4 (300 mg, 0.88 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and dioxane (5 mL), tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate (378 mg, 1.76 mmol, 2.0 eq), Cs2CO3 (859 mg, 2.64 mmol, 3.0 eq), palladium catalyst (CAS No.: 1814936-54-3) (85 mg, 0.09 mmol, 0.1 eq) were added to the reaction solution and stirred at 100 ° C for 2 h. The reaction solution was added with DCM (30 mL), filtered, and the filtrate was concentrated under reduced pressure, separated and purified by column chromatography (PE: EA = 5: 1 to 0: 1), and 77-5 (300 mg, 0.63 mmol, yield 71.7%) was obtained as a light yellow solid. ESI-MS (m / z): 476.2 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δppm 10.53(s,1H),7.33(d,J=12.87Hz,1H),7.12(d,J=7.15Hz,1H),4.58(s,1H),3.94(s,3H),3.90(t,J=6.68Hz,2H),3.12- 3.22(m,2H),3.01-3.10(m,2H),2.74(t,J=6.68Hz,2H),2.40(s,2H),1.81-1.91(m,2H),1.70-1.79(m,2H),1.43(s,9H). Step 5: 77-5 (270 mg, 0.57 mmol, 1.0 eq) was placed in a 50 mL single-necked bottle, DCM (6 mL) was added, and a hydrochloric acid dioxane solution (4 mL) was added and stirred at room temperature for 12 h. The reaction solution was concentrated under reduced pressure to obtain 77-6 (238 mg, 0.57 mmol) as a white solid. ESI-MS (m / z): 420.1 [M+H] + . Step 6: 77-6 (238 mg, 0.57 mmol, 1.0 eq) was placed in a 50 mL single-necked bottle and DMF (6 mL), 1-1 (262.48 mg, 0.57 mmol, 1.0 eq), DIEA (0.3 mL, 1.70 mmol, 3.0 eq), and HATU (237 mg, 0.62 mmol, 3.0 eq) were added to the reaction solution and stirred at room temperature for 1 h. After the reaction solution was filtered, it was separated and purified by HPLC to obtain Example 77 (176 mg, 0.20 mmol, 36.0%) as a yellow solid. ESI-MS (m / z): 864.6 [M+H] + 1 H NMR (400MHz, DMSO-d6) δ10.47-10.54(m,2H),9.36(d,J=7.00Hz,1H),8.90(d,J=2.88Hz,1H),8.68(s,1H),8.36(s,1H),7.30-7.38(m,2H) ,7.13(d,J=7.00Hz,1H),6.76(s,1H),5.01(s,1H),4.55(t,J=5.07Hz,1H),3.95(s,3H),3.89(t,J=6.63Hz,3H),3.71-3.79(m,1H),3.55- 3.65(m,1H),3.38-3.48(m,3H),3.18(m,2H),3.03-3.12(m,4H),2.93(m,2H),2.74(t,J= 6.63Hz,2H),2.59-2.68(m,4H),1.78-1.90(m,5H),1.68-1.77(m,5H),1.46-1.65(m,3H). Embodiment 78: Step 1: M29 (500 mg, 1.48 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, and DMA (5 mL), 4-(dimethoxymethyl)piperidine (941 mg, 5.91 mmol, 4.0 eq), sodium tert-butoxide (426 mg, 4.44 mmol, 3.0 eq), and palladium catalyst (CAS No.: 1814936-54-3) (143 mg, 0.15 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100°C for 2 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 20:1 to 1:1), and the product was added with ethyl acetate (10 mL) and stirred for 1 h, then filtered, and the filter cake was collected to obtain 78-1 (100 mg, 0.24 mmol, yield 16.2%) as a white solid. ESI-MS (m / z): 417.2 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.12(s,1H),6.94-7.04(m,1H),6.86-6.93(m,2H),5.37(br dd,J=12.41,5.32Hz,1H),4.15(br d,J=5.75Hz,1H),3.63(s,3H),3.31(s,6H),3.13(br d,J=11.49Hz,2H),2.86-2.95(m,1H),2.61-2.77(m,4H),1.97-2.06(m,1H),1.67-1.81(m,3H),1.41-1.57(m,2H). Step 2: 78-1 (100 mg, 0.24 mmol, 1.0 eq) was placed in a 10 mL single-necked bottle, formic acid (2 mL) was added, and the system was stirred at 25 °C for 1 h. The reaction solution was concentrated under reduced pressure to obtain 78-2 (80 mg, 0.22 mmol, yield 89.9%) as a yellow oil. ESI-MS (m / z): 371.2 [M+H] + . Step 3: 78-2 (70 mg, 0.19 mmol, 1.0 eq) was placed in a 10 mL single-necked bottle, DMA (2 mL) was added, and then 1-1 (87 mg, 0.19 mmol, 1.0eq), potassium acetate (47mg, 0.23mmol, 3.0eq) and sodium acetate borohydride (55mg, 0.57mmol, 1.2eq), stirred at 25°C for 12h. The reaction solution was concentrated under reduced pressure and separated and purified by high performance liquid chromatography to obtain Example 78 (53mg, 0.07mmol, yield 34.5%) as a yellow solid. ESI-MS (m / z): 817.5 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ10.49(s,1H),9.36(dd,J=7.00,1.38Hz,1H),8.90(dd,J=4.06,1.31Hz,1H),8.68(s,1H),8.3 4(s,1H),7.34(dd,J=6.94,4.19Hz,1H),6.95-7.01(m,1H),6.88(dd,J=12.07,8.07Hz,2H),6.74(s,1H),5.36(dd,J=1 2.63,5.38Hz,1H),4.57(t,J=5.25Hz,1H),3.64(s,3H),3.39-3.42(m,3H),3.12(m,2H),3.00(s,2H),2.93(m,3H),2.6 0-2.76(m,8H),2.44(m,2H),2.26(m,2H),1.97-2.04(m,1H),1.68-1.88(m,9H),1.51-1.63(m,3H),1.27-1.41(m,2H). Embodiment 79: Step 1: 79-1 (6.00 g, 24.2 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, methanol (60 mL) and boron trifluoride ether (2.06 g, 0.6 eq) were added, and the reaction was stirred at 25 ° C for 2 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 20: 1 to 5: 1) to obtain 79-2 (3.40 g, 12.1 mmol, yield: 50.2%) as a yellow oil. ESI-MS (m / z): 280.3 [M+H] + . 1 H NMR (400MHz, CDCl3) δ7.30-7.42 (m, 5H), 5.14 (s, 2H), 3.87 (d, J = 12.96Hz, 2H) ,3.53(s,2H),3.17-3.28(m,5H),1.83(d,J=13.57Hz,2H),1.37-1.51(m,2H). Step 2: 10% wet palladium carbon (500 mg, 4.70 mmol, 1.4 eq) was placed in a 100 mL single-mouth bottle, ethanol (20 mL) was added, and then 79-2 (900 mg, 3.22 mmol, 1.0 eq) was added. After hydrogen replacement three times, the reaction solution was stirred at 15 Psi and 25 ° C for 12 h. The reaction solution was filtered and filtered. The liquid was concentrated under reduced pressure to obtain 79-3 (500 mg, 3.44 mmol, yield: 96.9%) as a yellow solid. ESI-MS (m / z): 146.2 [M+H] + . 1 H NMR (400MHz, CDCl3) δ3.69 (q, J = 7.00Hz, 1H), 3.50 (s, 2H), 3.16-3.28 (s, 3H), 2. 72-2.99(m,4H),1.76(d,J=13.63Hz,2H),1.45(ddd,J=13.70,9.94,4.25Hz,2H). Step 3: M29 (200 mg, 0.59 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, dioxane (2 mL) was added, and then 79-3 (128 mg, 0.89 mmol, 1.5 eq) and cesium carbonate (578 mg, 1.77 mmol, 3.0 eq) were added, and a catalyst (CAS No.: 1612891-29-8) (49 mg, 0.06 mmol, 0.1 eq) was added, and the reaction solution was stirred at 100 ° C for 2 h under nitrogen protection. The reaction solution was concentrated under reduced pressure, water (10 mL) was added, and ethyl acetate (10 mL × 3) was extracted, the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by thin layer chromatography (dichloromethane: methanol = 15: 1) to obtain 79-4 (50 mg, 0.12 mmol, yield: 21.0%) as a yellow solid. ESI-MS (m / z): 403.4 [M+H] + . 1 H NMR(400MHz, CDCl3)δ9.69(s,1H),8.28(dd,J=7.70,1.22Hz,1H),7.90-7.98(m,1H),7.73(t,J=7.27Hz,1H),5.22(dd,J=12.29,5.20Hz,1H), 3.76(s,3H),3.39(s,2H),3.02-3.11(s,3H),2.70-2.94(m,3H),2.18- 2.27(m,1H),1.85-2.05(m,4H),1.43-1.48(m,2H),1.22-1.28(m,2H). Step 4: 79-4 (20 mg, 0.05 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (1 mL) and DMP (31 mg, 0.07 mmol, 1.5 eq) were added, and the reaction solution was stirred at 25 ° C for 2 h. The reaction solution was quenched by adding saturated sodium bicarbonate solution, and ethyl acetate (10 mL × 3) was added for extraction. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 79-5 (20 mg, 0.05 mmol) crude product, which was directly used in the next step. ESI-MS (m / z): 401.4 [M+H] + . Step 5: 79-5 (25 mg, 0.06 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (1 mL) was added, and then 1-1 (28 mg, 0.06 mmol, 1.0 eq), acetic acid (37 mg, 0.01 mmol, 0.1 eq) and sodium acetate borohydride (13 mg, 0.06 mmol, 1.0 eq) were added, and the reaction solution was stirred at room temperature for 2 h. The reaction solution was filtered and purified by high performance liquid chromatography to obtain Example 79 (4.93 mg, 0.01 mmol, yield: 9.3%) as a yellow solid. ESI-MS (m / z): 847.9 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.09(s,1H),10.49(s,1H),9.36(dd,J=7.07,1.56Hz,1H),8.90(dd,J=4.19,1.56Hz,1H),8.68(s,1H),8.34(s,1H ),7.29-7.39(m,1H),6.91-7.01(m,2H),6.87(d,J=8.00Hz,1H),6.73(s,1H),5.36(dd,J=12.69,5.32Hz,1H),4.55(t,J=5.32Hz,1H),3.65 (s,3H),3.40(t,J=5.13Hz,3H),3.19(s,3H),3.00(s,2H),2.85-2.96(m,7H) ,2.61-2.75(m,8H),1.91-2.03(m,3H),1.69-1.85(m,8H),1.47-1.65(m,4H). Embodiment 80: Step 1: 80-1 (3.00 g, 15.5 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and THF (30 mL) was added. A tetrahydrofuran solution of lithium aluminum tetrahydride (6.50 mL, 16.3 mmol, 2.5 M, 1.05 eq) was added dropwise at 0°C. After the addition was complete, the mixture was stirred overnight at room temperature. The reaction solution was cooled to 0°C, 0.62 mL H2O, 0.62 mL 15% NaOH solution, and 1.24 mL H2O were added dropwise. After THF (30 mL) was added, the mixture was stirred for 10 min and filtered. The filtrate was concentrated under reduced pressure to obtain 80-2 (2.58 g, 15.63 mmol) as a colorless liquid. 1H NMR (400MHz, CDCl3) δ4.57 (quin, J = 7.05Hz, 1H), 3.67 (d, J = 6.43Hz, 2H), 2.71-2.83 (m, 1H), 2.50-2.65 (m, 4H). Step 2: 80-2 (2.50 g, 15.1 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, and dichloromethane (25 mL) and imidazole (2.06 g, 30.3 mmol, 2.0 eq) were added. TBSCl (3.42 g, 22.7 mmol, 1.5 eq) was added to the reaction solution, and the reaction solution was stirred at room temperature overnight. Water (80 mL) and dichloromethane (100 mL) were added to the reaction solution, and the organic phase was separated and backwashed once with saturated brine (80 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 80-3 (4.00 g, 14.3 mmol, yield 94.5%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ4.57 (quin, J = 7.16Hz, 1H), 3.60 (d, J = 5.25Hz, 2H), 2.66-2.78 (m, 1H), 2.52-2.62 (m, 4H), 0.91 (s, 9H), 0.06 (s, 6H). Step 3: M29 (1.00 g, 2.96 mmol, 1.0 eq) was dissolved in DME (25 mL), 80-3 (1.24 g, 4.44 mmol, 1.5 eq), TTMSS (1.10 g, 4.44 mmol, 1.5 eq), sodium carbonate (0.63 g, 5.91 mmol, 2.0 eq) were added, and nitrogen was replaced for 10 min. NiCl2.dtbbpy (0.06 g, 0.15 mmol, 0.05 eq) and [Ir(df(CF3)ppy)2(dtbbpy)]PF6 (CAS No.: 870987-63-6) (0.03 g, 0.03 mmol, 0.01 eq) were added under nitrogen protection, and nitrogen was replaced for 10 min. The flow rate was S1 = 0.17 mL / min, 50 ° C, Retention time 60min, flush the pipeline, turn on the light source (hv = 395nm, 24w) and pump, and collect the reaction solution after 60min. Add water (100mL) to the reaction solution, extract with ethyl acetate (100mL×2), combine the organic phases and backwash once with saturated sodium chloride aqueous solution (80mL), separate the organic phases, dry them with anhydrous sodium sulfate, and concentrate under reduced pressure, purify by column chromatography (petroleum ether: ethyl acetate = 5:1-1:2), and obtain 80-4 (560mg, 1.22mmol, yield 41.4%) as a yellow solid. ESI-MS (m / z): 458.2 [M+H] + . 1 H NMR(400MHz, CDCl3)δ8.02(br s,1H),7.15-7.24(m,1H),7.08(q,J=7.96Hz,1H),6.65-6.70(m,1H),5.18-5.24(m,1H),3.74-3.76(m,2H),3.64-3.72(m,3H),3 .61(d,J=5.13Hz,1H),2.92-3.02(m,2H),2.73-2.88(m,2H),2.12-2.38(m,5H),0.93(d,J=8.38Hz,9H),0.09(d,J=12.01Hz,6H). Step 4: 80-4 (560 mg, 1.22 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, THF (5 mL) was added, and a tetrahydrofuran solution of TBAF (2.40 mL, 2.45 mmol, 1 M, 2.0 eq) was added to the reaction solution, and the reaction solution was stirred at room temperature overnight. Water (30 mL) was added to the reaction solution, and ethyl acetate (50 mL × 2) was extracted, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 2: 1-0: 1), and the obtained oil was added with ethyl acetate (10 mL) and stirred for 30 min and filtered, and the filter cake was collected to obtain 80-5 (110 mg, 0.32 mmol, yield 26.2%) as a white solid. ESI-MS (m / z): 344.1 [M+H] + . 1 H NMR(400MHz, CDCl3)δ8.10(br s,1H),7.12-7.25(m,1H),7.08(q,J=8.13Hz,1H),6.69(dd,J=7.44,5.44Hz,1H),5.22(dd,J=12.01,5.13Hz,1H),4.09-4.19(m,1H),3.82(d,J =6.75Hz,1H),3.62-3.72(m,4H),2.92-2.99(m,1H),2.70-2.89(m,2H) ,2.59(m,1H),2.40-2.50(m,2H),2.19-2.32(m,2H),2.06-2.15(m,1H). Step 5: 80-5 (80 mg, 0.23 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (3 mL) and DMP (148 mg, 0.35 mmol, 1.5 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 5 h. Saturated sodium bicarbonate aqueous solution (10 mL) was added to the reaction solution, and dichloromethane (10 mL × 2) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 80-6 (50 mg, 0.15 mmol, yield 62.9%) as a light yellow solid. ESI-MS (m / z): 342.1 [M+H] + . 1H NMR(400MHz, CDCl3)δ9.75-10.10(m,1H),8.10(br s,1H),7.11-7.25(m,2H),6.75(d,J=7.70Hz,1H),5.20-5.30(m,1H),4.17-4.21(m,1H),3.66-3.77(m ,3H),3.26-3.36(m,1H),2.95-3.04(m,1H),2.74-2.92(m,3H),2.45-2.66(m,3H),2.24-2.30(m,1H). Step 6: 80-6 (50 mg, 0.15 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (2 mL), 1-1 (68 mg, 0.15 mmol, 1.0 eq), AcOH (18 mg, 0.29 mmol, 2.0 eq), sodium acetate borohydride (37 mg, 0.18 mmol, 1.2 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. The reaction solution was filtered and separated and purified by high performance liquid chromatography to obtain Example 80 (22.29 mg, 0.03 mmol, yield 19.3%) as a light yellow solid. ESI-MS (m / z): 788.5 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.09(s,1H),10.49(s,1H),9.36(dd,J=7.00,1.50Hz,1H),8.90(dd,J=4.25,1.50Hz,1H),8.68(s,1H),8.34(s,1H),7.34( dd,J=7.07,4.19Hz,1H),6.97-7.22(m,3H),6.74(s,1H),5.33-5.40(m,1 H),4.55(t,J=5.44Hz,1H),3.93-4.21(m,1H),3.51-3.62(m,3H),3.40(br t,J=5.00Hz,2H),2.84-3.03(m,5H),2.56-2.74(m,6H),2.32-2.46(m,6H),2.12-2.23(m,1H),1.69-2.05(m,9H),1.48-1.65(m,3H). Embodiment 81: Step 1: M29 (300 mg, 0.89 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, 1,4-dioxane (3 mL) was added, followed by tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate (287 mg, 1.33 mmol, 1.5 eq) and cesium carbonate (869 mg, 2.67 mmol, 3.0 eq), and finally palladium catalyst (CAS No.: 1612891-29-8) (74 mg, 0.09 mmol, 0.1 eq) was added, and the reaction solution was stirred at 100 ° C for 2 h. The reaction solution was concentrated under reduced pressure, water (30 mL) was added, and ethyl acetate (30 mL × 3) was extracted, the organic phase was washed with saturated sodium chloride, and then purified by thin layer chromatography (dichloromethane: methanol = 15: 1) to obtain 81-2 (120 mg, 0.25 mmol, yield: 28.6%) as a yellow solid. ESI-MS (m / z): 473.5 [M+H] + . 1 H NMR (400MHz, CDCl3) δ8.21 (s, 1H), 7.01 (br d, J = 4.82Hz, 2H), 6.53-6.62 (m, 1H), 5.21 (dd,J=12.37,5.20Hz,1H),3.77(s,3H),3.16-3.28(m,2H),2.89-2.99(m,3H),2. 67-2.87(m,3H),2.46(s,2H),2.17-2.27(m,1H),1.73-1.91(m,4H),1.50(s,9H). Step 2: 81-2 (110 mg, 0.23 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, and DCM (1 mL) was added followed by dioxane hydrochloride solution (1 mL), and the reaction was stirred at 25°C for 2 h. The reaction solution was concentrated under reduced pressure to obtain 81-3 (90 mg, 0.22 mmol, yield: 92.8%) as a yellow solid. ESI-MS (m / z): 417.4 [M+H] + . Step 3: 1-1 (99 mg, 0.22 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, 81-3 (90 mg, 0.22 mmol, 1.0 eq) was added, followed by DIEA (83 mg, 0.65 mmol, 3.0 eq), and finally HATU (90 mg, 0.24 mmol, 1.1 eq), and the reaction was stirred at 25 ° C for 2 h. The reaction solution was purified by high performance liquid chromatography to obtain Example 81 (89.26 mg, 0.10 mmol, yield: 48.0%) as a yellow solid. ESI-MS (m / z): 861.5 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.08(s,1H),10.50(s,1H),9.36(dd,J=7.03,1.53Hz,1H),8.90(dd,J=4.16,1.47Hz,1H),8.68(s,1H),8.36( s,1H),7.33(dd,J=6.97,4.16Hz,1H),6.90-7.01(m,2H),6.86(d,J=7.95Hz,1H),6.76(s,1H),5.35(dd,J=12.59,5.26Hz,1H),4.96(br s,1H),4.56(t,J=4.83Hz,1H),3.70-3.93(m,2H),3.55-3.67(m,4H),3.37-3.49(m,3H),3.00-3.11(m ,4H),2.82-2.97(m,5H),2.58-2.76(m,6H),1.95-2.04(m,1H),1.68-1.90(m,10H),1.46-1.65(m,3H). Embodiment 82: Step 1: 82-1 (2.00 g, 7.24 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, NMP (40 mL) was added, piperidin-4-ylmethanol (830 mg, 7.24 mmol, 1.0 eq) and DIEA (2.81 g, 21.72 mmol, 3.0 eq) were added, and stirred at 90 ° C for 12 h. H2O (50 mL) was added to the reaction solution, and ethyl acetate (80 mL × 2) was used for extraction. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 0: 1) to obtain 82-2 (1.60 g, 4.31 mmol, yield: 59.5%) as a yellow oil. ESI-MS (m / z): 372.1 [M+H] +. 1 H NMR(400MHz, CDCl3)δ8.11(br s,1H),7.62-7.71(m,1H),7.29(d,J=2.38Hz,1H),7.06(dd,J=8.58,2.38Hz,1H),4.94(dd,J=12.28,5.25Hz,1H),3.99(d,J=12.99 Hz,2H),3.51-3.58(m,2H),3.36-3.42(m,2H),3.00(m,2H),2.34-2.41(m,2H),2.08-2.17(m,1H),1.88(m,2H),1.31-1.43(m,2H). Step 2: 82-2 (500 mg, 1.35 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, DCM (5 mL) was added, the temperature was cooled to 0°C, DMP (599 mg, 1.41 mmol, 1.05 eq) was added, and the mixture was stirred at 25°C for 2 h. Saturated sodium bicarbonate solution was added to the reaction solution to quench and adjust the pH to 7-8, and then dichloromethane (10 mL×3) was added for extraction. The organic phase was washed with saturated sodium chloride and dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain 82-3 (140 mg, 0.38 mmol, yield: 28.2%) as a white solid. ESI-MS (m / z): 370.1 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.14(s,1H),9.68(s,1H),7.72(d,J=8.50Hz,1H),7.40 (s,1H),7.32(dd,J=8.57,1.94Hz,1H),5.13(dd,J=12.88,5.25Hz,1H),4.00(br d,J=13.26Hz,2H),3.18-3.29(m,2H),2.87-3.03(m,1H),2.58-2.80(m,4H),1.95-2.03(m,2H),1.57-1.69(m,2H). Step 3: 82-3 (100 mg, 0.27 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (2 mL), 1-1 (124 mg, 0.27 mmol, 1.0 eq), potassium acetate (79 mg, 0.81 mmol, 3.0 eq), sodium triacetoxyborohydride (57 mg, 0.27 mmol, 1.0 eq) were added to the reaction solution, and stirred at 25 ° C for 1 h. The reaction solution was separated and purified by high performance liquid chromatography to obtain Example 82 (83.64 mg, 0.10 mmol, yield: 37.9%) as a yellow solid. ESI-MS (m / z): 816.4 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.11(s,1H),10.51(s,1H),9.37(dd,J=6.97,1.47Hz,1H),8.91(dd,J=4.03,1.34Hz,1H),8.69(s,1H),8.35(s,1H) ,7.67(d,J=8.56Hz,1H),7.30-7.38(m,2H),7.20-7.28(m,1H),6.75(s,1H),5.08(dd,J=12.96,5.26Hz,1H),4.60(t,J=5.13Hz,1H),4.07(br d,J=12.71Hz,2H),3.41-3.43(m,3H),2.91-3.03(m,6H),2.55-2.72(m,5H),2.34-2.48(m, 2H),2.20(br d,J=6.97Hz,2H),1.98-2.08(m,1H),1.71-1.89(m,9H),1.50-1.66(m,3H),1.08-1.24(m,2H). Embodiment 83: 78-2 (53 mg, 0.14 mmol) was placed in a 40 mL single-mouth bottle, DMA (2 mL) was added, 61-2 (66 mg, 0.14 mmol, 1.0 eq), potassium acetate (28 mg, 0.29 mmol, 2.0 eq), sodium acetate borohydride (36 mg, 0.17 mmol, 1.2 eq) were added, and the reaction solution was stirred at room temperature for 2 h. After the reaction solution was filtered, the filtrate was collected and purified by high performance liquid chromatography to obtain Example 83 (34.8 mg, 0.04 mmol, yield 29.8%) as a white solid. ESI-MS (m / z): 817.5 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.09(br s,1H),10.93(s,1H),8.97(s,1H),8.75(br d,J=4.41Hz,1H),8.33(s,1H),8.25(br d,J=8.58Hz,1H),7.57(dd,J=8.34,4.77Hz,1H),6.94-7.01(m,1H),6.85-6.92(m,2H ),6.75(s,1H),5.36(dd,J=12.40,5.01Hz,1H),4.54(t,J=5.13Hz,1H),3.63(s,3H),3 .38(t,J=5.13Hz,2H),3.11(m,2H),2.84-3.04(m,5H),2.56-2.76(m,7H),2.42(m,2H ),2.25(m,2H),1.96-2.05(m,1H),1.67-1.91(m,9H),1.45-1.67(m,4H),1.32(m,2H). Embodiment 84 and Embodiment 85: Step 1: 84-1 (200 mg, 0.62 mmol) was placed in a 40 mL single-mouth bottle, and dioxane (4 mL), piperidin-4-ylmethanol (107 mg, 0.93 mmol, 1.5 eq), cesium carbonate (403 mg, 1.24 mmol, 2.0 eq), and catalyst (CAS No.: 1612891-29-8) (60 mg, 0.06 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100 ° C for 2 h. Dichloromethane (20 mL) was added to the reaction solution, filtered, and the filtrate was concentrated under reduced pressure and purified by column chromatography (dichloromethane: methanol = 15: 1-10: 1) to obtain 84-2 (120 mg, 0.34 mmol, yield 54.2%) as a white solid. ESI-MS (m / z): 358.1 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),7.50(br d,J=8.50Hz,1H),6.98-7.20(m,2H),5.05(dd,J=13.32,5.07Hz,1H),4.49(t,J=5.25Hz,1H),4.27-4.37(m,1H),4.16-4.25(m,1H),3.90(br d,J=12.76Hz,2H),3.28(br t,J=5.69Hz,2H),2.77-2.97(m,3H),2.37(br dd,J=13.01,4.38Hz,1H),1.92-2.02(m,1H),1.58-1.80(m,4H),1.15-1.30(m,2H). Step 2: 84-2 (100 mg, 0.28 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (3 mL) and DMP (125 mg, 0.29 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 1 h. Saturated sodium bicarbonate aqueous solution (10 mL) was added to the reaction solution, and dichloromethane was extracted (10 mL × 2). The organic phases were combined and dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thin layer chromatography separation and purification (dichloromethane: methanol = 10: 1) was performed to obtain 84-3 (80 mg, 0.23 mmol, yield 80.5%) as a yellow oil. ESI-MS (m / z): 356.1 [M+H] + . Step 3: 84-3 (80 mg, 0.23 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (2 mL), 1-1 (104 mg, 0.23 mmol, 1.0 eq), potassium acetate (44 mg, 0.45 mmol, 2.0 eq), sodium acetate borohydride (47 mg, 0.23 mmol, 1.0 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. The reaction solution was filtered, and the filtrate was sent to high performance liquid chromatography for separation and purification to obtain 84-4 (40 mg, 0.05 mmol, yield 22.2%) as a yellow solid, which was directly used for SFC separation. Step 4: 84-4 (40 mg, 0.05 mmol) was separated by SFC to obtain Example 84 and Example 85. Example 84 or Example 85 (15.15 mg, 0.02 mmol, yield 37.6%) is a yellow solid. Purity: 99.18%, 100% ee. ESI-MS (m / z): 802.5 [M+H]+ . 1 H NMR (400MHz, DMSO-d6) δ10.96(s,1H),10.50(s,1H),9.36(d,J=7.05Hz,1H),8.90(d,J=2.60Hz,1H),8.68(s,1H),8 .35(s,1H),7.51(d,J=8.04Hz,1H),7.34(dd,J=6.80,4.45Hz,1H),7.02-7.11(m,2H),6.74(s,1H),5.05(dd,J=13.4 2,4.64Hz,1H),4.58(t,J=5.44Hz,1H),4.16-4.37(m,2H),3.89(d,J=11.75Hz,2H),3.41(m,2H),2.79-3.03(m,7H) ,2.55-2.70(m,5H),2.32-2.45(m,3H),2.21(m,2H),1.93-2.02(m,1H),1.68-1.90(m,9H),1.48-1.66(m,3H),1.14- 1.27(m,2H). The other (15.98 mg, 0.02 mmol, yield 39.6%) was a yellow solid. ESI-MS (m / z): 802.5 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ10.96(s,1H),10.50(s,1H),9.37(d,J=6.31Hz,1H),8.91(d,J=3.22Hz,1H),8.69(s,1H),8.35( s,1H),7.51(d,J=8.41Hz,1H),7.35(dd,J=6.99,4.14Hz,1H),6.99-7.13(m,2H),6.74(s,1H),5.05(dd,J=13.36,4.95Hz ,1H),4.57(t,J=5.32Hz,1H),4.16-4.39(m,2H),3.83-3.96(m,2H),3.39-3.43(m,2H),2.79-3.05(m,7H),2.54-2.71(m ,5H),2.33-2.46(m,3H),2.16-2.26(m,2H),1.94-2.02(m,1H),1.69-1.89(m,9H),1.48-1.65(m,3H),1.14-1.27(m,2H). A similar synthesis method as in Example 34 was used to synthesize the corresponding intermediates. The structural characterization data are shown in the following table: Embodiment 91: Step 1: M1-1 (900 mg, 2.55 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, and a 30% methanol solution of sodium methoxide (2.29 g, 12.7 mmol, 5.0 eq) was added, and stirred at 40°C for 4 h. Water (20 mL) was added to the reaction solution, and it was extracted with ethyl acetate (20 mL × 3). The organic phases were combined and backwashed once with saturated brine (20 mL), and the organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 91-1 (900 mg, 2.47 mmol, yield 96.7%) as a yellow solid. ESI-MS (m / z): 365.2 [M+H] + . 1 H NMR(400MHz, CDCl3)δ7.85(s,1H),6.47(s,1H),3.93(s,3H),3.75(m,2H),3 .34-3.43(m,2H),2.98(s,2H),1.92(m,2H),1.69-1.79(m,2H),1.48(s,9H). Step 2: Pd / C 10% (900 mg) was added to a 75 mL hydrogenation bottle, THF (7 mL) was added, and 91-1 (900 mg, 2.47 mmol, 1.0 eq) of THF solution (10 mL) was added to the reaction flask and stirred at 25°C and 50 psi for 12 h. The reaction solution was filtered and the filtrate was concentrated under reduced pressure to obtain 91-2 (800 mg, 2.39 mmol, yield 96.9%) as a yellow solid. ESI-MS (m / z): 335.2 [M+H] + . 1 H NMR (400MHz, CDCl3) δ6.57(s,1H),6.37(s,1H),3.81(s,3H),3.75(br t,J=6.50Hz,2H),3.35-3.45(m,2H),2.89(s,2H),1.83-1.93(m,2H),1.63-1.72(m,2H),1.48(s,9H). Step 3: 91-2 (700 mg, 2.09 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, acetonitrile (7 mL), 6-(trifluoromethyl)pyridine-2-carboxylic acid (400 mg, 2.09 mmol, 1.0 eq), NMI (0.8 mL, 10.4 mmol, 5.0 eq) and TCFH (704 mg, 2.51 mmol, 1.2 eq) were added to the reaction solution and stirred at room temperature for 12 h. The precipitated solid was filtered and the filter cake was concentrated under reduced pressure to obtain 91-3 (1.00 g, 1.97 mmol, yield 94.1%) as a white solid. ESI-MS (m / z): 508.2 [M+H] + . 1 H NMR (400MHz, CDCl3) δ10.31(s,1H),8.47(d,J=7.75Hz,1H),8.33(s,1H),8.10(t,J=7.81Hz,1H),7.84(d,J=7.75Hz,1H ),6.47(s,1H),3.92(s,3H),3.74(m,2H),3.37-3.47(m,2H),3.00(s,2H),1.92(m,2H),1.68-1.77(m,2H),1.49(s,9H). Step 4: 91-3 (500 mg, 0.99 mmol, 1.0 eq) was placed in a 50 mL single-necked bottle, DCM (5 mL) was added, and dioxane hydrochloride solution (5 mL) was added, and stirred at 15 ° C for 2 h. The reaction solution was concentrated under reduced pressure and then saturated sodium bicarbonate aqueous solution was added to pH = 7-8, filtered, and the filter cake was rinsed with water and concentrated under reduced pressure to obtain 91-4 (400 mg, 0.98 mmol, yield 99.7%) as a yellow solid. ESI-MS (m / z): 408.0 [M+H] + . Step 5: 91-4 (200 mg, 0.49 mmol, 1.0 eq) was placed in a 50 mL single-mouth bottle, DMA (3.5 mL), M33 (207.89 mg, 0.49 mmol, 1.0 eq), KOAc (144 mg, 1.47 mmol, 3.0 eq), sodium acetate borohydride (103 mg, 0.49 mmol, 1.0 eq) were added to the reaction solution, and stirred at room temperature for 1 h. The reaction solution was purified by high performance liquid chromatography to obtain Example 91 (161 mg, 0.20 mmol, yield 40.2%) as a yellow solid. ESI-MS (m / z): 815.4 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ11.13(s,1H),10.12(s,1H),8.33-8.45(m,2H),8.11-8.23(m,2 H),7.18(d,J=7.75Hz,1H),7.10-7.14(m,1H),7.00-7.06(m,1H),6.68(s,1H),5.41(br dd,J=12.69,5.32Hz,1H),4.47(s,2H),3.86(s,3H),3.65(s,3H),3.41-3.51(m ,2H),2.97(s,2H),2.84-2.94(m,1H),2.59-2.78(m,2H),2.38(m,3H),2.11(br d,J=7.13Hz,2H),1.97-2.07(m,3H),1.68-1.88(m,6H),,1.38-1.52(m,1H),1.11-1.23(m,2H),0.82-0.96(m,2H). Embodiment 92: Step 1: Methyl 1-methoxy-4-oxyylidenecyclohexane-1-carboxylate (25.0 g, 134 mmol, 1.0 eq) was placed in a 250 mL three-necked flask, and MeOH (175 mL) was added. NaBH4 (10.2 g, 268 mmol, 2.0 eq) was slowly added at 0°C, and stirred in an ice bath for 1.5 h. Saturated aqueous ammonium chloride solution (200 mL) was added to the reaction solution, and water (100 mL) was added to dissolve the salt. The mixture was extracted with ethyl acetate (200 mL×3), and the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the mixture was purified by column chromatography (petroleum ether: ethyl acetate = 5:1-1:1) to obtain 92-1 (14.0 g, 74.38 mmol, yield 55.4%) as a transparent colorless oil. ESI-MS (m / z): 189.1 [M+H] + . 1 H NMR (400MHz, CDCl3) δ3.72(s,3H),3.59-3.68(m,1H),3.23(s,3H),1.98-2.07(m,2H),1.78-1.86(m,2H),1.67-1.75(m,2H),1.51-1.62(m,2H). Step 2: 92-1 (5.00 g, 26.5 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and DMA (35 mL) was added. NaH (1.59 g, 39.8 mmol, 1.5 eq) was slowly added at 0°C. The reaction was stirred at 0°C for 5 h. 3-Bromopropyne (5.93 g, 39.8 mmol, 1.5 eq) was added dropwise to the reaction solution at 0°C and stirred at room temperature for 12 h. The reaction solution was slowly poured into a saturated aqueous ammonium chloride solution (100 mL), extracted with ethyl acetate (150 mL × 3), the organic phase was separated and backwashed once with saturated brine (100 mL), the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 10:1-2:1) to obtain 92-2 (220 mg, 0.97 mmol, yield 18.3%) It is a yellow oil. 1 H NMR (400MHz, CDCl3) δ4.13 (d, J = 2.38Hz, 2H), 3.68 (s, 3H), 3.41-3.53 (m, 1H), 3.17 (s, 3H), 2 .34(t,J=2.32Hz,1H),1.98(m,2H),1.76-1.84(m,2H),1.63-1.73(m,2H),1.49-1.59(m,2H). Step 3: 92-2 (1.50 g, 6.63 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and THF (15 mL) was added. LiAlH4 tetrahydrofuran solution (8.0 mL, 19.9 mmol, 3.0 eq, 2.5 M) was added dropwise at 0°C and stirred at room temperature for 2 h. Water (1 mL), 15% NaOH aqueous solution (1 mL), and water (3 mL) were added under an ice bath to quench the reaction. Ethyl acetate (40 mL) was added and stirred for 10 min and then filtered. The filtrate was concentrated under reduced pressure to obtain 92-3 (1.13 g, 5.70 mmol, yield 86.0%) as a yellow oil. 1 H NMR (400MHz, CDCl3) δ4.20(s,2H),3.49-3.56(m,1H),3.46(br s,2H),3.20(s,3H),2.41(br s,1H),1.94(m,2H),1.74-1.87(m,3H),1.53-1.63(m,2H),1.18-1.33(m,2H). Step 4: M29 (800 mg, 2.37 mmol) was placed in a 100 mL single-mouth bottle, and DMF (10 mL), 92-3 (703 mg, 3.55 mmol, 1.5 eq) and Cs2CO3 (3.00 g, 9.46 mmol, 4.0 eq) were added to the reaction solution, and stirred at 100 ° C for 2 h. THF (50 mL) was added to the reaction solution and filtered, the filtrate was collected and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: THF = 2: 1-1: 2), ethyl acetate (10 mL) was added to the obtained solid, stirred for 10 min, and then filtered, and the filter cake was collected to obtain 92-4 (0.17 g, 0.37 mmol, yield 15.8%) as a white solid. ESI-MS (m / z): 478.2 [M+23] + . 1 H NMR(400MHz,DMSO-d6)δppm 11.12(s,1H),7.18(d,J=7.75Hz,1H),7.10-7.15(m,1H),7.00-7.07(m,1H),5.40 (dd,J=12.69,5.32Hz,1H),4.47(s,2H),4.44-4.46(m,1H),3.65(s,3H),3.44-3. 54(m,1H),3.29(d,J=5.63Hz,2H),3.11(s,3H),2.83-2.96(m,1H),2.63-2.79(m, 2H),1.99-2.09(m,1H),1.70-1.82(m,4H),1.32-1.45(m,2H),1.19-1.31(m,2H). Step 5: 92-4 (130 mg, 0.29 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (3 mL) and DMP (145 mg, 0.34 mmol, 1.2 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. Saturated sodium bicarbonate aqueous solution (10 mL) was added to the reaction solution, and dichloromethane (10 mL × 2) was used for extraction, and the organic phase was backwashed once with saturated brine (8 mL), and the organic phase was separated and dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 92-5 (80 mg, 0.18 mmol, yield 61.8%) as a white solid. ESI-MS (m / z): 454.2 [M+1] + . 1H NMR(400MHz,DMSO-d6)δ11.15(br s,1H),9.56(s,1H),7.20(d,J=7.82Hz,1H),7.15(d,J=7.34Hz,1H),7.03 -7.09(m,1H),5.43(dd,J=12.71,5.38Hz,1H),4.51(s,2H),3.67(s,3H), 3.54-3.64(m,1H),3.22(s,3H),2.86-2.98(m,1H),2.65-2.80(m,2H),2.01-2.10(m,1H),1.78-1.93(m,4H),1.39-1.61(m,4H). Step 6: 92-5 (80 mg, 0.18 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (3 mL), 1-1 (82 mg, 0.18 mmol, 1.0 eq), AcOH (21.19 mg, 0.35 mmol, 2.0 eq), sodium cyanoborohydride (22 mg, 0.35 mmol, 1.0 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. The reaction solution was filtered and separated and purified by high performance liquid chromatography to obtain Example 92 (40.79 mg, 0.05 mmol, yield 25.7%) as a yellow solid. ESI-MS (m / z): 900.5 [M+1] + . 1H NMR(400MHz,DMSO-d6)δ11.13(s,1H),10.49(s,1H),9.36(dd,J=7.00,1.38Hz,1H),8.90 (dd,J=4.13,1.50Hz,1H),8.68(s,1H),8.33(s,1H),7.34(dd,J=6.94,4.19Hz,1H),7.18( d,J=7.88Hz,1H),7.11-7.16(m,1H),7.01-7.07(m,1H),6.72(s,1H),5.41(dd,J=12.63,5 .25Hz,1H),4.55(t,J=5.32Hz,1H),4.48(s,2H),3.66(s,3H),3.47-3.56(m,1H),3.40(br t,J=5.19Hz,2H),3.10(s,3H),2.85-3.00(m,5H),2.60-2.76(m,6H),2.52-2.58(m,2H),2.33(br s,2H),2.00-2.11(m,1H),1.68-1.90(m,10H),1.48-1.64(m,3H),1.26-1.45(m,4H). Embodiment 93: Step 1: (1r, 4r)-ethyl 4-hydroxycyclohexanecarboxylate (20.0 g, 116 mmol, 1.0 eq) was placed in a 1L three-necked flask, and DMF (140 mL) and imidazole (8.70 g, 127 mmol, 1.1 eq) were added. Diphenyl tert-butyl chlorosilane (33.5 g, 122 mmol, 1.05 eq) was added dropwise to the reaction solution at room temperature, and the reaction solution was stirred at room temperature overnight. Water (200 mL) and ethyl acetate (500 mL) were added to the reaction solution, and the organic phase was separated and washed once with water (100 mL) and once with saturated sodium chloride (80 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 30:1-1:1) to obtain 93-1 (40.5 g, 98.63 mmol, yield 84.9%) as a colorless oil. 1H NMR(400MHz, CDCl3) δ7.67(dd,J=7.94,1.44Hz,4H),7.35-7.46(m,6H),4.07(q,J=7.13Hz,2H),3.55-3.66(m,1 H),2.21(tt,J=11.15,3.42Hz,1H),1.81-1.95(m,4H),1.27-1.47(m,4H),1.21(t,J=7.07Hz,3H),1.06(s,9H). Step 2: 93-1 (35.0 g, 85.2 mmol, 1.0 eq) was placed in a 1L three-necked flask and THF (150 mL) was added. LDA (51.1 mL, 102 mmol, 1.2 eq) was added dropwise at -65 °C under nitrogen protection. After the addition, it was stirred at -65 °C for 1 h. NFSI (22.3 mL, 102 mmol, 1.2 eq) was dissolved in THF (150 mL) and then added dropwise at -65 °C to the above reaction solution. The reaction solution was stirred at room temperature overnight. The reaction solution was poured into a saturated The mixture was added to an aqueous solution of ammonium chloride (300 mL), extracted with ethyl acetate (150 mL × 2), the combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: ethyl acetate = 100: 1-10: 1) to obtain 93-2 (36 g, 83.99 mmol, yield 98.5%) as a yellow oil. ESI-MS (m / z): 429.3 [M+H] + . 1 H NMR (400MHz, CDCl3) δ7.65-7.69(m,4H),7.36-7.45(m,6H),4.27(q,J=7.13Hz,2H),4.09-4.14(m, 1H),2.32-2.53(m,2H),1.76-1.85(m,2H),1.58-1.69(m,4H),1.35(t,J=7.13Hz,3H),1.10(s,8H). Step 3: 93-2 (36.0 g, 83.9 mmol, 1.0 eq) was placed in a 1L single-mouth bottle, THF (300 mL) and TBAF solution (168.0 mL, 167.98 mmol, 1 M, 2.0 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 10:1-1:1). 93-3 (4.20 g, 22.08 mmol, yield 26.3%) was obtained as a light yellow oil. 1H NMR (400MHz, CDCl3) δ4.25(q,J=7.13Hz,2H),4.10-4.16(m,1H),2.17-2.37(m,2H),1.79-1.98(m,4H),1.69-1.78(m,2H),1.32(t,J=7.13Hz,3H). Two-dimensional identification conclusion: NOESY: H-9 is related to H-8. Proton: H-7a (2.3ppm, J=36Hz) Conclusion: H-9e, F-13a. Step 4: 93-3 (5.00 g, 26.3 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and THF (50 mL) was added. A tetrahydrofuran solution of LiAlH4 (15.8 mL, 39.4 mmol, 2.5 M, 1.5 eq) was added dropwise at 0°C, and the reaction solution was stirred overnight at room temperature. Solid sodium sulfate decahydrate (5.0 g) was slowly added to the reaction solution at 0°C, stirred for 1 h, THF (100 mL) was added, filtered, and the filtrate was collected and concentrated under reduced pressure to obtain 93-4 (3.00 g, 20.3 mmol, yield 77.0%) as a light yellow oil. 1 H NMR (400MHz, CD3OD) δ3.92 (dt, J = 4.97, 2.45Hz, 1H), 3.53 (s, 1H), 3.48 (s, 1H), 1.72-1.86 (m, 4H), 1.53-1.68 (m, 4H). Step 5: 93-4 (3.00 g, 148 mmol, 1.0 eq) was placed in a 100 mL three-necked flask, and DCM (15 mL), TEA (2.25 g, 22.27 mmol, 1.1 eq) and DMAP (20 mg, 0.20 mmol, 0.01 eq) were added. The temperature was lowered to 0 °C and a solution of TBSCl (3.36 g, 22.27 mmol, 1.1 eq) in DCM (15 mL) was added dropwise. The reaction solution was stirred at room temperature overnight. Water (80 mL) and dichloromethane (100 mL) were added to the reaction solution, and the organic phase was separated and washed once with saturated brine (80 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (petroleum ether: ethyl acetate = 100: 1-10: 1) gave 93-5 (3.30 g, 12.6 mmol, yield 62.1%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ4.08 (br d, J=2.00Hz, 1H), 3.61 (d, J=19.76Hz, 2H), 1.77-1.95 (m,4H),1.60-1.72(m,4H),0.91(s,9H),0.08(s,6H). Step 6: 93-5 (5.50 g, 20.9 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and THF (50 mL) was added. NaH (1.26 g, 31.44 mmol, 1.5 eq) was added at 0°C and stirred at 0°C for 3 h. Propyl bromide (2.99 g, 25.2 mmol, 1.2 eq) was added dropwise to the reaction solution at 0°C and the reaction solution was stirred at room temperature overnight. The reaction solution was poured into a saturated aqueous ammonium chloride solution (80 mL) and extracted with ethyl acetate (100 mL × 2). The organic phase was separated and backwashed once with saturated brine (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography was used for separation and purification (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 93-6 (3.50 g, 11.6 mmol, yield 55.6%) as a yellow oil. 1 H NMR (400MHz, CDCl3) δ4.15 (d, J = 2.25Hz, 2H), 3.80-3.87 (m, 1H), 3.59 (d, J = 19.76Hz, 2H) ,2.40(t,J=2.31Hz,1H),1.75-1.84(m,5H),1.65-1.73(m,3H),0.91(s,9H),0.07(s,6H). Step 7: 93-6 (3.50 g, 11.7 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, THF (35 mL) and TBAF (23.3 mL, 23.3 mmol, 1 M, 2.0 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 93-7 (2.00 g, 10.7 mmol, yield 92.2%) as a light yellow oil. 1 H NMR (400MHz, CDCl3) δ4.16 (d, J = 2.25Hz, 2H), 3.84 (m, 1H), 3.55-3.66 (m, 2H), 2.41 (t, J = 2.38Hz, 1H), 1.72-1.83 (m, 8H). Step 8: 93-7 (1.00 g, 5.37 mmol, 2.0 eq) was placed in a 100 mL single-mouth bottle, and DMF (10 mL), M29 (0.91 g, 2.68 mmol, 1.0 eq), cesium carbonate (1.75 g, 5.37 mmol, 2.0 eq) and bistriphenylphosphine palladium dichloride (0.21 g, 0.27 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100 ° C for 2 h. THF (150 mL) was added to the reaction solution, and the mixture was stirred for 30 min and filtered. The filtrate was collected and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: tetrahydrofuran = 2: 1-1: 2). Ethyl acetate (8 mL) was added to the obtained product, stirred for 10 min, and filtered. The filter cake was collected to obtain 93-8 (350 mg, 0.79 mmol, yield 29.4%) as a white solid. ESI-MS (m / z): 444.1 [M+H] + . 1 H NMR(400MHz, DMSO-d6)δ11.13(s,1H),7.18(d,J=7.88Hz,1H),7.10-7.14(m,1H),7.00-7 .07(m,1H),5.40(dd,J=12.63,5.38Hz,1H),4.90(t,J=6.00Hz,1H),4.47(s,2H),3.83(br s,1H),3.64(s,3H),3.42(d,J=6.00Hz,1H),3.35-3.39(m,1H),2.86(m,1H),2.59-2.73(m,2H),2.01-2.09(m,1H),1.53-1.80(m,8H). Step 9: 93-8 (150 mg, 0.34 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle and DCM (4 mL) was added. DMP was slowly added at 0 °C. (288 mg, 0.68 mmol, 2.0 eq), the reaction solution was stirred at room temperature for 3 h. The reaction solution was slowly poured into a saturated sodium bicarbonate aqueous solution (10 mL), extracted with dichloromethane (10 mL × 2), the combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (petroleum ether: tetrahydrofuran = 1:2). 93-9 (100 mg, 0.23 mmol, yield 67.0%) was obtained as a white solid. ESI-MS (m / z): 442.3 [M+H] + . 1 H NMR (400MHz, CDCl3) δ9.72 (d, J = 5.38Hz, 1H), 8.18 (br s,1H),7.18(d,J=7.34Hz,1H),6.99-7.02(m,1H),6.77(d,J=7.34Hz,1H),5.21(dd,J=12.47,5.26Hz,1H),3.94(br s,1H),3.78(s,3H),2.68-3.01(m,3H),1.67-2.11(m,9H). Step 10: 93-9 (70 mg, 0.16 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle and DMA (2 mL), 1-1 (73 mg, 0.16 mmol, 1.0 eq), sodium cyanoborohydride (20 mg, 0.32 mmol, 2.0 eq), AcOH (10 mg, 0.16 mmol, 1.0 eq) were added, and the reaction solution was stirred at room temperature for 1 h. The reaction solution was filtered and purified by HPLC to obtain Example 93 (39.69 mg, 0.04 mmol, yield 27.9%) as a light yellow solid. ESI-MS (m / z): 888.4 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ11.16(s,1H),10.51(s,1H),9.33-9.42(m,1H),8.8 8-8.97(m,1H),8.70(s,1H),8.36(s,1H),7.36(dd,J=6.93,4.21Hz,1H),7. 20(d,J=7.92Hz,1H),7.13-7.17(m,1H),7.03-7.09(m,1H),6.76(s,1H),5. 43(dd,J=12.62,5.44Hz,1H),4.59(t,J=5.26Hz,1H),4.50(s,2H),3.85(br s,1H),3.67(s,3H),3.42(br t,J=5.01Hz,3H),2.87-3.04(m,5H),2.56-2.79(m,8H),2.01-2.10(m,1H),1.68-1.88(m,14H),1.51-1.66(m,3H). Embodiment 94: Step 1: 93-5 (6.80 g, 25.9 mmol) was placed in a 250 mL three-necked flask, THF (70 mL), p-nitrobenzoic acid (5.20 g, 31.1 mmol, 1.2 eq), triphenylphosphine (8.16 g, 31.1 mmol, 1.2 eq) were added to the reaction solution, DIAD (6.29 g, 31.1 mmol, 1.2 eq) was added dropwise to the reaction solution at 0°C, and stirred at room temperature for 2 h. Water (100 mL) was added to the reaction solution, and ethyl acetate (80 mL × 2) was used for extraction. The combined organic phases were backwashed once with saturated brine (50 mL), the organic phases were separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, separated and purified by column chromatography (petroleum ether: ethyl acetate = 30: 1-10: 1), and 94-1 (3.50 g, 8.50 mmol, yield 32.8%) was obtained as a white solid. 1 H NMR (400MHz, CDCl3) δ8.18-8.25(m,2H),8.11-8.17(m,2H),7.18(s,1H),4.89-4.98(m,1H) ,3.52(d,J=16.63Hz,2H),1.78-1.95(m,5H),1.44-1.69(m,3H),0.83(s,9H),0.00(s,6H). Step 2: 94-1 (3.50 g, 8.50 mmol) was placed in a 100 mL single-mouth bottle and THF (15 mL) was added. Lithium hydroxide (710 mg, 17.0 mmol, 2.0 eq) was dissolved in H2O (15 mL) and added to the reaction solution, and the reaction solution was stirred at room temperature overnight. Water (80 mL) was added to the reaction solution, and ethyl acetate was extracted (100 mL × 2). The organic phases were combined and dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography purification (petroleum ether: ethyl acetate = 10: 1-1: 1) was performed to obtain 94-2 (1.70 g, 6.48 mmol, yield 76.2%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ3.60-3.67 (m, 1H), 3.56 (d, J = 16.76Hz, 2H), 1.83-1. 97(m,4H),1.58-1.69(m,2H),1.37-1.51(m,2H),0.91(s,9H),0.07(s,6H). Step 3: 94-2 (1.70 g, 6.48 mmol, 1.0 eq) was placed in a 100 mL three-necked flask and THF (17 mL) was added. NaH (0.52 g, 12.9 mmol, 2.0 eq) was added at 0°C and stirred at 0°C for 3 h. Propyl bromide (1.16 g, 7.77 mmol, 1.2 eq) was added dropwise to the reaction solution at 0°C and the reaction solution was stirred at room temperature overnight. The reaction solution was poured into a saturated aqueous ammonium chloride solution (80 mL) and extracted with ethyl acetate (100 mL × 2). The organic phase was separated and backwashed once with saturated brine (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography was used for separation and purification (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 94-3 (1.30 g, 4.33 mmol, yield 66.8%) as a light yellow oil. 1 H NMR(400MHz, CDCl3)δ4.22(d,J=2.35Hz,2H),3.56(d,J=16.70Hz,2H),3.46-3.53(m,1H),2.41(t, J=2.23Hz,1H),1.87-1.98(m,4H),1.59-1.70(m,2H),1.39-1.55(m,2H),0.91(s,9H),0.07(s,6H). Step 4: 94-3 (1.30 g, 4.33 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, THF (10 mL) and TBAF solution (8.70 mL, 8.65 mmol, 1 M, 2.0 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 10:1-1:1) to obtain 94-4 (700 mg, 3.76 mmol, yield 86.9%) as a light yellow oil. 1H NMR (400MHz, CDCl3) δ4.22(d,J=2.35Hz,2H),3.59(d,J=19.67Hz,2H),3.50-3.55(m,1H),2.42 (t,J=2.35Hz,1H),2.04-2.10(m,2H),1.88-1.96(m,2H),1.59-1.72(m,2H),1.34-1.52(m,2H). Step 5: 94-4 (550 mg, 2.96 mmol, 2.0 eq) was placed in a 100 mL single-mouth bottle, and DMF (6 mL), M29 (500 mg, 1.48 mmol, 1.0 eq), cesium carbonate (963 mg, 2.96 mmol, 2.0 eq) and bistriphenylphosphine palladium dichloride (115 mg, 0.15 mmol, 0.1 eq) were added to the reaction solution, and the reaction solution was stirred at 100 ° C for 2 h. THF (30 mL) was added to the reaction solution, and the filtrate was concentrated under reduced pressure after filtration, and purified by column chromatography (petroleum ether: tetrahydrofuran = 2: 1-1: 2), and ethyl acetate (5 mL) was added to the obtained oil, and the mixture was stirred for 10 min and filtered. The filter cake was collected to obtain 94-5 (80 mg, 0.18 mmol, yield 12.2%) as a white solid. ESI-MS (m / z): 444.2 [M+H] + . 1 H NMR(400MHz, CDCl3)δ8.03(br s,1H),7.18(d,J=7.75Hz,1H),7.00(t,J=7.94Hz,1H),6.77(d,J=7.38Hz,1H),5.20(dd,J=12.57,5.32Hz,1H),4.49(s,2H),3.79(s,3H ),3.54-3.68(m,3H),2.70-3.02(m,3H),2.21-2.29(m,1H),2.04-2.14(m,2H),1.92-2.01(m,2H),1.65-1.79(m,3H),1.35-1.54(m,2H). Step 6: 94-5 (80 mg, 0.18 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DCM (3 mL) and DMP (114 mg, 0.27 mmol, 1.5 eq) were added to the reaction solution, and stirred at room temperature for 2 h. Saturated sodium bicarbonate aqueous solution (10 mL) and acetic acid were added to the reaction solution. The mixture was extracted with ethyl ester (10 mL×2), the combined organic phases were dried over anhydrous sodium sulfate and concentrated, and separated and purified by thin layer chromatography (petroleum ether:tetrahydrofuran=0:1) to obtain 94-6 (70 mg, 0.16 mmol, yield 87.9%) as a white solid. ESI-MS (m / z): 442.2 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ11.13(s,1H),9.67(d,J=6.50Hz,1H),7.11-7.21(m,2H),7.01-7.08(m,1H),5.41(dd,J=12.51,5.13Hz,1H),4.5 2(s,2H),3.63-3.68(m,4H),2.84-2.97(m,1H),2.59-2.78(m,2H),2.01(m,2H),1.81-1.94(m,3H),1.66-1.76(m,2H),1.40-1.53(m,2H). Step 7: 94-6 (70 mg, 0.16 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMA (2 mL), 1-1 (73 mg, 0.16 mmol, 1.0 eq), glacial acetic acid (10 mg, 0.16 mmol, 1.0 eq), sodium cyanoborohydride (15 mg, 0.24 mmol, 1.5 eq) were added to the reaction solution, and the reaction solution was stirred at room temperature for 2 h. After the reaction solution was filtered, it was separated and purified by high performance liquid chromatography to obtain Example 94 (21.05 mg, 0.02 mmol, yield 14.8%) as a light yellow solid. ESI-MS (m / z): 888.5 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.13(s,1H),10.49(s,1H),9.36(d,J=7.00Hz,1H),8.9 0(d,J=3.88Hz,1H),8.68(s,1H),8.33(s,1H),7.34(dd,J=6.94,4.19Hz,1H),7.1 8(d,J=7.75Hz,1H),7.11-7.16(m,1H),7.01-7.08(m,1H),6.73(s,1H),5.41(dd, J=12.63,5.25Hz,1H),4.55(t,J=5.19Hz,1H),4.50(s,2H),3.66(s,3H),3.59(br s,1H),3.40(t,J=5.07Hz,3H),2.86-3.02(m,5H),2.56-2.78(m,7H),2.47(br s,1H),2.00-2.07(m,1H),1.69-1.99(m,10H),1.42-1.63(m,7H). Embodiment 95: 19-1 (40 mg, 0.08 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, and DMF (1.5 mL), 70-2 (31 mg, 0.09 mmol, 1.2 eq), NaI (11 mg, 0.08 mmol, 1.0 eq), NaHCO3 (27 mg, 0.32 mmol, 4.0 eq), TEA (32 mg, 0.32 mmol, 4.0 eq) were added to the reaction solution, and the reaction solution was stirred at 60° C. overnight. The reaction solution was filtered and separated and purified by high performance liquid chromatography to obtain Example 95 (15.4 mg, 0.02 mmol, yield 22.9%) as a light yellow solid. ESI-MS (m / z): 832.5 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.12(s,1H),10.51(s,1H),9.38(dd,J=7.00,1.50Hz,1H),8.91(dd,J=4.13 ,1.38Hz,1H),8.69(s,1H),8.35(s,1H),7.35(dd,J=7.00,4.25Hz,1H),6.86-7.05(m,3H),6.75(s,1H ),5.37(dd,J=12.57,5.19Hz,1H),4.59(t,J=5.25Hz,1H),3.64(s,3H),3.41(m,3H),2.84-3.04(m,1 2H),2.56-2.75(m,10H),2.25-2.37(m,2H),1.97-2.05(m,1H),1.69-1.88(m,7H),1.45-1.67(m,4H). Embodiment 96: M29 (20 mg, 0.06 mmol, 1.0 eq) and 1-3 (33 mg, 0.06 mmol, 1.0 eq) were placed in a 40 mL single-necked bottle, and DMF (1 mL), sodium tert-butoxide (17 mg, 0.18 mmol, 3.0 eq) and CAS: 1612891-29-8 (5 mg, 0.01 mmol, 0.1 eq) were added, and stirred at 100° C. for 2 hours. The reaction solution was separated and purified by HPLC to obtain Example 96 (1.44 mg, yield 2.9%) as a light yellow solid. ESI-MS (m / z): 831.4 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ10.85-11.37(s,1H),10.49(s,1H),9.35(d,J=7.00Hz,1H),8.89(br d,J=3.25Hz,1H),8.67(s,1H),8.33(s,1H),7.33(dd,J=7.00,4.25Hz,1H),6.95-7.02(m,1H),6.89-6.94(m,1H),6.86(br d,J=8.00Hz,1H),6.70-6.75(m,1H),5.34(br dd,J=12.63,5.75Hz,1H),4.56(br t,J=5.13Hz,1H),3.63(s,3H),3.02-3.13(m,3H),2.88-3.01(m,5H),2.59-2.74(m ,7H),2.30-2.46(m,5H),1.96-2.06(m,1H),1.66-1.88(m,9H),1.35-1.64(m,8H). Embodiment 97: The synthesis process of compound 97-1 refers to patent WO2022143856A1 specification P79-P80. 1-1 (83 mg, 0.18 mmol), 97-1 (70 mg, 0.18 mmol), KOAc (35 mg, 0.36 mmol), sodium triacetoxyborohydride (114 mg, 0.54 mmol) and DMA (1 mL) were added to a 10 mL single-necked bottle and stirred at room temperature for 1 h. After the reaction was completed, Water (1 mL) was added, filtered, and separated by column chromatography. The eluent was DCM:MeOH = 1:0-10:1 to obtain Example 97 as a yellow solid (50 mg). The purity was 95.22%. ESI-MS (m / z): 834.6 [M+H] + . 1H NMR (500MHz, DMSO-d6) δ11.11(s,1H),10.49(s,1H),9.35(dd,J=6.96,1.44Hz,1H),8.89(dd,J=4.14,1.38Hz,1H),8.68(s,1H),8.34(s,1H),7. 70(d,J=11.42Hz,1H),7.43(d,J=7.40Hz,1H),7.27-7.38(m,1H),6.73(s,1H),5.11(dd,J=12.86,5.33Hz,1H),4.55(t,J=5.21Hz,1H),3.61(br d,J=11.54Hz,2H),3.40(br t,J=4.77Hz,2H),2.83-3.03(m,7H),2.52-2.70(m,6H),2.42(br s,2H),2.22(br d,J=6.65Hz,2H),2.00-2.09(m,1H),1.66-1.90(m,9H),1.48-1.65(m,3H),1.21-1.36(m,2H). Embodiment 98: The synthesis process of compound 98-1 refers to the synthesis method of P735 of WO2022147465A1 specification. 98-1 (88 mg, 0.19 mmol), 1-1 (70 mg, 0.19 mmol), KOAc (37 mg, 0.38 mmol), sodium triacetoxyborohydride (120 mg, 0.57 mmol) and DMA (1 mL) were added to a 100 mL single-mouth bottle and stirred at room temperature for 1 h. After the reaction was completed, water (1 mL) was added, filtered, and separated by column chromatography. The eluent was DCM:MeOH = 1:0-10:1. Example 98 was obtained as a yellow solid of 30 mg. ESI-MS (m / z): 816.7 [M+H] + . 1H NMR(500MHz,DMSO-d6)δ11.10(s,1H),10.49(s,1H),9.33-9.40(m,1H),8.90(br d,J=2.89Hz,1H),8.68(s,1H),8.35(s,1H),7.34(dd,J=6.84,4.33Hz,1H),6.94-7.09(m,3H),6.74(s,1H),5.38(br dd,J=12.42,5.40Hz,1H),4.56(t,J=5.21Hz,1H),3.56-3.61(m,3H),3.40(br t,J=4.89Hz,2H),3.18-3.30(m,1H),2.84-3.04(m,5H),2.54-2.78(m,6H),2.44(br d,J=7.28Hz,3H),1.49-2.06(m,20H). Embodiment 99: Step 1: Place p-bromoaniline (10.0 g, 58.1 mmol, 1.0 eq) in a 100 mL single-mouth bottle, add toluene (7 mL) and acrylic acid (5.03 g, 69.7 mmol, 1.2 eq), and stir at 100 ° C for 8 h. Add NaOH aqueous solution (1N, 200 mL) to the reaction solution, separate the aqueous phase, add 2M hydrochloric acid to adjust the pH to 3, and then extract with ethyl acetate (250 mL×3), combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (petroleum ether: ethyl acetate = 10:1 to 0:1) to obtain 99-1 (10 g, 40.9 mmol, 70.5%) as a light brown solid. ESI-MS (m / z): Br, 244.0 [M+1] + ,246.0[M+3] + . 1 H NMR (400MHz, CDCl3) δ7.22-7.27(m,2H),6.46-6.53(m,2H),3.42(t,J=6.26Hz,2H),2.65(t,J=6.26Hz,2H). Step 2: 99-1 (5.00 g, 20.4 mmol, 1.0 eq) was placed in a 100 mL single-necked bottle, AcOH (35 mL) and urea (2.46 g, 40.9 mmol, 2.0 eq) were added, and stirred at 120°C for 12 h. Water (100 mL) was added to the reaction solution to precipitate a white solid, which was filtered, and the filter cake was collected and concentrated under reduced pressure to obtain 99-2 (2.5 g, 9.29 mmol, yield 45.4%). ESI-MS (m / z): Br, 269.0 [M+1] + ,271.0[M+3] + . 1 H NMR (400MHz, DMSO-d6) δ10.43(s,1H),7.52-7.62(m,2H),7.26-7.34(m,2H),3.78(t,J=6.62Hz,2H),2.70(t,J=6.68Hz,2H). Step 3: 99-2 (300 mg, 1.11 mmol, 1.0 eq) and DMA (3 mL) were placed in a 50 mL single-mouth bottle, 4-(dimethoxymethyl)piperidine (532 mg, 3.34 mmol, 3.0 eq), Cs2CO3 (182 mg, 0.56 mmol, 3.0 eq), and catalyst (CAS No.: 1814936-54-3) (108 mg, 0.11 mmol, 0.1 eq) were added to the reaction solution, and stirred at 100 ° C for 2 h under nitrogen protection. The reaction solution was concentrated under reduced pressure, and dichloromethane was added, filtered, and the filtrate was concentrated under reduced pressure and purified by column chromatography (petroleum ether: ethyl acetate = 5:1-0:1) to obtain 99-3 (120 mg, 0.35 mmol, yield 31.0%) as a light yellow solid. ESI-MS (m / z): 348.1 [M+H] + . 1 H NMR (400MHz, CDCl3) δ7.53(br s,1H),7.15(d,J=9.01Hz,2H),6.94(d,J=9.01Hz,2H),4.09(d,J=7.13Hz,1H),3.81(t,J=6.69Hz,2H),3.71(br d,J=12.26Hz,2H),3.38(s,6H),2.81(t,J=6.69Hz,2H),2.70(td,J=12.26,2.25Hz,2H),1.85(m,2H),1.77(m,1H),1.37-1.54(m,2H). Step 4: 99-3 (72 mg, 0.21 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, formic acid (3 mL) was added, and stirred at 25 °C for 2 h. The reaction solution was concentrated under reduced pressure to obtain 99-4 (62 mg, 0.21 mmol, 100.0%) as a brown oil. ESI-MS (m / z): 302.1 [M+H] + . Step 5: 99-4 (62 mg, 0.21 mmol, 1.0 eq) was placed in a 50 mL single-mouth bottle, DMA (2 mL), 1-1 (95 mg, 0.21 mmol, 1.0 eq), KOAc (60 mg, 0.62 mmol, 3.0 eq), sodium triacetoxyborohydride (43 mg, 0.21 mmol, 1.0 eq) were added to the reaction solution, and stirred at room temperature for 1 h. The reaction solution was filtered and separated and purified by high performance liquid chromatography to obtain Example 99 (65.0 mg, 0.09 mmol, yield 42.2%) as a yellow solid. ESI-MS (m / z): 748.6 [M+H] + . 1 H NMR (400MHz, DMSO-d6) δ10.49(s,1H),10.25(s,1H),9.36(dd,J=6.88,1.50Hz,1H),8.90(dd,J=4.13,1.50Hz,1H),8.68(s,1H),8.35(s,1H),7 .34(dd,J=7.00,4.25Hz,1H),7.14(d,J=9.01Hz,2H),6.93(d,J=9.01Hz,2H),6.74(s,1H),4.55(t,J=5.32Hz,1H),3.65-3.73(m,4H),3.40(br t,J=5.25Hz,2H),3.00(s,2H),2.93(d,J=10.51Hz,2H),2.62-2.72(m,8H),2.2 2(d,J=6.75Hz,2H),1.67-1.90(m,10H),1.45-1.65(m,4H),1.16-1.30(m,2H). Embodiment 100: Example 100 was obtained by a similar synthesis method to Example 78 as a white solid. ESI-MS (m / z): 817.5 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ11.09(br s,1H),10.93(s,1H),8.97(s,1H),8.75(br d,J=4.41 Hz,1H),8.33(s,1H),8.25(br d,J=8.58Hz,1H),7.57(dd,J=8.34,4.77Hz,1H),6.94-7.01(m,1H),6.85-6.92(m,2H ),6.75(s,1H),5.36(dd,J=12.40,5.01Hz,1H),4.54(t,J=5.13Hz,1H),3.63(s,3H),3 .38(t,J=5.13Hz,2H),3.11(m,2H),2.84-3.04(m,5H),2.56-2.76(m,7H),2.42(m,2H ),2.25(m,2H),1.96-2.05(m,1H),1.67-1.91(m,9H),1.45-1.67(m,4H),1.32(m,2H). Embodiment 101: Step 1: (5-Bromo-2-fluorophenyl)acetonitrile (5.00 g, 23.36 mmol, 1.0 eq) was placed in a 100 mL single-mouth bottle, THF (35 mL) was added, methyl acrylate (2.21 g, 25.70 mmol, 1.1 eq) was added, the temperature was lowered to 0°C, sodium methoxide (0.13 g, 2.34 mmol, 0.1 eq) was added, and the mixture was stirred at 25°C for 2 h. The reaction solution was concentrated under reduced pressure, separated and purified by column chromatography (petroleum ether: ethyl acetate = 1:1), and 101-1 (670 mg, 1.43 mmol, yield 8.1%) was obtained as a white solid. ESI-MS (m / z): Br, 300.3 [M+1] + ,302.0[M+3] + . 1 HNMR (400MHz, CDCl3) δ7.59 (dd, J=6.54, 2.38Hz, 1H), 7.46 (m, 1H), 7.01 (t, J=9.17 Hz,1H),4.24(t,J=7.46Hz,1H),3.70(s,3H),2.45-2.61(m,2H),2.16-2.29(m,2H). Step 2: 101-1 (670 mg, 2.23 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, AcOH (6.7 mL) and H2SO4 (0.67 mL) were added, and the mixture was stirred at 90 °C for 2 h. Water was added to the reaction solution to precipitate a white solid. The mixture was filtered, and the filter cake was collected and concentrated under reduced pressure to obtain 101-2 (500 mg, 1.75 mmol, yield: 78.3%) as a white solid. ESI-MS (m / z): Br, 285.9 [M+1] + ,287.9[M+3] + . 1 H NMR (400MHz, DMSO-d6) δ10.92 (s, 1H), 7.50-7.61 (m, 2H), 7.20 (t, J = 9.36Hz, 1H), 4.08 (dd, J =12.87,4.89Hz,1H),2.67-2.79(m,1H),2.55-2.59(m,1H),2.24(m,1H),1.96-2.04(m,1H). Step 3: 101-2 (500 mg, 1.86 mmol, 1.0 eq) was placed in a 50 mL single-mouth bottle, and dioxane (5 mL), 4-(dimethoxymethyl)piperidine (834 mg, 5.24 mmol, 3.0 eq), Cs2CO3 (1708 mg, 5.24 mmol, 3.0 eq), and catalyst (CAS No.: 1814936-54-3) (170 mg, 0.17 mmol, 0.1 eq) were added to the reaction solution, and stirred at 100 ° C for 2 h under nitrogen protection. Dichloromethane (20 mL) was added to the reaction solution, filtered, and the filtrate was concentrated under reduced pressure and separated by column chromatography (petroleum ether: ethyl acetate = 5:1-0:1) to obtain 101-3 (175 mg, 0.48 mmol, yield: 27.5%) as a yellow solid with a purity of 88.4%. ESI-MS (m / z): 365.1 [M+H] + . 1 H NMR (400MHz, CDCl3) δ7.89 (br s,1H),6.86-6.96(m,1H),6.73-6.83(m,1H),6.59-6.68(m,1H),4.02(d,J=7.25Hz,1H),3.77(dd,J=11.26,5.25Hz,1H),3.45-3.5 2(m,2H),3.30(s,6H),2.67-2.76(m,1H),2.49-2.66(m,3H),2.11-2.30(m,2H),1.74-1.82(m,2H),1.65(m,1H),1.32-1.45(m,2H). Step 4: 101-3 (160 mg, 0.44 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, formic acid (5 mL) was added, and the mixture was stirred at 25 °C for 3 h. The reaction solution was concentrated under reduced pressure to obtain 101-4 (139 mg, 0.44 mmol) as a yellow oil. ESI-MS (m / z): 319.1 [M+H] + . Step 5: 101-4 (139 mg, 0.44 mmol, 1.0 eq) was placed in a 50 mL single-mouth bottle, DMA (4 mL), 1-1 (201 mg, 0.44 mmol, 1.0 eq), KOAc (128 mg, 1.31 mmol, 3.0 eq), sodium triacetoxyborohydride (92 mg, 0.44 mmol, 1.0 eq) were added to the reaction solution, and stirred at 20° C. for 1 h. After the reaction solution was filtered, the filtrate was separated and purified by high performance liquid chromatography to obtain Example 101 (127 mg, 0.17 mmol, yield: 38.3%) as a yellow solid with a purity of 98.2%. ESI-MS (m / z): 765.4 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ10.84(br s,1H),10.49(s,1H),9.36(dd,J=7.03,1.43Hz,1H),8.90(dd,J=4.05,1.43Hz,1H),8.68(s,1H),8.35(s,1H),7.33(dd,J=6.97,4. 23Hz,1H),7.01(t,J=9.30Hz,1H),6.80-6.91(m,2H),6.73(s,1H),4.56(t,J=5.25Hz,1H),3.95(dd,J=12.58,4.95Hz,1H),3.58(br d,J=10.97Hz,2H),3.40(br t,J=5.01Hz,2H),2.99(s,2H),2.93(br d,J=10.97Hz,2H),2.53-2.81(m,7H),2.33-2.50(m,3H),2.17-2.30(m,3H), 1.95-2.05(m,1H),1.69-1.90(m,8H),1.47-1.68(m,4H),1.14-1.28(m,2H). Embodiment 102: Step 1: 3-(4-bromophenyl)piperidine-2,6-dione (500 mg, 1.86 mmol, 1.0 eq) was placed in a 50 mL single-mouth bottle, and dioxane (5 mL), 4-(dimethoxymethyl)piperidine (890 mg, 5.59 mmol, 3.0 eq), Cs2CO3 (1.82 g, 5.59 mmol, 3.0 eq), 1814936-54-3 (181 mg, 0.19 mmol, 0.1 eq) were added to the reaction solution, and stirred at 100 ° C for 2 h under nitrogen protection. DCM (80 mL) was added to the reaction solution, filtered, and the filtrate was concentrated under reduced pressure and purified by column chromatography (PE: EA = 3: 1 to 0: 1) to obtain 102-1 (100 mg, 0.29 mmol, yield 15.5%) as a yellow solid. ESI-MS (m / z): 347.2 [M+H] + . 1 H NMR (400MHz, CDCl3) δ7.92 (br s,1H),7.08(d,J=8.63Hz,2H),6.93(d,J=8.63Hz,2H),4.09(d,J=7.25Hz,1H), 3.67-3.76(m,3H),3.38(s,6H),2.60-2.76(m,4H),2.15-2.33(m,2H),1.85(br d,J=13.26Hz,2H),1.70-1.78(m,1H),1.45(m,2H). Step 2: 102-1 (90 mg, 0.26 mmol, 1.0 eq) was placed in a 40 mL single-necked bottle, formic acid (4 mL) was added, and the mixture was stirred at 25 °C for 1 h. The reaction solution was concentrated under reduced pressure to obtain 102-2 (78.03 mg, 0.26 mmol) as a yellow oil. ESI-MS (m / z): 300.3 [M+H] + . Step 3: 102-2 (78 mg, 0.26 mmol, 1.0 eq) was placed in a 50 mL single-necked bottle, DMA (3 mL), 1-1 (120 mg, 0.26 mmol, 1.0 eq), KOAc (76 mg, 0.78 mmol, 3.0 eq), sodium triacetoxyborohydride (55 mg, 0.26 mmol, 1.0 eq) were added to the reaction solution and stirred at room temperature for 1 h. The reaction solution was filtered and separated and purified by high performance liquid chromatography to obtain Example 102 (67.41 mg, 0.09 mmol, yield 34.8%) as a yellow solid. ESI-MS (m / z): 747.4 [M+H]+ . 1 H NMR (400MHz, DMSO-d6) δ10.78(s,1H),10.49(s,1H),9.36(dd,J=7.03,1.43Hz,1H),8.90(dd,J=4.17,1.55Hz,1H),8.68(s,1H),8.34(s, 1H),7.30-7.37(m,1H),7.04(d,J=8.70Hz,2H),6.89(d,J=8.70Hz,2H),6.74(s,1H),4.56(t,J=5.25Hz,1H),3.63-3.77(m,3H),3.40(br t,J=5.13Hz,2H),2.99(s,2H),2.93(br d,J=11.09Hz,2H),2.59-2.70(m,5H),2.35-2.49(m,4H),2.21(br d,J=7.03Hz,2H),1.98-2.17(m,2H),1.45-1.91(m,13H),1.15-1.28(m,2H). Embodiment 103: 77-6 (300 mg, 0.72 mmol, 1.0 eq) was placed in a 40 mL single-mouth bottle, DMF (5 mL), 61-2 (330 mg, 0.72 mmol, 1.0 eq), DIEA (185 mg, 1.43 mmol, 2.0 eq) were added to the reaction solution, and finally HATU (299 mg, 0.79 mmol, 1.1 eq) was added and stirred at room temperature for 2 h. After the reaction solution was filtered, the filtrate was separated and purified by high performance liquid chromatography to obtain Example 103 (357.08 mg, 0.40 mmol, yield 55.6%) as a white solid. ESI-MS (m / z): 864.4 [M+H] + . 1H NMR (400MHz, DMSO-d6) δ10.94(s,1H),10.53(s,1H),8.98(s,1H),8.75(d,J=4.17Hz,1H),8.36(s,1H),8.22-8.3 0(m,1H),7.51-7.66(m,1H),7.34(d,J=12.87Hz,1H),7.13(d,J=7.15Hz,1H),6.78(s,1H),5.02(s,1H),4.54(t,J =5.13Hz,1H),3.95(s,3H),3.84-3.93(m,3H),3.75(m,1H),3.61(m,1H),3.36-3.50(m,3H),3.15-3.23(m,2H),3 .03-3.13(m,4H),2.96(m,2H),2.75(t,J=6.68Hz,2H),2.59-2.70(m,4H),1.66-1.95(m,10H),1.44-1.65(m,3H). Experimental Example 1 Degradation test of IRAK4 in THP-1 cells An appropriate amount of THP-1 cells were inoculated in a 6-well cell culture plate, and the cell plate was placed in a 5% carbon dioxide incubator at 37°C for overnight culture, and then a dimethyl sulfoxide solution of the compound to be tested was added, with the final concentration of the compound in the range of 0.0128 to 1000 nM. After continued culture for 24 hours, the culture medium was removed, and the cells were collected into a 1.5 mL centrifuge tube. After adding lysis buffer and grinding thoroughly, the cells were placed on ice for 30 minutes, centrifuged at 15000xg and 4°C for 20 minutes, and the supernatant was taken to detect the IRAK4 protein level by Western Blot. The experimental results are shown in Table 1: Table 1 IRAK4 protein degradation activity of the compounds of the present invention The experimental results show that the compounds of the present invention have a good degradation effect on IRAK4 protein. Experimental Example 2: Pharmacokinetics test in mice 1. Test method: Six male mice weighing 20-30 g were divided into two groups. One group was intravenously injected with 2 mg / kg, and the other group was gavaged with 10 mg / kg. Blood was collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h after administration. After pretreatment, plasma samples were detected by LC / MS / MS in MRM mode, and appropriate standard curves were established to quantify the target compounds in plasma samples to obtain the drug concentration-time curve in plasma. WinNonlin software was used to calculate pharmacokinetic parameters using a non-compartmental model. 2. Test results: The above pharmacokinetic test was carried out on the compound of the present invention, and the results are shown in Table 2: Table 2 Pharmacokinetic results of the compounds of the present invention in mice The experimental results show that the compound of the present invention has good pharmacokinetic properties in mice.

Claims

1. A compound, which is a compound as represented by formula (I), or an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as represented by formula (I), in: Ring A is an 8-13 membered spiro ring having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; Ring B is phenyl, naphthyl, 5-6 membered monocyclic heteroaryl or 9-10 membered bicyclic heteroaryl; R 1 , R 2 and R 3 are independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , C 1-6 Alkyl, C 2-6 Alkenyl, C 1- 6 Alkoxy, -(C 0-3 Alkylene)-C 3-6 Cycloalkyl or -(C 0-3 Alkylene)-3-8 membered heterocyclic group, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -(C 0-3 Alkylene)-C 3-6 Cycloalkyl and -(C 0-3 The 3- to 8-membered heterocyclic group may be independently optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , C 1-3 Alkyl, C 1-3 Alkoxy, C 1- 3 Halogenated alkoxy, C 1-3 Hydroxyalkyl and C 1-3 Substituted by a haloalkyl substituent; Each R a and R b are independently hydrogen, deuterium, halogen, oxo, CN, NO 2 , -R 4 、-OR c 、-SR c 、-N(R c ) 2 ,-C(R c ) 3 、-S(=O) 2 R c 、-S(=O) 2 N(R c ) 2 、-S(=O)R c ,-S(=O)(NR c )R c 、-P(=O)(OR c ) 2 、-P(=O)(N(R c ) 2 ) 2 、-CF(R c ) 2 , -CF 2 (R c ),-CF 3 ,-C(R c ) 2 -OR c ,-C(R c ) 2 -N(R c ) 2 、-C(=O)R c 、-C(=O)OR c or -C(=O)N(R c ) 2 ; or two R on the same atom a The group is optionally combined with its intermediate atom to form a C 3-4 Cycloalkyl or 3-4 membered heterocyclic group; each R 4 Independently for C 1-6 Alkyl, C 2-6 Alkenyl, phenyl, C 3-7 Cycloalkyl, 3-7 membered heterocyclic or 5-6 membered heteroaryl ring, said R 4 can be independently optionally substituted by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO 2 NH 2 , oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 Substituted by a haloalkyl substituent; Each R c are independently hydrogen, deuterium, C 1-6 Alkyl, phenyl, C 4-7 Cycloalkyl, 4-7 membered heterocyclyl or 5-6 membered heteroaryl, the C 1-6 Alkyl, phenyl, C 4-7 Cycloalkyl, 4-7 membered heterocyclyl and 5-6 membered heteroaryl may be independently optionally substituted by 1, 2 or 3 radicals selected from deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1- 3 or two R on the same atom c The group is optionally combined with its intermediate atom to form a C 4-7 Cycloalkyl, a 4-11 membered bridged bicyclic or spirocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, said C 4-7 Cycloalkyl and 4-11 membered bridged bicyclic or spirocyclic rings having 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur may be further optionally substituted by 1, 2 or 3 atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , C 1- 3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 Substituted by a haloalkyl substituent; m and n are each independently 0, 1, 2, 3, 4, 5, 6, 7 or 8; L is C 1-20 Alkylene, wherein 1, 2, 3, 4 or 5 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d ) 2 -, -Cy-, -O-, -C(=O)- and -N(R d )-unit is replaced; wherein each -Cy- is independently C 4-7 Cycloalkyl, 4-11 membered heterocyclyl, 5-11 membered spirocyclyl, 5-11 membered bridged bicyclic radical, phenyl, 5-6 membered heteroaryl, each -Cy- can be independently optionally replaced by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO 2 NH 2 , oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and -C 1-3 Substituted by a haloalkyl substituent; Each R d independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 or C 1-3 alkyl; And DIM is the E3 ubiquitin ligase binding part.

2. The compound according to claim 1, wherein ring A is: in: X 1 , X 2 , X 3 , X 4 , X 5 Each independently is CH 2 , -C(=O)-, NH, O or S; a and c are each independently 1 or 2; b and d are each independently 0, 1 or 2, wherein b and d are not 0 at the same time and the sum of b and d is 2, 3 or 4.

3. The compound according to claim 1 or 2, wherein each R a are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , -CF 3 or C 1-6 Alkyl; or two R on the same atom a Group formation C 3-4 Cycloalkyl.

4. The compound as described in any one of claims 1 to 3, wherein each R a are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , -CF 3 , methyl, ethyl, n-propyl or isopropyl; or two R a The group forms a cyclopropyl or cyclobutyl group.

5. The compound according to any one of claims 1 to 4, wherein ring B is:

6. The compound according to any one of claims 1 to 5, wherein each R b are independently hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , -COOH, C 1-6 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclyl or 7-8 membered bridged bicyclic ring; 1-6 Alkyl, C 3-6 Cycloalkyl, 4-6 membered heterocyclyl and 7-8 membered bridged bicyclic ring may be independently optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, OH, CN, oxo, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 The alkyl group is substituted with a haloalkyl substituent.

7. The compound according to any one of claims 1 to 6, in, Each R b independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl and may be independently optionally substituted by 1, 2 or 3 selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , methyl, ethyl, methoxy, ethoxy, -CHF 2 , -CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent.

8. A compound as described in any one of claims 1 to 7, wherein Parts are: in: R b1 and R b4 are independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , CH 3 , CH 2 CH 3 , -CF 2 or -CF 3 ; R b2 and R b3 are independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl and may be independently optionally substituted by 1, 2 or 3 selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 , NH 2 , methyl, ethyl, methoxy, ethoxy, -CHF 2 , -CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent.

9. The compound according to any one of claims 1 to 5, wherein Parts are: in: R b1 and R b4 are independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , CH 3 , CH 2 CH 3 , -CF 2 or -CF 3 ; R b2 and R b3 are independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , -COOH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, pyridine or The methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, pyridine and may be independently optionally substituted by 1, 2 or 3 selected from hydrogen, deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , methyl, ethyl, methoxy, ethoxy, -CHF 2 , -CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent.

10. The compound according to any one of claims 1 to 9, wherein R 1 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , C 1-6 Alkyl, C 1-6 Alkoxy or C 3-6 Cycloalkyl; R 2 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , C 1-6 Alkyl, C 1-6 Alkoxy or C 3-6 Cycloalkyl.

11. The compound according to any one of claims 1 to 10, wherein R 1 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, n-propyl, isopropyl, methoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R 2 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, n-propyl, isopropyl, methoxy, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

12. The compound according to any one of claims 1 to 11, wherein R 3 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , C 1-6 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl or 5-6 membered heterocyclic group, the C 1-6 Alkyl, C 1-4 Alkoxy, C 3-6 The cycloalkyl and 5-6 membered heterocyclic groups may be independently optionally substituted by 1, 2 or 3 groups selected from deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , C 1- 3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkyl and C 1-3 The alkyl group is substituted with a haloalkyl substituent.

13. The compound according to any one of claims 1 to 12, wherein R 3 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl or morpholinyl, wherein the methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl and morpholinyl may be independently and optionally substituted by 1, 2 or 3 deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , methyl, methoxy, -CH 2 OH, -CHF 2 , -CF 3 、-CHFCH 2 F, -CF 2 CHF 2 、-CH 2 CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent.

14. The compound according to any one of claims 1 to 12, wherein R 3 For hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl or morpholinyl, wherein the methyl, ethyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl and morpholinyl may be independently and optionally replaced by 1, 2 or 3 selected from -CH 2 CHF 2 and -C(CH 3 ) 2 OH is substituted by a substituent.

15. The compound of any one of claims 1 to 14, wherein the DIM moiety is: in: X is CH or N; Y is a bond, -CH 2 -, -NH-, -O-, -C(=O)- or -C(=O)NH-; Ring C is phenyl, 5-6 membered monocyclic heteroaryl or 9-10 membered bicyclic heteroaryl, and the ring C may be independently and optionally substituted by 1, 2 or 3 selected from deuterium, halogen, oxo, CN, OH, NO 2 NH 2 , C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 The alkyl group is substituted with a haloalkyl substituent.

16. The compound of any one of claims 1 to 15, wherein the DIM moiety is:

17. The compound of any one of claims 1 to 15, wherein the DIM moiety is:

18. The compound of any one of claims 1 to 15, wherein the DIM moiety is:

19. The compound of any one of claims 1 to 15, wherein the DIM moiety is:

20. The compound of any one of claims 1 to 14, wherein the DIM moiety is:

21. The compound according to any one of claims 1 to 20, wherein L is C 3-12 Alkylene, wherein 1, 2, 3, 4 or 5 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d ) 2 -, -Cy-, -O-, -C(=O)-, -N(R d )-unit is replaced.

22. The compound according to any one of claims 1 to 21, wherein L is C 3-9 Alkylene, wherein 1, 2 or 3 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d ) 2 -, -O-, -C(=O)-, -NH-, The unit is replaced by can be independently optionally substituted by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO 2 NH 2 , oxo, methyl, ethyl, isopropyl, methoxy, isopropoxy, -CHF 2 , -CF 3 、-CHFCH 2 F, -CF 2 CHF 2 、-CH 2 CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent; Each R d independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, n-propyl or isopropyl.

23. The compound of any one of claims 1 to 22, wherein L is:

24. The compound of any one of claims 1 to 20, wherein L is 1-9 Alkylene, wherein 1, 2, 3 or 4 methylene groups may be independently optionally selected from -CR d =CR d -、-C≡C-、-C(R d ) 2 -, -O-, -C(=O)-, -NH-, The unit is replaced by can be independently optionally substituted by 1, 2 or 3 selected from deuterium, halogen, CN, OH, NO 2 NH 2 , oxo, methyl, ethyl, isopropyl, methoxy, isopropoxy, -CHF 2 , -CF 3 、-CHFCH 2 F, -CF 2 CHF 2 、-CH 2 CF 3 、-OCHF 2 and-OCF 3 substituted by a substituent; Each R d independently hydrogen, deuterium, halogen, CN, OH, NO 2 NH 2 , methyl, ethyl, n-propyl or isopropyl.

25. The compound according to any one of claims 1 to 20 and 24, wherein L is:

26. The compound according to any one of claims 1 to 25, which has a structure represented by formula (II), formula (III), formula (IV), formula (V) or formula (VI): in: Z 1 , Z 3 and Z 4 Each independently is CH 2 , -C(=O)-, NH, O or S; Z 2 is CH or N; p and q are each independently 1 or 2.

27. A compound, which is a compound having one of the following structures or an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof of a compound having one of the following structures:

28. A pharmaceutical composition comprising the compound of any one of claims 1-27, wherein the pharmaceutical composition optionally further comprises a pharmaceutically acceptable excipient, carrier, adjuvant or any combination thereof.

29. Use of the compound according to any one of claims 1 to 27 or the pharmaceutical composition according to claim 28 in the preparation of a medicament for preventing, treating or alleviating a disease associated with IRAK4 in a patient.

30. The use of claim 29, wherein the disease is selected from inflammatory diseases, infections such as viral, bacterial, fungal and parasitic infections, HIV-1 infection, sepsis, autoimmune disorders or diseases such as rheumatoid arthritis and multiple sclerosis, gout, juvenile idiopathic arthritis, Muckle-Wells disease, familial Mediterranean fever, Behcet's disease, adult Still's disease, proliferative diseases such as cancer, hyperplasia, restenosis, cardiac hypertrophy, leukemia, intravascular coagulation, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cardiovascular diseases, fibrotic and allergic diseases, asthma, atopic dermatitis, hidradenitis suppurativa, Alzheimer's disease, hormone-related diseases, trauma, hemodialysis, ischemic diseases, non-infectious hepatitis, ultraviolet radiation, closed head injury, pancreatitis, periodontitis, graft-versus-host disease and / or transplant rejection.

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